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Upon assessment of the safety, these strains were negative for hemolytic activity and all tested virulence genes. In vivo safety assessment showed no adverse effects of isolated strains supplementation on the body weight gain and organ indices of the treated mice. This study revealed that these LAB isolates, especially L. salivarius M2-71, possess desirable probiotic properties and have great potentials for the development of feed additives for animals to promote health. Copyright © 2020 Li, Wang, Cui, Li, Sun and Qiu.Japanese encephalitis (JE) is a zoonotic, emerging disease transmitted by mosquito vectors infected with the Japanese encephalitis virus (JEV). Its potential for emergence into susceptible regions is high, including in the United States (US), and is a reason of economic concern among the agricultural community, and to public health due to high morbidity and mortality rates in humans. While exploring the complexities of interactions involved with viral transmission, we proposed a new outlook on the role of vectors, hosts and the environment under changing conditions. For instance, the role of feral pigs may have been underappreciated in our previous work, given research keeps pointing to the importance of susceptible populations of wild swine in naïve regions as key elements for the introduction of emergent vector-borne diseases. High risk of JEV introduction has been associated with the transportation of infected mosquitoes via aircraft. Nonetheless, no JEV outbreaks have been reported in the US to date and results from a qualitative risk assessment considered the risk of establishment to be negligible under the current conditions (environmental, vector, pathogen, and host). In this work, we discuss virus-vector-host interactions and ecological factors important for virus transmission and spread, review research on the risk of JEV introduction to the US considering the implications of risk dismissal as it relates to past experiences with similar arboviruses, and reflect on future directions, challenges, and implications of a JEV incursion. Copyright © 2020 Oliveira, Cohnstaedt, Noronha, Mitzel, McVey and Cernicchiaro.Broiler chickens are highly sensitive to high ambient temperatures due to their feathers, lack of skin sweat glands, and high productivity. Heat stress (HS) is a major concern for the poultry industry because it negatively affects growth as well as immune functions, which increase the potential risk of infectious disease outbreaks. Therefore, it is vital to elucidate HS's effect on the avian immune system, especially considering the global rise in average surface temperature. Our study identified a series of immunological disorders in heat-stressed broiler chickens. We exposed 22-day-old broiler chickens to a continuous HS condition (34.5 ± 0.5°C) for 14 days and immunized them with a prototype bovine serum albumin (BSA) antigen. The plasma and lymphoid tissues (thymus, bursa of Fabricius, and spleen) were harvested at the end of the experiments to investigate the induction of BSA-specific immune responses. Our results revealed that plasma titers of immunoglobulin (Ig)Y, IgM, and IgA antibodies specific for BSA were lower than those of thermoneutral chickens immunized with BSA. Furthermore, the spleens of the heat-stressed broiler chickens displayed severe depression of Bu1+ B cells and CD3+ T cells, including CD4+ T cells and CD8+ T cells, and lacked a fully developed germinal center (GC), which is crucial for B cell proliferation. These immunological abnormalities might be associated with severe depression of CD4-CD8- or CD4+CD8+ cells, which are precursors of either helper or killer T cells in the thymus and Bu1+ B cells in the bursa of Fabricius. Importantly, HS severely damaged the morphology of the thymic cortex and bursal follicles, where functional maturation of T and B cells occur. These results indicate that HS causes multiple immune abnormalities in broiler chickens by impairing the developmental process and functional maturation of T and B cells in both primary and secondary lymphoid tissues. Copyright © 2020 Hirakawa, Nurjanah, Furukawa, Murai, Kikusato, Nochi and Toyomizu.Bovine-viral-diarrhea virus (BVDV) can cause significant economic losses in livestock. The disease is controlled with vaccination and bovines are susceptible until vaccine immunity develops and may remain vulnerable if a persistently infected animal is left on the farm; therefore, an antiviral agent that reduces virus infectivity can be a useful tool in control programs. Although many compounds with promising in-vitro efficacy have been identified, the lack of laboratory-animal models limited their potential for further clinical development. Recently, we described the activity of type I and III interferons, IFN-α and IFN-λ respectively, against several BVDV strains in-vitro. In this study, we analyzed the in-vivo efficacy of both IFNs using a BALB/c-mouse model. Mice infected with two type-2 BVDV field strains developed a viremia with different kinetics, depending on the infecting strain's virulence, that persisted for 56 days post-infection (dpi). Mice infected with the low-virulence strain elicited high systemic TNF-α levels at 2 dpi. IFNs were first applied subcutaneously 1 day before or after infection. The two IFNs reduced viremia with different kinetics, depending on whether either one was applied before or after infection. In a second experiment, we increased the number of applications of both IFNs. All the treatments reduced viremia compared to untreated mice. The application of IFN-λ pre- and post-infection reduced viremia over time. This study is the first proof of the concept of the antiviral potency of IFN-λ against BVDV in-vivo, thus encouraging further trails for a potential use of this cytokine in cattle. Copyright © 2020 Quintana, Barone, Trotta, Turco, Mansilla, Capozzo and Cardoso.The usage of automatic feeding systems (AFS) in cattle offers multiple advantages, mostly due to the possibility of an increased feeding frequency. https://www.selleckchem.com/products/Cyclopamine.html While it is gaining more and more importance in dairy farming, there is still a lack of experience and scientific knowledge regarding its use in fattening cattle. The aim of this study was to describe the behavior of 56 Simmental bulls fed with an AFS six times daily a total mixed ration. The animals arrived at the farm with an average age of 148 ± 11 days. They were housed in four straw-bedded pens in groups of 14 animals each. Their average slaughter age was 558 ± 20 days. Behavioral observations were made during three observation periods (OP) at an average of 11, 14, and 16 months of age. Using scan sampling, feeding, and lying behavior of all animals and the order of bulls feeding after feed delivery were recorded. Furthermore, body condition and health status were monitored and complemented with the carcass weights. Body condition, health status, and carcass weights of the bulls were found to be satisfactory Mean body condition score increased from 2.

