Recent Updates

  • The surface and edge chemistry are vital points to assess a specific application of graphene and other carbon nanomaterials. Based on first-principles density functional theory, we investigate twenty-four chemical functional groups containing oxygen and nitrogen atoms anchored to the edges of armchair graphene nanoribbons (AGNRs). Results for the band structures, formation energy, band gaps, electronic charge deficit, oxidation energy, reduction energy, and global hydrophilicity index are analyzed. Among the oxygen functional groups, carbonyl, anhydride, quinone, lactone, phenol, ethyl-ester, carboxyl, α-ester-methyl, and methoxy act as electron-withdrawing groups and, conversely, pyrane, pyrone, and ethoxy act as electron-donating groups. In the case of nitrogen-functional groups, amine, N-p-toluidine, ethylamine, pyridine-N-oxide, pyridone, lactam, and pyridinium transfer electrons to the AGNRs. Nitro, amide, and N-ethylamine act as electron-withdrawing groups. The carbonyl and pyridinium group-AGNRs show metallic behavior. The formation energy calculations revealed that AGNRs with pyridinium, amine, pyrane, carbonyl, and phenol are the most stable structures. https://www.selleckchem.com/products/ABT-263.html In terms of the global hydrophilicity index, the quinone and N-ethylamine groups showed the most significant values, suggesting that they are highly efficient in accepting electrons from other chemical species. The oxidation and reduction energies as a function of the ribbon's width are discussed for AGNRs with quinone, hydroquinone, nitro, and nitro + 2H. Besides, we discuss the effect of nitrogen-doping in AGNRs on the oxidation and reduction energies for the quinone and hydroquinone functional groups.The elucidation of complex electrochemical reaction mechanisms requires advanced models with many intermediate reaction steps, which are governed by a large number of parameters like reaction rate constants and charge transfer coefficients. Overcomplicated models introduce high uncertainty in the choice of the parameters and cannot be used to obtain meaningful insights on the reaction pathway. We describe a new framework of optimal reaction mechanism selection based on the mean-field microkinetic modeling approach (MF-MKM) and adaptive sampling of model parameters. The optimal model is selected to provide both the accurate fitting of experimental data within the experimental error and low uncertainty of model parameters choice. Generally, this approach can be applied for any complex heterogeneous electrochemical reaction. We use the "2e-" electrocatalytic oxygen reduction reaction (ORR) on carbon nanotubes (CNTs) as a representative example of a sufficiently complex reaction. Rotating disk electrode (RDE) experimental data for both ORR in O2-saturated 0.1 M KOH solution and hydrogen peroxide oxidation/reduction reaction (HPRR/HPOR) in Ar-purged 0.1 M KOH solution with different HO2- concentrations were used to show the dependence of the model parameters uniqueness on the completeness of the experimental dataset. It is demonstrated that the optimal reaction mechanism for ORR on CNT and available experimental data consists of O2 adsorption step on the electrode surface and effective step of two-electron reduction to HO2- combined with its desorption from the electrode. The low uncertainty of estimated model parameters is provided only within the 2-step model being applied to the full available experimental dataset. The assessment of elementary step mechanisms on electro-catalytic materials including carbon-based electrodes requires more diverse experimental data and/or higher precision of experimental measurements to facilitate more precise microkinetic modeling of more complex reaction mechanisms.The organization of multiple subcellular compartments is controlled by liquid-liquid phase separation. Phase separation of this type occurs with the emergence of interfacial tension. Aqueous two-phase systems formed by two non-ionic polymers can be used to separate and analyze biological macromolecules, cells and viruses. Phase separation in these systems may serve as the simple model of phase separation in cells also occurring in aqueous media. To better understand liquid-liquid phase separation mechanisms, interfacial tension was measured in aqueous two-phase systems formed by dextran and polyethylene glycol and by polyethylene glycol and sodium sulfate in the presence of different additives. Interfacial tension values depend on differences between the solvent properties of the coexisting phases, estimated experimentally by parameters representing dipole-dipole, ion-dipole, ion-ion, and hydrogen bonding interactions. Based on both current and literature data, we propose a mechanism for phase separation in aqueous two-phase systems. This mechanism is based on the fundamental role of intermolecular forces. Although it remains to be confirmed, it is possible that these may underlie all liquid-liquid phase separation processes in biology.The unique molecular balloon system of [Pd6L8](NO3)12 (an inner cavity of 19 × 21 × 25 Å3⇄ 13 × 13 × 13 Å3) was carried out via the anion exchange of nitrate with alkyl sulfates.We demonstrate the ability of two tripeptides to promote proliferation and modulate the mechanical properties of human mesenchymal stem cells (hMSCs). Notably, Young's modulus of peptide-treated hMSCs was found to be ∼2 fold higher compared to the control group. These peptides promoted wound healing in hMSCs, without stimulating osteogenic and adipogenic differentiation, thus showing high potential in vascular tissue engineering applications.The uncapped tripeptide DPhe-Phe-Leu acts as self-assembly template to yield supramolecular hydrogel biomaterials. As an example, self-assembling DPhe-Phe-Leu-Asp-Val contains the LDV bioadhesive motif for β1 integrin activation. Hydrogels made of the two peptides successfully mimic fibronectin of the extracellular matrix and lead to high cell viability, adhesion, and spreading.Nucleus-targeting NPs based on RuO2 (RuO2NPs) were developed by controlling the size and the surface charge of nanoparticles (NPs). This study not only demonstrates a facile approach for the fabrication of ultrasmall CS-RuO2NPs with good biocompatibility and excellent photothermal properties but also their unique potential for the nucleus-targeted low-temperature PTT.
    The surface and edge chemistry are vital points to assess a specific application of graphene and other carbon nanomaterials. Based on first-principles density functional theory, we investigate twenty-four chemical functional groups containing oxygen and nitrogen atoms anchored to the edges of armchair graphene nanoribbons (AGNRs). Results for the band structures, formation energy, band gaps, electronic charge deficit, oxidation energy, reduction energy, and global hydrophilicity index are analyzed. Among the oxygen functional groups, carbonyl, anhydride, quinone, lactone, phenol, ethyl-ester, carboxyl, α-ester-methyl, and methoxy act as electron-withdrawing groups and, conversely, pyrane, pyrone, and ethoxy act as electron-donating groups. In the case of nitrogen-functional groups, amine, N-p-toluidine, ethylamine, pyridine-N-oxide, pyridone, lactam, and pyridinium transfer electrons to the AGNRs. Nitro, amide, and N-ethylamine act as electron-withdrawing groups. The carbonyl and pyridinium group-AGNRs show metallic behavior. The formation energy calculations revealed that AGNRs with pyridinium, amine, pyrane, carbonyl, and phenol are the most stable structures. https://www.selleckchem.com/products/ABT-263.html In terms of the global hydrophilicity index, the quinone and N-ethylamine groups showed the most significant values, suggesting that they are highly efficient in accepting electrons from other chemical species. The oxidation and reduction energies as a function of the ribbon's width are discussed for AGNRs with quinone, hydroquinone, nitro, and nitro + 2H. Besides, we discuss the effect of nitrogen-doping in AGNRs on the oxidation and reduction energies for the quinone and hydroquinone functional groups.The elucidation of complex electrochemical reaction mechanisms requires advanced models with many intermediate reaction steps, which are governed by a large number of parameters like reaction rate constants and charge transfer coefficients. Overcomplicated models introduce high uncertainty in the choice of the parameters and cannot be used to obtain meaningful insights on the reaction pathway. We describe a new framework of optimal reaction mechanism selection based on the mean-field microkinetic modeling approach (MF-MKM) and adaptive sampling of model parameters. The optimal model is selected to provide both the accurate fitting of experimental data within the experimental error and low uncertainty of model parameters choice. Generally, this approach can be applied for any complex heterogeneous electrochemical reaction. We use the "2e-" electrocatalytic oxygen reduction reaction (ORR) on carbon nanotubes (CNTs) as a representative example of a sufficiently complex reaction. Rotating disk electrode (RDE) experimental data for both ORR in O2-saturated 0.1 M KOH solution and hydrogen peroxide oxidation/reduction reaction (HPRR/HPOR) in Ar-purged 0.1 M KOH solution with different HO2- concentrations were used to show the dependence of the model parameters uniqueness on the completeness of the experimental dataset. It is demonstrated that the optimal reaction mechanism for ORR on CNT and available experimental data consists of O2 adsorption step on the electrode surface and effective step of two-electron reduction to HO2- combined with its desorption from the electrode. The low uncertainty of estimated model parameters is provided only within the 2-step model being applied to the full available experimental dataset. The assessment of elementary step mechanisms on electro-catalytic materials including carbon-based electrodes requires more diverse experimental data and/or higher precision of experimental measurements to facilitate more precise microkinetic modeling of more complex reaction mechanisms.The organization of multiple subcellular compartments is controlled by liquid-liquid phase separation. Phase separation of this type occurs with the emergence of interfacial tension. Aqueous two-phase systems formed by two non-ionic polymers can be used to separate and analyze biological macromolecules, cells and viruses. Phase separation in these systems may serve as the simple model of phase separation in cells also occurring in aqueous media. To better understand liquid-liquid phase separation mechanisms, interfacial tension was measured in aqueous two-phase systems formed by dextran and polyethylene glycol and by polyethylene glycol and sodium sulfate in the presence of different additives. Interfacial tension values depend on differences between the solvent properties of the coexisting phases, estimated experimentally by parameters representing dipole-dipole, ion-dipole, ion-ion, and hydrogen bonding interactions. Based on both current and literature data, we propose a mechanism for phase separation in aqueous two-phase systems. This mechanism is based on the fundamental role of intermolecular forces. Although it remains to be confirmed, it is possible that these may underlie all liquid-liquid phase separation processes in biology.The unique molecular balloon system of [Pd6L8](NO3)12 (an inner cavity of 19 × 21 × 25 Å3⇄ 13 × 13 × 13 Å3) was carried out via the anion exchange of nitrate with alkyl sulfates.We demonstrate the ability of two tripeptides to promote proliferation and modulate the mechanical properties of human mesenchymal stem cells (hMSCs). Notably, Young's modulus of peptide-treated hMSCs was found to be ∼2 fold higher compared to the control group. These peptides promoted wound healing in hMSCs, without stimulating osteogenic and adipogenic differentiation, thus showing high potential in vascular tissue engineering applications.The uncapped tripeptide DPhe-Phe-Leu acts as self-assembly template to yield supramolecular hydrogel biomaterials. As an example, self-assembling DPhe-Phe-Leu-Asp-Val contains the LDV bioadhesive motif for β1 integrin activation. Hydrogels made of the two peptides successfully mimic fibronectin of the extracellular matrix and lead to high cell viability, adhesion, and spreading.Nucleus-targeting NPs based on RuO2 (RuO2NPs) were developed by controlling the size and the surface charge of nanoparticles (NPs). This study not only demonstrates a facile approach for the fabrication of ultrasmall CS-RuO2NPs with good biocompatibility and excellent photothermal properties but also their unique potential for the nucleus-targeted low-temperature PTT.
