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1.
Sci Rep ; 12(1): 13807, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35970998

RESUMO

Stable or growing populations may go extinct when their sizes cannot withstand large swings in temporal variation and stochastic forces. Hence, the minimum abundance threshold defining when populations can persist without human intervention forms a key conservation parameter. We identify this threshold for many populations of Caprinae, typically threatened species lacking demographic data. Doing so helps triage conservation and management actions for threatened or harvested populations. Methodologically, we used population projection matrices and simulations, with starting abundance, recruitment, and adult female survival predicting future abundance, growth rate (λ), and population trend. We incorporated mean demographic rates representative of Caprinae populations and corresponding variances from desert bighorn sheep (Ovis canadensis nelsoni), as a proxy for Caprinae sharing similar life histories. We found a population's minimum abundance resulting in ≤ 0.01 chance of quasi-extinction (QE; population ≤ 5 adult females) in 10 years and ≤ 0.10 QE in 30 years as 50 adult females, or 70 were translocation (removals) pursued. Discovering the threshold required 3 demographic parameters. We show, however, that monitoring populations' relationships to this threshold requires only abundance and recruitment data. This applied approach avoids the logistical and cost hurdles in measuring female survival, making assays of population persistence more practical.


Assuntos
Espécies em Perigo de Extinção , Ruminantes/crescimento & desenvolvimento , Animais , Feminino , Humanos , Dinâmica Populacional , Ruminantes/fisiologia , Carneiro da Montanha/crescimento & desenvolvimento , Carneiro da Montanha/fisiologia
2.
ACS Omega ; 7(20): 17492-17500, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35647440

RESUMO

Core-shell colloids make attractive feedstocks for three-dimensional (3D) printing mixed oxide glass materials because they enable synthetic control of precursor dimensions and compositions, improving glass fabrication precision. Toward that end, we report the design and use of core-shell germania-silica (GeO2-SiO2) colloids and their use as precursors to fabricate GeO2-SiO2 glass monoliths by direct ink write (DIW) 3D printing. By this method, GeO2 colloids were prepared in solution using sol-gel chemistry and formed oblong, raspberry-like agglomerates with ∼15 nm diameter primary particles that were predominantly amorphous but contained polycrystalline domains. An ∼15 nm encapsulating SiO2 shell layer was formed directly on the GeO2 core agglomerates to form core-shell GeO2-SiO2 colloids. For glass 3D printing, GeO2-SiO2 colloidal sols were formulated into a viscous ink by solvent exchange, printed into monoliths by DIW additive manufacturing, and sintered to transparent glasses. Characterization of the glass components demonstrates that the core-shell GeO2-SiO2 presents a feasible route to prepare quality, optically transparent low wt % GeO2-SiO2 glasses by DIW printing. Additionally, the results offer a novel, hybrid colloid approach to fabricating 3D-printed Ge-doped silica glass.

3.
J Am Soc Nephrol ; 33(6): 1120-1136, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35292439

RESUMO

BACKGROUND: Glomerular endothelial cell (GEnC) fenestrations are recognized as an essential component of the glomerular filtration barrier, yet little is known about how they are regulated and their role in disease. METHODS: We comprehensively characterized GEnC fenestral and functional renal filtration changes including measurement of glomerular Kf and GFR in diabetic mice (BTBR ob-/ob- ). We also examined and compared human samples. We evaluated Eps homology domain protein-3 (EHD3) and its association with GEnC fenestrations in diabetes in disease samples and further explored its role as a potential regulator of fenestrations in an in vitro model of fenestration formation using b.End5 cells. RESULTS: Loss of GEnC fenestration density was associated with decreased filtration function in diabetic nephropathy. We identified increased diaphragmed fenestrations in diabetes, which are posited to increase resistance to filtration and further contribute to decreased GFR. We identified decreased glomerular EHD3 expression in diabetes, which was significantly correlated with decreased fenestration density. Reduced fenestrations in EHD3 knockdown b.End5 cells in vitro further suggested a mechanistic role for EHD3 in fenestration formation. CONCLUSIONS: This study demonstrates the critical role of GEnC fenestrations in renal filtration function and suggests EHD3 may be a key regulator, loss of which may contribute to declining glomerular filtration function through aberrant GEnC fenestration regulation. This points to EHD3 as a novel therapeutic target to restore filtration function in disease.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Fenômenos Fisiológicos do Sistema Urinário , Animais , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Células Endoteliais/metabolismo , Glomérulos Renais/metabolismo , Camundongos
4.
Int J Cancer ; 148(12): 3032-3040, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33521927

