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LIVER cells, HOMEOSTASIS, NON-alcoholic fatty liver disease, YAP signaling proteins, GENETIC overexpression, NUCLEOTIDE synthesis, and METABOLIC regulation

A primary role of the liver is to regulate whole body glucose homeostasis. Glucokinase (GCK) is the main hexokinase (HK) expressed in hepatocytes and functions to phosphorylate the glucose that enters via GLUT transporters to become glucose-6-phosphate (G6P), which subsequently commits glucose to enter downstream anabolic and catabolic pathways. In the recent years, hexokinase domain-containing-1 (HKDC1), a novel 5th HK, has been characterized by our group and others. Its expression profile varies but has been identified to have low basal expression in normal liver but increases during states of stress including pregnancy, nonalcoholic fatty liver disease (NAFLD), and liver cancer. Here, we have developed a stable overexpression model of hepatic HKDC1 in mice to examine its effect on metabolic regulation. We found that HKDC1 overexpression, over time, causes impaired glucose homeostasis in male mice and shifts glucose metabolism towards anabolic pathways with an increase in nucleotide synthesis. Furthermore, we observed these mice to have larger liver sizes due to greater hepatocyte proliferative potential and cell size, which in part, is mediated via yes-associated protein (YAP) signaling. [ABSTRACT FROM AUTHOR]

SECOND language acquisition, DOMINANT language, CHINESE language, LANGUAGE & languages, NATIVE language, and NATURAL languages

And even though I do not think that most domain-general models of L SB 1 sb /L SB 2 sb acquisition are going to come under further scrutiny, Mazuka's distinction is likely to be valuable for domain-specific models of acquisition (of phonology). Yes, L SB 2 sb learners do not parse de-RCs in the same way as native speakers do, but that only indicates that they have not achieved ultimate attainment; not that there are fundamental differences in L SB 1 sb and L SB 2 sb processing. Martohardjono, Valian and Klein (MVK) take up the deficit and transfer accounts (d/t) of L SB 2 sb acquisition in their chapter, while looking at acquisition of tense. [Extracted from the article]

FRENCH language, SOCIOLINGUISTICS, CONTINUITY, CANADIAN history, and TECHNOLOGICAL innovations

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The home-field advantage (HFA) hypothesis establishes that plant litter decomposes faster at 'home' sites than in 'away' sites due to more specialized decomposers acting at home sites. This hypothesis has predominantly been tested through 'yes or no' transplanting experiments, where the litter decomposition of a focal species is quantified near and away from their conspecifics. Herein, we evaluated the occurrence and magnitude of home-field effects on the leaf litter decomposition of Myrcia ramuliflora (O.Berg) N. Silveira (Myrtaceae) along a natural gradient of conspecific litterfall input and also if home-field effects are affected by litter and soil traits. Litter decomposition of M. ramuliflora was assessed through litterbags placed in 39 plots in a tropical heath vegetation over a period of 12 months. We also characterized abiotic factors, litter layer traits, and litter diversity. Our results indicated the occurrence of positive (i.e. Home-field advantage) and negative (i.e. Home-field disadvantage) effects in more than half of the plots. Positive and negative effects occurred in a similar frequency and magnitude. Among all predictors tested, only the community weighted mean C/N ratio of the litterfall input was associated with home-field effects. Our results reinforce the lack of generality for home-field effects found in the literature and thus challenge the understanding of litter-decomposer interaction in tropical ecosystems. [ABSTRACT FROM AUTHOR]

