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Young men who have sex with men (YMSM) represent one of the most at-risk groups for HIV infection and experience sexual minority stress especially in high-stigma settings, which affects their psychological health and increases likelihood of HIV-risk behaviors. The HIV epidemic in China is increasing rapidly among YMSM. However, no evidence-based intervention has specifically targeted Chinese YMSM's minority stress to improve their mental and sexual health. Adaptation of evidence-based interventions to promote the mental and sexual health of YMSM is one promising way to achieve the global target of HIV epidemic control. The current adaptation study followed the Assessment-Decision-Administration-Production-Topical Experts-Integration-Training-Testing model. YMSM (n = 41) and key stakeholders (n = 16) in China provided feedback into the selected intervention, a cognitive-behavioral therapy called Effective Skills to Empower Effective Men, originally developed with efficacy in the United States. An open pilot (n = 8) was also then conducted. Qualitative and quantitative data collected from each adaptation phase were analyzed to form the adapted intervention "Yi Si Tang ()." Adaptations addressed a cultural context prioritizing family needs, limited support from the health system, as well as YMSM delivery preferences. YMSM and key stakeholders deemed the intervention acceptable and preliminarily feasible for the Chinese context. The pre-post comparison of mental and sexual health outcomes indicated improvement in mental health and sexual health of Chinese YMSM. Outcomes of the small initial pilot suggest future promise for this first-of-its-kind intervention for Chinese YMSM. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Developmental epidemiological work shows that rates of depression as assessed by diagnostic interviews increase from childhood through early adulthood. It could be assumed that the trajectory of depression as assessed by self-report questionnaire measures would be characterized by a similar pattern. We aimed to evaluate this assumption and more clearly establish the longitudinal trajectory of depression in youth, when repeatedly assessed over time with a self-report questionnaire and with a diagnostic interview. Participants were 679 youth ages 7-16 years at baseline (Mage = 11.8, SD = 2.4, 56% girls). They completed the Children's Depression Inventory (CDI) every 3 months for 3 years (13 time points) and were interviewed every 6 months using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) to ascertain onset of depression diagnosis. A series of growth curve models was fit to the CDI and K-SADS data. A piecewise model characterized growth in depression as assessed by the CDI, with an initial negative linear slope (b = -0.64) spanning the first 3 assessments, and a positive quadratic second slope (b = 0.015; linear component b = -0.22) spanning the remaining 10 assessments. Depression, as assessed by the K-SADS, grew continuously over time (a positive linear slope, b = 0.23). Findings illustrate differences between longitudinal trajectories of depression when assessed repeatedly by self-report questionnaire and diagnostic interview. Implications for research designed to study longitudinal depression trajectories are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The social microcosm is defined as group members replicating their everyday (intersession) interpersonal behaviors in group sessions and new behaviors, learned in the group (in-session), replicating in the members' everyday life. We examined intersession and in-session intimate behaviors, at the within-member (differences in intimate behaviors between weeks/sessions), between-member (average differences in intimate behaviors between group members) and between-groups (group-level differences in intimate behaviors). Participants were 178 graduate students (86% identifying as women and 14% as men) participating in 10 5-session growth groups led by experienced group therapists. Before group sessions, group members completed the Interpersonal Relations Scale Checklist (IRScl; Shadish, 1984) indicating their number of intersession intimate behaviors for the previous week and, at the end of group sessions, they filled in the IRScl to indicate their in-session intimate behaviors. A 3-level HLM analysis (sessions, memd).Research suggests that plurisexual individuals face ongoing decisions about whether and how accurately to present their sexual orientation to others, in part because of stereotypes and negative attitudes specific to plurisexuality. This study tested a within-person model of theoretical predictors and outcomes of self-presentational accuracy in a sample of 165 cisgender plurisexual women. Participants completed online surveys to report on situations involving self-presentation decisions as they occurred over a 14-day period. https://www.selleckchem.com/products/dcemm1.html Participants also completed nightly surveys assessing facets of well-being. Self-presentational accuracy varied substantially from day to day. Several contextual and relational factors, including acceptance and rejection cues, interaction partners' sexual orientation, and interpersonal closeness, predicted self-presentational accuracy, both directly and through the mediator of anticipated acceptance. Self-presentational accuracy predicted daily life satisfaction, positive affect, and negative affect through the mediator of social support. Finally, exploratory analyses underscored the relevance of goals related to authenticity, closeness, privacy, communication, educating others, and safety in self-presentation decisions. Discussion highlights the importance of context in identity management decisions among plurisexual women and the impact of these decisions on day-to-day well-being. (PsycInfo Database Record (c) 2020 APA, all rights reserved).People are normally restricted from accessing property without permission from the owner. The principle that nonowners are excluded from property is central to theories of ownership, and previous findings suggest it could be a core feature of the psychology of ownership. However, we report six experiments on children (N = 480) and adults (N = 211) showing that this principle may not apply for actions that benefit the owner-actions like repairing broken property. In Experiment 1, 3-5-year-olds judged it more acceptable for a nonowner to repair broken property than to move it. Experiments 2 and 3 replicated this with 4-6-year-olds using different question wordings and showed that children also approve of replacing broken property. Experiment 4 showed these findings replicate regardless of whether the nonowner and owner are acquainted. Finally, Experiments 5 and 6 revealed a boundary condition on approval of unsolicited beneficial actions Both 4-6-year-olds and adults judged repairing property more acceptable than modifying it to suit the owner's preferences.
Young men who have sex with men (YMSM) represent one of the most at-risk groups for HIV infection and experience sexual minority stress especially in high-stigma settings, which affects their psychological health and increases likelihood of HIV-risk behaviors. The HIV epidemic in China is increasing rapidly among YMSM. However, no evidence-based intervention has specifically targeted Chinese YMSM's minority stress to improve their mental and sexual health. Adaptation of evidence-based interventions to promote the mental and sexual health of YMSM is one promising way to achieve the global target of HIV epidemic control. The current adaptation study followed the Assessment-Decision-Administration-Production-Topical Experts-Integration-Training-Testing model. YMSM (n = 41) and key stakeholders (n = 16) in China provided feedback into the selected intervention, a cognitive-behavioral therapy called Effective Skills to Empower Effective Men, originally developed with efficacy in the United States. An open pilot (n = 8) was also then conducted. Qualitative and quantitative data collected from each adaptation phase were analyzed to form the adapted intervention "Yi Si Tang ()." Adaptations addressed a cultural context prioritizing family needs, limited support from the health system, as well as YMSM delivery preferences. YMSM and key stakeholders deemed the intervention acceptable and preliminarily feasible for the Chinese context. The pre-post comparison of mental and sexual health outcomes indicated improvement in mental health and sexual health of Chinese YMSM. Outcomes of the small initial pilot suggest future promise for this first-of-its-kind intervention for Chinese YMSM. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Developmental epidemiological work shows that rates of depression as assessed by diagnostic interviews increase from childhood through early adulthood. It could be assumed that the trajectory of depression as assessed by self-report questionnaire measures would be characterized by a similar pattern. We aimed to evaluate this assumption and more clearly establish the longitudinal trajectory of depression in youth, when repeatedly assessed over time with a self-report questionnaire and with a diagnostic interview. Participants were 679 youth ages 7-16 years at baseline (Mage = 11.8, SD = 2.4, 56% girls). They completed the Children's Depression Inventory (CDI) every 3 months for 3 years (13 time points) and were interviewed every 6 months using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) to ascertain onset of depression diagnosis. A series of growth curve models was fit to the CDI and K-SADS data. A piecewise model characterized growth in depression as assessed by the CDI, with an initial negative linear slope (b = -0.64) spanning the first 3 assessments, and a positive quadratic second slope (b = 0.015; linear component b = -0.22) spanning the remaining 10 assessments. Depression, as assessed by the K-SADS, grew continuously over time (a positive linear slope, b = 0.23). Findings illustrate differences between longitudinal trajectories of depression when assessed repeatedly by self-report questionnaire and diagnostic interview. Implications for research designed to study longitudinal depression trajectories are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).The social microcosm is defined as group members replicating their everyday (intersession) interpersonal behaviors in group sessions and new behaviors, learned in the group (in-session), replicating in the members' everyday life. We examined intersession and in-session intimate behaviors, at the within-member (differences in intimate behaviors between weeks/sessions), between-member (average differences in intimate behaviors between group members) and between-groups (group-level differences in intimate behaviors). Participants were 178 graduate students (86% identifying as women and 14% as men) participating in 10 5-session growth groups led by experienced group therapists. Before group sessions, group members completed the Interpersonal Relations Scale Checklist (IRScl; Shadish, 1984) indicating their number of intersession intimate behaviors for the previous week and, at the end of group sessions, they filled in the IRScl to indicate their in-session intimate behaviors. A 3-level HLM analysis (sessions, memd).Research suggests that plurisexual individuals face ongoing decisions about whether and how accurately to present their sexual orientation to others, in part because of stereotypes and negative attitudes specific to plurisexuality. This study tested a within-person model of theoretical predictors and outcomes of self-presentational accuracy in a sample of 165 cisgender plurisexual women. Participants completed online surveys to report on situations involving self-presentation decisions as they occurred over a 14-day period. https://www.selleckchem.com/products/dcemm1.html Participants also completed nightly surveys assessing facets of well-being. Self-presentational accuracy varied substantially from day to day. Several contextual and relational factors, including acceptance and rejection cues, interaction partners' sexual orientation, and interpersonal closeness, predicted self-presentational accuracy, both directly and through the mediator of anticipated acceptance. Self-presentational accuracy predicted daily life satisfaction, positive affect, and negative affect through the mediator of social support. Finally, exploratory analyses underscored the relevance of goals related to authenticity, closeness, privacy, communication, educating others, and safety in self-presentation decisions. Discussion highlights the importance of context in identity management decisions among plurisexual women and the impact of these decisions on day-to-day well-being. (PsycInfo Database Record (c) 2020 APA, all rights reserved).People are normally restricted from accessing property without permission from the owner. The principle that nonowners are excluded from property is central to theories of ownership, and previous findings suggest it could be a core feature of the psychology of ownership. However, we report six experiments on children (N = 480) and adults (N = 211) showing that this principle may not apply for actions that benefit the owner-actions like repairing broken property. In Experiment 1, 3-5-year-olds judged it more acceptable for a nonowner to repair broken property than to move it. Experiments 2 and 3 replicated this with 4-6-year-olds using different question wordings and showed that children also approve of replacing broken property. Experiment 4 showed these findings replicate regardless of whether the nonowner and owner are acquainted. Finally, Experiments 5 and 6 revealed a boundary condition on approval of unsolicited beneficial actions Both 4-6-year-olds and adults judged repairing property more acceptable than modifying it to suit the owner's preferences.0 Comments 0 Shares 32 Views 0 ReviewsPlease log in to like, share and comment! -
Investigation of the longitudinal and transverse excitations in liquids is of great importance for understanding the fundamentals of the liquid state of matter. One of the important questions is the temperature and density dependence of the frequency of the excitations. In our recent works it was shown that while in simple liquids the frequency of longitudinal excitations increases when the temperature is increased isochorically, in water the frequency can anomalously decrease with the temperature increase. In the present manuscript we study the dispersion curves of longitudinal and transverse excitations of water and liquid silicon modelled by Stillinger-Weber (SW) potential. We show that both in liquid silicon and SW model of water the frequencies of longitudinal excitations slightly increase with temperature which is in contrast to the results for SPC/E model of water.Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes of breast cancer; however, it lacks effective targeted therapies clinically. In this study, we found FZU-0038-056, a novel compound derived from last-stage functionalization of tetrahydro-β-carboline scaffold, showed the most potent anti-cancer activity against TNBC cells among the 42 synthesized derivatives. We found FZU-0038-056 significantly induces apoptosis in HCC1806 and HCC1937 TNBC cells. FZU-0038-056 reduces the expression levels of several anti-apoptosis proteins, including Bcl-2, Mcl-1 and XIAP. Furthermore, we found FZU-0038-056 induces apoptosis partially through inhibiting the expression of Bcl-2. Finally, we found FZU-0038-056 significantly suppresses HCC1806 xenograft tumor growth in nude **** without affecting their body weight. Therefore, FZU-0038-056 has the potential to be a new anticancer agent for treating human TNBC.Type 2 resistant starch (RS2) is a fermentable dietary fiber conferring health benefits. We investigated the effects of RS2 on host, gut microbiota, and metabolites in aged **** on high-fat diet. In eighteen-month old **** randomly assigned to control, high-fat (HF), or high-fat+20% RS2 (HFRS) diet for 16 weeks, RS2 reversed the weight gain and hepatic steatosis induced by high-fat diet. Serum and fecal LPS, colonic IL-2 and hepatic IL-4 mRNA expressions decreased while colonic mucin 2 mRNA and protein expressions increased in the HFRS compared to the HF and the control group. 