RESUMO

Proteasome inhibitor (PI) therapy has improved the survival of multiple myeloma (MM) patients. However, inevitably, primary or acquired resistance to PIs leads to disease progression; resistance mechanisms are unclear. Obesity is a risk factor for MM mortality. Oxidized LDL (OxLDL), a central mediator of atherosclerosis that is elevated in metabolic syndrome (co-occurrence of obesity, insulin resistance, dyslipidemia and hypertension), has been linked to an increased risk of solid cancers and shown to stimulate pro-oncogenic/survival signaling. We hypothesized that OxLDL is a mediator of chemoresistance and evaluated its effects on MM cell killing by PIs. OxLDL potently suppressed the ability of the boronic acid-based PIs bortezomib (BTZ) and ixazomib, but not the epoxyketone-based PI carfilzomib, to kill human MM cell lines and primary cells. OxLDL suppressed BTZ-induced inhibition of proteasome activity and induction of pro-apoptotic signaling. These cytoprotective effects were abrogated when lipid hydroperoxides (LOOHs) associated with OxLDL were enzymatically reduced. We also demonstrated the presence of OxLDL in the MM bone marrow microenvironment as well as numerous granulocytes and monocytes capable of cell-mediated LDL oxidation through myeloperoxidase. Our findings suggest that OxLDL may be a potent mediator of boronic acid-based PI resistance, particularly for MM patients with metabolic syndrome, given their elevated systemic levels of OxLDL. LDL cholesterol-lowering therapy to reduce circulating OxLDL, and pharmacologic targeting of LOOH levels or resistance pathways induced by the modified lipoprotein, could deepen the response to these important agents and offer clinical benefit to MM patients with metabolic syndrome.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Lipoproteínas LDL/metabolismo , Mieloma Múltiplo/metabolismo , Inibidores de Proteassoma/farmacologia , Compostos de Boro/farmacologia , Bortezomib/farmacologia , Linhagem Celular Tumoral , Glicina/análogos & derivados , Glicina/farmacologia , Granulócitos/metabolismo , Humanos , Peróxidos Lipídicos/metabolismo , Monócitos/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Oligopeptídeos/farmacologia , Inibidores de Proteassoma/uso terapêutico
5.
Sci Rep ; 10(1): 17729, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082374

RESUMO

With most of the world's Caprinae taxa threatened with extinction, the IUCN appeals to the development of simple and affordable sampling methods that will produce credible abundance and distribution data for helping conserve these species inhabiting remote areas. Traditional sampling approaches, like aerial sampling or mark-capture-recapture, can generate bias by failing to meet sampling assumptions, or by incurring too much cost and logistical burden for most projects to address them. Therefore, we met the IUCN's challenge by testing a sampling technique that leverages imagery from camera traps with conventional distance sampling, validating its operability in mountainous topography by comparing results to known abundances. Our project occurred within a captive facility housing a wild population of desert bighorn sheep (Ovis canadensis) in the Chihuahuan desert of New Mexico, which is censused yearly. True abundance was always within our 90% confidence bounds, and the mean abundance estimates were within 4.9 individuals (average) of the census values. By demonstrating the veracity of this straightforward and inexpensive sampling method, we provide confidence in its operability, urging its use to fill conservation voids for Caprinae and other data-deficient species inhabiting rugged or heavily vegetated terrain.


