Interference of small compounds and Mg with dsRNA-binding fluorophores compromises the identification of SARS-CoV-2 RdRp inhibitors.

The COVID-19 pandemic highlighted the need for the rapid development of antiviral therapies. Viral RNA-dependent RNA polymerases (RdRp) are promising targets, and numerous virtual screenings for potential inhibitors were conducted without validation of the identified hits. Here we have tested a set of presumed RdRp inhibitors in biochemical assays based on fluorometric detection of RdRp activity or on the electrophoretic separation or RdRp products.

Cholangioscopy-based convoluted neuronal network vs. confocal laser endomicroscopy in identification of neoplastic biliary strictures.

Artificial intelligence (AI) models have demonstrated high diagnostic performance identifying neoplasia during digital single-operator cholangioscopy (DSOC). To date, there are no studies directly comparing AI vs. DSOC-guided probe-base confocal laser endomicroscopy (DSOC-pCLE).

(-)-Epicatechin treatment modify the expression of genes related to atrophy in gastrocnemius muscle of male rats obese by programing.

The aim of this study is to determine if the offspring of mothers with obesity, present disorders in the expression of genes related to atrophy or protein synthesis in the muscle and if these disorders are modified with the (-)-epicatechin (Epi) treatment. Six male offspring group were randomly assigned to the control groups [C and offspring of maternal obesity (MO)] or the Epi intervention groups, Epi treatment for 13 weeks (C + Epi long or MO + Epi long), or Epi administration for two weeks (C + Epi short or MO + Epi short). The effect of Epi in the gastrocnemius tissue was evaluated, analyzing mRNA and protein levels of Murf1, MAFbx, Foxo1, NFkB, and p70S6K-alpha.

A rewiring of DNA replication mediated by MRE11 exonuclease underlies primed-to-naive cell de-differentiation.

Mouse embryonic stem cells (mESCs) in the primed pluripotency state, which resembles the post-implantation epiblast, can be de-differentiated in culture to a naive state that resembles the pre-implantation inner cell mass. We report that primed-to-naive mESC transition entails a significant slowdown of DNA replication forks and the compensatory activation of dormant origins. Using isolation of proteins on nascent DNA coupled to mass spectrometry, we identify key changes in replisome composition that are responsible for these effects.

(-)-epicatechin treatment did not modify the thermogenic pathway in the gastrocnemius muscle of male rat offspring obeses by programming.

The aim of this study was to analyse the expression of genes related to the regulation of energy metabolism in skeletal muscle tissue by comparing male offspring in two age groups [at 110 and 245 postnatal days (pnd)] from a mother with obesity induced by a high-fat diet and (-)-epicatechin (Epi) administration. Four groups of six male offspring from different litters were randomly selected for the control groups [C and offspring of mothers with maternal obesity (MO)] or Epi intervention groups. We evaluated the effect of Epi on gastrocnemius tissue by analysing the mRNA and protein expression levels of Fndc5/irisin, Pgc-1α, Ucp3, and Sln.

RAD51 restricts DNA over-replication from re-activated origins.

Eukaryotic cells rely on several mechanisms to ensure that the genome is duplicated precisely once in each cell division cycle, preventing DNA over-replication and genomic instability. Most of these mechanisms limit the activity of origin licensing proteins to prevent the reactivation of origins that have already been used. Here, we have investigated whether additional controls restrict the extension of re-replicated DNA in the event of origin re-activation.

SIN3A histone deacetylase action counteracts MUS81 to promote stalled fork stability.

During genome duplication, replication forks (RFs) can be stalled by different obstacles or by depletion of replication factors or nucleotides. A limited number of histone post-translational modifications at stalled RFs are involved in RF protection and restart. Provided the recent observation that the SIN3A histone deacetylase complex reduces transcription-replication conflicts, we explore the role of the SIN3A complex in protecting RFs under stressed conditions.

Understanding of the role of serum creatinine in a subset of the Brazilian population.

Introduction: Chronic kidney disease is usually asymptomatic, and its diagnosis depends on laboratory tests, with emphasis on serum creatinine and proteinuria.

Objective: To assess knowledge on the role of serum creatinine as a biomarker of kidney function in a sample of the Brazilian population.

Method: Cross-sectional observational study conducted in São Paulo (SP, Brazil), in which a random adult population was interviewed.

PARP1, DIDO3, and DHX9 Proteins Mutually Interact in Mouse Fibroblasts, with Effects on DNA Replication Dynamics, Senescence, and Oncogenic Transformation.

The regulated formation and resolution of R-loops is a natural process in physiological gene expression. Defects in R-loop metabolism can lead to DNA replication stress, which is associated with a variety of diseases and, ultimately, with cancer. The proteins PARP1, DIDO3, and DHX9 are important players in R-loop regulation.

Uncovering anisotropic effects of electric high-moment dipoles on the tunneling current in [Formula: see text]-layer tunnel junctions.

The precise positioning of dopants in semiconductors using scanning tunneling microscopes has led to the development of planar dopant-based devices, also known as [Formula: see text]layer-based devices, facilitating the exploration of new concepts in classical and quantum computing. Recently, it has been shown that two distinct conductivity regimes (low- and high-bias regimes) exist in [Formula: see text]-layer tunnel junctions due to the presence of quasi-discrete and continuous states in the conduction band of [Formula: see text]-layer systems. Furthermore, discrete charged impurities in the tunnel junction region significantly influence the tunneling rates in [Formula: see text]-layer tunnel junctions.

