Differentially localizing isoforms of the migraine component calcitonin gene-related peptide (CGRP), in the mouse trigeminal ganglion: βCGRP is translated but, unlike αCGRP, not sorted into axons.

Objective: The neuropeptide calcitonin gene-related peptide (CGRP) has been established to be a key signaling molecule in migraine, but little is known about the differences between the two isoforms: αCGRP and βCGRP. Previous studies have been hampered by their close similarity, making the development of specific antibodies nearly impossible. In this study we sought to test the hypothesis that αCGRP and βCGRP localize differently within the neurons of the mouse trigeminal ganglion (TG), using αCGRP knock out (KO) animals.

Blood absolute lymphocyte count and trajectory are important in understanding severe COVID-19.

Background: Low blood absolute lymphocyte count (ALC) may predict severe COVID-19 outcomes. Knowledge gaps remain regarding the relationship of ALC trajectory with clinical outcomes and factors associated with lymphopenia.

Methods: Our post hoc analysis of the Therapeutics for Inpatients with COVID-19 platform trial utilized proportional hazards models to assess relationships between Day (D) 0 lymphopenia (ALC < 0.

Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.

The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.

Molecular dynamics-guided reaction discovery reveals endoperoxide-to-alkoxy radical isomerization as key branching point in α-pinene ozonolysis.

Secondary organic aerosols (SOAs) significantly impact Earth's climate and human health. Although the oxidation of volatile organic compounds (VOCs) has been recognized as the major contributor to the atmospheric SOA budget, the mechanisms by which this process produces SOA-forming highly oxygenated organic molecules (HOMs) remain unclear. A major challenge is navigating the complex chemical landscape of these transformations, which traditional hypothesis-driven methods fail to thoroughly investigate.

Integrated TWAS, GWAS, and RNAseq results identify candidate genes associated with reproductive traits in cows.

Low fertility in cows leads to early removal from herds. Since reproductive traits are complex and have low heritability, genetic analysis can aid in improving reproduction. This study identified key genes linked to fertility by conducting genome- and transcriptome-wide association studies, RNA-seq analysis, meta-analysis, weighted gene co-expression network analysis, and functional enrichment analysis.

Metagenome-guided culturomics for the targeted enrichment of gut microbes.

The gut microbiome significantly impacts human health, yet cultivation challenges hinder its exploration. Here, we combine deep whole-metagenome sequencing with culturomics to selectively enrich for taxa and functional capabilities of interest. Using a modified commercial base medium, 50 growth modifications were evaluated, spanning antibiotics, physico-chemical conditions, and bioactive compounds.

Mixed effect model confirms increased risk of image changes with increasing linear energy transfer in proton therapy of gliomas.

Background And Purpose: Radiation induced image changes (IC) on MRI have been observed after proton therapy for brain tumours. This study aims to create predictive models, with and without taking into account patient variation, based on dose, linear energy transfer (LET) and periventricular zone (PVZ) in a national cohort of patients with glioma treated with pencil beam scanning (PBS).

Materials And Methods: A cohort of 87 consecutive patients with oligodendroglioma or astrocytoma (WHO grade 2-4) treated with PBS from January 2019 to December 2021 was included.

Occlusal acuity and bite force in young adults.

Occlusal tactile acuity (OTA) and bite force are essential components of the sensorimotor control of oral behaviors. While these variables have been studied independently, it has not yet been revealed whether compressive force impacts the occlusal perception mediated by the mechanoreceptive afferents in the periodontal ligament. The present study examined the effect of repetition and maximum bite force on OTA by testing nine aluminum foils of different thicknesses together with a sham test with no foil, three times each, in randomized order in 36 healthy individuals.

Molecular ecology of novel amdoparvoviruses and old protoparvoviruses in Spanish wild carnivorans.

Wild carnivorans are key hosts of parvoviruses of relevance for animal health and wildlife conservation. However, the distribution and diversity of parvoviruses among wild carnivorans are under-investigated, particularly in Southern Europe. We evaluated the presence, spread, and diversity of multi-host protoparvoviruses (canine parvovirus type 2 (CPV-2), feline panleukopenia virus (FPV)), and amdoparvoviruses in 12 carnivoran species from Northern Spain to explore viral ecology.

Anything but small: Microarousals stand at the crossroad between noradrenaline signaling and key sleep functions.

Continuous sleep restores the brain and body, whereas fragmented sleep harms cognition and health. Microarousals (MAs), brief (3- to 15-s-long) wake intrusions into sleep, are clinical markers for various sleep disorders. Recent rodent studies show that MAs during healthy non-rapid eye movement (NREM) sleep are driven by infraslow fluctuations of noradrenaline (NA) in coordination with electrophysiological rhythms, vasomotor activity, cerebral blood volume, and glymphatic flow.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.

Unveiling the interplay between soluble guanylate cyclase activation and redox signalling in stroke pathophysiology and treatment.

Soluble guanylate cyclase (sGC) stands as a pivotal regulatory element in intracellular signalling pathways, mediating the formation of cyclic guanosine monophosphate (cGMP) and impacting diverse physiological processes across tissues. Increased formation of reactive oxygen species (ROS) is widely recognized to modulate cGMP signalling. Indeed, oxidatively damaged, and therefore inactive sGC, contributes to poor vascular reactivity and more severe neurological damage upon stroke.

Experiments and modelling of pulmonary surfactant disruption by aerosolised compounds.

