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  • The discovery of non-coding RNAs (ncRNAs), and the subsequent elucidation of their functional roles, was largely delayed due to the misidentification of non-protein-coding parts of DNA as "junk DNA," which forced ncRNAs into the shadows of their protein-coding counterparts. However, over the past decade, insight into the important regulatory roles of ncRNAs has led to rapid progress in their identification and characterization. Of the different types of ncRNAs, long non-coding RNAs (lncRNAs), has attracted considerable attention due to their mRNA-like structures and gene regulatory functions in plant stress responses. While RNA sequencing has been commonly used for mining lncRNAs, a lack of widespread conservation at the sequence level in addition to relatively low and highly tissue-specific expression patterns challenges high-throughput in silico identification approaches. The complex folding characteristics of lncRNA molecules also complicate target predictions, as the knowledge about the interaction interfaces between lncRNAs and potential targets is insufficient. Progress in characterizing lncRNAs and their targets from different species may hold the key to efficient identification of this class of ncRNAs from transcriptomic and potentially genomic resources. In wheat and barley, two of the most important crops, the knowledge about lncRNAs is very limited. However, recently published high-quality genomes of these crops are considered as promising resources for the identification of not only lncRNAs, but any class of molecules. Considering the increasing demand for food, these resources should be used efficiently to discover molecular mechanisms lying behind development and a/biotic stress responses. https://www.selleckchem.com/products/finerenone.html As our understanding of lncRNAs expands, interactions among ncRNA classes, as well as interactions with the coding sequences, will likely define novel functional networks that may be modulated for crop improvement. Copyright © 2020 Budak, Kaya and Cagirici.Salinity stress severely inhibits the growth of plant via ionic toxicity and osmotic constraint. Exogenous silicon (Si) can alleviate salinity stress, but the mechanisms behind remain unclear. To investigate the role of Si in alleviating ionic and osmotic components of salinity, rice (Oryza sativa L.) seedlings were grown hydroponically in iso-osmotic stress conditions developed from NaCl or polyethylene glycol (PEG). The effects of Si on the growth of shoot and root of rice under salinity and PEG-derived osmotic stress were evaluated and further compared using principal coordinate analysis (PCoA). We also analyzed the concentrations of Na, K, and compatible osmolytes, tissue sap osmotic potential, antioxidant enzymes activities, and the expression of aquaporin genes. Generally, Si significantly promoted shoot and root growth in rice exposed to both NaCl and PEG. PCoA shows that the Si-induced distance change under NaCl treatment was larger than that under PEG treatment in the shoot, while the Si-induced dist. Si ameliorates ionic toxicity by decreasing Na uptake and increasing root Na reservation. Si alleviates osmotic constraint by regulating root morphological traits and root osmotic potential but not aquaporin gene expression for water uptake, and promoting transpiration force but not osmotic force in shoot for root-to-shoot water transport. Copyright © 2020 Yan, Fan, Peng, Yin, Xiao and Liang.Calcium has long been known to regulate the metabolism of chloroplasts, concerning both light and carbon reactions of photosynthesis, as well as additional non photosynthesis-related processes. In addition to undergo Ca2+ regulation, chloroplasts can also influence the overall Ca2+ signaling pathways of the plant cell. Compelling evidence indicate that chloroplasts can generate specific stromal Ca2+ signals and contribute to the fine tuning of cytoplasmic Ca2+ signaling in response to different environmental stimuli. The recent set up of a toolkit of genetically encoded Ca2+ indicators, targeted to different chloroplast subcompartments (envelope, stroma, thylakoids) has helped to unravel the participation of chloroplasts in intracellular Ca2+ handling in resting conditions and during signal transduction. Intra-chloroplast Ca2+ signals have been demonstrated to occur in response to specific environmental stimuli, suggesting a role for these plant-unique organelles in transducing Ca2+-mediated stress signals. In this mini-review we present current knowledge of stimulus-specific intra-chloroplast Ca2+ transients, as well as recent advances in the identification and characterization of Ca2+-permeable channels/transporters localized at chloroplast membranes. In particular, the potential role played by cMCU, a chloroplast-localized member of the mitochondrial calcium uniporter (MCU) family, as component of plant environmental sensing is discussed in detail, taking into account some specific structural features of cMCU. In summary, the recent molecular identification of some players of chloroplast Ca2+ signaling has opened new avenues in this rapidly developing field and will hopefully allow a deeper understanding of the role of chloroplasts in shaping physiological responses in plants. Copyright © 2020 Navazio, Formentin, Cendron and Szabò.Strawberry shelf life is limited, and little is known about the postharvest regulation of senescence in different fruit tissues. Strawberry is classified as a non-climacteric fruit, yet it is known that ethylene affects strawberry ripening. Here the effects of continuous exogenous ethylene (50 µl l-1) were investigated in cold stored strawberry (5°C). The physiological and biochemical responses of ripe strawberry were evaluated across 6 days, together with hormonal profiles of the whole fruit and individual tissues (achenes and receptacle). Continuous exposure to ethylene induced as a first response an accumulation of abscisic acid (ABA) in the receptacle tissue, followed by an increase in CO2 production. Ethylene also elicited sucrose hydrolysis and malic acid catabolism, with the major effect seen after 4 days of ethylene exposure. Additionally, accumulation of phenolics (epicatechin and chlorogenic acid) were also observed in ethylene treated strawberry. Achenes did not exhibit a response to ethylene, yet catabolism of both ABA and auxins increased by two thirds during air storage.
    The discovery of non-coding RNAs (ncRNAs), and the subsequent elucidation of their functional roles, was largely delayed due to the misidentification of non-protein-coding parts of DNA as "junk DNA," which forced ncRNAs into the shadows of their protein-coding counterparts. However, over the past decade, insight into the important regulatory roles of ncRNAs has led to rapid progress in their identification and characterization. Of the different types of ncRNAs, long non-coding RNAs (lncRNAs), has attracted considerable attention due to their mRNA-like structures and gene regulatory functions in plant stress responses. While RNA sequencing has been commonly used for mining lncRNAs, a lack of widespread conservation at the sequence level in addition to relatively low and highly tissue-specific expression patterns challenges high-throughput in silico identification approaches. The complex folding characteristics of lncRNA molecules also complicate target predictions, as the knowledge about the interaction interfaces between lncRNAs and potential targets is insufficient. Progress in characterizing lncRNAs and their targets from different species may hold the key to efficient identification of this class of ncRNAs from transcriptomic and potentially genomic resources. In wheat and barley, two of the most important crops, the knowledge about lncRNAs is very limited. However, recently published high-quality genomes of these crops are considered as promising resources for the identification of not only lncRNAs, but any class of molecules. Considering the increasing demand for food, these resources should be used efficiently to discover molecular mechanisms lying behind development and a/biotic stress responses. https://www.selleckchem.com/products/finerenone.html As our understanding of lncRNAs expands, interactions among ncRNA classes, as well as interactions with the coding sequences, will likely define novel functional networks that may be modulated for crop improvement. Copyright © 2020 Budak, Kaya and Cagirici.Salinity stress severely inhibits the growth of plant via ionic toxicity and osmotic constraint. Exogenous silicon (Si) can alleviate salinity stress, but the mechanisms behind remain unclear. To investigate the role of Si in alleviating ionic and osmotic components of salinity, rice (Oryza sativa L.) seedlings were grown hydroponically in iso-osmotic stress conditions developed from NaCl or polyethylene glycol (PEG). The effects of Si on the growth of shoot and root of rice under salinity and PEG-derived osmotic stress were evaluated and further compared using principal coordinate analysis (PCoA). We also analyzed the concentrations of Na, K, and compatible osmolytes, tissue sap osmotic potential, antioxidant enzymes activities, and the expression of aquaporin genes. Generally, Si significantly promoted shoot and root growth in rice exposed to both NaCl and PEG. PCoA shows that the Si-induced distance change under NaCl treatment was larger than that under PEG treatment in the shoot, while the Si-induced dist. Si ameliorates ionic toxicity by decreasing Na uptake and increasing root Na reservation. Si alleviates osmotic constraint by regulating root morphological traits and root osmotic potential but not aquaporin gene expression for water uptake, and promoting transpiration force but not osmotic force in shoot for root-to-shoot water transport. Copyright © 2020 Yan, Fan, Peng, Yin, Xiao and Liang.Calcium has long been known to regulate the metabolism of chloroplasts, concerning both light and carbon reactions of photosynthesis, as well as additional non photosynthesis-related processes. In addition to undergo Ca2+ regulation, chloroplasts can also influence the overall Ca2+ signaling pathways of the plant cell. Compelling evidence indicate that chloroplasts can generate specific stromal Ca2+ signals and contribute to the fine tuning of cytoplasmic Ca2+ signaling in response to different environmental stimuli. The recent set up of a toolkit of genetically encoded Ca2+ indicators, targeted to different chloroplast subcompartments (envelope, stroma, thylakoids) has helped to unravel the participation of chloroplasts in intracellular Ca2+ handling in resting conditions and during signal transduction. Intra-chloroplast Ca2+ signals have been demonstrated to occur in response to specific environmental stimuli, suggesting a role for these plant-unique organelles in transducing Ca2+-mediated stress signals. In this mini-review we present current knowledge of stimulus-specific intra-chloroplast Ca2+ transients, as well as recent advances in the identification and characterization of Ca2+-permeable channels/transporters localized at chloroplast membranes. In particular, the potential role played by cMCU, a chloroplast-localized member of the mitochondrial calcium uniporter (MCU) family, as component of plant environmental sensing is discussed in detail, taking into account some specific structural features of cMCU. In summary, the recent molecular identification of some players of chloroplast Ca2+ signaling has opened new avenues in this rapidly developing field and will hopefully allow a deeper understanding of the role of chloroplasts in shaping physiological responses in plants. Copyright © 2020 Navazio, Formentin, Cendron and Szabò.Strawberry shelf life is limited, and little is known about the postharvest regulation of senescence in different fruit tissues. Strawberry is classified as a non-climacteric fruit, yet it is known that ethylene affects strawberry ripening. Here the effects of continuous exogenous ethylene (50 µl l-1) were investigated in cold stored strawberry (5°C). The physiological and biochemical responses of ripe strawberry were evaluated across 6 days, together with hormonal profiles of the whole fruit and individual tissues (achenes and receptacle). Continuous exposure to ethylene induced as a first response an accumulation of abscisic acid (ABA) in the receptacle tissue, followed by an increase in CO2 production. Ethylene also elicited sucrose hydrolysis and malic acid catabolism, with the major effect seen after 4 days of ethylene exposure. Additionally, accumulation of phenolics (epicatechin and chlorogenic acid) were also observed in ethylene treated strawberry. Achenes did not exhibit a response to ethylene, yet catabolism of both ABA and auxins increased by two thirds during air storage.