4 hrs ago


Industry and state policies may also play a role supporting the conditions that will improve the agility, capacity and readiness of businesses operating in volatile resource-based economies.Older adults with the human immunodeficiency virus or HIV (OAWH), people 50 years and older, are aging with the disease and experience low quality of life. Mental health disorders trigger and worsen health inequalities with larger impacts on the quality of life of OAWH. This paper evaluated two rival health interventions using a standard decision-analytic model and quantified the cost per quality-adjusted life-years (QALY) to understand the differential in cost and effectiveness of an additional unit of perfect health. HIV medical care was compared with a combined strategy that includes both HIV medical and behavioral care. Primary data from a convenience sample (n=139) collected in New York City and outcomes for healthy older adults from the literature were used in this study. The incremental cost-effectiveness ratio (ICER) evaluating the economic cost and health benefits of the new intervention was $36,166 per QALY, which is less than the willingness to pay ($75,000). The ICER for Hispanics was $35,325 and for White/Caucasians was $40,499. Integrated medical plus behavioral care is cost-effective and improves quality of life among OAWH. Given the high rates of mental health disorders along with an underutilization of behavioral care among OAWH, timely and effective mental health programs are paramount to increase quality of life.This JASA rejoinder concerns the problem of individualized decision making under point, sign, and partial identification. The paper unifies various classical decision making strategies through a lower bound perspective proposed in Cui and Tchetgen Tchetgen (2020b) in the context of optimal treatment regimes under uncertainty due to unmeasured confounding. Building on this unified framework, the paper also provides a novel minimax solution (i.e., a rule that minimizes the maximum regret for so-called opportunists) for individualized decision making/policy assignment.Tolerance is claimed not just as central to liberalism, but increasingly as the sole preserve of a liberal order. This essay opens up a critical space for examining the naturalized relationship between liberalism and tolerance by focusing on the political thought of Javed Ahmad Ghamidi (1951-), a prominent Pakistani public intellectual who is often labeled as a "liberal" Islamic thinker. Ghamidi has never identified himself as one. Using as an investigative opportunity the disjuncture between his self-identification and how his ideas are labeled, and placing Ghamidi's ideas within the wider tradition of Islamic thought, this essay elaborates on his vision of non-liberal tolerance predicated on individual responsibility infused with humility and shari'a-inspired state minimalism. Insight into the depth of nonliberal conceptions can facilitate a reconsideration of the relationship between liberalism and tolerance.This article examines the ethics of using ethnographic methods in contemporary conflict zones. Ethnographic research is an embodied research practice of immersion within a field site whereby researchers use ethnographic sensibility to study how people make sense of their world. Feminist, conflict and peacebuilding scholars who research vulnerable populations and local dynamics especially value ethnographic approaches for their emphasis on contextual understanding, human agency, egalitarian research relationships and researcher empathy. While immersion leads to knowledge that can hardly be replaced by using more formal approaches, it also elicits ethical dilemmas. These arise not only from the specific research context but also from who the researcher is and how they may navigate violent and often misogynous settings. I argue that many dilemmas may and perhaps should not be overcome by researcher skill and perseverance. Instead, ethical challenges may lead researchers to adopt limited and/or uneven immersion in their field site, not as failed or flawed ethnography but as an ethical research strategy that incorporates ethnographic sensibility to a varying extent. Examining why researchers may opt for limited and uneven immersion is important because in conflict research, stereotypes of the intrepid (male) researcher with a neutral gaze still tend to mute open discussions of how gender, race, ethnicity, nationality, class and other background factors inevitably shape immersion. This article seeks to contribute to creating discursive space for these conversations, which are vital for researchers to analyse, reflect and write from the position of a 'vulnerable observer' and incorporate greater transparency in the discussion of research findings.
The Endoscopic sleeve gastroplasty (ESG) is one of the new advanced restrictive techniques of bariatric endoscopy. The principle of this bariatric technique is the reduction of stomach volume through endoscopic plication. The long-term efficacy and metabolic effects of this procedure are the subject of this study.

20 patients were enrolled; four men, sixteen women. https://www.selleckchem.com/products/Gefitinib.html Then they were followed for 24 months in terms of glycemic control, body composition, vitamin, and nutritional status. Observed parameters included glucose, triacylglycerols, high- and low-density lipoprotein cholesterol, micro and macro nutrients, fat mass, and lean body mass.

We observed significant weight loss and a decrease body composition resulted from procedure vs. baseline, with levels of blood glucose also showing statistically significant reductions. The most notable decline in measured values was observed in period six months after the procedure. No significant changes were observed in measurement of micronutrients.

Good restriction results were obtained following ESG, which might be mediated via altered glucose metabolism. The ESG method has shown a positive effect on fat and muscle mass. Unlike surgical methods, there were no deficits or deficiencies, especially in terms of essential vitamin levels.
Good restriction results were obtained following ESG, which might be mediated via altered glucose metabolism. The ESG method has shown a positive effect on fat and muscle mass. Unlike surgical methods, there were no deficits or deficiencies, especially in terms of essential vitamin levels.

