Leveraging large-scale multi-omics evidences to identify therapeutic targets from genome-wide association studies.

Background: Therapeutic targets supported by genetic evidence from genome-wide association studies (GWAS) show higher probability of success in clinical trials. GWAS is a powerful approach to identify links between genetic variants and phenotypic variation; however, identifying the genes driving associations identified in GWAS remains challenging. Integration of molecular quantitative trait loci (molQTL) such as expression QTL (eQTL) using mendelian randomization (MR) and colocalization analyses can help with the identification of causal genes.

History and genetic diversity of African sheep: Contrasting phenotypic and genomic diversity.

Domesticated sheep have adapted to contrasting and extreme environments and continue to play important roles in local community-based economies throughout Africa. Here we review the Neolithic migrations of thin-tailed sheep and the later introductions of fat-tailed sheep into eastern Africa. According to contemporary pictorial evidence, the latter occurred in Egypt not before the Ptolemaic period (305-25 BCE).

Widespread Misinterpretation of p Terminology for Zwitterionic Compounds and Its Consequences.

The acid dissociation constant (p), which quantifies the propensity for a solute to donate a proton to its solvent, is crucial for drug design and synthesis, environmental fate studies, chemical manufacturing, and many other fields. Unfortunately, the terminology used for describing acid-base phenomena is sometimes inconsistent, causing large potential for misinterpretation. In this work, we examine a systematic confusion underlying the definition of "acidic" and "basic" p values for zwitterionic compounds.

Comparative thermo- and piezostability study of photosynthetic core complexes containing bacteriochlorophyll a or b.

The resilience of biological systems to fluctuating environmental conditions is a crucial evolutionary advantage. In this study, we examine the thermo- and piezo-stability of the LH1-RC pigment-protein complex, the simplest photosynthetic unit, in three species of phototropic purple bacteria, each containing only this core complex. Among these species, Blastochloris viridis and Blastochloris tepida utilize bacteriochlorophyll b as the main light-harvesting pigment, while Rhodospirillum rubrum relies on bacteriochlorophyll a.

Virus-bacterium interaction involved in element cycles in biological treatment of coking wastewater.

Although prokaryotic microbes in coking wastewater (CWW) treatment have been comprehensively studied, the ecological functions of viruses remain unclear. A full-scale CWW biological treatment AOHO combination was studied for the virus-bacterium interactions involved in element cycles by metaviromics, metagenomics and physicochemical characteristics. Results showed the unique viromic profile with Cirlivirales and Petitvirales as the dominant viruses infecting functional bacteria hosts.

Attenuated Getah virus confers protection against multiple arthritogenic alphaviruses.

Alphaviruses are important arthropod-transmitted pathogens of humans and livestock. Getah virus (GETV) is an arthritogenic alphavirus that causes disease in horses and piglets; it also poses a potential threat to humans. A live attenuated vaccine candidate named GETV-3ΔS2-CM1, harbouring a deletion in nonstructural protein 3 and substitutions in the capsid protein, is genetically stable and exhibits robust immunogenicity.

Temporal change in minimum mortality temperature under changing climate: A multicountry multicommunity observational study spanning 1986-2015.

Background: The minimum mortality temperature (MMT) or MMT percentile (MMTP) is an indicator of population susceptibility to nonoptimum temperatures. MMT and MMTP change over time; however, the changing directions show region-wide heterogeneity. We examined the heterogeneity of temporal changes in MMT and MMTP across multiple communities and in multiple countries.

Incidence of post-acute COVID-19 symptoms across healthcare settings in seven countries: an international retrospective cohort study using routinely-collected data.

Background: The World Health Organisation (WHO) has identified a range of symptomatic manifestations to aid in the clinical diagnosis of post-COVID conditions, herein referred to as post-acute COVID-19 symptoms. We conducted an international network cohort study to estimate the burden of these symptoms in North American, European, and Asian populations.

Methods: A federated analysis was conducted including 10 databases from the United Kingdom, Netherlands, Norway, Estonia, Spain, France, South Korea, and the United States, between September 1st 2020 and latest data availability (which varied from December 31st 2021 to February 28th 2023), covering primary and secondary care, nationwide registries, and claims data, all mapped to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM).

Exploring the anti-inflammatory effects of curcumin encapsulated within ferritin nanocages: a comprehensive in vivo and in vitro study in Alzheimer's disease.

Background: The global demographic shift towards an aging population is generating a rise in neurodegenerative conditions, with Alzheimer's disease (AD) as the most prominent problem. In this landscape, the use of natural supplements has garnered attention for their potential in dementia prevention. Curcumin (Cur), derived from Curcuma longa, has demonstrated promising pharmacological effects against AD by reducing the levels of inflammatory mediators.

Ecological intensification index: reducing global footprint of agriculture.

Because of the growing human population, increasing agricultural yields is becoming increasingly more important. However, various environmental crises have led society to demand a reduction in the environmental damage caused by agriculture. Until now, the economic and ecological aspects of plant cultivation have developed largely independently.

Comparison of the activity of two elastin-like recombinant carriers fused to the antimicrobial peptide indolicidin.

Recombinant fusion biotechnology is a powerful tool for producing antimicrobial peptides (AMPs), which can contribute to limiting the number of potentially infectious microorganisms. AMPs are often expressed in fusion with a carrier protein, a strategy that prevents toxic effects on host bacterial cells and protects them from proteolytic degradation. Among the many fusion carriers available, elastin-like polypeptides offer several valuable advantages related to their unique thermo-responsive behavior.