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  • (1) Background Variants of the interleukin-1 receptor antagonist (IL1RN) gene, encoding an anti-inflammatory cytokine, are associated with asthma. Asthma is a chronic inflammatory disease of the airway influenced by interactions between genetic variants and environmental factors. We discovered a gene-environment interaction (GEI) of IL1RN polymorphisms with childhood environmental tobacco smoke (ETS) exposure on asthma susceptibility in an urban adult population. (2) Methods DNA samples from the NYU/Bellevue Asthma Registry were genotyped for tag SNPs in IL1RN in asthma cases and unrelated healthy controls. Logistic regressions were used to study the GEI between IL1RN variants and childhood ETS exposures on asthma and early onset asthma, respectively, adjusting for population admixture and other covariates. (3) Results Whereas the rare genotypes of IL1RN SNPs (e.g., GG in SNP rs2234678) were associated with decreased risk for asthma among those without ETS exposure (odds ratio OR = 0.215, p = 0.021), they are associated with increased risk for early onset asthma among those with childhood ETS (OR = 4.467, p = 0.021). (4) Conclusions We identified a GEI between polymorphisms of IL1RN and childhood ETS exposure in asthma. Analysis of GEI indicated that childhood ETS exposure disrupted the protective effect of some haplotypes/genotypes of IL1RN for asthma and turned them into high-risk polymorphisms for early onset asthma.Skeletal muscle injuries in competitive sports cause lengthy absences of athletes from tournaments. This is of tremendous competitive and economic relevance for both the athletes and their respective clubs. Therapy for structural muscle lesions aims to promote regeneration and fast-track return-to-play. A common clinical treatment strategy for muscle injuries is the intramuscular injection of calf blood compound and the homeopathic drug, Tr14. Although the combination of these two agents was reported to reduce recovery time, the regulatory mechanism whereby this occurs remains unknown. In this in vivo study, we selected a rat model of mechanical muscle injury to investigate the effect of this combination therapy on muscle regeneration. Gene expression analysis and histological images revealed that this combined intramuscular injection for muscle lesions can enhance the expression of pro-myogenic genes and proteins and accelerate muscle regeneration. These findings are novel and depict the positive effects of calf blood compound and the homeopathic drug, Tr14, which are utilized in the field of Sports medicine.The aim of this study was to assess occupational exposure to diisononyl phthalate (DiNP) and di(2-propylheptyl) phthalate (DPHP] in Finland. Four companies took part in the research project A cable factory, a plastic producing company, a producer of coated textiles, and a tarpaulin producer. The cable factory used DPHP (and occasionally also diisodecyl phthalate, DiDP), the plastic producing company used both DPHP and DiNP, and the latter two companies used DiNP in their production. Exposure was assessed by measuring phthalate metabolites in urine samples (biomonitoring) and by performing air measurements. Low-level occupational exposure to DiNP was observed in the company that produced coated textiles-out of eight workers, one extruder operator was exposed to DiNP at levels exceeding the non-occupationally exposed population background levels. Some workers in the cable factory and the plastics producing company were occupationally exposed to DPHP. Air levels of phthalates were generally low, mostly below the limit of quantification. All phthalate metabolite concentrations were, however, well below the calculated biomonitoring equivalents, which suggests that the health risks related to the exposure are low.In vivo gene delivery involves direct injection of nucleic acids (NAs) into tissues, organs, or tail-veins. https://www.selleckchem.com/products/ly3039478.html It has been recognized as a useful tool for evaluating the function of a gene of interest (GOI), creating models for human disease and basic research targeting gene therapy. Cargo frequently used for gene delivery are largely divided into viral and non-viral vectors. Viral vectors have strong infectious activity and do not require the use of instruments or reagents helpful for gene delivery but bear immunological and tumorigenic problems. In contrast, non-viral vectors strictly require instruments (i.e., electroporator) or reagents (i.e., liposomes) for enhanced uptake of NAs by cells and are often accompanied by weak transfection activity, with less immunological and tumorigenic problems. Chromosomal integration of GOI-bearing transgenes would be ideal for achieving long-term expression of GOI. piggyBac (PB), one of three transposons (PB, Sleeping Beauty (SB), and Tol2) found thus far, has been used for efficient transfection of GOI in various mammalian cells in vitro and in vivo. In this review, we outline recent achievements of PB-based production of genetically modified animals and organs and will provide some experimental concepts using this system.Recent discoveries on the neurobiology of the immunocompetent cells of the central nervous system (CNS), microglia, have been recognized as a growing field of investigation on the interactions between the brain and the immune system. Several environmental contexts such as stress, lesions, infectious diseases, and nutritional and hormonal disorders can interfere with CNS homeostasis, directly impacting microglial physiology. Despite many encouraging discoveries in this field, there are still some controversies that raise issues to be discussed, especially regarding the relationship between the microglial phenotype assumed in distinct contexts and respective consequences in different neurobiological processes, such as disorders of brain development and neuroplasticity. Also, there is an increasing interest in discussing microglial-immune system cross-talk in health and in pathological conditions. In this review, we discuss recent literature concerning microglial function during development and homeostasis. In addition, we explore the contribution of microglia to synaptic disorders mediated by different neuroinflammatory outcomes during pre- and postnatal development, with long-term consequences impacting on the risk and vulnerability to the emergence of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.
    (1) Background Variants of the interleukin-1 receptor antagonist (IL1RN) gene, encoding an anti-inflammatory cytokine, are associated with asthma. Asthma is a chronic inflammatory disease of the airway influenced by interactions between genetic variants and environmental factors. We discovered a gene-environment interaction (GEI) of IL1RN polymorphisms with childhood environmental tobacco smoke (ETS) exposure on asthma susceptibility in an urban adult population. (2) Methods DNA samples from the NYU/Bellevue Asthma Registry were genotyped for tag SNPs in IL1RN in asthma cases and unrelated healthy controls. Logistic regressions were used to study the GEI between IL1RN variants and childhood ETS exposures on asthma and early onset asthma, respectively, adjusting for population admixture and other covariates. (3) Results Whereas the rare genotypes of IL1RN SNPs (e.g., GG in SNP rs2234678) were associated with decreased risk for asthma among those without ETS exposure (odds ratio OR = 0.215, p = 0.021), they are associated with increased risk for early onset asthma among those with childhood ETS (OR = 4.467, p = 0.021). (4) Conclusions We identified a GEI between polymorphisms of IL1RN and childhood ETS exposure in asthma. Analysis of GEI indicated that childhood ETS exposure disrupted the protective effect of some haplotypes/genotypes of IL1RN for asthma and turned them into high-risk polymorphisms for early onset asthma.Skeletal muscle injuries in competitive sports cause lengthy absences of athletes from tournaments. This is of tremendous competitive and economic relevance for both the athletes and their respective clubs. Therapy for structural muscle lesions aims to promote regeneration and fast-track return-to-play. A common clinical treatment strategy for muscle injuries is the intramuscular injection of calf blood compound and the homeopathic drug, Tr14. Although the combination of these two agents was reported to reduce recovery time, the regulatory mechanism whereby this occurs remains unknown. In this in vivo study, we selected a rat model of mechanical muscle injury to investigate the effect of this combination therapy on muscle regeneration. Gene expression analysis and histological images revealed that this combined intramuscular injection for muscle lesions can enhance the expression of pro-myogenic genes and proteins and accelerate muscle regeneration. These findings are novel and depict the positive effects of calf blood compound and the homeopathic drug, Tr14, which are utilized in the field of Sports medicine.The aim of this study was to assess occupational exposure to diisononyl phthalate (DiNP) and di(2-propylheptyl) phthalate (DPHP] in Finland. Four companies took part in the research project A cable factory, a plastic producing company, a producer of coated textiles, and a tarpaulin producer. The cable factory used DPHP (and occasionally also diisodecyl phthalate, DiDP), the plastic producing company used both DPHP and DiNP, and the latter two companies used DiNP in their production. Exposure was assessed by measuring phthalate metabolites in urine samples (biomonitoring) and by performing air measurements. Low-level occupational exposure to DiNP was observed in the company that produced coated textiles-out of eight workers, one extruder operator was exposed to DiNP at levels exceeding the non-occupationally exposed population background levels. Some workers in the cable factory and the plastics producing company were occupationally exposed to DPHP. Air levels of phthalates were generally low, mostly below the limit of quantification. All phthalate metabolite concentrations were, however, well below the calculated biomonitoring equivalents, which suggests that the health risks related to the exposure are low.In vivo gene delivery involves direct injection of nucleic acids (NAs) into tissues, organs, or tail-veins. https://www.selleckchem.com/products/ly3039478.html It has been recognized as a useful tool for evaluating the function of a gene of interest (GOI), creating models for human disease and basic research targeting gene therapy. Cargo frequently used for gene delivery are largely divided into viral and non-viral vectors. Viral vectors have strong infectious activity and do not require the use of instruments or reagents helpful for gene delivery but bear immunological and tumorigenic problems. In contrast, non-viral vectors strictly require instruments (i.e., electroporator) or reagents (i.e., liposomes) for enhanced uptake of NAs by cells and are often accompanied by weak transfection activity, with less immunological and tumorigenic problems. Chromosomal integration of GOI-bearing transgenes would be ideal for achieving long-term expression of GOI. piggyBac (PB), one of three transposons (PB, Sleeping Beauty (SB), and Tol2) found thus far, has been used for efficient transfection of GOI in various mammalian cells in vitro and in vivo. In this review, we outline recent achievements of PB-based production of genetically modified animals and organs and will provide some experimental concepts using this system.Recent discoveries on the neurobiology of the immunocompetent cells of the central nervous system (CNS), microglia, have been recognized as a growing field of investigation on the interactions between the brain and the immune system. Several environmental contexts such as stress, lesions, infectious diseases, and nutritional and hormonal disorders can interfere with CNS homeostasis, directly impacting microglial physiology. Despite many encouraging discoveries in this field, there are still some controversies that raise issues to be discussed, especially regarding the relationship between the microglial phenotype assumed in distinct contexts and respective consequences in different neurobiological processes, such as disorders of brain development and neuroplasticity. Also, there is an increasing interest in discussing microglial-immune system cross-talk in health and in pathological conditions. In this review, we discuss recent literature concerning microglial function during development and homeostasis. In addition, we explore the contribution of microglia to synaptic disorders mediated by different neuroinflammatory outcomes during pre- and postnatal development, with long-term consequences impacting on the risk and vulnerability to the emergence of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.
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  • © 2020 Wiley Periodicals, Inc.Root-knot nematodes (RKNs; Meloidogyne spp.) induce new post-embryogenic organs within the roots (galls) were they stablish and differentiate nematode's feeding cells, giant-cells (GCs). Developmental programs and functional genes involved are scarcely defined. Arabidopsis root apical meristem (RAM), lateral root (LR) and callus marker lines SHORT-ROOT/SHR, SCARECROW/SCR, SCHIZORIZA/SCZ, WUSCHEL-RELATED-HOMEOBOX-5/WOX5, AUXIN-RESPONSIVE-FACTOR-5/ARF5, ARABIDOPSIS-HISTIDINE PHOSPHOTRANSFER-PROTEIN-6/AHP6, GATA-TRANSCRIPTION FACTOR-23/GATA23, S-PHASE-KINASE-ASSOCIATED-PROTEIN2B/SKP2B were analysed for nematode-dependent expression. Their corresponding loss-of-function lines, including those for LR upstream regulators SOLITARY ROOT/SLR/IAA14, BONDELOS/BDL/IAA12 and INDOLE-3-ACETIC-ACID-INDUCIBLE-28/IAA28 were tested for RKNs resistance/tolerance. LR genes, e.g. ARF5 (key factor for root stem-cell niche regeneration), GATA23 (that specify pluripotent founder cells), and AHP6 (cytokinin-signalling-inhibitor regulating pericycle cell-divisions orientation), show a crucial function during gall formation. RKNs do not compromise the number of founder cells or LR primordia but locally induce gall formation possibly by tuning the auxin/cytokinin balance where AHP6 might be necessary. Key RAM marker genes were induced and functional in galls. Therefore, the activation of plant developmental programs promoting transient-pluripotency/stemness leads to the generation of quiescent-centre and meristematic-like cell identities within the vascular cylinder of galls. Nematodes enlist developmental pathways of new-organogenesis and/or root regeneration in the vascular cells of galls. This should determine meristematic cell identities with enough transient-pluripotency for gall organogenesis. This article is protected by copyright. All rights reserved.Microgreens are rich functional crops with valuable nutritional elements that have health benefits when used as food supplements. Growth characterization, nutritional composition profile of 21 varieties representing five species of the Brassica genus as microgreens were assessed under light-emitting diodes (LEDs) conditions. Microgreens were grown under four different LEDs ratios (%); redblue 8020 and 2080 (R80 B20 and R20 B80 ), or redgreenblue 701020 and 201070 (R70 G10 B20 and R20 G10 B70 ). Results indicated that supplemental lighting with green LEDs (R70 G10 B20 ) enhanced vegetative growth and morphology, while blue LEDs (R20 B80 ) increased the mineral and vitamin contents. Interestingly, by linking the nutritional content with the growth yield to define the optimal LEDs setup, we found that the best lighting to promote the microgreen growth was the green LEDs combination (R70 G10 B20 ). Remarkably, under the green LEDs combination (R70 G10 B20 ) conditions, the microgreens of Kohlrabi purple, Cabbage red, Broccoli, Kale Tucsan, Komatsuna red, Tatsoi and Cabbage green, which can benefit human health in conditions with limited food, had the highest growth and nutritional content. © 2020 Scandinavian Plant Physiology Society.PURPOSE To predict biological effects of Targeted Alpha Therapy (TAT) in pre-clinical studies, dosimetry calculations based on the micro-level distributions of emitters are essential. Due to the saturation of the tumor antigenic sites and bonding breaks by decay, some of Alpha-immuno-conjugate and decay daughters may inevitably be transported by convection and diffusion along with blood or lymphatic circulation. This results in highly non-uniform and unsteady distributions of irradiation sources. Since the micro level distribution of emitters cannot be measured and obtained in patients with current technology, a modelling toolset to give more insight of the internal dose could be an alternative. METHODS A multi-physics model based on a Monte Carlo microdosimetry technique and Computational Fluid Dynamics (CFD) modelling was developed and applied to multiple internal irradiation sources. The CFD model tracks the path of the radionuclides and the dose model is capable of evaluating the time-dependent absorbed dose to the target. RESULTS The conceptual model is capable of handling complex non-uniform irradiation sources in vasculature. The results from the simulations indicate that the assumption of homogeneous and motionless distribution of the administered activity used in the conventional dose calculation tends to significantly underestimate or overestimate the absorbed dose to the vascular system in various scenarios. https://www.selleckchem.com/products/zen-3694.html CONCLUSION Modeling the in vivo transport of radionuclides has the potential to improve the accuracy of TAT dose estimates. It could be the first step to develop a simulation tool set for assessing absorbed dose to tumor or normal tissues and predict the corresponding biological responses in the future. This article is protected by copyright. All rights reserved.Photosynthetic stimulation by elevated [CO2 ] (e[CO2 ]) may be limited by the capacity of sink organs to use photosynthates. In many legumes, N2 -fixing symbionts in root nodules provide an additional sink, so that legumes may be better able to profit from e[CO2 ]. However, drought not only constrains photosynthesis but also size and activity of sinks, and little is known about the interaction of e[CO2 ] and drought on carbon sink strength of nodules and other organs. To compare carbon sink strength, faba bean was grown under ambient (400 ppm) or elevated (700 ppm) atmospheric [CO2 ] and subjected to well-watered or drought treatments, and then exposed to 13 C pulse-labelling using custom-built chambers to track the fate of new photosynthates. Drought decreased 13 C uptake and nodule sink strength, and this effect was even greater under e[CO2 ], and associated with an accumulation of amino acids in nodules. This resulted in decreased N2 fixation, increased accumulation of new photosynthates (13 C/sugars) in leaves, which in turn can feed **** on photosynthesis. Our study suggests that nodule C sink activity is key to avoid sink limitation in legumes under e[CO2 ], and legumes may only be able to achieve greater C gain if nodule activity is maintained. This article is protected by copyright. All rights reserved.
