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1.
J Affect Disord ; 294: 543-557, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34330051

RESUMO

BACKGROUND: Risk factors exploring the link between trauma and Post-traumatic stress disorder (PTSD) have been extensively explored in adults, however, less is known about child and adolescent populations. METHODS: The current meta-analysis aimed to systematically evaluate and summarise the child focused literature to estimate the strength of the relationship between social support and PTSD symptoms following traumatic events. RESULTS: Fifty primary studies reporting an effect size for the relationship between total social support scale or a source of social support with PTSD were included. A small effect size was found for the relationship between social support and PTSD (r = -0.12, 95% CI -0.16 to -0.07, k = 41), with large heterogeneity (I2 = 90.3%). The effect sizes between peer support (r = -0.18, 95% CI -0.10 to -0.25, k = 12), family support (r = -0.16, 95% CI -0.09 to -0.24, k = 13) and teacher support (r = -0.20, 95% CI -0.15 to -0.24, k = 5) and PTSD were also small. Moderator analyses indicated that studies reporting on participants exposed to abuse (r = -0.25) and correlations based on univariate data (r = -0.14) had higher correlations and medium heterogeneity. The main effect size was robust to publication bias and study quality. LIMITATIONS: The cross-sectional design of the studies limits the findings and future research using prospective and longitudinal design would help to explain the relationship between social support and PTSD further. CONCLUSIONS: The current review suggests that social support may only play a small role in protecting against PTSD and future research may benefit from exploring the link between post-trauma cognitions and social support.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Adolescente , Adulto , Criança , Estudos Transversais , Humanos , Estudos Prospectivos , Psicoterapia , Apoio Social , Transtornos de Estresse Pós-Traumáticos/epidemiologia
2.
Artigo em Inglês | MEDLINE | ID: mdl-34300097

RESUMO

Obesity is an increasing public health concern in the U.S. and a contributor to chronic illness, with trends revealing a rise in adult obesity and chronic disease rates among the most vulnerable and disadvantaged populations, including those in rural communities. A mixed-methods approach was used to examine perspectives on perceived physical activity barriers, resources, and level of community support. Researchers utilized the socioecological model to examine the multiple domains that support physical activity in rural Appalachia. The present study focuses on baseline data, including a cohort survey to assess physical activity, health status, and barriers to physical activity, and five focus groups with elected community leaders, community residents, members, and key stakeholders to assess perspectives on physical activity barriers and resources within the county. The cohort survey sample (N = 152) reported a median of 6 barriers (range 0-13) to participating in at least 30 min of physical activity daily. The qualitative analysis yielded three overarching themes related to physical activity participation: lack of motivation, physical environment, and cultural barriers. This mixed-methods study revealed the challenges and perceptions among rural residents across the socioecological model when assessing physical inactivity. Findings can be used to tailor future interventions focused on expanding social support, designing infrastructure, and creating policies that promote physical activity.


Assuntos
Exercício Físico , População Rural , Adulto , Região dos Apalaches , Grupos Focais , Humanos , Kentucky
3.
Ecol Evol ; 11(12): 7544-7556, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34188833

RESUMO

Maternal environmental effects create lagged population responses to past environments. Although they are ubiquitous and vary in expression across taxa, it remains unclear if and how their presence alters competitive interactions in ecological communities.Here, we use a discrete-time competition model to simulate how maternal effects alter competitive dynamics in fluctuating and constant environments. Further, we explore how omitting maternal effects alter estimates of known model parameters from observational time series data.Our simulations demonstrate that (i) maternal effects change competitive outcomes, regardless of whether competitors otherwise interact neutrally or exhibit non-neutral competitive differences, (ii) the consequences of maternal effects for competitive outcomes are mediated by the temporal structure of environmental variation, (iii) even in constant conditions, competitive outcomes are influenced by species' maternal effects strategies, and (iv) in observational time series data, omitting maternal effects reduces variation explained by models and biases parameter estimates, including competition coefficients.Our findings demonstrate that the ecological consequences of maternal effects hinge on the competitive environment. Evolutionary biologists have long recognized that maternal effects can be an important but often overlooked strategy buffering populations from environmental change. We suggest that maternal effects are similarly critical to ecology and call for research into maternal effects as drivers of dynamics in populations and communities.