Assuntos
Monitorização de Parâmetros Ecológicos/métodos , Ecossistema , Densidade Demográfica , Carneiro da Montanha , Animais , Artiodáctilos , Conservação dos Recursos Naturais , New Mexico , Robótica , Tamanho da Amostra
6.
JCI Insight ; 5(19)2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-32870819

RESUMO

Lupus nephritis (LN) is a major organ complication and cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). There is an unmet medical need for developing more efficient and specific, mechanism-based therapies, which depends on improved understanding of the underlying LN pathogenesis. Here we present direct visual evidence from high-power intravital imaging of the local kidney tissue microenvironment in mouse models showing that activated memory T cells originated in immune organs and the LN-specific robust accumulation of the glomerular endothelial glycocalyx played central roles in LN development. The glomerular homing of T cells was mediated via the direct binding of their CD44 to the hyaluronic acid (HA) component of the endothelial glycocalyx, and glycocalyx-degrading enzymes efficiently disrupted homing. Short-course treatment with either hyaluronidase or heparinase III provided long-term organ protection as evidenced by vastly improved albuminuria and survival rate. This glycocalyx/HA/memory T cell interaction is present in multiple SLE-affected organs and may be therapeutically targeted for SLE complications, including LN.


Assuntos
Endotélio Vascular/imunologia , Glicocálix/metabolismo , Hialuronoglucosaminidase/administração & dosagem , Glomérulos Renais/imunologia , Nefrite Lúpica/prevenção & controle , Polissacarídeo-Liases/administração & dosagem , Linfócitos T/imunologia , Animais , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Ácido Hialurônico/metabolismo , Memória Imunológica/imunologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Linfócitos T/metabolismo , Linfócitos T/patologia
7.
Proc Natl Acad Sci U S A ; 117(27): 15862-15873, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32561647

RESUMO

Albuminuria is an independent risk factor for the progression to end-stage kidney failure, cardiovascular morbidity, and premature death. As such, discovering signaling pathways that modulate albuminuria is desirable. Here, we studied the transcriptomes of podocytes, key cells in the prevention of albuminuria, under diabetic conditions. We found that Neuropeptide Y (NPY) was significantly down-regulated in insulin-resistant vs. insulin-sensitive mouse podocytes and in human glomeruli of patients with early and late-stage diabetic nephropathy, as well as other nondiabetic glomerular diseases. This contrasts with the increased plasma and urinary levels of NPY that are observed in such conditions. Studying NPY-knockout mice, we found that NPY deficiency in vivo surprisingly reduced the level of albuminuria and podocyte injury in models of both diabetic and nondiabetic kidney disease. In vitro, podocyte NPY signaling occurred via the NPY2 receptor (NPY2R), stimulating PI3K, MAPK, and NFAT activation. Additional unbiased proteomic analysis revealed that glomerular NPY-NPY2R signaling predicted nephrotoxicity, modulated RNA processing, and inhibited cell migration. Furthermore, pharmacologically inhibiting the NPY2R in vivo significantly reduced albuminuria in adriamycin-treated glomerulosclerotic mice. Our findings suggest a pathogenic role of excessive NPY-NPY2R signaling in the glomerulus and that inhibiting NPY-NPY2R signaling in albuminuric kidney disease has therapeutic potential.


Assuntos
Albuminúria/metabolismo , Nefropatias/metabolismo , Neuropeptídeo Y/metabolismo , Receptores de Neuropeptídeo Y/metabolismo , Transdução de Sinais/fisiologia , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Benzazepinas/farmacologia , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas , Modelos Animais de Doenças , Regulação para Baixo , Doxorrubicina/farmacologia , Humanos , Insulina/metabolismo , Nefropatias/patologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Neuropeptídeo Y/farmacologia , Neuropeptídeo Y/urina , Podócitos/metabolismo , Proteômica , Receptores de Neuropeptídeo Y/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
9.
Am J Pathol ; 190(4): 742-751, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32035881

RESUMO

The endothelial glycocalyx is a vital regulator of vascular permeability. Damage to this delicate layer can result in increased protein and water transit. The clinical importance of albuminuria as a predictor of kidney disease progression and vascular disease has driven research in this area. This review outlines how research to date has attempted to measure the contribution of the endothelial glycocalyx to vessel wall permeability. We discuss the evidence for the role of the endothelial glycocalyx in regulating permeability in discrete areas of the vasculature and highlight the inherent limitations of the data that have been produced to date. In particular, this review emphasizes the difficulties in interpreting urinary albumin levels in early disease models. In addition, the research that supports the view that glycocalyx damage is a key pathologic step in a diverse array of clinical conditions, including diabetic complications, sepsis, preeclampsia, and atherosclerosis, is summarized. Finally, novel methods are discussed, including an ex vivo glomerular permeability assay that enhances the understanding of permeability changes in disease.