16s rRNA sequencing of fecal microbial DNA demonstrated that RS2 decreased the abundance of pathogen taxa associated with obesity, inflammation, and aging including Desulfovibrio (Proteobacteria phylum), Ruminiclostridium 9, Lachnoclostridium, Helicobacteria, Oscillibacter, Alistipes, Peptococcus, and Rikenella. Additionally, RS2 increased the colonic butyric acid by 2.6-fold while decreasing the isobutyric and isovaleric acid levels by half compared to the HF group. Functional analyses based on Clusters of Orthologous Groups showed that RS2 increased carbohydrate while decreasing amino acid metabolism. These findings demonstrate that RS2 can reverse weight gain, hepatic steatosis, inflammation, and increased intestinal permeability in aged **** on high-fat diet mediated by changes in gut microbiome and metabolites.Mesenchymal stromal/stem cells (****) are promising carriers in cell-based therapies against central nervous system diseases, and have been evaluated in various clinical trials in recent years. However, bone marrow-derived **** (BMSCs) are reportedly involved in tumorigenesis initiated by glioma stem-like cells (GSCs). We therefore established three different orthotopic models of GSC-****interactions in vivo using dual-color fluorescence tracing. Cell sorting and micropipetting techniques were used to obtain highly proliferative ****monoclones from each model, and these cells were identified as transformed ****lines 1, 2 and 3. Nineteen miRNAs were upregulated and 24 miRNAs were downregulated in all three transformed ****lines compared to normal BMSCs. Reduced miR-146a-5p expression in the transformed **** was associated with their proliferation, malignant transformation and overexpression of heterogeneous nuclear ribonucleoprotein D. These findings suggest that downregulation of miR-146a-5p leads to overexpression of its target gene, heterogeneous nuclear ribonucleoprotein D, thereby promoting malignant transformation of **** during interactions with GSCs. Given the risk that **** will undergo malignant transformation in the glioma microenvironment, targeted glioma therapies employing **** as therapeutic carriers should be considered cautiously.Glaucoma filtration surgery (GFS) is an effective clinical treatment for glaucoma when intraocular pressure (IOP) control is poor. However, the occurrence of conjunctival scarring at the surgical site is the main reason for failure of the surgery. In a previous study, we isolated and developed S58, a novel nucleic acid aptamer targeting TβR II, by systematic evolution of ligands by exponential enrichment (SELEX). Here, we show how S58 sterically inhibits the TβR II interaction with TGF-β. The effects of topical S58 treatment were studied in a rabbit model of GFS. At 6 postoperative weeks, S58 reduced fibrosis and prolonged bleb survival in rabbits after GFS. Further in vitro tests showed that the levels of fibrosis in S58 treated-Human Conjunctival Fibroblasts (HConFs) were decreased and that antioxidant defense was increased. In addition, the loss of nuclear factor erythroid 2-related factor 2 (Nrf2) or the inhibition of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) reversed the anti-fibrotic effects of S58. The present work suggests that S58 could effectively improve GFS surgical outcomes by activating the intracellular antioxidant defense PI3K/Akt/Nrf2 signaling pathway.Background Parkinson's disease (PD) is one of the most common neurodegenerative diseases with complex etiology in sporadic cases. Accumulating evidence suggests that oxidative stress and defects in mitochondrial dynamics are associated with the pathogenesis of PD. The oxidative stress and mitochondrial dynamics are regulated strictly by peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). We investigated whether acetylation and phosphorylation of PGC-1α contribute to protecting neuronal cell against oxidative stress. Results We found that acetylation and phosphorylation mediated the nuclear translocation of PGC-1α protects against oxidative damage. https://www.selleckchem.com/products/Pyroxamide(NSC-696085).html In contrast to the increased nuclear PGC-1α, the cytosolic PGC-1α was decreased upon inhibition of GCN5 acetyltransferase. Similarly to the inhibition of GCN5 acetyltransferase, the increased nuclear PGC-1α and the decreased cytosolic PGC-1α were observed upon p38MAPK and AMPK activation. Briefly, the significantly increased nuclear PGC-1α is regulated either by inhibiting the acetylation of PGC-1α or by the phosphorylating PGC-1α, which results in a reduction in ROS.
Investigation of the longitudinal and transverse excitations in liquids is of great importance for understanding the fundamentals of the liquid state of matter. One of the important questions is the temperature and density dependence of the frequency of the excitations. In our recent works it was shown that while in simple liquids the frequency of longitudinal excitations increases when the temperature is increased isochorically, in water the frequency can anomalously decrease with the temperature increase. In the present manuscript we study the dispersion curves of longitudinal and transverse excitations of water and liquid silicon modelled by Stillinger-Weber (SW) potential. We show that both in liquid silicon and SW model of water the frequencies of longitudinal excitations slightly increase with temperature which is in contrast to the results for SPC/E model of water.Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes of breast cancer; however, it lacks effective targeted therapies clinically. In this study, we found FZU-0038-056, a novel compound derived from last-stage functionalization of tetrahydro-β-carboline scaffold, showed the most potent anti-cancer activity against TNBC cells among the 42 synthesized derivatives. We found FZU-0038-056 significantly induces apoptosis in HCC1806 and HCC1937 TNBC cells. FZU-0038-056 reduces the expression levels of several anti-apoptosis proteins, including Bcl-2, Mcl-1 and XIAP. Furthermore, we found FZU-0038-056 induces apoptosis partially through inhibiting the expression of Bcl-2. Finally, we found FZU-0038-056 significantly suppresses HCC1806 xenograft tumor growth in nude mice without affecting their body weight. Therefore, FZU-0038-056 has the potential to be a new anticancer agent for treating human TNBC.Type 2 resistant starch (RS2) is a fermentable dietary fiber conferring health benefits. We investigated the effects of RS2 on host, gut microbiota, and metabolites in aged mice on high-fat diet. In eighteen-month old mice randomly assigned to control, high-fat (HF), or high-fat+20% RS2 (HFRS) diet for 16 weeks, RS2 reversed the weight gain and hepatic steatosis induced by high-fat diet. Serum and fecal LPS, colonic IL-2 and hepatic IL-4 mRNA expressions decreased while colonic mucin 2 mRNA and protein expressions increased in the HFRS compared to the HF and the control group. 16s rRNA sequencing of fecal microbial DNA demonstrated that RS2 decreased the abundance of pathogen taxa associated with obesity, inflammation, and aging including Desulfovibrio (Proteobacteria phylum), Ruminiclostridium 9, Lachnoclostridium, Helicobacteria, Oscillibacter, Alistipes, Peptococcus, and Rikenella. Additionally, RS2 increased the colonic butyric acid by 2.6-fold while decreasing the isobutyric and isovaleric acid levels by half compared to the HF group. Functional analyses based on Clusters of Orthologous Groups showed that RS2 increased carbohydrate while decreasing amino acid metabolism. These findings demonstrate that RS2 can reverse weight gain, hepatic steatosis, inflammation, and increased intestinal permeability in aged mice on high-fat diet mediated by changes in gut microbiome and metabolites.Mesenchymal stromal/stem cells (MSCs) are promising carriers in cell-based therapies against central nervous system diseases, and have been evaluated in various clinical trials in recent years. However, bone marrow-derived MSCs (BMSCs) are reportedly involved in tumorigenesis initiated by glioma stem-like cells (GSCs). We therefore established three different orthotopic models of GSC-MSC interactions in vivo using dual-color fluorescence tracing. Cell sorting and micropipetting techniques were used to obtain highly proliferative MSC monoclones from each model, and these cells were identified as transformed MSC lines 1, 2 and 3. Nineteen miRNAs were upregulated and 24 miRNAs were downregulated in all three transformed MSC lines compared to normal BMSCs. Reduced miR-146a-5p expression in the transformed MSCs was associated with their proliferation, malignant transformation and overexpression of heterogeneous nuclear ribonucleoprotein D. These findings suggest that downregulation of miR-146a-5p leads to overexpression of its target gene, heterogeneous nuclear ribonucleoprotein D, thereby promoting malignant transformation of MSCs during interactions with GSCs. Given the risk that MSCs will undergo malignant transformation in the glioma microenvironment, targeted glioma therapies employing MSCs as therapeutic carriers should be considered cautiously.Glaucoma filtration surgery (GFS) is an effective clinical treatment for glaucoma when intraocular pressure (IOP) control is poor. However, the occurrence of conjunctival scarring at the surgical site is the main reason for failure of the surgery. In a previous study, we isolated and developed S58, a novel nucleic acid aptamer targeting TβR II, by systematic evolution of ligands by exponential enrichment (SELEX). Here, we show how S58 sterically inhibits the TβR II interaction with TGF-β. The effects of topical S58 treatment were studied in a rabbit model of GFS. At 6 postoperative weeks, S58 reduced fibrosis and prolonged bleb survival in rabbits after GFS. Further in vitro tests showed that the levels of fibrosis in S58 treated-Human Conjunctival Fibroblasts (HConFs) were decreased and that antioxidant defense was increased. In addition, the loss of nuclear factor erythroid 2-related factor 2 (Nrf2) or the inhibition of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) reversed the anti-fibrotic effects of S58. The present work suggests that S58 could effectively improve GFS surgical outcomes by activating the intracellular antioxidant defense PI3K/Akt/Nrf2 signaling pathway.Background Parkinson's disease (PD) is one of the most common neurodegenerative diseases with complex etiology in sporadic cases. Accumulating evidence suggests that oxidative stress and defects in mitochondrial dynamics are associated with the pathogenesis of PD. The oxidative stress and mitochondrial dynamics are regulated strictly by peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). We investigated whether acetylation and phosphorylation of PGC-1α contribute to protecting neuronal cell against oxidative stress. Results We found that acetylation and phosphorylation mediated the nuclear translocation of PGC-1α protects against oxidative damage. https://www.selleckchem.com/products/Pyroxamide(NSC-696085).html In contrast to the increased nuclear PGC-1α, the cytosolic PGC-1α was decreased upon inhibition of GCN5 acetyltransferase. Similarly to the inhibition of GCN5 acetyltransferase, the increased nuclear PGC-1α and the decreased cytosolic PGC-1α were observed upon p38MAPK and AMPK activation. Briefly, the significantly increased nuclear PGC-1α is regulated either by inhibiting the acetylation of PGC-1α or by the phosphorylating PGC-1α, which results in a reduction in ROS.0 Comments 0 Shares 34 Views 0 Reviews -
We report the complete genome sequence of Mycoplasma bovis strain XBY01, which was isolated from a severely diseased young calf in Henan Province, China, in 2019. The genome of XBY01 contains a single circular chromosome of 986,067 bp, with a GC content of 29.30%. Copyright © 2020 Shen et al.The immune system evolved for adequate surveillance and killing of pathogens while minimizing host damage, such as due to chronic or exaggerated inflammation and autoimmunity. This is achieved by negative regulators and checkpoints that limit the magnitude and time course of the immune response. Tumor cells often escape immune surveillance and killing. Therefore, disrupting the brakes built into the immune system should effectively boost the anticancer immune response. The success of anti-CTLA4, anti-PD-1 and anti-PD-L1 have firmly established this proof of concept. Since the response rate of anti-CTLA4, anti-PD-1 and anti-PD-L1 is still limited, there is an intense effort for the identification of new targets and development of approaches that can expand the benefits of immunotherapy to a larger patient pool. Additional T cell checkpoints are obvious targets; however, here we focus on the unusual suspects-cells that function to initiate and guide T cell activity. Innate immunity is both an obligate prerequisite for the initiation of adaptive immune responses and a requirement for the recruitment of activated T cells to the site of action. We discuss some of the molecules present in innate immune cells, including natural killer cells, dendritic cells, macrophages, myeloid-derived suppressor cells, endothelial cells and stromal cells, that can activate or enhance innate immune cell functions, and more importantly, the inhibitors or checkpoints present in these cells that restrain their functions. Boosting innate immunity, either by enhancing activator functions or, preferably, by blocking the inhibitors, may represent a new anticancer treatment modality or at least function as adjuvants to T cell checkpoint inhibitors. © Author(s) (or their employer(s)) 2020. https://www.selleckchem.com/products/recilisib.html Re-use permitted under CC BY. Published by BMJ.BACKGROUND Type 1 conventional dendritic cells (cDC1s) possess efficient antigen presentation and cross-presentation activity, as well as potent T cell priming ability. Tissue-resident cDC1s (CD103+ cDC1s in ****, CD141+ cDC1s in humans) are linked with improved tumor control, yet the efficacy of immunotherapy using this population is understudied. METHODS We generated murine CD103+ cDC1s in vitro and examined their expression of cDC1-related factors, antigen cross-presentation activity, and accumulation in tumor-draining lymph nodes (TdLNs). The antitumor efficacy of the in vitro-generated CD103+ cDC1s was studied in murine melanoma and osteosarcoma models. We evaluated tumor responses on vaccination with CD103+ cDC1s, compared these to vaccination with monocyte-derived DCs (MoDCs), tested CD103+ cDC1 vaccination with checkpoint blockade, and examined the antimetastatic activity of CD103+ cDC1s. RESULTS In vitro-generated CD103+ cDC1s produced cDC1-associated factors such as interleukin-12p70 and CXCL10, andto MoDCs and enhanced response to immune checkpoint blockade. These results indicate the potential for new immunotherapies based on use of cDC1s alone or in combination with checkpoint blockade. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND First-in-human (FIH) clinical trials require careful selection of a safe yet biologically relevant starting dose. Typically, such starting doses are selected based on toxicity studies in a pharmacologically relevant animal model. However, with the advent of target-specific and highly active immunotherapeutics, both the Food and Drug Administration and the European Medicines Agency have provided guidance that recommend determining a safe starting dose based on a minimum anticipated biological effect level (MABEL) approach. METHODS We recently developed a T cell activating bispecific antibody that effectively treats orthotopic patient-derived malignant glioma and syngeneic glioblastoma in **** (hEGFRvIIICD3 bi-scFv). hEGFRvIIICD3 bi-scFv is comprized of two single chain antibody fragments (bi-scFvs) that bind mutant epidermal growth factor receptor variant III (EGFRvIII), a mutation frequently seen in malignant glioma, and human CD3ε on T cells, respectively. In order to establish a FIH dose, we used a MABEL approach to select a safe starting dose for hEGFRvIIICD3 bi-scFv, based on a combination of in vitro data, in vivo animal studies, and theoretical human receptor occupancy modeling. RESULTS Using the most conservative approach to the MABEL assessment, a dose of 57.4 ng hEGFRvIIICD3 bi-scFv/kg body weight was selected as a safe starting dose for a FIH clinical study. CONCLUSIONS The comparison of our MABEL-based starting dose to our in vivo efficacious dose and the theoretical human receptor occupancy strongly supports that our human starting dose of 57.4 ng hEGFRvIIICD3 bi-scFv/patient kg will be safe. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.The mitochondrion of malaria parasites contains several clinically validated drug targets. Within Plasmodium spp., the causative agents of malaria, the mitochondrial DNA (mtDNA) is only 6 kb long, being the smallest mitochondrial genome among all eukaryotes. The mtDNA encodes only three proteins of the mitochondrial electron transport chain and ~27 small, fragmented rRNA genes having lengths of 22-195 nucleotides. The rRNA fragments are thought to form a mitochondrial ribosome (mitoribosome), together with ribosomal proteins imported from the cytosol. The mitoribosome of Plasmodium falciparum is essential for maintenance of the mitochondrial membrane potential and parasite viability. However, the role of the mitoribosome in sustaining the metabolic status of the parasite mitochondrion remains unclear. The small ribosomal subunit in P. falciparum has 14 annotated mitoribosomal proteins, and employing a CRISPR/Cas9-based conditional knockdown tool, here we verified the location and tested the essentiality of three candidates (PfmtRPS12, PfmtRPS17, and PfmtRPS18).