Within the deep lung, pulmonary surfactant coats the air-liquid interface at the surface of the alveoli. This complex mixture of amphiphilic molecules and proteins modifies the surface tension and mechanical properties of this interface to assist with breathing. In this study, we examine the effects on pulmonary surfactant function by two industrially used compounds composing surfactants and polymers.

Absorption cross section of gas phase isoprene in the infrared-visible range.

We have recorded the gas phase spectrum of isoprene at room temperature from the mid-infrared range and into the visible range (600 cm to 17050 cm). Absorption spectra were obtained by Fourier transform infrared, conventional dispersion ultraviolet-visible-near-infrared and cavity ring-down spectroscopy to cover the entire range with a resolution comparable to that of the instruments on the James Webb Space Telescope. We have assigned the CH-stretching fundamental and overtone bands corresponding to the Δv=1-6 transitions based on anharmonic vibrational calculations using normal mode and local mode models, for the lower- and higher-energy regions, respectively.

Risk factors for the incursion of highly pathogenic avian influenza virus into poultry and other captive bird holdings in Denmark from 2020 to 2023: A case-control study.

Highly pathogenic avian influenza (HPAI) is a major concern in terms of animal and human health. Between October 2020 and September 2023, there were 36 HPAI outbreaks detected in poultry and other captive birds in Denmark. However, it is often not possible to determine the exact route of introduction.

Design, Synthesis, and Pharmacological Evaluation of Nonsteroidal Tricyclic Ligands as Modulators of GABA Receptors.

GABA receptors (GABARs) are the major elements of inhibitory neurotransmission in the central nervous system (CNS). They are established targets for regulation by endogenous brain neuroactive steroids (NASs) such as pregnanolone. However, the complexity of de novo synthesis of NAS derivatives has hindered attempts to circumvent the principal limitations of using endogenous NASs, including selectivity and limited oral bioavailability.

Decoding the elite soccer player's psychological profile.

Soccer is arguably the most widely followed sport worldwide, and many dream of becoming soccer players. However, only a few manage to achieve this dream, which has cast a significant spotlight on elite soccer players who possess exceptional skills to rise above the rest. Originally, such attention was focused on their great physical abilities.

Independently engaging protein tethers of different length enhance synaptic vesicle trafficking to the plasma membrane.

Synaptic vesicle (SV) trafficking toward the plasma membrane (PM) and subsequent SV maturation are essential for neurotransmitter release. These processes, including SV docking and priming, are co-ordinated by various proteins, such as SNAREs, Munc13 and synaptotagmin (Syt), which connect (tether) the SV to the PM. Here, we investigated how tethers of varying lengths mediate SV docking using a simplified mathematical model.

Transperitoneal robot-assisted partial nephrectomy: a comparison of operative and oncological outcomes between posterior and anterolateral tumours.

Objective: To compare operative and oncological outcomes, as well as the risk of postoperative complications in patients who underwent transperitoneal robot-assisted partial nephrectomy (RAPN) for renal tumours located either posteriorly or anterolaterally.

Methods: Retrospective, consecutive study including 451 patients who underwent transperitoneal RAPN for non-metastatic, localised renal tumours from May 2016 to April 2023. Operative data included duration of the procedure, warm ischaemia time, and blood loss; oncological data included surgical margins and recurrence; and 90-day postoperative complications were classified according to the Clavien-Dindo classification.

Reconstruction of reverberant sound fields over large spatial domains.

Characterising acoustic fields in rooms is challenging due to the complexity of data acquisition. Sound field reconstruction methods aim at predicting the acoustic quantities at positions where no data are available, incorporating generalisable physical priors of the sound in a room. This study introduces a model that exploits the general time structure of the room impulse response, where a wave-based expansion addresses the direct sound and early reflections, localising their apparent origin, and kernel methods are applied to the late part.

Optimizing automated photo identification for population assessments.

Several legal acts mandate that management agencies regularly assess biological populations. For species with distinct markings, these assessments can be conducted noninvasively via capture-recapture and photographic identification (photo-ID), which involves processing considerable quantities of photographic data. To ease this burden, agencies increasingly rely on automated identification (ID) algorithms.

Advancing Principled Pharmacoepidemiologic Research to Support Regulatory and Healthcare Decision Making: The Era of Real-World Evidence.

A compilation of factors over the past decade-including the availability of increasingly large and rich healthcare datasets, advanced technologies to extract unstructured information from health records and digital sources, advancement of principled study design and analytic methods to emulate clinical trials, and frameworks to support transparent study conduct-has ushered in a new era of real-world evidence (RWE). This review article describes the evolution of the RWE era, including pharmacoepidemiologic methods designed to support causal inferences regarding treatment effects, the role of regulators and other health authorities in establishing distributed real-world data networks enabling analytics at scale, and the many global guidance documents on principled methods of producing RWE. This article also highlights the growing opportunity for RWE to support decision making by regulators, health technology assessment groups, clinicians, patients, and other stakeholders and provides examples of influential RWE studies.

Twisting nanoporous graphene on graphene: electronic decoupling and chiral currents.

Nanoporous graphene (NPG), laterally bonded carbon nanoribbons, is a promising platform for controlling coherent electron propagation in the nanoscale. However, for its successful device integration NPG should ideally be on a substrate that preserves or enhances its anisotropic transport properties. Here, using an atomistic tight-binding model combined with nonequilibrium Green's functions, we study NPG on graphene and show that their electronic coupling is modulated as a function of the interlayer twist angle.