A global reptile assessment highlights shared conservation needs of tetrapods.

Comprehensive assessments of species' extinction risks have documented the extinction crisis1 and underpinned strategies for reducing those risks2. Global assessments reveal that, among tetrapods, 40.7% of amphibians, 25.4% of mammals and 13.6% of birds are threatened with extinction3. Because global assessments have been lacking, reptiles have been omitted from conservation-prioritization analyses that encompass other tetrapods4-7. Reptiles are unusually diverse in arid regions, suggesting that they may have different conservation needs6. Here we provide a comprehensive extinction-risk assessment of reptiles and show that at least 1,829 out of 10,196 species (21.1%) are threatened-confirming a previous extrapolation8 and representing 15.6 billion years of phylogenetic diversity. Reptiles are threatened by the same major factors that threaten other tetrapods-agriculture, logging, urban development and invasive species-although the threat posed by climate change remains uncertain. Reptiles inhabiting forests, where these threats are strongest, are more threatened than those in arid habitats, contrary to our prediction. Birds, mammals and amphibians are unexpectedly good surrogates for the conservation of reptiles, although threatened reptiles with the smallest ranges tend to be isolated from other threatened tetrapods. Although some reptiles-including most species of crocodiles and turtles-require urgent, targeted action to prevent extinctions, efforts to protect other tetrapods, such as habitat preservation and control of trade and invasive species, will probably also benefit many reptiles.

Molecular Basis for the Involvement of Mammalian Serum Albumin in the AGE/RAGE Axis: A Comprehensive Computational Study.

In mammals, glycated serum albumin (gSA) contributes to the pathogenesis of many metabolic diseases by activating the receptors (RAGE) for advanced glycation end products (AGEs). Many aspects of the gSA-RAGE interaction remain unknown. The purpose of the present paper was to study the interaction of glycated human albumin (gHSA) with RAGE using molecular modeling methods. Ten models of gHSA modified with different lysine residues to carboxymethyl-lysines were prepared. Complexes of gHSA-RAGE were obtained by the macromolecular docking method with subsequent molecular dynamics simulation (MD). According to the MD, the RAGE complexes with gHSA glycated at Lys233, Lys64, Lys525, Lys262 and Lys378 are the strongest. Three-dimensional models of the RAGE dimers with gHSA were proposed. Additional computational experiments showed that the binding of fatty acids (FAs) to HSA does not affect the ability of Lys525 (the most reactive lysine) to be glycated. In contrast, modification of Lys525 reduces the affinity of albumin for FA. The interspecies differences in the molecular structure of albumin that may affect the mechanism of the gSA-RAGE interaction were discussed. The obtained results will help us to learn more about the molecular basis for the involvement of serum albumin in the AGE/RAGE axis and improve the methodology for studying cellular signaling pathways involving RAGE.

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments.

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. Further, damage to the endothelium can be both a cause and a consequence of many diseases, especially in elderly people. The purpose of this study was to carry out immunological and biochemical profiling of elderly people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), and subcortical ischemic vascular dementia (SIVD). Socio-demographic, lifestyle, and cognitive data were obtained. Biochemical, hematological, and immunological analyses were carried out, and extracellular vesicles (EVs) with endothelial CD markers were assessed. The greatest number of significant deviations from conditionally healthy donors (HDs) of the same age were registered in the SIVD group, a total of 20, of which 12 were specific and six were non-specific but with maximal differences (as compared to the other three groups) from the HDs group. The non-specific deviations were for the MOCA (Montreal Cognitive Impairment Scale), the MMSE (Mini Mental State Examination) and life satisfaction self-assessment scores, a decrease of albumin levels, and ADAMTS13 (a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13) activity, and an increase of the VWF (von Willebrand factor) level. Considering the significant changes in immunological parameters (mostly Th17-like cells) and endothelial CD markers (CD144 and CD34), vascular repair was impaired to the greatest extent in the DM group. The AIS patients showed 12 significant deviations from the HD controls, including three specific to this group. These were high NEFAs (non-esterified fatty acids) and CD31 and CD147 markers of EVs. The lowest number of deviations were registered in the CCCI group, nine in total. There were significant changes from the HD controls with no specifics to this group, and just one non-specific with a maximal difference from the control parameters, which was α1-AGP (alpha 1 acid glycoprotein, orosomucoid). Besides the DM patients, impairments of vascular repair were also registered in the CCCI and AIS patients, with a complete absence of such in patients with dementia (SIVD group). On the other hand, microvascular damage seemed to be maximal in the latter group, considering the biochemical indicators VWF and ADAMTS13. In the DM patients, a maximum immune response was registered, mainly with Th17-like cells. In the CCCI group, the reaction was not as pronounced compared to other groups of patients, which may indicate the initial stages and/or compensatory nature of organic changes (remodeling). At the same time, immunological and biochemical deviations in SIVD patients indicated a persistent remodeling in microvessels, chronic inflammation, and a significant decrease in the anabolic function of the liver and other tissues. The data obtained support two interrelated assumptions. Taking into account the primary biochemical factors that trigger the pathological processes associated with vascular pathology and related diseases, the first assumption is that purine degradation in skeletal muscle may be a major factor in the production of uric acid, followed by its production by non-muscle cells, the main of which are endothelial cells. Another assumption is that therapeutic factors that increase the levels of endothelial progenitor cells may have a therapeutic effect in reducing the risk of cerebrovascular disease and related neurodegenerative diseases.

