Monodisperse Chemical Oligophosphorylation of Peptides via Protected Oligophosphorimidazolide Reagents.

Protein poly- and oligophosphorylation are recently discovered post-translational modifications that remain poorly characterized due to (1) the difficulty of extracting endogenously polyphosphorylated species without degradation and (2) the absence of synthetic and analytical tools to prepare and characterize poly- and oligophosphorylated species in biochemical contexts. Herein, we report a methodology for the selective oligophosphorylation of peptides with monodisperse phosphate chain lengths (P=3-6). A library of oligophosphorimidazolide (oligoP-imidazolide) reagents featuring benzyl and o-nitrophenylethyl protecting groups was synthesized in moderate-to-good yields (65-93 %).

The European Nucleotide Archive in 2024.

The European Nucleotide Archive (ENA, https://www.ebi.ac.

Effects of snake fungal disease (ophidiomycosis) on the skin microbiome across two major experimental scales.

Emerging infectious diseases are increasingly recognized as a significant threat to global biodiversity conservation. Elucidating the relationship between pathogens and the host microbiome could lead to novel approaches for mitigating disease impacts. Pathogens can alter the host microbiome by inducing dysbiosis, an ecological state characterized by a reduction in bacterial alpha diversity, an increase in pathobionts, or a shift in beta diversity.

Arene extrusion as an approach to reductive elimination at boron: implication of carbene-ligated haloborylene as a transient reactive intermediate.

Herein, we report boron-centered arene extrusion reactions to afford putative cyclic(alkyl)(amino) carbene (CAAC)-ligated chloroborylene and bromoborylene intermediates. The borylene precursors, chloro-boranorbornadiene (ClB(CMe), 2) and bromo-boranorbornadiene (BrB(CMe), 2) were synthesized through the reaction of the corresponding 1-halo-2,3,4,5-tetramethylborole dimer (XBCMe) (X = Cl, 1; X = Br, 1) with 2-butyne. Treatment of 2 with CAACs resulted in the release of di-coordinate chloro-borylene (CAAC)BCl from hexamethylbenzene (CMe) at room temperature.

Computationally-Assisted Discovery and Assignment of a New Class of 6/6/5/5 Fused-Ring Diterpene Acting as Pregnane X Receptor Ligands from .

We report here the orchestration of molecular ion networking (MoIN) and a set of computationally assisted structural elucidation approaches in the discovery and assignment of a new class of rearranged 4,5--abietane diterpenoids including serra A (), which possesses an unusual 6/6/5/5 fused-ring skeleton system, together with two previously unreported diterpenoids serras B-C (-) and five known compounds were isolated from (). The structures were elucidated by spectroscopic analysis in conjunction with computationally assisted structure elucidation tools. , serras A-C (-) bind well to PXR, suggesting their potential role in reducing inflammation.

Transportable, portable, wearable and (partially) implantable haemodialysis systems: comparison of technologies and readiness levels.

Background: Dialysis modalities and their various treatment schedules result from complex compromises ('trade-offs') between medical, financial, technological, ergonomic, and ecological factors. This study targets summarizing the mutual influence of these trade-offs on (trans)portable, wearable, or even (partially) implantable haemodialysis (HD) systems, identify what systems are in development, and how they might improve quality of life (QoL) for patients with kidney failure.

Methods: HD as defined by international standard IEC 60601-2-16 was applied on a PUBMED database query regarding (trans)portable, wearable, and (partly) implantable HD systems.

Emergency Maternal Hospital Readmissions in the Postnatal Period: A Population-Based Cohort Study.

Objective: To determine the change in English emergency postnatal maternal readmissions 2007-2017 (pre-COVID-19) and the association with maternal demographics, obstetric risk factors and postnatal length of stay (LOS).

Design: National cohort study.

Setting: All English National Health Service hospitals.

Temperature dependence of leaf breakdown in streams differs between organismal groups and leaf species.

Increased temperatures are altering rates of organic matter (OM) breakdown in stream ecosystems with implications for carbon (C) cycling in the face of global change. The metabolic theory of ecology (MTE) provides a framework for predicting temperature effects on OM breakdown, but differences in the temperature dependence of breakdown driven by different organismal groups (i.e.

LXR-dependent enhancer activation regulates the temporal organization of the liver's response to refeeding leading to lipogenic gene overshoot.

Transitions between the fed and fasted state are common in mammals. The liver orchestrates adaptive responses to feeding/fasting by transcriptionally regulating metabolic pathways of energy usage and storage. Transcriptional and enhancer dynamics following cessation of fasting (refeeding) have not been explored.

Endothelial extracellular vesicles enhance vascular self-assembly in engineered human cardiac tissues.

The fabrication of complex and stable vasculature in engineered cardiac tissues represents a significant hurdle towards building physiologically relevant models of the heart. Here, we implemented a 3D model of cardiac vasculogenesis, incorporating endothelial cells (EC), stromal cells, and human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) in a fibrin hydrogel. The presence of CMs disrupted vessel formation in 3D tissues, resulting in the upregulation of endothelial activation markers and altered extracellular vesicle (EV) signaling in engineered tissues as determined by the proteomic analysis of culture supernatant.

New anti-inflammatory mechanism of glucocorticoids uncovered.

