Conditional gene targeting of the ENaC subunit genes Scnn1b and Scnn1g

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The cell cycle is a fundamental process in eukaryotic biology and is accordingly controlled by a highly conserved core signaling cascade. However, whether recently evolved proteins also influence this process is unclear. Here, we systematically map the inf ...

The adaptation of organisms to their environment depends on the innovative potential inherent to genetic variation. In complex organisms such as mammals, processes like development and immunity require tight gene regulation. Complex forms emerge more often ...

Analysis of single-cell datasets generated from diverse organisms offers unprecedented opportunities to unravel fundamental evolutionary processes of conservation and diversification of cell types. However, interspecies genomic differences limit the joint ...

Gene regulatory networks (GRNs) play a crucial role in an organism's response to changing environmental conditions. Cellular behaviors typically result from the integration of multiple gene outputs, and their regulation often demands precise control of num ...

Cis-genetic effects are key determinants of transcriptional divergence in discrete tissues and cell types. However, how cis- and trans-effects act across continuous trajectories of cellular differentiation in vivo is poorly understood. Here, we quantify al ...

Lung cancer is the leading cause of cancer-related deaths worldwide and the most common lung cancer subtype is lung adenocarcinoma (LUAD). Frequently mutated genes involve activating mutations in KRAS and loss of function mutations in TP53. LUADs primarily ...

High-throughput transcriptomics is of increasing fundamental biological and clinical interest. The generation of molecular data from large collections of samples, such as biobanks and drug libraries, is boosting the development of new biomarkers and treatm ...

Background: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney,caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpre ...

Infectious agents contribute significantly to the global burden of diseases through both acute infection and their chronic sequelae. We leveraged the UK Biobank to identify genetic loci that influence humoral immune response to multiple infections. From 45 ...

Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is spread by infected ticks or direct contact with blood, tissues and fluids from infected patients or livestock. Infection with CCHFV causes severe haemorrhagic fever in humans which is fatal in up to 83 % of ...

Background Excessive inflammation, hemolysis, and accumulation of labile heme play an essential role in the pathophysiology of multi-organ dysfunction syndrome (MODS) in sepsis. Alpha1-antitrypsin (AAT), an acute phase protein with heme binding capacity, i ...

Long-term consumption of lipid-rich foods can contribute to common metabolic diseases and systemic low-grade inflammation. However, dietary responses and the development of non-communicable diseases are shaped by genetic factors and gene-by-environment int ...

Mutations to gene regulatory networks can be maladaptive or a source of evolutionary novelty. Epistasis con-founds our understanding of how mutations affect the expression patterns of gene regulatory networks, a chal-lenge exacerbated by the dependence of ...

Emerging evidence suggest that transcription factors play multiple roles in the development of pancreatitis, a necroinflammatory condition lacking specific therapy. Estrogen-related receptor γ (ERRγ), a pleiotropic transcription factor, has been reported t ...

Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across the organism remain unclear. Here, we present the Aging Fly Cell Atlas, a single-nucleus transcriptomic map of the whole aging Drosophila. We c ...

Co-expression of two or more genes at the single-cell level is usually associated with functional co-regulation. While mRNA co-expression-measured as the correlation in mRNA levels-can be influenced by both transcriptional and post-transcriptional events, ...

Background: Transposable elements (TEs) have colonized the genomes of most metazoans, and many TE-embedded sequences function as cis-regulatory elements (CREs) for genes involved in a wide range of biological processes from early embryo- genesis to innate ...

The serine proteases CAP1/Prss8 and CAP3/St14 are identified as ENaC channel-activating proteases in vitro, highly suggesting that they are required for proteolytic activation of ENaC in vivo. The present study tested whether CAP3/St14 is relevant for rena ...

BackgroundIt is generally accepted that most evolutionary transformations at the phenotype level are associated either with rearrangements of genomic regulatory elements, which control the activity of gene networks, or with changes in the amino acid conten ...

Regulation of gene expression is a complex but highly guided process. While genomic technologies and computational approaches have allowed high-throughput mapping of cis-regulatory elements (CREs) and their interactions in 3D, their precise role in regulat ...

Conditional gene targeting of the ENaC subunit genes Scnn1b and Scnn1g

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Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles

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Convalescent human plasma candidate reference materials protect against Crimean-Congo haemorrhagic fever virus (CCHFV) challenge in an A129 mouse model

Alpha1-antitrypsin improves survival in murine abdominal sepsis model by decreasing inflammation and sequestration of free heme

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Environment-dependent epistasis increases phenotypic diversity in gene regulatory networks

Upregulation of the ERR γ-VDAC1 axis underlies the molecular pathogenesis of pancreatitis

Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution

Exploring the role of transcriptional and post-transcriptional processes in mRNA co-expression

Statistical learning quantifies transposable element-mediated cis-regulation

Kidney-Specific Membrane-Bound Serine Proteases CAP1/Prss8 and CAP3/St14 Affect ENaC Subunit Abundances but Not Its Activity

Wide-scale identification of novel/eliminated genes responsible for evolutionary transformations

Chromatin modules and their implication in genomic organization and gene regulation