Serum Albumin in Health and Disease: From Comparative Biochemistry to Translational Medicine.

Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions, electrically neutral molecules and in maintaining the colloid osmotic pressure of the blood [...].

Albumin Is a Component of the Esterase Status of Human Blood Plasma.

The esterase status of blood plasma can claim to be one of the universal markers of various diseases; therefore, it deserves attention when searching for markers of the severity of COVID-19 and other infectious and non-infectious pathologies. When analyzing the esterase status of blood plasma, the esterase activity of serum albumin, which is the major protein in the blood of mammals, should not be ignored. The purpose of this study is to expand understanding of the esterase status of blood plasma and to evaluate the relationship of the esterase status, which includes information on the amount and enzymatic activity of human serum albumin (HSA), with other biochemical parameters of human blood, using the example of surviving and deceased patients with confirmed COVID-19. In experiments in vitro and in silico, the activity of human plasma and pure HSA towards various substrates was studied, and the effect of various inhibitors on this activity was tested. Then, a comparative analysis of the esterase status and a number of basic biochemical parameters of the blood plasma of healthy subjects and patients with confirmed COVID-19 was performed. Statistically significant differences have been found in esterase status and biochemical indices (including albumin levels) between healthy subjects and patients with COVID-19, as well as between surviving and deceased patients. Additional evidence has been obtained for the importance of albumin as a diagnostic marker. Of particular interest is a new index, [Urea] × [MDA] × 1000/(BChEb × [ALB]), which in the group of deceased patients was 10 times higher than in the group of survivors and 26 times higher than the value in the group of apparently healthy elderly subjects.

HIV-Related Stigma Research as a Priority at the National Institutes of Health.

The National Institutes of Health (NIH) recognizes that, despite HIV scientific advances, stigma and discrimination continue to be critical barriers to the uptake of evidence-based HIV interventions. Achieving the Ending the HIV Epidemic: A Plan for America (EHE) goals will require eliminating HIV-related stigma. NIH has a significant history of supporting HIV stigma research across its Institutes, Centers, and Offices (ICOs) as a research priority. This article provides an overview of NIH HIV stigma research efforts. Each ICO articulates how their mission shapes their interest in HIV stigma research and provides a summary of ICO-relevant scientific findings. Research gaps and/or future opportunities are identified throughout, with key research themes and approaches noted. Taken together, the collective actions on the part of the NIH, in tandem with a whole of government and whole of society approach, will contribute to achieving EHE's milestones.