    0 Comments 0 Shares 1 Views 0 Reviews

  • Black carbon (**) is a substance that significantly affects the migration and transformation of hydrophobic organic compounds (HOCs) in soil/sediment. High-temperature ** is an important form of ** in the environment, and, currently, there is relatively little research on the influence of high-temperature ** on the sorption and the desorption behavior of HOCs and its mechanism. In this study, the sorption isotherms and TENAX-aided desorption kinetics of PCB1 by three typical high-temperature BCs (fly ash (FC), soot (SC), and high-temperature biochar (** 900)) and a low-temperature biochar (** 400) were compared. In addition, the sorption-desorption mechanism was clarified through its correlation with the physicochemical properties of **. The results indicated that the Freundlich sorption parameters of FC, SC, ** 900, and ** 400 were 9947.90, 5417.57, 77690.16, and 2804.54 (mg kg-1)/(mg L-1), respectively, indicating that these high-temperature BCs had stronger sorption capacity. The desorption rate of PCB1 on ** 900 was slow, and the ratio of the difficult desorption fraction (Fr) was as high as 96.2%, while those of FC, SC, and ** 400 were only 35.3%, 19.1%, and 54.7%, respectively. The sorption and desorption mechanisms of the three high-temperature BCs were similar to those of ** 400. They exhibited nonlinear adsorption at low PCB1 concentrations and linear partition at high PCB1 concentrations. Moreover, the results demonstrated that different types of high-temperature BCs in the environment have different sequestration effects on HOCs. Frap, the part that can be quickly desorbed, was predominantly PCB1 sorbed onto ** through a linear partition mechanism, but the surface acidic functional groups and larger pores would also increase the Frap. https://www.selleckchem.com/products/irpagratinib.html Meanwhile, the slow desorption ratio (Fslow) was mainly affected by the degree of surface aromatization; the difficult-to-desorb PCB1 (Fr) was combined with ** through a nonlinear adsorption mechanism and was mainly related to the micropore volume. Graphical abstract.In the context of the continued increased global uptake of fingerprinting procedures to explore fluvial sediment sources, far less attention has been paid to dust source tracing and especially using different particle size fractions and low-cost tracers such as colour and magnetic susceptibility. The objective of this study, therefore, was to apportion local dust storm source contributions for the less then 63-μm and 63-125-μm fractions of dust samples in a case study in central Iran. Colour and magnetic susceptibility properties were measured on 62 source samples and six dust storm samples. Statistical methods were used to select four different composite fingerprints for discriminating the dust sediment sources. These statistical approaches comprised (1) the Kruskal-Wallis H test (KW-H), (2) a combination of KW-H and discriminant function analysis (DFA), (3) a combination of KW-H and principal components and classification analysis (PCCA), and (4) a combination of KW-H and a general classification and regrwith a corresponding mean value of 9.4%). The equivalent estimates for the 63-125-μm fraction were 1.2-20.1% (8.3%). The findings clearly demonstrate that colour and magnetic susceptibility tracers offer low-cost options for apportioning dust sources.In this study, we evaluated the possible effects of sequenced pulsed magnetic fields (PMF) of 1-mT treatments with designed different frequencies (PMF-1-1, 3, 5, 7 Hz or PMF-2-7, 9, 12, 14 Hz) on the inflammatory signs such as abnormal pain behaviors, hyperalgesia and allodynia, edema, and fever in carrageenan (CG)-induced hind paw inflammation model in rats. Paw tissues were also histologically examined. PMF exposure was applied 3 times in 24 h. CG injection gradually decreased the thermal latencies and mechanical threshold and caused significant increases in temperature and mass of paw. PMF treatments significantly reduced the temperature and mass in the paw of rats with inflammation. PMF-1 treatments caused significant increases in the latencies and thresholds. However, administration of PMF-2 treatment was significantly decreased the latency and threshold. Furthermore, the histological pieces of evidence also suggested the anti-inflammatory effects of PMF-1 treatments or inflammatory actions of PMF-2 treatments. Findings presented in this paper suggest that 1-mT PMF treatments may have anti-edematous and antipyretics activities in inflamed rats. However, the effects of PMF treatments on abnormal pain hypersensitivities may be different. PMF treatments may make inflammatory pain relief or worse in inflamed rats depending on the PMF frequencies in sequence.Heavy metal contamination of river water has become a major issue affecting environmental and human health worldwide. This study makes an effort to observe the heavy metal incidence of River Brahmaputra, India, and its river restoration assessment for 2 years, 2017-2018 and 2018-2019. River Brahmaputra is the second longest and a major transboundary river of the South Asian region, which transcends the political boundaries of China, India and Bangladesh. The Pearson correlation analysis was used to analyse the interrelationships between physico-chemical parameters (which was also analysed during our study) and heavy metals. Heavy metal pollution index and multivariate analyses such as hierarchical cluster analysis and principal component analysis were used to establish our scientific observations. An assessment involving people's willingness to pay for river restoration was also done. Arsenic (As), lead (Pb), antimony (Sb), nickel (Ni), chromium (Cr), mercury (Hg) and cadmium (Cd) were monitored in three state Brahmaputra river and citizens willingness to contribute towards restoring its water quality, the need for an appropriate river restoration strategy and water policy is strongly felt as an outcome of this study.In practical conditions, the remediation efficiency is always very limited due to the rapid aggregation and deactivation of nanoscale zero-valent iron (nZVI). Porous SiO2-coated technology can effectively suppress the agglomeration and oxidation of nZVI particle, resulting in the excellent dispersion and stability in water. A series of characterization results show that the porous SiO2-coated Fe0 (Fe0@p-SiO2) was a core-shell structure composite, with Fe0 as the core and the porous SiO2 as the shell. Moreover, the prepared composite material has a large specific surface area (244.04 m2/g). The experiments of nitrobenzene (NB) reduction and one-dimensional simulation column indicated that the different amounts of NaOH in the preparation process lead to the different structures, shapes, and particle sizes of prepared composite materials, which have significant effects on its activity and transportability. Under the conditions investigated, the optimum ratio of Fe0@p-SiO2 synthesis was nFe3+n(Tetraethoxy silane, TEOS)nNaOH = 11.
    Black carbon (BC) is a substance that significantly affects the migration and transformation of hydrophobic organic compounds (HOCs) in soil/sediment. High-temperature BC is an important form of BC in the environment, and, currently, there is relatively little research on the influence of high-temperature BC on the sorption and the desorption behavior of HOCs and its mechanism. In this study, the sorption isotherms and TENAX-aided desorption kinetics of PCB1 by three typical high-temperature BCs (fly ash (FC), soot (SC), and high-temperature biochar (BC 900)) and a low-temperature biochar (BC 400) were compared. In addition, the sorption-desorption mechanism was clarified through its correlation with the physicochemical properties of BC. The results indicated that the Freundlich sorption parameters of FC, SC, BC 900, and BC 400 were 9947.90, 5417.57, 77690.16, and 2804.54 (mg kg-1)/(mg L-1), respectively, indicating that these high-temperature BCs had stronger sorption capacity. The desorption rate of PCB1 on BC 900 was slow, and the ratio of the difficult desorption fraction (Fr) was as high as 96.2%, while those of FC, SC, and BC 400 were only 35.3%, 19.1%, and 54.7%, respectively. The sorption and desorption mechanisms of the three high-temperature BCs were similar to those of BC 400. They exhibited nonlinear adsorption at low PCB1 concentrations and linear partition at high PCB1 concentrations. Moreover, the results demonstrated that different types of high-temperature BCs in the environment have different sequestration effects on HOCs. Frap, the part that can be quickly desorbed, was predominantly PCB1 sorbed onto BC through a linear partition mechanism, but the surface acidic functional groups and larger pores would also increase the Frap. https://www.selleckchem.com/products/irpagratinib.html Meanwhile, the slow desorption ratio (Fslow) was mainly affected by the degree of surface aromatization; the difficult-to-desorb PCB1 (Fr) was combined with BC through a nonlinear adsorption mechanism and was mainly related to the micropore volume. Graphical abstract.In the context of the continued increased global uptake of fingerprinting procedures to explore fluvial sediment sources, far less attention has been paid to dust source tracing and especially using different particle size fractions and low-cost tracers such as colour and magnetic susceptibility. The objective of this study, therefore, was to apportion local dust storm source contributions for the less then 63-μm and 63-125-μm fractions of dust samples in a case study in central Iran. Colour and magnetic susceptibility properties were measured on 62 source samples and six dust storm samples. Statistical methods were used to select four different composite fingerprints for discriminating the dust sediment sources. These statistical approaches comprised (1) the Kruskal-Wallis H test (KW-H), (2) a combination of KW-H and discriminant function analysis (DFA), (3) a combination of KW-H and principal components and classification analysis (PCCA), and (4) a combination of KW-H and a general classification and regrwith a corresponding mean value of 9.4%). The equivalent estimates for the 63-125-μm fraction were 1.2-20.1% (8.3%). The findings clearly demonstrate that colour and magnetic susceptibility tracers offer low-cost options for apportioning dust sources.In this study, we evaluated the possible effects of sequenced pulsed magnetic fields (PMF) of 1-mT treatments with designed different frequencies (PMF-1-1, 3, 5, 7 Hz or PMF-2-7, 9, 12, 14 Hz) on the inflammatory signs such as abnormal pain behaviors, hyperalgesia and allodynia, edema, and fever in carrageenan (CG)-induced hind paw inflammation model in rats. Paw tissues were also histologically examined. PMF exposure was applied 3 times in 24 h. CG injection gradually decreased the thermal latencies and mechanical threshold and caused significant increases in temperature and mass of paw. PMF treatments significantly reduced the temperature and mass in the paw of rats with inflammation. PMF-1 treatments caused significant increases in the latencies and thresholds. However, administration of PMF-2 treatment was significantly decreased the latency and threshold. Furthermore, the histological pieces of evidence also suggested the anti-inflammatory effects of PMF-1 treatments or inflammatory actions of PMF-2 treatments. Findings presented in this paper suggest that 1-mT PMF treatments may have anti-edematous and antipyretics activities in inflamed rats. However, the effects of PMF treatments on abnormal pain hypersensitivities may be different. PMF treatments may make inflammatory pain relief or worse in inflamed rats depending on the PMF frequencies in sequence.Heavy metal contamination of river water has become a major issue affecting environmental and human health worldwide. This study makes an effort to observe the heavy metal incidence of River Brahmaputra, India, and its river restoration assessment for 2 years, 2017-2018 and 2018-2019. River Brahmaputra is the second longest and a major transboundary river of the South Asian region, which transcends the political boundaries of China, India and Bangladesh. The Pearson correlation analysis was used to analyse the interrelationships between physico-chemical parameters (which was also analysed during our study) and heavy metals. Heavy metal pollution index and multivariate analyses such as hierarchical cluster analysis and principal component analysis were used to establish our scientific observations. An assessment involving people's willingness to pay for river restoration was also done. Arsenic (As), lead (Pb), antimony (Sb), nickel (Ni), chromium (Cr), mercury (Hg) and cadmium (Cd) were monitored in three state Brahmaputra river and citizens willingness to contribute towards restoring its water quality, the need for an appropriate river restoration strategy and water policy is strongly felt as an outcome of this study.In practical conditions, the remediation efficiency is always very limited due to the rapid aggregation and deactivation of nanoscale zero-valent iron (nZVI). Porous SiO2-coated technology can effectively suppress the agglomeration and oxidation of nZVI particle, resulting in the excellent dispersion and stability in water. A series of characterization results show that the porous SiO2-coated Fe0 (Fe0@p-SiO2) was a core-shell structure composite, with Fe0 as the core and the porous SiO2 as the shell. Moreover, the prepared composite material has a large specific surface area (244.04 m2/g). The experiments of nitrobenzene (NB) reduction and one-dimensional simulation column indicated that the different amounts of NaOH in the preparation process lead to the different structures, shapes, and particle sizes of prepared composite materials, which have significant effects on its activity and transportability. Under the conditions investigated, the optimum ratio of Fe0@p-SiO2 synthesis was nFe3+n(Tetraethoxy silane, TEOS)nNaOH = 11.