Assuntos
Permeabilidade Capilar , Endotélio Vascular/metabolismo , Glicocálix/fisiologia , Doenças Vasculares/patologia , Animais , Humanos , Doenças Vasculares/metabolismo
10.
Kidney Int ; 97(3): 450-452, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32087885

RESUMO

Patients with end-stage renal disease have a high risk of dying from cardiovascular disease that cannot be explained solely by traditional cardiovascular disease risk factors. Hesse et al. suggest that dysfunctional high-density lipoprotein cholesterol generated in patients with end-stage renal disease causes endothelial glycocalyx degradation. Glycocalyx degradation may represent one of the earliest insults leading to atheroma formation, and so this work suggests a novel link between renal failure and cardiovascular disease.


Assuntos
Glicocálix , Insuficiência Renal Crônica , Arginina/análogos & derivados , Humanos , Lipoproteínas HDL
11.
Kidney Int ; 97(5): 951-965, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32037077

RESUMO

The endothelial glycocalyx is a key component of the glomerular filtration barrier. We have shown that matrix metalloproteinase (MMP)-mediated syndecan 4 shedding is a mechanism of glomerular endothelial glycocalyx damage in vitro, resulting in increased albumin permeability. Here we sought to determine whether this mechanism is important in early diabetic kidney disease, by studying streptozotocin-induced type 1 diabetes in DBA2/J mice. Diabetic mice were albuminuric, had increased glomerular albumin permeability and endothelial glycocalyx damage. Syndecan 4 mRNA expression was found to be upregulated in isolated glomeruli and in flow cytometry-sorted glomerular endothelial cells. In contrast, glomerular endothelial luminal surface syndecan 4 and Marasmium oreades agglutinin lectin labelling measurements were reduced in the diabetic mice. Similarly, syndecan 4 protein expression was significantly decreased in isolated glomeruli but increased in plasma and urine, suggesting syndecan 4 shedding. Mmp-2, 9 and 14 mRNA expression were upregulated in isolated glomeruli, suggesting a possible mechanism of glycocalyx damage and albuminuria. We therefore characterised in detail the activity of MMP-2 and 9 and found significant increases in kidney cortex, plasma and urine. Treatment with MMP-2/9 inhibitor I for 21 days, started six weeks after diabetes induction, restored endothelial glycocalyx depth and coverage and attenuated diabetes-induced albuminuria and reduced glomerular albumin permeability. MMP inhibitor treatment significantly attenuated glomerular endothelial and plasma syndecan 4 shedding and inhibited plasma MMP activity. Thus, our studies confirm the importance of MMPs in endothelial glycocalyx damage and albuminuria in early diabetes and demonstrate that this pathway is amenable to therapeutic intervention. Hence, treatments targeted at glycocalyx protection by MMP inhibition may be of benefit in diabetic kidney disease.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Animais , Células Endoteliais , Barreira de Filtração Glomerular , Glicocálix , Metaloproteinases da Matriz , Camundongos , Sindecana-4/genética
12.
Kidney Int ; 95(1): 94-107, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30389198

RESUMO

Aldosterone contributes to end-organ damage in heart failure and chronic kidney disease. Mineralocorticoid-receptor inhibitors limit activation of the receptor by aldosterone and slow disease progression, but side effects, including hyperkalemia, limit their clinical use. Damage to the endothelial glycocalyx (a luminal biopolymer layer) has been implicated in the pathogenesis of endothelial dysfunction and albuminuria, but to date no one has investigated whether the glomerular endothelial glycocalyx is affected by aldosterone. In vitro, human glomerular endothelial cells exposed to 0.1 nM aldosterone and 145 mMol NaCl exhibited reduced cell surface glycocalyx components (heparan sulfate and syndecan-4) and disrupted shear sensing consistent with damage of the glycocalyx. In vivo, administration of 0.6 µg/g/d of aldosterone (subcutaneous minipump) and 1% NaCl drinking water increased glomerular matrix metalloproteinase 2 activity, reduced syndecan 4 expression, and caused albuminuria. Intravital multiphoton imaging confirmed that aldosterone caused damage of the glomerular endothelial glycocalyx and increased the glomerular sieving coefficient for albumin. Targeting matrix metalloproteinases 2 and 9 with a specific gelatinase inhibitor preserved the glycocalyx, blocked the rise in glomerular sieving coefficient, and prevented albuminuria. Together these data suggest that preservation of the glomerular endothelial glycocalyx may represent a novel strategy for limiting the pathological effects of aldosterone.