We report the complete genome sequence of Mycoplasma bovis strain XBY01, which was isolated from a severely diseased young calf in Henan Province, China, in 2019. The genome of XBY01 contains a single circular chromosome of 986,067 bp, with a GC content of 29.30%. Copyright © 2020 Shen et al.The immune system evolved for adequate surveillance and killing of pathogens while minimizing host damage, such as due to chronic or exaggerated inflammation and autoimmunity. This is achieved by negative regulators and checkpoints that limit the magnitude and time course of the immune response. Tumor cells often escape immune surveillance and killing. Therefore, disrupting the brakes built into the immune system should effectively boost the anticancer immune response. The success of anti-CTLA4, anti-PD-1 and anti-PD-L1 have firmly established this proof of concept. Since the response rate of anti-CTLA4, anti-PD-1 and anti-PD-L1 is still limited, there is an intense effort for the identification of new targets and development of approaches that can expand the benefits of immunotherapy to a larger patient pool. Additional T cell checkpoints are obvious targets; however, here we focus on the unusual suspects-cells that function to initiate and guide T cell activity. Innate immunity is both an obligate prerequisite for the initiation of adaptive immune responses and a requirement for the recruitment of activated T cells to the site of action. We discuss some of the molecules present in innate immune cells, including natural killer cells, dendritic cells, macrophages, myeloid-derived suppressor cells, endothelial cells and stromal cells, that can activate or enhance innate immune cell functions, and more importantly, the inhibitors or checkpoints present in these cells that restrain their functions. Boosting innate immunity, either by enhancing activator functions or, preferably, by blocking the inhibitors, may represent a new anticancer treatment modality or at least function as adjuvants to T cell checkpoint inhibitors. © Author(s) (or their employer(s)) 2020. https://www.selleckchem.com/products/recilisib.html Re-use permitted under CC BY. Published by BMJ.BACKGROUND Type 1 conventional dendritic cells (cDC1s) possess efficient antigen presentation and cross-presentation activity, as well as potent T cell priming ability. Tissue-resident cDC1s (CD103+ cDC1s in mice, CD141+ cDC1s in humans) are linked with improved tumor control, yet the efficacy of immunotherapy using this population is understudied. METHODS We generated murine CD103+ cDC1s in vitro and examined their expression of cDC1-related factors, antigen cross-presentation activity, and accumulation in tumor-draining lymph nodes (TdLNs). The antitumor efficacy of the in vitro-generated CD103+ cDC1s was studied in murine melanoma and osteosarcoma models. We evaluated tumor responses on vaccination with CD103+ cDC1s, compared these to vaccination with monocyte-derived DCs (MoDCs), tested CD103+ cDC1 vaccination with checkpoint blockade, and examined the antimetastatic activity of CD103+ cDC1s. RESULTS In vitro-generated CD103+ cDC1s produced cDC1-associated factors such as interleukin-12p70 and CXCL10, andto MoDCs and enhanced response to immune checkpoint blockade. These results indicate the potential for new immunotherapies based on use of cDC1s alone or in combination with checkpoint blockade. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND First-in-human (FIH) clinical trials require careful selection of a safe yet biologically relevant starting dose. Typically, such starting doses are selected based on toxicity studies in a pharmacologically relevant animal model. However, with the advent of target-specific and highly active immunotherapeutics, both the Food and Drug Administration and the European Medicines Agency have provided guidance that recommend determining a safe starting dose based on a minimum anticipated biological effect level (MABEL) approach. METHODS We recently developed a T cell activating bispecific antibody that effectively treats orthotopic patient-derived malignant glioma and syngeneic glioblastoma in mice (hEGFRvIIICD3 bi-scFv). hEGFRvIIICD3 bi-scFv is comprized of two single chain antibody fragments (bi-scFvs) that bind mutant epidermal growth factor receptor variant III (EGFRvIII), a mutation frequently seen in malignant glioma, and human CD3ε on T cells, respectively. In order to establish a FIH dose, we used a MABEL approach to select a safe starting dose for hEGFRvIIICD3 bi-scFv, based on a combination of in vitro data, in vivo animal studies, and theoretical human receptor occupancy modeling. RESULTS Using the most conservative approach to the MABEL assessment, a dose of 57.4 ng hEGFRvIIICD3 bi-scFv/kg body weight was selected as a safe starting dose for a FIH clinical study. CONCLUSIONS The comparison of our MABEL-based starting dose to our in vivo efficacious dose and the theoretical human receptor occupancy strongly supports that our human starting dose of 57.4 ng hEGFRvIIICD3 bi-scFv/patient kg will be safe. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.The mitochondrion of malaria parasites contains several clinically validated drug targets. Within Plasmodium spp., the causative agents of malaria, the mitochondrial DNA (mtDNA) is only 6 kb long, being the smallest mitochondrial genome among all eukaryotes. The mtDNA encodes only three proteins of the mitochondrial electron transport chain and ~27 small, fragmented rRNA genes having lengths of 22-195 nucleotides. The rRNA fragments are thought to form a mitochondrial ribosome (mitoribosome), together with ribosomal proteins imported from the cytosol. The mitoribosome of Plasmodium falciparum is essential for maintenance of the mitochondrial membrane potential and parasite viability. However, the role of the mitoribosome in sustaining the metabolic status of the parasite mitochondrion remains unclear. The small ribosomal subunit in P. falciparum has 14 annotated mitoribosomal proteins, and employing a CRISPR/Cas9-based conditional knockdown tool, here we verified the location and tested the essentiality of three candidates (PfmtRPS12, PfmtRPS17, and PfmtRPS18).0 Comments 0 Shares 33 Views 0 Reviews -
The rapid development of information communication technology (ICT), represented by mobile phones and the Internet, allows capitalizing to a greater extent on the wealth of information and knowledge available for agriculture knowledge and can be used to increase production, conserve the environment, etc. This study analyzes the current market-oriented behavioral effects of information communication technologies on farmers, based on data of 1263 rural households in two highly environmentally affected and major vegetable producing provinces-Shandong and Hebei. A probit model was used to analyze the impact of information communication technology on the choice of farmers' sales channels. The results show that the differences between the farm households with and without access to ICT, as well as those who actively or passively acquire information, have a significant impact on the choice of sales channels. Using ICT increases the probability that farmers choose sales through middlemen and cooperatives and reduces the probability of self-sales. Actively acquiring information has a positive impact on the cooperative channel choice and a significant negative impact on self-sales. Accordingly, we recommend that the government should increase the penetration rate of ICT, strengthen the information technology in rural areas, emphasize the construction of information sources, such as the collection and distribution of market information, enhance information literacy among farmers, reduce their transaction costs, and increase overall farmer participation in the market.Overweight/obesity modified the effects of ambient particulate matter (PM) exposure on blood pressure (BP). This study aims to assess whether interaction of underweight and short-term PM exposure on BP exists in Chinese children. A cross-sectional analysis including 144,513 children aged 6 to 17 years in 2016 Health Promotion Program for Children and Adolescents of Suzhou, China, was performed. Daily concentrations of inhalable PM (PM10) and fine PM (PM2.5) were extracted from air monitoring stations close to students' schools. We applied generalized linear mixed-effects models to estimate the interactions. Estimated changes (95% confidence intervals (CIs)) of systolic BP (SBP), diastolic BP (DBP), and odds ratios (ORs) (95% CIs) for prevalence of HBP were calculated. Significant interactions between PM and underweight on BP and prevalence of high BP (HBP) were observed. For example, at lag 6, the ORs (95% CIs) for HBP by each 10 μg/m3 changes of PM2.5 were 1.066 (1.039, 1.093) and 1.036 (1.028, 1.043) among underweight and normal weight subjects, respectively; these values for PM10 were 1.048 (1.031, 1.065) and 1.025 (1.021, 1.030). At lag 5, the increases of SBP for PM2.5 were 0.32 (95% CI 0.22, 0.43) mmHg and 0.23 (95% CI 0.29, 0.26) mmHg, while changes of DBP were 0.27 (95% CI 0.18, 0.35) mmHg and 0.19 (95% CI 0.16, 0.21) mmHg among underweight and normal weight subjects, respectively. Stratified analyses demonstrated that these interactions were only obtained in males. Effects of short-term PM exposure on BP and prevalence of HBP are enhanced in underweight children and adolescents.Limited epidemiologic studies questioned the association between pre- and postnatal lead exposure and the development of cerebral palsy (CP). Moreover, the genotypes of δ-aminolevulinic acid dehydratase (δ-ALAD) in CP patients and their mothers and their association to the blood lead levels (BLLs) were not previously studied. This study aimed to evaluate the association between δ-ALAD gene polymorphism and BLL in cases of CP and their mothers. A case control study was carried out on 23 CP cases and equal number of healthy matched controls. The mothers of the included children were asked to answer a questionnaire involving the baseline clinical and demographic characteristics. Also, questionnaires were done to detect the sources of environmental lead exposure and screen lead exposure during the pregnancy period. BLL, δ-ALAD enzyme activity, and genetic analysis for ALAD G177C were done for each child and his mother. There was significant (p 0.05) differences between CP and the control group regarding frequency of ALAD G177C genotypes, while there was a significant (p = 0.04) increase in the frequency of ALAD 1-2 (GC) genotype in the mothers of the CP group associated with high BLL and significant decrease in δ-ALAD activity (p less then 0.001). The study can indicate the significance of δ-ALAD gene polymorphism in the prenatal exposure to lead and the affection of the developing brain, pointing to the importance of controlling lead in pregnant women especially those with ALAD 1-2 genotype.The Mitis group of streptococci includes an important human pathogen, Streptococcus pneumoniae (pneumococcus) and about 20 other related species with **** lower pathogenicity. In clinical practice, some representatives of these species, especially Streptococcus pseudopneumoniae and Streptococcus mitis, are sometimes mistaken for S. https://www.selleckchem.com/products/mki-1.html pneumoniae based on the results of classical microbiological methods, such as optochin susceptibility and bile solubility. Several various molecular approaches that address the issue of correct identification of pneumococci and other Mitis streptococci have been proposed and are discussed in this review, including PCR- and gene sequencing-based tests as well as new developments in the genomic field that represents an important advance in our understanding of relationships within the Mitis group.Little is known about iodine adequacy and gestational thyroid disorders (GTDs) in Saudi Arabia. This study measured the rates of GTDs and iodine adequacy in 810 healthy Saudi women. Concentrations of serum thyroid hormones and 24-h urine iodine (24-h UIC), and GTDs were diagnosed according to the American Thyroid Association guidelines. Dietary and socioeconomic data to determine factors associated with GTDs and iodine insufficiency were collected. GTDs were detected in 265 women (32.7%) as follows subclinical (SCH; 20.2%) and overt (OH; 5.8%) hypothyroidism, isolated hypothyroxinemia (ISH; 4.7%) and hyperthyroidism (2%). The SCH (109.2 μg/L; IQR 77.2-149.7), OH (95.3 μg/L; IQR 74.3-130.5) and ISH (107.3 μg/L; IQR 65.5-133.1) groups had median 24-h UIC below the WHO recommended limit, whereas the euthyroid (191.4 μg/L; IQR 170.03-219.8) and hyperthyroid (159.5 μg/L; IQR 152.9-238.3) groups were iodine sufficient. Numbers of pregnancies, less education, not consuming iodized salt and not using iodine supplements increased risk of hypothyroidism and ISH.
