Heterologous Expression and Optimization of Fermentation Conditions for Recombinant Ikarugamycin Production.

Ikarugamycin is a member of the natural product family of the polycyclic tetramate macrolactams (PoTeMs). The compound exhibits a diverse range of biological activities, including antimicrobial, antiprotozoal, anti-leukemic, and anti-inflammatory properties. In addition, it interferes with several crucial cellular functions, such as oxidized low-density lipoprotein uptake in macrophages, Nef-induced CD4 cell surface downregulation, and mechanisms of endocytosis.

A plug-and-play system for polycyclic tetramate macrolactam production and functionalization.

Background: The biosynthesis of the natural product family of the polycyclic tetramate macrolactams (PoTeMs) employs an uncommon iterative polyketide synthase/non-ribosomal peptide synthetase (iPKS/NRPS). This machinery produces a universal PoTeM biosynthetic precursor that contains a tetramic acid moiety connected to two unsaturated polyene side chains. The enormous structural and hence functional diversity of PoTeMs is enabled by pathway-specific tailoring enzymes, particularly cyclization-catalyzing oxidases that process the polyene chains to form distinct ring systems, and further modifying enzymes.

Think-Aloud Testing of a Companion App for Colonoscopy Exams: Usability Study.

Background: Colonoscopies, are vital for initial screening, follow-ups, surveillance of neoplasia, and assessing symptoms like rectal bleeding. Successful colonoscopies require thorough colon preparation, but up to 25% fail due to poor preparation. This can lead to longer procedures, repeat colonoscopies, inconvenience, poorer health outcomes, and higher costs.

Evaluation of vascular photobiomodulation for orofacial pain and tension type headache following COVID 19 in a pragmatic randomized clinical trial.

This pragmatic double-blind randomized clinical trial aims to assess the impact of vascular photobiomodulation on post-COVID-19 patients experiencing tension-type headache, orofacial pain, or both persisting for more than 3 months. Participants were divided into two groups: vascular photobiomodulation (VPBM) and simulated VPBM. Their conditions were evaluated using the Brief Pain Inventory (BPI), Visual Analogue Scale, and Headache Impact Test (HIT-6).

Expanding Polycyclic Tetramate Macrolactam (PoTeM) Core Structure Diversity by Chemo-Enzymatic Synthesis and Bioengineering.

Polycyclic tetramate macrolactams (PoTeMs) represent a growing class of bioactive natural products that are derived from a common tetramate polyene precursor, lysobacterene A, produced by an unusual bacterial iterative polyketide synthase (PKS) / non-ribosomal peptide synthetase (NRPS). The structural and functional diversity of PoTeMs is biosynthetically elaborated from lysobacterene A by pathway-specific cyclizing and modifying enzymes. This results in diverse core structure decoration and cyclization patterns.

Fit for purpose? Evaluating benthic invertebrate DNA metabarcoding for ecological status class assessment in streams under the Water Framework Directive.

The ecological state of aquatic ecosystems is systematically monitored using various bioindicators in many countries worldwide. In the European Union, freshwater biomonitoring is the central component of the EU Water Framework Directive (WFD, 2000/60/EC) and currently based on morpho-taxonomic methods. DNA metabarcoding is a novel approach to assess the ecological state fast and efficiently based on organismal DNA signatures and thereby support and upscale biomonitoring.

Dosimetry model for photobiomodulation based on anthropometric and hemodynamic variables in patients with orofacial pain post-Covid-19: Study protocol for randomized clinical trial.

Introduction: Orofacial pain and tension headache are symptoms that affect a large portion of the population, compromising productivity, social ability, and functional development. The treatment for reducing painful sensation should be chosen carefully, as pharmacological treatment may bring side effects and overload the organism of patients in pain. Low-level laser therapy has been used with local and systemic [vascular] applications for pain control.

Amyotrophic lateral sclerosis caused by the expansion in Norway - prevalence, ancestry, clinical characteristics and sociodemographic status.