TALAROMYCES, CACAO, FUNGAL growth, NATURAL resources, SOIL pollution, and SOILS

Inorganic pollutants in Colombian cocoa (Theobroma cacao L.) agrosystems cause problems in the production, quality, and exportation of this raw material worldwide. There has been an increased interest in bioprospecting studies of different fungal species focused on the biosorption of heavy metals. Furthermore, fungi constitute a valuable, profitable, ecological, and efficient natural soil resource that could be considered in the integrated management of cadmium mitigation. This study reports a new species of Talaromyces isolated from a cocoa soil sample collected in San Vicente de Chucurí, Colombia. T. santanderensis is featured by Lemon Yellow (R. Pl. IV) mycelium on CYA, mono-to-biverticillade conidiophores, and acerose phialides. T. santanderensis is distinguished from related species by its growth rate on CYAS and powdery textures on MEA, YES and OA, high acid production on CREA and smaller conidia. It is differentiated from T. lentulus by its growth rate on CYA medium at 37 °C without exudate production, its cream (R. PI. XVI) margin on MEA, and dense sporulation on YES and CYA. Phylogenetic analysis was performed using a polyphasic approach, including different phylogenetic analyses of combined and individual ITS, CaM, BenA, and RPB2 gene sequences that indicate that it is new to science and is named Talaromyces santanderensis sp. nov. This new species belongs to the Talaromyces section and is closely related to T. lentulus, T. soli, T. tumuli, and T. pratensis (inside the T. pinophilus species complex) in the inferred phylogeny. Mycelia growth of the fungal strains was subjected to a range of 0–400 mg/kg Cd and incorporated into malt extract agar (MEA) in triplicates. Fungal radial growth was recorded every three days over a 13-day incubation period and In vitro cadmium tolerance tests showed a high tolerance index (0.81) when the mycelium was exposed to 300 mg/kg of Cd. Results suggest that T. santanderensis showed tolerance to Cd concentrations that exceed the permissible limits for contaminated soils, and it is promising for its use in bioremediation strategies to eliminate Cd from highly contaminated agricultural soils. [ABSTRACT FROM AUTHOR]

Background: Congenital hydrocephalus (CH) comprises a heterogeneous group of birth anomalies with a wide‐ranging prevalence across geographic regions and registry type. The aim of the present study was to analyze the early neonatal case fatality rate (CFR) and total birth prevalence of newborns diagnosed with CH. Methods: Data were provided by 25 registries from four continents participating in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) on births ascertained between 2000 and 2014. Two CH rates were calculated using a Poisson distribution: early neonatal CFR (death within 7 days) per 100 liveborn CH cases (CFR) and total birth prevalence rate (BPR) per 10,000 births (including live births and stillbirths) (BPR). Heterogeneity between registries was calculated using a meta‐analysis approach with random effects. Temporal trends in CFR and BPR within registries were evaluated through Poisson regression modeling. Results: A total of 13,112 CH cases among 19,293,280 total births were analyzed. The early neonatal CFR was 5.9 per 100 liveborn cases, 95% confidence interval (CI): 5.4–6.8. The CFR among syndromic cases was 2.7 times (95% CI: 2.2–3.3) higher than among non‐syndromic cases (10.4% [95% CI: 9.3–11.7] and 4.4% [95% CI: 3.7–5.2], respectively). The total BPR was 6.8 per 10,000 births (95% CI: 6.7–6.9). Stratified by elective termination of pregnancy for fetal anomalies (ETOPFA), region and system, higher CFR were observed alongside higher BPR rates. The early neonatal CFR and total BPR did not show temporal variation, with the exception of a CFR decrease in one registry. Conclusions: Findings of early neonatal CFR and total BPR were highly heterogeneous among registries participating in ICBDSR. Most registries with higher CFR also had higher BPR. Differences were attributable to type of registry (hospital‐based vs. population‐based), ETOPFA (allowed yes or no) and geographical regions. These findings contribute to the understanding of regional differences of CH occurrence and early neonatal deaths. [ABSTRACT FROM AUTHOR]