9 hrs ago


Understanding how the mechanical environment influences protein translational mechanisms in the cardiovascular system, will help to inform disease pathogenesis and potential areas of therapeutic intervention. Copyright © 2020 Simpson, Reader and Tzima.The dynamic interplay between virus and host proteins is critical for establishing efficient viral replication and virus-induced pathogenesis. Phosphorylation-dependent prolyl isomerization by Pin1 provides a unique mechanism of molecular switching to control both protein function and stability. We demonstrate here that Pin1 binds and stabilizes hepatitis B virus core protein (HBc) in a phosphorylation-dependent manner, and promotes the efficient viral propagation. Phos-tag gel electrophoresis with various site-directed mutants of HBc revealed that Thr160 and Ser162 residues within the C terminal arginine-rich domain are phosphorylated concomitantly. GST pull-down assay and co-immunoprecipitation analysis demonstrated that Pin1 associated with phosphorylated HBc at the Thr160-Pro and Ser162-Pro motifs. Chemical or genetic inhibition of Pin1 significantly accelerated the rapid degradation of HBc via a lysosome-dependent pathway. Furthermore, we found that the pyruvate dehydrogenase phosphatase catalytic subunit 2 (PDP2) could dephosphorylate HBc at the Pin1-binding sites, thereby suppressing Pin1-mediated HBc stabilization. Our findings reveal an important regulatory mechanism of HBc stability catalyzed by Pin1 and may facilitate the development of new antiviral therapeutics targeting Pin1 function. Copyright © 2020 Nishi, Miyakawa, Matsunaga, Khatun, Yamaoka, Watashi, Sugiyama, Kimura, Wakita and Ryo.WNT signaling is crucial for tissue morphogenesis during development in all multicellular animals. After birth, WNT/CTNNB1 responsive stem cells are responsible for tissue homeostasis in various organs and hyperactive WNT/CTNNB1 signaling is observed in many different human cancers. The first link between WNT signaling and breast cancer was established almost 40 years ago, when Wnt1 was identified as a proto-oncogene capable of driving mammary tumor formation in mice. Since that discovery, there has been a dedicated search for aberrant WNT signaling in human breast cancer. However, much debate and controversy persist regarding the importance of WNT signaling for the initiation, progression or maintenance of different breast cancer subtypes. As the first drugs designed to block functional WNT signaling have entered clinical trials, many questions about the role of aberrant WNT signaling in human breast cancer remain. Here, we discuss three major research gaps in this area. First, we still lack a basic understanding of the function of WNT signaling in normal human breast development and physiology. Second, the overall extent and precise effect of (epi)genetic changes affecting the WNT pathway in different breast cancer subtypes are still unknown. Which underlying molecular and cell biological mechanisms are disrupted as a result also awaits further scrutiny. Third, we survey the current status of targeted therapeutics that are aimed at interfering with the WNT pathway in breast cancer patients and highlight the importance and complexity of selecting the subset of patients that may benefit from treatment. Copyright © 2020 van Schie and van Amerongen.Several lines of evidence have confirmed the magnitude of crosstalk between HGF/c-Met axis (hepatocyte growth factor and its high-affinity receptor c-mesenchymal-epithelial transition factor) and non-coding RNAs (ncRNAs) in tumorigenesis. Through activating canonical or non-canonical signaling pathways, the HGF/c-Met axis mediates a range of oncogenic processes such as cell proliferation, invasion, apoptosis, and angiogenesis and is increasingly becoming a promising target for cancer therapy. Meanwhile, ncRNAs are a cluster of functional RNA molecules that perform their biological roles at the RNA level and are essential regulators of gene expression. The expression of ncRNAs is cell/tissue/tumor-specific, which makes them excellent candidates for cancer research. Many studies have revealed that ncRNAs play a crucial role in cancer initiation and progression by regulating different downstream genes or signal transduction pathways, including HGF/c-Met axis. In this review, we discuss the regulatory association between ncRNAs and the HGF/c-Met axis by providing a comprehensive understanding of their potential mechanisms and roles in cancer development. These findings could reveal their possible clinical applications as biomarkers for therapeutic interventions. Copyright © 2020 Liu, Sun, Chen, Liu, Cui, Shen, Cui, Ren and Yu.Cytoplasmic dynein-1 (hereafter referred to as dynein) is a major microtubule-based motor critical for cell division. Dynein is essential for the formation and positioning of the mitotic spindle as well as the transport of various cargos in the cell. A striking feature of dynein is that, despite having a wide variety of functions, the catalytic subunit is coded in a single gene. To perform various cellular activities, there seem to be different types of dynein that share a common catalytic subunit. In this review, we will refer to the different kinds of dynein as "dyneins." This review attempts to classify the mechanisms underlying the emergence of multiple dyneins into four layers. Inside a cell, multiple dyneins generated through the multi-layered regulations interact with each other to form a network of dyneins. https://www.selleckchem.com/products/Obatoclax-Mesylate.html These dynein networks may be responsible for the accurate regulation of cellular activities, including cell division. How these networks function inside a cell, with a focus on the early embryogenesis of Caenorhabditis elegans embryos, is discussed, as well as future directions for the integration of our understanding of molecular layering to understand the totality of dynein's function in living cells. Copyright © 2020 Torisawa and Kimura.Botulinum neurotoxin (BoNT) has become a powerful therapeutic tool, and is extensively used in aesthetic medicine and in the treatment of neurological disorders. However, its duration of effect is limited, mainly owing to nerve sprouting. Inhibition of nerve sprouting to prolong the effective duration of BoNT is therefore of great clinical interest. However, appropriate interventional strategies to accomplish this are currently unavailable. In this study, we determined the role of the neurogenic regulator agrin in BoNT type A (BoNT/A)-induced nerve sprouting in a rat model. We then determined whether agrin could be used as an interventional target for prolonging the duration of effect of BoNT/A, and made a preliminary study of the upstream and downstream regulatory mechanisms by which agrin could influence the effective duration of BoNT/A. Our results showed that agrin was involved in the regulation of BoNT/A-induced nerve sprouting, and blocking of agrin function with anti-agrin antibody temporarily could delay muscle strength recovery and prolong the duration of BoNT/A effect.