    0 Comments 0 Shares 1 Views 0 Reviews

  • The pRb-E2F pathway is a critical point of regulation in the cell cycle and loss of control of the pathway is a hallmark of cancer. E2F1 is the major target through which pRb exerts its effects and arginine methylation by PRMT5 plays a key role in dictating E2F1 activity. Here we have explored the functional role of the PRMT5-E2F1 axis and highlight its influence on different aspects of cancer cell biology including viability, migration, invasion and adherence. Through a genome-wide expression analysis, we identified a distinct set of genes under the control of PRMT5 and E2F1, including some highly regulated genes, which influence cell migration, invasio and adherence through a PRMT5-dependent mechanism. Most significantly, a coincidence was apparent between the expression of PRMT5 and E2F1 in human tumours, and elevated levels of PRMT5 and E2F1 correlated with poor prognosis disease. Our results suggest a causal relationship between PRMT5 and E2F1 in driving the malignant phenotype and thereby highlight an important pathway for therapeutic intervention.The aim of this review is to summarize evidence regarding rat emotional experiences during carbon dioxide (CO2) exposure. The studies reviewed show that CO2 exposure is aversive to rats, and that rats respond to CO2 exposure with active and passive defense behaviors. Plasma corticosterone and bradycardia increased in rats exposed to CO2. As with anxiogenic drugs, responses to CO2 are counteracted by the administration of anxiolytics, SRIs, and SSRI's. Human studies reviewed indicate that, when inhaling CO2, humans experience feelings of anxiety fear and panic, and that administration of benzodiazepines, serotonin precursors, and SSRIs ameliorate these feelings. In vivo and in vitro rat studies reviewed show that brain regions, ion channels, and neurotransmitters involved in negative emotional responses are activated by hypercapnia and acidosis associated with CO2 exposure. On the basis of the behavioral, physiological, and neurobiological evidence reviewed, we conclude that CO2 elicits negative emotions in rats.Most people's cognitive abilities decline with age, with significant and partly genetically driven, individual differences in rate of change. Although APOE É›4 and genetic scores for late-onset Alzheimer's disease (LOAD) have been related to cognitive decline during preclinical stages of dementia, there is limited knowledge concerning genetic factors implied in normal cognitive aging. In the present study, we examined three potential genetic predictors of age-related cognitive decline as follows (1) the APOE É›4 allele, (2) a polygenic score for general cognitive ability (PGS-cog), and (3) a polygenic risk score for late-onset AD (PRS-LOAD). We examined up to six time points of cognitive measurements in the longitudinal population-based Betula study, covering a 25-year follow-up period. Only participants that remained alive and non-demented until the most recent dementia screening (1-3 years after the last test occasion) were included (n = 1087). Individual differences in rate of cognitive change (composite score) were predicted by the PRS-LOAD and APOE É›4, but not by PGS-cog. To control for the possibility that the results reflected a preclinical state of Alzheimer's disease in some participants, we re-ran the analyses excluding cognitive data from the last test occasion to model cognitive change up-until a minimum of 6 years before potential onset of clinical Alzheimers. Strikingly, the association of PRS-LOAD, but not APOE É›4, with cognitive change remained. The results indicate that PRS-LOAD predicts individual difference in rate of cognitive decline in normal aging, but it remains to be determined to what extent this reflects preclinical Alzheimer's disease brain pathophysiology and subsequent risk to develop the disease.Esophageal squamous cell carcinoma (ESCC) is prevalent in some geographical regions of the world. ESCC development presents a multistep pathogenic process from inflammation to invasive cancer; however, what is critical in these processes and how they evolve is largely unknown, obstructing early diagnosis and effective treatment. Here, we create a mouse model mimicking human ESCC development and construct a single-cell ESCC developmental atlas. We identify a set of key transitional signatures associated with oncogenic evolution of epithelial cells and depict the landmark dynamic tumorigenic trajectories. An early downregulation of CD8+ response against the initial tissue damage accompanied by the transition of immune response from type 1 to type 3 results in accumulation and activation of macrophages and neutrophils, which may create a chronic inflammatory environment that promotes carcinogen-transformed epithelial cell survival and proliferation. These findings shed light on how ESCC is initiated and developed.Cryo-electron tomography combined with subtomogram averaging (StA) has yielded high-resolution structures of macromolecules in their native context. However, high-resolution StA is not commonplace due to beam-induced sample drift, images with poor signal-to-noise ratios (SNR), challenges in CTF correction, and limited particle number. Here we address these issues by collecting tilt series with a higher electron dose at the zero-degree tilt. Particles of interest are then located within reconstructed tomograms, processed by conventional StA, and then re-extracted from the high-dose images in 2D. Single particle analysis tools are then applied to refine the 2D particle alignment and generate a reconstruction. Use of our hybrid StA (hStA) workflow improved the resolution for tobacco mosaic virus from 7.2 to 4.4 Å and for the ion channel RyR1 in crowded native membranes from 12.9 to 9.1 Å. These resolution gains make hStA a promising approach for other StA projects aimed at achieving subnanometer resolution.Metal hydrides have been rarely used in biomedicine. Herein, we fabricate titanium hydride (TiH1.924) nanodots from its powder form via the liquid-phase exfoliation, and apply these metal hydride nanodots for effective cancer treatment. The liquid-phase exfoliation is an effective method to synthesize these metal hydride nanomaterials, and its efficiency is determined by the matching of surface energy between the solvent and the metal hydrides. The obtained TiH1.924 nanodots can produce reactive oxygen species (ROS) under ultrasound, presenting a highly efficient sono-sensitizing effect. Meanwhile, TiH1.924 nanodots with strong near-infrared (NIR) absorbance can serve as a robust photothermal agent. By using the mild photothermal effect to enhance intra-tumoral blood flow and improve tumor oxygenation, a remarkable synergistic therapeutic effect is achieved in the combined photothermal-sonodynamic therapy. https://www.selleckchem.com/products/crenolanib-cp-868596.html Importantly, most of these TiH1.924 nanodots can be cleared out from the body. This work presents the promises of functional metal hydride nanomaterials for biomedical applications.
    The pRb-E2F pathway is a critical point of regulation in the cell cycle and loss of control of the pathway is a hallmark of cancer. E2F1 is the major target through which pRb exerts its effects and arginine methylation by PRMT5 plays a key role in dictating E2F1 activity. Here we have explored the functional role of the PRMT5-E2F1 axis and highlight its influence on different aspects of cancer cell biology including viability, migration, invasion and adherence. Through a genome-wide expression analysis, we identified a distinct set of genes under the control of PRMT5 and E2F1, including some highly regulated genes, which influence cell migration, invasio and adherence through a PRMT5-dependent mechanism. Most significantly, a coincidence was apparent between the expression of PRMT5 and E2F1 in human tumours, and elevated levels of PRMT5 and E2F1 correlated with poor prognosis disease. Our results suggest a causal relationship between PRMT5 and E2F1 in driving the malignant phenotype and thereby highlight an important pathway for therapeutic intervention.The aim of this review is to summarize evidence regarding rat emotional experiences during carbon dioxide (CO2) exposure. The studies reviewed show that CO2 exposure is aversive to rats, and that rats respond to CO2 exposure with active and passive defense behaviors. Plasma corticosterone and bradycardia increased in rats exposed to CO2. As with anxiogenic drugs, responses to CO2 are counteracted by the administration of anxiolytics, SRIs, and SSRI's. Human studies reviewed indicate that, when inhaling CO2, humans experience feelings of anxiety fear and panic, and that administration of benzodiazepines, serotonin precursors, and SSRIs ameliorate these feelings. In vivo and in vitro rat studies reviewed show that brain regions, ion channels, and neurotransmitters involved in negative emotional responses are activated by hypercapnia and acidosis associated with CO2 exposure. On the basis of the behavioral, physiological, and neurobiological evidence reviewed, we conclude that CO2 elicits negative emotions in rats.Most people's cognitive abilities decline with age, with significant and partly genetically driven, individual differences in rate of change. Although APOE É›4 and genetic scores for late-onset Alzheimer's disease (LOAD) have been related to cognitive decline during preclinical stages of dementia, there is limited knowledge concerning genetic factors implied in normal cognitive aging. In the present study, we examined three potential genetic predictors of age-related cognitive decline as follows (1) the APOE É›4 allele, (2) a polygenic score for general cognitive ability (PGS-cog), and (3) a polygenic risk score for late-onset AD (PRS-LOAD). We examined up to six time points of cognitive measurements in the longitudinal population-based Betula study, covering a 25-year follow-up period. Only participants that remained alive and non-demented until the most recent dementia screening (1-3 years after the last test occasion) were included (n = 1087). Individual differences in rate of cognitive change (composite score) were predicted by the PRS-LOAD and APOE É›4, but not by PGS-cog. To control for the possibility that the results reflected a preclinical state of Alzheimer's disease in some participants, we re-ran the analyses excluding cognitive data from the last test occasion to model cognitive change up-until a minimum of 6 years before potential onset of clinical Alzheimers. Strikingly, the association of PRS-LOAD, but not APOE É›4, with cognitive change remained. The results indicate that PRS-LOAD predicts individual difference in rate of cognitive decline in normal aging, but it remains to be determined to what extent this reflects preclinical Alzheimer's disease brain pathophysiology and subsequent risk to develop the disease.Esophageal squamous cell carcinoma (ESCC) is prevalent in some geographical regions of the world. ESCC development presents a multistep pathogenic process from inflammation to invasive cancer; however, what is critical in these processes and how they evolve is largely unknown, obstructing early diagnosis and effective treatment. Here, we create a mouse model mimicking human ESCC development and construct a single-cell ESCC developmental atlas. We identify a set of key transitional signatures associated with oncogenic evolution of epithelial cells and depict the landmark dynamic tumorigenic trajectories. An early downregulation of CD8+ response against the initial tissue damage accompanied by the transition of immune response from type 1 to type 3 results in accumulation and activation of macrophages and neutrophils, which may create a chronic inflammatory environment that promotes carcinogen-transformed epithelial cell survival and proliferation. These findings shed light on how ESCC is initiated and developed.Cryo-electron tomography combined with subtomogram averaging (StA) has yielded high-resolution structures of macromolecules in their native context. However, high-resolution StA is not commonplace due to beam-induced sample drift, images with poor signal-to-noise ratios (SNR), challenges in CTF correction, and limited particle number. Here we address these issues by collecting tilt series with a higher electron dose at the zero-degree tilt. Particles of interest are then located within reconstructed tomograms, processed by conventional StA, and then re-extracted from the high-dose images in 2D. Single particle analysis tools are then applied to refine the 2D particle alignment and generate a reconstruction. Use of our hybrid StA (hStA) workflow improved the resolution for tobacco mosaic virus from 7.2 to 4.4 Å and for the ion channel RyR1 in crowded native membranes from 12.9 to 9.1 Å. These resolution gains make hStA a promising approach for other StA projects aimed at achieving subnanometer resolution.Metal hydrides have been rarely used in biomedicine. Herein, we fabricate titanium hydride (TiH1.924) nanodots from its powder form via the liquid-phase exfoliation, and apply these metal hydride nanodots for effective cancer treatment. The liquid-phase exfoliation is an effective method to synthesize these metal hydride nanomaterials, and its efficiency is determined by the matching of surface energy between the solvent and the metal hydrides. The obtained TiH1.924 nanodots can produce reactive oxygen species (ROS) under ultrasound, presenting a highly efficient sono-sensitizing effect. Meanwhile, TiH1.924 nanodots with strong near-infrared (NIR) absorbance can serve as a robust photothermal agent. By using the mild photothermal effect to enhance intra-tumoral blood flow and improve tumor oxygenation, a remarkable synergistic therapeutic effect is achieved in the combined photothermal-sonodynamic therapy. https://www.selleckchem.com/products/crenolanib-cp-868596.html Importantly, most of these TiH1.924 nanodots can be cleared out from the body. This work presents the promises of functional metal hydride nanomaterials for biomedical applications.
    0 Comments 0 Shares 1 Views 0 Reviews

  • Setting the condylar inclination of a dental articulator enables the delivery of prostheses without occlusal interferences. This technique article describes obtaining the sagittal condylar inclination (SCI) by using a facial and an intraoral scan of the protrusive interocclusal position. The SCI can be used on a virtual articulator in dental computer-aided design (***) software programs, which can facilitate the fabrication of functional prostheses without occlusal interferences. BACKGROUND We aimed to investigate possible causes of leukoplakia and squamous cell carcinoma. We particularly sought to characterize the effect of smoking history because leukoplakia has been observed in nonsmokers. METHODS We retrospectively identified patients with a diagnosis of leukoplakia who were treated at Mayo Clinic (Jacksonville, Florida), in the Department of Otorhinolaryngology, from 1/1/2006 through 8/31/2019. Each patient was age- and sex-matched (12 ratio) to control patients without leukoplakia. Information about possible risk factors, chief symptoms, and social history with smoking and alcohol use was obtained from health records. Nine risk factors were analyzed independently with multivariate analysis. Continuous risk factors were compared between cases and controls with the Wilcoxon rank sum test; categorical variables were compared with the χ2 test. RESULTS The final cohort consisted of 72 patients with leukoplakia (mean [SD] age, 66 [11] years; 61 men [85%]) and 144 age- and sex-matched controls. Compared with the control group, significantly more cases were current smokers (26% vs. 5%) and fewer were never-smokers. (17% vs. 51%) (P 0.99). When assessing never-smokers and those who had not smoked for more than 25 years, a history of smoking (P = 0.002) and the number of years smoked (P = 0.002) were significantly different for cases and controls. CONCLUSION Most vocal fold leukoplakia lesions have a low risk of malignancy. It is important to evaluate the characteristics of the lesion and assess the patient's risk factors. Follow-up is a key factor in patient management, but for patients with recurrent leukoplakia, the duration and frequency of surveillance is still controversial and varies among medical centers. Future prospective studies with advanced analyses are warranted because they may strengthen the ability to identify clinical factors that influence the development of squamous cell carcinoma. Published by Elsevier Inc.Substance P (SP) is an 11-amino acid tachykinin-related peptide that has anorexigenic effects in birds and mammals although the central mechanism is not well understood. Hence, the objective was to identify appetite-associated hypothalamic mechanisms in Japanese quail (Coturnix japonica). Seven days post-hatch, quail were intracerebroventricularly injected with 0, 0.25, 0.5 or 1.0 nmol of SP and monitored for 180 min. On a cumulative basis, quail that received 0.5 and 1.0 nmol of SP consumed less food for 90 min post-injection. On a non-cumulative basis, food intake was reduced in 0.5 nmol-injected birds at 30 min post-injection. https://www.selleckchem.com/products/epacadostat-incb024360.html Water intake was not affected. A comprehensive behavior analysis was performed, revealing that SP-injected chicks displayed less feeding pecks and reduced locomotion compared to vehicle-injected birds. To identify molecular mechanisms, the hypothalamus was isolated at 1 h post-injection and real-time PCR was performed to measure mRNA. Agouti-related peptide (AgRP) mRNA was reduced in SP-injected chicks. Immunohistochemistry was used to quantify c-Fos-expressing cells in appetite-associated hypothalamic nuclei. There were more reactive cells in the lateral hypothalamus (LH) and the paraventricular nucleus (PVN) of SP- than vehicle-injected chicks. The LH and PVN were collected for gene expression analysis. Corticotropin-releasing factor (CRF) and urotensin 2 (UTS2) mRNAs were greater in SP- than vehicle-injected chicks in the PVN. In the LH, CRF receptor sub-type 2 (CRFR2) mRNA was greater and kappa opioid receptor mRNA was reduced in SP- compared to vehicle-injected quail. Thus, SP induces a potent anorexia in quail that coincides with increased LH-specific CRFR2 mRNA and increased UTS2 mRNA in the PVN. Future studies will evaluate whether SP-induced anorexigenic effects are mediated through CRF receptors. BACKGROUND Effects of clinical practice changes on ICU delirium are not well understood. OBJECTIVES Determine ICU delirium rates over time. METHODS Data from a previously described screening cohort of the Pharmacological Management of Delirium trial was analyzed. Richmond Agitation-Sedation Scale (RASS) and Confusion Assessment Method for the ICU (CAM-ICU) were assessed twice daily. We defined Any delirium (positive CAM-ICU at any time during ICU stay) and ICU-acquired delirium (1st CAM-ICU negative with a subsequent positive CAM-ICU). Mixed-effects logistic regression models were used to test for differences. RESULTS 2742 patient admissions were included. Delirium occurred in 16.5%, any delirium decreased [22.7% to 10.2% (p  less then  0.01)], and ICU-acquired delirium decreased [8.4% to 4.4% (p = 0.01)]. Coma decreased from 24% to 17.4% (p = 0.04). Later ICU years and higher mean RASS scores were associated with lower odds of delirium. CONCLUSIONS Delirium rates were not explained by the measured variables and further prospective research is needed. BACKGROUNDS The still high poor outcome of ARDS may be more consequence of circulatory failure than hypoxemia per se. For patients with circulatory failure and ARDS, hemodynamic instability is directly related to ARDS following pulmonary circulation dysfunction and its consequence - right ventricular (RV) dysfunction. OBJECTIVES We hypothesize that in the era of protective ventilation, echocardiographic abnormalities did not parallel ARDS severity, defined by the degree of hypoxemia. METHODS We included 63 consecutively identified mechanically ventilated ARDS patients (1st January 2015 to 31th December 2016). All had echocardiography performed routinely within the first 12 h after ICU admission. RESULTS The analysis included 110 exams. Twenty-eight patients had severe ARDS (28/63, 44.4%), 27 had moderate ARDS (27/63, 42.1%) and 8 mild ARDS (8/63, 12.7%).There was no difference in echocardiographic findings between mild-moderate and severe ARDS. At Pearson's linear regression analysis, TAPSE was directly correlated with LVEF (r = 0.