    © 2020 Wiley Periodicals, Inc.Root-knot nematodes (RKNs; Meloidogyne spp.) induce new post-embryogenic organs within the roots (galls) were they stablish and differentiate nematode's feeding cells, giant-cells (GCs). Developmental programs and functional genes involved are scarcely defined. Arabidopsis root apical meristem (RAM), lateral root (LR) and callus marker lines SHORT-ROOT/SHR, SCARECROW/SCR, SCHIZORIZA/SCZ, WUSCHEL-RELATED-HOMEOBOX-5/WOX5, AUXIN-RESPONSIVE-FACTOR-5/ARF5, ARABIDOPSIS-HISTIDINE PHOSPHOTRANSFER-PROTEIN-6/AHP6, GATA-TRANSCRIPTION FACTOR-23/GATA23, S-PHASE-KINASE-ASSOCIATED-PROTEIN2B/SKP2B were analysed for nematode-dependent expression. Their corresponding loss-of-function lines, including those for LR upstream regulators SOLITARY ROOT/SLR/IAA14, BONDELOS/BDL/IAA12 and INDOLE-3-ACETIC-ACID-INDUCIBLE-28/IAA28 were tested for RKNs resistance/tolerance. LR genes, e.g. ARF5 (key factor for root stem-cell niche regeneration), GATA23 (that specify pluripotent founder cells), and AHP6 (cytokinin-signalling-inhibitor regulating pericycle cell-divisions orientation), show a crucial function during gall formation. RKNs do not compromise the number of founder cells or LR primordia but locally induce gall formation possibly by tuning the auxin/cytokinin balance where AHP6 might be necessary. Key RAM marker genes were induced and functional in galls. Therefore, the activation of plant developmental programs promoting transient-pluripotency/stemness leads to the generation of quiescent-centre and meristematic-like cell identities within the vascular cylinder of galls. Nematodes enlist developmental pathways of new-organogenesis and/or root regeneration in the vascular cells of galls. This should determine meristematic cell identities with enough transient-pluripotency for gall organogenesis. This article is protected by copyright. All rights reserved.Microgreens are rich functional crops with valuable nutritional elements that have health benefits when used as food supplements. Growth characterization, nutritional composition profile of 21 varieties representing five species of the Brassica genus as microgreens were assessed under light-emitting diodes (LEDs) conditions. Microgreens were grown under four different LEDs ratios (%); redblue 8020 and 2080 (R80 B20 and R20 B80 ), or redgreenblue 701020 and 201070 (R70 G10 B20 and R20 G10 B70 ). Results indicated that supplemental lighting with green LEDs (R70 G10 B20 ) enhanced vegetative growth and morphology, while blue LEDs (R20 B80 ) increased the mineral and vitamin contents. Interestingly, by linking the nutritional content with the growth yield to define the optimal LEDs setup, we found that the best lighting to promote the microgreen growth was the green LEDs combination (R70 G10 B20 ). Remarkably, under the green LEDs combination (R70 G10 B20 ) conditions, the microgreens of Kohlrabi purple, Cabbage red, Broccoli, Kale Tucsan, Komatsuna red, Tatsoi and Cabbage green, which can benefit human health in conditions with limited food, had the highest growth and nutritional content. © 2020 Scandinavian Plant Physiology Society.PURPOSE To predict biological effects of Targeted Alpha Therapy (TAT) in pre-clinical studies, dosimetry calculations based on the micro-level distributions of emitters are essential. Due to the saturation of the tumor antigenic sites and bonding breaks by decay, some of Alpha-immuno-conjugate and decay daughters may inevitably be transported by convection and diffusion along with blood or lymphatic circulation. This results in highly non-uniform and unsteady distributions of irradiation sources. Since the micro level distribution of emitters cannot be measured and obtained in patients with current technology, a modelling toolset to give more insight of the internal dose could be an alternative. METHODS A multi-physics model based on a Monte Carlo microdosimetry technique and Computational Fluid Dynamics (CFD) modelling was developed and applied to multiple internal irradiation sources. The CFD model tracks the path of the radionuclides and the dose model is capable of evaluating the time-dependent absorbed dose to the target. RESULTS The conceptual model is capable of handling complex non-uniform irradiation sources in vasculature. The results from the simulations indicate that the assumption of homogeneous and motionless distribution of the administered activity used in the conventional dose calculation tends to significantly underestimate or overestimate the absorbed dose to the vascular system in various scenarios. https://www.selleckchem.com/products/zen-3694.html CONCLUSION Modeling the in vivo transport of radionuclides has the potential to improve the accuracy of TAT dose estimates. It could be the first step to develop a simulation tool set for assessing absorbed dose to tumor or normal tissues and predict the corresponding biological responses in the future. This article is protected by copyright. All rights reserved.Photosynthetic stimulation by elevated [CO2 ] (e[CO2 ]) may be limited by the capacity of sink organs to use photosynthates. In many legumes, N2 -fixing symbionts in root nodules provide an additional sink, so that legumes may be better able to profit from e[CO2 ]. However, drought not only constrains photosynthesis but also size and activity of sinks, and little is known about the interaction of e[CO2 ] and drought on carbon sink strength of nodules and other organs. To compare carbon sink strength, faba bean was grown under ambient (400 ppm) or elevated (700 ppm) atmospheric [CO2 ] and subjected to well-watered or drought treatments, and then exposed to 13 C pulse-labelling using custom-built chambers to track the fate of new photosynthates. Drought decreased 13 C uptake and nodule sink strength, and this effect was even greater under e[CO2 ], and associated with an accumulation of amino acids in nodules. This resulted in decreased N2 fixation, increased accumulation of new photosynthates (13 C/sugars) in leaves, which in turn can feed back on photosynthesis. Our study suggests that nodule C sink activity is key to avoid sink limitation in legumes under e[CO2 ], and legumes may only be able to achieve greater C gain if nodule activity is maintained. This article is protected by copyright. All rights reserved.
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  • Personnel with predeployment psychiatric diagnoses had a statistically significant higher risk for both postdeployment long-term sickness absence, hazard ratio (HR) = 2.06, 95% CI [1.52, 2.80]; and postdeployment MHPs, HR = 2.38, 95% CI [1.73, 3.27], than personnel without a predeployment psychiatric diagnosis. Personnel with a predeployment psychiatric diagnosis demonstrated a higher risk of reporting high levels of perceived combat exposure. Perceived combat exposure was not found to moderate or mediate the effect of a predeployment psychiatric diagnosis on the two outcomes. Additional findings, limitations, and implications are discussed. © 2020 International Society for Traumatic Stress Studies.Neurocognitive symptoms are common in individuals with somatic symptom and related disorders (SSRD), but little is known about the specific impairments in neurocognitive domains in patients with conversion disorder (CD)/functional neurological disorder (FND). https://www.selleckchem.com/products/acy-738.html This study examines neurocognitive functioning in patients with CD/FND compared to patients with other SSRD. The sample consisted of 318 patients. Twenty-nine patients were diagnosed with CD/FND, mean age 42.4, standard deviation (SD) = 13.8 years, 79.3% women, and 289 patients had other SSRD (mean age 42.1, SD = 13.3, 60.2% women). Patients completed a neuropsychological test battery that addressed a broad range of neurocognitive domains, including information processing speed, attention and executive functioning. Patients with CD/FND had clinically significant neurocognitive deficits in all neurocognitive domains based on normative data comparison. Patients with CD/FND also performed significantly worse than patients with other SSRD on information processing speed (Digit Symbol Substitution Test (V = .115, p = .035), Stroop Color-Word Test (SCWT) card 1 (V = .190, p = .006), and SCWT card 2 (V = .244, p  less then  .001). No CD/FND vs. other SSRD differences were observed in other neurocognitive domains. These findings indicate the patients with CD/FND perform worse on information processing speed tests compared to patients with other SSRD. © 2020 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.Postpartum depression is a serious mental illnessdisorder that occurs after delivery and is one of the most common post-partum complications. With the increasing popularity and extensive use of smartphones worldwide and the fact that China has become the country with the largest number of smartphone users, it is necessary to have a deep understanding of the use and influence of smartphones and discuss the role of smartphone applications in postpartum depression. This study evaluated and analysed the contents of all postpartum depression applications available in China, applying the US Preventive Services Task Force Recommendation Statement (Interventions to Prevent Perinatal Depression) and expert consensus on the guidelines for the prevention and treatment of postpartum depression. We used the keywords 'postpartum depression; and 'PPD' to search Android, iOS, and WeChat in the Chinese application market. Two reviewers agreed on the coding guidelines and coded the content and functionality of the application through content analysis to determine its intervention and adherence to the guidelines. In addition, we used the Mobile App Rating Scale (MARS) to evaluate the application for engagement, functionality, aesthetics, and information domains and recorded the features of the postpartum depression application. The current findings suggest that despite the recent expansion of smartphone platforms and increased availability of applications, existing Chinese apps for postpartum depression have low levels of adherence to clinical practice-based guidelines. New apps need to be developed, and existing apps need to be revised following evidence-based principles. © 2020 Australian College of Mental Health Nurses Inc.Borna disease virus 1 (BoDV-1) is the causative agent of Borna disease, an often fatal neurologic condition of domestic mammals, including New World camelids, in endemic areas in Central Europe. Recently, BoDV-1 gained further attention by the confirmation of fatal zoonotic infections in humans. Although Borna disease and BoDV-1 have been described already over the past decades, comprehensive reports of Borna disease outbreaks in domestic animals employing state of the art diagnostic methods are missing. Here, we report a series of BoDV-1 infections in a herd of 27 alpacas (Vicugna pacos) in the federal state of Brandenburg, Germany, which resulted in eleven fatalities (41%) within ten months. Clinical courses ranged from sudden death without previous clinical signs to acute or chronic neurologic disease with death occurring after up to six months. All animals that underwent necropsy exhibited a non-suppurative encephalitis. In addition, six apparently healthy seropositive individuals were identified within ts reserved.The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 2019 in Wuhan, China has spread to over 113 countries with 118,326 infected and 4,292 died as of 11 March 2020 and the World Health Organization (WHO) has just announced COVID-19 a global pandemic. A person under investigation (PUI) for COVID-19 is less likely to present initially to the ophthalmologists compared to emergency care or internal medicine physicians. However, in late February 2020, 2 patients presented simultaneously to our eye casualty with sudden onset of unilateral painful red eye associated with a decline in visual acuity, their intraocular pressure (IOP) were over 40 mmHg and slit-lamp examination findings were suggestive of acute primary angle closure (APAC). This article is protected by copyright. All rights reserved.Limited data exist on the effect of continuous renal replacement therapy (CRRT) methods on anti-epileptic drug pharmacokinetics (PK). This prospective practice-based PK study aims to assess the impact of continuous venovenous hemofiltration (CVVH), a modality of CRRT, on levetiracetam PK in critically ill patients and to derive individualized dosing recommendations. Eleven patients receiving oral or intravenous levetiracetam and CVVH in various intensive care units at a large academic medical center were enrolled to investigate the need for dosing adjustments. Prefilter, postfilter, and ultrafiltrate samples were obtained before dosing, after the completion of the infusion or 1-hour postoral dose, and up to 6 additional time points postinfusion or postoral administration. Patient-specific blood and ultrafiltrate flow rates and laboratory values were also collected at the time of sampling. The average sieving coefficient (SC) for levetiracetam was 0.89 ± 0.1, indicating high filter efficiency. Six of the 11 patients experienced concentrations outside the reported therapeutic range (12-46 mg/L).