4.
Nat Struct Mol Biol ; 28(4): 388-397, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33782614

RESUMO

The structural conservation across the AAA (ATPases associated with diverse cellular activities) protein family makes designing selective chemical inhibitors challenging. Here, we identify a triazolopyridine-based fragment that binds the AAA domain of human katanin, a microtubule-severing protein. We have developed a model for compound binding and designed ASPIR-1 (allele-specific, proximity-induced reactivity-based inhibitor-1), a cell-permeable compound that selectively inhibits katanin with an engineered cysteine mutation. Only in cells expressing mutant katanin does ASPIR-1 treatment increase the accumulation of CAMSAP2 at microtubule minus ends, confirming specific on-target cellular activity. Importantly, ASPIR-1 also selectively inhibits engineered cysteine mutants of human VPS4B and FIGL1-AAA proteins, involved in organelle dynamics and genome stability, respectively. Structural studies confirm our model for compound binding at the AAA ATPase site and the proximity-induced reactivity-based inhibition. Together, our findings suggest a chemical genetics approach to decipher AAA protein functions across essential cellular processes and to test hypotheses for developing therapeutics.


Assuntos
Proteínas AAA/genética , Katanina/genética , Proteínas Associadas aos Microtúbulos/genética , Piridinas/química , Proteínas AAA/antagonistas & inibidores , Proteínas AAA/ultraestrutura , ATPases Associadas a Diversas Atividades Celulares/genética , ATPases Associadas a Diversas Atividades Celulares/ultraestrutura , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/ultraestrutura , Humanos , Katanina/ultraestrutura , Proteínas Associadas aos Microtúbulos/ultraestrutura , Microtúbulos/genética , Microtúbulos/ultraestrutura , Conformação Proteica/efeitos dos fármacos , Domínios Proteicos/genética , Piridinas/farmacologia , Triazóis/química
5.
Neurobiol Learn Mem ; 180: 107404, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33609735

RESUMO

Over the last decade, strong evidence has emerged that protein degradation mediated by the ubiquitin-proteasome system is critical for fear memory formation in the amygdala. However, this work has been done primarily in males, leaving unanswered questions about whether females also require protein degradation during fear memory formation. Here, we found that male and female rats differed in their engagement and regulation of, but not need for, protein degradation in the amygdala during fear memory formation. Male, but not female, rats had increased protein degradation in the nuclei of amygdala cells after fear conditioning. Conversely, females had elevated baseline levels of overall ubiquitin-proteasome activity in amygdala nuclei. Gene expression and DNA methylation analyses identified that females had increased baseline expression of the ubiquitin coding gene Uba52, which had increased DNA 5-hydroxymethylation (5hmc) in its promoter region, indicating a euchromatin state necessary for increased levels of ubiquitin in females. Consistent with this, persistent CRISPR-dCas9 mediated silencing of Uba52 and proteasome subunit Psmd14 in the amygdala reduced baseline protein degradation levels and impaired fear memory in male and female rats, while enhancing baseline protein degradation in the amygdala of both sexes promoted fear memory formation. These results suggest that while both males and females require protein degradation in the amygdala for fear memory formation, they differ in their baseline regulation and engagement of this process following learning. These results have important implications for understanding the etiology of sex-related differences in fear memory formation.