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Upon assessment of the safety, these strains were negative for hemolytic activity and all tested virulence genes. In vivo safety assessment showed no adverse effects of isolated strains supplementation on the body weight gain and organ indices of the treated mice. This study revealed that these LAB isolates, especially L. salivarius M2-71, possess desirable probiotic properties and have great potentials for the development of feed additives for animals to promote health. Copyright © 2020 Li, Wang, Cui, Li, Sun and Qiu.Japanese encephalitis (JE) is a zoonotic, emerging disease transmitted by mosquito vectors infected with the Japanese encephalitis virus (JEV). Its potential for emergence into susceptible regions is high, including in the United States (US), and is a reason of economic concern among the agricultural community, and to public health due to high morbidity and mortality rates in humans. While exploring the complexities of interactions involved with viral transmission, we proposed a new outlook on the role of vectors, hosts and the environment under changing conditions. For instance, the role of feral pigs may have been underappreciated in our previous work, given research keeps pointing to the importance of susceptible populations of wild swine in naïve regions as key elements for the introduction of emergent vector-borne diseases. High risk of JEV introduction has been associated with the transportation of infected mosquitoes via aircraft. Nonetheless, no JEV outbreaks have been reported in the US to date and results from a qualitative risk assessment considered the risk of establishment to be negligible under the current conditions (environmental, vector, pathogen, and host). In this work, we discuss virus-vector-host interactions and ecological factors important for virus transmission and spread, review research on the risk of JEV introduction to the US considering the implications of risk dismissal as it relates to past experiences with similar arboviruses, and reflect on future directions, challenges, and implications of a JEV incursion. Copyright © 2020 Oliveira, Cohnstaedt, Noronha, Mitzel, McVey and Cernicchiaro.Broiler chickens are highly sensitive to high ambient temperatures due to their feathers, lack of skin sweat glands, and high productivity. Heat stress (HS) is a major concern for the poultry industry because it negatively affects growth as well as immune functions, which increase the potential risk of infectious disease outbreaks. Therefore, it is vital to elucidate HS's effect on the avian immune system, especially considering the global rise in average surface temperature. Our study identified a series of immunological disorders in heat-stressed broiler chickens. We exposed 22-day-old broiler chickens to a continuous HS condition (34.5 ± 0.5°C) for 14 days and immunized them with a prototype bovine serum albumin (BSA) antigen. The plasma and lymphoid tissues (thymus, bursa of Fabricius, and spleen) were harvested at the end of the experiments to investigate the induction of BSA-specific immune responses. Our results revealed that plasma titers of immunoglobulin (Ig)Y, IgM, and IgA antibodies specific for BSA were lower than those of thermoneutral chickens immunized with BSA. Furthermore, the spleens of the heat-stressed broiler chickens displayed severe depression of Bu1+ B cells and CD3+ T cells, including CD4+ T cells and CD8+ T cells, and lacked a fully developed germinal center (GC), which is crucial for B cell proliferation. These immunological abnormalities might be associated with severe depression of CD4-CD8- or CD4+CD8+ cells, which are precursors of either helper or killer T cells in the thymus and Bu1+ B cells in the bursa of Fabricius. Importantly, HS severely damaged the morphology of the thymic cortex and bursal follicles, where functional maturation of T and B cells occur. These results indicate that HS causes multiple immune abnormalities in broiler chickens by impairing the developmental process and functional maturation of T and B cells in both primary and secondary lymphoid tissues. Copyright © 2020 Hirakawa, Nurjanah, Furukawa, Murai, Kikusato, Nochi and Toyomizu.Bovine-viral-diarrhea virus (BVDV) can cause significant economic losses in livestock. The disease is controlled with vaccination and bovines are susceptible until vaccine immunity develops and may remain vulnerable if a persistently infected animal is left on the farm; therefore, an antiviral agent that reduces virus infectivity can be a useful tool in control programs. Although many compounds with promising in-vitro efficacy have been identified, the lack of laboratory-animal models limited their potential for further clinical development. Recently, we described the activity of type I and III interferons, IFN-α and IFN-λ respectively, against several BVDV strains in-vitro. In this study, we analyzed the in-vivo efficacy of both IFNs using a BALB/c-mouse model. Mice infected with two type-2 BVDV field strains developed a viremia with different kinetics, depending on the infecting strain's virulence, that persisted for 56 days post-infection (dpi). Mice infected with the low-virulence strain elicited high systemic TNF-α levels at 2 dpi. IFNs were first applied subcutaneously 1 day before or after infection. The two IFNs reduced viremia with different kinetics, depending on whether either one was applied before or after infection. In a second experiment, we increased the number of applications of both IFNs. All the treatments reduced viremia compared to untreated mice. The application of IFN-λ pre- and post-infection reduced viremia over time. This study is the first proof of the concept of the antiviral potency of IFN-λ against BVDV in-vivo, thus encouraging further trails for a potential use of this cytokine in cattle. Copyright © 2020 Quintana, Barone, Trotta, Turco, Mansilla, Capozzo and Cardoso.The usage of automatic feeding systems (AFS) in cattle offers multiple advantages, mostly due to the possibility of an increased feeding frequency. https://www.selleckchem.com/products/Cyclopamine.html While it is gaining more and more importance in dairy farming, there is still a lack of experience and scientific knowledge regarding its use in fattening cattle. The aim of this study was to describe the behavior of 56 Simmental bulls fed with an AFS six times daily a total mixed ration. The animals arrived at the farm with an average age of 148 ± 11 days. They were housed in four straw-bedded pens in groups of 14 animals each. Their average slaughter age was 558 ± 20 days. Behavioral observations were made during three observation periods (OP) at an average of 11, 14, and 16 months of age. Using scan sampling, feeding, and lying behavior of all animals and the order of bulls feeding after feed delivery were recorded. Furthermore, body condition and health status were monitored and complemented with the carcass weights. Body condition, health status, and carcass weights of the bulls were found to be satisfactory Mean body condition score increased from 2.