The rapid development of information communication technology (ICT), represented by mobile phones and the Internet, allows capitalizing to a greater extent on the wealth of information and knowledge available for agriculture knowledge and can be used to increase production, conserve the environment, etc. This study analyzes the current market-oriented behavioral effects of information communication technologies on farmers, based on data of 1263 rural households in two highly environmentally affected and major vegetable producing provinces-Shandong and Hebei. A probit model was used to analyze the impact of information communication technology on the choice of farmers' sales channels. The results show that the differences between the farm households with and without access to ICT, as well as those who actively or passively acquire information, have a significant impact on the choice of sales channels. Using ICT increases the probability that farmers choose sales through middlemen and cooperatives and reduces the probability of self-sales. Actively acquiring information has a positive impact on the cooperative channel choice and a significant negative impact on self-sales. Accordingly, we recommend that the government should increase the penetration rate of ICT, strengthen the information technology in rural areas, emphasize the construction of information sources, such as the collection and distribution of market information, enhance information literacy among farmers, reduce their transaction costs, and increase overall farmer participation in the market.Overweight/obesity modified the effects of ambient particulate matter (PM) exposure on blood pressure (BP). This study aims to assess whether interaction of underweight and short-term PM exposure on BP exists in Chinese children. A cross-sectional analysis including 144,513 children aged 6 to 17 years in 2016 Health Promotion Program for Children and Adolescents of Suzhou, China, was performed. Daily concentrations of inhalable PM (PM10) and fine PM (PM2.5) were extracted from air monitoring stations close to students' schools. We applied generalized linear mixed-effects models to estimate the interactions. Estimated changes (95% confidence intervals (CIs)) of systolic BP (SBP), diastolic BP (DBP), and odds ratios (ORs) (95% CIs) for prevalence of HBP were calculated. Significant interactions between PM and underweight on BP and prevalence of high BP (HBP) were observed. For example, at lag 6, the ORs (95% CIs) for HBP by each 10 μg/m3 changes of PM2.5 were 1.066 (1.039, 1.093) and 1.036 (1.028, 1.043) among underweight and normal weight subjects, respectively; these values for PM10 were 1.048 (1.031, 1.065) and 1.025 (1.021, 1.030). At lag 5, the increases of SBP for PM2.5 were 0.32 (95% CI 0.22, 0.43) mmHg and 0.23 (95% CI 0.29, 0.26) mmHg, while changes of DBP were 0.27 (95% CI 0.18, 0.35) mmHg and 0.19 (95% CI 0.16, 0.21) mmHg among underweight and normal weight subjects, respectively. Stratified analyses demonstrated that these interactions were only obtained in males. Effects of short-term PM exposure on BP and prevalence of HBP are enhanced in underweight children and adolescents.Limited epidemiologic studies questioned the association between pre- and postnatal lead exposure and the development of cerebral palsy (CP). Moreover, the genotypes of δ-aminolevulinic acid dehydratase (δ-ALAD) in CP patients and their mothers and their association to the blood lead levels (BLLs) were not previously studied. This study aimed to evaluate the association between δ-ALAD gene polymorphism and BLL in cases of CP and their mothers. A case control study was carried out on 23 CP cases and equal number of healthy matched controls. The mothers of the included children were asked to answer a questionnaire involving the baseline clinical and demographic characteristics. Also, questionnaires were done to detect the sources of environmental lead exposure and screen lead exposure during the pregnancy period. BLL, δ-ALAD enzyme activity, and genetic analysis for ALAD G177C were done for each child and his mother. There was significant (p 0.05) differences between CP and the control group regarding frequency of ALAD G177C genotypes, while there was a significant (p = 0.04) increase in the frequency of ALAD 1-2 (GC) genotype in the mothers of the CP group associated with high BLL and significant decrease in δ-ALAD activity (p less then 0.001). The study can indicate the significance of δ-ALAD gene polymorphism in the prenatal exposure to lead and the affection of the developing brain, pointing to the importance of controlling lead in pregnant women especially those with ALAD 1-2 genotype.The Mitis group of streptococci includes an important human pathogen, Streptococcus pneumoniae (pneumococcus) and about 20 other related species with much lower pathogenicity. In clinical practice, some representatives of these species, especially Streptococcus pseudopneumoniae and Streptococcus mitis, are sometimes mistaken for S. https://www.selleckchem.com/products/mki-1.html pneumoniae based on the results of classical microbiological methods, such as optochin susceptibility and bile solubility. Several various molecular approaches that address the issue of correct identification of pneumococci and other Mitis streptococci have been proposed and are discussed in this review, including PCR- and gene sequencing-based tests as well as new developments in the genomic field that represents an important advance in our understanding of relationships within the Mitis group.Little is known about iodine adequacy and gestational thyroid disorders (GTDs) in Saudi Arabia. This study measured the rates of GTDs and iodine adequacy in 810 healthy Saudi women. Concentrations of serum thyroid hormones and 24-h urine iodine (24-h UIC), and GTDs were diagnosed according to the American Thyroid Association guidelines. Dietary and socioeconomic data to determine factors associated with GTDs and iodine insufficiency were collected. GTDs were detected in 265 women (32.7%) as follows subclinical (SCH; 20.2%) and overt (OH; 5.8%) hypothyroidism, isolated hypothyroxinemia (ISH; 4.7%) and hyperthyroidism (2%). The SCH (109.2 μg/L; IQR 77.2-149.7), OH (95.3 μg/L; IQR 74.3-130.5) and ISH (107.3 μg/L; IQR 65.5-133.1) groups had median 24-h UIC below the WHO recommended limit, whereas the euthyroid (191.4 μg/L; IQR 170.03-219.8) and hyperthyroid (159.5 μg/L; IQR 152.9-238.3) groups were iodine sufficient. Numbers of pregnancies, less education, not consuming iodized salt and not using iodine supplements increased risk of hypothyroidism and ISH.0 Comments 0 Shares 24 Views 0 Reviews -
However, there are several methodological inconsistencies which hinder research implications, such as; inadequate description or omission of ethnicity and on-field positions. Furthermore, there is a limited amount of research on several key areas crucial to footballing performance, in particular; psychological related traits. Moving forward, improved research designs, larger sample sizes, and the utilisation of genome-wide and polygenic profiling approaches are recommended. Finally, we introduce the Football Gene Project, which aims to address several of these limitations and ultimately facilitate greater individualised athlete development within football.Efforts to develop anti-cancer therapies have largely focused on targeting the epithelial compartment, despite the presence of non-neoplastic stromal components that substantially contribute to the progression of the tumor. Indeed, cancer cell survival, growth, migration and even dormancy are influenced by the surrounding tumor microenvironment (TME). Within the TME, cancer-associated fibroblasts (CAFs) have been shown to play several roles in the development of a tumor. They secrete growth factors, inflammatory ligands and extracellular matrix proteins that promote cancer cell proliferation, therapy resistance and immune exclusion. However, recent work indicates that CAFs may also restrain tumor progression in some circumstances. In this review, we summarize the body of work on CAFs, with a particular focus on the most recent discoveries about fibroblast heterogeneity, plasticity and functions. We also highlight the commonalities of fibroblasts present across different cancer types, and in normal and inflammatory states. Finally, we present the latest advances regarding therapeutic strategies targeting CAFs that are undergoing pre-clinical and clinical evaluation.A method to determine T-2 and HT-2 toxins, both in feed and food, is described. The method is based on sample clean-up by immunoaffinity columns, followed by triple quadrupole LC-MS/MS determination. It was in-house validated in compliance with the European Union legislation, in the concentration range 5.0-750 µg kg-1 and accredited according to the ISO/IEC 17025 standard, for the scope of official control of feed and food. The method was applied to monitor the contamination levels of T-2 and HT-2 toxins in 105 feed samples, both raw materials and compound feed and 17 cereals and derived products for human consumption, collected in Southern Italy between 2015 and 2019. T-2 toxin was quantified in 32 feed (30.5%) and in 2 food samples (11.8%). HT-2 toxin was quantified in 65 feed (61.9%) and in 3 food (17.6%) samples.Aims To study the associations between and timing of psychosocial and physical work factors and health status on sick leave among Danish pregnant employees. Methods A total of 910 pregnant women completed a questionnaire in gestational weeks 12 (baseline) and 27 (follow-up). Information about psychosocial and physical work factors and health status was obtained at baseline. Associations with sick leave ⩾14 days were estimated using logistic regression. Further, the impact of timing and duration of exposure on sick leave were examined. Results A total of 133 women (14.6%) reported ⩾14 days of sick leave at follow-up (27 weeks of gestation). Work-related risk factors for sick leave were high work pace, low influence, low recognition, low job satisfaction, conflict in work-family balance, standing/walking, heavy lifting, and shift work/night shift. Health-related risk factors were burnout, stress, possibility of depression, low work ability, previous sick leave, and poor self-rated health. Being exposed to work-related risk factors during the first 27 weeks of pregnancy or at follow-up increased the risk of sick leave compared with those not exposed at any time or only exposed at baseline. Poor health status increased the risk if women were exposed in the first 27 weeks of pregnancy; however, high possibility of depression was also a risk factor when experienced in early pregnancy. Conclusions Psychosocial and physical work-related risk factors and poor health status were associated with more sick leave in pregnant employees. Early adjustment of work-related risk factors at the workplace is needed to reduce sick leave.Aims Worldwide, smokeless-tobacco use is a major risk factor for oral cancer. Evidence regarding the particular association between Swedish snus use and oral cancer is, however, less clear. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between snus use and oral cancer. Methods A total of 418,369 male participants from nine cohort studies were followed up for oral cancer incidence through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. https://www.selleckchem.com/products/mki-1.html Results During 9,201,647 person-years of observation, 628 men developed oral cancer. Compared to never-snus use, ever-snus use was not associated with oral cancer (adjusted HR 0.90, 95% CI 0.74, 1.09). There were no clear trends in risk with duration or intensity of snus use, although lower intensity use (⩽ 4 cans/week) was associated with a reduced risk (HR 0.65, 95% CI 0.45, 0.94). Snus use was not associated with oral cancer among never smokers (HR 0.87, 95% CI 0.57, 1.32). Conclusions Swedish snus use does not appear to be implicated in the development of oral cancer in men.Amino acid cysteine has been used as reducing mediator with the aim of improving dye degradation by homogeneous Fenton processes (Fe2+/H2O2 and Fe3+/H2O2). Through its known Fe3+-reducing activity, this amino acid can enhance the production of reactive oxygen species as HO• (hydroxyl radical) and its pro-oxidant properties have been verified while decolorizing diverse dyes in the present work. Its presence enhanced decolorization of Methyl Orange, Phenol Red, Safranin T, Rhodamine B, Reactive Black 5 and Reactive Yellow 2, mainly in reactions initially containing Fe3+ as a catalyst (Fe3+-reactions). E.g. Fe3+/H2O2 and Fe3+/H2O2/cysteine systems decolorized 27% and 44% of Phenol Red after 60 min, respectively. A kinetic modeling analysis has revealed that 1st-order and mainly 2nd-order kinetic models were well fitted to both Fe2+- and Fe3+-reactions data. Improvements in reaction rate constants have been observed by adding cysteine. In experiments performed at varied temperatures, it was found a decrease in activation energy (Ea) due to cysteine addition while decolorizing Safranin T Ea decreased from 104.