    Setting the condylar inclination of a dental articulator enables the delivery of prostheses without occlusal interferences. This technique article describes obtaining the sagittal condylar inclination (SCI) by using a facial and an intraoral scan of the protrusive interocclusal position. The SCI can be used on a virtual articulator in dental computer-aided design (CAD) software programs, which can facilitate the fabrication of functional prostheses without occlusal interferences. BACKGROUND We aimed to investigate possible causes of leukoplakia and squamous cell carcinoma. We particularly sought to characterize the effect of smoking history because leukoplakia has been observed in nonsmokers. METHODS We retrospectively identified patients with a diagnosis of leukoplakia who were treated at Mayo Clinic (Jacksonville, Florida), in the Department of Otorhinolaryngology, from 1/1/2006 through 8/31/2019. Each patient was age- and sex-matched (12 ratio) to control patients without leukoplakia. Information about possible risk factors, chief symptoms, and social history with smoking and alcohol use was obtained from health records. Nine risk factors were analyzed independently with multivariate analysis. Continuous risk factors were compared between cases and controls with the Wilcoxon rank sum test; categorical variables were compared with the χ2 test. RESULTS The final cohort consisted of 72 patients with leukoplakia (mean [SD] age, 66 [11] years; 61 men [85%]) and 144 age- and sex-matched controls. Compared with the control group, significantly more cases were current smokers (26% vs. 5%) and fewer were never-smokers. (17% vs. 51%) (P 0.99). When assessing never-smokers and those who had not smoked for more than 25 years, a history of smoking (P = 0.002) and the number of years smoked (P = 0.002) were significantly different for cases and controls. CONCLUSION Most vocal fold leukoplakia lesions have a low risk of malignancy. It is important to evaluate the characteristics of the lesion and assess the patient's risk factors. Follow-up is a key factor in patient management, but for patients with recurrent leukoplakia, the duration and frequency of surveillance is still controversial and varies among medical centers. Future prospective studies with advanced analyses are warranted because they may strengthen the ability to identify clinical factors that influence the development of squamous cell carcinoma. Published by Elsevier Inc.Substance P (SP) is an 11-amino acid tachykinin-related peptide that has anorexigenic effects in birds and mammals although the central mechanism is not well understood. Hence, the objective was to identify appetite-associated hypothalamic mechanisms in Japanese quail (Coturnix japonica). Seven days post-hatch, quail were intracerebroventricularly injected with 0, 0.25, 0.5 or 1.0 nmol of SP and monitored for 180 min. On a cumulative basis, quail that received 0.5 and 1.0 nmol of SP consumed less food for 90 min post-injection. On a non-cumulative basis, food intake was reduced in 0.5 nmol-injected birds at 30 min post-injection. https://www.selleckchem.com/products/epacadostat-incb024360.html Water intake was not affected. A comprehensive behavior analysis was performed, revealing that SP-injected chicks displayed less feeding pecks and reduced locomotion compared to vehicle-injected birds. To identify molecular mechanisms, the hypothalamus was isolated at 1 h post-injection and real-time PCR was performed to measure mRNA. Agouti-related peptide (AgRP) mRNA was reduced in SP-injected chicks. Immunohistochemistry was used to quantify c-Fos-expressing cells in appetite-associated hypothalamic nuclei. There were more reactive cells in the lateral hypothalamus (LH) and the paraventricular nucleus (PVN) of SP- than vehicle-injected chicks. The LH and PVN were collected for gene expression analysis. Corticotropin-releasing factor (CRF) and urotensin 2 (UTS2) mRNAs were greater in SP- than vehicle-injected chicks in the PVN. In the LH, CRF receptor sub-type 2 (CRFR2) mRNA was greater and kappa opioid receptor mRNA was reduced in SP- compared to vehicle-injected quail. Thus, SP induces a potent anorexia in quail that coincides with increased LH-specific CRFR2 mRNA and increased UTS2 mRNA in the PVN. Future studies will evaluate whether SP-induced anorexigenic effects are mediated through CRF receptors. BACKGROUND Effects of clinical practice changes on ICU delirium are not well understood. OBJECTIVES Determine ICU delirium rates over time. METHODS Data from a previously described screening cohort of the Pharmacological Management of Delirium trial was analyzed. Richmond Agitation-Sedation Scale (RASS) and Confusion Assessment Method for the ICU (CAM-ICU) were assessed twice daily. We defined Any delirium (positive CAM-ICU at any time during ICU stay) and ICU-acquired delirium (1st CAM-ICU negative with a subsequent positive CAM-ICU). Mixed-effects logistic regression models were used to test for differences. RESULTS 2742 patient admissions were included. Delirium occurred in 16.5%, any delirium decreased [22.7% to 10.2% (p  less then  0.01)], and ICU-acquired delirium decreased [8.4% to 4.4% (p = 0.01)]. Coma decreased from 24% to 17.4% (p = 0.04). Later ICU years and higher mean RASS scores were associated with lower odds of delirium. CONCLUSIONS Delirium rates were not explained by the measured variables and further prospective research is needed. BACKGROUNDS The still high poor outcome of ARDS may be more consequence of circulatory failure than hypoxemia per se. For patients with circulatory failure and ARDS, hemodynamic instability is directly related to ARDS following pulmonary circulation dysfunction and its consequence - right ventricular (RV) dysfunction. OBJECTIVES We hypothesize that in the era of protective ventilation, echocardiographic abnormalities did not parallel ARDS severity, defined by the degree of hypoxemia. METHODS We included 63 consecutively identified mechanically ventilated ARDS patients (1st January 2015 to 31th December 2016). All had echocardiography performed routinely within the first 12 h after ICU admission. RESULTS The analysis included 110 exams. Twenty-eight patients had severe ARDS (28/63, 44.4%), 27 had moderate ARDS (27/63, 42.1%) and 8 mild ARDS (8/63, 12.7%).There was no difference in echocardiographic findings between mild-moderate and severe ARDS. At Pearson's linear regression analysis, TAPSE was directly correlated with LVEF (r = 0.
    0 Comments 0 Shares 1 Views 0 Reviews

  • Different plant hormones are involved in plant adaptation to water deficit. In comparison to angiosperms, little is known about the impact of drought on the pool of phytohormones in gymnosperms. Therefore, we studied the effect of polyethylene glycol-induced water deficit on the changes in content of different phytohormones in Scots pine and Norway spruce seedlings, which are known for their different strategies of adaptation to water deficit. The following hormone classes were analysed cytokinins, auxins, jasmonates, salicylic and benzoic acids, and 1-aminocyclopropane-1-carboxylic acid (an ethylene precursor). No consistent reaction to water stress was observed for the content of well-known stress-related hormones - salicylic acid and jasmonates. In contrast, drought induced a dose-dependent accumulation of cytokinins in pine needles, with less profound changes in spruce needles. The most prominent changes were observed for 1-aminocyclopropane-1-carboxylic acid content, which increased several-fold in spruce roots and pine needles under water deficit. Water-deficit-induced changes in the contents of cytokinins and 1-aminocyclopropane-1-carboxylic acid were accompanied by the differential regulation of genes involved in the metabolism of these hormones. Possible links between changes in hormone pools and the adaptation of seedlings to water deficit are discussed. Chenopodium quinoa, a halophytic crop belonging to the Amaranthaceae, has remarkable resistance to harsh growth conditions and produces seed with excellent nutritional value. This makes it a suitable crop for marginal soils. However, to date most of the commercial cultivars are susceptible to preharvest sprouting (PHS). Meanwhile, understanding of the PHS regulatory mechanisms is still limited. Abscisic acid (ABA) has been demonstrated to be tightly associated with seed dormancy and germination regulation in many crops. Whether ABA metabolism pathway could be manipulated to prevent PHS in quinoa is worth investigating. In the present study, we tested the inhibitory effects of exogenous ABA on quinoa seed germination. By RNA-seq analysis we investigated the global gene expression changes during seed germination, and obtained 1066 ABA-repressed and 392 ABA-induced genes. Cis-elements enrichment analysis indicated that the promoters of these genes were highly enriched in motifs "AAAAAAAA" and "ACGTGKC (K = G/T)", the specific binding motifs of ABI3/VP1 and ABI5. Transcription factor annotation showed that 13 genes in bHLH, MADS-box, G2-like and NF-YB, and five genes in B3, bZIP, GATA and LBD families were specifically ABA-repressed and -induced, respectively. Furthermore, expression levels of 53 key homologs involved in seed dormancy and germination regulation were markedly changed. Hence, we speculated that the 18 transcription factors and the homologs were potential candidates involved in ABA-mediated seed dormancy and germination regulation, which could be manipulated for molecular breeding of quinoa elites with PHS tolerance in future. Acetohydroxyacid synthase (AHAS, E.C. 2.2.1.6) is the target site of several herbicide classes including imidazolinones. Imidazolinone resistance in wheat is conferred by two major genes AhasL-D1 and AhasL-B1. The objective of this work was to evaluate the in vitro and in vivo AHAS activity and plant growth in response to imazamox of nine wheat cultivars. Dose-response curves for two-gene resistant cultivars were significantly different from the single-gene resistant and susceptible cultivars in the in vitro AHAS assay. Resistance levels at the in vivo AHAS and whole-plant assays for resistant cultivars were >10-fold higher than susceptible cultivars. Moreover, in vivo dose-response curves showed differences among cultivars with the same number of resistance genes. https://www.selleckchem.com/products/turi.html It was concluded that in the in vitro AHAS assay cultivar variability was due to differences in target-site sensitivity while the in vivo AHAS assay reflected the resistance at whole-plant level. Both in vitro and in vivo AHAS dose-response curves could be useful tools when exploring mechanisms involved in imidazolinone resistance in different wheat genetic backgrounds and for the selection of higher resistant genotypes. Potassium (K+) has been reported to alleviate ammonium (NH4+) toxicity in rice through some underlying mechanisms, but it still not clear. In addition, K+ is an important cation for activation of plasma membrane (PM) H+-ATPase activity. Here, we hypothesized that K+ alleviated NH4+ toxicity by mediating PM H+-ATPase function in rice root. In this study, rice plants were cultivated in hydroponic solution with various concentrations of K+ and NH4+. By concurrently supplying K+ with NH4+ or re-supplying K+ after NH4+ toxicity, we found that high K+ concentration reduced the NH4+ uptake rate, enhanced the H+ extrusion rate by the roots, and alleviated rice NH4+ toxicity. The gene expression levels of PM H+-ATPase members (OsA1, 3, 7, 8, and 9) were upregulated by application of increasing concentrations of K+ under NH4+ toxicity. The PM H+-ATPase activity and protein expression in rice roots were also enhanced. Furthermore, the enhancement of PM H+-ATPase activity by a specific stimulator (fusicoccin) rescued rice seedlings from NH4+ toxicity. Taken together, these results indicate that K+ can alleviate NH4+ toxicity, possibly by activating PM H+-ATPase to extrude more H+ and inhibit NH4+ uptake by root. Our results may enhance understanding of the strategy of applying K+ fertilizer to mitigate crop NH4+ toxicity in agriculture. Caffeate 3-O-methyltransferase (COMT) catalyzes the methylation of the 3-hydroxyl group of caffeate to produce ferulate, an important precursor of the lignin biosynthesis. As a crucial drawback for biofuel production, lignin limits the enzymatic hydrolysis of polysaccharides to result in fermentable sugars. We hypothesized that a controlled inhibition of maize COMT can be an efficient approach to reduce ferulate and lignin, thus improving the saccharification process. First, we applied in silico techniques to prospect potential inhibitors of ZmaysCOMT, and the nitrocatechol entacapone was selected. Second, in vitro assays confirmed the inhibitory effect of entacapone on maize COMT. Finally, in vivo experiments revealed that entacapone reduced the contents of cell-wall-esterified hydroxycinnamates and increased saccharification of stems (18%) and leaves (70%), without negatively affecting maize growth and lignin biosynthesis. This non-genetically modified approach can be an alternative strategy to facilitate the enzymatic hydrolysis of biomass polysaccharides and increase saccharification for bioethanol production.