Assuntos
Albuminúria/patologia , Aldosterona/metabolismo , Glicocálix/patologia , Insuficiência Renal Crônica/patologia , Albuminúria/urina , Animais , Linhagem Celular , Modelos Animais de Doenças , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Glicocálix/efeitos dos fármacos , Heparitina Sulfato/metabolismo , Humanos , Glomérulos Renais/citologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Insuficiência Renal Crônica/urina , Cloreto de Sódio/farmacologia , Sindecana-4/metabolismo
14.
Kidney Int ; 93(5): 1086-1097, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29433915

RESUMO

Increased urinary albumin excretion is a key feature of glomerular disease but has limitations as a measure of glomerular permeability. Here we describe a novel assay to measure the apparent albumin permeability of single capillaries in glomeruli, isolated from perfused kidneys cleared of red blood cells. The rate of decline of the albumin concentration within the capillary lumen was quantified using confocal microscopy and used to calculate apparent permeability. The assay was extensively validated and provided robust, reproducible estimates of glomerular albumin permeability. These values were comparable with previous in vivo data, showing this assay could be applied to human as well as rodent glomeruli. To confirm this, we showed that targeted endothelial glycocalyx disruption resulted in increased glomerular albumin permeability in mice. Furthermore, incubation with plasma from patients with post-transplant recurrence of nephrotic syndrome increased albumin permeability in rat glomeruli compared to remission plasma. Finally, in glomeruli isolated from rats with early diabetes there was a significant increase in albumin permeability and loss of endothelial glycocalyx, both of which were ameliorated by angiopoietin-1. Thus, a glomerular permeability assay, producing physiologically relevant values with sufficient sensitivity to measure changes in glomerular permeability and independent of tubular function, was developed and validated. This assay significantly advances the ability to study biology and disease in rodent and human glomeruli.


Assuntos
Bioensaio/métodos , Capilares/metabolismo , Permeabilidade Capilar , Glomérulos Renais/irrigação sanguínea , Albumina Sérica/metabolismo , Albuminúria/metabolismo , Albuminúria/fisiopatologia , Angiopoietina-1/farmacologia , Animais , Capilares/efeitos dos fármacos , Capilares/fisiopatologia , Permeabilidade Capilar/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Glicocálix/metabolismo , Humanos , Técnicas In Vitro , Cinética , Masculino , Camundongos Endogâmicos C57BL , Microscopia Confocal , Síndrome Nefrótica/sangue , Síndrome Nefrótica/fisiopatologia , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
15.
J Nurs Scholarsh ; 50(1): 102-108, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29116683

RESUMO

BACKGROUND: The gender pay gap in the United States is an ongoing issue, affecting women in nearly all occupations. Jobs traditionally associated with men tend to pay better than traditionally female-dominated jobs, and there is evidence to suggest within-occupation gender pay differences as well. PURPOSE: We compared and contrasted gender wage disparities for registered nurses (RNs), relative to gender wage disparities for another female-dominated occupation, teachers, while controlling for sociodemographic factors. METHODS: Using data in the American Community Survey, we analyzed the largest U.S. random representative sample of self-identified RNs and primary or secondary school teachers from 2000 to 2013 using fixed-effects regression analysis. RESULTS: There is greater disparity between nurse pay by gender than in teacher pay by gender. In addition, the net return in wages for additional education is higher for school teachers (21.7%) than for RNs (4.7%). CONCLUSIONS: Findings support preferential wages for men in nursing, more so than for men in teaching. CLINICAL RELEVANCE: The substantial gender disparities are an indirect measure of the misallocation of resources in effective patient care.