    Personnel with predeployment psychiatric diagnoses had a statistically significant higher risk for both postdeployment long-term sickness absence, hazard ratio (HR) = 2.06, 95% CI [1.52, 2.80]; and postdeployment MHPs, HR = 2.38, 95% CI [1.73, 3.27], than personnel without a predeployment psychiatric diagnosis. Personnel with a predeployment psychiatric diagnosis demonstrated a higher risk of reporting high levels of perceived combat exposure. Perceived combat exposure was not found to moderate or mediate the effect of a predeployment psychiatric diagnosis on the two outcomes. Additional findings, limitations, and implications are discussed. © 2020 International Society for Traumatic Stress Studies.Neurocognitive symptoms are common in individuals with somatic symptom and related disorders (SSRD), but little is known about the specific impairments in neurocognitive domains in patients with conversion disorder (CD)/functional neurological disorder (FND). https://www.selleckchem.com/products/acy-738.html This study examines neurocognitive functioning in patients with CD/FND compared to patients with other SSRD. The sample consisted of 318 patients. Twenty-nine patients were diagnosed with CD/FND, mean age 42.4, standard deviation (SD) = 13.8 years, 79.3% women, and 289 patients had other SSRD (mean age 42.1, SD = 13.3, 60.2% women). Patients completed a neuropsychological test battery that addressed a broad range of neurocognitive domains, including information processing speed, attention and executive functioning. Patients with CD/FND had clinically significant neurocognitive deficits in all neurocognitive domains based on normative data comparison. Patients with CD/FND also performed significantly worse than patients with other SSRD on information processing speed (Digit Symbol Substitution Test (V = .115, p = .035), Stroop Color-Word Test (SCWT) card 1 (V = .190, p = .006), and SCWT card 2 (V = .244, p  less then  .001). No CD/FND vs. other SSRD differences were observed in other neurocognitive domains. These findings indicate the patients with CD/FND perform worse on information processing speed tests compared to patients with other SSRD. © 2020 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.Postpartum depression is a serious mental illnessdisorder that occurs after delivery and is one of the most common post-partum complications. With the increasing popularity and extensive use of smartphones worldwide and the fact that China has become the country with the largest number of smartphone users, it is necessary to have a deep understanding of the use and influence of smartphones and discuss the role of smartphone applications in postpartum depression. This study evaluated and analysed the contents of all postpartum depression applications available in China, applying the US Preventive Services Task Force Recommendation Statement (Interventions to Prevent Perinatal Depression) and expert consensus on the guidelines for the prevention and treatment of postpartum depression. We used the keywords 'postpartum depression; and 'PPD' to search Android, iOS, and WeChat in the Chinese application market. Two reviewers agreed on the coding guidelines and coded the content and functionality of the application through content analysis to determine its intervention and adherence to the guidelines. In addition, we used the Mobile App Rating Scale (MARS) to evaluate the application for engagement, functionality, aesthetics, and information domains and recorded the features of the postpartum depression application. The current findings suggest that despite the recent expansion of smartphone platforms and increased availability of applications, existing Chinese apps for postpartum depression have low levels of adherence to clinical practice-based guidelines. New apps need to be developed, and existing apps need to be revised following evidence-based principles. © 2020 Australian College of Mental Health Nurses Inc.Borna disease virus 1 (BoDV-1) is the causative agent of Borna disease, an often fatal neurologic condition of domestic mammals, including New World camelids, in endemic areas in Central Europe. Recently, BoDV-1 gained further attention by the confirmation of fatal zoonotic infections in humans. Although Borna disease and BoDV-1 have been described already over the past decades, comprehensive reports of Borna disease outbreaks in domestic animals employing state of the art diagnostic methods are missing. Here, we report a series of BoDV-1 infections in a herd of 27 alpacas (Vicugna pacos) in the federal state of Brandenburg, Germany, which resulted in eleven fatalities (41%) within ten months. Clinical courses ranged from sudden death without previous clinical signs to acute or chronic neurologic disease with death occurring after up to six months. All animals that underwent necropsy exhibited a non-suppurative encephalitis. In addition, six apparently healthy seropositive individuals were identified within ts reserved.The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 2019 in Wuhan, China has spread to over 113 countries with 118,326 infected and 4,292 died as of 11 March 2020 and the World Health Organization (WHO) has just announced COVID-19 a global pandemic. A person under investigation (PUI) for COVID-19 is less likely to present initially to the ophthalmologists compared to emergency care or internal medicine physicians. However, in late February 2020, 2 patients presented simultaneously to our eye casualty with sudden onset of unilateral painful red eye associated with a decline in visual acuity, their intraocular pressure (IOP) were over 40 mmHg and slit-lamp examination findings were suggestive of acute primary angle closure (APAC). This article is protected by copyright. All rights reserved.Limited data exist on the effect of continuous renal replacement therapy (CRRT) methods on anti-epileptic drug pharmacokinetics (PK). This prospective practice-based PK study aims to assess the impact of continuous venovenous hemofiltration (CVVH), a modality of CRRT, on levetiracetam PK in critically ill patients and to derive individualized dosing recommendations. Eleven patients receiving oral or intravenous levetiracetam and CVVH in various intensive care units at a large academic medical center were enrolled to investigate the need for dosing adjustments. Prefilter, postfilter, and ultrafiltrate samples were obtained before dosing, after the completion of the infusion or 1-hour postoral dose, and up to 6 additional time points postinfusion or postoral administration. Patient-specific blood and ultrafiltrate flow rates and laboratory values were also collected at the time of sampling. The average sieving coefficient (SC) for levetiracetam was 0.89 ± 0.1, indicating high filter efficiency. Six of the 11 patients experienced concentrations outside the reported therapeutic range (12-46 mg/L).
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  • ular alterations that occur with DEE exposure. https://www.selleckchem.com/products/gsk2982772.html Contemporary evidence suggests that submerged macrophytes are experiencing a global decline due to the multiple compounding anthropogenic stressors impacting shallow lake ecosystems. Eutrophication and climate change are two main widespread, often co-occurring stressors, yet evidence concerning their interactive effects on aquatic plants remains partial and fragmented. Predicting the response of submerged aquatic vegetation to the combined effects of nutrient pollution and compound climate warming (mean + variability) is therefore crucial for the conservation and management of these valuable and vulnerable ecosystems. Here, we present the results of an outdoor mesocosm experiment examining the combined effects of nutrient enrichment (phosphorus addition) and warming (a 4 °C increase in mean temperature above present ambient conditions applied as either a constant increase or a variable increase ranging between 0 and 8 °C to mimic the effect of extreme events but keeping an equivalent total amount of warming) on Potamogeton crispus L. Warming accelerated the growth and senescence of P. crispus suggesting a more important role in maintaining the clear water state in winter-early spring but concomitant to possible earlier turbid states in summer. Warming also consistently advanced the flowering phenology but had no significant effect on flowering duration. There were no significant differences in the life cycle between the two warming treatments, while phosphorus addition also had little effect. However, under phosphorus enrichment, P. crispus increased sexual reproduction investment producing higher seed setting rate per infructescence. In contrast, warming, especially variable warming, may decrease sexual reproduction investment by reducing the number of infructescences. Seed and turion stoichiometry were altered by the combination of warming and phosphorus addition, but the changes were complex and difficult to interpret. Despite considerable interest in enhancing, preserving, and rehabilitating working memory (WM), efforts to elicit sustained behavioral improvements have been met with limited success. Here, we paired WM training with transcranial direct current stimulation (tDCS) to the frontoparietal network over four days. Active tDCS enhanced WM performance by modulating interactions between frontoparietal theta oscillations and gamma activity, as measured by pre- and post-training high-density electroencephalography (EEG). Increased phase-amplitude coupling (PAC) between the prefrontal stimulation site and temporo-parietal gamma activity explained behavioral improvements, and was most effective when gamma occurred near the prefrontal theta peak. These results demonstrate for the first time that tDCS-linked WM training elicits lasting changes in behavior by optimizing the oscillatory substrates of prefrontal control. 23Na provides the second strongest MR-observable signal in biological tissue and exhibits bi-exponential T2∗ relaxation in micro-environments such as the brain. There is significant interest in developing 23Na biomarkers for neurological diseases that are associated with sodium channel dysfunction such as multiple sclerosis and epilepsy. We have previously reported methods for acquisition of multi-echo sodium MRI and continuous distribution modelling of sodium relaxation properties as surrogate markers of brain microstructure. This study aimed to compare 23Na T2∗ relaxation times to more established measures of tissue microstructure derived from advanced diffusion MRI at 7 â€‹T. Six healthy volunteers were scanned using a 3D multi-echo radial ultra-short TE sequence using a dual-tuned 1H/23Na birdcage coil, and a high-resolution multi-shell, high angular resolution diffusion imaging sequence using a 32-channel 1H receive coil. 23Na T2∗ relaxation parameters [mean T2∗ (T2∗mean) and fast relaxation fraction (T2∗ff)] were calculated from a voxel-wise continuous gamma distribution signal model. White matter (restricted anisotropic diffusion) and grey matter (restricted isotropic diffusion) density were calculated from multi-shell multi-tissue constrained spherical deconvolution. Sodium parameters were compared with white and grey matter diffusion properties. Sodium T2∗mean and T2∗ff showed little variation across a range of white matter axonal fibre and grey matter densities. We conclude that sodium T2∗ relaxation parameters are not greatly influenced by relative differences in intra- and extracellular partial volumes. We suggest that care be taken when interpreting sodium relaxation changes in terms of tissue microstructure in healthy tissue. Sensory gating (SG) is a well-studied phenomenon in which neural responses are reduced to identical stimuli presented in succession, and is thought to represent the functional inhibition of primary sensory information that is redundant in nature. SG is traditionally considered pre-attentive, but little is known about the effects of attentional state on this process. In this study, we investigate the impact of directed attention on somatosensory SG using magnetoencephalography. Healthy young adults (n â€‹= â€‹26) performed a novel somato-visual paired-pulse oddball paradigm, in which attention was directed towards or away from paired-pulse stimulation of the left median nerve. We observed a robust evoked (i.e., phase-locked) somatosensory response in the time domain, and three stereotyped oscillatory responses in the time-frequency domain including an early theta response (4-8 â€‹Hz), and later alpha (8-14 â€‹Hz) and beta (20-26 â€‹Hz) responses across attentional states. The amplitudes of the evoked response and the theta and beta oscillations were gated for the second stimulus, however, only the gating of the oscillatory responses was altered by attention. Specifically, directing attention to the somatosensory domain enhanced SG of the early theta response, while reducing SG of the later alpha and beta responses. Further, prefrontal alpha-band coherence with the primary somatosensory cortex was greater when attention was directed towards the somatosensory domain, supporting a frontal modulatory effect on the alpha response in primary somatosensory regions. These findings highlight the dynamic effects of attentional modulation on somatosensory processing, and the importance of considering attentional state in studies of SG.