Objective: We aimed to understand the role of the transcriptional co-factor Yes-associated protein (Yap) in the molecular pathway underpinning the pathogenic transformation of synovial fibroblasts (SF) in rheumatoid arthritis (RA) to become invasive and cause joint destruction.Methods: Synovium from patients with RA and mice with antigen-induced arthritis (AIA) was analysed by immunostaining and qRT-PCR. SF were targeted using Pdgfrα-CreER and Gdf5-Cre mice, crossed with fluorescent reporters for cell tracing and Yap-flox mice for conditional Yap ablation. Fibroblast phenotypes were analysed by flow cytometry, and arthritis severity was assessed by histology. Yap activation was detected using Yap-Tead reporter cells and Yap-Snail interaction by proximity ligation assay. SF invasiveness was analysed using matrigel-coated transwells.Results: Yap, its binding partner Snail and downstream target connective tissue growth factor were upregulated in hyperplastic human RA and in mouse AIA synovium, with Yap detected in SF but not macrophages. Lineage tracing showed polyclonal expansion of Pdgfrα-expressing SF during AIA, with predominant expansion of the Gdf5-lineage SF subpopulation descending from the embryonic joint interzone. Gdf5-lineage SF showed increased expression of Yap and adopted an erosive phenotype (podoplanin+Thy-1 cell surface antigen-), invading cartilage and bone. Conditional ablation of Yap in Gdf5-lineage cells or Pdgfrα-expressing fibroblasts ameliorated AIA. Interleukin (IL)-6, but not tumour necrosis factor alpha (TNF-α) or IL-1β, Jak-dependently activated Yap and induced Yap-Snail interaction. SF invasiveness induced by IL-6 stimulation or Snail overexpression was prevented by Yap knockdown, showing a critical role for Yap in SF transformation in RA.Conclusions: Our findings uncover the IL-6-Yap-Snail signalling axis in pathogenic SF in inflammatory arthritis. [ABSTRACT FROM AUTHOR]

Background Sociodemographic and environmental factors are associated with incidence, severity, and mortality of COVID-19. However, little is known about the role of such factors in persisting symptoms among recovering patients. We designed a cohort study of hospitalized COVID-19 survivors to describe persistent symptoms and identify factors associated with post-COVID-19 syndrome. Methods We included patients hospitalized between March to August 2020 who were alive six months after hospitalization. We collected individual and clinical characteristics during hospitalization and at follow-up assessed ten symptoms with standardized scales, 19 yes/no symptoms, a functional status and a quality-of-life scale and performed four clinical tests. We examined individual exposure to greenspace and air pollution and considered neighbourhood's population density and socioeconomic conditions as contextual factors in multilevel regression analysis. Results We included 749 patients with a median follow-up of 200 (IQR = 185-235) days, and 618 (83%) had at least one of the ten symptoms measured with scales. Pain (41%), fatigue (38%) and posttraumatic stress disorder (35%) were the most frequent. COVID-19 severity, comorbidities, BMI, female sex, younger age, and low socioeconomic position were associated with different symptoms. Exposure to ambient air pollution was associated with higher dyspnoea and fatigue scores and lower functional status. Conclusions We identified a high frequency of persistent symptoms among COVID-19 survivors that were associated with clinical, sociodemographic, and environmental variables. These findings indicate that most patients recovering from COVID-19 will need post-discharge care, and an additional burden to health care systems, especially in LMICs, should be expected. [ABSTRACT FROM AUTHOR]

PROSTATE cancer, ANDROGEN deprivation therapy, LABORATORY mice, CANCER genes, TRANSCRIPTION factors, and DIAGNOSIS

Neuroendocrine prostate cancer (NEPC) is a rare but aggressive histologic variant of prostate cancer that responds poorly to androgen deprivation therapy. Hybrid NEPC‐adenocarcinoma (AdCa) tumors are common, often eluding accurate pathologic diagnosis and requiring ancillary markers for classification. We recently performed an outlier‐based meta‐analysis across a number of independent gene expression microarray datasets to identify novel markers that differentiate NEPC from AdCa, including up‐regulation of insulinoma‐associated protein 1 (INSM1) and loss of Yes‐associated protein 1 (YAP1). Here, using diverse cancer gene expression datasets, we show that Hippo pathway‐related genes, including YAP1, are among the top down‐regulated gene sets with expression of the neuroendocrine transcription factors, including INSM1. In prostate cancer cell lines, transgenic mouse models, and human prostate tumor cohorts, we confirm that YAP1 RNA and YAP1 protein expression are silenced in NEPC and demonstrate that the inverse correlation of INSM1 and YAP1 expression helps to distinguish AdCa from NEPC. Mechanistically, we find that YAP1 loss in NEPC may help to maintain INSM1 expression in prostate cancer cell lines and we further demonstrate that YAP1 silencing likely occurs epigenetically, via CpG hypermethylation near its transcriptional start site. Taken together, these data nominate two additional markers to distinguish NEPC from AdCa and add to data from other tumor types suggesting that Hippo signaling is tightly reciprocally regulated with neuroendocrine transcription factor expression. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]