Assuntos
Enfermeiras e Enfermeiros/economia , Salários e Benefícios/estatística & dados numéricos , Sexismo , Feminino , Humanos , Masculino , Enfermeiras e Enfermeiros/estatística & dados numéricos , Estados Unidos
16.
Trends Cancer ; 3(12): 871-882, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29198442

RESUMO

The effective deployment of rationally developed therapies for diffuse large B cell lymphoma (DLBCL) requires rapid assimilation of new biological data. Within this framework, here we address topical issues at the intersection of DLBCL biology and the clinic. We discuss targeting of B cell receptor (BCR) signaling, with emphasis on identifying patients who may benefit from this maneuver and how to best achieve it. We address strategies to modulate the DLBCL microenvironment, including the use of immune checkpoint inhibitors in selected DLBCL subsets, and the potential activity of alternative antiangiogenic therapies. Lastly, we highlight the emerging recognition of MYC and BCL2 coexpression as the most robust predictor of DLBCL outcome, and discuss rationally conceived experimental approaches to treat these high-risk patients.


Assuntos
Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Receptores de Antígenos de Linfócitos B/antagonistas & inibidores , Receptores de Antígenos de Linfócitos B/genética , Rituximab , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Vincristina/efeitos adversos , Vincristina/uso terapêutico
17.
Ecol Evol ; 7(8): 2821-2834, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28428872

RESUMO

Identifying climatic drivers of an animal population's vital rates and locating where they operate steers conservation efforts to optimize species recovery. The population growth of endangered whooping cranes (Grus americana) hinges on juvenile recruitment. Therefore, we identify climatic drivers (solar activity [sunspots] and weather) of whooping crane recruitment throughout the species' life cycle (breeding, migration, wintering). Our method uses a repeated cross-validated absolute shrinkage and selection operator approach to identify drivers of recruitment. We model effects of climate change on those drivers to predict whooping crane population growth given alternative scenarios of climate change and solar activity. Years with fewer sunspots indicated greater recruitment. Increased precipitation during autumn migration signified less recruitment. On the breeding grounds, fewer days below freezing during winter and more precipitation during breeding suggested less recruitment. We predicted whooping crane recruitment and population growth may fall below long-term averages during all solar cycles when atmospheric CO2 concentration increases, as expected, to 500 ppm by 2050. Species recovery during a typical solar cycle with 500 ppm may require eight times longer than conditions without climate change and the chance of population decline increases to 31%. Although this whooping crane population is growing and may appear secure, long-term threats imposed by climate change and increased solar activity may jeopardize its persistence. Weather on the breeding grounds likely affects recruitment through hydrological processes and predation risk, whereas precipitation during autumn migration may influence juvenile mortality. Mitigating threats or abating climate change should occur within ≈30 years or this wild population of whooping cranes may begin declining.

18.
J Nurs Scholarsh ; 48(6): 608-615, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27737516

RESUMO

PURPOSE: No studies quantify the labor market disparities between nurses with and without activity difficulties (physical impairment or disability). We explore disparate treatment of nurses with activity difficulties at three margins of the labor market: the ability to get a job, the relative wage rate offered once a nurse has a job, and the annual hours of work given that wage rate. DESIGN: Key variables from the American Community Survey (ACS) were analyzed, including basic demographic information, wages, hours of work, and employment status of registered nurses from 2006 to 2014. FINDINGS: Although there is relatively little disparity in hourly wages, there is enormous disparity in the disabled's employment and hours of work opportunities, and hence a moderate amount of disparity in annual wages. CONCLUSIONS: This has significant implications for the nursing labor force, particularly as the nursing workforce continues to age and physical limitations or disabilities increase by 15-fold from 25 to 65 years of age. CLINICAL RELEVANCE: Physical or psychological difficulties increase sharply over the course of a nurse's career, and employers must heighten efforts to facilitate an aging workforce and provide appropriate job accommodations for nurses with activity limitations.