Objective: The most common genetic cause of amyotrophic lateral sclerosis (ALS) is the expansion. A high incidence of this expansion has been detected in Sweden and Finland. This Norwegian population-based study aimed to identify the prevalence, geographic distribution, ancestry, and relatedness of ALS patients with a expansion (C9).

The Arabidopsis U1 snRNP regulates mRNA 3'-end processing.

The removal of introns by the spliceosome is a key gene regulatory mechanism in eukaryotes, with the U1 snRNP subunit playing a crucial role in the early stages of splicing. Studies in metazoans show that the U1 snRNP also conducts splicing-independent functions, but the lack of genetic tools and knowledge about U1 snRNP-associated proteins have limited the study of such splicing-independent functions in plants. Here we describe an RNA-centric approach that identified more than 200 proteins associated with the Arabidopsis U1 snRNP and revealed a tight link to mRNA cleavage and polyadenylation factors.

Observation of the ϒ(3S) Meson and Suppression of ϒ States in Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The production of ϒ(2S) and ϒ(3S) mesons in lead-lead (Pb-Pb) and proton-proton (pp) collisions is studied in their dimuon decay channel using the CMS detector at the LHC. The ϒ(3S) meson is observed for the first time in Pb-Pb collisions, with a significance above 5 standard deviations. The ratios of yields measured in Pb-Pb and pp collisions are reported for both the ϒ(2S) and ϒ(3S) mesons, as functions of transverse momentum and Pb-Pb collision centrality.

A dual-color PAX7 and MYF5 in vivo reporter to investigate muscle stem cell heterogeneity in regeneration and aging.

Increasing evidence suggests that the muscle stem cell (MuSC) pool is heterogeneous. In particular, a rare subset of PAX7-positive MuSCs that has never expressed the myogenic regulatory factor MYF5 displays unique self-renewal and engraftment characteristics. However, the scarcity and limited availability of protein markers make the characterization of these cells challenging.

Spatiotemporal drivers of Nature's contributions to people: A county-level study.

Nature's contributions to people (NCP) encompass both the beneficial and detrimental effects of living nature on human quality of life, including regulatory, material, and non-material contributions. Globally, vital NCPs have been deteriorating, accelerated by changes in both natural and anthropogenic drivers over recent decades. Despite the often inevitable trade-offs between NCPs due to their spatially and temporally uneven distributions, few studies have quantitatively assessed the impacts of different drivers on the spatial and temporal changes in multiple NCPs and their interrelationships.

Product Selectivity in Baeyer-Villiger Monooxygenase-Catalyzed Bacterial Alkaloid Core Structure Maturation.

Baeyer-Villiger monooxygenases (BVMOs) play crucial roles in the core-structure modification of natural products. They catalyze lactone formation by selective oxygen insertion into a carbon-carbon bond adjacent to a carbonyl group (Baeyer-Villiger oxidation, BVO). The homologous bacterial BVMOs, BraC and PxaB, thereby process bicyclic dihydroindolizinone substrates originating from a bimodular nonribosomal peptide synthetase (BraB or PxaA).

Search for exotic decays of the Higgs boson to a pair of pseudoscalars in the and final states.

A search for exotic decays of the Higgs boson () with a mass of 125 to a pair of light pseudoscalars is performed in final states where one pseudoscalar decays to two quarks and the other to a pair of muons or leptons. A data sample of proton-proton collisions at corresponding to an integrated luminosity of 138 recorded with the CMS detector is analyzed. No statistically significant excess is observed over the standard model backgrounds.

Comparative finite element analysis of the first thoracic vertebra in artiodactyls.

Artiodactyls exhibit a striking diversity of the cervical vertebral column in terms of length and overall mobility. Using finite element analysis, this study explores the morphology at the cervico-thoracic boundary and its performance under loads in artiodactyls with different habitual neck postures and body sizes. The first thoracic vertebra of 36 species was loaded with (i) a compressive load on the vertebral body to model the weight of the head and neck exerted onto the trunk; and (ii) a tensile load at the spinous process to model the pull via the nuchal ligament.

