Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney.

A gradual decline in renal function occurs even in healthy aging individuals. In addition to aging, per se, concurrent metabolic syndrome and hypertension, which are common in the aging population, can induce mitochondrial dysfunction and inflammation, which collectively contribute to age-related kidney dysfunction and disease. This study examined the role of the nuclear hormone receptors, the estrogen-related receptors (ERRs), in regulation of age-related mitochondrial dysfunction and inflammation.

Posttraumatic stress disorder comorbidity in patients undergoing ECT for major depressive disorder.

Background: Posttraumatic stress disorder (PTSD) is not recognized as an indication for electroconvulsive therapy (ECT). However, research indicates promise for this treatment modality. To elucidate the effects of ECT for treating PTSD, prospective research is needed.

NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease.

Diabetes mellitus is the leading cause of cardiovascular and renal disease in the United -States. Despite the beneficial interventions available for patients with diabetes, there remains a need for additional therapeutic targets and therapies in diabetic kidney disease (DKD). Inflammation and oxidative stress are increasingly recognized as important causes of renal diseases.

Physiological changes during torpor favor association with endosymbionts in the urochordate .

Environmental perturbations evoke down-regulation of metabolism in some multicellular organisms, leading to dormancy, or torpor. Colonies of the urochordate enter torpor in response to changes in seawater temperature and may survive for months as small vasculature remnants that lack feeding and reproductive organs but possess torpor-specific microbiota. Upon returning to milder conditions, the colonies rapidly restore their original morphology, cytology and functionality while harboring re-occurring microbiota, a phenomenon that has not been described in detail to date.

A spatiotemporal ensemble machine learning framework for generating land use/land cover time-series maps for Europe (2000-2019) based on LUCAS, CORINE and GLAD Landsat.

A spatiotemporal machine learning framework for automated prediction and analysis of long-term Land Use/Land Cover dynamics is presented. The framework includes: (1) harmonization and preprocessing of spatial and spatiotemporal input datasets (GLAD Landsat, NPP/VIIRS) including five million harmonized LUCAS and CORINE Land Cover-derived training samples, (2) model building based on spatial k-fold cross-validation and hyper-parameter optimization, (3) prediction of the most probable class, class probabilities and model variance of predicted probabilities per pixel, (4) LULC change analysis on time-series of produced maps. The spatiotemporal ensemble model consists of a random forest, gradient boosted tree classifier, and an artificial neural network, with a logistic regressor as meta-learner.

Transcriptome landscapes that signify Botrylloides leachi (Ascidiacea) torpor states.

Harsh environments enforce the expression of behavioural, morphological, physiological, and reproductive rejoinders, including torpor. Here we study the morphological, cellular, and molecular alterations in torpor architype in the colonial urochordate Botrylloides aff. leachii by employing whole organism Transmission electron (TEM) and light microscope observations, RNA sequencing, real-time polymerase chain reaction (qPCR) quantification of selected genes, and immunolocalization of WNT, SMAD and SOX2 gene expressions.

A defective viral genome strategy elicits broad protective immunity against respiratory viruses.

RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2.

Comparative Genomics Analysis of Repetitive Elements in Ten Gymnosperm Species: "Dark Repeatome" and Its Abundance in Conifer and Species.

Repetitive elements (RE) and transposons (TE) can comprise up to 80% of some plant genomes and may be essential for regulating their evolution and adaptation. The "repeatome" information is often unavailable in assembled genomes because genomic areas of repeats are challenging to assemble and are often missing from final assembly. However, raw genomic sequencing data contain rich information about RE/TEs.

Development of infrastructure for a systemic multidisciplinary approach to study aging in retired sled dogs.

Canines represent a valuable model for mammalian aging studies as large animals with short lifespans, allowing longitudinal analyses within a reasonable time frame. Moreover, they develop a spectrum of aging-related diseases resembling that of humans, are exposed to similar environments, and have been reasonably well studied in terms of physiology and genetics. To overcome substantial variables that complicate studies of privately-owned household dogs, we have focused on a more uniform population composed of retired Alaskan sled dogs that shared similar lifestyles, including exposure to natural stresses, and are less prone to breed-specific biases than a pure breed population.

Intra- and Inter-cellular Modeling of Dynamic Interaction between Zika Virus and Its Naturally Occurring Defective Viral Genomes.

Here, we examine the infection dynamics and interactions of two Zika virus (ZIKV) genomes: one is the full-length ZIKV genome (wild type [WT]), and the other is one of the naturally occurring defective viral genomes (DVGs), which can replicate in the presence of the WT genome, appears under high-MOI (multiplicity of infection) passaging conditions, and carries a deletion encompassing part of the structural and NS1 protein-coding region. Ordinary differential equations (ODEs) were used to simulate the infection of cells by virus particles and the intracellular replication of the WT and DVG genomes that produce these particles. For each virus passage in Vero and C6/36 cell cultures, the rates of the simulated processes were fitted to two types of observations: virus titer data and the assembled haplotypes of the replicate passage samples.