Assuntos
Pessoas com Deficiência/estatística & dados numéricos , Emprego/estatística & dados numéricos , Enfermeiras e Enfermeiros/economia , Enfermeiras e Enfermeiros/estatística & dados numéricos , Salários e Benefícios/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Estados Unidos
19.
PLoS One ; 10(11): e0141355, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26560518

RESUMO

Throughout many arid lands of Africa, Australia and the United States, wildlife agencies provide water year-round for increasing game populations and enhancing biodiversity, despite concerns that water provisioning may favor species more dependent on water, increase predation, and reduce biodiversity. In part, understanding the effects of water provisioning requires identifying why and when animals visit water. Employing this information, by matching water provisioning with use by target species, could assist wildlife management objectives while mitigating unintended consequences of year-round watering regimes. Therefore, we examined if weather variables (maximum temperature, relative humidity [RH], vapor pressure deficit [VPD], long and short-term precipitation) and predator-prey relationships (i.e., prey presence) predicted water visitation by 9 mammals. We modeled visitation as recorded by trail cameras at Sevilleta National Wildlife Refuge, New Mexico, USA (June 2009 to September 2014) using generalized linear modeling. For 3 native ungulates, elk (Cervus Canadensis), mule deer (Odocoileus hemionus), and pronghorn (Antilocapra americana), less long-term precipitation and higher maximum temperatures increased visitation, including RH for mule deer. Less long-term precipitation and higher VPD increased oryx (Oryx gazella) and desert cottontail rabbits (Sylvilagus audubonii) visitation. Long-term precipitation, with RH or VPD, predicted visitation for black-tailed jackrabbits (Lepus californicus). Standardized model coefficients demonstrated that the amount of long-term precipitation influenced herbivore visitation most. Weather (especially maximum temperature) and prey (cottontails and jackrabbits) predicted bobcat (Lynx rufus) visitation. Mule deer visitation had the largest influence on coyote (Canis latrans) visitation. Puma (Puma concolor) visitation was solely predicted by prey visitation (elk, mule deer, oryx). Most ungulate visitation peaked during May and June. Coyote, elk and puma visitation was relatively consistent throughout the year. Within the diel-period, activity patterns for predators corresponded with prey. Year-round water management may favor species with consistent use throughout the year, and facilitate predation. Providing water only during periods of high use by target species may moderate unwanted biological costs.


Assuntos
Animais Selvagens/fisiologia , Comportamento de Ingestão de Líquido/fisiologia , Comportamento Predatório/fisiologia , Água/metabolismo , Tempo (Meteorologia) , Animais , Animais Selvagens/classificação , Conservação dos Recursos Naturais , Ecossistema , Geografia , Mamíferos/classificação , Mamíferos/fisiologia , Modelos Teóricos , New Mexico , Dinâmica Populacional , Estações do Ano , Especificidade da Espécie , Fatores de Tempo
20.
FASEB J ; 28(11): 4686-99, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25122554

RESUMO

The endothelial surface glycocalyx is a hydrated mesh in which proteoglycans are prominent. It is damaged in diseases associated with elevated levels of tumor necrosis factor α (TNF-α). We investigated the mechanism of TNF-α-induced disruption of the glomerular endothelial glycocalyx. We used conditionally immortalized human glomerular endothelial cells (GEnCs), quantitative PCR arrays, Western blotting, immunoprecipitation, immunofluorescence, and dot blots to examine the effects of TNF-α. TNF-α induced syndecan 4 (SDC4) mRNA up-regulation by 2.5-fold, whereas cell surface SDC4 and heparan sulfate (HS) were reduced by 36 and 30%, respectively, and SDC4 and sulfated glycosaminoglycan in the culture medium were increased by 52 and 65%, respectively, indicating TNF-α-induced shedding. Small interfering (siRNA) knockdown of SDC4 (by 52%) caused a corresponding loss of cell surface HS of similar magnitude (38%), and immunoprecipitation demonstrated that SDC4 and HS are shed as intact proteoglycan ectodomains. All of the effects of TNF-α on SDC4 and HS were abrogated by the metalloproteinase (MMP) inhibitor batimastat. Also abrogated was the associated 37% increase in albumin passage across GEnC monolayers. Specific MMP9 knockdown by siRNA similarly blocked TNF-α effects. SDC4 is the predominant HS proteoglycan in the GEnC glycocalyx. TNF-α-induced MMP9-mediated shedding of SDC4 is likely to contribute to the endothelial glycocalyx disruption observed in diabetes and inflammatory states.


Assuntos
Glicocálix/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Sindecana-4/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Membrana Celular , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Metaloproteinase 9 da Matriz/genética , Proteoglicanas/metabolismo
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