Glucocorticoids (GCs) are potent anti-inflammatory drugs. A new study by Auger et al. found that GCs increase itaconate, an anti-inflammatory tricarboxylic acid (TCA) cycle intermediate, by promoting movement of cytosolic pyruvate dehydrogenase (PDH) to mitochondria.

Pentaphosphorylation via the Anhydride of Dihydrogen Pentametaphosphate: Access to Nucleoside Hexa- and Heptaphosphates and Study of Their Interaction with Ribonuclease A.

Pentametaphosphate is the little studied cyclic pentamer of the metaphosphate ion, [PO] . We show that the doubly protonated form of this pentamer can be selectively dehydrated to provide the anhydride [PO] (). This trianion is the well-defined condensed phosphate component of a novel reagent for attachment of a pentaphosphate chain to biomolecules all in one go.

Long term outcome in non-multiple sclerosis paediatric acquired demyelinating syndromes.

Objectives: We aimed to study the risks of relapse and long term disability in children with non-MS acquired demyelinating syndromes (ADS).

Methods: In this prospective, multi-centre study, from the 14 UK pediatric neurology centres, children (<16 years) experiencing a first episode of ADS were recruited from 2010 to 2014. Case report forms were collected prospectively.

Synthesis and reactivity of an N-heterocyclic carbene-stabilized diazoborane.

Diazo compounds and organic azides are widely used as reagents for accessing valuable molecules in multiple areas of fundamental and applied chemistry. Their capacity to undergo versatile chemical transformations arises from the reactive nature of an incipient dinitrogen molecule at the terminal position. In this work, we report the synthesis and characterization of an N-heterocyclic carbene (NHC)-stabilized diazoborane-a boron-centered analog of organic azides and diazoalkanes.

Stopping anticoagulation for isolated or incidental pulmonary embolism: the STOPAPE RCT protocol.

Research Question: Is withholding anticoagulation for patients with isolated or incidental subsegmental pulmonary embolism clinically and cost-effective compared with full anticoagulation for 3 months?

Background: There has been an increase in the diagnosis of subsegmental pulmonary embolism since the advent of computed tomography pulmonary angiogram to investigate patients with suspected pulmonary embolism. Subsegmental pulmonary embolism is not often detectable with older nuclear medicine-based diagnostic imaging for ventilation/perfusion mismatch. The case fatality of pulmonary embolism has reduced as subsegmental pulmonary embolism diagnoses from computed tomography pulmonary angiogram have increased.

Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms.

The intricate anatomical structure and high cellular density of the myocardium complicate the bioengineering of perfusable vascular networks within cardiac tissues. In vivo neonatal studies highlight the key role of resident cardiac macrophages in post-injury regeneration and angiogenesis. Here, we integrate human pluripotent stem-cell-derived primitive yolk-sac-like macrophages within vascularized heart-on-chip platforms.

A novel fatty acid mimetic with pan-PPAR partial agonist activity inhibits diet-induced obesity and metabolic dysfunction-associated steatotic liver disease.

Objective: The prevalence of metabolic diseases is increasing globally at an alarming rate; thus, it is essential that effective, accessible, low-cost therapeutics are developed. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that tightly regulate glucose homeostasis and lipid metabolism and are important drug targets for the treatment of type 2 diabetes and dyslipidemia. We previously identified LDT409, a fatty acid-like compound derived from cashew nut shell liquid, as a novel pan-active PPARα/γ/δ compound.

Need a break? The locomotor and tackle pacing profile and loads of women's rugby league match-play following various between-match turnaround durations.

Objectives: The study investigated the locomotor and tackle pacing profile and loads of female rugby league players following various between-match turnaround durations. Specifically, the study examined the (1) pacing of locomotor and tackle loads across the time-course of a match and; (2) whole-match and peak locomotor and tackle loads of match-play.

Methods: Microtechnology data were collected from elite female rugby league players ( = 172) representing all National Rugby League Women's teams ( = 6 teams) across two seasons.

Resisting the (re-)medicalisation of dying and grief in the post-digital age: Natural language processing and qualitative analysis of data from internet support forums.

In the mid-twentieth century, the social movement of death revivalism sought to resist the medicalisation of dying and grief through promotion of the dying person retaining autonomy, and societal openness toward death and bereavement. Despite this advocacy, present-day dying in high income countries is largely institutionalised, with value placed on control over the body and emotions. These phenomena are at odds with the ambitions of death revivalism, and demonstrate the re-medicalisation of dying and grief.

Mobilisation and analyses of publicly available SARS-CoV-2 data for pandemic responses.

The COVID-19 pandemic has seen large-scale pathogen genomic sequencing efforts, becoming part of the toolbox for surveillance and epidemic research. This resulted in an unprecedented level of data sharing to open repositories, which has actively supported the identification of SARS-CoV-2 structure, molecular interactions, mutations and variants, and facilitated vaccine development and drug reuse studies and design. The European COVID-19 Data Platform was launched to support this data sharing, and has resulted in the deposition of several million SARS-CoV-2 raw reads.

Hagfish genome elucidates vertebrate whole-genome duplication events and their evolutionary consequences.

Polyploidy or whole-genome duplication (WGD) is a major event that drastically reshapes genome architecture and is often assumed to be causally associated with organismal innovations and radiations. The 2R hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution. However, the timing of the 2R event relative to the divergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and lampreys) is unresolved and whether these WGD events underlie vertebrate phenotypic diversification remains elusive.