6.
Soc Psychiatry Psychiatr Epidemiol ; 56(9): 1679-1686, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32926182

RESUMO

PURPOSE: Millions of people are evicted from rental properties in the U.S. annually, but little is known about them and their mental health. This study followed a cohort of eviction court participants over time and assessed their housing and mental health outcomes. METHODS: One hundred and twenty-one tenants were recruited from an eviction court in New Haven, Connecticut, and their housing, mental health, and psychosocial status were assessed at baseline, 1, 3, 6, and 9 months following their encounter with the court. Inverse probability weighting was used for missing data. RESULTS: At baseline, 42% of participants had appeared in eviction court before, 28% had experienced eviction, and 44% had been previously homeless. In addition, 39% screened positive for generalized anxiety disorder, 37% for posttraumatic stress disorder, 33% for major depressive disorder, and 17% reported suicidal ideation. At follow-up, participants experienced increased days of housing instability and homelessness over time with some persistent mental health symptoms. Less than one-quarter of participants received any mental health treatment during the 9-month follow-up period. About 54% of participants followed reported that they had to change their residence after their court appearance consistent with court records. Participants who had an eviction-related move experienced greater housing instability over time than participants who did not. CONCLUSION: Together, these findings suggest that there is a sizable subgroup of adults who present to eviction court with persistent housing and mental health issues who do not receive adequate assistance in addressing these issues.


Assuntos
Transtorno Depressivo Maior , Pessoas em Situação de Rua , Adulto , Habitação , Humanos , Estudos Longitudinais , Avaliação de Resultados em Cuidados de Saúde
7.
Eval Program Plann ; 84: 101896, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33285397

RESUMO

Many in the data visualization and evaluation communities recommend conveying the message or takeaway of the visualization in the visualization's title. This study tested that recommendation by examining how informative or generic titles impact a visualization's visual efficiency, aesthetics, credibility, and the perceived effectiveness of the hypothetical program examined. Furthermore, this study tested how simple or complex graphs, and positive, negative, or mixed results (i.e., valence of the results) affected outcomes. Participants were randomly assigned to one of 12 conditions, representing a 2 (graph: simple or complex) x 2 (title: generic or informative) x 3 (valence: positive, negative, mixed) between-subjects study. The results indicated that informative titles required less mental effort and were viewed as more aesthetically pleasing, but otherwise did not lead to greater accuracy, credibility, or perceived effectiveness. Furthermore, titles did not interact with graph type or the valence of the findings. While the results suggest it is worthwhile to consider adding an informative title to data visualizations as they can reduce mental effort for the viewer, the intended goal of the visualization should be taken into consideration. Considering the goal of the visualization can be a deciding factor of the type of graph and title that will best serve its intended purposes. Overall, this suggests that data visualization recommendations that impact evaluation reporting practices should be scrutinized more closely through research.

8.
Prev Chronic Dis ; 17: E165, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33357305

RESUMO

INTRODUCTION: Obesity disproportionately affects rural communities, and Appalachia has some of the highest obesity rates in the nation. Successful policy, systems, and environmental (PSE) interventions to reduce obesity must reflect the circumstances of the population. We used a health equity lens to identify barriers and facilitators for healthy food access in Martin County, Kentucky, to design interventions responsive to social, cultural, and historical contexts. METHODS: We conducted 5 focus groups in Martin County, Kentucky, in fall 2019 to obtain perspectives on the local food system and gauge acceptability of PSE interventions. We used grounded theory to identify perceived barriers and facilitators for healthy eating. RESULTS: Thirty-four adults (27 women; median age, 46 years) participated in 5 groups. One prominent theme was declining interest in farming; many participants believed this decline was generational. One participant noted, "Most of my adult male relatives worked in the coal mines, and they worked 6 days a week. . . . My grandpa had the garden, but then my dad's generation is the one quit gardening." Another shared, "You would probably have to have someone to teach [gardening]." Instead of enhancing farmers markets, participants suggested building community capacity for home gardens to increase vegetable consumption. CONCLUSION: Our findings demonstrate the importance of obtaining community input on the development of PSE interventions to mitigate inequities in obesity. Although farmers market interventions were deemed not feasible, other solutions to enhance access to produce were identified. Developers of community-responsive PSE interventions to improve healthy eating in rural, food-insecure locations should consider using an equity-oriented prevention framework to ensure acceptable interventions.