Multimodal in-vehicle lighting system increases daytime light exposure and alertness in truck drivers under Arctic winter conditions.

Drowsiness while driving negatively impacts road safety, especially in truck drivers. The present study investigated the feasibility and alerting effects of a daylight-supplementing in-truck lighting system (DS) providing short-wavelength enriched light before, during, and after driving. In a within-participants design, eight truck drivers drove a fully-loaded truck under wintry Scandinavian conditions (low daylight levels) with a DS or placebo system for five days.

Observation of WWγ Production and Search for Hγ Production in Proton-Proton Collisions at sqrt[s]=13 TeV.

The observation of WWγ production in proton-proton collisions at a center-of-mass energy of 13 TeV with an integrated luminosity of 138  fb^{-1} is presented. The observed (expected) significance is 5.6 (5.

New Structures in the J/ψJ/ψ Mass Spectrum in Proton-Proton Collisions at sqrt[s]=13 TeV.

A search is reported for near-threshold structures in the J/ψJ/ψ invariant mass spectrum produced in proton-proton collisions at sqrt[s]=13  TeV from data collected by the CMS experiment, corresponding to an integrated luminosity of 135  fb^{-1}. Three structures are found, and a model with quantum interference among these structures provides a good description of the data. A new structure is observed with a local significance above 5 standard deviations at a mass of 6638_{-38}^{+43}(stat)_{-31}^{+16}(syst)  MeV.

Denervation alters the secretome of myofibers and thereby affects muscle stem cell lineage progression and functionality.

Skeletal muscle function crucially depends on innervation while repair of skeletal muscle relies on resident muscle stem cells (MuSCs). However, it is poorly understood how innervation affects MuSC properties and thereby regeneration of skeletal muscle. Here, we report that loss of innervation causes precocious activation of MuSCs concomitant with the expression of markers of myogenic differentiation.

Search for Scalar Leptoquarks Produced via τ-Lepton-Quark Scattering in pp Collisions at sqrt[s]=13 TeV.

The first search for scalar leptoquarks produced in τ-lepton-quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138  fb^{-1}. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays.

Search for Inelastic Dark Matter in Events with Two Displaced Muons and Missing Transverse Momentum in Proton-Proton Collisions at sqrt[s]=13 TeV.

A search for dark matter in events with a displaced nonresonant muon pair and missing transverse momentum is presented. The analysis is performed using an integrated luminosity of 138  fb^{-1} of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV produced by the LHC in 2016-2018. No significant excess over the predicted backgrounds is observed.

[Development of criteria for the prospective assessment of the need for updating guideline recommendations: The AGIL criteria].

Background: Evidence-based guideline and vaccination recommendations should continuously be updated to appropriately support health care decisions. However, resources for updating guidelines are often limited. The aim of this project was to develop a list of criteria for the prospective assessment of the need for updating individual guideline or vaccination recommendations, which can be applied from the time a guideline or guideline update is finalised.

Probing Small Bjorken-x Nuclear Gluonic Structure via Coherent J/ψ Photoproduction in Ultraperipheral Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

Quasireal photons exchanged in relativistic heavy ion interactions are powerful probes of the gluonic structure of nuclei. The coherent J/ψ photoproduction cross section in ultraperipheral lead-lead collisions is measured as a function of photon-nucleus center-of-mass energies per nucleon (W_{γN}^{Pb}) over a wide range of 40 View Article and Find Full Text PDF

Preparation of Spirocyclic Vinylic Carbonates from Allylic Alcohols.

We present the synthesis of - and -spirovinylethylene carbonates, starting from various cyclic allylic alcohols. This one-pot cascade reaction to the spirocyclic scaffold was optimized using a design of experiments approach. The introduction of spirovinylethylene carbonates broadens the scope of using these in catalytic applications and provides an easy synthetic entry into spirocyclic scaffolds of various ring sizes.