RESUMEN: Los Institutos de Salud Nacional (NIH, siglas en inglés) reconocen que, a pesar de los avances en la prevención y el tratamiento, el estigma y la discriminación continúan siendo barreras críticas a la adopción de la prevención y el cuido basados en la evidencia. Las metas de Logrando el Fin de la Epidemia de VIH: Plan para América (EHE, siglas en inglés) requerirán la eliminación del estigma relacionado al VIH. Los NIH tienen una historia significativa apoyando la investigación del estigma relacionado al VIH a través de sus Institutos, Centros, y Oficinas (ICOs, siglas en inglés). Esta investigación es una prioridad fundamental y entrelazada para los ICOs. En este artículo, los autores de los NIH proveen una reseña sobre la investigación del estigma relacionado al VIH a través de los ICOs selectos. Cada ICO articula como su misión y prioridad dan forma a su interés en la investigación del estigma al VIH y provee una breve reseña de los hallazgos científicos pertinentes al ICO. Lagunas en la investigación relacionada a la misión, prioridades, y/o áreas de investigación futuras se identifican a través del artículo. También se apuntan en el resumen los temas de investigación claves y sus estrategias. En conjunto, las acciones colectivas de parte de los NIH, junto a la estrategia necesaria de parte del gobierno en su totalidad y de la sociedad en su totalidad, contribuirán al logro de las metas del EHE.

The relative importance of COVID-19 pandemic impacts on biodiversity conservation globally.

The COVID-19 pandemic has had an enormous impact on almost all aspects of human society and endeavor; the natural world and its conservation have not been spared. Through a process of expert consultation, we identified and categorized, into 19 themes and 70 subthemes, the ways in which biodiversity and its conservation have been or could be affected by the pandemic globally. Nearly 60% of the effects have been broadly negative. Subsequently, we created a compendium of all themes and subthemes, each with explanatory text, and in August 2020 a diverse group of experienced conservationists with expertise from across sectors and geographies assessed each subtheme for its likely impact on biodiversity conservation globally. The 9 subthemes ranked highest all have a negative impact. These were, in rank order, governments sidelining the environment during their economic recovery, reduced wildlife-based tourism income, increased habitat destruction, reduced government funding, increased plastic and other solid waste pollution, weakening of nature-friendly regulations and their enforcement, increased illegal harvest of wild animals, reduced philanthropy, and threats to survival of conservation organizations. In combination, these impacts present a worrying future of increased threats to biodiversity conservation but reduced capacity to counter them. The highest ranking positive impact, at 10, was the beneficial impact of wildlife-trade restrictions. More optimistically, among impacts ranked 11-20, 6 were positive and 4 were negative. We hope our assessment will draw attention to the impacts of the pandemic and, thus, improve the conservation community's ability to respond to such threats in the future.

La pandemia de COVID-19 ha tenido un impacto enorme sobre casi todos los aspectos de la sociedad humana y sus proyectos; el mundo natural y su conservación no han sido la excepción. Por medio de un proceso de consultas a expertos, identificamos y categorizamos en 19 temas y 70 subtemas las maneras en las que la biodiversidad y su conservación han sido o podrían ser afectadas mundialmente por la pandemia. Casi el 60% de los efectos han sido claramente negativos. Posteriormente, creamos un compendio de todos los temas y subtemas, cada uno con textos explicativos, para que en agosto de 2020 un grupo diverso de conservacionistas experimentados con conocimiento de todos los sectores y geografías evaluara cada subtema de acuerdo con su probabilidad de impactar sobre la conservación de la biodiversidad en todo el mundo. Los nueve subtemas con la clasificación más alta tienen un impacto negativo. Estos temas son, en orden de clasificación: los gobiernos dejando de lado al ambiente durante su recuperación económica, reducción de los ingresos basados en el turismo de fauna, incremento en la destrucción de hábitat, financiamiento reducido del gobierno, aumento de la contaminación por plásticos y otros desechos sólidos, debilitamiento de las regulaciones en pro de la naturaleza y su aplicación, incremento en la captura ilegal de animales, disminución de la filantropía y amenazas para la supervivencia de las organizaciones de conservación. La combinación de estos impactos representa un futuro preocupante lleno de amenazas para la conservación de la biodiversidad y una capacidad reducida para contrarrestarlas. El impacto positivo con la clasificación más alta, el 10, fue el impacto benéfico de las restricciones en el mercado de fauna. De manera más optimista, entre los impactos clasificados de los lugares del 11 al 20, seis fueron positivos y cuatro fueron negativos. Esperamos que nuestra evaluación enfoque la atención hacia los impactos de la pandemia y así mejore la habilidad de la comunidad conservacionista para responder a tales amenazas en el futuro. Importancia Relativa de los Impactos de la Pandemia de COVID-19 sobre la Conservación Mundial de la Biodiversidad.

