Enhanced phosphorus weathering contributed to Late Miocene cooling.

Late Miocene climate evolution provides an opportunity to assess Earth's climate sensitivity to carbon cycle perturbation under warmer-than-modern conditions. Despite its relevance for understanding the climate system, the driving mechanisms underlying profound climate and carbon cycle changes - including the enigmatic Late Miocene cooling from 7 to 5.4 million years ago - remain unclear.

Clinically probable RBD is an early predictor of malignant non-motor Parkinson's disease phenotypes.

Non-motor symptoms (NMS) in Parkinson's disease (PD) significantly impact quality of life, especially in later stages. REM sleep behavior disorder (RBD) affects approximately 42% of all PD patients and frequently precedes motor PD symptoms. RBD is linked to increased rates of depression and cognitive decline.

Structure and function of a near fully-activated intermediate GPCR-Gαβγ complex.

Unraveling the signaling roles of intermediate complexes is pivotal for G protein-coupled receptor (GPCR) drug development. Despite hundreds of GPCR-Gαβγ structures, these snapshots primarily capture the fully activated complex. Consequently, the functions of intermediate GPCR-G protein complexes remain elusive.

Renal and Peripheral Blood Transcriptome Signatures That Predict Treatment Response in Proliferative Lupus Nephritis-A Prospective Study.

Mechanisms contributing to non-response to treatment in lupus nephritis (LN) are unclear. We characterised the transcriptome of paired peripheral blood mononuclear cells (PBMCs) and renal tissues in LN before and after cyclophosphamide (CYC) treatment and identified markers that predicted treatment response. Total RNA isolated from paired PBMCs (n = 32) and renal tissues (n = 25) of 16 proliferative LN before CYC treatment, 6 months post-treatment, and during renal flare, was sequenced on Illumina Novaseq-6000 platform.

The number of central nervous system-driven symptoms predicts subsequent chronic primary pain: evidence from UK Biobank.

Background: Chronic primary pain describes conditions where pain is the principal problem rather than a consequence of another disease. Primary pain is thought to be primarily owing to nociplastic pain (i.e.

Evaluating pathogenicity of variants of unknown significance in APP, PSEN1, and PSEN2.

Autosomal dominant Alzheimer's disease (ADAD) is driven by rare variants in APP, PSEN1, and PSEN2. Although more than 200 pathogenic variants in these genes are known to cause ADAD, other variants are benign, may act as risk factors, or may even reduce Alzheimer's disease risk (e.g.

The relationship between optical coherence tomography and magnetic resonance imaging measurements in people with multiple sclerosis: A systematic review and meta-analysis.

Background: Several studies show that optical coherence tomography (OCT) metrics e with cognition, disability, and brain structure in people with multiple sclerosis (PwMS). This review the correlation between OCT parameters and magnetic resonance imaging (MRI) measurements in PwMS.

Methods: A comprehensive search of PubMed/MEDLINE, Embase, Scopus, and Web of Science was performed, including studies published in English up to November 29, 2024 to identify studies reporting quantitative data on the correlation between baseline OCT parameters and MRI measurements in PwMS.

Self-Management Strategies for Low Back Pain Among Horticulture Workers: Protocol for a Type II Hybrid Effectiveness-Implementation Study.

Background: Low back pain (LBP) is highly prevalent and disabling, especially in agriculture sectors. However, there is a gap in LBP prevention and intervention studies in these physically demanding occupations, and to date, no studies have focused on horticulture workers. Given the challenges of implementing interventions for those working in small businesses, self-management offers an attractive and feasible option to address work-related risk factors and manage LBP.

Feasibility of a Mobile App-Based Cognitive-Behavioral Perinatal Skills Program: Protocol for Nonrandomized Pilot Trial.

Background: Mental illness is one of the top causes of preventable pregnancy-related deaths in the United States. There are many barriers that interfere with the ability of perinatal individuals to access traditional mental health care. Digital health interventions, including app-based programs, have the potential to increase access to useful tools for these individuals.

Strategic Mutations in Designer Native Peptides Combat NLRP3 Inflammasome Activation in Neurodegenerative Disorders.

Nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)-, and pyrin domain (PYD)-containing protein 3 (NLRP3) form an inflammasome by assembling with apoptosis-associated speck-like protein containing a CARD (ASC) and procaspase-1 that plays a pivotal role in various neurodegenerative diseases such as Alzheimer's and Parkinson diseases. We designed native peptides derived from the PYDs of NLRP3 and ASC based on their interfacial interaction to inhibit NLRP3 inflammasome formation. Screening revealed that , derived from NLRP3, inhibits inflammasome activation.

Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.

Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson's disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact endogenous LRRK2-mediated Rab phosphorylation nor do we see significant effect of mutant LRRK2 on PINK1-mediated Rab and Ub phosphorylation.

One-Year Real-World Outcomes of Ab-Externo Gel Stent Placement From the EXPAND Study.

Prcis: In the real-world, retrospective, EXPAND study of consecutive adults with glaucoma, ab-externo gel stent implantation effectively lowered intraocular pressure (34%) and the medication burden (61%), with transient/self-resolving hypotony as the most frequent adverse event (28%).

Purpose: To assess effectiveness and safety of ab-externo gel stent (GS) implantation in glaucoma.

Methods: Multicenter, real-world, retrospective study.

Segment specific loss of NFAT5 function in the kidneys is sufficient to induce a global kidney injury like phenotype.