4 hrs ago


Industry and state policies may also play a role supporting the conditions that will improve the agility, capacity and readiness of businesses operating in volatile resource-based economies.Older adults with the human immunodeficiency virus or HIV (OAWH), people 50 years and older, are aging with the disease and experience low quality of life. Mental health disorders trigger and worsen health inequalities with larger impacts on the quality of life of OAWH. This paper evaluated two rival health interventions using a standard decision-analytic model and quantified the cost per quality-adjusted life-years (QALY) to understand the differential in cost and effectiveness of an additional unit of perfect health. HIV medical care was compared with a combined strategy that includes both HIV medical and behavioral care. Primary data from a convenience sample (n=139) collected in New York City and outcomes for healthy older adults from the literature were used in this study. The incremental cost-effectiveness ratio (ICER) evaluating the economic cost and health benefits of the new intervention was $36,166 per QALY, which is less than the willingness to pay ($75,000). The ICER for Hispanics was $35,325 and for White/Caucasians was $40,499. Integrated medical plus behavioral care is cost-effective and improves quality of life among OAWH. Given the high rates of mental health disorders along with an underutilization of behavioral care among OAWH, timely and effective mental health programs are paramount to increase quality of life.This JASA rejoinder concerns the problem of individualized decision making under point, sign, and partial identification. The paper unifies various classical decision making strategies through a lower bound perspective proposed in Cui and Tchetgen Tchetgen (2020b) in the context of optimal treatment regimes under uncertainty due to unmeasured confounding. Building on this unified framework, the paper also provides a novel minimax solution (i.e., a rule that minimizes the maximum regret for so-called opportunists) for individualized decision making/policy assignment.Tolerance is claimed not just as central to liberalism, but increasingly as the sole preserve of a liberal order. This essay opens up a critical space for examining the naturalized relationship between liberalism and tolerance by focusing on the political thought of Javed Ahmad Ghamidi (1951-), a prominent Pakistani public intellectual who is often labeled as a "liberal" Islamic thinker. Ghamidi has never identified himself as one. Using as an investigative opportunity the disjuncture between his self-identification and how his ideas are labeled, and placing Ghamidi's ideas within the wider tradition of Islamic thought, this essay elaborates on his vision of non-liberal tolerance predicated on individual responsibility infused with humility and shari'a-inspired state minimalism. Insight into the depth of nonliberal conceptions can facilitate a reconsideration of the relationship between liberalism and tolerance.This article examines the ethics of using ethnographic methods in contemporary conflict zones. Ethnographic research is an embodied research practice of immersion within a field site whereby researchers use ethnographic sensibility to study how people make sense of their world. Feminist, conflict and peacebuilding scholars who research vulnerable populations and local dynamics especially value ethnographic approaches for their emphasis on contextual understanding, human agency, egalitarian research relationships and researcher empathy. While immersion leads to knowledge that can hardly be replaced by using more formal approaches, it also elicits ethical dilemmas. These arise not only from the specific research context but also from who the researcher is and how they may navigate violent and often misogynous settings. I argue that many dilemmas may and perhaps should not be overcome by researcher skill and perseverance. Instead, ethical challenges may lead researchers to adopt limited and/or uneven immersion in their field site, not as failed or flawed ethnography but as an ethical research strategy that incorporates ethnographic sensibility to a varying extent. Examining why researchers may opt for limited and uneven immersion is important because in conflict research, stereotypes of the intrepid (male) researcher with a neutral gaze still tend to mute open discussions of how gender, race, ethnicity, nationality, class and other background factors inevitably shape immersion. This article seeks to contribute to creating discursive space for these conversations, which are vital for researchers to analyse, reflect and write from the position of a 'vulnerable observer' and incorporate greater transparency in the discussion of research findings.
The Endoscopic sleeve gastroplasty (ESG) is one of the new advanced restrictive techniques of bariatric endoscopy. The principle of this bariatric technique is the reduction of stomach volume through endoscopic plication. The long-term efficacy and metabolic effects of this procedure are the subject of this study.

20 patients were enrolled; four men, sixteen women. https://www.selleckchem.com/products/Gefitinib.html Then they were followed for 24 months in terms of glycemic control, body composition, vitamin, and nutritional status. Observed parameters included glucose, triacylglycerols, high- and low-density lipoprotein cholesterol, micro and macro nutrients, fat mass, and lean body mass.

We observed significant weight loss and a decrease body composition resulted from procedure vs. baseline, with levels of blood glucose also showing statistically significant reductions. The most notable decline in measured values was observed in period six months after the procedure. No significant changes were observed in measurement of micronutrients.

Good restriction results were obtained following ESG, which might be mediated via altered glucose metabolism. The ESG method has shown a positive effect on fat and muscle mass. Unlike surgical methods, there were no deficits or deficiencies, especially in terms of essential vitamin levels.
Good restriction results were obtained following ESG, which might be mediated via altered glucose metabolism. The ESG method has shown a positive effect on fat and muscle mass. Unlike surgical methods, there were no deficits or deficiencies, especially in terms of essential vitamin levels.

