Do coping mechanisms moderate the effect of stressful life events on depression and anxiety in young people? A case-control study from Latin America.

Background: Stressful life events (SLEs) are associated with increased risk of depression or anxiety. Coping mechanisms may moderate this relationship but little is known on this topic in young people or in Latin America.

Aim: To investigate whether coping strategies predict odds of depression and/or anxiety and moderate the relationship between SLEs and depression and/or anxiety in young people in Peru, Lima and Bogotá.

Salidroside and exercise performance in healthy active young adults - an exploratory, randomized, double-blind, placebo-controlled study.

Background: Rhodiola rosea extract is purported to improve physical performance and support resilience to stress. Salidroside is considered to be one of the main constituents responsible for the ergogenic actions of R. rosea.

Evaluating the Effectiveness of Indigenous Health Curricula: Validation and Application of the NOSM CAST Instrument.

Objectives: In recent years, Indigenous health curricula have been integrated into medical education in response to international calls to improve Indigenous health care. Instruments to evaluate Indigenous health education are urgently needed. We set out to validate a tool to measure self-reported medical student preparedness to provide culturally safe care to Indigenous Peoples.

Variant load of mitochondrial DNA in single human mesenchymal stem cells.

Heteroplasmic mitochondrial DNA (mtDNA) variants accumulate as humans age, particularly in the stem-cell compartments, and are an important contributor to age-related disease. Mitochondrial dysfunction has been observed in osteoporosis and somatic mtDNA pathogenic variants have been observed in animal models of osteoporosis. However, this has never been assessed in the relevant human tissue.

Relationships of mitochondrial DNA mutations and select clinical diagnoses in perinatally HIV- and ART-exposed uninfected children.

The prevalence of pathogenic mutations within mitochondrial (mt) DNA of youth who were perinatally exposed to HIV and ART but remained uninfected (YHEU) were assessed relative to phenotypic clinical indicators of mitochondrial dysfunction (MtD). This was a cross-sectional, nested case-control study. A total of 144 cases met at least one clinical MtD definition and were matched with up to two controls each (n = 287).

Verazine biosynthesis from simple sugars in engineered Saccharomyces cerevisiae.

Steroidal alkaloids are FDA-approved drugs (e.g., Zytiga) and promising drug candidates/leads (e.

Nanobiopsy investigation of the subcellular mtDNA heteroplasmy in human tissues.

Mitochondrial function is critical to continued cellular vitality and is an important contributor to a growing number of human diseases. Mitochondrial dysfunction is typically heterogeneous, mediated through the clonal expansion of mitochondrial DNA (mtDNA) variants in a subset of cells in a given tissue. To date, our understanding of the dynamics of clonal expansion of mtDNA variants has been technically limited to the single cell-level.

A systematic review of pharmacogenetic testing to guide antipsychotic treatment.

Pharmacogenomics could optimize antipsychotic treatment by preventing adverse drug reactions, improving treatment efficacy or relieving the cost burden on the healthcare system. Here we conducted a systematic review to investigate whether pharmacogenetic testing in individuals undergoing antipsychotic treatment influences clinical or economic outcomes. On 12 January 2024, we searched MEDLINE, EMBASE, PsycINFO and Cochrane Centrale Register of Controlled Trials.

Discovery of Borosin Catalytic Strategies and Function through Bioinformatic Profiling.

Borosins are ribosomally synthesized and post-translationally modified peptides (RiPPs) containing backbone α--methylations. These modifications confer favorable pharmacokinetic properties including increased membrane permeability and resistance to proteolytic degradation. Previous studies have biochemically and bioinformatically explored several borosins, revealing (1) numerous domain architectures and (2) diverse core regions lacking conserved sequence elements.

Engineered as a Biosynthetic Platform of Nucleotide Sugars.

Glycosylation of biomolecules can greatly alter their physicochemical properties, cellular recognition, subcellular localization, and immunogenicity. Glycosylation reactions rely on the stepwise addition of sugars using nucleotide diphosphate (NDP)-sugars. Making these substrates readily available will greatly accelerate the characterization of new glycosylation reactions, elucidation of their underlying regulation mechanisms, and production of glycosylated molecules.

Computationally guided exploration of borosin biosynthetic strategies.

Borosins are ribosomally synthesized and post-translationally modified peptides containing backbone α- -methylations. Identification of borosin precursor peptides is difficult because (1) there are no conserved sequence elements among borosin precursor peptides and (2) the biosynthetic gene clusters contain numerous domain architectures and peptide fusions. To tackle this problem, we updated the genome mining tool RODEO to automatically evaluate putative borosin BGCs and identify precursor peptides.

