Christieprater9721
Interhospital variation in NICU admissions is mostly driven by admissions for mild diagnoses, suggesting potential overuse.Hippo signalling regulates eye growth during embryogenesis through its effectors YAP and TAZ. Taking advantage of a Yap heterozygous mouse line, we here sought to examine its function in adult neural retina, where YAP expression is restricted to Müller glia. We first discovered an unexpected temporal dynamic of gene compensation. At postnatal stages, Taz upregulation occurs, leading to a gain of function-like phenotype characterised by EGFR signalling potentiation and delayed cell-cycle exit of retinal progenitors. In contrast, Yap+/- adult retinas no longer exhibit TAZ-dependent dosage compensation. In this context, Yap haploinsufficiency in aged individuals results in Müller glia dysfunction, late-onset cone degeneration, and reduced cone-mediated visual response. Alteration of glial homeostasis and altered patterns of cone opsins were also observed in Müller cell-specific conditional Yap-knockout aged mice. Together, this study highlights a novel YAP function in Müller cells for the maintenance of retinal tissue homeostasis and the preservation of cone integrity. It also suggests that YAP haploinsufficiency should be considered and explored as a cause of cone dystrophies in human.The relationships between long-term antibiotic use during early life and mental traits remain elusive now. A total of 158,444 subjects from UK Biobank were used in this study. Linear regression analyses were first conducted to assess the correlations between long-term antibiotic use during early life and mental traits. Gene-environment-wide interaction study (GEWIS) was then performed by PLINK2.0 to detect the interaction effects between long-term antibiotic use during early life and genes on the risks of mental traits. Finally, DAVID tool was used to conduct gene ontology (GO) analysis of the identified genes interacting with long-term antibiotic use during early life. We found negative associations of long-term antibiotic use during early life with remembrance (p value=1.74 × 10-6, b = -0.10) and intelligence (p value=2.64 × 10-26, b = -0.13), and positive associations of long-term antibiotic use during early life with anxiety (p value = 2.75 × 10-47, b = 0.12) and depression (p value=2.01 × 10-195, b = 0.25). GEWIS identified multiple significant genes-long-term antibiotic use during early life interaction effects, such as ANK3 (rs773585997, p value = 1.78 × 10-8) for anxiety and STRN (rs140049205, p value = 1.88 × 10-8) for depression. GO enrichment analysis detected six GO terms enriched in the identified genes interacting with long-term antibiotic use during early life for anxiety, such as GO0030425~dendrite (p value = 3.41 × 10-2) and GO0005886~plasma membrane (p value = 3.64 × 10-3). Our study results suggest the impact of long-term antibiotic use during early life on the development of mental traits.This study evaluates the use of acellular dermal matrix (ADM) in conjunction with negative pressure wound therapy (NPWT) and delayed split-thickness skin graft (STSG) application as an alternative to free tissue transfer for defect coverage of the penile shaft. Five patients with genital lymphedema and one with penile skin deficiency underwent penile shaft reconstruction with a two-stage surgical procedure. The first procedure aimed to the correction of skin defect and to neodermis regeneration through the use of an ADM (Integra®, Integra Lifesciences Corp., Plainsboro, NJ, USA) and NPWT. The second procedure 3 weeks later aimed to the covering of the skin defect with an unmeshed STSG. Both the Integra and skin graft showed completely taking at 7 days postop. No major complications occurred. At 6 months grafts gained sufficient elasticity to allow the sliding of the epidermis over the dermal layer, similarly the physiological penile shaft skin. Our results suggest that combined therapy might be an alternative to free tissue transfer for defect coverage of the penile shaft, leading to a good esthetic result, an optimal shaft coverage and providing adequate extensibility during erections. For best results we advise that in these cases urologists should collaborate with plastic surgeons.DNA methylation can be environmentally modulated and plays a role in phenotypic plasticity. To understand the role of environmentally induced epigenetic variation and its dynamics in natural populations and ecosystems, it is relevant to place studies in a real-world context. Our experimental model is the wild potato Solanum kurtzianum, a close relative of the cultivated potato S. tuberosum. It was evaluated in its natural habitat, an arid Andean region in Argentina characterised by spatial and temporal environmental fluctuations. The dynamics of phenotypic and epigenetic variability (with Methyl Sensitive Amplified Polymorphism markers, MSAP) were assayed in three genotypes across three growing seasons. These genotypes were cultivated permanently and also reciprocally transplanted between experimental gardens (EG) differing in ca. 1000 m of altitude. In two seasons, the genotypes presented differential methylation patterns associated to the EG. In the reciprocal transplants, a rapid epigenomic remodelling occurred according to the growing season. Phenotypic plasticity, both spatial (between EGs within season) and temporal (between seasons), was detected. The epigenetic and phenotypic variability was positively correlated. The lack of an evident mitotic epigenetic memory would be a common response to short-term environmental fluctuations. Thus, the environmentally induced phenotypic and epigenetic variation could contribute to populations persistence through time. These results have implications for understanding the great ecological diversity of wild potatoes.
High probability of metastasis limited the long-term survival of patients with hepatocellular carcinoma (HCC). find more Our previous study revealed that Galectin-3 was closely associated with poor prognosis in HCC patients.
The effects of Galectin-3 on tumour metastasis were investigated in vitro and in vivo, and the underlying biological and molecular mechanisms involved in this process were evaluated.
Galectin-3 showed a close correlation with vascular invasion and poor survival in a large-scale study in HCC patients from multiple sets. Galectin-3 was significantly involved in diverse metastasis-related processes in HCC cells, such as angiogenesis and epithelial-to-mesenchymal transition (EMT). Mechanistically, Galectin-3 activated the PI3K-Akt-GSK-3β-β-catenin signalling cascade; the β-catenin/TCF4 transcriptional complex directly targeted IGFBP3 and vimentin to regulate angiogenesis and EMT, respectively. In animal models, Galectin-3 enhanced the tumorigenesis and metastasis of HCC cells via β-catenin signalling.