Long G4-rich enhancers target promoters via a G4 DNA-based mechanism.

Several studies have now described instances where G-rich sequences in promoters and enhancers regulate gene expression through forming G-quadruplex (G4) structures. Relatedly, our group recently identified 301 long genomic stretches significantly enriched for minimal G4 motifs (LG4s) in humans and found the majority of these overlap annotated enhancers, and furthermore, that the promoters regulated by these LG4 enhancers are similarly enriched with G4-capable sequences. While the generally accepted model for enhancer:promoter specificity maintains that interactions are dictated by enhancer- and promoter-bound transcriptional activator proteins, the current study tested an alternative hypothesis: that LG4 enhancers interact with cognate promoters via a direct G4:G4 DNA-based mechanism.

Oxidative Injury to Lung Mitochondrial DNA is a Key Contributor for the Development of Chemical Lung Injury.

The mechanisms and extent to which inhalation of oxidant gases damage the mitochondrial genome contributing to the development of acute and chronic lung injury have not been investigated. C57BL/6 mice exposed to chlorine (Cl ) gas and returned to room air, developed progressive loss of lung DNA glycosylase OGG1, significant oxidative injury to mtDNA, decreased intact lung mitochondrial (mt) DNA, generation of inflammatory pathway by DAMPs causing airway and alveolar injury with significant mortality. Global proteomics identified over 1400 lung proteins with alteration of key mitochondrial proteins at 24 h post Cl exposure.

Systemic inflammation and lymphocyte activation precede rheumatoid arthritis.

Some autoimmune diseases, including rheumatoid arthritis (RA), are preceded by a critical subclinical phase of disease activity. Proactive clinical management is hampered by a lack of biological understanding of this subclinical 'at-risk' state and the changes underlying disease development. In a cross-sectional and longitudinal multi-omics study of peripheral immunity in the autoantibody-positive at-risk for RA period, we identified systemic inflammation, proinflammatory-skewed B cells, expanded Tfh17-like cells, epigenetic bias in naive T cells, TNF+IL1B+ monocytes resembling a synovial macrophage population, and CD4 T cell transcriptional features resembling those suppressed by abatacept (CTLA4-Ig) in RA patients.

Diminishing warming effects on plant phenology over time.

Plant phenology, the timing of recurrent biological events, shows key and complex response to climate warming, with consequences for ecosystem functions and services. A key challenge for predicting plant phenology under future climates is to determine whether the phenological changes will persist with more intensive and long-term warming. Here, we conducted a meta-analysis of 103 experimental warming studies around the globe to investigate the responses of four phenophases - leaf-out, first flowering, last flowering, and leaf coloring.

Exploring COVID-19 patient's dignity and satisfaction: A cross-sectional study.

Aim: With the outbreak of COVID-19 and associated challenges such as increased workload for health providers and shortage of equipment, it became more challenging to maintain patients' dignity and satisfaction. This study evaluated the patients' dignity and satisfaction with COVID-19 in Kashan, Iran, in 2021.

Design: A cross-sectional descriptive study.

Impacts of recent climate change on crop yield can depend on local conditions in climatically diverse regions of Norway.

Globally, climate change greatly impacts the production of major crops, and there have been many attempts to model future yields under warming scenarios in recent years. However, projections of future yields may not be generalisable to all crop growing regions, particularly those with diverse topography and bioclimates. In this study, we demonstrate this by evaluating the links between changes in temperature and precipitation and changes in wheat, barley, and potato yields at the county-level during 1980-2019 in Norway, a Nordic country with a range of climates across a relatively small spatial scale.

Absolute quantification of plasma mitochondrial DNA by droplet digital PCR marks COVID-19 severity over time during intensive care unit admissions.

Increased plasma mitochondrial DNA concentrations are associated with poor outcomes in multiple critical illnesses, including COVID-19. However, current methods of cell-free mitochondrial DNA quantification in plasma are time-consuming and lack reproducibility. Here, we used next-generation sequencing to characterize the size and genome location of circulating mitochondrial DNA in critically ill subjects with COVID-19 to develop a facile and optimal method of quantification by droplet digital PCR.

PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains T homeostasis during ageing.

Pyruvate dehydrogenase (PDH) is the gatekeeper enzyme of the tricarboxylic acid (TCA) cycle. Here we show that the deglycase DJ-1 (encoded by PARK7, a key familial Parkinson's disease gene) is a pacemaker regulating PDH activity in CD4 regulatory T cells (T cells). DJ-1 binds to PDHE1-β (PDHB), inhibiting phosphorylation of PDHE1-α (PDHA), thus promoting PDH activity and oxidative phosphorylation (OXPHOS).

Landscape-scale drivers of pollinator communities may depend on land-use configuration.

Research into pollinators in managed landscapes has recently combined approaches of pollination ecology and landscape ecology, because key stressors are likely to interact across wide areas. While laboratory and field experiments are valuable for furthering understanding, studies are required to investigate the interacting drivers of pollinator health and diversity across a broader range of landscapes and a wider array of taxa. Here, we use a network of 96 study landscapes in six topographically diverse regions of Britain, to test the combined importance of honeybee density, insecticide loadings, floral resource availability and habitat diversity to pollinator communities.