Assuntos
Dieta Saudável , População Rural , Região dos Apalaches , Feminino , Abastecimento de Alimentos , Jardinagem , Humanos , Masculino , Pessoa de Meia-Idade , Verduras
9.
Proc Biol Sci ; 287(1936): 20201526, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33049167

RESUMO

Predicting the effects of seasonality and climate change on the emergence and spread of infectious disease remains difficult, in part because of poorly understood connections between warming and the mechanisms driving disease. Trait-based mechanistic models combined with thermal performance curves arising from the metabolic theory of ecology (MTE) have been highlighted as a promising approach going forward; however, this framework has not been tested under controlled experimental conditions that isolate the role of gradual temporal warming on disease dynamics and emergence. Here, we provide experimental evidence that a slowly warming host-parasite system can be pushed through a critical transition into an epidemic state. We then show that a trait-based mechanistic model with MTE functional forms can predict the critical temperature for disease emergence, subsequent disease dynamics through time and final infection prevalence in an experimentally warmed system of Daphnia and a microsporidian parasite. Our results serve as a proof of principle that trait-based mechanistic models using MTE subfunctions can predict warming-induced disease emergence in data-rich systems-a critical step towards generalizing the approach to other systems.


Assuntos
Mudança Climática , Interações Hospedeiro-Parasita , Parasitos , Animais , Daphnia , Ecologia , Epidemias , Microsporídios , Temperatura
10.
Case Rep Dent ; 2020: 8826945, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33005459

RESUMO

Background: Megalencephaly-capillary malformation (MCAP) is a rare overgrowth syndrome caused by postzygotic activating mutations in the PIK3CA gene. Aim: To illustrate the benefits of gingival biopsy in the genetic diagnosis of overgrowth syndromes. Design: Gingival biopsy was performed on a 13-year-old patient and a 16-year-old patient with MCAP and who suffered from periodontal disease. PIK3CA sequencing was performed on DNA extracted from gingival biopsies, blood, and saliva. Results: Pathogenic p.Glu365Lys and p.Glu545Asp PIK3CA mutations were found in the gingival biopsies with an allelic frequency of 22% and 35%, respectively, while they were undetectable in blood or saliva. The genetic diagnosis of MCAP through detection of PIK3CA somatic mosaicism in a periodontal biopsy is unprecedented. Conclusions: Considering the tissue distribution and level of somatic mosaicism for PIK3CA mutation, the composite embryologic origin of periodontium and its high fibroblast cell content make it an ideal target for molecular analysis in overgrowth syndromes, and multidisciplinary approach including paediatric dentists should be encouraged. In addition, our clinical findings suggest that periodontal disease is part of the MCAP phenotypic spectrum and should be systematically investigated.

11.
Behav Brain Res ; 393: 112787, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603798

RESUMO

Studies have shown that long-term exposure to high fat and other obesogenic diets results in insulin resistance and altered blood brain barrier permeability, dysregulation of intracellular signaling mechanisms, changes in DNA methylation levels and gene expression, and increased oxidative stress and neuroinflammation in the hippocampus, all of which are associated with impaired spatial memory. The ubiquitin-proteasome system controls the majority of protein degradation in cells and is a critical regulator of synaptic plasticity and memory formation. Yet, whether protein degradation in the hippocampus becomes dysregulated following weight gain and is associated with obesity-induced memory impairments is unknown. Here, we used a high fat diet procedure in combination with behavioral and subcellular fractionation protocols and a variety of biochemical assays to determine if ubiquitin-proteasome activity becomes altered in the hippocampus during obesity development and whether this is associated with impaired spatial memory. We found that only 6 weeks of exposure to a high fat diet was sufficient to impair performance on an object location task in rats and resulted in dynamic dysregulation of ubiquitin-proteasome activity in the nucleus and cytoplasm of cells in the hippocampus. Furthermore, these changes in the protein degradation process extended into cortical regions also involved in spatial memory formation. Collectively, these results indicate that weight gain-induced memory impairments may be due to altered ubiquitin-proteasome signaling that occurs during the early stages of obesity development.