    Different plant hormones are involved in plant adaptation to water deficit. In comparison to angiosperms, little is known about the impact of drought on the pool of phytohormones in gymnosperms. Therefore, we studied the effect of polyethylene glycol-induced water deficit on the changes in content of different phytohormones in Scots pine and Norway spruce seedlings, which are known for their different strategies of adaptation to water deficit. The following hormone classes were analysed cytokinins, auxins, jasmonates, salicylic and benzoic acids, and 1-aminocyclopropane-1-carboxylic acid (an ethylene precursor). No consistent reaction to water stress was observed for the content of well-known stress-related hormones - salicylic acid and jasmonates. In contrast, drought induced a dose-dependent accumulation of cytokinins in pine needles, with less profound changes in spruce needles. The most prominent changes were observed for 1-aminocyclopropane-1-carboxylic acid content, which increased several-fold in spruce roots and pine needles under water deficit. Water-deficit-induced changes in the contents of cytokinins and 1-aminocyclopropane-1-carboxylic acid were accompanied by the differential regulation of genes involved in the metabolism of these hormones. Possible links between changes in hormone pools and the adaptation of seedlings to water deficit are discussed. Chenopodium quinoa, a halophytic crop belonging to the Amaranthaceae, has remarkable resistance to harsh growth conditions and produces seed with excellent nutritional value. This makes it a suitable crop for marginal soils. However, to date most of the commercial cultivars are susceptible to preharvest sprouting (PHS). Meanwhile, understanding of the PHS regulatory mechanisms is still limited. Abscisic acid (ABA) has been demonstrated to be tightly associated with seed dormancy and germination regulation in many crops. Whether ABA metabolism pathway could be manipulated to prevent PHS in quinoa is worth investigating. In the present study, we tested the inhibitory effects of exogenous ABA on quinoa seed germination. By RNA-seq analysis we investigated the global gene expression changes during seed germination, and obtained 1066 ABA-repressed and 392 ABA-induced genes. Cis-elements enrichment analysis indicated that the promoters of these genes were highly enriched in motifs "AAAAAAAA" and "ACGTGKC (K = G/T)", the specific binding motifs of ABI3/VP1 and ABI5. Transcription factor annotation showed that 13 genes in bHLH, MADS-box, G2-like and NF-YB, and five genes in B3, bZIP, GATA and LBD families were specifically ABA-repressed and -induced, respectively. Furthermore, expression levels of 53 key homologs involved in seed dormancy and germination regulation were markedly changed. Hence, we speculated that the 18 transcription factors and the homologs were potential candidates involved in ABA-mediated seed dormancy and germination regulation, which could be manipulated for molecular breeding of quinoa elites with PHS tolerance in future. Acetohydroxyacid synthase (AHAS, E.C. 2.2.1.6) is the target site of several herbicide classes including imidazolinones. Imidazolinone resistance in wheat is conferred by two major genes AhasL-D1 and AhasL-B1. The objective of this work was to evaluate the in vitro and in vivo AHAS activity and plant growth in response to imazamox of nine wheat cultivars. Dose-response curves for two-gene resistant cultivars were significantly different from the single-gene resistant and susceptible cultivars in the in vitro AHAS assay. Resistance levels at the in vivo AHAS and whole-plant assays for resistant cultivars were >10-fold higher than susceptible cultivars. Moreover, in vivo dose-response curves showed differences among cultivars with the same number of resistance genes. https://www.selleckchem.com/products/turi.html It was concluded that in the in vitro AHAS assay cultivar variability was due to differences in target-site sensitivity while the in vivo AHAS assay reflected the resistance at whole-plant level. Both in vitro and in vivo AHAS dose-response curves could be useful tools when exploring mechanisms involved in imidazolinone resistance in different wheat genetic backgrounds and for the selection of higher resistant genotypes. Potassium (K+) has been reported to alleviate ammonium (NH4+) toxicity in rice through some underlying mechanisms, but it still not clear. In addition, K+ is an important cation for activation of plasma membrane (PM) H+-ATPase activity. Here, we hypothesized that K+ alleviated NH4+ toxicity by mediating PM H+-ATPase function in rice root. In this study, rice plants were cultivated in hydroponic solution with various concentrations of K+ and NH4+. By concurrently supplying K+ with NH4+ or re-supplying K+ after NH4+ toxicity, we found that high K+ concentration reduced the NH4+ uptake rate, enhanced the H+ extrusion rate by the roots, and alleviated rice NH4+ toxicity. The gene expression levels of PM H+-ATPase members (OsA1, 3, 7, 8, and 9) were upregulated by application of increasing concentrations of K+ under NH4+ toxicity. The PM H+-ATPase activity and protein expression in rice roots were also enhanced. Furthermore, the enhancement of PM H+-ATPase activity by a specific stimulator (fusicoccin) rescued rice seedlings from NH4+ toxicity. Taken together, these results indicate that K+ can alleviate NH4+ toxicity, possibly by activating PM H+-ATPase to extrude more H+ and inhibit NH4+ uptake by root. Our results may enhance understanding of the strategy of applying K+ fertilizer to mitigate crop NH4+ toxicity in agriculture. Caffeate 3-O-methyltransferase (COMT) catalyzes the methylation of the 3-hydroxyl group of caffeate to produce ferulate, an important precursor of the lignin biosynthesis. As a crucial drawback for biofuel production, lignin limits the enzymatic hydrolysis of polysaccharides to result in fermentable sugars. We hypothesized that a controlled inhibition of maize COMT can be an efficient approach to reduce ferulate and lignin, thus improving the saccharification process. First, we applied in silico techniques to prospect potential inhibitors of ZmaysCOMT, and the nitrocatechol entacapone was selected. Second, in vitro assays confirmed the inhibitory effect of entacapone on maize COMT. Finally, in vivo experiments revealed that entacapone reduced the contents of cell-wall-esterified hydroxycinnamates and increased saccharification of stems (18%) and leaves (70%), without negatively affecting maize growth and lignin biosynthesis. This non-genetically modified approach can be an alternative strategy to facilitate the enzymatic hydrolysis of biomass polysaccharides and increase saccharification for bioethanol production.
    0 Comments 0 Shares 1 Views 0 Reviews

  • Our findings provide critical molecular insight into ECT2-mediated regulation of rDNA transcription in cancer cells and offer a rationale for therapeutic targeting of UBF1- and ECT2-stimulated rDNA transcription for the management of NSCLC. https://www.selleckchem.com/GSK-3.html Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Z-DNA-binding protein 1 (ZBP1) is an innate immune sensor of nucleic acids that regulates both host defense responses and development. ZBP1 activation triggers inflammation and pyroptosis, necroptosis, and apoptosis (PANoptosis) by activating receptor-interacting Ser/Thr kinase 3 (RIPK3), caspase-8, and the NLRP3 inflammasome. ZBP1 is unique among innate immune sensors because of its N-terminal Zα1 and Zα2 domains, which bind to nucleic acids in the Z-conformation. However, the specific role of these Zα domains in orchestrating ZBP1 activation and subsequent inflammation and cell death is not clear. Here we generated Zbp1ΔZα2/ΔZα2 **** that express ZBP1 lacking the Zα2 domain and demonstrate that this domain is critical for influenza A virus (IAV)-induced PANoptosis and underlies the perinatal lethality in **** in which the RHIM domain of RIPK1 had been mutated (Ripk1mRHIM/mRHIM). Deletion of the Zα2 domain in ZBP1 abolished IAV-induced PANoptosis and NLRP3 inflammasome activation. Furthermore, deletion of the Zα2 domain of ZBP1 was sufficient to rescue Ripk1mRHIM/mRHIM **** from the perinatal lethality which is caused by ZBP1-driven cell death and inflammation. Our findings identify the essential role of the Zα2 domain of ZBP1 in several physiological functions and establish a link between Z-RNA sensing via the Zα2 domain and the promotion of influenza-induced PANoptosis and perinatal lethality. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.The Ser/Thr protein kinase MELK (maternal embryonic leucine zipper kinase) has been considered an attractive therapeutic target for managing cancer since 2005. Studies using expression analysis have indicated that MELK expression is higher in numerous cancer cells and tissues than in their normal, non-neoplastic counterparts. Further, RNAi-mediated MELK depletion impairs proliferation of multiple cancers, including triple-negative breast cancer (TNBC), and these growth defects can be rescued with exogenous wild-type MELK, but not kinase-dead MELK complementation. Pharmacological MELK inhibition with OTS167 (alternatively called OTSSP167) and NVS-MELK8a, among other small molecules, also impairs cancer cell growth. These collective results led to MELK being classified as essential for cancer proliferation. More recently, in 2017, the proliferation of TNBC and other cancer cell lines was reported to be unaffected by genetic CRISPR/Cas9-mediated MELK deletion, calling into question the essentiality of this kinase in cancer. To date, the requirement of MELK in cancer remains controversial, and mechanisms underlying the disparate growth effects observed with RNAi, pharmacological inhibition, and CRISPR remain unclear. Our objective with this review is to highlight the evidence on both sides of this controversy, to provide commentary on the purported requirement of MELK in cancer, and to emphasize the need for continued elucidation of the functions of MELK. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Many plant-pathogenic bacteria and fungi deploy effector proteins that down-regulate plant defense responses and reprogram plant metabolism for colonization and survival in planta. Kiwellin (KWL) proteins are a widespread family of plant-defense proteins that target these microbial effectors. The KWL1 protein from maize (corn, Zea mays) specifically inhibits the enzymatic activity of the secreted chorismate mutase Cmu1, a virulence-promoting effector of the smut fungus Ustilago maydis. Besides KWL1, 19 additional KWL paralogs have been identified in maize. Here, we investigated the structure and mechanism of the closest KWL1 homolog, KWL1-b (ZEAMA_GRMZM2G305329). We solved the Cmu1-KWL1-b complex to 2.75 Å resolution, revealing a highly symmetric Cmu1-KWL1-b heterotetramer in which each KWL1-b monomer interacts with a monomer of the Cmu1 homodimer. The structure also revealed that the overall architecture of the heterotetramer is highly similar to that of the previously reported Cmu1-KWL1 complex. We found that upon U. maydis infection of Z. mays, KWL1-b is expressed at significantly lower levels than KWL1 and exhibits differential tissue-specific expression patterns. We also show that KWL1-b inhibits Cmu1 activity similarly to KWL1. We conclude that KWL1 and KWL1-b are part of a redundant defense system that tissue-specifically targets Cmu1. This notion was supported by the observation that both KWL proteins are carbohydrate-binding proteins with distinct and likely tissue-related specificities. Moreover, binding by Cmu1 modulated the carbohydrate-binding properties of both KWLs. These findings indicate that KWL proteins are part of a spatiotemporally coordinated, plant-wide defense response comprising proteins with overlapping activities. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Growth differentiation factor-9 (GDF9) and bone morphogenetic protein-15 (BMP15) are co-expressed exclusively in oocytes throughout most of folliculogenesis and play central roles in controlling ovarian physiology. Although both growth factors exist as homodimers, recent evidence indicates that GDF9 and BMP15 can also heterodimerize to form the potent growth factor cumulin. Within the cumulin complex, BMP15 "activates" latent GDF9, enabling potent signaling in granulosa cells via type I receptors (i.e., activin receptor-like kinase-4/5 [ALK4/5]) and SMAD2/3 transcription factors. In the cumulin heterodimer, two distinct type I receptor interfaces are formed compared with homodimeric GDF9 and BMP15. Previous studies have highlighted the potential of cumulin to improve treatment of female infertility, but, as a non-covalent heterodimer, cumulin is difficult to produce and purify without contaminating GDF9 and BMP15 homodimers. In this study we addressed this challenge by focusing on the cumulin interface formed by the helix of the GDF9 chain and the fingers of the BMP15 chain.
