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30, p < .001). Depressive symptoms also predicted insulin change, but only for pubertal adolescents (B = -0.23, SE = 0.11, p = .038). This relationship was moderated by race (p = .047); depressive symptoms predicted insulin change only among pubertal black adolescents (p = .030), not white (p = .49), and in the direction opposite that hypothesized (Bblacks = -0.51, SE = 0.23). Post hoc analyses revealed that pubertal black adolescents with high depressive symptoms had the highest baseline insulin, which stayed high across the follow-up period.
Among pubertal black adolescents, elevated depressive symptoms are associated with increased risk for sustained hyperinsulinemia from adolescence into adulthood. These youths may be particularly vulnerable for Type 2 diabetes.
Among pubertal black adolescents, elevated depressive symptoms are associated with increased risk for sustained hyperinsulinemia from adolescence into adulthood. These youths may be particularly vulnerable for Type 2 diabetes.The major fungal pathogen of humans, Candida albicans, mounts robust responses to oxidative stress that are critical for its virulence. These responses counteract the reactive oxygen species (ROS) that are generated by host immune cells in an attempt to kill the invading fungus. Knowledge of the dynamical processes that instigate C. albicans oxidative stress responses is required for a proper understanding of fungus-host interactions. Therefore, we have adopted an interdisciplinary approach to explore the dynamical responses of C. albicans to hydrogen peroxide (H2O2). Our deterministic mathematical model integrates two major oxidative stress signalling pathways (Cap1 and Hog1 pathways) with the three major antioxidant systems (catalase, glutathione and thioredoxin systems) and the pentose phosphate pathway, which provides reducing equivalents required for oxidative stress adaptation. The model encapsulates existing knowledge of these systems with new genomic, proteomic, transcriptomic, molecular and cellular datasets. Our integrative approach predicts the existence of alternative states for the key regulators Cap1 and Hog1, thereby suggesting novel regulatory behaviours during oxidative stress. Baf-A1 The model reproduces both existing and new experimental observations under a variety of scenarios. Time- and dose-dependent predictions of the oxidative stress responses for both wild type and mutant cells have highlighted the different temporal contributions of the various antioxidant systems during oxidative stress adaptation, indicating that catalase plays a critical role immediately following stress imposition. This is the first model to encapsulate the dynamics of the transcriptional response alongside the redox kinetics of the major antioxidant systems during H2O2 stress in C. albicans.
To compare patient experiences and disparities for older adults with depressive symptoms in managed care (Medicare Advantage [MA]) versus Medicare Fee-for-Service (FFS).
Data came from the 2010 Medicare CAHPS survey, to which 220,040 MA and 135,874 FFS enrollees aged 65 and older responded.
Multivariate linear regression was used to test whether case-mix-adjusted associations between depressive symptoms and patient experience differed for beneficiaries in MA versus FFS. Dependent measures included four measures of beneficiaries’ experiences with doctors (e.g., reports of doctor communication) and seven measures of beneficiaries’ experiences with plans (e.g., customer service).
Beneficiaries with depressive symptoms reported worse experiences than those without depressive symptoms regardless of coverage type. For measures assessing interactions with the plan (but not for measures assessing interactions with doctors), the disadvantage for beneficiaries with versus without depressive symptoms was larger in MA than in FFS.
Disparities in care experienced by older Medicare beneficiaries with depressive symptoms tend to be more negative in managed care than in FFS. Efforts are needed to identify and address the barriers these beneficiaries encounter to help them better traverse the managed care environment.
