Krogsgaardsamuelsen6816

We show that LINC01119 and SOCS5 exhibit tight correlation across multiple breast cancer gene sets and that they are highly enriched in TNBC patient cohorts. Importantly, we present evidence that the LINC01119-SOCS5 axis represents a powerful prognostic indicator of adverse outcomes in TNBC patients, and demonstrate that its repression severely impairs cancer cell growth. Altogether, our findings identify LINC01119 as a major driver of TNBC development and delineate critical non-coding RNA theranostics of potential translational utility in the management of advanced TNBC, a class of tumors in most need of effective and targeted therapy.A fundamental scientific question concerns the neural basis of perceptual consciousness and perceptual monitoring resulting from the processing of sensory events. Although recent studies identified neurons reflecting stimulus visibility, their functional role remains unknown. Here, we show that perceptual consciousness and monitoring involve evidence accumulation. We recorded single-neuron activity in a participant with a microelectrode in the posterior parietal cortex, while they detected vibrotactile stimuli around detection threshold and provided confidence estimates. We find that detected stimuli elicited neuronal responses resembling evidence accumulation during decision-making, irrespective of motor confounds or task demands. We generalize these findings in healthy volunteers using electroencephalography. Behavioral and neural responses are reproduced with a computational model considering a stimulus as detected if accumulated evidence reaches a bound, and confidence as the distance between maximal evidence and that bound. We conclude that gradual changes in neuronal dynamics during evidence accumulation relates to perceptual consciousness and perceptual monitoring in humans.Maintaining functional stability of microbial electrolysis cell (MEC) treating wastewater depends on maintaining functional redundancy of efficient electroactive bacteria (EAB) on the anode biofilm. Therefore, investigating whether efficient EAB competing for the same resources (electron donor and acceptor) co-exist at the anode biofilm is key for the successful application of MEC for wastewater treatment. Here, we compare the electrochemical and kinetic properties of two efficient acetoclastic EAB, Geobacter sulfurreducens (GS) and Desulfuromonas acetexigens (DA), grown as monoculture in MECs fed with acetate. Additionally, we monitor the evolution of DA and GS in co-culture MECs fed with acetate or domestic wastewater using fluorescent in situ hybridization. The apparent Monod kinetic parameters reveal that DA possesses higher jmax (10.7 ± 0.4 A/m2) and lower KS, app (2 ± 0.15 mM) compared to GS biofilms (jmax 9.6 ± 0.2 A/m2 and KS, app 2.9 ± 0.2 mM). Further, more donor electrons are diverted to the anode for respiration in DA compared to GS. In acetate-fed co-culture MECs, DA (98% abundance) outcompete GS for anode-dependent growth. In contrast, both EAB co-exist (DA 55 ± 2%; GS 24 ± 1.1%) in wastewater-fed co-culture MECs despite the advantage of DA over GS based on kinetic parameters alone. The co-existence of efficient acetoclastic EAB with high current density in MECs fed with wastewater is significant in the context of functional redundancy to maintain stable performance. Our findings also provide insight to future studies on bioaugmentation of wastewater-fed MECs with efficient EAB to enhance performance.Increasing greenhouse gas emissions are likely to impact not only natural systems but economies worldwide. If these impacts alter future economic development, the financial losses will be significantly higher than the mere direct damages. So far, potentially aggravating investment responses were considered negligible. Here we consistently incorporate an empirically derived temperature-growth relation into the simple integrated assessment model DICE. In this framework we show that, if in the next eight decades varying temperatures impact economic growth as has been observed in the past three decades, income is reduced by ~ 20% compared to an economy unaffected by climate change. Hereof ~ 40% are losses due to growth effects of which ~ 50% result from reduced incentive to invest. This additional income loss arises from a reduced incentive for future investment in anticipation of a reduced return and not from an explicit climate protection policy. Under economically optimal climate-change mitigation, however, optimal investment would only be reduced marginally as mitigation efforts keep returns high.Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis.The success of immunotherapy was overshadowed by its low response rate, and the hot or cold tumor microenvironment was reported to be responsible for it. Wnt antagonist However, due to the lack of an appropriate method, it is still a huge challenge for researchers to understand the molecular differences between hot and cold tumor microenvironments. Further research is needed to gain deeper insight into the molecular characteristics of the hot/cold tumor microenvironment. A large-scale clinical cohort and single-cell RNA-seq technology were used to identify the molecular characteristics of inflamed or noninflamed tumors. With single-cell RNA sequencing technology, we provided a novel method to dissect the tumor microenvironment into a hot/cold tumor microenvironment to help us understand the molecular differences between hot and cold tumor microenvironments. Compared with cold tumors, hot tumors highly expressed B cell-related genes, such as MS4A1 and CXCR5, neurogenesis-related miRNA such as MIR650, and immune molecule-related lncRNA such as MIR155HG and LINC00426. In cold tumors, the expression of genes related to multiple biological processes, such as the neural system, was significantly upregulated, and methylome analysis indicated that the promoter methylation level of genes related to neurogenesis was significantly reduced. Finally, we investigated the pan-cancer prognostic value of the cold/hot microenvironment and performed pharmacogenomic analysis to predict potential drugs that may have the potential to convert the cold microenvironment into a hot microenvironment. Our study reveals the multiomics characteristics of cold/hot microenvironments. These molecular characteristics may contribute to the understanding of immune exclusion and the development of microenvironment-targeted therapy.Water scarcity is rapidly spreading across the planet, threatening the population across the five continents and calling for global sustainable solutions. Water reclamation is the most ecological approach for supplying clean drinking water. However, current water purification technologies are seldom sustainable, due to high-energy consumption and negative environmental footprint. Here, we review the cutting-edge technologies based on protein nanofibrils as water purification agents and we highlight the benefits of this green, efficient and affordable solution to alleviate the global water crisis. We discuss the different protein nanofibrils agents available and analyze them in terms of performance, range of applicability and sustainability. We underline the unique opportunity of designing protein nanofibrils for efficient water purification starting from food waste, as well as cattle, agricultural or dairy industry byproducts, allowing simultaneous environmental, economic and social benefits and we present a case analysis, including a detailed life cycle assessment, to establish their sustainable footprint against other common natural-based adsorbents, anticipating a bright future for this water purification approach.Truly sustainable plastics require renewable feedstocks coupled with efficient production and end-of-life degradation/recycling processes. Some of the most useful degradable materials are aliphatic polyesters, polycarbonates and polyamides, which are often prepared via ring-opening (co)polymerisation (RO(CO)P) using an organometallic catalyst. While there has been extensive research into ligand development, heterometallic cooperativity offers an equally promising yet underexplored strategy to improve catalyst performance, as heterometallic catalysts often exhibit significant activity and selectivity enhancements compared to their homometallic counterparts. This review describes advances in heterometallic RO(CO)P catalyst design, highlighting the overarching structure-activity trends and reactivity patterns to inform future catalyst design.Coronavirus disease 2019 (COVID-19) was detected in China during the 2019-2020 seasonal influenza epidemic. Non-pharmaceutical interventions (NPIs) and behavioral changes to mitigate COVID-19 could have affected transmission dynamics of influenza and other respiratory diseases. By comparing 2019-2020 seasonal influenza activity through March 29, 2020 with the 2011-2019 seasons, we found that COVID-19 outbreaks and related NPIs may have reduced influenza in Southern and Northern China and the United States by 79.2% (lower and upper bounds 48.8%-87.2%), 79.4% (44.9%-87.4%) and 67.2% (11.5%-80.5%). Decreases in influenza virus infection were also associated with the timing of NPIs. Without COVID-19 NPIs, influenza activity in China and the United States would likely have remained high during the 2019-2020 season. Our findings provide evidence that NPIs can partially mitigate seasonal and, potentially, pandemic influenza.Muscle stem cell function has been suggested to be regulated by Acetyl-CoA and NAD+ availability, but the mechanisms remain unclear. Here we report the identification of two acetylation sites on PAX7 that positively regulate its transcriptional activity. Lack of PAX7 acetylation reduces DNA binding, specifically to the homeobox motif. The acetyltransferase MYST1 stimulated by Acetyl-CoA, and the deacetylase SIRT2 stimulated by NAD +, are identified as direct regulators of PAX7 acetylation and asymmetric division in muscle stem cells. Abolishing PAX7 acetylation in mice using CRISPR/Cas9 mutagenesis leads to an expansion of the satellite stem cell pool, reduced numbers of asymmetric stem cell divisions, and increased numbers of oxidative IIA myofibers. Gene expression analysis confirms that lack of PAX7 acetylation preferentially affects the expression of target genes regulated by homeodomain binding motifs. Therefore, PAX7 acetylation status regulates muscle stem cell function and differentiation potential to facilitate metabolic adaptation of muscle tissue.