    Our findings provide critical molecular insight into ECT2-mediated regulation of rDNA transcription in cancer cells and offer a rationale for therapeutic targeting of UBF1- and ECT2-stimulated rDNA transcription for the management of NSCLC. https://www.selleckchem.com/GSK-3.html Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Z-DNA-binding protein 1 (ZBP1) is an innate immune sensor of nucleic acids that regulates both host defense responses and development. ZBP1 activation triggers inflammation and pyroptosis, necroptosis, and apoptosis (PANoptosis) by activating receptor-interacting Ser/Thr kinase 3 (RIPK3), caspase-8, and the NLRP3 inflammasome. ZBP1 is unique among innate immune sensors because of its N-terminal Zα1 and Zα2 domains, which bind to nucleic acids in the Z-conformation. However, the specific role of these Zα domains in orchestrating ZBP1 activation and subsequent inflammation and cell death is not clear. Here we generated Zbp1ΔZα2/ΔZα2 mice that express ZBP1 lacking the Zα2 domain and demonstrate that this domain is critical for influenza A virus (IAV)-induced PANoptosis and underlies the perinatal lethality in mice in which the RHIM domain of RIPK1 had been mutated (Ripk1mRHIM/mRHIM). Deletion of the Zα2 domain in ZBP1 abolished IAV-induced PANoptosis and NLRP3 inflammasome activation. Furthermore, deletion of the Zα2 domain of ZBP1 was sufficient to rescue Ripk1mRHIM/mRHIM mice from the perinatal lethality which is caused by ZBP1-driven cell death and inflammation. Our findings identify the essential role of the Zα2 domain of ZBP1 in several physiological functions and establish a link between Z-RNA sensing via the Zα2 domain and the promotion of influenza-induced PANoptosis and perinatal lethality. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.The Ser/Thr protein kinase MELK (maternal embryonic leucine zipper kinase) has been considered an attractive therapeutic target for managing cancer since 2005. Studies using expression analysis have indicated that MELK expression is higher in numerous cancer cells and tissues than in their normal, non-neoplastic counterparts. Further, RNAi-mediated MELK depletion impairs proliferation of multiple cancers, including triple-negative breast cancer (TNBC), and these growth defects can be rescued with exogenous wild-type MELK, but not kinase-dead MELK complementation. Pharmacological MELK inhibition with OTS167 (alternatively called OTSSP167) and NVS-MELK8a, among other small molecules, also impairs cancer cell growth. These collective results led to MELK being classified as essential for cancer proliferation. More recently, in 2017, the proliferation of TNBC and other cancer cell lines was reported to be unaffected by genetic CRISPR/Cas9-mediated MELK deletion, calling into question the essentiality of this kinase in cancer. To date, the requirement of MELK in cancer remains controversial, and mechanisms underlying the disparate growth effects observed with RNAi, pharmacological inhibition, and CRISPR remain unclear. Our objective with this review is to highlight the evidence on both sides of this controversy, to provide commentary on the purported requirement of MELK in cancer, and to emphasize the need for continued elucidation of the functions of MELK. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Many plant-pathogenic bacteria and fungi deploy effector proteins that down-regulate plant defense responses and reprogram plant metabolism for colonization and survival in planta. Kiwellin (KWL) proteins are a widespread family of plant-defense proteins that target these microbial effectors. The KWL1 protein from maize (corn, Zea mays) specifically inhibits the enzymatic activity of the secreted chorismate mutase Cmu1, a virulence-promoting effector of the smut fungus Ustilago maydis. Besides KWL1, 19 additional KWL paralogs have been identified in maize. Here, we investigated the structure and mechanism of the closest KWL1 homolog, KWL1-b (ZEAMA_GRMZM2G305329). We solved the Cmu1-KWL1-b complex to 2.75 Å resolution, revealing a highly symmetric Cmu1-KWL1-b heterotetramer in which each KWL1-b monomer interacts with a monomer of the Cmu1 homodimer. The structure also revealed that the overall architecture of the heterotetramer is highly similar to that of the previously reported Cmu1-KWL1 complex. We found that upon U. maydis infection of Z. mays, KWL1-b is expressed at significantly lower levels than KWL1 and exhibits differential tissue-specific expression patterns. We also show that KWL1-b inhibits Cmu1 activity similarly to KWL1. We conclude that KWL1 and KWL1-b are part of a redundant defense system that tissue-specifically targets Cmu1. This notion was supported by the observation that both KWL proteins are carbohydrate-binding proteins with distinct and likely tissue-related specificities. Moreover, binding by Cmu1 modulated the carbohydrate-binding properties of both KWLs. These findings indicate that KWL proteins are part of a spatiotemporally coordinated, plant-wide defense response comprising proteins with overlapping activities. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Growth differentiation factor-9 (GDF9) and bone morphogenetic protein-15 (BMP15) are co-expressed exclusively in oocytes throughout most of folliculogenesis and play central roles in controlling ovarian physiology. Although both growth factors exist as homodimers, recent evidence indicates that GDF9 and BMP15 can also heterodimerize to form the potent growth factor cumulin. Within the cumulin complex, BMP15 "activates" latent GDF9, enabling potent signaling in granulosa cells via type I receptors (i.e., activin receptor-like kinase-4/5 [ALK4/5]) and SMAD2/3 transcription factors. In the cumulin heterodimer, two distinct type I receptor interfaces are formed compared with homodimeric GDF9 and BMP15. Previous studies have highlighted the potential of cumulin to improve treatment of female infertility, but, as a non-covalent heterodimer, cumulin is difficult to produce and purify without contaminating GDF9 and BMP15 homodimers. In this study we addressed this challenge by focusing on the cumulin interface formed by the helix of the GDF9 chain and the fingers of the BMP15 chain.
    0 Comments 0 Shares 1 Views 0 Reviews

  • The results showed high expression levels of lacZ and galKTM genes and reabsorption of extracellular galactose. S. thermophilus MN-ZLW-002 can metabolize and utilize galactose. Overall, this comprehensive network of carbohydrate metabolism is useful for further studies of the control of glycolytic pathway during the high-density culture of S. thermophilus.Table olives are one of the most well-known traditionally fermented products, and their global consumption is exponentially increasing. In direct brining, table olives are produced spontaneously, without any debittering pre-treatment. Up to date, fermentation process remains empirical and inconstant, as it is affected by the physicochemical attributes of the fruit, tree and fruit management of pro and post-harvest. In the present study, whole and cracked Picual table olives were fermented at industrial scale for 120 days, using three distinct methods (natural fermentation, inoculation with lactic acid bacteria (LAB) at a 7 or a 10% NaCl concentration). Microbial, physicochemical and sensorial alterations monitored during the whole process, and several differences were observed between treatments. Results indicated that in all treatments, the dominant microflora were LAB. Yeasts also detected in noteworthy populations, especially in non-inoculated samples. However, LAB population was significantly higher in inontent was highly appreciated by the sensory panel, enhancing the hypothesis that the production of Picual table olives at reduced NaCl levels is achievable.Adult T-cell leukemia-lymphoma (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) infection that often occurs in HTLV-1-endemic areas, such as Japan, the Caribbean islands, Central and South America, Intertropical Africa, and the Middle East. In Japan, the nationwide estimation of the number of HTLV-1 carriers was at least 1.08 million in 2006-2007. Furthermore, in 2016, the nationwide annual incidence of newly infected with HTLV-1 was first estimated to be 3.8 per 100,000 person-years based on the age-specific seroconversion rates of blood donors in almost all areas of Japan. The incidence rate was three times higher in women than in men, and it was estimated that at least 4,000 new HTLV-1 infections occur yearly among adolescents and adults in Japan. As well known that HTLV-1 infection alone is not a sufficient condition for ATL to develop. To date, a variety of molecular abnormalities and host susceptibilities have been reported as candidate progression factors fy stable, at around 1,000 patients annually, without significant decline from 1999 to 2017. Because the current epidemiological evidence about HTLV-1 and ATL is insufficient, further epidemiological studies are required.The use of volatile organic compounds (VOCs) produced by microorganisms for the biological control of plant diseases has attracted **** attention in recent years. In this study, the antifungal activity and identity of VOCs produced by Rahnella aquatilis JZ-GX1 isolated from the rhizosphere soil of pine were determined and analyzed. The effect of the VOCs on the mycelial growth of Colletotrichum gloeosporioides, the pathogen of Liriodendron chinense × tulipifera black spot, was determined by a joined-petri dish fumigation method. An in vitro leaf inoculation method was used to determine the fumigation effect of the VOCs on Liriodendron black spot. VOCs with antifungal activity were collected by headspace solid-phase microextraction (SPME), and their components were analyzed by gas chromatography-mass spectrometry (GC-MS). The results showed that the VOCs secreted by JZ-GX1 inhibited the mycelial growth of the tested pathogen. The VOCs destroyed the morphology of the mycelium, significantly increased the permeability of the cell membrane and downregulated the expression of pathogenicity-related genes during mycelial infection, thus inhibiting the expansion of anthracnose disease spots in leaves. In the volatile compound profile, 3-methyl-1-butanol and 2-phenylethyl methyl ether significantly inhibited the mycelial growth and spore germination of C. gloeosporioides. This work provides a new strategy for the research and application of microorganisms and bioactive compounds to control plant anthracnose.The virus-to-prokaryote ratio (VPR), which reflects the numerical dominance of viruses over their hosts, has been proposed as a proxy for assessing the relationship between viruses and prokaryotes. Previous studies showed that VPR values fluctuate over six orders of magnitude within and across various benthic ecosystems, with an average value of approximately 10. We hypothesize that this high VPR value is largely due to the inaccurate enumeration of viruses and prokaryotes (e.g., centrifugation treatments may lead to a three-fourfold overestimation of VPR). In this study, we evaluated the impact of processing methods on the determination of VPR values. Using an optimized procedure, we investigated the marine benthic VPR at 31 sites, from intertidal zones through continental shelves to abyssal plains, and assessed its monthly variation in two contrasting intertidal habitats (muddy-sand and sandy). By compiling 135 VPR data points of surface sediments from 37 publications, we reveal the effect of centrifugation approximately one order of magnitude lower and **** less varied than that observed in pelagic habitats, indicating that the virus-host relationship and the ecological function of viruses in the two ecosystems may be very different.H-NS family proteins regulate the expression of many genes by preferably binding to AT-rich genomic regions and altering DNA topology. They are found in both bacterial chromosomes and plasmids, and plasmid-encoded H-NS family proteins have sometimes been suggested to act as a molecular backup of the chromosomally encoded ones. Pmr is an H-NS family protein encoded on the catabolic plasmid pCAR1, which belongs to incompatibility P-7 group. We have investigated the function of Pmr in Pseudomonas putida KT2440, where two H-NS family proteins (TurA and TurB) encoded on the chromosome are expressed predominantly. Previous transcriptome analyses suggested that TurA, TurB, and Pmr cooperatively regulate numerous genes, but the differentially transcribed genes in KT2440ΔturA(pCAR1), KT2440ΔturB(pCAR1), and KT2440(pCAR1Δpmr) compared with those in KT2440(pCAR1) were somewhat different. https://www.selleckchem.com/products/azd9291.html Here, we performed RNA sequencing analyses to compare the differentially transcribed genes after the deletion of turA or turB in KT2440, and turA, turB or pmr in KT2440(pCAR1).