    ular alterations that occur with DEE exposure. https://www.selleckchem.com/products/gsk2982772.html Contemporary evidence suggests that submerged macrophytes are experiencing a global decline due to the multiple compounding anthropogenic stressors impacting shallow lake ecosystems. Eutrophication and climate change are two main widespread, often co-occurring stressors, yet evidence concerning their interactive effects on aquatic plants remains partial and fragmented. Predicting the response of submerged aquatic vegetation to the combined effects of nutrient pollution and compound climate warming (mean + variability) is therefore crucial for the conservation and management of these valuable and vulnerable ecosystems. Here, we present the results of an outdoor mesocosm experiment examining the combined effects of nutrient enrichment (phosphorus addition) and warming (a 4 °C increase in mean temperature above present ambient conditions applied as either a constant increase or a variable increase ranging between 0 and 8 °C to mimic the effect of extreme events but keeping an equivalent total amount of warming) on Potamogeton crispus L. Warming accelerated the growth and senescence of P. crispus suggesting a more important role in maintaining the clear water state in winter-early spring but concomitant to possible earlier turbid states in summer. Warming also consistently advanced the flowering phenology but had no significant effect on flowering duration. There were no significant differences in the life cycle between the two warming treatments, while phosphorus addition also had little effect. However, under phosphorus enrichment, P. crispus increased sexual reproduction investment producing higher seed setting rate per infructescence. In contrast, warming, especially variable warming, may decrease sexual reproduction investment by reducing the number of infructescences. Seed and turion stoichiometry were altered by the combination of warming and phosphorus addition, but the changes were complex and difficult to interpret. Despite considerable interest in enhancing, preserving, and rehabilitating working memory (WM), efforts to elicit sustained behavioral improvements have been met with limited success. Here, we paired WM training with transcranial direct current stimulation (tDCS) to the frontoparietal network over four days. Active tDCS enhanced WM performance by modulating interactions between frontoparietal theta oscillations and gamma activity, as measured by pre- and post-training high-density electroencephalography (EEG). Increased phase-amplitude coupling (PAC) between the prefrontal stimulation site and temporo-parietal gamma activity explained behavioral improvements, and was most effective when gamma occurred near the prefrontal theta peak. These results demonstrate for the first time that tDCS-linked WM training elicits lasting changes in behavior by optimizing the oscillatory substrates of prefrontal control. 23Na provides the second strongest MR-observable signal in biological tissue and exhibits bi-exponential T2∗ relaxation in micro-environments such as the brain. There is significant interest in developing 23Na biomarkers for neurological diseases that are associated with sodium channel dysfunction such as multiple sclerosis and epilepsy. We have previously reported methods for acquisition of multi-echo sodium MRI and continuous distribution modelling of sodium relaxation properties as surrogate markers of brain microstructure. This study aimed to compare 23Na T2∗ relaxation times to more established measures of tissue microstructure derived from advanced diffusion MRI at 7 â€‹T. Six healthy volunteers were scanned using a 3D multi-echo radial ultra-short TE sequence using a dual-tuned 1H/23Na birdcage coil, and a high-resolution multi-shell, high angular resolution diffusion imaging sequence using a 32-channel 1H receive coil. 23Na T2∗ relaxation parameters [mean T2∗ (T2∗mean) and fast relaxation fraction (T2∗ff)] were calculated from a voxel-wise continuous gamma distribution signal model. White matter (restricted anisotropic diffusion) and grey matter (restricted isotropic diffusion) density were calculated from multi-shell multi-tissue constrained spherical deconvolution. Sodium parameters were compared with white and grey matter diffusion properties. Sodium T2∗mean and T2∗ff showed little variation across a range of white matter axonal fibre and grey matter densities. We conclude that sodium T2∗ relaxation parameters are not greatly influenced by relative differences in intra- and extracellular partial volumes. We suggest that care be taken when interpreting sodium relaxation changes in terms of tissue microstructure in healthy tissue. Sensory gating (SG) is a well-studied phenomenon in which neural responses are reduced to identical stimuli presented in succession, and is thought to represent the functional inhibition of primary sensory information that is redundant in nature. SG is traditionally considered pre-attentive, but little is known about the effects of attentional state on this process. In this study, we investigate the impact of directed attention on somatosensory SG using magnetoencephalography. Healthy young adults (n â€‹= â€‹26) performed a novel somato-visual paired-pulse oddball paradigm, in which attention was directed towards or away from paired-pulse stimulation of the left median nerve. We observed a robust evoked (i.e., phase-locked) somatosensory response in the time domain, and three stereotyped oscillatory responses in the time-frequency domain including an early theta response (4-8 â€‹Hz), and later alpha (8-14 â€‹Hz) and beta (20-26 â€‹Hz) responses across attentional states. The amplitudes of the evoked response and the theta and beta oscillations were gated for the second stimulus, however, only the gating of the oscillatory responses was altered by attention. Specifically, directing attention to the somatosensory domain enhanced SG of the early theta response, while reducing SG of the later alpha and beta responses. Further, prefrontal alpha-band coherence with the primary somatosensory cortex was greater when attention was directed towards the somatosensory domain, supporting a frontal modulatory effect on the alpha response in primary somatosensory regions. These findings highlight the dynamic effects of attentional modulation on somatosensory processing, and the importance of considering attentional state in studies of SG.
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  • Background Cognitive decline is age relevant and it can start as early as middle age. The decline becomes more obvious among older adults, which is highly associated with increased risk of developing dementia (e.g., Alzheimer's disease). White matter damage was found to be related to cognitive decline through aging. The purpose of the current study was to compare the effects of Tai Chi (TC) versus walking on the brain white matter network among Chinese elderly women. Methods A cross-sectional study was conducted where 42 healthy elderly women were included. Tai Chi practitioners (20 females, average age 62.9 ± 2.38 years, education level 9.05 ± 1.8 years) and the matched walking participants (22 females, average age 63.27 ± 3.58 years, educational level 8.86 ± 2.74 years) underwent resting-state functional magnetic resonance imaging (rsfMRI) scans. Diffusion tensor imaging (DTI) and graph theory were employed to study the data, construct the white matter matrix, and compare the brain network attributes between the two groups. Results Results from graph-based analyses showed that the small-world attributes were higher for the TC group than for the walking group (p 0.05). However, no significant difference was found between the two groups in node attributes and edge analysis. Conclusion Regular TC training is more conducive to optimize the brain functioning and networking of the elderly. The results of the current study help to identify the mechanisms underlying the cognitive protective effects of TC.Inhibitors of apoptosis (IAPs) are a family of proteins that regulate cell death and inflammation. XIAP (X-linked IAP) is the only family member that suppresses apoptosis by directly binding to and inhibiting caspases. https://www.selleckchem.com/products/umi-77.html On the other hand, cIAPs suppress the activation of the extrinsic apoptotic pathway by preventing the formation of pro-apoptotic signaling complexes. IAPs are negatively regulated by IAP-antagonist proteins such as Smac/Diablo and ARTS. ARTS can promote apoptosis by binding and degrading XIAP via the ubiquitin proteasome-system (UPS). Smac can induce the degradation of cIAPs but not XIAP. Many types of cancer overexpress IAPs, thus enabling tumor cells to evade apoptosis. Therefore, IAPs, and in particular XIAP, have become attractive targets for cancer therapy. In this review, we describe the differences in the mechanisms of action between Smac and ARTS, and we summarize efforts to develop cancer therapies based on mimicking Smac and ARTS. Several Smac-mimetic small molecules are currently under evaluation in clinical trials. Initial efforts to develop ARTS-mimetics resulted in a novel class of compounds, which bind and degrade XIAP but not cIAPs. Smac-mimetics can target tumors with high levels of cIAPs, whereas ARTS-mimetics are expected to be effective for cancers with high levels of XIAP.Superelastic shape memory alloy (SMA) exhibits the ability to undergo large deformations before reverting **** to its undeformed shape following the removal of the load. This unique property underlies its great potential in the seismic design and retrofitting of structure members. In this paper, superelastic SMA wires were utilized to confine concrete cylinders to enhance their axial compressive behavior. The axial carrying and deformation capacities of SMA-confined concrete cylinders are assessed by uniaxial compression testing on a total of eight SMA-confined concrete columns and one unconfined column. The influence of the amount of SMA and the prestrain level of SMA wires, as well as the reinforcing mode, on the axial carrying and deformation capacity of confined concrete columns were considered. The analysis focuses on the axial carrying capacity and deformation performance of concrete columns reinforced with superelastic SMA under different loading conditions. Based on the experimental data and analysis results, it is found that superelastic SMA wires can increase the axial loading capacity and enhance deformation performance of concrete columns. Under the same loading condition, the ultimate bearing capacity of SMA-confined concrete columns increases as the increasing of the amount of SMA wire. The results of this study verify the effectiveness of superelastic SMA in enhancing the loading capacity and deformation behavior of concrete cylinders.Distractors might display discriminatory power with respect to the construct of interest (e.g., intelligence), which was shown in recent applications of nested logit models to the short-form of Raven's progressive matrices and other reasoning tests. In this vein, a simulation study was carried out to examine two effect size measures (i.e., a variant of Cohen's ω and the canonical correlation RCC) for their potential to detect distractors with ability-related discriminatory power. The simulation design was adopted to item selection scenarios relying on rather small sample sizes (e.g., N = 100 or N = 200). Both suggested effect size measures (Cohen's ω only when based on two ability groups) yielded acceptable to conservative type-I-error rates, whereas, the canonical correlation outperformed Cohen's ω in terms of empirical power. The simulation results further suggest that an effect size threshold of 0.30 is more appropriate as compared to more lenient (0.10) or stricter thresholds (0.50). The suggested item-analysis procedure is illustrated with an analysis of twelve Raven's progressive matrices items in a sample of N = 499 participants. Finally, strategies for item selection for cognitive ability tests with the goal of scaling by means of nested logit models are discussed.The semi-enclosed estuary is very susceptible to changes in the physical and environmental characteristics of the inflow from the land. Therefore, continuous and comprehensive monitoring of such changes is necessary for managing the estuary. Nevertheless, the procedure or framework has not been proposed appropriately to determine how many instruments are necessary and where they need to be monitored and standardized to detect critical changes. The present work proposes a systematical strategy for the deployments of the monitoring array by using the combination of graphical optimization with the objective mapping technique. In order to reflect the spatiotemporal characteristics of the bay, the representative variables and eigenvectors were determined by the Empirical Orthogonal Function (EOF), and the cosine angle among them calculated and used as a design index of optimization. At the recommended locations, the sampled representative variables were interpolated to reconstruct their spatiotemporal distribution and compared with the true distribution.
    Background Cognitive decline is age relevant and it can start as early as middle age. The decline becomes more obvious among older adults, which is highly associated with increased risk of developing dementia (e.g., Alzheimer's disease). White matter damage was found to be related to cognitive decline through aging. The purpose of the current study was to compare the effects of Tai Chi (TC) versus walking on the brain white matter network among Chinese elderly women. Methods A cross-sectional study was conducted where 42 healthy elderly women were included. Tai Chi practitioners (20 females, average age 62.9 ± 2.38 years, education level 9.05 ± 1.8 years) and the matched walking participants (22 females, average age 63.27 ± 3.58 years, educational level 8.86 ± 2.74 years) underwent resting-state functional magnetic resonance imaging (rsfMRI) scans. Diffusion tensor imaging (DTI) and graph theory were employed to study the data, construct the white matter matrix, and compare the brain network attributes between the two groups. Results Results from graph-based analyses showed that the small-world attributes were higher for the TC group than for the walking group (p 0.05). However, no significant difference was found between the two groups in node attributes and edge analysis. Conclusion Regular TC training is more conducive to optimize the brain functioning and networking of the elderly. The results of the current study help to identify the mechanisms underlying the cognitive protective effects of TC.Inhibitors of apoptosis (IAPs) are a family of proteins that regulate cell death and inflammation. XIAP (X-linked IAP) is the only family member that suppresses apoptosis by directly binding to and inhibiting caspases. https://www.selleckchem.com/products/umi-77.html On the other hand, cIAPs suppress the activation of the extrinsic apoptotic pathway by preventing the formation of pro-apoptotic signaling complexes. IAPs are negatively regulated by IAP-antagonist proteins such as Smac/Diablo and ARTS. ARTS can promote apoptosis by binding and degrading XIAP via the ubiquitin proteasome-system (UPS). Smac can induce the degradation of cIAPs but not XIAP. Many types of cancer overexpress IAPs, thus enabling tumor cells to evade apoptosis. Therefore, IAPs, and in particular XIAP, have become attractive targets for cancer therapy. In this review, we describe the differences in the mechanisms of action between Smac and ARTS, and we summarize efforts to develop cancer therapies based on mimicking Smac and ARTS. Several Smac-mimetic small molecules are currently under evaluation in clinical trials. Initial efforts to develop ARTS-mimetics resulted in a novel class of compounds, which bind and degrade XIAP but not cIAPs. Smac-mimetics can target tumors with high levels of cIAPs, whereas ARTS-mimetics are expected to be effective for cancers with high levels of XIAP.Superelastic shape memory alloy (SMA) exhibits the ability to undergo large deformations before reverting back to its undeformed shape following the removal of the load. This unique property underlies its great potential in the seismic design and retrofitting of structure members. In this paper, superelastic SMA wires were utilized to confine concrete cylinders to enhance their axial compressive behavior. The axial carrying and deformation capacities of SMA-confined concrete cylinders are assessed by uniaxial compression testing on a total of eight SMA-confined concrete columns and one unconfined column. The influence of the amount of SMA and the prestrain level of SMA wires, as well as the reinforcing mode, on the axial carrying and deformation capacity of confined concrete columns were considered. The analysis focuses on the axial carrying capacity and deformation performance of concrete columns reinforced with superelastic SMA under different loading conditions. Based on the experimental data and analysis results, it is found that superelastic SMA wires can increase the axial loading capacity and enhance deformation performance of concrete columns. Under the same loading condition, the ultimate bearing capacity of SMA-confined concrete columns increases as the increasing of the amount of SMA wire. The results of this study verify the effectiveness of superelastic SMA in enhancing the loading capacity and deformation behavior of concrete cylinders.Distractors might display discriminatory power with respect to the construct of interest (e.g., intelligence), which was shown in recent applications of nested logit models to the short-form of Raven's progressive matrices and other reasoning tests. In this vein, a simulation study was carried out to examine two effect size measures (i.e., a variant of Cohen's ω and the canonical correlation RCC) for their potential to detect distractors with ability-related discriminatory power. The simulation design was adopted to item selection scenarios relying on rather small sample sizes (e.g., N = 100 or N = 200). Both suggested effect size measures (Cohen's ω only when based on two ability groups) yielded acceptable to conservative type-I-error rates, whereas, the canonical correlation outperformed Cohen's ω in terms of empirical power. The simulation results further suggest that an effect size threshold of 0.30 is more appropriate as compared to more lenient (0.10) or stricter thresholds (0.50). The suggested item-analysis procedure is illustrated with an analysis of twelve Raven's progressive matrices items in a sample of N = 499 participants. Finally, strategies for item selection for cognitive ability tests with the goal of scaling by means of nested logit models are discussed.The semi-enclosed estuary is very susceptible to changes in the physical and environmental characteristics of the inflow from the land. Therefore, continuous and comprehensive monitoring of such changes is necessary for managing the estuary. Nevertheless, the procedure or framework has not been proposed appropriately to determine how many instruments are necessary and where they need to be monitored and standardized to detect critical changes. The present work proposes a systematical strategy for the deployments of the monitoring array by using the combination of graphical optimization with the objective mapping technique. In order to reflect the spatiotemporal characteristics of the bay, the representative variables and eigenvectors were determined by the Empirical Orthogonal Function (EOF), and the cosine angle among them calculated and used as a design index of optimization. At the recommended locations, the sampled representative variables were interpolated to reconstruct their spatiotemporal distribution and compared with the true distribution.