Molecular Mechanisms of Acute Organophosphate Nephrotoxicity.

Organophosphates (OPs) are toxic chemicals produced by an esterification process and some other routes. They are the main components of herbicides, pesticides, and insecticides and are also widely used in the production of plastics and solvents. Acute or chronic exposure to OPs can manifest in various levels of toxicity to humans, animals, plants, and insects. OPs containing insecticides were widely used in many countries during the 20th century, and some of them continue to be used today. In particular, 36 OPs have been registered in the USA, and all of them have the potential to cause acute and sub-acute toxicity. Renal damage and impairment of kidney function after exposure to OPs, accompanied by the development of clinical manifestations of poisoning back in the early 1990s of the last century, was considered a rare manifestation of their toxicity. However, since the beginning of the 21st century, nephrotoxicity of OPs as a manifestation of delayed toxicity is the subject of greater attention of researchers. In this article, we present a modern view on the molecular pathophysiological mechanisms of acute nephrotoxicity of organophosphate compounds.

The fourth wave of the US opioid epidemic and its implications for the rural US: A federal perspective.

The current opioid epidemic in the United States has been characterized as having three waves: prescription opioid use, followed by heroin use, and then use of synthetic opioids (e.g., fentanyl), with early waves affecting a population that was younger, less predominantly male, and more likely to be Caucasian and rural than in past opioid epidemics. A variety of recent data suggest that we have entered a fourth wave which can be characterized as a stimulant/opioid epidemic, with mental illness co-morbidities being more evident than in the past. Stimulant use has introduced new complexities in terms of behavioral consequences (e.g., neurological deficits, suicidal ideation, psychosis, hostility, violence), available treatments, and engagement into services. These compound existing issues in addressing the opioid epidemic in rural areas, including the low density of populations and the scarcity of behavioral health resources (e.g., fewer credentialed behavioral health professionals, particularly those able to prescribe Buprenorphine). Considerations for addressing this new wave are discussed, along with the drawbacks of a wave perspective and persistent concerns in confronting drug abuse such as stigma.

Testing a global standard for quantifying species recovery and assessing conservation impact.

Recognizing the imperative to evaluate species recovery and conservation impact, in 2012 the International Union for Conservation of Nature (IUCN) called for development of a "Green List of Species" (now the IUCN Green Status of Species). A draft Green Status framework for assessing species' progress toward recovery, published in 2018, proposed 2 separate but interlinked components: a standardized method (i.e., measurement against benchmarks of species' viability, functionality, and preimpact distribution) to determine current species recovery status (herein species recovery score) and application of that method to estimate past and potential future impacts of conservation based on 4 metrics (conservation legacy, conservation dependence, conservation gain, and recovery potential). We tested the framework with 181 species representing diverse taxa, life histories, biomes, and IUCN Red List categories (extinction risk). Based on the observed distribution of species' recovery scores, we propose the following species recovery categories: fully recovered, slightly depleted, moderately depleted, largely depleted, critically depleted, extinct in the wild, and indeterminate. Fifty-nine percent of tested species were considered largely or critically depleted. Although there was a negative relationship between extinction risk and species recovery score, variation was considerable. Some species in lower risk categories were assessed as farther from recovery than those at higher risk. This emphasizes that species recovery is conceptually different from extinction risk and reinforces the utility of the IUCN Green Status of Species to more fully understand species conservation status. Although extinction risk did not predict conservation legacy, conservation dependence, or conservation gain, it was positively correlated with recovery potential. Only 1.7% of tested species were categorized as zero across all 4 of these conservation impact metrics, indicating that conservation has, or will, play a role in improving or maintaining species status for the vast majority of these species. Based on our results, we devised an updated assessment framework that introduces the option of using a dynamic baseline to assess future impacts of conservation over the short term to avoid misleading results which were generated in a small number of cases, and redefines short term as 10 years to better align with conservation planning. These changes are reflected in the IUCN Green Status of Species Standard.