12.
Bioorg Med Chem Lett ; 30(19): 127433, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32717371

RESUMO

Spleen tyrosine kinase (SYK) is a non-receptor cytosolic kinase. Due to its pivotal role in B cell receptor and Fc-receptor signaling, inhibition of SYK has been targeted in a variety of disease areas. Herein, we report the optimization of a series of potent and selective SYK inhibitors, focusing on improving metabolic stability, pharmacokinetics and hERG inhibition. As a result, we identified 30, which exhibited no hERG activity but unfortunately was poorly absorbed in rats and mice. We also identified a SYK chemical probe, 17, which exhibits excellent potency at SYK, and an adequate rodent PK profile to support in vivo efficacy/PD studies.


Assuntos
Indazóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinase Syk/antagonistas & inibidores , Animais , Sítios de Ligação , Células CACO-2 , Cristalografia por Raios X , Canal de Potássio ERG1/antagonistas & inibidores , Humanos , Indazóis/síntese química , Indazóis/metabolismo , Indazóis/farmacocinética , Camundongos , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacocinética , Ratos Wistar , Relação Estrutura-Atividade , Quinase Syk/química , Quinase Syk/metabolismo
13.
Mol Ecol ; 29(11): 2080-2093, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32578266

RESUMO

Warming, eutrophication (nutrient fertilization) and brownification (increased loading of allochthonous organic matter) are three global trends impacting lake ecosystems. However, the independent and synergistic effects of resource addition and warming on autotrophic and heterotrophic microorganisms are largely unknown. In this study, we investigate the independent and interactive effects of temperature, dissolved organic carbon (DOC, both allochthonous and autochthonous) and nitrogen (N) supply, in addition to the effect of spatial variables, on the composition, richness, and evenness of prokaryotic and eukaryotic microbial communities in lakes across elevation and N deposition gradients in the Sierra Nevada mountains of California, USA. We found that both prokaryotic and eukaryotic communities are structured by temperature, terrestrial (allochthonous) DOC and latitude. Prokaryotic communities are also influenced by total and aquatic (autochthonous) DOC, while eukaryotic communities are also structured by nitrate. Additionally, increasing N availability was associated with reduced richness of prokaryotic communities, and both lower richness and evenness of eukaryotes. We did not detect any synergistic or antagonistic effects as there were no interactions among temperature and resource variables. Together, our results suggest that (a) organic and inorganic resources, temperature, and geographic location (based on latitude and longitude) independently influence lake microbial communities; and (b) increasing N supply due to atmospheric N deposition may reduce richness of both prokaryotic and eukaryotic microbes, probably by reducing niche dimensionality. Our study provides insight into abiotic processes structuring microbial communities across environmental gradients and their potential roles in material and energy fluxes within and between ecosystems.


Assuntos
Lagos/microbiologia , Microbiota , Temperatura , California , Carbono , Ecossistema , Eutrofização , Nitrogênio
14.
J Anim Ecol ; 89(10): 2378-2388, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32592594

RESUMO

Increased global temperatures caused by climate change are causing species to shift their ranges and colonize new sites, creating novel assemblages that have historically not interacted. Species interactions play a central role in the response of ecosystems to climate change, but the role of trophic interactions in facilitating or preventing range expansions is largely unknown. The goal of our study was to understand how predators influence the ability of range-shifting prey to successfully establish in newly available habitat following climate warming. We hypothesized that fish predation facilitates the establishment of colonizing zooplankton populations, because fish preferentially consume larger species that would otherwise competitively exclude smaller-bodied colonists. We conducted a mesocosm experiment with zooplankton communities and their fish predators from lakes of the Sierra Nevada Mountains in California, USA. We tested the effect of fish predation on the establishment and persistence of a zooplankton community when introduced in the presence of higher- and lower-elevation communities at two experimental temperatures in field mesocosms. We found that predators reduce the abundance of larger-bodied residents from the alpine and facilitate the establishment of new lower-elevation species. In addition, fish predation and warming independently reduced the average body size of zooplankton by up to 30%. This reduction in body size offset the direct effect of warming-induced increases in population growth rates, leading to no net change in zooplankton biomass or trophic cascade strength. We found support for a shift to smaller species with climate change through two mechanisms: (a) the direct effects of warming on developmental rates and (b) size-selective predation that altered the identity of species' that could colonize new higher elevation habitat. Our results suggest that predators can amplify the rate of range shifts by consuming larger-bodied residents and facilitating the establishment of new species. However, the effects of climate warming were dampened by reducing the average body size of community members, leading to no net change in ecosystem function, despite higher growth rates. This work suggests that trophic interactions play a role in the reorganization of regional communities under climate warming.