Nuclear factor of activated T-cells 5 (NFAT5) is a transcription factor known for its role in osmotic stress adaptation in the renal inner medulla, due to the osmotic gradient that is generated between the renal cortex and renal inner medulla. However, its broader implications in kidney injury and chronic kidney disease (CKD) are less understood. Here we used two different Cre deleter mice (Ksp1.

Pharmacological Aspects in the Management of Children and Adolescents with Prader-Willi Syndrome.

Prader-Willi syndrome is a rare neurodevelopmental disorder that impacts the musculoskeletal, endocrine, pulmonary, neurologic, ocular, and gastrointestinal systems. In addition, individuals with Prader-Willi syndrome have issues with cognitive development, characteristic behavioral problems, and perhaps most profoundly, appetite control. Currently, the only US Food and Drug Administration-approved therapy for Prader-Willi syndrome is growth hormone, which has been Food and Drug Administration approved for > 20 years for the treatment of growth failure in Prader-Willi syndrome.

Emerging Immunotherapies for Disease Modification of Type 1 Diabetes.

Type 1 diabetes mellitus (T1DM) is characterized by the progressive, autoimmune-mediated destruction of β cells. As such, restoring immunoregulation early in the disease course is sought to retain endogenous insulin production. Nevertheless, in the more than 100 years since the discovery of insulin, treatment of T1DM has focused primarily on hormone replacement and glucose monitoring.

Pudendal Neuralgia: A Review of the Current Literature.

Purpose Of Review: This paper aims to review pudendal neuralgia pathophysiology, risk factors, diagnosis, and treatment options.

Recent Findings: Conservative and pharmacologic options are first line treatments for the treatment of pudendal neuralgia. Interventional treatment such as, pudendal nerve blocks can be tried if first line treatments feel to provide adequate analgesia.

Evidence for the anxiolytic- and antidepressant-like effects of three semi-synthetic derivatives of xylopic acid in mice.

Purpose: Major depressive disorder is one of the most common and burdensome psychiatric disorders worldwide. This study evaluated the anxiolytic- and antidepressant-like activity of three semi-synthetic derivatives of xylopic acid (XA) to identify the most promising derivative based on mechanism(s) of action, in vivo pharmacokinetics and in vitro cytotoxicity.

Methods: The anxiolytic potential and the involvement of GABAergic mechanisms were assessed in the elevated plus-maze and open field tests in mice.

Comprehensive Echocardiographic Protocol for Pigs with Emphasis on Diastolic Function: Advantages over MRI Assessment.

Swine are increasingly utilized in cardiovascular research due to their anatomical and physiological similarities to humans, particularly for studying diastolic dysfunction. While MRI offers excellent structural imaging, echocardiography provides superior real-time assessment of diastolic parameters. To address the lack of standardized methods and reduce variability across studies, we present a comprehensive guide for performing echocardiography in Yorkshire pigs, detailing anatomical considerations, equipment requirements, and technical approaches.

Deep Learning Superresolution for Simultaneous Multislice Parallel Imaging-Accelerated Knee MRI Using Arthroscopy Validation.

Background Deep learning (DL) methods can improve accelerated MRI but require validation against an independent reference standard to ensure robustness and accuracy. Purpose To validate the diagnostic performance of twofold-simultaneous-multislice (SMSx2) twofold-parallel-imaging (PIx2)-accelerated DL superresolution MRI in the knee against conventional SMSx2-PIx2-accelerated MRI using arthroscopy as the reference standard. Materials and Methods Adults with painful knee conditions were prospectively enrolled from December 2021 to October 2022.

Regulated microbe vaccines: from concept to (pre-clinical) reduction to practice.

Introduction: Vaccines to prevent important infections involving, e.g. influenza viruses, severe acute respiratory syndrome-causing coronaviruses (e.

Ablation of LRP6 in alpha-smooth muscle actin-expressing cells abrogates lung inflammation and fibrosis upon bleomycin-induced lung injury.

Tissue fibrosis is a progressive pathological process with excessive deposition of extracellular matrix proteins (ECM). Myofibroblasts, identified by alpha-smooth muscle actin (αSMA) expression, play an important role in tissue fibrosis by producing ECM. Here, we found that the Wnt antagonist Dickkopf1 (DKK1) induced gene expressions associated with inflammation and fibrosis in lung fibroblasts.

Measurement of multidifferential cross sections for dijet production in proton-proton collisions at .

A measurement of the dijet production cross section is reported based on proton-proton collision data collected in 2016 at by the CMS experiment at the CERN LHC, corresponding to an integrated luminosity of up to 36.3 . Jets are reconstructed with the anti- algorithm for distance parameters of and 0.

Inhibition of HMGA2 binding to AT-rich DNA by its negatively charged C-terminus.

The mammalian high mobility group protein AT-hook 2 (HMGA2) is a small DNA-binding protein that specifically targets AT-rich DNA sequences. Structurally, HMGA2 is an intrinsically disordered protein (IDP), comprising three positively charged 'AT-hooks' and a negatively charged C-terminus. HMGA2 can form homodimers through electrostatic interactions between its 'AT-hooks' and C-terminus.

An Introduction to the Complete Blood Count for Clinical Chemists: White Blood Cells.

Background: The most frequently ordered laboratory test worldwide is the complete blood count (CBC). As clinical chemists are increasingly assigned to assist or direct laboratories outside of the traditional clinical chemistry sections, such as the automated hematology section, expertise must be established. This review article is a dedication to that ongoing effort.