RESUMEN: Reconociendo que era imperativo evaluar la recuperación de especies y el impacto de la conservación, la Unión Internacional para la Conservación de la Naturaleza (UICN) convocó en 2012 al desarrollo de una "Lista Verde de Especies" (ahora el Estatus Verde de las Especies de la UICN). Un marco de referencia preliminar de una Lista Verde de Especies para evaluar el progreso de las especies hacia la recuperación, publicado en 2018, proponía 2 componentes separados pero interconectados: un método estandarizado (i.e., medición en relación con puntos de referencia de la viabilidad de especies, funcionalidad y distribución antes del impacto) para determinar el estatus de recuperación actual (puntuación de recuperación de la especie) y la aplicación de ese método para estimar impactos en el pasado y potenciales de conservación basados en 4 medidas (legado de conservación, dependencia de conservación, ganancia de conservación y potencial de recuperación). Probamos el marco de referencia con 181 especies representantes de diversos taxa, historias de vida, biomas, y categorías (riesgo de extinción) en la Lista Roja de la IUCN. Con base en la distribución observada de la puntuación de recuperación de las especies, proponemos las siguientes categorías de recuperación de la especie: totalmente recuperada, ligeramente mermada, moderadamente mermada, mayormente mermada, gravemente mermada, extinta en estado silvestre, e inderterminada. Cincuenta y nueve por ciento de las especies se consideraron mayormente o gravemente mermada. Aunque hubo una relación negativa entre el riesgo de extinción y la puntuación de recuperación de la especie, la variación fue considerable. Algunas especies en las categorías de riesgo bajas fueron evaluadas como más lejos de recuperarse que aquellas con alto riesgo. Esto enfatiza que la recuperación de especies es diferente conceptualmente al riesgo de extinción y refuerza la utilidad del Estado Verde de las Especies de la UICN para comprender integralmente el estatus de conservación de especies. Aunque el riesgo de extinción no predijo el legado de conservación, la dependencia de conservación o la ganancia de conservación, se correlacionó positivamente con la potencial de recuperación. Solo 1.7% de las especies probadas fue categorizado como cero en los 4 indicadores de impacto de la conservación, lo que indica que la conservación ha jugado, o jugará, un papel en la mejoría o mantenimiento del estatus de la especie la gran mayoría de ellas. Con base en nuestros resultados, diseñamos una versión actualizada del marco de referencia para la evaluación que introduce la opción de utilizar una línea de base dinámica para evaluar los impactos futuros de la conservación en el corto plazo y redefine corto plazo como 10 años.

Nephrotoxic Effects of Paraoxon in Three Rat Models of Acute Intoxication.

The delayed effects of acute intoxication by organophosphates (OPs) are poorly understood, and the various experimental animal models often do not take into account species characteristics. The principal biochemical feature of rodents is the presence of carboxylesterase in blood plasma, which is a target for OPs and can greatly distort their specific effects. The present study was designed to investigate the nephrotoxic effects of paraoxon (O,O-diethyl O-(4-nitrophenyl) phosphate, POX) using three models of acute poisoning in outbred Wistar rats. In the first model (M1, POX2x group), POX was administered twice at doses 110 µg/kg and 130 µg/kg subcutaneously, with an interval of 1 h. In the second model (M2, CBPOX group), 1 h prior to POX poisoning at a dose of 130 µg/kg subcutaneously, carboxylesterase activity was pre-inhibited by administration of specific inhibitor cresylbenzodioxaphosphorin oxide (CBDP, 3.3 mg/kg intraperitoneally). In the third model (M3), POX was administered subcutaneously just once at doses of LD16 (241 µg/kg), LD50 (250 µg/kg), and LD84 (259 µg/kg). Animal observation and sampling were performed 1, 3, and 7 days after the exposure. Endogenous creatinine clearance (ECC) decreased in 24 h in the POX2x group (p = 0.011). Glucosuria was observed in rats 24 h after exposure to POX in both M1 and M2 models. After 3 days, an increase in urinary excretion of chondroitin sulfate (CS, p = 0.024) and calbindin (p = 0.006) was observed in rats of the CBPOX group. Morphometric analysis revealed a number of differences most significant for rats in the CBPOX group. Furthermore, there was an increase in the area of the renal corpuscles (p = 0.0006), an increase in the diameter of the lumen of the proximal convoluted tubules (PCT, p = 0.0006), and narrowing of the diameter of the distal tubules (p = 0.001). After 7 days, the diameter of the PCT lumen was still increased in the nephrons of the CBPOX group (p = 0.0009). In the M3 model, histopathological and ultrastructural changes in the kidneys were revealed after the exposure to POX at doses of LD50 and LD84. Over a period from 24 h to 3 days, a significant (p = 0.018) expansion of Bowman's capsule was observed in the kidneys of rats of both the LD50 and LD84 groups. In the epithelium of the proximal tubules, stretching of the basal labyrinth, pycnotic nuclei, and desquamation of microvilli on the apical surface were revealed. In the epithelium of the distal tubules, partial swelling and destruction of mitochondria and pycnotic nuclei was observed, and nuclei were displaced towards the apical surface of cells. After 7 days of the exposure to POX, an increase in the thickness of the glomerular basement membrane (GBM) was observed in the LD50 and LD84 groups (p = 0.019 and 0.026, respectively). Moreover, signs of damage to tubular epithelial cells persisted with blockage of the tubule lumen by cellular detritus and local destruction of the surface of apical cells. Comparison of results from the three models demonstrates that the nephrotoxic effects of POX, evaluated at 1 and 3 days, appear regardless of prior inhibition of carboxylesterase activity.