    The results showed high expression levels of lacZ and galKTM genes and reabsorption of extracellular galactose. S. thermophilus MN-ZLW-002 can metabolize and utilize galactose. Overall, this comprehensive network of carbohydrate metabolism is useful for further studies of the control of glycolytic pathway during the high-density culture of S. thermophilus.Table olives are one of the most well-known traditionally fermented products, and their global consumption is exponentially increasing. In direct brining, table olives are produced spontaneously, without any debittering pre-treatment. Up to date, fermentation process remains empirical and inconstant, as it is affected by the physicochemical attributes of the fruit, tree and fruit management of pro and post-harvest. In the present study, whole and cracked Picual table olives were fermented at industrial scale for 120 days, using three distinct methods (natural fermentation, inoculation with lactic acid bacteria (LAB) at a 7 or a 10% NaCl concentration). Microbial, physicochemical and sensorial alterations monitored during the whole process, and several differences were observed between treatments. Results indicated that in all treatments, the dominant microflora were LAB. Yeasts also detected in noteworthy populations, especially in non-inoculated samples. However, LAB population was significantly higher in inontent was highly appreciated by the sensory panel, enhancing the hypothesis that the production of Picual table olives at reduced NaCl levels is achievable.Adult T-cell leukemia-lymphoma (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) infection that often occurs in HTLV-1-endemic areas, such as Japan, the Caribbean islands, Central and South America, Intertropical Africa, and the Middle East. In Japan, the nationwide estimation of the number of HTLV-1 carriers was at least 1.08 million in 2006-2007. Furthermore, in 2016, the nationwide annual incidence of newly infected with HTLV-1 was first estimated to be 3.8 per 100,000 person-years based on the age-specific seroconversion rates of blood donors in almost all areas of Japan. The incidence rate was three times higher in women than in men, and it was estimated that at least 4,000 new HTLV-1 infections occur yearly among adolescents and adults in Japan. As well known that HTLV-1 infection alone is not a sufficient condition for ATL to develop. To date, a variety of molecular abnormalities and host susceptibilities have been reported as candidate progression factors fy stable, at around 1,000 patients annually, without significant decline from 1999 to 2017. Because the current epidemiological evidence about HTLV-1 and ATL is insufficient, further epidemiological studies are required.The use of volatile organic compounds (VOCs) produced by microorganisms for the biological control of plant diseases has attracted much attention in recent years. In this study, the antifungal activity and identity of VOCs produced by Rahnella aquatilis JZ-GX1 isolated from the rhizosphere soil of pine were determined and analyzed. The effect of the VOCs on the mycelial growth of Colletotrichum gloeosporioides, the pathogen of Liriodendron chinense × tulipifera black spot, was determined by a joined-petri dish fumigation method. An in vitro leaf inoculation method was used to determine the fumigation effect of the VOCs on Liriodendron black spot. VOCs with antifungal activity were collected by headspace solid-phase microextraction (SPME), and their components were analyzed by gas chromatography-mass spectrometry (GC-MS). The results showed that the VOCs secreted by JZ-GX1 inhibited the mycelial growth of the tested pathogen. The VOCs destroyed the morphology of the mycelium, significantly increased the permeability of the cell membrane and downregulated the expression of pathogenicity-related genes during mycelial infection, thus inhibiting the expansion of anthracnose disease spots in leaves. In the volatile compound profile, 3-methyl-1-butanol and 2-phenylethyl methyl ether significantly inhibited the mycelial growth and spore germination of C. gloeosporioides. This work provides a new strategy for the research and application of microorganisms and bioactive compounds to control plant anthracnose.The virus-to-prokaryote ratio (VPR), which reflects the numerical dominance of viruses over their hosts, has been proposed as a proxy for assessing the relationship between viruses and prokaryotes. Previous studies showed that VPR values fluctuate over six orders of magnitude within and across various benthic ecosystems, with an average value of approximately 10. We hypothesize that this high VPR value is largely due to the inaccurate enumeration of viruses and prokaryotes (e.g., centrifugation treatments may lead to a three-fourfold overestimation of VPR). In this study, we evaluated the impact of processing methods on the determination of VPR values. Using an optimized procedure, we investigated the marine benthic VPR at 31 sites, from intertidal zones through continental shelves to abyssal plains, and assessed its monthly variation in two contrasting intertidal habitats (muddy-sand and sandy). By compiling 135 VPR data points of surface sediments from 37 publications, we reveal the effect of centrifugation approximately one order of magnitude lower and much less varied than that observed in pelagic habitats, indicating that the virus-host relationship and the ecological function of viruses in the two ecosystems may be very different.H-NS family proteins regulate the expression of many genes by preferably binding to AT-rich genomic regions and altering DNA topology. They are found in both bacterial chromosomes and plasmids, and plasmid-encoded H-NS family proteins have sometimes been suggested to act as a molecular backup of the chromosomally encoded ones. Pmr is an H-NS family protein encoded on the catabolic plasmid pCAR1, which belongs to incompatibility P-7 group. We have investigated the function of Pmr in Pseudomonas putida KT2440, where two H-NS family proteins (TurA and TurB) encoded on the chromosome are expressed predominantly. Previous transcriptome analyses suggested that TurA, TurB, and Pmr cooperatively regulate numerous genes, but the differentially transcribed genes in KT2440ΔturA(pCAR1), KT2440ΔturB(pCAR1), and KT2440(pCAR1Δpmr) compared with those in KT2440(pCAR1) were somewhat different. https://www.selleckchem.com/products/azd9291.html Here, we performed RNA sequencing analyses to compare the differentially transcribed genes after the deletion of turA or turB in KT2440, and turA, turB or pmr in KT2440(pCAR1).
    0 Comments 0 Shares 1 Views 0 Reviews

  • Background Plant biomass is an abundant and renewable carbon source that is recalcitrant towards both chemical and biochemical degradation. Xylan is the second most abundant polysaccharide in biomass after cellulose, and it possesses a variety of carbohydrate substitutions and non-carbohydrate decorations which can impede enzymatic degradation by glycoside hydrolases. Carbohydrate esterases are able to cleave the ester-linked decorations and thereby improve the accessibility of the xylan backbone to glycoside hydrolases, thus improving the degradation process. Enzymes comprising multiple catalytic glycoside hydrolase domains on the same polypeptide have previously been shown to exhibit intramolecular synergism during degradation of biomass. Similarly, natively fused carbohydrate esterase domains are encoded by certain bacteria, but whether these enzymes can result in similar synergistic boosts in biomass degradation has not previously been evaluated. Results Two carbohydrate esterases with similar architecturtramolecular synergy between the esterase domains. Despite high sequence similarities between the esterase domains from B. ovatus and F. johnsoniae, their addition to the xylanolytic reaction led to different degradation patterns. Conclusion We demonstrated that multidomain carbohydrate esterases, targeting the non-carbohydrate decorations on different xylan polysaccharides, can considerably facilitate glycoside hydrolase-mediated hydrolysis of xylan and xylan-rich biomass. Moreover, we demonstrated for the first time a synergistic effect between the two fused catalytic domains of a multidomain carbohydrate esterase. © The Author(s) 2020.Background Suicide is a behaviour that results from a complex interplay of factors, including biological, psychological, social, cultural, and environmental factors, among others. A participatory model building workshop was conducted with fifteen employees working in suicide prevention at a federal public health organization to develop a conceptual model illustrating the interconnections between such factors. Through this process, knowledge emerged from participants and consensus building occurred, leading to the development of a conceptual model that is useful to organize and communicate the complex interrelationships between factors related to suicide. Methods A model building script was developed for the facilitators to lead the participants through a series of group and individual activities that were designed to elicit participants' implicit models of risk and protective factors for suicide in Canada. Participants were divided into three groups and tasked with drawing the relationships between factors associated with suicide over a simplified suicide process model. Participants were also tasked with listing prevention levers that are in use in Canada and/or described in the scientific literature. Results Through the workshop, risk and prevention factors and prevention levers were listed and a conceptual model was drafted. Several "lessons learned" which could improve future workshops were generated through reflection on the process. Conclusions This workshop yielded a helpful conceptual model contextualising upstream factors that can be used to better understand suicide prevention efforts in Canada. © The Author(s) 2020.The goal of this article is to introduce readers to theories, tools, and evidence from the field of neuroeconomics and to describe how health psychology and neuroeconomics can be mutually informative in the study of preventative health behaviors. Preventative health behavior here refers to both individual actions that impact one's health (e.g., exercise) and broader behavioral patterns, such as those captured in personality constructs. Although neuroeconomic researchers have begun to incorporate health-relevant behaviors into their studies, the full potential of this research to inform preventative health models is as yet unrealized. https://www.selleckchem.com/products/vb124.html What is needed to "translate up" is the unification of rich theoretical content from health psychology with investigations by neuroeconomic researchers of the decision-making process during health-relevant choices. We identify choice as a central, shared feature across models of preventative health behavior that can serve as an inroad for neuroeconomics to contribute to existing models and highlight commonalities that might not otherwise be apparent. A central premise of our argument is that, because health decisions are nearly always multiply determined, a more precise and mechanistic understanding of how choices are made is an important but understudied topic in health psychology. A partnership between health psychologists and neuroeconomic researchers can yield valuable insights into how preventative health choice is made and to identify targets and methods for intervention.Hepatocellular carcinoma is a primary liver malignancy in which the risk of development is always multifunctional. Interleukin-6 is a proinflammatory and multifunctional cytokine, which plays an important role in the immune response, haematopoiesis and defence against viral infection. We aimed to evaluate the frequency of Interleukin-6 mutations (rs2069837 and rs17147230) associated with genetic risk of hepatocellular carcinoma in Khyber Pakthunkhwa population. A total of 72 hepatocellular carcinoma cases and 38 controls were included in this study. The genomic DNA was extracted from the peripheral blood cells and Interleukin-6 genotyping was performed using T-ARMS-PCR technique. Our results show a significant increase risk of developing hepatocellular carcinoma with the mutation within Interleukin-6 gene with heterozygous G allele (rs2069837) (OR = 10.667, 95%CI = 3.923-29.001, p =  less then  0.0001) and heterozygous T allele (rs17147230) (OR = 75.385, 95%CI = 9.797-580.065, p =  less then  0.0001). However, under recessive gene model the results were insignificant in case of Interleukin-6 rs2069837 (OR = 0.605, 95%CI = 0.217-1.689, p = 0.337), while significant in case of Interleukin-6 rs17147230 (OR = 0.298, 95%CI = 0.121-0.734, p = 0.0085). In conclusion, Interleukin-6 mutation is associated with hepatocellular carcinoma susceptibility. More related studies with other associated interleukins and their whole gene sequencing will be required. © The Author(s) 2020.
    Background Plant biomass is an abundant and renewable carbon source that is recalcitrant towards both chemical and biochemical degradation. Xylan is the second most abundant polysaccharide in biomass after cellulose, and it possesses a variety of carbohydrate substitutions and non-carbohydrate decorations which can impede enzymatic degradation by glycoside hydrolases. Carbohydrate esterases are able to cleave the ester-linked decorations and thereby improve the accessibility of the xylan backbone to glycoside hydrolases, thus improving the degradation process. Enzymes comprising multiple catalytic glycoside hydrolase domains on the same polypeptide have previously been shown to exhibit intramolecular synergism during degradation of biomass. Similarly, natively fused carbohydrate esterase domains are encoded by certain bacteria, but whether these enzymes can result in similar synergistic boosts in biomass degradation has not previously been evaluated. Results Two carbohydrate esterases with similar architecturtramolecular synergy between the esterase domains. Despite high sequence similarities between the esterase domains from B. ovatus and F. johnsoniae, their addition to the xylanolytic reaction led to different degradation patterns. Conclusion We demonstrated that multidomain carbohydrate esterases, targeting the non-carbohydrate decorations on different xylan polysaccharides, can considerably facilitate glycoside hydrolase-mediated hydrolysis of xylan and xylan-rich biomass. Moreover, we demonstrated for the first time a synergistic effect between the two fused catalytic domains of a multidomain carbohydrate esterase. © The Author(s) 2020.Background Suicide is a behaviour that results from a complex interplay of factors, including biological, psychological, social, cultural, and environmental factors, among others. A participatory model building workshop was conducted with fifteen employees working in suicide prevention at a federal public health organization to develop a conceptual model illustrating the interconnections between such factors. Through this process, knowledge emerged from participants and consensus building occurred, leading to the development of a conceptual model that is useful to organize and communicate the complex interrelationships between factors related to suicide. Methods A model building script was developed for the facilitators to lead the participants through a series of group and individual activities that were designed to elicit participants' implicit models of risk and protective factors for suicide in Canada. Participants were divided into three groups and tasked with drawing the relationships between factors associated with suicide over a simplified suicide process model. Participants were also tasked with listing prevention levers that are in use in Canada and/or described in the scientific literature. Results Through the workshop, risk and prevention factors and prevention levers were listed and a conceptual model was drafted. Several "lessons learned" which could improve future workshops were generated through reflection on the process. Conclusions This workshop yielded a helpful conceptual model contextualising upstream factors that can be used to better understand suicide prevention efforts in Canada. © The Author(s) 2020.The goal of this article is to introduce readers to theories, tools, and evidence from the field of neuroeconomics and to describe how health psychology and neuroeconomics can be mutually informative in the study of preventative health behaviors. Preventative health behavior here refers to both individual actions that impact one's health (e.g., exercise) and broader behavioral patterns, such as those captured in personality constructs. Although neuroeconomic researchers have begun to incorporate health-relevant behaviors into their studies, the full potential of this research to inform preventative health models is as yet unrealized. https://www.selleckchem.com/products/vb124.html What is needed to "translate up" is the unification of rich theoretical content from health psychology with investigations by neuroeconomic researchers of the decision-making process during health-relevant choices. We identify choice as a central, shared feature across models of preventative health behavior that can serve as an inroad for neuroeconomics to contribute to existing models and highlight commonalities that might not otherwise be apparent. A central premise of our argument is that, because health decisions are nearly always multiply determined, a more precise and mechanistic understanding of how choices are made is an important but understudied topic in health psychology. A partnership between health psychologists and neuroeconomic researchers can yield valuable insights into how preventative health choice is made and to identify targets and methods for intervention.Hepatocellular carcinoma is a primary liver malignancy in which the risk of development is always multifunctional. Interleukin-6 is a proinflammatory and multifunctional cytokine, which plays an important role in the immune response, haematopoiesis and defence against viral infection. We aimed to evaluate the frequency of Interleukin-6 mutations (rs2069837 and rs17147230) associated with genetic risk of hepatocellular carcinoma in Khyber Pakthunkhwa population. A total of 72 hepatocellular carcinoma cases and 38 controls were included in this study. The genomic DNA was extracted from the peripheral blood cells and Interleukin-6 genotyping was performed using T-ARMS-PCR technique. Our results show a significant increase risk of developing hepatocellular carcinoma with the mutation within Interleukin-6 gene with heterozygous G allele (rs2069837) (OR = 10.667, 95%CI = 3.923-29.001, p =  less then  0.0001) and heterozygous T allele (rs17147230) (OR = 75.385, 95%CI = 9.797-580.065, p =  less then  0.0001). However, under recessive gene model the results were insignificant in case of Interleukin-6 rs2069837 (OR = 0.605, 95%CI = 0.217-1.689, p = 0.337), while significant in case of Interleukin-6 rs17147230 (OR = 0.298, 95%CI = 0.121-0.734, p = 0.0085). In conclusion, Interleukin-6 mutation is associated with hepatocellular carcinoma susceptibility. More related studies with other associated interleukins and their whole gene sequencing will be required. © The Author(s) 2020.