Association of baseline subject characteristics with changes in coronary calcification assessed by F-sodium fluoride PET/CT.

Objective: The goal of this study was to test if changes in coronary microcalcification over a two year period assessed by fluorine-18-sodium fluoride (F-NaF) positron emission tomography/computed tomography (PET/CT) are associated with baseline subject characteristics.

Subjects And Methods: This prospective study included healthy female (N=8, age 52±10 years, body mass index(BMI) 24±1.7kg/m) and male (N=15, age 50±10 years, BMI 27±2.

Genome evolution of blind subterranean mole rats: Adaptive peripatric versus sympatric speciation.

Speciation mechanisms remain controversial. Two speciation models occur in Israeli subterranean mole rats, genus : a regional speciation cline southward of four peripatric climatic chromosomal species and a local, geologic-edaphic, genic, and sympatric speciation. Here we highlight their genome evolution.

An unexpected paradox: wall shear stress in the aorta is less in patients with severe atherosclerosis regardless of obesity.

Background: Obesity is a widespread condition that is more prevalent in Western countries compared to others. Aortic atherosclerosis (AA) is a condition that frequently has been associated with obesity. An obesity paradox, where morbidly obese decedents had either no or minimal AA compared to nonobese decedents, recently has been described by some of us.

Extensive editing of cellular and viral double-stranded RNA structures accounts for innate immunity suppression and the proviral activity of ADAR1p150.

The interferon (IFN)-mediated innate immune response is the first line of defense against viruses. However, an IFN-stimulated gene, the adenosine deaminase acting on RNA 1 (ADAR1), favors the replication of several viruses. ADAR1 binds double-stranded RNA and converts adenosine to inosine by deamination.

Currently and recently used pesticides in Central European arable soils.

Although large amounts of pesticides are used annually and a majority enters the soil to form short- or long-term residues, extensive soil surveys for currently used pesticides (CUPs) are scarce. To determine the status of CUPs' occurrence in arable land in Central Europe, 51 CUPs and 9 transformation products (TPs) were analysed in 75 arable soils in the Czech Republic (CR) several months after the last pesticide application. Moreover, two banned triazines (simazine and atrazine) and their TPs were analysed because of their frequent detection in CR waters.

Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses.

RNA viruses, such as poliovirus, have a great evolutionary capacity, allowing them to quickly adapt and overcome challenges encountered during infection. Here we show that poliovirus infection in immune-competent mice requires adaptation to tissue-specific innate immune microenvironments. The ability of the virus to establish robust infection and virulence correlates with its evolutionary capacity.

The evidence for a microRNA product of human DROSHA gene.

MicroRNAs are short RNA molecules that regulate function and stability of a large subset of eukaryotic mRNAs. In the main pathway of microRNA biogenesis, a short "hairpin" is excised from a primary transcript by ribonuclease DROSHA, followed by additional nucleolytic processing by DICER and inclusion of the mature microRNA into the RNA-induced silencing complex. We report that a microRNA-like molecule is encoded by human DROSHA gene within a predicted stem-loop element of the respective transcript.

FACT is a sensor of DNA torsional stress in eukaryotic cells.

Transitions of B-DNA to alternative DNA structures (ADS) can be triggered by negative torsional strain, which occurs during replication and transcription, and may lead to genomic instability. However, how ADS are recognized in cells is unclear. We found that the binding of candidate anticancer drug, curaxin, to cellular DNA results in uncoiling of nucleosomal DNA, accumulation of negative supercoiling and conversion of multiple regions of genomic DNA into left-handed Z-form.

RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence.

Mutation and recombination are central processes driving microbial evolution. A high mutation rate fuels adaptation but also generates deleterious mutations. Recombination between two different genomes may resolve this paradox, alleviating effects of clonal interference and purging deleterious mutations.

The ethics and regulatory landscape of including vulnerable populations in pragmatic clinical trials.

Policies have been developed to protect vulnerable populations in clinical research, including the US federal research regulations (45 Code of Federal Regulations 46 Subparts B, C, and D). These policies generally recognize vulnerable populations to include pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. The aim has been to protect these populations from harm, often by creating regulatory and ethical checks that may limit their participation in many clinical trials.

Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax.

The blind mole rat (BMR), Spalax galili, is an excellent model for studying mammalian adaptation to life underground and medical applications. The BMR spends its entire life underground, protecting itself from predators and climatic fluctuations while challenging it with multiple stressors such as darkness, hypoxia, hypercapnia, energetics and high pathonecity. Here we sequence and analyse the BMR genome and transcriptome, highlighting the possible genomic adaptive responses to the underground stressors.