9 hrs ago


Understanding how the mechanical environment influences protein translational mechanisms in the cardiovascular system, will help to inform disease pathogenesis and potential areas of therapeutic intervention. Copyright © 2020 Simpson, Reader and Tzima.The dynamic interplay between virus and host proteins is critical for establishing efficient viral replication and virus-induced pathogenesis. Phosphorylation-dependent prolyl isomerization by Pin1 provides a unique mechanism of molecular switching to control both protein function and stability. We demonstrate here that Pin1 binds and stabilizes hepatitis B virus core protein (HBc) in a phosphorylation-dependent manner, and promotes the efficient viral propagation. Phos-tag gel electrophoresis with various site-directed mutants of HBc revealed that Thr160 and Ser162 residues within the C terminal arginine-rich domain are phosphorylated concomitantly. GST pull-down assay and co-immunoprecipitation analysis demonstrated that Pin1 associated with phosphorylated HBc at the Thr160-Pro and Ser162-Pro motifs. Chemical or genetic inhibition of Pin1 significantly accelerated the rapid degradation of HBc via a lysosome-dependent pathway. Furthermore, we found that the pyruvate dehydrogenase phosphatase catalytic subunit 2 (PDP2) could dephosphorylate HBc at the Pin1-binding sites, thereby suppressing Pin1-mediated HBc stabilization. Our findings reveal an important regulatory mechanism of HBc stability catalyzed by Pin1 and may facilitate the development of new antiviral therapeutics targeting Pin1 function. Copyright © 2020 Nishi, Miyakawa, Matsunaga, Khatun, Yamaoka, Watashi, Sugiyama, Kimura, Wakita and Ryo.WNT signaling is crucial for tissue morphogenesis during development in all multicellular animals. After birth, WNT/CTNNB1 responsive stem cells are responsible for tissue homeostasis in various organs and hyperactive WNT/CTNNB1 signaling is observed in many different human cancers. The first link between WNT signaling and breast cancer was established almost 40 years ago, when Wnt1 was identified as a proto-oncogene capable of driving mammary tumor formation in mice. Since that discovery, there has been a dedicated search for aberrant WNT signaling in human breast cancer. However, much debate and controversy persist regarding the importance of WNT signaling for the initiation, progression or maintenance of different breast cancer subtypes. As the first drugs designed to block functional WNT signaling have entered clinical trials, many questions about the role of aberrant WNT signaling in human breast cancer remain. Here, we discuss three major research gaps in this area. First, we still lack a basic understanding of the function of WNT signaling in normal human breast development and physiology. Second, the overall extent and precise effect of (epi)genetic changes affecting the WNT pathway in different breast cancer subtypes are still unknown. Which underlying molecular and cell biological mechanisms are disrupted as a result also awaits further scrutiny. Third, we survey the current status of targeted therapeutics that are aimed at interfering with the WNT pathway in breast cancer patients and highlight the importance and complexity of selecting the subset of patients that may benefit from treatment. Copyright © 2020 van Schie and van Amerongen.Several lines of evidence have confirmed the magnitude of crosstalk between HGF/c-Met axis (hepatocyte growth factor and its high-affinity receptor c-mesenchymal-epithelial transition factor) and non-coding RNAs (ncRNAs) in tumorigenesis. Through activating canonical or non-canonical signaling pathways, the HGF/c-Met axis mediates a range of oncogenic processes such as cell proliferation, invasion, apoptosis, and angiogenesis and is increasingly becoming a promising target for cancer therapy. Meanwhile, ncRNAs are a cluster of functional RNA molecules that perform their biological roles at the RNA level and are essential regulators of gene expression. The expression of ncRNAs is cell/tissue/tumor-specific, which makes them excellent candidates for cancer research. Many studies have revealed that ncRNAs play a crucial role in cancer initiation and progression by regulating different downstream genes or signal transduction pathways, including HGF/c-Met axis. In this review, we discuss the regulatory association between ncRNAs and the HGF/c-Met axis by providing a comprehensive understanding of their potential mechanisms and roles in cancer development. These findings could reveal their possible clinical applications as biomarkers for therapeutic interventions. Copyright © 2020 Liu, Sun, Chen, Liu, Cui, Shen, Cui, Ren and Yu.Cytoplasmic dynein-1 (hereafter referred to as dynein) is a major microtubule-based motor critical for cell division. Dynein is essential for the formation and positioning of the mitotic spindle as well as the transport of various cargos in the cell. A striking feature of dynein is that, despite having a wide variety of functions, the catalytic subunit is coded in a single gene. To perform various cellular activities, there seem to be different types of dynein that share a common catalytic subunit. In this review, we will refer to the different kinds of dynein as "dyneins." This review attempts to classify the mechanisms underlying the emergence of multiple dyneins into four layers. Inside a cell, multiple dyneins generated through the multi-layered regulations interact with each other to form a network of dyneins. https://www.selleckchem.com/products/Obatoclax-Mesylate.html These dynein networks may be responsible for the accurate regulation of cellular activities, including cell division. How these networks function inside a cell, with a focus on the early embryogenesis of Caenorhabditis elegans embryos, is discussed, as well as future directions for the integration of our understanding of molecular layering to understand the totality of dynein's function in living cells. Copyright © 2020 Torisawa and Kimura.Botulinum neurotoxin (BoNT) has become a powerful therapeutic tool, and is extensively used in aesthetic medicine and in the treatment of neurological disorders. However, its duration of effect is limited, mainly owing to nerve sprouting. Inhibition of nerve sprouting to prolong the effective duration of BoNT is therefore of great clinical interest. However, appropriate interventional strategies to accomplish this are currently unavailable. In this study, we determined the role of the neurogenic regulator agrin in BoNT type A (BoNT/A)-induced nerve sprouting in a rat model. We then determined whether agrin could be used as an interventional target for prolonging the duration of effect of BoNT/A, and made a preliminary study of the upstream and downstream regulatory mechanisms by which agrin could influence the effective duration of BoNT/A. Our results showed that agrin was involved in the regulation of BoNT/A-induced nerve sprouting, and blocking of agrin function with anti-agrin antibody temporarily could delay muscle strength recovery and prolong the duration of BoNT/A effect.