    0 Comments 0 Shares 7 Views 0 Reviews

  • The data suggest that Qβ VLPs is an excellent approach to elicit high-titer CHIKV E2-protein antibodies at a lower dose of antigen and future studies should assess whether Qβ-CHIKV E2 aa 2800-2818 VLPs and Qβ-CHIKV E2 aa 3025-3058 VLPs can neutralize a Singapore Strain of CHIKV. Determination of influenza-specific antibody titers is commonly done using the hemagglutination inhibition assay (HAI) and the viral microneutralization assay (MN). Both assays are characterized by high intra- and inter-laboratory variability. The HAI assay offers little opportunity for standardization. For the MN assay, variability might be due to the use of different assay protocols employing different readouts. We therefore aimed at investigating which of the MN assay readout methods currently in use would be the most suitable choice for a standardized MN assay that could serve as a substitute for the HAI assay. For this purpose, human serum samples were tested for the presence of influenza specific neutralizing antibodies against A/California/7/09 H1N1 (49 sera) or A/Hong Kong/4801/2014 (50 sera) using four different infection readout methods for the MN assay (cytopathic effect, hemagglutination, ELISA, RT qPCR) and using the HAI assay. The results were compared by correlation analysis and by determining the level of agreement before and after normalization to a standard serum. Titers as measured by the 4 MN assay readouts showed good correlation, with high Person's r for most comparisons. However, agreement between nominal titers varied with readouts compared and virus strain used. In addition, Pearson's correlation of MN titers with HAI titers was high but agreement of nominal titers was moderate and the average difference between the readings of two assays (bias) was virus strain-dependent. Normalization to a standard serum did not result in better agreement of assay results. Our study demonstrates that different MN readouts result in nominally different antibody titers. Accordingly, the use of a common and standardized MN assay protocol will be crucial to minimize inter-laboratory variability. https://www.selleckchem.com/products/AZD0530.html Based on reproducibility, cost effectiveness and unbiased assessment of results we elected the MN assay with ELISA readout as most suitable for a possible replacement of the HAI assay. Japanese encephalitis (JE) poses a serious threat to the world's public health yet without a cure, the only way to prevent Japanese encephalitis virus (JEV) infection is vaccination. Live attenuated vaccine (SA14-14-2 strain) is the most widely used JE vaccine, and clinical data have confirmed its safety and effectiveness. Eight sitesassociated with virulence in the Envelope (E) protein are often the focus of quality control of JE vaccine. However, sequences retrieved from NCBI, as well as our previous results showed that the wild strain SA14 may harbor two different amino acids at amino acid residue 244 of the E glycoprotein (E244), and it may be related to virulence. In this study, we introduced a single mutation at nt1708 (G → A) in the full-length cDNA clone of SA14-14-2, replacing a Gly with Glu at amino acid residue 244 of the E glycoprotein, and successfully constructed the mutant virus (JEV E244). JEV E244 exhibited a similar plaque morphology and growth characteristics to JEV SA14-14-2 in cell culture. However, it had lethal neurovirulence in **** and could enter the brain following intraperitoneal inoculation. Moreover, the virulence of JEV E244 in the context of vaccine in **** is significantly different from that of the JEV E244 alone. These results suggested that E244 site should be included in the assessment of the genetic stability of the attenuated JE vaccine. The detection of minor mutations in vaccine population and influence on the safety of vaccine is discussed. BACKGROUND The patients with shoulder instability or disorders in overhead athletes have been considered to have an abnormal micromotion at the glenohumeral joint. However, the normal range of the micromotion has not been available during axial rotation with various abduction angles, especially above 90° abduction. This study aimed to investigate the glenohumeral translation and influence of the glenohumeral ligaments during axial rotation with up to maximum abduction. METHODS Fourteen healthy volunteers performed active axial rotations at 0°, 90°, 135°, and maximal abduction angles. The positions of the humeral head center relative to the glenoid at maximally external, neutral, and maximally internal rotations (ER, NR, IR, respectively) for each abduction angle were evaluated using two- (2D) and three-dimensional (3D) shape matching registration techniques. The shortest pathway and its length between the origin and insertion of the superior, middle, and inferior glenohumeral ligaments (SGHL, MGHL, and IGHL, respectively) were calculated for each position. RESULTS The glenohumeral joint showed 3.1 mm of superoinferior translation during axial rotation at 0° abduction (P  less then  0.0001), and 2.6 mm and 4.5 mm anteroposterior translation at 135° and maximal abduction (P  less then  0.0001), respectively. The SGHL and MGHL reached a maximum length at ER with 0° abduction, and the anterior and posterior bands of the IGHL reached a maximum at ER with 90° abduction and IR with 0° abduction. CONCLUSIONS These findings indicated that the SGHL played a role as an inferior suppressor at 0° abduction, while the anterior band of IGHL played a role as an anterior stabilizer at 90° abduction. Every glenohumeral ligament did not get taut and the anteroposterior translation became greater with increasing abduction angle, above 90°. These results could be used as a reference when comparing with the pathological shoulders in the future study. PURPOSE The role of prophylactic cranial irradiation (PCI) in treatment of extensive-stage small-cell lung cancer (SCLC) is controversial. The aim of this study was to systematically evaluate the efficacy and safety of using PCI in the treatment of extensive-stage SCLC. In the present study, we examined whether PCI was essential for the optimal treatment of extensive-disease small-cell lung cancer. MATERIAL AND METHODS We searched the PubMed, Embase, Medline, and China National Knowledge Infrastructure databases to identify articles that assessed the efficacy of PCI in treating extensive-stage small-cell lung cancer patients. RESULTS We identified 8 studies that involved a total of 982 patients who received PCI (PCI group) and a total of 4509 patients who did not receive PCI (control group). The results showed that PCI significantly improved the 1-year overall survival rate (HR=1.50; 95% CI 1.23-1.82; I2=67%; P less then 0.0001) and reduced the incidence of brain metastasis (HR=0.46; 95% CI 0.37-0.58; I2=6%; P less then 0.
    The data suggest that Qβ VLPs is an excellent approach to elicit high-titer CHIKV E2-protein antibodies at a lower dose of antigen and future studies should assess whether Qβ-CHIKV E2 aa 2800-2818 VLPs and Qβ-CHIKV E2 aa 3025-3058 VLPs can neutralize a Singapore Strain of CHIKV. Determination of influenza-specific antibody titers is commonly done using the hemagglutination inhibition assay (HAI) and the viral microneutralization assay (MN). Both assays are characterized by high intra- and inter-laboratory variability. The HAI assay offers little opportunity for standardization. For the MN assay, variability might be due to the use of different assay protocols employing different readouts. We therefore aimed at investigating which of the MN assay readout methods currently in use would be the most suitable choice for a standardized MN assay that could serve as a substitute for the HAI assay. For this purpose, human serum samples were tested for the presence of influenza specific neutralizing antibodies against A/California/7/09 H1N1 (49 sera) or A/Hong Kong/4801/2014 (50 sera) using four different infection readout methods for the MN assay (cytopathic effect, hemagglutination, ELISA, RT qPCR) and using the HAI assay. The results were compared by correlation analysis and by determining the level of agreement before and after normalization to a standard serum. Titers as measured by the 4 MN assay readouts showed good correlation, with high Person's r for most comparisons. However, agreement between nominal titers varied with readouts compared and virus strain used. In addition, Pearson's correlation of MN titers with HAI titers was high but agreement of nominal titers was moderate and the average difference between the readings of two assays (bias) was virus strain-dependent. Normalization to a standard serum did not result in better agreement of assay results. Our study demonstrates that different MN readouts result in nominally different antibody titers. Accordingly, the use of a common and standardized MN assay protocol will be crucial to minimize inter-laboratory variability. https://www.selleckchem.com/products/AZD0530.html Based on reproducibility, cost effectiveness and unbiased assessment of results we elected the MN assay with ELISA readout as most suitable for a possible replacement of the HAI assay. Japanese encephalitis (JE) poses a serious threat to the world's public health yet without a cure, the only way to prevent Japanese encephalitis virus (JEV) infection is vaccination. Live attenuated vaccine (SA14-14-2 strain) is the most widely used JE vaccine, and clinical data have confirmed its safety and effectiveness. Eight sitesassociated with virulence in the Envelope (E) protein are often the focus of quality control of JE vaccine. However, sequences retrieved from NCBI, as well as our previous results showed that the wild strain SA14 may harbor two different amino acids at amino acid residue 244 of the E glycoprotein (E244), and it may be related to virulence. In this study, we introduced a single mutation at nt1708 (G → A) in the full-length cDNA clone of SA14-14-2, replacing a Gly with Glu at amino acid residue 244 of the E glycoprotein, and successfully constructed the mutant virus (JEV E244). JEV E244 exhibited a similar plaque morphology and growth characteristics to JEV SA14-14-2 in cell culture. However, it had lethal neurovirulence in mice and could enter the brain following intraperitoneal inoculation. Moreover, the virulence of JEV E244 in the context of vaccine in mice is significantly different from that of the JEV E244 alone. These results suggested that E244 site should be included in the assessment of the genetic stability of the attenuated JE vaccine. The detection of minor mutations in vaccine population and influence on the safety of vaccine is discussed. BACKGROUND The patients with shoulder instability or disorders in overhead athletes have been considered to have an abnormal micromotion at the glenohumeral joint. However, the normal range of the micromotion has not been available during axial rotation with various abduction angles, especially above 90° abduction. This study aimed to investigate the glenohumeral translation and influence of the glenohumeral ligaments during axial rotation with up to maximum abduction. METHODS Fourteen healthy volunteers performed active axial rotations at 0°, 90°, 135°, and maximal abduction angles. The positions of the humeral head center relative to the glenoid at maximally external, neutral, and maximally internal rotations (ER, NR, IR, respectively) for each abduction angle were evaluated using two- (2D) and three-dimensional (3D) shape matching registration techniques. The shortest pathway and its length between the origin and insertion of the superior, middle, and inferior glenohumeral ligaments (SGHL, MGHL, and IGHL, respectively) were calculated for each position. RESULTS The glenohumeral joint showed 3.1 mm of superoinferior translation during axial rotation at 0° abduction (P  less then  0.0001), and 2.6 mm and 4.5 mm anteroposterior translation at 135° and maximal abduction (P  less then  0.0001), respectively. The SGHL and MGHL reached a maximum length at ER with 0° abduction, and the anterior and posterior bands of the IGHL reached a maximum at ER with 90° abduction and IR with 0° abduction. CONCLUSIONS These findings indicated that the SGHL played a role as an inferior suppressor at 0° abduction, while the anterior band of IGHL played a role as an anterior stabilizer at 90° abduction. Every glenohumeral ligament did not get taut and the anteroposterior translation became greater with increasing abduction angle, above 90°. These results could be used as a reference when comparing with the pathological shoulders in the future study. PURPOSE The role of prophylactic cranial irradiation (PCI) in treatment of extensive-stage small-cell lung cancer (SCLC) is controversial. The aim of this study was to systematically evaluate the efficacy and safety of using PCI in the treatment of extensive-stage SCLC. In the present study, we examined whether PCI was essential for the optimal treatment of extensive-disease small-cell lung cancer. MATERIAL AND METHODS We searched the PubMed, Embase, Medline, and China National Knowledge Infrastructure databases to identify articles that assessed the efficacy of PCI in treating extensive-stage small-cell lung cancer patients. RESULTS We identified 8 studies that involved a total of 982 patients who received PCI (PCI group) and a total of 4509 patients who did not receive PCI (control group). The results showed that PCI significantly improved the 1-year overall survival rate (HR=1.50; 95% CI 1.23-1.82; I2=67%; P less then 0.0001) and reduced the incidence of brain metastasis (HR=0.46; 95% CI 0.37-0.58; I2=6%; P less then 0.
    0 Comments 0 Shares 5 Views 0 Reviews
More Stories