However, there are several methodological inconsistencies which hinder research implications, such as; inadequate description or omission of ethnicity and on-field positions. Furthermore, there is a limited amount of research on several key areas crucial to footballing performance, in particular; psychological related traits. Moving forward, improved research designs, larger sample sizes, and the utilisation of genome-wide and polygenic profiling approaches are recommended. Finally, we introduce the Football Gene Project, which aims to address several of these limitations and ultimately facilitate greater individualised athlete development within football.Efforts to develop anti-cancer therapies have largely focused on targeting the epithelial compartment, despite the presence of non-neoplastic stromal components that substantially contribute to the progression of the tumor. Indeed, cancer cell survival, growth, migration and even dormancy are influenced by the surrounding tumor microenvironment (TME). Within the TME, cancer-associated fibroblasts (CAFs) have been shown to play several roles in the development of a tumor. They secrete growth factors, inflammatory ligands and extracellular matrix proteins that promote cancer cell proliferation, therapy resistance and immune exclusion. However, recent work indicates that CAFs may also restrain tumor progression in some circumstances. In this review, we summarize the body of work on CAFs, with a particular focus on the most recent discoveries about fibroblast heterogeneity, plasticity and functions. We also highlight the commonalities of fibroblasts present across different cancer types, and in normal and inflammatory states. Finally, we present the latest advances regarding therapeutic strategies targeting CAFs that are undergoing pre-clinical and clinical evaluation.A method to determine T-2 and HT-2 toxins, both in feed and food, is described. The method is based on sample clean-up by immunoaffinity columns, followed by triple quadrupole LC-MS/MS determination. It was in-house validated in compliance with the European Union legislation, in the concentration range 5.0-750 µg kg-1 and accredited according to the ISO/IEC 17025 standard, for the scope of official control of feed and food. The method was applied to monitor the contamination levels of T-2 and HT-2 toxins in 105 feed samples, both raw materials and compound feed and 17 cereals and derived products for human consumption, collected in Southern Italy between 2015 and 2019. T-2 toxin was quantified in 32 feed (30.5%) and in 2 food samples (11.8%). HT-2 toxin was quantified in 65 feed (61.9%) and in 3 food (17.6%) samples.Aims To study the associations between and timing of psychosocial and physical work factors and health status on sick leave among Danish pregnant employees. Methods A total of 910 pregnant women completed a questionnaire in gestational weeks 12 (baseline) and 27 (follow-up). Information about psychosocial and physical work factors and health status was obtained at baseline. Associations with sick leave ⩾14 days were estimated using logistic regression. Further, the impact of timing and duration of exposure on sick leave were examined. Results A total of 133 women (14.6%) reported ⩾14 days of sick leave at follow-up (27 weeks of gestation). Work-related risk factors for sick leave were high work pace, low influence, low recognition, low job satisfaction, conflict in work-family balance, standing/walking, heavy lifting, and shift work/night shift. Health-related risk factors were burnout, stress, possibility of depression, low work ability, previous sick leave, and poor self-rated health. Being exposed to work-related risk factors during the first 27 weeks of pregnancy or at follow-up increased the risk of sick leave compared with those not exposed at any time or only exposed at baseline. Poor health status increased the risk if women were exposed in the first 27 weeks of pregnancy; however, high possibility of depression was also a risk factor when experienced in early pregnancy. Conclusions Psychosocial and physical work-related risk factors and poor health status were associated with more sick leave in pregnant employees. Early adjustment of work-related risk factors at the workplace is needed to reduce sick leave.Aims Worldwide, smokeless-tobacco use is a major risk factor for oral cancer. Evidence regarding the particular association between Swedish snus use and oral cancer is, however, less clear. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between snus use and oral cancer. Methods A total of 418,369 male participants from nine cohort studies were followed up for oral cancer incidence through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. https://www.selleckchem.com/products/mki-1.html Results During 9,201,647 person-years of observation, 628 men developed oral cancer. Compared to never-snus use, ever-snus use was not associated with oral cancer (adjusted HR 0.90, 95% CI 0.74, 1.09). There were no clear trends in risk with duration or intensity of snus use, although lower intensity use (⩽ 4 cans/week) was associated with a reduced risk (HR 0.65, 95% CI 0.45, 0.94). Snus use was not associated with oral cancer among never smokers (HR 0.87, 95% CI 0.57, 1.32). Conclusions Swedish snus use does not appear to be implicated in the development of oral cancer in men.Amino acid cysteine has been used as reducing mediator with the aim of improving dye degradation by homogeneous Fenton processes (Fe2+/H2O2 and Fe3+/H2O2). Through its known Fe3+-reducing activity, this amino acid can enhance the production of reactive oxygen species as HO• (hydroxyl radical) and its pro-oxidant properties have been verified while decolorizing diverse dyes in the present work. Its presence enhanced decolorization of Methyl Orange, Phenol Red, Safranin T, Rhodamine B, Reactive Black 5 and Reactive Yellow 2, mainly in reactions initially containing Fe3+ as a catalyst (Fe3+-reactions). E.g. Fe3+/H2O2 and Fe3+/H2O2/cysteine systems decolorized 27% and 44% of Phenol Red after 60 min, respectively. A kinetic modeling analysis has revealed that 1st-order and mainly 2nd-order kinetic models were well fitted to both Fe2+- and Fe3+-reactions data. Improvements in reaction rate constants have been observed by adding cysteine. In experiments performed at varied temperatures, it was found a decrease in activation energy (Ea) due to cysteine addition while decolorizing Safranin T Ea decreased from 104.0 Comments 0 Shares 58 Views 0 Reviews -
Airfoil tip vortex formation noise is a significant noise source in many aerodynamic applications such as aircraft, fans, rotors and propellers. The data collection presented in this paper examines the effects of sinusoidal geometry and porosity on the tip vortex formation noise produced by finite length airfoils. The use of serrated and porous materials is inspired by silent owl-wings and is a promising approach to control flow-induced noise. Noise measurements have been taken using a 47-channel planar microphone array in the anechoic wind tunnel at the Brandenburg University of Technology. Over 2600 unique test cases with variations in sinusoidal tip geometry (amplitude and wavelength) and flat tip porosity were measured during the experimental campaign for a NACA0012 and NACA614 airfoil. The microphone data have been processed using acoustic beamforming software named Acoular to produce one-third-octave band tip noise spectra. © 2020 The Author(s).Presented paper describes spectroscopic dataset and calibration models database of near infrared spectroscopy (NIRS) used to predict agricultural soil fertility properties. Near infrared spectra data in form of absorbance spectrum were acquired in wavelength range from 1000 to 2500 nm for a total of 40 bulk soil samples amounted of 10 g per each bulk. Soil fertility properties, presented as soil nitrogen (N), phosphorus (P). potassium (K), soil pH, magnesium (Mg) and calcium (Ca), were measured by means of wet chemical analysis. Calibration models, used to predict those soil fertility parameters were developed using two different regression algorithms namely principal component regression (PCR) and partial least square regression (PLSR) respectively. Prediction performance can be evaluated and justified by looking their statistical indicators correlation of determination (R2), correlation coefficient (r), root mean square error (RMSE) and residual predictive deviation (RPD). Spectra data can also be corrected in order to improve and enhance prediction performance. Obtained NIRS dataset and models database can be used as a rapid and simultaneous method to determine agricultural soil fertility properties. © 2020 The Author(s).The identification of non-fermentative Gram negative bacilli from run-off and spring water, including fluorescent Pseudomonas is very complex and investigations are needed to contribute to the systematic of these bacteria. In this dataset, the phenotypical profiles of three strains isolated from Vosges mountains first identified as Pseudomonas fluorescens were determined using APIⓇ 50 CH galleries. Then, the identification of their proteins released directly into water was carried out using tandem/mass spectrometry after separating proteins on native two-dimensional polyacrylamide gels. Finally, genotypic analysis data is presented, that illustrates biodiversity in this fluorescent bacterial group. This data is referred by a research article entitled "Fluorescent Pseudomonas strains from mid-mountain water able to release antioxidant proteins directly into water". © 2020 The Author(s). Published by Elsevier Inc.A dataset in this report is regarding a research article "Crucial Role of Thioacetamide for ZrO2 Coating on the Fragile Surface of Ni-rich Layered Cathode in Lithium Ion Batteries" [1]. Thioacetamide (TA) is introduced to form a homogeneous ZrO2-coating in a facile method through washing with Zr(SO4)2 aqueous solution. The presence of the data in this paper indicated the role of TA for surface modification of LiNi0.82Co0.09Mn0.09O2 (NCM82) materials by ZrO2, leading to improve the electrochemical performance of NCM82 Ni-rich cathode materials. These data were proceeded measurement electrochemical properties of cathode electrode on a battery cycler, the surface characteristics of the cathode materials were investigated by SEM, EDS mapping, TEM and XPS. X-ray diffraction (XRD, Rigaku, SmartLab) was used to evaluate the influence of the coating layer on the microstructure of active materials. © 2020 The Authors.These datasets contain Computed Tomography (CT) images of 19 patients with Abdominal Aortic Aneurysm (AAA) together with 19 patient-specific geometry data and computational grids (finite element meshes) created from these images applied in the research reported in Journal of Surgical Research article "Is There A Relationship Between Stress in Walls of Abdominal Aortic Aneurysm and Symptoms?"[1]. The images were randomly selected from the retrospective database of University Hospitals Leuven (Leuven, Belgium) and provided to The University of Western Australia's Intelligent Systems for Medicine Laboratory. The analysis was conducted using our freely-available open-source software BioPARR (Joldes et al., 2017) created at The University of Western Australia. The analysis steps include image segmentation to obtain the patient-specific AAA geometry, construction of computational grids (finite element meshes), and AAA stress computation. We use well-established and widely used data file formats (Nearly Raw Raster Data or NRRD for the images, Stereolitography or STL format for geometry, and Abaqus finite element code keyword format for the finite element meshes). This facilitates re-use of our datasets in practically unlimited range of studies that rely on medical image analysis and computational biomechanics to investigate and formulate indicators and predictors of AAA symptoms. © 2020 The Authors.The data presented in this article relates to the individual intrinsic and extrinsic motivations to share travel experience in social media. The 381 records were gathered in Portugal using an online survey. A statistical analysis of the data was carried out using partial least squares (PLS). This dataset shows a relationship between identification, internalization, and compliance to perceived enjoyment, and also, between perceived enjoyment, altruistic motivations, personal fulfillment, and self-actualization as well as security and privacy reasons to actual travel experience sharing. For further findings and interpretation, please refer to the research article entitled "Why do people share their travel experiences on social media?" [1]. https://www.selleckchem.com/products/gsk864.html We suggest the use of this data to compare with data collected by other researchers to develop cross-country analyses based on the model proposed by Oliveira, Araujo, and Tam [1]. © 2020 The Author(s). Published by Elsevier Inc.