Assuntos
Ecossistema , Zooplâncton , Animais , Biomassa , Cadeia Alimentar , Lagos , Comportamento Predatório
15.
Hypertension ; 75(5): 1213-1222, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32200679

RESUMO

GPR81 (G-protein-coupled receptor 81) is highly expressed in adipocytes, and activation by the endogenous ligand lactate inhibits lipolysis. GPR81 is also expressed in the heart, liver, and kidney, but roles in nonadipose tissues are poorly defined. GPR81 agonists, developed to improve blood lipid profile, might also provide insights into GPR81 physiology. Here, we assessed the blood pressure and renal hemodynamic responses to the GPR81 agonist, AZ'5538. In male wild-type mice, intravenous AZ'5538 infusion caused a rapid and sustained increase in systolic and diastolic blood pressure. Renal artery blood flow, intrarenal tissue perfusion, and glomerular filtration rate were all significantly reduced. AZ'5538 had no effect on blood pressure or renal hemodynamics in Gpr81-/- mice. Gpr81 mRNA was expressed in renal artery vascular smooth muscle, in the afferent arteriole, in glomerular and medullary perivascular cells, and in pericyte-like cells isolated from kidney. Intravenous AZ'5538 increased plasma ET-1 (endothelin 1), and pretreatment with BQ123 (endothelin-A receptor antagonist) prevented the pressor effects of GPR81 activation, whereas BQ788 (endothelin-B receptor antagonist) did not. Renal ischemia-reperfusion injury, which increases renal extracellular lactate, increased the renal expression of genes encoding ET-1, KIM-1 (Kidney Injury Molecule 1), collagen type 1-α1, TNF-α (tumor necrosis factor-α), and F4/80 in wild-type mice but not in Gpr81-/- mice. In summary, activation of GPR81 in vascular smooth muscle and perivascular cells regulates renal hemodynamics, mediated by release of the potent vasoconstrictor ET-1. This suggests that lactate may be a paracrine regulator of renal blood flow, particularly relevant when extracellular lactate is high as occurs during ischemic renal disease.


Assuntos
Endotelina-1/fisiologia , Hemodinâmica/efeitos dos fármacos , Receptores Acoplados a Proteínas G/agonistas , Animais , Artérias/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Bosentana/farmacologia , Endotelina-1/sangue , Taxa de Filtração Glomerular/efeitos dos fármacos , Coração/efeitos dos fármacos , Hemodinâmica/fisiologia , Infusões Intravenosas , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Lactatos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Oligopeptídeos/farmacologia , Comunicação Parácrina , Peptídeos Cíclicos/farmacologia , Pericitos/efeitos dos fármacos , Pericitos/metabolismo , Piperidinas/farmacologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores Acoplados a Proteínas G/deficiência , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/fisiologia , Circulação Renal/efeitos dos fármacos , Circulação Renal/fisiologia , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/fisiopatologia
16.
Dalton Trans ; 49(14): 4230-4243, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32104876