Early-stage idiopathic Parkinson's disease is associated with reduced circular RNA expression.

Neurodegeneration in Parkinson's disease (PD) precedes diagnosis by years. Early neurodegeneration may be reflected in RNA levels and measurable as a biomarker. Here, we present the largest quantification of whole blood linear and circular RNAs (circRNA) in early-stage idiopathic PD, using RNA sequencing data from two cohorts (PPMI = 259 PD, 161 Controls; ICICLE-PD = 48 PD, 48 Controls).

From Cullowhee Creek to Conley: genome sequence and annotation of a cluster DJ phage.

We report the discovery of phage Conley, a siphovirus isolated from Cullowhee Creek in the Fall of 2022. The 60,078bp genome contains 90 predicted protein-coding genes all transcribed in the same direction and has been assigned to genetic cluster DJ based on gene content similarity.

Development of Corynebacterium glutamicum as a monoterpene production platform.

Monoterpenes are commonly known for their role in the flavors and fragrances industry and are also gaining attention for other uses like insect repellant and as potential renewable fuels for aviation. Corynebacterium glutamicum, a Generally Recognized as Safe microbe, has been a choice organism in industry for the annual million ton-scale bioproduction of amino acids for more than 50 years; however, efforts to produce monoterpenes in C. glutamicum have remained relatively limited.

Deciphering triterpenoid saponin biosynthesis by leveraging transcriptome response to methyl jasmonate elicitation in Saponaria vaccaria.

Methyl jasmonate (MeJA) is a known elicitor of plant specialized metabolism, including triterpenoid saponins. Saponaria vaccaria is an annual herb used in traditional Chinese medicine, containing large quantities of oleanane-type triterpenoid saponins with anticancer properties and structural similarities to the vaccine adjuvant QS-21. Leveraging the MeJA-elicited saponin biosynthesis, we identify multiple enzymes catalyzing the oxidation and glycosylation of triterpenoids in S.

Feasibility and impact of haplogroup matching for mitochondrial replacement treatment.

Mitochondrial replacement technology (MRT) aims to reduce the risk of serious disease in children born to women who carry pathogenic mitochondrial DNA (mtDNA) variants. By transplanting nuclear genomes from eggs of an affected woman to enucleated eggs from an unaffected donor, MRT creates new combinations of nuclear and mtDNA. Based on sets of shared sequence variants, mtDNA is classified into ~30 haplogroups.

Parkinson's disease neurons exhibit alterations in mitochondrial quality control proteins.

Mitochondrial dysfunction has been suggested to contribute to Parkinson's disease pathogenesis, though an understanding of the extent or exact mechanism of this contribution remains elusive. This has been complicated by challenging nature of pathway-based analysis and an inability simultaneously study multiple related proteins within human brain tissue. We used imaging mass cytometry (IMC) to overcome these challenges, measuring multiple protein targets, whilst retaining the spatial relationship between targets in post-mortem midbrain sections.

The contributions of mitochondrial and nuclear mitochondrial genetic variation to neuroticism.

Neuroticism is a heritable trait composed of separate facets, each conferring different levels of protection or risk, to health. By examining mitochondrial DNA in 269,506 individuals, we show mitochondrial haplogroups explain 0.07-0.

Codeveloping and Evaluating a Campaign to Reduce Dementia Misconceptions on Twitter: Machine Learning Study.

Background: Dementia misconceptions on Twitter can have detrimental or harmful effects. Machine learning (ML) models codeveloped with carers provide a method to identify these and help in evaluating awareness campaigns.

Objective: This study aimed to develop an ML model to distinguish between misconceptions and neutral tweets and to develop, deploy, and evaluate an awareness campaign to tackle dementia misconceptions.

Genomic Strategies in Mitochondrial Diagnostics.

Pathogenic variants in both mitochondrial and nuclear genes contribute to the clinical and genetic heterogeneity of mitochondrial diseases. There are now pathogenic variants in over 300 nuclear genes linked to human mitochondrial diseases. Nonetheless, diagnosing mitochondrial disease with a genetic outcome remains challenging.

The impact of patient involvement on participant opinions of information sheets.

Background: Patient and public involvement (PPI) groups can provide valuable input to create more accessible study documents with less jargon. However, we don't know whether this procedure improves accessibility for potential participants.

Aims: We assessed whether participant information sheets were rated as more accessible after PPI review and which aspects of information sheets and study design were important to mental health patients compared with a control group with no mental health service use.