Transcriptional signatures of hippocampal tau pathology in primary age-related tauopathy and Alzheimer's disease.

In primary age-related tauopathy (PART) and Alzheimer's disease (AD), tau aggregates share a similar structure and anatomic distribution, which is distinct from tau pathology in other diseases. However, transcriptional similarities between PART and AD and gene expression changes within tau-pathology-bearing neurons are largely unknown. Using GeoMx spatial transcriptomics, mRNA was quantified in hippocampal neurons with and without tau pathology in PART and AD.

A comparison of calcification mechanisms in haploid and diploid cells of the coccolithophore Calcidiscus leptoporus (Murray & Blackman 1898).

Coccolithophores are prominent marine pelagic calcifiers due to their production of calcite coccoliths. Diploid coccolithophores produce heterococcoliths intracellularly, with an organic cellulose baseplate scale acting as a nucleating substrate. However, coccolith production in the haploid life phase has not been extensively studied.

The evolutionary dynamics of plant mating systems: how bias for studying 'interesting' plant reproductive systems could backfire.

Background And Aims: An "abominable mystery": angiosperm sexual systems have been a source of both interest and frustration for the botanical community since Darwin. The evolutionary stability, overall frequency, and distribution of self-fertilization and mixed-mating systems have been explored in a variety of studies. However, there has been no recent study which directly addresses our knowledge of mating systems across families, the adequacy of existing data, or the potential for biases.

Feasibility and benefits of a simplified physics direct patient care protocol.

Purpose: To investigate the benefits and challenges of implementing a medical physics consult program in a small clinic.

Methods: A Simplified Physics Direct Patient Care (SPDPC) protocol was developed based on previously described programs. The program was streamlined to one consult with a physicist during a 30-minute time block.

RCL glycosylation of serum corticosteroid-binding globulin: implications in cortisol delivery and septic shock.

Corticosteroid-binding globulin (CBG) is a serum glycoprotein that binds and delivers anti-inflammatory cortisol to inflammatory sites through neutrophil elastase-mediated proteolysis of an exposed reactive Centre loop (RCL) on CBG. Timely and tissue-specific delivery of cortisol is critical to alleviate inflammation including in life-threatening septic shock conditions. In this two-part communication, we firstly summarise our recently published report of functional RCL O- and N-glycosylation events of serum CBG (Chernykh, J biol Chem, 2023).

Influence of Carcinoma and Sarcoma on Neutrophil Gelatinase-Associated Lipocalin and Symmetric Dimethylarginine Concentrations in Dogs.

Background: It is unknown if tumors or concomitant renal disease influence neutrophil gelatinase-associated lipocalin (NGAL) and symmetric dimethylarginine (SDMA) concentrations in tumor-bearing dogs.

Objectives: Determine the effect of tumor presence, tumor type, and metastasis on concentrations of serum NGAL (sNGAL), SDMA, urinary NGAL (uNGAL), and uNGAL-to-creatinine ratio (uNGAL/Cr) in dogs with carcinoma or sarcoma without clinically relevant renal disease.

Animals: Twenty-one dogs with carcinoma, 18 with sarcoma, and 20 healthy age-controlled dogs.

A high-throughput assay platform to discover small molecule activators of the phospholipase PLC-γ2 to treat Alzheimer's disease.

A naturally occurring missense variant of the phospholipase C isozyme, PLC-γ2, harboring a single substitution (P522R) protects against several neurodegenerative diseases, including Alzheimer's disease. The phospholipase activity of PLC-γ2 (P522R) is slightly elevated relative to its wild-type counterpart, and the general consensus is that this increased activity in microglia confers protection against neurodegeneration. In order to phenocopy this protection, we have developed a high-throughput assay to identify small molecule activators of PLC-γ2.

Outcome in Critically Ill Dogs and Dogs With Acute Kidney Injury Based on Neutrophil Gelatinase-Associated Lipocalin and Tissue Inhibitor of Metalloproteinase-2.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) and tissue inhibitor of metalloproteinase-2 (TIMP-2) have potential as early biomarkers for acute kidney injury (AKI) in dogs.

Objectives: Assess whether NGAL and TIMP-2 at admission (T0) and 24 h later (T1) identify survival in critically ill (CI) and AKI dogs, development of hospital-acquired AKI in CI dogs, and development of chronic kidney disease (CKD) in AKI dogs after 3 months.

Animals: Sixty-two client-owned dogs: 10 healthy, 24 with AKI, and 28 CI.

-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation.

Heterozygous mutations in are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal and cervical involvement. Although -related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease.

The complex I subunit B22 contains a LYR domain that is crucial for an interaction with the mitochondrial acyl carrier protein SDAP1.

Mitochondrial complex I (CI), a large multi-subunit respiratory complex contains two LYR (leucine/tyrosine/arginine) domain-containing subunits, B14 (NDUA6/LYRM6) and B22 (NDUB9/LYRM3). Mitochondrial LYR (LYRM) proteins are soluble matrix-located proteins that have been implicated in diverse functions such as iron-sulphur cluster insertion, OXPHOS complex assembly, and mitoribosome biogenesis. B14 and B22 are unique to other LYRM proteins in that they are integral components of CI.

Disease diagnostics using machine learning of B cell and T cell receptor sequences.

Clinical diagnosis typically incorporates physical examination, patient history, various laboratory tests, and imaging studies but makes limited use of the human immune system's own record of antigen exposures encoded by receptors on B cells and T cells. We analyzed immune receptor datasets from 593 individuals to develop MAchine Learning for Immunological Diagnosis, an interpretive framework to screen for multiple illnesses simultaneously or precisely test for one condition. This approach detects specific infections, autoimmune disorders, vaccine responses, and disease severity differences.

