Danielsenborup2879

Extracellular vesicles (EVs) including exosomes act as intercellular communicators by transferring protein and microRNA cargoes, yet the role of EV lipids remains unclear. Here, we show that the pro-tumorigenic action of lymphoma-derived EVs is augmented via secreted phospholipase A2 (sPLA2)-driven lipid metabolism. Hydrolysis of EV phospholipids by group X sPLA2, which was induced in macrophages of Epstein-Barr virus (EBV) lymphoma, increased the production of fatty acids, lysophospholipids, and their metabolites. sPLA2-treated EVs were smaller and self-aggregated, showed better uptake, and increased cytokine expression and lipid mediator signaling in tumor-associated macrophages. Pharmacological inhibition of endogenous sPLA2 suppressed lymphoma growth in EBV-infected humanized mice, while treatment with sPLA2-modified EVs reversed this phenotype. Furthermore, sPLA2 expression in human large B cell lymphomas inversely correlated with patient survival. Overall, the sPLA2-mediated EV modification promotes tumor development, highlighting a non-canonical mechanistic action of EVs as an extracellular hydrolytic platform of sPLA2.The epigenetic process of genomic imprinting results in the monoallelic expression of genes based on their parental origin. Comparative analysis of imprinted genes between species is useful for investigating the biological significance and regulatory mechanisms of genomic imprinting. Mouse Impact is an imprinted gene, but its human ortholog IMPACT escapes genomic imprinting. Hrh4 and Osbpl1a are the two nearest neighbors of the Impact located in distal and proximal regions, respectively. This study aims to assess the allelic expression of bovine IMPACT, OSBPL1A and HRH4 genes and examine the differentially methylated regions (DMRs) associated with these three genes. Based on an expressed single-nucleotide polymorphism (SNP) approach, we found that both the IMPACT and OSBPL1A genes exhibit isoform-specific monoallelic expression in bovine adult tissues. In the seven detected bovine IMPACT transcripts, only one transcript variant (X6) is monoallelically expressed in bovine adult tissues and paternally expressed in the placenta. However, no DMR was found in the promoter region of the IMPACT gene. We obtained five transcript variants (V1-V5) of the bovine OSBPL1A gene of different lengths that start transcription from distinct alternative promoters by RT-PCR. Only the longest variant V1 was found to be expressed monoallelically in bovine adult tissues and a DMR was identified in its promoter region using the bisulfite sequencing method. Thus, the DMR in OSBPL1A V1 promoter region may contribute to its isoform-specific monoallelic expression. The bovine HRH4 gene is expressed biallelically. Hypermethylation was observed in brains without HRH4 expression, while hypomethylation was found in the spleens with HRH4 expression, so and the level of DNA methylation in the promoter seemed to be related to its expression in tissues.

Anorexia nervosa is a serious illness leading to substantial morbidity and mortality. The Anorexia Nervosa Treatment of Outpatients (ANTOP) study is the largest randomised controlled trial (RCT) globally that uses psychotherapy in outpatients with anorexia nervosa. In this Article, we report the results of the 5-year follow-up.

The ANTOP study is an open-label, multicentre RCT involving 242 adult female outpatients with anorexia nervosa. Participants were recruited from ten university hospitals in Germany, had to be aged at least 18 years and female, and have a diagnosis of anorexia nervosa with a body-mass index (BMI) of 15·0-18·5 kg/m

. Participants were randomly allocated (111) to 10 months of treatment with focal psychodynamic therapy, enhanced cognitive behaviour therapy, or optimised treatment as usual; complete masking of the participants was not possible. The mean duration of the follow-up was 5·96 years (SD 0·2) after randomisation. The primary outcome was change in BMI from baseline at the end h a clear focus on weight gain and considering other comorbidities (especially depression).

German Federal Ministry of Education and Research.

