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Identifying specific inhibitors of the MYC oncogene has been challenging, due to off target effects associated with MYC inhibition. This study investigated how the recombinant Escherichia coli Lon protease (rLon), which targets MYC in human cells, inhibits MYC over-activation in models of infection and cancer. In silico predictions identified specific peptide domains of bacterial Lon that target M
The formation of a lipid vesicle from a lamellar phase involves a cost in bending energy of 100–1000 times the thermal energy for values of the membrane bending rigidity κ typical for phospholipid bilayers. The bending rigidity of a bilayer is however a strongly decreasing function of its thickness h, and the bilayer can thus reduce its bending energy by stretching (and thus thinning) the bilayer.
Studying how single nucleotide polymorphisms (SNPs) crosstalk with non-autologous factors to cause complex autoimmune diseases is challenging. An amino acid replacement in the neutrophil cytosolic factor 1 (NCF1-339/NCF1R90H) leading to lower reactive oxygen species induction has been reported as the major SNP for systemic lupus erythematosus (SLE). Here we show that infection with the murine noro
Musculoskeletal disorders are a significant public health burden concern, projected to increase in the coming decades, and will substantially contribute to the rising prevalence of functional impairment, frailty and disability in a growing global population. Since persons with musculoskeletal disorders tend to have immune dysfunction, inflammation or be taking immunosuppressive medication, prevent
Developing accurate large-scale drought prediction models is challenging due to the complex temporal and spatial correlation patterns that govern drought dynamics, as well as the compounding effects of anthropogenic activities and global climate change. Although recent advances in deep learning have yielded effective drought prediction models, many struggle to fully capture the heterogeneous spati
Purpose: Incisional hernia (IH) after open liver surgery is a well-recognized complication. The clinical importance of IH detected on computed tomography in terms of objective abdominal wall discomfort and impairment of quality of life (QoL) is less well known. Methods: Patients who underwent curative surgery for colorectal liver metastases between 2010 and 2015 at a single center and were alive i
IntroductionThe ESCAPER project explores cardiovascular resilience in individuals who, despite a high-risk factor burden-longstanding Type 1 Diabetes (T1D), obesity, or kidney failure-avoid or delay macrovascular complications. This suggests underlying protective mechanisms. Initiated in September 2022, this exploratory study aims to uncover and define these mechanisms, potentially leading to nove
The application of Agent-Based Modeling and Simulation (ABMS) has few established guidelines and often suffers from insufficient model documentation. We assess the prevalence of best practices associated with different types of model documentation in light of the European Union’s AI Act (AI Act). Our analysis reveals that best practices are often implemented together but ultimately reinforce the p
The Ordovician of Scandinavia (i.e. Denmark, Norway and Sweden) has been investigated for over two centuries and, through time, various chronostratigraphic schemes have been introduced, facilitating regional correlation. However, a modern chronostratigraphy has never been proposed. Here, we delineate ten regional stages for the Ordovician of Scandinavia, comprising, in ascending order, the Slemmes
We introduce the point process [Formula presented] where Zn is the normalization constant. This point process is attractive: it involves n dependent, uniformly distributed random variables on the unit circle that attract each other. (For comparison, the well-studied CβE involves n uniformly distributed random variables on the unit circle that repel each other.) We consider linear statistics of the
Background & aims: We have previously reported that the serum levels of gut-derived tryptophan metabolite indole-3-propionic acid (IPA) are lower in individuals with liver fibrosis. Now, we explored the transcriptome and DNA methylome associated with serum IPA levels in human liver from obese individuals together with IPA effects on shifting the hepatic stellate cell (HSC) phenotype to inactiv
Slow sand filters (SSFs) for drinking water production are habitats for diverse microbes from multiple domains of life, which are integral to the ability of SSFs to purify water. While cultivation-independent analyses of the prokaryotic communities of SSFs have provided valuable insights, little attention has been paid to fungi inhabiting SSFs. This study characterized the fungal communities in th
Platform trials have become widely adopted across multiple disease areas over recent years, however, guidelines for operationalising these trials have not kept pace. We outline a series of documents that summarise the statistical components, and implicit processes, of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial to provide an informal template for other researchers and reviewer
Purpose: Defunctioning stoma (DS) has been suggested to mitigate the consequences of anastomotic leak (AL) after low anterior resection. Stoma reversal (SR) is commonly delayed for nonmedical reasons in many healthcare systems. This study investigated the impact of the elapsed time from AR to SR on postoperative 90-day complications. The secondary aim was to explore the independent factors associa
The membranous ER spans the entire cell, creating a network for the biosynthesis of proteins and lipids, cell-wide communication, and nuclear delivery of molecules, including therapeutic agents. Here, we identify a novel ER response triggered by the tumoricidal complex alpha1-oleate, defined by a loss of peripheral ER structure, extensive ER vesiculation. Alpha1-oleate was present in the ER-derive
Using detailed hand-collected data on firm ownership and board cultural diversity from Sweden, we find that foreign ownership is positively associated with board cultural diversity. This relationship is not an artifact of foreign owners joining the board, and it is not driven by firms with substantial foreign focus. The presence of foreign owners on nomination committees seems to be the channel th
Background: Despite recent advances in neuroimaging and neurocritical care, severe traumatic brain injury (TBI) is still a major cause of severe disability and mortality, with increasing incidence worldwide. Antisecretory factor (AF), commercially available as Salovum®, has been shown to lower intracranial pressure (ICP) in experimental models of, e.g., TBI and herpes encephalitis. The aim of this
Objective: Exercise is a first-line intervention for osteoarthritis (OA). However, exercise adherence remains low, and existing studies exploring factors influencing adherence have yielded inconclusive results based on quantitative data. This study aims to synthesise qualitative studies focused on the perceived facilitators and barriers affecting exercise adherence in individuals with OA. Design:
In this work we present a simultaneous shape and topology optimization framework that generates large-scale 3D designs on unstructured grids. We consider a “parameter-free” shape optimization approach, wherein the nodal coordinates in the finite element mesh serve as design variables. To regularize the design changes we use a PDE-based filter, similar to the filtering techniques used in topology o
