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Cardiovascular risk in non-alcoholic fatty liver disease : Mechanisms and therapeutic implications

New evidence suggests that non-alcoholic fatty liver disease (NAFLD) has a strong multifaceted relationship with diabetes and metabolic syndrome, and is associated with increased risk of cardiovascular events, regardless of traditional risk factors, such as hypertension, diabetes, dyslipidemia, and obesity. Given the pandemic-level rise of NAFLD—in parallel with the increasing prevalence of obesit

Single-Molecule Detection with Lightguiding Nanowires : Determination of Protein Concentration and Diffusivity in Supported Lipid Bilayers

Determining the surface concentration and diffusivity of cell-membrane-bound molecules is central to the understanding of numerous important biochemical processes taking place at cell membranes. Here we use the high aspect ratio and lightguiding properties of semiconductor nanowires (NWs) to detect the presence of single freely diffusing proteins bound to a lipid bilayer covering the NW surface. S

Vertical III-V Nanowire MOSFETs

Vertical III-V nanowire MOSFETs are interesting candidates for future digital and analog applications. High electron velocity III-V materials allow fabrication of low power and high frequency MOSFETs. Vertical vapor-liquid-solid growth enables fabrication of axial and radial heterostructure nanowires. This enables fabrication of novel structures where the band-gap can be engineered in the electron

Macroevolutionary origin and adaptive function of a polymorphic female signal involved in sexual conflict

Intersexual signals that reveal developmental or mating status in females have evolved repeatedly in many animal lineages. Such signals have functions in sexual conflict over mating and can therefore influence sexually antagonistic coevolution. However, we know little about how female signal development modifies male mating harassment and thereby sexual conflict. Here, we combine phylogenetic comp

Lessons learnt from checking the quality of openly accessible river flow data worldwide

Advances in open data science serve large-scale model developments and, subsequently, hydroclimate services. Local river flow observations are key in hydrology but data sharing remains limited due to unclear quality, or to political, economic or infrastructure reasons. This paper provides methods for quality checking openly accessible river-flow time series. Availability, outliers, homogeneity and

Synthesis, spectroscopy and QM/MM simulations of a biomimetic ultrafast light-driven molecular motor

A molecular motor potentially performing a continuous unidirectional rotation is studied by a multidisciplinary approach including organic synthesis, transient spectroscopy and excited state trajectory calculations. A stereogenic center was introduced in the N-alkylated indanylidene-pyrroline Schiff base framework of a previously investigated light-driven molecular switch in order to achieve the u

CDK2 regulates the NRF1/Ehmt1 axis during meiotic prophase I

Meiosis generates four genetically distinct haploid gametes over the course of two reductional cell divisions. Meiotic divisions are characterized by the coordinated deposition and removal of various epigenetic marks. Here we propose that nuclear respiratory factor 1 (NRF1) regulates transcription of euchromatic histone methyltransferase 1 (EHMT1) to ensure normal patterns of H3K9 methylation duri

Metabolic Remodeling during Liver Regeneration

Liver disease is linked to a decreased capacity of hepatocytes to divide. In addition, cellular metabolism is important for tissue homeostasis and regeneration. Since metabolic changes are a hallmark of liver disease, we investigated the connections between metabolism and cell division. We determined global metabolic changes at different stages of liver regeneration using a combination of integrat

Modulation of Protein-Interaction States through the Cell Cycle

Global profiling of protein expression through the cell cycle has revealed subsets of periodically expressed proteins. However, expression levels alone only give a partial view of the biochemical processes determining cellular events. Using a proteome-wide implementation of the cellular thermal shift assay (CETSA) to study specific cell-cycle phases, we uncover changes of interaction states for mo

Thermal proximity coaggregation for system-wide profiling of protein complex dynamics in cells

Proteins differentially interact with each other across cellular states and conditions, but an efficient proteome-wide strategy to monitor them is lacking. We report the application of thermal proximity coaggregation (TPCA) for high-throughput intracellular monitoring of protein complex dynamics. Significant TPCA signatures observed among well-validated protein-protein interactions correlate posit

Premature activation of Cdk1 leads to mitotic events in S phase and embryonic lethality

Cell cycle regulation, especially faithful DNA replication and mitosis, are crucial to maintain genome stability. Cyclin-dependent kinase (CDK)/cyclin complexes drive most processes in cellular proliferation. In response to DNA damage, cell cycle surveillance mechanisms enable normal cells to arrest and undergo repair processes. Perturbations in genomic stability can lead to tumor development and

Dual roles of TRF1 in tethering telomeres to the nuclear envelope and protecting them from fusion during meiosis

Telomeres integrity is indispensable for chromosomal stability by preventing chromosome erosion and end-to-end fusions. During meiosis, telomeres attach to the inner nuclear envelope and cluster into a highly crowded microenvironment at the bouquet stage, which requires specific mechanisms to protect the telomeres from fusion. Here, we demonstrate that germ cell-specific knockout of a shelterin co

Loss of cyclin-dependent kinase 1 impairs bone formation, but does not affect the bone-anabolic effects of parathyroid hormone

Bone mass is maintained by a balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Although recent genetic studies have uncovered various mechanisms that regulate osteoblast differentiation, the molecular basis of osteoblast proliferation remains unclear. Here, using an osteoblast-specific loss-of-function mouse model, we demonstrate that cyclin-dependent kina

The three cytokines IL-1β, IL-18, and IL-1α share related but distinct secretory routes

Interleukin (IL)-1 family cytokines potently regulate inflammation, with the majority of the IL-1 family proteins being secreted from immune cells via unconventional pathways. In many cases, secretion of IL-1 cytokines appears to be closely coupled to cell death, yet the secretory mechanisms involved remain poorly understood. Here, we studied the secretion of the three best-characterized members o

Priors and Posteriors in Bayesian Timing of Divergence Analyses : The Age of Butterflies Revisited

The need for robust estimates of times of divergence is essential for downstream analyses, yet assessing this robustness is still rare. We generated a time-calibrated genus-level phylogeny of butterflies (Papilionoidea), including 994 taxa, up to 10 gene fragments and an unprecedented set of 12 fossils and 10 host-plant node calibration points. We compared marginal priors and posterior distributio

Genetic and pharmacological inhibition of Cdk1 provides neuroprotection towards ischemic neuronal death

Cell cycle proteins are mainly expressed by dividing cells. However, it is well established that these molecules play additional non-canonical activities in several cell death contexts. Increasing evidence shows expression of cell cycle regulating proteins in post-mitotic cells, including mature neurons, following neuronal insult. Several cyclin-dependent kinases (Cdks) have already been shown to