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties.

Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions-electrically neutral and charged molecules-and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind to almost all known drugs, as well as many nutraceuticals and toxic substances, largely determining their pharmaco- and toxicokinetics. Albumin of humans and respective representatives in cattle and rodents have their own structural features that determine species differences in functional properties. However, albumin is not only passive, but also an active participant of pharmacokinetic and toxicokinetic processes, possessing a number of enzymatic activities. Numerous experiments have shown esterase or pseudoesterase activity of albumin towards a number of endogeneous and exogeneous esters. Due to the free thiol group of Cys34, albumin can serve as a trap for reactive oxygen and nitrogen species, thus participating in redox processes. Glycated albumin makes a significant contribution to the pathogenesis of diabetes and other diseases. The interaction of albumin with blood cells, blood vessels and tissue cells outside the vascular bed is of great importance. Interactions with endothelial glycocalyx and vascular endothelial cells largely determine the integrative role of albumin. This review considers the esterase, antioxidant, transporting and signaling properties of albumin, as well as its structural and functional modifications and their significance in the pathogenesis of certain diseases.

Esterase Activity of Serum Albumin Studied by 1H NMR Spectroscopy and Molecular Modelling.

Serum albumin possesses esterase and pseudo-esterase activities towards a number of endogenous and exogenous substrates, but the mechanism of interaction of various esters and other compounds with albumin is still unclear. In the present study, proton nuclear magnetic resonance (1H NMR) has been applied to the study of true esterase activity of albumin, using the example of bovine serum albumin (BSA) and p-nitrophenyl acetate (NPA). The site of BSA esterase activity was then determined using molecular modelling methods. According to the data obtained, the accumulation of acetate in the presence of BSA in the reaction mixture is much more intense as compared with the spontaneous hydrolysis of NPA, which indicates true esterase activity of albumin towards NPA. Similar results were obtained for p-nitophenyl propionate (NPP) as substrate. The rate of acetate and propionate release confirms the assumption that there is a site of true esterase activity in the albumin molecule, which is different from the site of the pseudo-esterase activity Sudlow II. The results of molecular modelling of BSA and NPA interaction make it possible to postulate that Sudlow site I is the site of true esterase activity of albumin.

Inhibition of protein tyrosine phosphatases unmasks vasoconstriction and potentiates calcium signaling in rat aorta smooth muscle cells in response to an agonist of 5-HT2B receptors BW723C86.