Airfoil tip vortex formation noise is a significant noise source in many aerodynamic applications such as aircraft, fans, rotors and propellers. The data collection presented in this paper examines the effects of sinusoidal geometry and porosity on the tip vortex formation noise produced by finite length airfoils. The use of serrated and porous materials is inspired by silent owl-wings and is a promising approach to control flow-induced noise. Noise measurements have been taken using a 47-channel planar microphone array in the anechoic wind tunnel at the Brandenburg University of Technology. Over 2600 unique test cases with variations in sinusoidal tip geometry (amplitude and wavelength) and flat tip porosity were measured during the experimental campaign for a NACA0012 and NACA614 airfoil. The microphone data have been processed using acoustic beamforming software named Acoular to produce one-third-octave band tip noise spectra. © 2020 The Author(s).Presented paper describes spectroscopic dataset and calibration models database of near infrared spectroscopy (NIRS) used to predict agricultural soil fertility properties. Near infrared spectra data in form of absorbance spectrum were acquired in wavelength range from 1000 to 2500 nm for a total of 40 bulk soil samples amounted of 10 g per each bulk. Soil fertility properties, presented as soil nitrogen (N), phosphorus (P). potassium (K), soil pH, magnesium (Mg) and calcium (Ca), were measured by means of wet chemical analysis. Calibration models, used to predict those soil fertility parameters were developed using two different regression algorithms namely principal component regression (PCR) and partial least square regression (PLSR) respectively. Prediction performance can be evaluated and justified by looking their statistical indicators correlation of determination (R2), correlation coefficient (r), root mean square error (RMSE) and residual predictive deviation (RPD). Spectra data can also be corrected in order to improve and enhance prediction performance. Obtained NIRS dataset and models database can be used as a rapid and simultaneous method to determine agricultural soil fertility properties. © 2020 The Author(s).The identification of non-fermentative Gram negative bacilli from run-off and spring water, including fluorescent Pseudomonas is very complex and investigations are needed to contribute to the systematic of these bacteria. In this dataset, the phenotypical profiles of three strains isolated from Vosges mountains first identified as Pseudomonas fluorescens were determined using APIⓇ 50 CH galleries. Then, the identification of their proteins released directly into water was carried out using tandem/mass spectrometry after separating proteins on native two-dimensional polyacrylamide gels. Finally, genotypic analysis data is presented, that illustrates biodiversity in this fluorescent bacterial group. This data is referred by a research article entitled "Fluorescent Pseudomonas strains from mid-mountain water able to release antioxidant proteins directly into water". © 2020 The Author(s). Published by Elsevier Inc.A dataset in this report is regarding a research article "Crucial Role of Thioacetamide for ZrO2 Coating on the Fragile Surface of Ni-rich Layered Cathode in Lithium Ion Batteries" [1]. Thioacetamide (TA) is introduced to form a homogeneous ZrO2-coating in a facile method through washing with Zr(SO4)2 aqueous solution. The presence of the data in this paper indicated the role of TA for surface modification of LiNi0.82Co0.09Mn0.09O2 (NCM82) materials by ZrO2, leading to improve the electrochemical performance of NCM82 Ni-rich cathode materials. These data were proceeded measurement electrochemical properties of cathode electrode on a battery cycler, the surface characteristics of the cathode materials were investigated by SEM, EDS mapping, TEM and XPS. X-ray diffraction (XRD, Rigaku, SmartLab) was used to evaluate the influence of the coating layer on the microstructure of active materials. © 2020 The Authors.These datasets contain Computed Tomography (CT) images of 19 patients with Abdominal Aortic Aneurysm (AAA) together with 19 patient-specific geometry data and computational grids (finite element meshes) created from these images applied in the research reported in Journal of Surgical Research article "Is There A Relationship Between Stress in Walls of Abdominal Aortic Aneurysm and Symptoms?"[1]. The images were randomly selected from the retrospective database of University Hospitals Leuven (Leuven, Belgium) and provided to The University of Western Australia's Intelligent Systems for Medicine Laboratory. The analysis was conducted using our freely-available open-source software BioPARR (Joldes et al., 2017) created at The University of Western Australia. The analysis steps include image segmentation to obtain the patient-specific AAA geometry, construction of computational grids (finite element meshes), and AAA stress computation. We use well-established and widely used data file formats (Nearly Raw Raster Data or NRRD for the images, Stereolitography or STL format for geometry, and Abaqus finite element code keyword format for the finite element meshes). This facilitates re-use of our datasets in practically unlimited range of studies that rely on medical image analysis and computational biomechanics to investigate and formulate indicators and predictors of AAA symptoms. © 2020 The Authors.The data presented in this article relates to the individual intrinsic and extrinsic motivations to share travel experience in social media. The 381 records were gathered in Portugal using an online survey. A statistical analysis of the data was carried out using partial least squares (PLS). This dataset shows a relationship between identification, internalization, and compliance to perceived enjoyment, and also, between perceived enjoyment, altruistic motivations, personal fulfillment, and self-actualization as well as security and privacy reasons to actual travel experience sharing. For further findings and interpretation, please refer to the research article entitled "Why do people share their travel experiences on social media?" [1]. https://www.selleckchem.com/products/gsk864.html We suggest the use of this data to compare with data collected by other researchers to develop cross-country analyses based on the model proposed by Oliveira, Araujo, and Tam [1]. © 2020 The Author(s). Published by Elsevier Inc.0 Comments 0 Shares 35 Views 0 Reviews -
Using crosstabulation, DTR allowed identification of PD-MCI patients with an accuracy of 80%. Delayed free and cued recall was associated with decreased GMV and increased MD in multiple fronto-temporal and parietal areas. Conclusion Encoding and retrieval deficits are a main characteristic of PD-MCI and are associated with structural damage in temporal, parietal and prefrontal areas. https://www.selleckchem.com/products/acetalax-oxyphenisatin-acetate.html Copyright © 2020 Horta-Barba, Pagonabarraga, Martínez-Horta, Marín-Lahoz, Sampedro, Fernández-Bobadilla, Botí, Bejr-Kasem, Aracil-Bolaños, Pérez-Pérez, Pascual-Sedano, Campolongo, Izquierdo, Gómez-Ansón and Kulisevsky.Introduction Early magnetic resonance imaging (MRI) provides important information for management and prognosis in patients with severe traumatic brain injury (sTBI). Yet, optimal timing of MRI remains unknown. The aim of our study was to evaluate the safety of early MRI and to identify a method for appropriate patient selection to minimize adverse events related to the intrahospital transport (IHT) and the MRI examination. Methods Twenty-six patients with sTBI [mean Glasgow Coma Scale (GCS) 6, range 3-8] admitted to our neurosurgical ICU from 03/2015 to 12/2017 and receiving at least one MRI within the first 14 days after initial traumatic event were prospectively included in the study. The following requirements were fulfilled for at least 4 h prior to anticipated MRI MAP > 70 mmHg, aPCO2 30-40 mmHg, stable ICP less then 25 mmHg. All relevant cardiopulmonary and cerebral parameters and medication were recorded. The following MRI sequences were performed DWI, FLAIR, 3D T2-space, 3D T1 MPRAGE, 3D SWI, 3D TOF, pASL, and 1H/31P-MRS. Results Four females and 22 males (aged 23-78 years, mean 46.4 years) with a median GCS on admission of 5 (range 3-8) were analyzed. In total, 40 IHTs were performed within the first 14 days (mean 6 days, range 1-14 days). Mean pre-MRI ICP was 14.1 mmHg (range 3-32 mmHg). The mean post-MRI ICP was 14.3 mmHg (range 3-29 mmHg), decreasing to a mean ICP of 13.2 mmHg after 1 h (range 3-29 mmHg). There were no significant differences in ICP measurements before and after MRI (p = 0.30). MAP remained stable with no significant changes during the entire IHT and MRI. No other adverse events were observed as well. Conclusion Early MRI in acute severe TBI is feasible and safe. Yet, careful patient selection with prior adequate testing of cardiopulmonary and cerebral parameters is crucial to minimize transport- or examination-related morbidity. Copyright © 2020 Pinggera, Luger, Bürgler, Bauer, Thomé and Petr.Background Cognitive impairment following a minor stroke or transient ischemic attack (TIA) is common; however, due to diagnostic difficulties, the prevalence and underlying cause of impairment remain poorly defined. We compared cognition in patients after a minor stroke, TIA, or mimic event at three time points in the first year following the event. We examine whether cognitive impairment occurs following these events and whether this impairment differs based on the event type. Further, we measure whether these findings persist after controlling for age, education, and the presence of vascular risk factors and whether the presence of vascular risk factors, independent of event etiology, is associated with cognitive impairment. Lastly, we investigate whether increased stroke risk, as assessed by the ABCD2, is associated with reduced cognition. Methods Medical information, a cognitive screening test, and a measure of executive functioning were collected from 613 patients (123 minor stroke, 175 TIA, and 315 mimular risk factors in these patients. This highlights the importance of long-term management of vascular risk factors beyond event recovery to reduce the risk of cognitive impairment. Increased stroke risk (i.e., ABCD2 score) was also associated with reduced cognition, suggesting that it may be helpful in signaling the need for further cognitive evaluation and intervention post-event. Copyright © 2020 Nicolas, Levi, Evans, Michie, Magin, Quain, Bivard and Karayanidis.Botulinum NeuroToxin-A (BoNT-A) injections to the medial gastrocnemius (MG) and lower-leg casts are commonly combined to treat ankle equinus in children with spastic cerebral palsy (CP). However, the decomposed treatment effects on muscle or tendon structure, stretch reflexes, and joint are unknown. In this study, BoNT-A injections to the MG and casting of the lower legs were applied separately to gain insight into the working mechanisms of the isolated treatments on joint, muscle, and tendon levels. Thirty-one children with spastic CP (GMFCS I-III, age 7.4 ± 2.6 years) received either two weeks of lower-leg casts or MG BoNT-A injections. During full range of motion slow and fast passive ankle rotations, joint resistance and MG stretch reflexes were measured. MG muscle and tendon lengths were assessed at resting and at maximum dorsiflexion ankle angles using 3D-freehand ultrasound. Treatment effects were compared using non-parametric statistics. Associations between the effects on joint and muscle or tendon lsed dorsiflexion without any changes to the muscle length. This supports the need for further investigation on the effect of the combined treatments and the development of treatments that more effectively lengthen the muscle. Copyright © 2020 Peeters, Van Campenhout, Hanssen, Cenni, Schless, Van den Broeck, Desloovere and Bar-On.Background Intracranial aneurysm wall degradation can be associated with lipid infiltration. However, the relationship between lipid infiltration and aneurysm rupture has not been explored quantitatively. To investigate the correlation between lipid infiltration and aneurysm rupture, we utilized patient-specific simulation of low-density lipoprotein (LDL) transport to analyze lipid infiltration in the cerebral aneurysm wall. Methods Sixty-two aneurysms were analyzed. Patient blood pressure, plasma LDL concentration, and three-dimensional angiographic images were obtained to simulate LDL transport in aneurysms. Morphological, hemodynamic, and lipid accumulation parameters were compared between ruptures and unruptured groups. Multivariate logistic regression was also performed to determine parameters that are independently associated with rupture. Results Size ratio, wall shear stress, low shear area, relative residence time, area-averaged LDL infiltration rate, and maximum LDL infiltration rate were significant parameters in univariate analysis (P less then 0.