RESUMO

Novel molecular Re and Mn tricarbonyl complexes bearing a bipyridyl ligand functionalised with sterically hindering substituents in the 6,6'-position, [M(HPEAB)(CO)3(X)] (M/X = Re/Cl, Mn/Br; HPEAB = 6,6'-{N-(4-hexylphenyl)-N(ethyl)-amido}-2,2'-bipyridine) have been synthesised, fully characterised including by single crystal X-ray crystallography, and their propensity to act as catalysts for the electrochemical and photochemical reduction of CO2 has been established. Controlled potential electrolysis showed that the catalysts are effective for electrochemical CO2-reduction, yielding CO as the product (in MeCN for the Re-complex, in 95 : 5 (v/v) MeCN : H2O mixture for the Mn-complex). The recyclability of the catalysts was demonstrated through replenishment of CO2 within solution. The novel catalysts had similar reduction potentials to previously reported complexes of similar structure, and results of the foot-of-the-wave analysis showed comparable maximum turnover rates, too. The tentative mechanisms for activation of the pre-catalysts were proposed on the basis of IR-spectroelectrochemical data aided by DFT calculations. It is shown that the typical dimerisation of the Mn-catalyst was prevented by incorporation of sterically hindering groups, whilst the Re-catalyst undergoes the usual mechanism following chloride ion loss. No photochemical CO2 reduction was observed for the rhenium complex in the presence of a sacrificial donor (triethylamine), which was attributed to the short triplet excited state lifetime (3.6 ns), insufficient for diffusion-controlled electron transfer. Importantly, [Mn(HPEAB)(CO)3Br] can act as a CO2 reduction catalyst when photosensitised by a zinc porphyrin under red light irradiation (λ > 600 nm) in MeCN : H2O (95 : 5); there has been only one reported example of photoactivating Mn-catalysts with porphyrins in this manner. Thus, this work demonstrates the wide utility of sterically protected Re- and Mn-diimine carbonyl catalysts, where the rate and yield of CO-production can be adjusted based on the metal centre and catalytic conditions, with the advantage of suppressing unwanted side-reactions through steric protection of the vacant coordination site.

17.
Ecology ; 101(5): e02991, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31994172

RESUMO

The keystone roles of mega-fauna in many terrestrial ecosystems have been lost to defaunation. Large predators and herbivores often play keystone roles in their native ranges, and some have established invasive populations in new biogeographic regions. However, few empirical examples are available to guide expectations about how mega-fauna affect ecosystems in novel environmental and evolutionary contexts. We examined the impacts on aquatic ecosystems of an emerging population of hippopotamus (Hippopotamus amphibus) that has been growing in Colombia over the last 25 yr. Hippos in Africa fertilize lakes and rivers by grazing on land and excreting wastes in the water. Stable isotopes indicate that terrestrial sources contribute more carbon in Colombian lakes containing hippo populations, and daily dissolved oxygen cycles suggest that their presence stimulates ecosystem metabolism. Phytoplankton communities were more dominated by cyanobacteria in lakes with hippos, and bacteria, zooplankton, and benthic invertebrate communities were similar regardless of hippo presence. Our results suggest that hippos recapitulate their role as ecosystem engineers in Colombia, importing terrestrial organic matter and nutrients with detectable impacts on ecosystem metabolism and community structure in the early stages of invasion. Ongoing range expansion may pose a threat to water resources.


Assuntos
Ecossistema , Zooplâncton , África , Animais , Colômbia , Lagos , Fitoplâncton
18.
Community Ment Health J ; 56(2): 294-297, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31587114

RESUMO

Mental health providers who serve clients with severe mental illness may be particularly prone to job burnout given the nature of the work. This study examined levels of job burnout among mental health providers who serve clients with severe mental illness. Forty-two mental health staff at a Veterans Affairs psychosocial rehabilitation center completed an online survey that assessed burnout and work-life balance. Maslach Burnout Inventory (MBI) scores were compared to published scores of workers in other professions. Participants reported moderate MBI Emotional Exhaustion, Depersonalization, and Personal Accomplishment scores and overall had lower burnout scores than other healthcare providers and service workers. Being younger and white were associated with higher MBI Emotional Exhaustion scores. These findings suggest job burnout among mental health staff is a concern that should be closely monitored even among staff who express a sense of personal accomplishment from the work.


Assuntos
Esgotamento Profissional , Reabilitação Psiquiátrica , Veteranos , Esgotamento Profissional/epidemiologia , Esgotamento Psicológico , Humanos , Satisfação no Emprego , Saúde Mental , Inquéritos e Questionários
19.
Am J Physiol Renal Physiol ; 317(6): F1536-F1548, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31588796