In blood vessels, serotonin 5-HT2B receptors mainly mediate relaxation, although their activation by the selective agonist BW723C86 is known to exert contraction of aorta in deoxycorticosterone acetate (DOCA)-salt and N(omega)-nitro-l-arginine (l-NAME) hypertensive rats [Russel et al., 2002; Banes et al., 2003] and in mice with type 2 diabetes [Nelson et al., 2012]. The unmasking effect on vasoconstriction can be caused by a shift in the balance of tyrosine phosphorylation in smooth muscle cells (SMC) due to oxidative stress induced inhibition of protein tyrosine phosphatases (PTP). We have demonstrated that BW723C86 which does not cause contraction of rat aorta and mesenteric artery rings, evoked a vasoconstrictor effect in the presence of PTP inhibitors sodium orthovanadate (Na3VO4) or BVT948. BW723C86 induced a weak rise of [Ca2+]i in the SMC isolated from rat aorta; however, after pre-incubation with Na3VO4 the response to BW723C86 increased more than 5-fold. This effect was diminished by protein tyrosine kinase (PTK) inhibitor genistein, inhibitor of Src-family kinases PP2, inhibitor of NADPH-oxidase VAS2870 and completely suppressed by N-acetylcysteine and 5-HT2B receptor antagonist RS127445. Using fluorescent probe DCFH-DA we have shown that Na3VO4 induces oxidative stress in SMC. In the presence of Na3VO4 BW723C86 considerably increased formation of reactive oxygen species while alone had no appreciable effect on DCFH oxidation. We suggest that oxidative stress causes inhibition of PTP and unmasking of 5-HT2B receptors functional activity.

Serum Albumin Binding and Esterase Activity: Mechanistic Interactions with Organophosphates.

The albumin molecule, in contrast to many other plasma proteins, is not covered with a carbohydrate moiety and can bind and transport various molecules of endogenous and exogenous origin. The enzymatic activity of albumin, the existence of which many scientists perceive skeptically, is much less studied. In toxicology, understanding the mechanistic interactions of organophosphates with albumin is a special problem, and its solution could help in the development of new types of antidotes. In the present work, the history of the issue is briefly examined, then our in silico data on the interaction of human serum albumin with soman, as well as comparative in silico data of human and bovine serum albumin activities in relation to paraoxon, are presented. Information is given on the substrate specificity of albumin and we consider the possibility of its affiliation to certain classes in the nomenclature of enzymes.

Clinical Community Psychology: Reflections on the Decades Following Swampscott.

The Swampscott report was foundational, but in some ways reflected divisions within community psychology that have continued into the present. Community psychologists trained in the 1970s and, especially, the 1980s confronted a period where the original focus of community mental health began to have less influence in the mental health field due to a variety of public policies, and the growth of third party payments as a significant source of health care funding. Programs that engaged communities and provided a base for prevention interventions were greatly curtailed because of changes in federal legislation and limited opportunities for state and local funding, although prevention interventions found growing interest from research funders. Clinical and community psychologists who trained in this period increasingly looked to a variety of areas outside of mental health. Consequently, the field of community psychology has become more applied and less academic, with increased attention to advocacy, theory, and global perspectives. The sweep of these changes and their implications for the future of the field are discussed here.

Detection of new genetic variants of Betacoronaviruses in Endemic Frugivorous Bats of Madagascar.

BACKGROUND: Bats are amongst the natural reservoirs of many coronaviruses (CoVs) of which some can lead to severe infection in human. African bats are known to harbor a range of pathogens (e.g., Ebola and Marburg viruses) that can infect humans and cause disease outbreaks. A recent study in South Africa isolated a genetic variant closely related to MERS-CoV from an insectivorous bat. Though Madagascar is home to 44 bat species (41 insectivorous and 3 frugivorous) of which 34 are endemic, no data exists concerning the circulation of CoVs in the island's chiropteran fauna. Certain Malagasy bats can be frequently found in close contact with humans and frugivorous bats feed in the same trees where people collect and consume fruits and are hunted and consumed as bush meat. The purpose of our study is to detect and identify CoVs from frugivorous bats in Madagascar to evaluate the risk of human infection from infected bats. METHODS: Frugivorous bats belonging to three species were captured in four different regions of Madagascar. We analyzed fecal and throat swabs to detect the presence of virus through amplification of the RNA-dependent RNA polymerase (RdRp) gene, which is highly conserved in all known coronaviruses. Phylogenetic analyses were performed from positive specimens. RESULTS: From 351 frugivorous bats, we detected 14 coronaviruses from two endemic bats species, of which 13 viruses were identified from Pteropus rufus and one from Eidolon dupreanum, giving an overall prevalence of 4.5%. Phylogenetic analysis revealed that the Malagasy strains belong to the genus Betacoronavirus but form three distinct clusters, which seem to represent previously undescribed genetic lineages. CONCLUSIONS: Our findings suggest that CoVs circulate in frugivorous bats of Madagascar, demonstrating the needs to evaluate spillover risk to human populations especially for individuals that hunt and consume infected bats. Possible dispersal mechanisms as to how coronaviruses arrived on Madagascar are discussed.