German Federal Ministry of Education and Research.Transmembrane β barrel proteins are folded into the outer membrane (OM) of Gram-negative bacteria by the β barrel assembly machinery (BAM) via a poorly understood process that occurs without known external energy sources. Here, we used single-particle cryo-EM to visualize the folding dynamics of a model β barrel protein (EspP) by BAM. We found that BAM binds the highly conserved "β signal" motif of EspP to correctly orient β strands in the OM during folding. We also found that the folding of EspP proceeds via "hybrid-barrel" intermediates in which membrane integrated β sheets are attached to the essential BAM subunit, BamA. The structures show an unprecedented deflection of the membrane surrounding the EspP intermediates and suggest that β sheets progressively fold toward BamA to form a β barrel. Along with in vivo experiments that tracked β barrel folding while the OM tension was modified, our results support a model in which BAM harnesses OM elasticity to accelerate β barrel folding.G protein-coupled receptors (GPCRs) relay extracellular stimuli into specific cellular functions. Cells express many different GPCRs, but all these GPCRs signal to only a few second messengers such as cAMP. It is largely unknown how cells distinguish between signals triggered by different GPCRs to orchestrate their complex functions. Here, we demonstrate that individual GPCRs signal via receptor-associated independent cAMP nanodomains (RAINs) that constitute self-sufficient, independent cell signaling units. Low concentrations of glucagon-like peptide 1 (GLP-1) and isoproterenol exclusively generate highly localized cAMP pools around GLP-1- and β2-adrenergic receptors, respectively, which are protected from cAMP originating from other receptors and cell compartments. Mapping local cAMP concentrations with engineered GPCR nanorulers reveals gradients over only tens of nanometers that define the size of individual RAINs. The coexistence of many such RAINs allows a single cell to operate thousands of independent cellular signals simultaneously, rather than function as a simple "on/off" switch.Based on claims that dogs are less aggressive and show more sophisticated socio-cognitive skills compared with wolves, dog domestication has been invoked to support the idea that humans underwent a similar 'self-domestication' process. Here, we review studies on wolf-dog differences and conclude that results do not support such claims dogs do not show increased socio-cognitive skills and they are not less aggressive than wolves. Rather, compared with wolves, dogs seek to avoid conflicts, specifically with higher ranking conspecifics and humans, and might have an increased inclination to follow rules, making them amenable social partners. These conclusions challenge the suitability of dog domestication as a model for human social evolution and suggest that dogs need to be acknowledged as animals adapted to a specific socio-ecological niche as well as being shaped by human selection for specific traits.The COVID-19 pandemic has changed forever how we plan, respond to, and deliver health care. The lived experience of hospital infrastructure design to support a pandemic is currently not well described in the literature. Much of what is known covers generic elements of hospital design and/or assumptions about in-built disaster design features. The Central Adelaide Local Health Network became a key stakeholder in South Australia's response when the Royal Adelaide Hospital (RAH) became the designated receiving hospital for the state. Preparation for a pandemic commenced back in 2007 when a new build for the RAH was announced. Several disaster response infrastructure design features were incorporated into the RAH design specifications to provide a resilient facility that could respond to any type of disaster event while continuing to provide core clinical services. Key pandemic design elements included patient room design, pandemic air handling capability, and a 7-step scalability function. We describe these key elements based on real-time experience along with the key lessons learnt as the pandemic response evolved with the aim of guiding future hospital building design to not only support the more frequent time-limited disasters but, more specifically, a pandemic response. The RAH capitalised on its key design features to support its pandemic response and contributed to the overall success of South Australia's pandemic response.Introduction Intensive care unit telemedicine (ICU-TM) is expanding due to increasing demands for critical care, but impact on outcomes remains controversial. This study evaluated the association of ICU-TM and other clinical factors with 30-day, in-hospital mortality. Methods This retrospective, cohort study included 151,780 consecutive ICU patients admitted to nine hospitals in the Cleveland Clinic Health System from 2010 to 2020. Patients were identified from an institutional datamart and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) registry. Primary outcome was 30-day in-hospital mortality. Analyses included multivariate logistic regression modeling, and survival analysis. Results Overall, unadjusted 30-day, in-hospital mortality incidence was significantly different with (5.6%) or without ICU-TM (7.2%), and risk ratio was 0.78 (95% confidence interval [CI] 0.75-0.81) (p less then 0.0001). Mortality rate for ICU-TM and no ICU-TM was 2.4/1,000 versus 3.2/1,000 patient days, respectively (p less then 0.0001). Multivariate logistic regression showed that ICU-TM was associated with reduced 30-day mortality (odds ratio 0.78, 95% CI 0.72-0.83). Increased risk was seen with cardiac arrest admissions, males, acute stroke, weekend admission, emergency admission, race (non-white), sepsis, APACHE IV score, ICU length of stay (LOS), and the interaction term, emergency surgical admissions. Reduced risk was associated with hospital LOS, surgical admission, and the interaction terms (weekend admissions with ICU-TM and after-hour admissions with ICU-TM). The model c-statistic was 0.77. https://www.selleckchem.com/products/dl-thiorphan.html Median ICU and hospital lengths of stay were significantly reduced with ICU-TM, with no difference in 48-h mortality or 48-h mortality rate. Conclusion ICU telemedicine exposure appears to be one of several operational and clinical factors associated with reduced 30-day, in-hospital mortality.Based on one-year's ethnographic fieldwork, this article unpacks experiences of assisted reproductive technology (ART) among queer parents and queer wannabe parents in Guangdong, China. Although existing state regulation on the use of ART and birth planning tends to deny parenthood to single and queer people and further limits their ability to form legible family units, queer parents who have had children through ART are growing in number in urban China. This research delineates how state and cultural conventions, together with market and economic conditions, have shaped queer individuals' decision making regarding whether, when and how to have children. Findings make an original contribution to studies of the use of reproductive technology in Chinese queer lives. Narratives regarding how queer parents employ ART services unscramble links between sexual citizenship and reproductive agency, as individuals make consumer choices and reproductive decisions synchronously. The paper also explores alleged LGBT-friendly ART companies and the image of a desirable 'rainbow baby' they have created.