RESUMO

The sodium-chloride cotransporter (NCC) in the distal convoluted tubule contributes importantly to sodium balance and blood pressure (BP) regulation. NCC phosphorylation determines transport activity and has a diurnal rhythm influenced by glucocorticoids. Disturbing this rhythm induces "nondipping" BP, an abnormality that increases cardiovascular risk. The receptor through which glucocorticoids regulate NCC is not known. In this study, we found that acute administration of corticosterone to male C57BL6 mice doubled NCC phosphorylation without affecting total NCC abundance in both adrenalectomized and adrenal-intact mice. Corticosterone also increased the whole kidney expression of canonical clock genes: period circadian protein homolog 1 (Per1), Per2, cryptochrome 1, and aryl hydrocarbon receptor nuclear translocator-like protein 1. In adrenal-intact mice, chronic blockade of glucocorticoid receptor (GR) with RU486 did not change total NCC but prevented corticosterone-induced NCC phosphorylation and activation of clock genes. Blockade of mineralocorticoid receptor (MR) with spironolactone reduced the total pool of NCC but did not affect stimulation by corticosterone. The diurnal rhythm of NCC phosphorylation, measured at 6-h intervals, was blunted by chronic GR blockade, and a similar dampening of diurnal variation was seen in GR heterozygous null mice. These effects on NCC phosphorylation did not reflect altered rhythmicity of plasma corticosterone or serum and glucocorticoid-induced kinase 1 activity. Both mineralocorticoids and glucocorticoids emerge as regulators of NCC, acting via distinct receptor pathways. MR activation provides maintenance of the NCC protein pool; GR activation dynamically regulates NCC phosphorylation and establishes the diurnal rhythm of NCC activity. This study has implications for circadian BP homeostasis, particularly in individuals with abnormal glucocorticoid signaling as is found in chronic stress and corticosteroid therapy.


Assuntos
Ritmo Circadiano/fisiologia , Rim/metabolismo , Receptores de Glucocorticoides/metabolismo , Simportadores de Cloreto de Sódio/metabolismo , Adrenalectomia , Animais , Proteínas CLOCK/biossíntese , Proteínas CLOCK/genética , Ritmo Circadiano/efeitos dos fármacos , Corticosterona/sangue , Corticosterona/farmacologia , Rim/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mifepristona/farmacologia , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Fosforilação/efeitos dos fármacos , Receptores de Glucocorticoides/antagonistas & inibidores , Receptores de Glucocorticoides/efeitos dos fármacos , Espironolactona/farmacologia
20.
Neuroscience ; 418: 1-14, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31449987

RESUMO

The ubiquitin-proteasome system (UPS) controls the degradation of ~90% of short-lived proteins in cells and is involved in activity- and learning-dependent synaptic plasticity in the brain. Calcium/calmodulin dependent protein kinase II (CaMKII) and Protein Kinase A (PKA) can regulate activity of the proteasome. However, there have been a number of conflicting reports regarding under what conditions CaMKII and PKA regulate proteasome activity in the brain. Furthermore, this work has been done exclusively in males, leaving questions about whether these kinases also regulate the proteasome in females. Here, using subcellular fractionation protocols in combination with in vitro pharmacology and proteasome activity assays, we investigated the conditions under which CaMKII and PKA regulate proteasome activity in the brains of male and female rats. In males, nuclear proteasome chymotrypsin activity was regulated by PKA in the amygdala but CaMKII in the hippocampus. Conversely, in females CaMKII regulated nuclear chymotrypsin activity in the amygdala, but not hippocampus. Additionally, in males CaMKII and PKA regulated proteasome trypsin activity in the cytoplasm of hippocampal, but not amygdala cells, while in females both CaMKII and PKA could regulate this activity in the nucleus of cells in both regions. Proteasome peptidylglutamyl activity was regulated by CaMKII and PKA activity in the nuclei of amygdala and hippocampus cells in males. However, in females PKA regulated nuclear peptidylglutamyl activity in the amygdala, but not hippocampus. Collectively, these results suggest that CaMKII- and PKA-dependent regulation of proteasome activity in the brain varies significantly across subcellular compartments and between males and females.


Assuntos
Encéfalo/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Animais , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Feminino , Masculino , Plasticidade Neuronal/fisiologia , Ratos Sprague-Dawley , Caracteres Sexuais
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