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racterization of oral fungi and bacteria in order to better elucidate the dynamic changes in microbial community structure and interkingdom functional interactions during the injury of chemotherapy and antibiotic exposure as well as the clinical consequences of these interrelated alterations. Copyright © 2020 Robinson et al.Candida albicans adapts to various conditions in different body niches by regulating gene expression, protein synthesis, and metabolic pathways. These adaptive reactions not only allow survival but also influence the interaction with host cells, which is governed by the composition and structure of the fungal cell wall. Numerous studies had shown linkages between mitochondrial functionality, cell wall integrity and structure, and pathogenicity. Thus, we decided to inhibit single complexes of the respiratory chain of C. albicans and to analyze the resultant interaction with macrophages via their phagocytic activity. Remarkably, inhibition of the fungal bc1 complex by antimycin A increased phagocytosis, which correlated with an increased accessibility of β-glucans. To contribute to mechanistic insights, we performed metabolic studies, which highlighted significant changes in the abundance of constituents of the plasma membrane. Collectively, our results reinforce the strong linkage between fungal energy metabolvance of energy metabolism, indirectly also for host-pathogen interactions, without affecting viability. Copyright © 2020 Cui et al.Alternative polyadenylation (APA) determines stability, localization and translation potential of the majority of mRNA in eukaryotic cells. The heterodimeric mammalian cleavage factor II (CF IIm) is required for pre-mRNA 3' end cleavage and is composed of the RNA kinase hClp1 and the termination factor hPcf11, the latter protein binds to RNA and the RNA polymerase II carboxy terminal domain. https://www.selleckchem.com/products/cenicriviroc.html Here, we used siRNA mediated knock-down and poly(A) targeted RNA sequencing to analyze the role of CF IIm in gene expression and APA in estrogen receptor positive MCF7 breast cancer cells. Identified gene ontology terms link CF IIm function to regulation of growth factor activity, protein heterodimerization and the cell cycle. An overlapping requirement for hClp1 and hPcf11 suggested that CF IIm protein complex was involved in the selection of proximal poly(A) sites. In addition to APA shifts within 3' un-translated regions (3' UTRs) we observed shifts from promoter proximal regions to the 3' UTR facilitating synthesis of full-length mRNAs. Moreover, we show that several truncated mRNAs that resulted from APA within introns in MCF7 cells co-sedimented with ribosomal components in an EDTA sensitive manner suggesting that those are translated into protein. We propose that CF IIm contributes to the regulation of mRNA function in breast cancer. Published by Cold Spring Harbor Laboratory Press for the RNA Society.The nadA motif is the first known NAD+-dependent riboswitch, comprising two similar tandem bulged stem-loop structures. We have determined the structure of the 5' domain 1 of the riboswitch. It has three coaxial helical segments, separated by an ACANCCCC bulge and by an internal loop, with a tertiary contact between them that includes two CG base pairs. We have determined the structure with a number of ligands related to NADH, but in each case only the ADP moiety is observed. The adenosine adopts an anti conformation, and forms multiple hydrogen bonds across the width of the sugar edge of the penultimate CG base pair of the helix preceding the bulge, and the observed contacts have been confirmed by mutagenesis and calorimetry. Two divalent metal ions play a key structural role at the narrow neck of the bulge. One makes direct bonding contacts to the di-phosphate moiety, locking it into position. Thus the nucleobase, ribose and phosphate groups of the ADP moiety are all specifically recognised by the RNA. The NAD+ riboswitch is modular. Domain 1 is an ADP binding domain that may be ancient, and could potentially be used in combination with other ligand binding motifs such as CoA. Published by Cold Spring Harbor Laboratory Press for the RNA Society.Cells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. However, most transcriptomic studies do not distinguish the relative contribution of transcription, RNA processing and RNA degradation processes to cellular homeostasis. Here we used metabolic labeling followed by massive parallel sequencing of newly transcribed and preexisting RNA fractions to simultaneously analyze RNA synthesis and decay in primary endothelial cells exposed to low oxygen tension. We found that changes in transcription rates induced by hypoxia are the major determinant of changes in RNA levels. However, degradation rates also had a significant contribution, accounting for 24% of the observed variability in total mRNA. In addition, our results indicated that hypoxia led to a reduction of the overall mRNA stability from a median half-life in normoxia of 8.7 hours, to 5.7 hours in hypoxia. Analysis of RNA content per cell confirmed a decrease of both mRNA and total RNA in hypoxic samples and that this effect is dependent on the EGLN/HIF/TSC2 axis. This effect could potentially contribute to fundamental global responses such as inhibition of translation in hypoxia. In summary, our study provides a quantitative analysis of the contribution of RNA synthesis and stability to the transcriptional response to hypoxia and uncovers an unexpected effect on the latter. Published by Cold Spring Harbor Laboratory Press for the RNA Society.Compendial testing methods are not required to be fully validated but their suitability should be verified under actual conditions of use. This requirement is established in 21 CFR 211.194(a)(2) of the current Good Manufacturing Practice regulations in United States. ANVISA (Agéncia Nacional de Vigiláncia Sanitária) also requires that compendial analytical methods shall have their suitability demonstrated for the intended use by a partial validation study. Suitability verification or partial validation can be divided into two major categories visual and instrumental methods. For visual methods, the color and clarity interferences should be evaluated. If the color or clarity/opalescence of the sample is outside of the range of the Pharmacopeia standards/reference solutions, the validity of test results should be evaluated. Specificity is usually waived since the methods are not specific to products, and accuracy/precision can be addressed by comparing results from analyst to analyst. For instrument methods, specificity can also be waived for certain assays.