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Introduction: Oxygen is pivotal for wound healing. Its lack or hypoxia can delay this process, especially in individuals with comorbidities, potentially resulting in complex or hard-to-heal wounds. The Colombian Association of Diabetes (ACD) and the Colombian Association of Internal Medicine (ACMI) collaborated with a diverse group of experts to provide recommendations on the efficacy and best practices of continuous transdermal oxygen therapy (TOTc) in the care of such wounds.

miR-28-based combination therapy impairs aggressive B cell lymphoma growth by rewiring DNA replication.

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive B cell lymphoma and accounts for nearly 40% of cases of B cell non-Hodgkin lymphoma. DLBCL is generally treated with R-CHOP chemotherapy, but many patients do not respond or relapse after treatment. Here, we analyzed the therapeutic potential of the tumor suppressor microRNA-28 (miR-28) for DLBCL, alone and in combination with the Bruton's tyrosine kinase inhibitor ibrutinib.

Development of convolutional neural network models that recognize normal anatomic structures during real-time radial-array and linear-array EUS (with videos).

Background And Aims: EUS is a high-skill technique that requires numerous procedures to achieve competence. However, training facilities are limited worldwide. Convolutional neural network (CNN) models have been previously implemented for object detection.

Variable cardiac responses in rhesus macaque monkeys after discrete mediodorsal thalamus manipulations.

The control of some physiological parameters, such as the heart rate, is known to have a role in cognitive and emotional processes. Cardiac changes are also linked to mental health issues and neurodegeneration. Thus, it is not surprising that many of the brain structures typically associated with cognition and emotion also comprise a circuit-the central automatic network-responsible for the modulation of cardiovascular output.

Usefulness of artificial intelligence-assisted digital single-operator cholangioscopy as a second-opinion consultation tool during interhospital assessment of an indeterminate biliary stricture: a case report.

Video 1Application of a novel digital single-operator cholangioscopy-based convolutional neuronal network to detect neoplastic lesions as a second-opinion consultation tool between 2 hospitals and biopsy sampling.

Distinct beta frequencies reflect categorical decisions.

Based on prior findings of content-specific beta synchronization in working memory and decision making, we hypothesized that beta oscillations support the (re-)activation of cortical representations by mediating neural ensemble formation. We found that beta activity in monkey dorsolateral prefrontal cortex (dlPFC) and pre-supplementary motor area (preSMA) reflects the content of a stimulus in relation to the task context, regardless of its objective properties. In duration- and distance-categorization tasks, we changed the boundary between categories from one block of trials to the next.

Artificial intelligence for diagnosing neoplasia on digital cholangioscopy: development and multicenter validation of a convolutional neural network model.

Background: We aimed to develop a convolutional neural network (CNN) model for detecting neoplastic lesions during real-time digital single-operator cholangioscopy (DSOC) and to clinically validate the model through comparisons with DSOC expert and nonexpert endoscopists.

Methods: In this two-stage study, we first developed and validated CNN1. Then, we performed a multicenter diagnostic trial to compare four DSOC experts and nonexperts against an improved model (CNN2).

Pesticide Residues in Bananas from the Canary Islands.

There are a large number of pests which are detrimental to plant production, specifically to banana cultivation, and the use of pesticides is the main method of control of these pests. Therefore, the number of active substances in pesticides has been steadily increasing since before the Second World War. There is growing consumer concern about the health effects of pesticide residues and there is certainly evidence of a link between pesticide exposure and the prevalence of chronic diseases.

3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.

In mammalian cells, chromosomal replication starts at thousands of origins at which replisomes are assembled. Replicative stress triggers additional initiation events from 'dormant' origins whose genomic distribution and regulation are not well understood. In this study, we have analyzed origin activity in mouse embryonic stem cells in the absence or presence of mild replicative stress induced by aphidicolin, a DNA polymerase inhibitor, or by deregulation of origin licensing factor CDC6.

Conductivity and size quantization effects in semiconductor [Formula: see text]-layer systems.

We present an open-system quantum-mechanical 3D real-space study of the conduction band structure and conductive properties of two semiconductor systems, interesting for their beyond-Moore and quantum computing applications: phosphorus [Formula: see text]-layers and P [Formula: see text]-layer tunnel junctions in silicon. In order to evaluate size quantization effects on the conductivity, we consider two principal cases: nanoscale finite-width structures, used in transistors, and infinitely-wide structures, electrical properties of which are typically known experimentally. For devices widths [Formula: see text] nm, quantization effects are strong and it is shown that the number of propagating modes determines not only the conductivity, but the distinctive spatial distribution of the current-carrying electron states.

Stress-triggered hematopoietic stem cell proliferation relies on PrimPol-mediated repriming.

Stem cell division is linked to tumorigenesis by yet-elusive mechanisms. The hematopoietic system reacts to stress by triggering hematopoietic stem and progenitor cell (HSPC) proliferation, which can be accompanied by chromosomal breakage in activated hematopoietic stem cells (HSCs). However, whether these lesions persist in their downstream progeny and induce a canonical DNA damage response (DDR) remains unclear.

Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage.

Stress-activated protein kinases (SAPKs) enhance survival in response to environmental changes. In yeast, the Hog1 SAPK and Mrc1, a protein required for DNA replication, define a safeguard mechanism that allows eukaryotic cells to prevent genomic instability upon stress during S-phase. Here we show that, in mammals, the p38 SAPK and Claspin-the functional homolog of Mrc1-protect cells from DNA damage upon osmostress during S-phase.

Cortico-thalamocortical interactions for learning, memory and decision-making.

The thalamus and cortex are interconnected both functionally and anatomically and share a common developmental trajectory. Interactions between the mediodorsal thalamus (MD) and different parts of the prefrontal cortex are essential in cognitive processes, such as learning and adaptive decision-making. Cortico-thalamocortical interactions involving other dorsal thalamic nuclei, including the anterior thalamus and pulvinar, also influence these cognitive processes.