Using crosstabulation, DTR allowed identification of PD-MCI patients with an accuracy of 80%. Delayed free and cued recall was associated with decreased GMV and increased MD in multiple fronto-temporal and parietal areas. Conclusion Encoding and retrieval deficits are a main characteristic of PD-MCI and are associated with structural damage in temporal, parietal and prefrontal areas. https://www.selleckchem.com/products/acetalax-oxyphenisatin-acetate.html Copyright © 2020 Horta-Barba, Pagonabarraga, Martínez-Horta, Marín-Lahoz, Sampedro, Fernández-Bobadilla, Botí, Bejr-Kasem, Aracil-Bolaños, Pérez-Pérez, Pascual-Sedano, Campolongo, Izquierdo, Gómez-Ansón and Kulisevsky.Introduction Early magnetic resonance imaging (MRI) provides important information for management and prognosis in patients with severe traumatic brain injury (sTBI). Yet, optimal timing of MRI remains unknown. The aim of our study was to evaluate the safety of early MRI and to identify a method for appropriate patient selection to minimize adverse events related to the intrahospital transport (IHT) and the MRI examination. Methods Twenty-six patients with sTBI [mean Glasgow Coma Scale (GCS) 6, range 3-8] admitted to our neurosurgical ICU from 03/2015 to 12/2017 and receiving at least one MRI within the first 14 days after initial traumatic event were prospectively included in the study. The following requirements were fulfilled for at least 4 h prior to anticipated MRI MAP > 70 mmHg, aPCO2 30-40 mmHg, stable ICP less then 25 mmHg. All relevant cardiopulmonary and cerebral parameters and medication were recorded. The following MRI sequences were performed DWI, FLAIR, 3D T2-space, 3D T1 MPRAGE, 3D SWI, 3D TOF, pASL, and 1H/31P-MRS. Results Four females and 22 males (aged 23-78 years, mean 46.4 years) with a median GCS on admission of 5 (range 3-8) were analyzed. In total, 40 IHTs were performed within the first 14 days (mean 6 days, range 1-14 days). Mean pre-MRI ICP was 14.1 mmHg (range 3-32 mmHg). The mean post-MRI ICP was 14.3 mmHg (range 3-29 mmHg), decreasing to a mean ICP of 13.2 mmHg after 1 h (range 3-29 mmHg). There were no significant differences in ICP measurements before and after MRI (p = 0.30). MAP remained stable with no significant changes during the entire IHT and MRI. No other adverse events were observed as well. Conclusion Early MRI in acute severe TBI is feasible and safe. Yet, careful patient selection with prior adequate testing of cardiopulmonary and cerebral parameters is crucial to minimize transport- or examination-related morbidity. Copyright © 2020 Pinggera, Luger, Bürgler, Bauer, Thomé and Petr.Background Cognitive impairment following a minor stroke or transient ischemic attack (TIA) is common; however, due to diagnostic difficulties, the prevalence and underlying cause of impairment remain poorly defined. We compared cognition in patients after a minor stroke, TIA, or mimic event at three time points in the first year following the event. We examine whether cognitive impairment occurs following these events and whether this impairment differs based on the event type. Further, we measure whether these findings persist after controlling for age, education, and the presence of vascular risk factors and whether the presence of vascular risk factors, independent of event etiology, is associated with cognitive impairment. Lastly, we investigate whether increased stroke risk, as assessed by the ABCD2, is associated with reduced cognition. Methods Medical information, a cognitive screening test, and a measure of executive functioning were collected from 613 patients (123 minor stroke, 175 TIA, and 315 mimular risk factors in these patients. This highlights the importance of long-term management of vascular risk factors beyond event recovery to reduce the risk of cognitive impairment. Increased stroke risk (i.e., ABCD2 score) was also associated with reduced cognition, suggesting that it may be helpful in signaling the need for further cognitive evaluation and intervention post-event. Copyright © 2020 Nicolas, Levi, Evans, Michie, Magin, Quain, Bivard and Karayanidis.Botulinum NeuroToxin-A (BoNT-A) injections to the medial gastrocnemius (MG) and lower-leg casts are commonly combined to treat ankle equinus in children with spastic cerebral palsy (CP). However, the decomposed treatment effects on muscle or tendon structure, stretch reflexes, and joint are unknown. In this study, BoNT-A injections to the MG and casting of the lower legs were applied separately to gain insight into the working mechanisms of the isolated treatments on joint, muscle, and tendon levels. Thirty-one children with spastic CP (GMFCS I-III, age 7.4 ± 2.6 years) received either two weeks of lower-leg casts or MG BoNT-A injections. During full range of motion slow and fast passive ankle rotations, joint resistance and MG stretch reflexes were measured. MG muscle and tendon lengths were assessed at resting and at maximum dorsiflexion ankle angles using 3D-freehand ultrasound. Treatment effects were compared using non-parametric statistics. Associations between the effects on joint and muscle or tendon lsed dorsiflexion without any changes to the muscle length. This supports the need for further investigation on the effect of the combined treatments and the development of treatments that more effectively lengthen the muscle. Copyright © 2020 Peeters, Van Campenhout, Hanssen, Cenni, Schless, Van den Broeck, Desloovere and Bar-On.Background Intracranial aneurysm wall degradation can be associated with lipid infiltration. However, the relationship between lipid infiltration and aneurysm rupture has not been explored quantitatively. To investigate the correlation between lipid infiltration and aneurysm rupture, we utilized patient-specific simulation of low-density lipoprotein (LDL) transport to analyze lipid infiltration in the cerebral aneurysm wall. Methods Sixty-two aneurysms were analyzed. Patient blood pressure, plasma LDL concentration, and three-dimensional angiographic images were obtained to simulate LDL transport in aneurysms. Morphological, hemodynamic, and lipid accumulation parameters were compared between ruptures and unruptured groups. Multivariate logistic regression was also performed to determine parameters that are independently associated with rupture. Results Size ratio, wall shear stress, low shear area, relative residence time, area-averaged LDL infiltration rate, and maximum LDL infiltration rate were significant parameters in univariate analysis (P less then 0.0 Comments 0 Shares 34 Views 0 Reviews -
Conclusion Sleep across all groups was consistent and below national guidelines. Although the survivor group did not have poorer sleep compared to their siblings or matched controls, within the survivor group, those who were diagnosed at an earlier age and those who were further off treatment had more disrupted sleep. Parent reports suggested that survivor siblings may be at risk for sleep problems.Erythropoietin (Epo) provides the major survival signal to maturing erythroid precursors (EPs) and is essential for terminal erythropoiesis. Nonetheless, progenitor cells can irreversibly commit to an erythroid fate well before Epo acts; risking inefficiency if these progenitors are unneeded to maintain red blood cell (RBC) counts. We identified a new modular organization of erythropoiesis and, for the first time, demonstrate that the pre-Epo module is coupled to late Epo-dependent erythropoiesis by megakaryocyte signals. Disrupting megakaryocytic Tgfb1 disorganized hematopoiesis by expanding the pre-Epo pool of progenitor cells and consequently triggering significant apoptosis of Epo-dependent erythroid precursors. Similarly, pharmacologic blockade of TGFβ signaling in normal **** boosted the pre-Epo module leading to apoptosis of Epo-sensitive EPs. Subsequent treatment with low-dose Epo triggered robust RBC production in both models. This work reveals modular regulation of erythropoiesis and offers a new strategy to overcome chronic anemias.Pseudoaneurysm of the internal thoracic artery (ITA) or bleeding from the ITA is an extremely rare complication after cardiovascular surgery via a median sternotomy. Early treatment is needed in the case of massive haemorrhage or a rapidly enlarging pseudoaneurysm. Herein, we present a rare case of a delayed large pseudoaneurysm of the right ITA in a 49-year-old woman with Marfan syndrome who underwent redo aortic root replacement via re-median sternotomy and pacemaker implantation. Diagnostic selective angiography revealed the origin of the pseudoaneurysm, and simultaneous transcatheter embolisation of the ITA was successfully performed. Follow-up computed tomography imaging showed no evidence of contrast media extravasation from the ITA and recurrent extra-pleural haemorrhage. Our findings suggest that postoperative management of patients who have undergone median sternotomy, including cardiovascular surgeries, should also focus on the prevention or early detection of pseudoaneurysm of the ITA to avoid life-threatening conditions.Three patients diagnosed with peri-implant disease after osseointegration exhibited soft tissue oedema and fistulae. Treatment options for controlling the fistulae were investigated. Free subepithelial connective tissue grafts (SCTGs) and microinvasive surgery were used to improve the soft tissue biotype of the patients with fistulae. After SCTG surgery, the fistulae disappeared. The clinical outcomes were stable and aesthetic outcomes were satisfactory after 3-5 years of follow-up. Based on this study, utilising SCTG to improve the tissue biotype may be an effective clinical approach for controlling fistulae occurring during peri-implant disease.Objective To compare the biological characteristics of dental pulp stem cells (DPSCs) and inflamed dental pulp derived stem cells (I-DPSCs) in vitro and their regeneration potential in Beagle immature premolars. Methods Pulpitis was induced in the premolars of one beagle dog by opening the pulp chamber for 2 weeks, and inflammation was histologically confirmed. DPSCs and I-DPSCs were isolated from normal and inflamed dental pulp, and cell morphology, expression of mesenchymal stem cell markers, clone formation ability, cell proliferation and osteogenic/odontogenic differentiation potential were compared. The dental pulp of 20 roots from 10 immature premolars was extracted and divided into two groups. DPSCs or I-DPSCs with scaffolds were transplanted into the root canals. The roots were extracted after 3 months, and pulp regeneration was evaluated by histological analysis. The data were statistically analysed using one-way ANOVA and a Student t test. Results Histological analyses showed lymphocyte infiltration and elevated TNF-α expression, which confirmed the diagnosis of pulpitis. I-DPSCs showed similar morphology, marker gene expression and clone formation ability but greater proliferation ability and osteogenic/odontogenic differentiation potential. Pulp-like tissue formation and bone- and dentine-like tissue deposition were observed in both DPSC- and I-DPSC-transplanted roots. Conclusion DPSCs derived from inflammatory dental pulp tissue have similar biological characteristics to those from normal dental pulp and could mediate pulp and dentine regeneration in immature premolars.Objective To explore the self-assembly and gelation properties of synthetic peptides, and their efficacy on hydroxyapatite (HAP) nucleation and in situ remineralisation of initial caries lesions. Methods Mass spectrometry and reversed-phase high performance liquid chromatography (RPHPLC) were used to confirm the successful synthesis of peptides. Their self-assembly properties and conformation stability were evaluated using circular dichroism (CD) spectroscopy and Fourier-transform infrared spectroscopy (FTIR). Cell Counting Kit-8 (CCK-8; Dojindo, Kumamoto, Japan) was used to evaluate their cytotoxicity. The efficacy of the peptides on HAP nucleation and in situ remineralisation of initial caries lesions was explored using FTIR, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction and transverse microradiography analysis. Results Two kinds of self-assembly β-sheet peptides named ID4 and ID8, respectively, were successfully synthesised with purities greater than 95%. Both were stable under neutral physiological conditions and had low cytotoxicity. ID4 and ID8 showed calcium responsive self-assembly properties and could self-assemble into nanofibres. Compared with ID4, ID8 resulted in the rapid formation of hydrogel with a lower concentration of calcium, and self-assembled ID8 hydrogel induced the formation of flower-like HAP and significantly promoted the remineralisation of initial enamel caries. Conclusion ID8 could serve as the template to induce HAP nucleation and promote biomimetic remineralisation of initial caries lesions. https://www.selleckchem.com/ These results underpin future research on peptide design, and ID8 may be a promising bioactive component for anti-caries applications.
Conclusion Sleep across all groups was consistent and below national guidelines. Although the survivor group did not have poorer sleep compared to their siblings or matched controls, within the survivor group, those who were diagnosed at an earlier age and those who were further off treatment had more disrupted sleep. Parent reports suggested that survivor siblings may be at risk for sleep problems.Erythropoietin (Epo) provides the major survival signal to maturing erythroid precursors (EPs) and is essential for terminal erythropoiesis. Nonetheless, progenitor cells can irreversibly commit to an erythroid fate well before Epo acts; risking inefficiency if these progenitors are unneeded to maintain red blood cell (RBC) counts. We identified a new modular organization of erythropoiesis and, for the first time, demonstrate that the pre-Epo module is coupled to late Epo-dependent erythropoiesis by megakaryocyte signals. Disrupting megakaryocytic Tgfb1 disorganized hematopoiesis by expanding the pre-Epo pool of progenitor cells and consequently triggering significant apoptosis of Epo-dependent erythroid precursors. Similarly, pharmacologic blockade of TGFβ signaling in normal mice boosted the pre-Epo module leading to apoptosis of Epo-sensitive EPs. Subsequent treatment with low-dose Epo triggered robust RBC production in both models. This work reveals modular regulation of erythropoiesis and offers a new strategy to overcome chronic anemias.Pseudoaneurysm of the internal thoracic artery (ITA) or bleeding from the ITA is an extremely rare complication after cardiovascular surgery via a median sternotomy. Early treatment is needed in the case of massive haemorrhage or a rapidly enlarging pseudoaneurysm. Herein, we present a rare case of a delayed large pseudoaneurysm of the right ITA in a 49-year-old woman with Marfan syndrome who underwent redo aortic root replacement via re-median sternotomy and pacemaker implantation. Diagnostic selective angiography revealed the origin of the pseudoaneurysm, and simultaneous transcatheter embolisation of the ITA was successfully performed. Follow-up computed tomography imaging showed no evidence of contrast media extravasation from the ITA and recurrent extra-pleural haemorrhage. Our findings suggest that postoperative management of patients who have undergone median sternotomy, including cardiovascular surgeries, should also focus on the prevention or early detection of pseudoaneurysm of the ITA to avoid life-threatening conditions.Three patients diagnosed with peri-implant disease after osseointegration exhibited soft tissue oedema and fistulae. Treatment options for controlling the fistulae were investigated. Free subepithelial connective tissue grafts (SCTGs) and microinvasive surgery were used to improve the soft tissue biotype of the patients with fistulae. After SCTG surgery, the fistulae disappeared. The clinical outcomes were stable and aesthetic outcomes were satisfactory after 3-5 years of follow-up. Based on this study, utilising SCTG to improve the tissue biotype may be an effective clinical approach for controlling fistulae occurring during peri-implant disease.Objective To compare the biological characteristics of dental pulp stem cells (DPSCs) and inflamed dental pulp derived stem cells (I-DPSCs) in vitro and their regeneration potential in Beagle immature premolars. Methods Pulpitis was induced in the premolars of one beagle dog by opening the pulp chamber for 2 weeks, and inflammation was histologically confirmed. DPSCs and I-DPSCs were isolated from normal and inflamed dental pulp, and cell morphology, expression of mesenchymal stem cell markers, clone formation ability, cell proliferation and osteogenic/odontogenic differentiation potential were compared. The dental pulp of 20 roots from 10 immature premolars was extracted and divided into two groups. DPSCs or I-DPSCs with scaffolds were transplanted into the root canals. The roots were extracted after 3 months, and pulp regeneration was evaluated by histological analysis. The data were statistically analysed using one-way ANOVA and a Student t test. Results Histological analyses showed lymphocyte infiltration and elevated TNF-α expression, which confirmed the diagnosis of pulpitis. I-DPSCs showed similar morphology, marker gene expression and clone formation ability but greater proliferation ability and osteogenic/odontogenic differentiation potential. Pulp-like tissue formation and bone- and dentine-like tissue deposition were observed in both DPSC- and I-DPSC-transplanted roots. Conclusion DPSCs derived from inflammatory dental pulp tissue have similar biological characteristics to those from normal dental pulp and could mediate pulp and dentine regeneration in immature premolars.Objective To explore the self-assembly and gelation properties of synthetic peptides, and their efficacy on hydroxyapatite (HAP) nucleation and in situ remineralisation of initial caries lesions. Methods Mass spectrometry and reversed-phase high performance liquid chromatography (RPHPLC) were used to confirm the successful synthesis of peptides. Their self-assembly properties and conformation stability were evaluated using circular dichroism (CD) spectroscopy and Fourier-transform infrared spectroscopy (FTIR). Cell Counting Kit-8 (CCK-8; Dojindo, Kumamoto, Japan) was used to evaluate their cytotoxicity. The efficacy of the peptides on HAP nucleation and in situ remineralisation of initial caries lesions was explored using FTIR, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction and transverse microradiography analysis. Results Two kinds of self-assembly β-sheet peptides named ID4 and ID8, respectively, were successfully synthesised with purities greater than 95%. Both were stable under neutral physiological conditions and had low cytotoxicity. ID4 and ID8 showed calcium responsive self-assembly properties and could self-assemble into nanofibres. Compared with ID4, ID8 resulted in the rapid formation of hydrogel with a lower concentration of calcium, and self-assembled ID8 hydrogel induced the formation of flower-like HAP and significantly promoted the remineralisation of initial enamel caries. Conclusion ID8 could serve as the template to induce HAP nucleation and promote biomimetic remineralisation of initial caries lesions. https://www.selleckchem.com/ These results underpin future research on peptide design, and ID8 may be a promising bioactive component for anti-caries applications.0 Comments 0 Shares 51 Views 0 Reviews -