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These findings provide compelling clinical and molecular evidence to support the conclusion that CXCL8 contributes to the genesis and progression of CRC. Copyright © 2020 Li, Liu, Huang, Cai, Song, Xie, Liu, Chen, Xu, Zeng, Chu and Zeng.Pathogen-host interactions play an important role in understanding the mechanism by which a pathogen can infect its host. Some approaches for predicting pathogen-host association have been developed, but prediction accuracy is still low. In this paper, we propose a bipartite network module-based approach to improve prediction accuracy. First, a bipartite network with pathogens and hosts is constructed. Next, pathogens and hosts are divided into different modules respectively. Then, modular information on the pathogens and hosts is added into a bipartite network projection model and the association scores between pathogens and hosts are calculated. Finally, leave-one-out cross-validation is used to estimate the performance of the proposed method. https://www.selleckchem.com/products/pemigatinib-incb054828.html Experimental results show that the proposed method performs better in predicting pathogen-host association than other methods, and some potential pathogen-host associations with higher prediction scores are also confirmed by the results of biological experiments in the publically available literature. Copyright © 2020 Li, Wang, Chen and Wang.As an important approach to cancer classification, cancer sample clustering is of particular importance for cancer research. For high dimensional gene expression data, examining approaches to selecting characteristic genes with high identification for cancer sample clustering is an important research area in the bioinformatics field. In this paper, we propose a novel integrated framework for cancer clustering known as the non-negative symmetric low-rank representation with graph regularization based on score function (NSLRG-S). First, a lowest rank matrix is obtained after NSLRG decomposition. The lowest rank matrix preserves the local data manifold information and the global data structure information of the gene expression data. Second, we construct the Score function based on the lowest rank matrix to weight all of the features of the gene expression data and calculate the score of each feature. Third, we rank the features according to their scores and select the feature genes for cancer sample clustering. Finally, based on selected feature genes, we use the K-means method to cluster the cancer samples. The experiments are conducted on The Cancer Genome Atlas (TCGA) data. Comparative experiments demonstrate that the NSLRG-S framework can significantly improve the clustering performance. Copyright © 2020 Lu, Wang, Liu, Zheng, Kong and Zhang.Shandong indigenous pig breeds are an invaluable source of data on genetics in Chinese pigs. However, information on the genetic basis of these breeds remains limited. In this study, we used specific-locus amplified fragment sequencing to conduct whole-genome screening to investigate genetic diversity in Shandong indigenous breeds and Western pig breeds. The results showed that Duroc pigs (DD) had clear genetic relationships with Dapulian pigs (DPL; Fst = 0.4386) and Laiwu pigs (LW; Fst = 0.5134), and DPL and LW were relatively close genetically (Fst = 0.2334). In general, Shandong indigenous breeds showed greater genetic variety than the Western breeds. Both neighbor-joining trees and principal components analyses were able to differentiate the breeds, but population structure analyses indicated that the Western breeds genetically influenced the Shandong indigenous breeds to some extent. A total of 162 differentially selected regions (DSRs) with 841 genes and 157 DSRs with 707 genes were identified in DPL and LW, respectively. Gene annotation of the selected regions identified a series of genes regulating immunity and fat deposition. Our data confirm the rationality and accuracy of the current classification of pig breeds in Shandong province. Our results point to candidate genes in Shandong indigenous pig breeds and further promote the importance of follow-up research on functional verification. Copyright © 2020 Qin, Li, Li, Chen and Zeng.Different genes have their protein products localized in various subcellular compartments. The diversity in protein localization may serve as a gene characteristic, revealing gene essentiality from a subcellular perspective. To measure this diversity, we introduced a Subcellular Diversity Index (SDI) based on the Gene Ontology-Cellular Component Ontology (GO-CCO) and a semantic similarity measure of GO terms. Analyses revealed that SDI of human genes was well correlated with some known measures of gene essentiality, including protein-protein interaction (PPI) network topology measurements, dN/dS ratio, homologous gene number, expression level and tissue specificity. In addition, SDI had a good performance in predicting human essential genes (AUC = 0.702) and drug target genes (AUC = 0.704), and drug targets with higher SDI scores tended to cause more side-effects. The results suggest that SDI could be used to identify novel drug targets and to guide the filtering of drug targets with fewer potential side effects. Finally, we developed a user-friendly online database for querying SDI score for genes across eight species, and the predicted probabilities of human drug target based on SDI. The online database of SDI is available at http//www.cuilab.cn/sdi. Copyright © 2020 Jia, Zhou and Cui.Long non-coding RNAs (lncRNAs) play important roles in various biological processes, where lncRNA-protein interactions are usually involved. Therefore, identifying lncRNA-protein interactions is of great significance to understand the molecular functions of lncRNAs. Since the experiments to identify lncRNA-protein interactions are always costly and time consuming, computational methods are developed as alternative approaches. However, existing lncRNA-protein interaction predictors usually require prior knowledge of lncRNA-protein interactions with experimental evidences. Their performances are limited due to the number of known lncRNA-protein interactions. In this paper, we explored a novel way to predict lncRNA-protein interactions without direct prior knowledge. MiRNAs were picked up as mediators to estimate potential interactions between lncRNAs and proteins. By validating our results based on known lncRNA-protein interactions, our method achieved an AUROC (Area Under Receiver Operating Curve) of 0.821, which is comparable to the state-of-the-art methods.