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  • In Npt2cKO ****, plasma Pi levels began to decrease around the age of 15 days and significant hypophosphatemia developed within 21 days. The findings of the present study suggest that Npt2c contributes to regulating plasma Pi levels in the juvenile stage and affects Pi retention in the soft and vascular tissues in KLKO ****. © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.BACKGROUND Childhood obesity is a significant global problem. Childhood obesity prevention interventions may be more effective when started very early in life before metabolic and behavioural patterns are established. METHODS AND FINDINGS A prospectively planned, individual participant data meta-analysis of four randomized controlled trials. Participants were first-time mothers of term infants. Trial interventions commenced during pregnancy or early infancy and comprised education and support delivered via group sessions and/or home visits. Control group families accessed existing local well-child health care. The primary outcome was body mass index (BMI) z score at 18 to 24 months; 2196 mother-child dyads were available for analysis. Intervention children had lower BMI z scores at 18 to 24 months than control children (-0.12 adjusted mean; 95% confidence interval, -0.22 to -0.02, P = .017). There was some evidence that the BMI z score reduction was greater in settings with limited well-child health care programmes (interaction P value = .03). Improvements were also detected in television viewing time, feeding practices, and breastfeeding duration. CONCLUSIONS Parent-focused intervention programmes that commence by early infancy and which aim to establish a trajectory of healthy lifestyle behaviours produced a modest but statistically significant reduction in BMI z score, which if replicated on a wider scale may have important public health implications. © 2020 World Obesity Federation.in German Die atopische Dermatitis (AD) ist eine chronisch-entzündliche Erkrankung, die mit einer Reihe von Komorbidität assoziiert sein kann, hierzu zählen auch psychosoziale Erkrankungen, zu denen hier eine Übersicht gegeben werden soll. Hierzu erfolgten eine Literaturrecherche in PubMed sowie gezieltes Screening von Übersichtsarbeiten und Leitlinien. Bei Patienten mit AD wird ein gehäuftes Auftreten von Depression, Angststörung, Schlafstörung und Suizidalität berichtet. Die Erkrankung hat negative Effekte auf die Lebensqualität. Bei Kindern wurde vermehrt das gemeinsame Auftreten der AD mit der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung nachgewiesen. Weniger gut untersucht ist der Zusammenhang zwischen AD und Erkrankungen wie Schizophrenie, Essstörung und Zwangsstörung. Bezüglich der Komorbidität bei der AD gibt es hohen Forschungsbedarf, gerade auch im Hinblick darauf, ob und wie neuere Therapien diese Komorbidität beeinflussen.in German Die Tinea capitis ist eine durch Dermatophyten hervorgerufene, vor allem im Kindesalter auftretende Mykose der behaarten Kopfhaut. Die Diagnostik erfolgt mittels mikroskopischer, kultureller und/oder molekularer Methoden. Die Therapie sollte systemisch und begleitend topisch erfolgen und ist abhängig von dem jeweiligen Erreger. Das Ziel des Updates dieser interdisziplinären deutschen S1-Leitlinie ist es, vor allem Dermatologen, Kinderärzten und Allgemeinmedizinern eine Entscheidungshilfe für die Auswahl sowie Durchführung einer geeigneten und suffizienten Diagnostik und Therapie für Patienten mit Tinea capitis zur Verfügung zu stellen. Die Leitlinie wurde unter Berücksichtigung aktueller internationaler Leitlinien, insbesondere der Leitlinien der European Society for Pediatric Dermatology 2010 sowie der British Association of Dermatologists 2014 und den Ergebnissen einer Literaturrecherche durch die Leitlinienkommission erstellt. Diese Kommission ist multidisziplinär und besteht aus Vertretern der Deutschen Dermatologischen Gesellschaft (DDG), der Deutschsprachigen Mykologischen Gesellschaft (DMykG), der Deutschen Gesellschaft für Hygiene und Mikrobiologie (DGHM), der Deutschen Gesellschaft für Kinder- und Jugendmedizin e.V. (DGKJ) und der deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI). Methodisch wurde die Leitliniengruppe durch die Division of Evidence-based Medicine (dEBM) begleitet. Die Leitlinie wurde nach einem umfangreichen internen und externen Review durch die beteiligten Fachgesellschaften freigegeben.Atopic dermatitis (AD) is a chronic inflammatory disease that may be associated with a number of comorbidities including psychosocial disorders, which are the primary focus of this article. The data presented is based on a literature search in PubMed and subsequent screening of relevant review articles and guidelines. There is a greater prevalence of depression, anxiety, sleep disorders and suicidal ideation among individuals with AD. The disease negatively impacts patients' quality of life. https://www.selleckchem.com/products/zcl278.html Children with AD have been shown to more commonly exhibit signs of attention-deficit/hyperactivity disorder. Only little data exists on the association of AD with schizophrenia, eating disorders or obsessive-compulsive disorder. There is a great need for research in the field of AD-related comorbidities, especially with respect to the question as to whether and how novel treatment options may potentially affect these comorbidities. © 2020 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.in German Multiple Chemikaliensensibilität (MCS) ist eine subjektiv erlebte, erhöhte Empfindlichkeit gegenüber Chemikalien aus der Umwelt. Betroffene reagieren mit vielfältigen, unspezifischen Beschwerden. Symptome an Haut und Schleimhäuten werden von Personen mit MCS häufig auf eine Exposition gegenüber Chemikalien zurückgeführt. Auch Dermatologen sollten sich deshalb mit dieser Gesundheitsstörung auseinandersetzen. Multiple Chemikaliensensibilität ist eine Ausschlussdiagnose. Durch Basisdiagnostik, Allergiediagnostik oder Umweltdiagnostik sollen andere mögliche Ursachen für Symptome ausgeschlossen werden. Die Dermatologie sollte in erster Linie Hauterkrankungen und Allergien als mögliche Ursachen für Beschwerden abklären. Interdisziplinäre Betreuung der Betroffenen ist insbesondere bei schweren Verläufen von Relevanz, beispielsweise, wenn Betroffene in Ihrer Alltagsbewältigung eingeschränkt sind. Wichtige Disziplinen sind dabei unter anderen Umweltmedizin, Psychosomatik, Arbeits- und Sozialmedizin. Hautbeschwerden werden durch die Dermatologie symptomatisch, zum Beispiel mit Hautbasispflege, behandelt.
    In Npt2cKO mice, plasma Pi levels began to decrease around the age of 15 days and significant hypophosphatemia developed within 21 days. The findings of the present study suggest that Npt2c contributes to regulating plasma Pi levels in the juvenile stage and affects Pi retention in the soft and vascular tissues in KLKO mice. © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.BACKGROUND Childhood obesity is a significant global problem. Childhood obesity prevention interventions may be more effective when started very early in life before metabolic and behavioural patterns are established. METHODS AND FINDINGS A prospectively planned, individual participant data meta-analysis of four randomized controlled trials. Participants were first-time mothers of term infants. Trial interventions commenced during pregnancy or early infancy and comprised education and support delivered via group sessions and/or home visits. Control group families accessed existing local well-child health care. The primary outcome was body mass index (BMI) z score at 18 to 24 months; 2196 mother-child dyads were available for analysis. Intervention children had lower BMI z scores at 18 to 24 months than control children (-0.12 adjusted mean; 95% confidence interval, -0.22 to -0.02, P = .017). There was some evidence that the BMI z score reduction was greater in settings with limited well-child health care programmes (interaction P value = .03). Improvements were also detected in television viewing time, feeding practices, and breastfeeding duration. CONCLUSIONS Parent-focused intervention programmes that commence by early infancy and which aim to establish a trajectory of healthy lifestyle behaviours produced a modest but statistically significant reduction in BMI z score, which if replicated on a wider scale may have important public health implications. © 2020 World Obesity Federation.in German Die atopische Dermatitis (AD) ist eine chronisch-entzündliche Erkrankung, die mit einer Reihe von Komorbidität assoziiert sein kann, hierzu zählen auch psychosoziale Erkrankungen, zu denen hier eine Übersicht gegeben werden soll. Hierzu erfolgten eine Literaturrecherche in PubMed sowie gezieltes Screening von Übersichtsarbeiten und Leitlinien. Bei Patienten mit AD wird ein gehäuftes Auftreten von Depression, Angststörung, Schlafstörung und Suizidalität berichtet. Die Erkrankung hat negative Effekte auf die Lebensqualität. Bei Kindern wurde vermehrt das gemeinsame Auftreten der AD mit der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung nachgewiesen. Weniger gut untersucht ist der Zusammenhang zwischen AD und Erkrankungen wie Schizophrenie, Essstörung und Zwangsstörung. Bezüglich der Komorbidität bei der AD gibt es hohen Forschungsbedarf, gerade auch im Hinblick darauf, ob und wie neuere Therapien diese Komorbidität beeinflussen.in German Die Tinea capitis ist eine durch Dermatophyten hervorgerufene, vor allem im Kindesalter auftretende Mykose der behaarten Kopfhaut. Die Diagnostik erfolgt mittels mikroskopischer, kultureller und/oder molekularer Methoden. Die Therapie sollte systemisch und begleitend topisch erfolgen und ist abhängig von dem jeweiligen Erreger. Das Ziel des Updates dieser interdisziplinären deutschen S1-Leitlinie ist es, vor allem Dermatologen, Kinderärzten und Allgemeinmedizinern eine Entscheidungshilfe für die Auswahl sowie Durchführung einer geeigneten und suffizienten Diagnostik und Therapie für Patienten mit Tinea capitis zur Verfügung zu stellen. Die Leitlinie wurde unter Berücksichtigung aktueller internationaler Leitlinien, insbesondere der Leitlinien der European Society for Pediatric Dermatology 2010 sowie der British Association of Dermatologists 2014 und den Ergebnissen einer Literaturrecherche durch die Leitlinienkommission erstellt. Diese Kommission ist multidisziplinär und besteht aus Vertretern der Deutschen Dermatologischen Gesellschaft (DDG), der Deutschsprachigen Mykologischen Gesellschaft (DMykG), der Deutschen Gesellschaft für Hygiene und Mikrobiologie (DGHM), der Deutschen Gesellschaft für Kinder- und Jugendmedizin e.V. (DGKJ) und der deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI). Methodisch wurde die Leitliniengruppe durch die Division of Evidence-based Medicine (dEBM) begleitet. Die Leitlinie wurde nach einem umfangreichen internen und externen Review durch die beteiligten Fachgesellschaften freigegeben.Atopic dermatitis (AD) is a chronic inflammatory disease that may be associated with a number of comorbidities including psychosocial disorders, which are the primary focus of this article. The data presented is based on a literature search in PubMed and subsequent screening of relevant review articles and guidelines. There is a greater prevalence of depression, anxiety, sleep disorders and suicidal ideation among individuals with AD. The disease negatively impacts patients' quality of life. https://www.selleckchem.com/products/zcl278.html Children with AD have been shown to more commonly exhibit signs of attention-deficit/hyperactivity disorder. Only little data exists on the association of AD with schizophrenia, eating disorders or obsessive-compulsive disorder. There is a great need for research in the field of AD-related comorbidities, especially with respect to the question as to whether and how novel treatment options may potentially affect these comorbidities. © 2020 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.in German Multiple Chemikaliensensibilität (MCS) ist eine subjektiv erlebte, erhöhte Empfindlichkeit gegenüber Chemikalien aus der Umwelt. Betroffene reagieren mit vielfältigen, unspezifischen Beschwerden. Symptome an Haut und Schleimhäuten werden von Personen mit MCS häufig auf eine Exposition gegenüber Chemikalien zurückgeführt. Auch Dermatologen sollten sich deshalb mit dieser Gesundheitsstörung auseinandersetzen. Multiple Chemikaliensensibilität ist eine Ausschlussdiagnose. Durch Basisdiagnostik, Allergiediagnostik oder Umweltdiagnostik sollen andere mögliche Ursachen für Symptome ausgeschlossen werden. Die Dermatologie sollte in erster Linie Hauterkrankungen und Allergien als mögliche Ursachen für Beschwerden abklären. Interdisziplinäre Betreuung der Betroffenen ist insbesondere bei schweren Verläufen von Relevanz, beispielsweise, wenn Betroffene in Ihrer Alltagsbewältigung eingeschränkt sind. Wichtige Disziplinen sind dabei unter anderen Umweltmedizin, Psychosomatik, Arbeits- und Sozialmedizin. Hautbeschwerden werden durch die Dermatologie symptomatisch, zum Beispiel mit Hautbasispflege, behandelt.