Species undersampling in tropical bat surveys: effects on emerging biodiversity patterns.

Undersampling is commonplace in biodiversity surveys of species-rich tropical assemblages in which rare taxa abound, with possible repercussions for our ability to implement surveys and monitoring programmes in a cost-effective way. We investigated the consequences of information loss due to species undersampling (missing subsets of species from the full species pool) in tropical bat surveys for the emerging patterns of species richness (SR) and compositional variation across sites. For 27 bat assemblage data sets from across the tropics, we used correlations between original data sets and subsets with different numbers of species deleted either at random, or according to their rarity in the assemblage, to assess to what extent patterns in SR and composition in data subsets are congruent with those in the initial data set. We then examined to what degree high sample representativeness (r ≥ 0·8) was influenced by biogeographic region, sampling method, sampling effort or structural assemblage characteristics. For SR, correlations between random subsets and original data sets were strong (r ≥ 0·8) with moderate (ca. 20%) species loss. Bias associated with information loss was greater for species composition; on average ca. 90% of species in random subsets had to be retained to adequately capture among-site variation. For nonrandom subsets, removing only the rarest species (on average c. 10% of the full data set) yielded strong correlations (r > 0·95) for both SR and composition. Eliminating greater proportions of rare species resulted in weaker correlations and large variation in the magnitude of observed correlations among data sets. Species subsets that comprised ca. 85% of the original set can be considered reliable surrogates, capable of adequately revealing patterns of SR and temporal or spatial turnover in many tropical bat assemblages. Our analyses thus demonstrate the potential as well as limitations for reducing survey effort and streamlining sampling protocols, and consequently for increasing the cost-effectiveness in tropical bat surveys or monitoring programmes. The dependence of the performance of species subsets on structural assemblage characteristics (total assemblage abundance, proportion of rare species), however, underscores the importance of adaptive monitoring schemes and of establishing surrogate performance on a site by site basis based on pilot surveys.

Special section on LGBT resilience across cultures: introduction.

This special section addresses a gap area of resilience and LGBT well-being. Although comprehensive global diversity regarding LGBT resilience was challenging to find, the special section includes representation from outside the US (Israel and Hong Kong), ethnic/racially diverse domestic populations, immigration, and one population for which LGBT identities might be considered marginalized-Christians in the US. The full range of LGBT identities are represented in the issue along with persons identifying as queer or questioning, although transgendered people were less well represented than lesbian, gay or bisexual identities.

Islets of Langerhans from prohormone convertase-2 knockout mice show α-cell hyperplasia and tumorigenesis with elevated α-cell neogenesis.

Antagonism of the effects of glucagon as an adjunct therapy with other glucose-lowering drugs in the chronic treatment of diabetes has been suggested to aggressively control blood glucose levels. Antagonism of glucagon effects, by targeting glucagon secretion or disabling the glucagon receptor, is associated with α-cell hyperplasia. We evaluated the influence of total glucagon withdrawal on islets of Langerhans using prohormone convertase-2 knockout mice (PC2-ko), in which α-cell hyperplasia is present from a young age and persists throughout life, in order to understand whether or not sustained glucagon deficit would lead to islet tumorigenesis. PC2-ko and wild-type (WT) mice were maintained drug-free, and cohorts of these groups sampled at 3, 12 and 18 months for plasma biochemical and morphological (histological, immunohistochemical, electron microscopical and image analytical) assessments. WT mice showed no islet tumours up to termination of the study, but PC2-ko animals displayed marked changes in islet morphology from α-cell hypertrophy/hyperplasia/atypical hyperplasia, to adenomas and carcinomas, these latter being first encountered at 6-8 months. Islet hyperplasias and tumours primarily consisted of α-cells associated to varying degrees with other islet endocrine cell types. In addition to substantial increases in islet neoplasia, increased α-cell neogenesis associated primarily with pancreatic duct(ule)s was present. We conclude that absolute blockade of the glucagon signal results in tumorigenesis and that the PC2-ko mouse represents a valuable model for investigation of islet tumours and pancreatic ductal neogenesis.