Disparities in care experienced by older Medicare beneficiaries with depressive symptoms tend to be more negative in managed care than in FFS. Efforts are needed to identify and address the barriers these beneficiaries encounter to help them better traverse the managed care environment.The α-thyroid hormone receptor gene (TRα) codes for two functionally distinct proteins TRα1, the α-thyroid hormone receptor; and TRα2, a non-hormone-binding variant. The final exon of TRα2 mRNA overlaps the 3′ end of Rev-erbα mRNA, which encodes another nuclear receptor on the opposite strand of DNA. To understand the evolution of this antisense overlap, we sequenced these genes and mRNAs in the platypus Orthorhynchus anatinus. Despite its strong homology with other mammals, the platypus TRα/Rev-erbα locus lacks elements essential for expression of TRα2. Comparative analysis suggests that alternative splicing of TRα2 mRNA expression evolved in a stepwise fashion before the divergence of eutherian and marsupial mammals. A short G-rich element (G30) located downstream of the alternative 3’splice site of TRα2 mRNA and antisense to the 3’UTR of Rev-erbα plays an important role in regulating TRα2 splicing. G30 is tightly conserved in eutherian mammals, but is absent in marsupials and monotremes. Systematic deletions and substitutions within G30 have dramatically different effects on TRα2 splicing, leading to either its inhibition or its enhancement. Mutations that disrupt one or more clusters of G residues enhance splicing two- to three-fold. These results suggest the G30 sequence can adopt a highly structured conformation, possibly a G-quadruplex, and that it is part of a complex splicing regulatory element which exerts both positive and negative effects on TRα2 expression. Since mutations that strongly enhance splicing in vivo have no effect on splicing in vitro, it is likely that the regulatory role of G30 is mediated through linkage of transcription and splicing.Cognitive control has been extensively studied from Event-Related Potential (ERP) point of view in visual modality using Stroop paradigms. Little work has been done in auditory Stroop paradigms, and inconsistent conclusions have been reported, especially on the conflict detection stage of cognitive control. This study investigated the early ERP components in an auditory Stroop paradigm, during which participants were asked to identify the volume of spoken words and ignore the word meanings. A series of significant ERP components were revealed that distinguished incongruent and congruent trials two declined negative polarity waves (the N1 and the N2) and three declined positive polarity wave (the P1, the P2 and the P3) over the fronto-central area for the incongruent trials. These early ERP components imply that both a perceptual stage and an identification stage exist in the auditory Stroop effect. A 3-stage cognitive control model was thus proposed for a more detailed description of the human cognitive control mechanism in the auditory Stroop tasks.It was previously shown that a small lesion in the primary somatosensory cortex (S1) prevented both cortical plasticity and sensory learning in the adult mouse visual system While 3-month-old control mice continued to show ocular dominance (OD) plasticity in their primary visual cortex (V1) after monocular deprivation (MD), age-matched mice with a small photothrombotically induced (PT) stroke lesion in S1, positioned at least 1 mm anterior to the anterior border of V1, no longer expressed OD-plasticity. In addition, in the S1-lesioned mice, neither the experience-dependent increase of the spatial frequency threshold (“visual acuity”) nor of the contrast threshold (“contrast sensitivity”) of the optomotor reflex through the open eye was present. To assess whether these plasticity impairments can also occur if a lesion is placed more distant from V1, we tested the effect of a PT-lesion in the secondary motor cortex (M2). We observed that mice with a small M2-lesion restricted to the superficial cortical layers no longer expressed an OD-shift towards the open eye after 7 days of MD in V1 of the lesioned hemisphere. Consistent with previous findings about the consequences of an S1-lesion, OD-plasticity in V1 of the nonlesioned hemisphere of the M2-lesioned mice was still present. In addition, the experience-dependent improvements of both visual acuity and contrast sensitivity of the open eye were severely reduced. In contrast, sham-lesioned mice displayed both an OD-shift and improvements of visual capabilities of their open eye. To summarize, our data indicate that even a very small lesion restricted to the superficial cortical layers and more than 3mm anterior to the anterior border of V1 compromised V1-plasticity and impaired learning-induced visual improvements in adult mice. Thus both plasticity phenomena cannot only depend on modality-specific and local nerve cell networks but are clearly influenced by long-range interactions even from distant brain regions.
Leptospirosis is an important but neglected bacterial zoonosis that has been largely overlooked in Africa. link2 In this systematic review, we aimed to summarise and compare current knowledge of (1) the geographic distribution, prevalence, incidence and diversity of acute human leptospirosis in Africa; and (2) the geographic distribution, host range, prevalence and diversity of Leptospira spp. infection in animal hosts in Africa.
Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we searched for studies that described (1) acute human leptospirosis and (2) pathogenic Leptospira spp. infection in animals. We performed a literature search using eight international and regional databases for English and non-English articles published between January 1930 to October 2014 that met out pre-defined inclusion criteria and strict case definitions.
We identified 97 studies that described acute human leptospirosis (n = 46) or animal Leptospira infection (n = 51) in 26 Africaan transmission of leptospirosis on the African continent.Organismal metabolic rate, a fundamental metric in biology, demonstrates an allometric scaling relationship with body size. Fractal-like vascular distribution networks of biological systems are proposed to underlie metabolic rate allometric scaling laws from individual organisms to cells, mitochondria, and enzymes. Tissue-specific metabolic scaling is notably absent from this paradigm. In the current study, metabolic scaling relationships of hearts and brains with body size were examined by improving on a high-throughput whole-organ oxygen consumption rate (OCR) analysis method in five biomedically and environmentally relevant teleost model species. Tissue-specific metabolic scaling was compared with organismal routine metabolism (RMO2), which was measured using whole organismal respirometry. Basal heart OCR and organismal RMO2 scaled identically with body mass in a species-specific fashion across all five species tested. link3 However, organismal maximum metabolic rates (MMO2) and pharmacologically-induced maximum cardiac metabolic rates in zebrafish Danio rerio did not show a similar relationship with body mass.