Effectiveness of sodium bicarbonate and zinc chloride mouthwashes in the treatment of oral mucositis and quality of life in patients with cancer under chemotherapy.

Aim: The purpose of the study is to evaluate the effectiveness of sodium bicarbonate and zinc chloride mouthwashes on oral mucositis and quality of life in patients undergoing chemotherapy.

Design: The present study was a randomized controlled trial study.

Methods: One hundred forty-four patients with a cancer diagnosis were randomly assigned into three groups: sodium bicarbonate mouthwash (n = 48), zinc chloride mouthwash (n = 48) and placebo group (n = 48).

Mitochondrial Damage-associated Molecular Patterns as Potential Biomarkers in DCD Heart Transplantation: Lessons From Myocardial Infarction and Cardiac Arrest.

Heart transplantation with donation after circulatory death (DCD) has become a real option to increase graft availability. However, given that DCD organs are exposed to the potentially damaging conditions of warm ischemia before procurement, new strategies for graft evaluation are of particular value for the safe expansion of DCD heart transplantation. Mitochondria-related parameters are very attractive as biomarkers because of their intimate association with cardiac ischemia-reperfusion injury.

The dignity of burn patients: a qualitative descriptive study of nurses, family caregivers, and patients.

Background: As an ethical principle, showing respect for human dignity is a professional duty of all nurses. The aggressive nature of severe burn injuries makes it hard to respect the existential values and dignity of burn patients. However, only a few studies have been conducted on the preservation of the dignity of burn patients.

Does acute and persistent metabolic dysregulation in COVID-19 point to novel biomarkers and future therapeutic strategies?

https://bit.ly/2XkJeU8

Development and assessment of the psychometric properties of a compassionate care questionnaire for nurses.

Background: Compassionate care is emphasized within professional ethics codes for nursing and is a key indicator of care quality. The purpose of the present study is to develop and assess the psychometric properties of a compassionate care instrument for nurses.

Methods: This methodological study was carried out in two phases -qualitative and quantitative-from February 2016 to October 2018.

A metabolomic endotype of bioenergetic dysfunction predicts mortality in critically ill patients with acute respiratory failure.

Acute respiratory failure (ARF) requiring mechanical ventilation, a complicating factor in sepsis and other disorders, is associated with high morbidity and mortality. Despite its severity and prevalence, treatment options are limited. In light of accumulating evidence that mitochondrial abnormalities are common in ARF, here we applied broad spectrum quantitative and semiquantitative metabolomic analyses of serum from ARF patients to detect bioenergetic dysfunction and determine its association with survival.

Moral courage, moral sensitivity and safe nursing care in nurses caring of patients with COVID-19.

Aim: Evaluation the moral courage, moral sensitivity and safe nursing care in nurses caring of infected patients by the COVID-19.

Design: This study employed cross-sectional research.

Methods: 520 nurses caring for COVID-19 patients in 5 hospitals were selected via convenience sampling.

Chromatin-Associated Protein Complexes Link DNA Base J and Transcription Termination in .

Unlike most other eukaryotes, and other trypanosomatid protozoa have largely eschewed transcriptional control of gene expression, relying instead on posttranscriptional regulation of mRNAs derived from polycistronic transcription units (PTUs). In these parasites, a novel modified nucleotide base (β-d-glucopyranosyloxymethyluracil) known as J plays a critical role in ensuring that transcription termination occurs only at the end of each PTU, rather than at the polyadenylation sites of individual genes. To further understand the biology of J-associated processes, we used tandem affinity purification (TAP) tagging and mass spectrometry to reveal proteins that interact with the glucosyltransferase performing the final step in J synthesis.

Nonlinear trends in abundance and diversity and complex responses to climate change in Arctic arthropods.

Time series data on arthropod populations are critical for understanding the magnitude, direction, and drivers of change. However, most arthropod monitoring programs are short-lived and restricted in taxonomic resolution. Monitoring data from the Arctic are especially underrepresented, yet critical to uncovering and understanding some of the earliest biological responses to rapid environmental change.

Absolute quantification of transcription factors in human erythropoiesis using selected reaction monitoring mass spectrometry.

Quantitative changes in transcription factor (TF) abundance regulate dynamic cellular processes, including cell fate decisions. Protein copy number provides information about the relative stoichiometry of TFs that can be used to determine how quantitative changes in TF abundance influence gene regulatory networks. In this protocol, we describe a targeted selected reaction monitoring (SRM)-based mass-spectrometry method to systematically measure the absolute protein concentration of nuclear TFs as human hematopoietic stem and progenitor cells differentiate along the erythropoietic lineage.

Characterization of long G4-rich enhancer-associated genomic regions engaging in a novel loop:loop 'G4 Kissing' interaction.

Mammalian antibody switch regions (∼1500 bp) are composed of a series of closely neighboring G4-capable sequences. Whereas numerous structural and genome-wide analyses of roles for minimal G4s in transcriptional regulation have been reported, Long G4-capable regions (LG4s)-like those at antibody switch regions-remain virtually unexplored. Using a novel computational approach we have identified 301 LG4s in the human genome and find LG4s prone to mutation and significantly associated with chromosomal rearrangements in malignancy.