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  • BACKGROUND Congenital lobar emphysema (CLE) is a rare developmental malformation of the lung but can be associated with high morbidity and mortality. The objective of this study is to review our experience with 45 patients with CLE highlighting clinical features, aspects of diagnosis, and management. METHODS The medical records of all patients diagnosed with CLE in our center were reviewed. Patients age at the time of diagnosis, sex, clinical presentation, associated anomalies, the lobes affected, treatment modality, and outcome were described. A comparison was made between those who had lobectomy via open thoracotomy and those treated thoracoscopically. RESULTS From January 2000 to December 2018, a total of 45 infants with CLE were presented to our institution. There were 30 male and 15 female, and the mean age at presentation was 3.35 months. Twenty-five patients presented with respiratory distress. Nine patients presented immediately after birth, and two of them had surgery within the 1st week of life. Twecic Medicine.BACKGROUND Organizing pneumonia (OP) usually responds spectacularly well to initial treatment, but relapses can occur and some cases run a fatal course. Still, the issue of relapse has been addressed in relatively few studies, and predictors have not been clarified. The purpose of this study was to examine the pattern of relapses in OP, to determine whether relapse affects morbidity and mortality, and to identify possible predictors of relapse. METHODS Blood sampling, pulmonary function testing, computed tomography (CT) of the chest, and bronchofiberscopy were performed for all patients and were retrospectively reviewed along with clinical information. Periodical chest CT was conducted and additional chest CT was performed when relapse of OP was clinically suspected. All patients were followed regarding treatment response, treatment duration, and presence of relapse. Results were compared between two groups based on serum concentrations of surfactant protein (SP)-D normal SP-D and high SP-D. RESULTS Twenty-two patients were analyzed in this study. SP-D showed a negative correlation with percutaneous oxygen saturation and positive correlations with serum lactate dehydrogenase, Krebs von den Lungen (KL)-6, and percentage of lymphocytes in bronchoalveolar lavage (BAL). Prognosis was good for all patients, but relapse was significantly more frequent in the high SP-D group (6 cases) than in the normal SP-D group (0 cases; P = 0.049). Serum KL-6 and percentage of monocytes in BAL were significantly higher, and pulmonary vital capacity and forced expiratory volume in 1 s were significantly lower in the high SP-D group than in the low SP-D group. CONCLUSIONS When treating cases of OP with high serum concentrations of SP-D, attention should be paid to the possibility of relapse. Copyright © 2020 Annals of Thoracic Medicine.BACKGROUND This cross-sectional case-control study aimed to assess the prevalence of restless legs syndrome (RLS) and its correlates and severity among Arab (Saudi) pregnant women attending antenatal care clinics. METHODS We interviewed 742 consecutive pregnant women attending antenatal clinics face-to-face using the International RLS Study Group (IRLSSG) criteria. We assessed the severity of RLS using the IRLSSG severity scale for RLS (IRLS). A similar number of age-matched nonpregnant women were enrolled in a control group. RESULTS Among the cases, 104 (14%) were in the first trimester, 232 (31.3%) in the second trimester, and 406 (54.7%) in the third trimester. The RLS prevalence in cases and controls was 30% and 26.5%, respectively, (P = 0.134). Among cases, severe/very severe RLS was diagnosed in 25% and mild/moderate in 75%, compared with 15% of controls having severe/very severe RLS and 85% having mild/moderate RLS (P less then 0.001). Multivariate binary logistic regression analysis identified the following parameters as independent predictors of RLS parity (odds ratio [OR] 1.113 [confidence intervals [CI] 1.012-1.223], P = 0.027), anemia (OR 1.452 [1.033-2.042], P = 0.03), diabetes mellitus (OR 1.734 [CI 1.084-2.774], P = 0.022), Vitamin D deficiency (OR 2.376 [CI 1.488-3.794],P less then 0.001), and smoking (OR 3.839 [CI 1.463-10.074], P = 0.006). None of the cases had been diagnosed or treated for RLS in the antenatal clinics. CONCLUSION RLS is common, but underdiagnosed, among Saudi pregnant women and nonpregnant women of childbearing age. The study revealed that RLS during pregnancy is linked to parity, anemia, diabetes mellitus, Vitamin D deficiency, and smoking. Copyright © 2020 Annals of Thoracic Medicine.Patient-ventilator asynchrony (PVA) is common in patients receiving noninvasive ventilation (NIV). This occurs primarily when the triggering and cycling-off of ventilatory assistance are not synchronized with the patient's inspiratory efforts and could result in increased work of breathing and niv failure. https://www.selleckchem.com/products/incb054329.html In general, five types of asynchrony can occur during NIV ineffective inspiratory efforts, double-triggering, auto-triggering, short-ventilatory cycling, and long-ventilatory cycling. Many factors that affect PVA are mostly related to the degree of air leakage, level of pressure support, and the type and properties of the interface used. Careful monitoring and adjustment of these factors are essential to reduce PVA and improve patient comfort. In this article, we discuss the machine and interface-related factors that influence PVA during NIV and its effect on the respiratory mechanics during pressure support ventilation, which is the ventilatory mode used most commonly during NIV. For that, we critically evaluated studies that assessed ventilator- and interface-related factors that influence PVA during NIV and proposed therapeutic solutions. Copyright © 2020 Annals of Thoracic Medicine.As the most common type of cancer in female patients, the morbidity and mortality rates of breast cancer (**) are high, and its incidence is gradually increasing worldwide. However, the underlying molecular and genetic mechanisms involved in the etiopathogenesis of ** remain unclear. Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have been verified to serve a crucial role in tumorigenesis. However, the majority of functions and mechanisms of circRNAs remain unknown. The present study identified 47 differentially expressed circRNAs in a dataset from Gene Expression Omnibus. Using the cancer-specific circRNA database, the potential microRNA (miRNA) response elements, RNA-binding proteins and open reading frames of the candidate circRNAs were predicted. Combing the predictions of miRNAs and target mRNAs, a competing endogenous RNA network was constructed, which may serve as the theoretical basis for further research. Furthermore, the analyses conducted using Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways indicated that candidate circRNAs may serve a role in transcriptional regulation.
    BACKGROUND Congenital lobar emphysema (CLE) is a rare developmental malformation of the lung but can be associated with high morbidity and mortality. The objective of this study is to review our experience with 45 patients with CLE highlighting clinical features, aspects of diagnosis, and management. METHODS The medical records of all patients diagnosed with CLE in our center were reviewed. Patients age at the time of diagnosis, sex, clinical presentation, associated anomalies, the lobes affected, treatment modality, and outcome were described. A comparison was made between those who had lobectomy via open thoracotomy and those treated thoracoscopically. RESULTS From January 2000 to December 2018, a total of 45 infants with CLE were presented to our institution. There were 30 male and 15 female, and the mean age at presentation was 3.35 months. Twenty-five patients presented with respiratory distress. Nine patients presented immediately after birth, and two of them had surgery within the 1st week of life. Twecic Medicine.BACKGROUND Organizing pneumonia (OP) usually responds spectacularly well to initial treatment, but relapses can occur and some cases run a fatal course. Still, the issue of relapse has been addressed in relatively few studies, and predictors have not been clarified. The purpose of this study was to examine the pattern of relapses in OP, to determine whether relapse affects morbidity and mortality, and to identify possible predictors of relapse. METHODS Blood sampling, pulmonary function testing, computed tomography (CT) of the chest, and bronchofiberscopy were performed for all patients and were retrospectively reviewed along with clinical information. Periodical chest CT was conducted and additional chest CT was performed when relapse of OP was clinically suspected. All patients were followed regarding treatment response, treatment duration, and presence of relapse. Results were compared between two groups based on serum concentrations of surfactant protein (SP)-D normal SP-D and high SP-D. RESULTS Twenty-two patients were analyzed in this study. SP-D showed a negative correlation with percutaneous oxygen saturation and positive correlations with serum lactate dehydrogenase, Krebs von den Lungen (KL)-6, and percentage of lymphocytes in bronchoalveolar lavage (BAL). Prognosis was good for all patients, but relapse was significantly more frequent in the high SP-D group (6 cases) than in the normal SP-D group (0 cases; P = 0.049). Serum KL-6 and percentage of monocytes in BAL were significantly higher, and pulmonary vital capacity and forced expiratory volume in 1 s were significantly lower in the high SP-D group than in the low SP-D group. CONCLUSIONS When treating cases of OP with high serum concentrations of SP-D, attention should be paid to the possibility of relapse. Copyright © 2020 Annals of Thoracic Medicine.BACKGROUND This cross-sectional case-control study aimed to assess the prevalence of restless legs syndrome (RLS) and its correlates and severity among Arab (Saudi) pregnant women attending antenatal care clinics. METHODS We interviewed 742 consecutive pregnant women attending antenatal clinics face-to-face using the International RLS Study Group (IRLSSG) criteria. We assessed the severity of RLS using the IRLSSG severity scale for RLS (IRLS). A similar number of age-matched nonpregnant women were enrolled in a control group. RESULTS Among the cases, 104 (14%) were in the first trimester, 232 (31.3%) in the second trimester, and 406 (54.7%) in the third trimester. The RLS prevalence in cases and controls was 30% and 26.5%, respectively, (P = 0.134). Among cases, severe/very severe RLS was diagnosed in 25% and mild/moderate in 75%, compared with 15% of controls having severe/very severe RLS and 85% having mild/moderate RLS (P less then 0.001). Multivariate binary logistic regression analysis identified the following parameters as independent predictors of RLS parity (odds ratio [OR] 1.113 [confidence intervals [CI] 1.012-1.223], P = 0.027), anemia (OR 1.452 [1.033-2.042], P = 0.03), diabetes mellitus (OR 1.734 [CI 1.084-2.774], P = 0.022), Vitamin D deficiency (OR 2.376 [CI 1.488-3.794],P less then 0.001), and smoking (OR 3.839 [CI 1.463-10.074], P = 0.006). None of the cases had been diagnosed or treated for RLS in the antenatal clinics. CONCLUSION RLS is common, but underdiagnosed, among Saudi pregnant women and nonpregnant women of childbearing age. The study revealed that RLS during pregnancy is linked to parity, anemia, diabetes mellitus, Vitamin D deficiency, and smoking. Copyright © 2020 Annals of Thoracic Medicine.Patient-ventilator asynchrony (PVA) is common in patients receiving noninvasive ventilation (NIV). This occurs primarily when the triggering and cycling-off of ventilatory assistance are not synchronized with the patient's inspiratory efforts and could result in increased work of breathing and niv failure. https://www.selleckchem.com/products/incb054329.html In general, five types of asynchrony can occur during NIV ineffective inspiratory efforts, double-triggering, auto-triggering, short-ventilatory cycling, and long-ventilatory cycling. Many factors that affect PVA are mostly related to the degree of air leakage, level of pressure support, and the type and properties of the interface used. Careful monitoring and adjustment of these factors are essential to reduce PVA and improve patient comfort. In this article, we discuss the machine and interface-related factors that influence PVA during NIV and its effect on the respiratory mechanics during pressure support ventilation, which is the ventilatory mode used most commonly during NIV. For that, we critically evaluated studies that assessed ventilator- and interface-related factors that influence PVA during NIV and proposed therapeutic solutions. Copyright © 2020 Annals of Thoracic Medicine.As the most common type of cancer in female patients, the morbidity and mortality rates of breast cancer (BC) are high, and its incidence is gradually increasing worldwide. However, the underlying molecular and genetic mechanisms involved in the etiopathogenesis of BC remain unclear. Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have been verified to serve a crucial role in tumorigenesis. However, the majority of functions and mechanisms of circRNAs remain unknown. The present study identified 47 differentially expressed circRNAs in a dataset from Gene Expression Omnibus. Using the cancer-specific circRNA database, the potential microRNA (miRNA) response elements, RNA-binding proteins and open reading frames of the candidate circRNAs were predicted. Combing the predictions of miRNAs and target mRNAs, a competing endogenous RNA network was constructed, which may serve as the theoretical basis for further research. Furthermore, the analyses conducted using Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways indicated that candidate circRNAs may serve a role in transcriptional regulation.