A new species of the Trichia botrytis complex from the cloud forest in Ecuador.

The paper describes a new myxomycete species, Trichia tuberculata, from the Ecuadorian cloud forest. The phylogeny constructed with nuclear 18S rDNA and mitochondrial 17S rDNA sequences indicates that the taxon is closely related to recently described species T. acetocorticola, T.

Correction: Psychological Safety Competency Training During the Clinical Internship From the Perspective of Health Care Trainee Mentors in 11 Pan-European Countries: Mixed Methods Observational Study.

[This corrects the article DOI: 10.2196/64125.].

The phenotypic spectrum of deficiency.

The gene product (protein PTCD3 or MRPS39) forms the entry channel of the mitochondrial small ribosomal subunit and binds to single-stranded mRNA. Here, we expand on the clinical manifestations of pathogenic variants by describing an early-onset patient with Leigh-like syndrome and two patients with milder form of disease, with combined oxidative phosphorylation deficiency. A 34-year-old male and his 33-year-old sister both have horizontal nystagmus, pronounced rough tremor, truncal ataxia, dysmetria, spasticity and hyperreflexia.

The last decade of air pollution epidemiology and the challenges of quantitative risk assessment.

Epidemiologic research and quantitative risk assessment play a crucial role in transferring fundamental scientific knowledge to policymakers so they can take action to reduce the burden of ambient air pollution. This commentary addresses several challenges in quantitative risk assessment of air pollution that require close attention. The background to this discussion provides a summary of and conclusions from the epidemiological evidence on ambient air pollution and health outcomes accumulated since the 1990s.

Fecal microbial load is a major determinant of gut microbiome variation and a confounder for disease associations.

The microbiota in individual habitats differ in both relative composition and absolute abundance. While sequencing approaches determine the relative abundances of taxa and genes, they do not provide information on their absolute abundances. Here, we developed a machine-learning approach to predict fecal microbial loads (microbial cells per gram) solely from relative abundance data.

Glaciation of liquid clouds, snowfall, and reduced cloud cover at industrial aerosol hot spots.

The ability of anthropogenic aerosols to freeze supercooled cloud droplets remains debated. In this work, we present observational evidence for the glaciation of supercooled liquid-water clouds at industrial aerosol hot spots at temperatures between -10° and -24°C. Compared with the nearby liquid-water clouds, shortwave reflectance was reduced by 14% and longwave radiance was increased by 4% in the glaciation-affected regions.

PharmFreq: a comprehensive atlas of ethnogeographic allelic variation in clinically important pharmacogenes.

Genetic polymorphisms in drug metabolizing enzymes, drug transporters as well as in genes encoding the human major histocompatibility complex contribute to inter-individual differences in drug efficacy and safety. The extent, pattern and complexity of such pharmacogenetic variation differ drastically across human populations. Here, we present PharmFreq, a global repository of pharmacogenetic frequency information that aggregates frequency data of 658 allelic variants from over 10 million individuals collected from >1200 studies across 144 countries.

In vitro impacts of glyphosate on manatee lymphocytes.

Exposure to contaminants, such as the herbicide glyphosate, can suppress protective immune functions. Glyphosate is the herbicide most used worldwide and has been found in the plasma of more than 50 % of the Florida manatees (Trichechus manatus latirostris) and all-year-round in their aquatic environment. Our objectives were to analyze the consequences of glyphosate exposure on their immune responses via T-lymphocyte proliferation assays and transcriptomics.

Prognostic significance of gastrointestinal dysfunction in critically ill patients with COVID-19.

Objective: To analyze in-hospital and 1-year morbidity and mortality associated with acute gastrointestinal dysfunction in critically ill patients with COVID-19 via a prespecified scoring system.

Methods: Between March and July 2020, consecutive hospitalized patients with COVID-19 from a single institution were retrospectively analyzed by medical chart review. Only those who remained in the intensive care unit for more than 24 hours were included.

Toxic small alarmone synthetase FaRel2 inhibits translation by pyrophosphorylating tRNA and tRNA.

Translation-targeting toxic small alarmone synthetases (toxSAS) are effectors of bacterial toxin-antitoxin systems that pyrophosphorylate the 3'-CCA end of transfer RNA (tRNA) to prevent aminoacylation. toxSAS are implicated in antiphage immunity: Phage detection triggers the toxSAS activity to shut down viral production. We show that the toxSAS FaRel2 inspects the tRNA acceptor stem to specifically select tRNA and tRNA.

The final plague outbreak in Scotland 1644-1649: Historical, archaeological, and genetic evidence.

This paper has several aims: to determine if Yersinia pestis was the causative agent in the last Scottish plague outbreak in the mid-17th century; map the geographic spread of the epidemic and isolate potential contributing factors to its spread and severity; and examine funerary behaviours in the context of a serious plague epidemic in early modern Scotland. Results confirm the presence of Y. pestis in individuals associated with a mid-17th century plague pit in Aberdeen.

Evaluation of an Active Rehabilitation Program With Early Weightbearing and No Immobilization After Tibial Tubercle Distalization.

Background: Abnormal patellar height (patella alta) has been reported to be one of the main predisposing factors for recurrent patellar dislocation, and it can be surgically corrected by distalizing tibial tubercle osteotomy (DTTO). Rehabilitation after DTTO often includes limitations on weightbearing and restrictions on knee range of motion by means of bracing, increasing the risk of slow progression of the rehabilitation.

Hypothesis: An active rehabilitation program with no restrictions on weightbearing and range of movement would yield a low risk of postoperative complications and a fast recovery period.