Furthermore, musical expertise had a double impact on the connectivity of the music region. First, music tracts were significantly larger in musicians than in non-musicians, associated with marginally higher connectivity to perisylvian music-related areas. Second, the spatial similarity between music and word tracts was significantly increased in musicians, consistently with the increased overlap of language and music functional activations in musicians, as compared to non-musicians. These results support the view that, for music as for words, very specific anatomical connections influence the specialization of distinct VOT areas, and that reciprocally those connections are selectively enhanced by the expertise for word or music reading. Listening to pleasant music engages a complex distributed network including pivotal areas for auditory, reward, emotional and memory processing. On the other hand, frontal theta rhythms appear to be relevant in the process of giving value to music. However, it is not clear to which extent this oscillatory mechanism underlies the brain interactions that characterize music-evoked pleasantness and its related processes. https://www.selleckchem.com/products/triparanol-mer-29.html The goal of the present experiment was to study brain synchronization in this oscillatory band as a function of music-evoked pleasantness. EEG was recorded from 25 healthy subjects while they were listening to music and rating the experienced degree of induced pleasantness. By using a multilevel Bayesian approach we found that phase synchronization in the theta band between right temporal and frontal signals increased with the degree of pleasure experienced by participants. These results show that slow fronto-temporal loops play a key role in music-evoked pleasantness. Event-related potentials (ERP) waveforms are the summation of many overlapping signals. Changes in the peak or mean amplitude of a waveform over a given time period, therefore, cannot reliably be attributed to a particular ERP component of ex ante interest, as is the standard approach to ERP analysis. Though this problem is widely recognized, it is not well addressed in practice. Our approach begins by presuming that any observed ERP waveform - at any electrode, for any trial type, and for any participant - is approximately a weighted combination of signals from an underlying set of what we refer to as principle ERPs, or pERPs. We propose an accessible approach to analyzing complete ERP waveforms in terms of their underlying pERPs. First, we propose the principle ERP reduction (pERP-RED) algorithm for investigators to estimate a suitable set of pERPs from their data, which may span multiple tasks. Next, we provide tools and illustrations of pERP-space analysis, whereby observed ERPs are decomposed into the amplitudes of the contributing pERPs, which can be contrasted across conditions or groups to reveal which pERPs differ (substantively and/or significantly) between conditions/groups. Differences on all pERPs can be reported together rather than selectively, providing complete information on all components in the waveform, thereby avoiding selective reporting or user discretion regarding the choice of which components or windows to use. The scalp distribution of each pERP can also be plotted for any group/condition. We demonstrate this suite of tools through simulations and on real data collected from multiple experiments on participants diagnosed with Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder. Software for conducting these analyses is provided in the pERPred package for R. Tillering is a major determinant of rice plant architecture and grain yield. Here, we report that depletion of rice OsNRPD1a and OsNRPD1b, two orthologs of the largest subunit of RNA polymerase IV, leads to a high-tillering phenotype, in addition to dwarfism and smaller panicles. OsNRPD1a and OsNRPD1b are required for the production of 24-nt small interfering RNAs that direct DNA methylation at transposable elements (TEs) including miniature inverted-repeat TEs (MITEs). Interestingly, many genes are regulated either positively or negatively by TE methylation. Among them, OsMIR156d and OsMIR156j, which promote rice tillering, are repressed by CHH methylation at two MITEs in the promoters. By contrast, D14, which suppresses rice tillering, is activated by CHH methylation at an MITE in its downstream. Our findings reveal regulation of rice tillering by RNA-directed DNA methylation at MITEs and provide potential targets for agronomic trait enhancement through epigenome editing. Protein abundance and localization at the plasma membrane (PM) shapes plant development and mediates adaptation to changing environmental conditions. It is regulated by ubiquitination, a post-translational modification crucial for the proper sorting of endocytosed PM proteins to the vacuole for subsequent degradation. To understand the significance and the variety of roles played by this reversible modification, the function of ubiquitin receptors, which translate the ubiquitin signature into a cellular response, needs to be elucidated. In this study, we show that TOL (TOM1-like) proteins function in plants as multivalent ubiquitin receptors, governing ubiquitinated cargo delivery to the vacuole via the conserved Endosomal Sorting Complex Required for Transport (ESCRT) pathway. TOL2 and TOL6 interact with components of the ESCRT machinery and bind to K63-linked ubiquitin via two tandemly arranged conserved ubiquitin-binding domains. Mutation of these domains results not only in a loss of ubiquitin binding but also altered localization, abolishing TOL6 ubiquitin receptor activity. Function and localization of TOL6 is itself regulated by ubiquitination, whereby TOL6 ubiquitination potentially modulates degradation of PM-localized cargoes, assisting in the fine-tuning of the delicate interplay between protein recycling and downregulation. Taken together, our findings demonstrate the function and regulation of a ubiquitin receptor that mediates vacuolar degradation of PM proteins in higher plants. The ubiquitin-proteasome system (UPS) is an important post-translational regulatory mechanism that controls many cellular functions in eukaryotes. Here, we show that stable expression of P3 protein encoded by Rice grassy stunt virus (RGSV), a negative-strand RNA virus in the Bunyavirales, causes developmental abnormities similar to the disease symptoms caused by RGSV, such as dwarfing and excess tillering, in transgenic rice plants. We found that both transgenic expression of P3 and RGSV infection induce ubiquitination and UPS-dependent degradation of rice NUCLEAR RNA POLYMERASE D1a (OsNRPD1a), one of two orthologs of the largest subunit of plant-specific RNA polymerase IV (Pol IV), which is required for RNA-directed DNA methylation (RdDM). Furthermore, we identified a P3-inducible U-box type E3 ubiquitin ligase, designated as P3-inducible protein 1 (P3IP1), which interacts with OsNRPD1a and mediates its ubiquitination and UPS-dependent degradation in vitro and in vivo. Notably, both knockdown of OsNRPD1 and overexpression of P3IP1 in rice plants induced developmental phenotypes similar to RGSV disease symptomss.
Furthermore, musical expertise had a double impact on the connectivity of the music region. First, music tracts were significantly larger in musicians than in non-musicians, associated with marginally higher connectivity to perisylvian music-related areas. Second, the spatial similarity between music and word tracts was significantly increased in musicians, consistently with the increased overlap of language and music functional activations in musicians, as compared to non-musicians. These results support the view that, for music as for words, very specific anatomical connections influence the specialization of distinct VOT areas, and that reciprocally those connections are selectively enhanced by the expertise for word or music reading. Listening to pleasant music engages a complex distributed network including pivotal areas for auditory, reward, emotional and memory processing. On the other hand, frontal theta rhythms appear to be relevant in the process of giving value to music. However, it is not clear to which extent this oscillatory mechanism underlies the brain interactions that characterize music-evoked pleasantness and its related processes. https://www.selleckchem.com/products/triparanol-mer-29.html The goal of the present experiment was to study brain synchronization in this oscillatory band as a function of music-evoked pleasantness. EEG was recorded from 25 healthy subjects while they were listening to music and rating the experienced degree of induced pleasantness. By using a multilevel Bayesian approach we found that phase synchronization in the theta band between right temporal and frontal signals increased with the degree of pleasure experienced by participants. These results show that slow fronto-temporal loops play a key role in music-evoked pleasantness. Event-related potentials (ERP) waveforms are the summation of many overlapping signals. Changes in the peak or mean amplitude of a waveform over a given time period, therefore, cannot reliably be attributed to a particular ERP component of ex ante interest, as is the standard approach to ERP analysis. Though this problem is widely recognized, it is not well addressed in practice. Our approach begins by presuming that any observed ERP waveform - at any electrode, for any trial type, and for any participant - is approximately a weighted combination of signals from an underlying set of what we refer to as principle ERPs, or pERPs. We propose an accessible approach to analyzing complete ERP waveforms in terms of their underlying pERPs. First, we propose the principle ERP reduction (pERP-RED) algorithm for investigators to estimate a suitable set of pERPs from their data, which may span multiple tasks. Next, we provide tools and illustrations of pERP-space analysis, whereby observed ERPs are decomposed into the amplitudes of the contributing pERPs, which can be contrasted across conditions or groups to reveal which pERPs differ (substantively and/or significantly) between conditions/groups. Differences on all pERPs can be reported together rather than selectively, providing complete information on all components in the waveform, thereby avoiding selective reporting or user discretion regarding the choice of which components or windows to use. The scalp distribution of each pERP can also be plotted for any group/condition. We demonstrate this suite of tools through simulations and on real data collected from multiple experiments on participants diagnosed with Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder. Software for conducting these analyses is provided in the pERPred package for R. Tillering is a major determinant of rice plant architecture and grain yield. Here, we report that depletion of rice OsNRPD1a and OsNRPD1b, two orthologs of the largest subunit of RNA polymerase IV, leads to a high-tillering phenotype, in addition to dwarfism and smaller panicles. OsNRPD1a and OsNRPD1b are required for the production of 24-nt small interfering RNAs that direct DNA methylation at transposable elements (TEs) including miniature inverted-repeat TEs (MITEs). Interestingly, many genes are regulated either positively or negatively by TE methylation. Among them, OsMIR156d and OsMIR156j, which promote rice tillering, are repressed by CHH methylation at two MITEs in the promoters. By contrast, D14, which suppresses rice tillering, is activated by CHH methylation at an MITE in its downstream. Our findings reveal regulation of rice tillering by RNA-directed DNA methylation at MITEs and provide potential targets for agronomic trait enhancement through epigenome editing. Protein abundance and localization at the plasma membrane (PM) shapes plant development and mediates adaptation to changing environmental conditions. It is regulated by ubiquitination, a post-translational modification crucial for the proper sorting of endocytosed PM proteins to the vacuole for subsequent degradation. To understand the significance and the variety of roles played by this reversible modification, the function of ubiquitin receptors, which translate the ubiquitin signature into a cellular response, needs to be elucidated. In this study, we show that TOL (TOM1-like) proteins function in plants as multivalent ubiquitin receptors, governing ubiquitinated cargo delivery to the vacuole via the conserved Endosomal Sorting Complex Required for Transport (ESCRT) pathway. TOL2 and TOL6 interact with components of the ESCRT machinery and bind to K63-linked ubiquitin via two tandemly arranged conserved ubiquitin-binding domains. Mutation of these domains results not only in a loss of ubiquitin binding but also altered localization, abolishing TOL6 ubiquitin receptor activity. Function and localization of TOL6 is itself regulated by ubiquitination, whereby TOL6 ubiquitination potentially modulates degradation of PM-localized cargoes, assisting in the fine-tuning of the delicate interplay between protein recycling and downregulation. Taken together, our findings demonstrate the function and regulation of a ubiquitin receptor that mediates vacuolar degradation of PM proteins in higher plants. The ubiquitin-proteasome system (UPS) is an important post-translational regulatory mechanism that controls many cellular functions in eukaryotes. Here, we show that stable expression of P3 protein encoded by Rice grassy stunt virus (RGSV), a negative-strand RNA virus in the Bunyavirales, causes developmental abnormities similar to the disease symptoms caused by RGSV, such as dwarfing and excess tillering, in transgenic rice plants. We found that both transgenic expression of P3 and RGSV infection induce ubiquitination and UPS-dependent degradation of rice NUCLEAR RNA POLYMERASE D1a (OsNRPD1a), one of two orthologs of the largest subunit of plant-specific RNA polymerase IV (Pol IV), which is required for RNA-directed DNA methylation (RdDM). Furthermore, we identified a P3-inducible U-box type E3 ubiquitin ligase, designated as P3-inducible protein 1 (P3IP1), which interacts with OsNRPD1a and mediates its ubiquitination and UPS-dependent degradation in vitro and in vivo. Notably, both knockdown of OsNRPD1 and overexpression of P3IP1 in rice plants induced developmental phenotypes similar to RGSV disease symptomss.0 Comments 0 Shares 29 Views 0 Reviews
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