275 research outputs found
Preventing and Treating Women’s Postpartum Depression: A Qualitative Systematic Review on Partner-Inclusive Interventions
Partner-related factors associated with the occurrence of Postpartum Depression (PPD) may justify the partner’s inclusion in preventive and treatment approaches. The aim of this qualitative systematic review was to synthesize the literature on partner-inclusive interventions designed to prevent or treat postpartum depression (PPD) in women. In accordance with the PRISMA guidelines, the systematic search of studies published between 1967 and May 2015 in PsycINFO and PubMed identified 26 studies that met the inclusion criteria, which reported on 24 interventions. The following partner parameters were analyzed: participation type, session content, mental health assessment, attendance assessment, and the effects of partner’s participation on the women’s response to the interventions. Total participation by the partner was mostly reported in the prevention studies, whereas partial participation was reported in the treatment studies. The session content was mostly based on psychoeducation about PPD and parenthood, coping strategies to facilitate the transition to parenthood such as the partner’s emotional and instrumental support, and problem-solving and communication skills. Some benefits perceived by the couples underscore the relevance of the partner’s inclusion in PPD interventions. However, the scarce information about the partner’s attendance and the associated effects on the women’s intervention outcomes, along with methodological limitations of the studies, made it difficult to determine if the partner’s participation was associated with the intervention’s efficacy. Conclusions about the clinical value of including partners in PPD interventions are still limited. More research is warranted to better inform health policy strategies
Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease
Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its
molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these
experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related,
liver injury and to assess novel candidate biomarkers in NAFLD patients.
Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE−/−)
animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation
(iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential
protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine
tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked
immunosorbent assay in serum from adult NAFLD patients.
Results: Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a
murine model. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In
vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then
ubiquitinated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult
NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct,
hydroimidazolone (MG-H1) were significantly correlated with body mass index (r = 0.520, p < 0.0001).
Conclusion: Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the
acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role
of GLO1 in the molecular pathogenesis of NAFLD is warranted.
Keywords: Non-alcoholic fatty liver disease, Glyoxalase, Methylglyoxal, Proteomics, iTRA
Pichia pastoris regulates its gene-specific response to different carbon sources at the transcriptional, rather than the translational, level
Background: The methylotrophic, Crabtree-negative yeast Pichia pastoris is widely used as a heterologous protein production host. Strong inducible promoters derived from methanol utilization genes or constitutive glycolytic promoters are typically used to drive gene expression. Notably, genes involved in methanol utilization are not only repressed by the presence of glucose, but also by glycerol. This unusual regulatory behavior prompted us to study the regulation of carbon substrate utilization in different bioprocess conditions on a genome wide scale. Results: We performed microarray analysis on the total mRNA population as well as mRNA that had been fractionated according to ribosome occupancy. Translationally quiescent mRNAs were defined as being associated with single ribosomes (monosomes) and highly-translated mRNAs with multiple ribosomes (polysomes). We found that despite their lower growth rates, global translation was most active in methanol-grown P. pastoris cells, followed by excess glycerol- or glucose-grown cells. Transcript-specific translational responses were found to be minimal, while extensive transcriptional regulation was observed for cells grown on different carbon sources. Due to their respiratory metabolism, cells grown in excess glucose or glycerol had very similar expression profiles. Genes subject to glucose repression were mainly involved in the metabolism of alternative carbon sources including the control of glycerol uptake and metabolism. Peroxisomal and methanol utilization genes were confirmed to be subject to carbon substrate repression in excess glucose or glycerol, but were found to be strongly de-repressed in limiting glucose-conditions (as are often applied in fed batch cultivations) in addition to induction by methanol. Conclusions: P. pastoris cells grown in excess glycerol or glucose have similar transcript profiles in contrast to S. cerevisiae cells, in which the transcriptional response to these carbon sources is very different. The main response to different growth conditions in P. pastoris is transcriptional; translational regulation was not transcript-specific. The high proportion of mRNAs associated with polysomes in methanol-grown cells is a major finding of this study; it reveals that high productivity during methanol induction is directly linked to the growth condition and not only to promoter strength
A Comparison of Mathematical Models for Polarization of Single Eukaryotic Cells in Response to Guided Cues
Polarization, a primary step in the response of an individual eukaryotic cell to a spatial stimulus, has attracted numerous theoretical treatments complementing experimental studies in a variety of cell types. While the phenomenon itself is universal, details differ across cell types, and across classes of models that have been proposed. Most models address how symmetry breaking leads to polarization, some in abstract settings, others based on specific biochemistry. Here, we compare polarization in response to a stimulus (e.g., a chemoattractant) in cells typically used in experiments (yeast, amoebae, leukocytes, keratocytes, fibroblasts, and neurons), and, in parallel, responses of several prototypical models to typical stimulation protocols. We find that the diversity of cell behaviors is reflected by a diversity of models, and that some, but not all models, can account for amplification of stimulus, maintenance of polarity, adaptation, sensitivity to new signals, and robustness
Language development after cochlear implantation: an epigenetic model
Growing evidence supports the notion that dynamic gene expression, subject to epigenetic control, organizes multiple influences to enable a child to learn to listen and to talk. Here, we review neurobiological and genetic influences on spoken language development in the context of results of a longitudinal trial of cochlear implantation of young children with severe to profound sensorineural hearing loss in the Childhood Development after Cochlear Implantation study. We specifically examine the results of cochlear implantation in participants who were congenitally deaf (N = 116). Prior to intervention, these participants were subject to naturally imposed constraints in sensory (acoustic–phonologic) inputs during critical phases of development when spoken language skills are typically achieved rapidly. Their candidacy for a cochlear implant was prompted by delays (n = 20) or an essential absence of spoken language acquisition (n = 96). Observations thus present an opportunity to evaluate the impact of factors that influence the emergence of spoken language, particularly in the context of hearing restoration in sensitive periods for language acquisition. Outcomes demonstrate considerable variation in spoken language learning, although significant advantages exist for the congenitally deaf children implanted prior to 18 months of age. While age at implantation carries high predictive value in forecasting performance on measures of spoken language, several factors show significant association, particularly those related to parent–child interactions. Importantly, the significance of environmental variables in their predictive value for language development varies with age at implantation. These observations are considered in the context of an epigenetic model in which dynamic genomic expression can modulate aspects of auditory learning, offering insights into factors that can influence a child’s acquisition of spoken language after cochlear implantation. Increased understanding of these interactions could lead to targeted interventions that interact with the epigenome to influence language outcomes with intervention, particularly in periods in which development is subject to time-sensitive experience
The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice
More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease
SNAPSHOT USA 2019 : a coordinated national camera trap survey of the United States
This article is protected by copyright. All rights reserved.With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August - 24 November of 2019). We sampled wildlife at 1509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the USA. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as well as future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication.Publisher PDFPeer reviewe
RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients
Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p
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