Unveiling the novel role of circadian rhythms in sepsis and septic shock: unexplored implications for chronotherapy.

Circadian rhythms are critical to coordinating body processes to external environmental cues, such as light and feeding, to ensure efficiency and maintain optimal health. These rhythms are controlled by 'clock' transcription factors, such as Clock, Bmal1, Per1/2, Cry1/2, and Rev-erbs, which are present in almost every tissue. In modern society, disruptions to normal circadian rhythms are increasingly prevalent due to extended lighting, shift work, and long-distance travel.

Data-informed selection of evidence-based treatments for posttraumatic stress disorder and co-occurring symptoms.

Posttraumatic stress disorder (PTSD) commonly co-occurs with other disorders. Although there are several evidence-based treatments available for PTSD and co-occurring disorders, including cognitive processing therapy (CPT), prolonged exposure (PE), acceptance and commitment therapy (ACT), and the unified protocol for transdiagnostic treatment of emotional disorders (UP), limited findings clarify the use of baseline symptom data to help providers and patients choose among treatments. To address this, the current study examined baseline symptoms and treatment trajectories among 90 veterans and veteran family members with probable PTSD (based on PCL-5) receiving either trauma-focused (CPT, PE) or transdiagnostic (ACT, UP) treatment via telehealth, with the aim of assisting providers in recognizing patterns to inform data-driven treatment selection.

Barriers and drivers to COVID-19 protective behaviours of forcibly displaced myanmar nationals (FDMN)/ rohingya refugees in Cox's bazar, Bangladesh: A scoping review.

About 900.000 Forcibly Displaced Myanmar Nationals (FDMN)/ Rohingya refugees live in makeshift camps in Cox's Bazar, Bangladesh. During the COVID-19 pandemic, protective behaviors were particularly important in this setting of previous severe infectious disease outbreaks.

Tissue expression and urinary excretion of liver-type fatty acid binding protein in older dogs with or without early signs of chronic kidney disease.

Liver-type fatty acid-binding protein (L-FABP) is expressed by several tissues, plays a role in fatty acid metabolism, and has antioxidant effects. Its renal expression is upregulated by stress. Urinary L-FABP (uL-FABP) is a promising kidney biomarker in people for detection of early acute and chronic kidney disease (CKD) and as a marker for progression in patients with glomerulonephritis.

Millihertz oscillations near the innermost orbit of a supermassive black hole.

Recent discoveries from time-domain surveys are defying our expectations for how matter accretes onto supermassive black holes (SMBHs). The increased rate of short-timescale, repetitive events around SMBHs, including the recently discovered quasi-periodic eruptions, are garnering further interest in stellar-mass companions around SMBHs and the progenitors to millihertz-frequency gravitational-wave events. Here we report the discovery of a highly significant millihertz quasi-periodic oscillation (QPO) in an actively accreting SMBH, 1ES 1927+654, which underwent a major optical, ultraviolet and X-ray outburst beginning in 2018.

Comparative main effects, mediators, and moderators of cognitive behavioral therapy, acceptance and commitment therapy, and emotional awareness and expression therapy for chronic spinal pain: Randomized controlled trial rationale and protocol.

Background: Chronic spinal (back/neck) pain is common and costly. Psychosocial treatments are available but have modest effects. Knowledge of treatment mechanisms (mediators and moderators) can be used to enhance efficacy.

The atypical proteome of mitochondria from mature pollen grains.

To propagate their genetic material, flowering plants rely on the production of large amounts of pollen grains that are capable of germinating on a compatible stigma. Pollen germination and pollen tube growth are thought to be extremely energy-demanding processes. This raises the question of whether mitochondria from pollen grains are specifically tuned to support this developmental process.

Impact of different pathogen classes on the serum -glycome in septic shock.

The morbidity and mortality of sepsis remain high. Clinicians lack effective markers to rapidly diagnose sepsis and identify the underlying pathogen infection particularly for patients with candidaemia or cases of culture-negative sepsis where culture-based diagnostics are inadequate. In our search for new lines of potential sepsis biomarkers, we here explore the impact of various classes of infectious agents on the serum -glycome in a septic shock cohort.

A Critical Review of the Hydrometallurgy and Pyrometallurgical Recovery Processes of Platinum Group Metals from End-of-Life Fuel Cells.

Recently, the recovery of metals extracted from the spent membrane electrode assemblies (MEAs) of fuel cells has attracted significant scientific attention due to its detrimental environmental impacts. Two major approaches, i.e.

Why and how should we simulate platform trials? Learnings from EU-PEARL.

Background: Platform trials are innovative clinical trials governed by a master protocol that allows for the evaluation of multiple investigational treatments that enter and leave the trial over time. Interest in platform trials has been steadily increasing over the last decade. Due to their highly adaptive nature, platform trials provide sufficient flexibility to customize important trial design aspects to the requirements of both the specific disease under investigation and the different stakeholders.

Individual Assembly of Radical Molecules on Superconductors: Demonstrating Quantum Spin Behavior and Bistable Charge Rearrangement.

High-precision molecular manipulation techniques are used to control the distance between radical molecules on superconductors. Our results show that the molecules can host single electrons with a spin 1/2. By changing the distance between tip and sample, a quantum phase transition from the singlet to doublet ground state can be induced.

Expansion of a conserved architecture drives the evolution of the primate visual cortex.

Human brain evolution is marked by a disproportionate expansion of cortical regions associated with advanced perceptual and cognitive functions. While this expansion is often attributed to the emergence of novel specialized brain areas, modifications to evolutionarily conserved cortical regions also have been linked to species-specific behaviors. Distinguishing between these two evolutionary outcomes has been limited by the ability to make direct comparisons between species.