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  • Emotions are part and parcel of the human condition, but their nature is debated. Three broad classes of theories about the nature of emotions can be distinguished affect-program theories, constructionist theories, and appraisal theories. Integrating these broad classes of theories into a unifying theory is challenging. An integrative psychometric model of emotions can inform such a theory because psychometric models are intertwined with theoretical perspectives about constructs. To identify an integrative psychometric model, we delineate properties of emotions stated by emotion theories and investigate whether psychometric models account for these properties. Specifically, an integrative psychometric model of emotions should allow (a) identifying distinct emotions (central in affect-program theories), (b) between- and within-person variations of emotions (central in constructionist theories), and (c) causal relationships between emotion components (central in appraisal theories). Evidence suggests that the popular reflective and formative latent variable models-in which emotions are conceptualized as unobservable causes or consequences of emotion components-cannot account for all properties. Conversely, a psychometric network model-in which emotions are conceptualized as systems of causally interacting emotion components-accounts for all properties. The psychometric network model thus constitutes an integrative psychometric model of emotions, facilitating progress toward a unifying theory.Osteocytes are an ancient cell, appearing in fossilized skeletal remains of early fish and dinosaurs. Despite its relative high abundance, even in the context of nonskeletal cells, the osteocyte is perhaps among the least studied cells in all of vertebrate biology. Osteocytes are cells embedded in bone, able to modify their surrounding extracellular matrix via specialized molecular remodeling mechanisms that are independent of the bone forming osteoblasts and bone-resorbing osteoclasts. Osteocytes communicate with osteoclasts and osteoblasts via distinct signaling molecules that include the RankL/OPG axis and the Sost/Dkk1/Wnt axis, among others. Osteocytes also extend their influence beyond the local bone environment by functioning as an endocrine cell that controls phosphate reabsorption in the kidney, insulin secretion in the pancreas, and skeletal muscle function. These cells are also finely tuned sensors of mechanical stimulation to coordinate with effector cells to adjust bone mass, size, and shape to conform to mechanical demands.Cardiac fibrosis is a pathological condition that occurs after injury and during aging. Currently, there are limited means to effectively reduce or reverse fibrosis. Key to identifying methods for curbing excess deposition of extracellular matrix is a better understanding of the cardiac fibroblast, the cell responsible for collagen production. In recent years, the diversity and functions of these enigmatic cells have been gradually revealed. In this review, I outline current approaches for identifying and classifying cardiac fibroblasts. An emphasis is placed on new insights into the heterogeneity of these cells as determined by lineage tracing and single-cell sequencing in development, adult, and disease states. https://www.selleckchem.com/products/fezolinetant.html These recent advances in our understanding of the fibroblast provide a platform for future development of novel therapeutics to combat cardiac fibrosis.The limits of evolution have long fascinated biologists. However, the causes of evolutionary constraint have remained elusive due to a poor mechanistic understanding of studied phenotypes. Recently, a range of innovative approaches have leveraged mechanistic information on regulatory networks and cellular biology. These methods combine systems biology models with population and single-cell quantification and with new genetic tools, and they have been applied to a range of complex cellular functions and engineered networks. In this article, we review these developments, which are revealing the mechanistic causes of epistasis at different levels of biological organization-in molecular recognition, within a single regulatory network, and between different networks-providing first indications of predictable features of evolutionary constraint. Expected final online publication date for the Annual Review of Biophysics, Volume 49 is May 6, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.We review the adaptations of enzyme activity to different temperatures. Psychrophilic (cold-adapted) enzymes show significantly different activation parameters (lower activation enthalpies and entropies) than their mesophilic counterparts. Furthermore, there is increasing evidence that the temperature dependence of many enzyme-catalyzed reactions is more complex than is widely believed. Many enzymes show curvature in plots of activity versus temperature that is not accounted for by denaturation or unfolding. This is explained by macromolecular rate theory A negative activation heat capacity for the rate-limiting chemical step leads directly to predictions of temperature optima; both entropy and enthalpy are temperature dependent. Fluctuations in the transition state ensemble are reduced compared to the ground state. We show how investigations combining experiment with molecular simulation are revealing fundamental details of enzyme thermoadaptation that are relevant for understanding aspects of enzyme evolution. Simulations can calculate relevant thermodynamic properties (such as activation enthalpies, entropies, and heat capacities) and reveal the molecular mechanisms underlying experimentally observed behavior. Expected final online publication date for the Annual Review of Biophysics, Volume 49 is May 6, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.Cleft palate is among the most common structural birth defects in humans. Previous studies have shown that mutations in FOXF2 are associated with cleft palate in humans and **** and that Foxf2 acts in a Shh-Foxf-Fgf18-Shh molecular network controlling palatal shelf growth. In this study, we combined RNA-seq and ChIP-seq approaches to identify direct transcriptional target genes mediating Foxf2 function in palate development in ****. Of 155 genes that exhibited Foxf2-dependent expression in the developing palatal mesenchyme, 88 contained or were located next to Foxf2-binding sites. Through in situ hybridization analyses, we demonstrate that expression of many of these target genes, including multiple genes encoding transcription factors and several encoding extracellular matrix-modifying proteins, were specifically upregulated in the posterior region of palatal shelves in Foxf2-/- mouse embryos. Foxf2 occupancy at many of these putative target loci, including Fgf18, in the developing palatal tissues was verified by ChIP-polymerase chain reaction analyses.
    Emotions are part and parcel of the human condition, but their nature is debated. Three broad classes of theories about the nature of emotions can be distinguished affect-program theories, constructionist theories, and appraisal theories. Integrating these broad classes of theories into a unifying theory is challenging. An integrative psychometric model of emotions can inform such a theory because psychometric models are intertwined with theoretical perspectives about constructs. To identify an integrative psychometric model, we delineate properties of emotions stated by emotion theories and investigate whether psychometric models account for these properties. Specifically, an integrative psychometric model of emotions should allow (a) identifying distinct emotions (central in affect-program theories), (b) between- and within-person variations of emotions (central in constructionist theories), and (c) causal relationships between emotion components (central in appraisal theories). Evidence suggests that the popular reflective and formative latent variable models-in which emotions are conceptualized as unobservable causes or consequences of emotion components-cannot account for all properties. Conversely, a psychometric network model-in which emotions are conceptualized as systems of causally interacting emotion components-accounts for all properties. The psychometric network model thus constitutes an integrative psychometric model of emotions, facilitating progress toward a unifying theory.Osteocytes are an ancient cell, appearing in fossilized skeletal remains of early fish and dinosaurs. Despite its relative high abundance, even in the context of nonskeletal cells, the osteocyte is perhaps among the least studied cells in all of vertebrate biology. Osteocytes are cells embedded in bone, able to modify their surrounding extracellular matrix via specialized molecular remodeling mechanisms that are independent of the bone forming osteoblasts and bone-resorbing osteoclasts. Osteocytes communicate with osteoclasts and osteoblasts via distinct signaling molecules that include the RankL/OPG axis and the Sost/Dkk1/Wnt axis, among others. Osteocytes also extend their influence beyond the local bone environment by functioning as an endocrine cell that controls phosphate reabsorption in the kidney, insulin secretion in the pancreas, and skeletal muscle function. These cells are also finely tuned sensors of mechanical stimulation to coordinate with effector cells to adjust bone mass, size, and shape to conform to mechanical demands.Cardiac fibrosis is a pathological condition that occurs after injury and during aging. Currently, there are limited means to effectively reduce or reverse fibrosis. Key to identifying methods for curbing excess deposition of extracellular matrix is a better understanding of the cardiac fibroblast, the cell responsible for collagen production. In recent years, the diversity and functions of these enigmatic cells have been gradually revealed. In this review, I outline current approaches for identifying and classifying cardiac fibroblasts. An emphasis is placed on new insights into the heterogeneity of these cells as determined by lineage tracing and single-cell sequencing in development, adult, and disease states. https://www.selleckchem.com/products/fezolinetant.html These recent advances in our understanding of the fibroblast provide a platform for future development of novel therapeutics to combat cardiac fibrosis.The limits of evolution have long fascinated biologists. However, the causes of evolutionary constraint have remained elusive due to a poor mechanistic understanding of studied phenotypes. Recently, a range of innovative approaches have leveraged mechanistic information on regulatory networks and cellular biology. These methods combine systems biology models with population and single-cell quantification and with new genetic tools, and they have been applied to a range of complex cellular functions and engineered networks. In this article, we review these developments, which are revealing the mechanistic causes of epistasis at different levels of biological organization-in molecular recognition, within a single regulatory network, and between different networks-providing first indications of predictable features of evolutionary constraint. Expected final online publication date for the Annual Review of Biophysics, Volume 49 is May 6, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.We review the adaptations of enzyme activity to different temperatures. Psychrophilic (cold-adapted) enzymes show significantly different activation parameters (lower activation enthalpies and entropies) than their mesophilic counterparts. Furthermore, there is increasing evidence that the temperature dependence of many enzyme-catalyzed reactions is more complex than is widely believed. Many enzymes show curvature in plots of activity versus temperature that is not accounted for by denaturation or unfolding. This is explained by macromolecular rate theory A negative activation heat capacity for the rate-limiting chemical step leads directly to predictions of temperature optima; both entropy and enthalpy are temperature dependent. Fluctuations in the transition state ensemble are reduced compared to the ground state. We show how investigations combining experiment with molecular simulation are revealing fundamental details of enzyme thermoadaptation that are relevant for understanding aspects of enzyme evolution. Simulations can calculate relevant thermodynamic properties (such as activation enthalpies, entropies, and heat capacities) and reveal the molecular mechanisms underlying experimentally observed behavior. Expected final online publication date for the Annual Review of Biophysics, Volume 49 is May 6, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.Cleft palate is among the most common structural birth defects in humans. Previous studies have shown that mutations in FOXF2 are associated with cleft palate in humans and mice and that Foxf2 acts in a Shh-Foxf-Fgf18-Shh molecular network controlling palatal shelf growth. In this study, we combined RNA-seq and ChIP-seq approaches to identify direct transcriptional target genes mediating Foxf2 function in palate development in mice. Of 155 genes that exhibited Foxf2-dependent expression in the developing palatal mesenchyme, 88 contained or were located next to Foxf2-binding sites. Through in situ hybridization analyses, we demonstrate that expression of many of these target genes, including multiple genes encoding transcription factors and several encoding extracellular matrix-modifying proteins, were specifically upregulated in the posterior region of palatal shelves in Foxf2-/- mouse embryos. Foxf2 occupancy at many of these putative target loci, including Fgf18, in the developing palatal tissues was verified by ChIP-polymerase chain reaction analyses.
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