SampleExplorer: Using language models to discover relevant transcriptome data.

Motivation: Over the last two decades, transcriptomics has become a standard technique in biomedical research. We now have large databases of RNA-seq data, accompanied by valuable metadata detailing scientific objectives and the experimental procedures employed. The metadata is crucial in understanding and replicating published studies, but so far has been underutilised in helping researchers to discover existing datasets.

Exploring the Tomato Root Protein Network Exploited by Core Type 3 Effectors from the Species Complex.

Proteomics has become a powerful approach for the identification and characterization of type III effectors (T3Es). Members of the species complex (RSSC) deploy T3Es to manipulate host cells and to promote root infection of, among others, a wide range of solanaceous plants such as tomato, potato, and tobacco. Here, we used TurboID-mediated proximity labeling (PL) in tomato hairy root cultures to explore the proxeomes of the core RSSC T3Es RipU, RipD, and RipB.

Molecular dynamics in pharmaceutical nanotechnology: simulating interactions and advancing applications.

Molecular Dynamics (MD) simulations are now widely utilized in pharmaceutical nanotechnology to gain deeper understanding of nanoscale processes imperative to drug design. This review has also detailed how MD simulation can be employed in the study of drug-nanocarrier interactions, controlling release of chemical compounds from drug delivery systems and increasing solubility and bioavailability of nanocarriers. Furthermore, MD contributes to examining the drug delivery systems, measuring the toxic effects, and determining biocompatibility of nanomedical systems.

Exploring the Conformational Space of MPS1 Kinase Using Metadynamics.

MPS1 kinase is a dual specificity kinase that plays an important role in the spindle assembly checkpoint mechanism during cell division. Overexpression of MPS1 kinase is reported in several cancers. However, drug discovery and development efforts targeting MPS1 kinase did not result in any clinically successful candidates.

EZH2-mediated downregulation of miR-155-5p contributes to prostate cancer cell malignancy through SMAD2 and TAB2.

miR-155 exhibits variable expression in different tumors and fulfills diverse biological roles. However, specific molecular mechanisms by which miR-155-5p, which is under-expressed in prostate cancer (PCa), operates are yet to be elucidated. The role of the enhancer of zeste 2 (EZH2)/miR-155-5p axis in PCa was determined by using bioinformatics tools and performing luciferase reporter assay, chromatin immunoprecipitation PCR, CCK-8 assays, cell migration and invasion assays, RNA isolation, reverse transcription quantity (RT-qPCR) and Western blot.

Biomarkers.

Background: It is challenging to distinguish which subcortical ischemic vascular disease (SIVD) patients will present with cognitive impairment. A blood-based biomarker to distinguish SIVD patients with cognitive impairment would be superior to neuropsychological measures and neuroimaging measures in terms of cost, time, and feasibility for repeated measures. Metabolomics profiling studies could help identify blood-based biomarkers for SIVD patients with cognitive impairment.

Biomarkers.

Background: A key neuropathological feature in the early stages of Alzheimer's disease (AD) involves hippocampal dysfunction arising from the accumulation of amyloid-β (Aβ). Previously, our laboratory identified a shift in the synaptic plasticity long term potentiation (LTP)/long term depression (LTD) induction threshold, leading to memory deficits in a non-transgenic murine model of early AD generated by intracerebroventricular (icv.) injections Aβ oligomers (oAβ), one of the most predominant pathogenetic factors in initial stages of the disease.

Biomarkers.

Background: Neuroimaging-based evidence suggests that changes in cerebral tissue determinants, including axonal density and myelin content, are associated with aging and neurodegenerative diseases. While neuroimaging markers show strong association with physiological changes, direct validation of their specificity remains challenging. Histology provides useful information for validation, however, faces limitations including denaturation of the sample during preparation.

Biomarkers.

Background: Autosomal dominant Alzheimer disease (ADAD) is characterized by genetic mutations affecting the beta-amyloid (Aβ) pathway. However, vascular and immune factors play important roles which are not completely understood. Understanding the function of the neurovascular unit (NVU) comprised of neurons, glial cells, and vasculature, at different disease stages appears ideal to developing and evaluating therapeutics.

Biomarkers.

Background: Detecting Alzheimer's disease (AD) biological hallmarks before clinical symptoms emerge is now possible with available blood-based biomarkers. However, the rate of cognitive decline varies among individuals at risk of AD, and accurate prognostic blood-based biomarkers are lacking. Our goal is to identify plasma proteins predictive of fast cognitive decline in asymptomatic individuals at risk of AD.

Biomarkers.

Background: Alzheimer's disease (AD) is a complex disorder with a strong genetic component, yet many genetic risk factors remain unknown. Integrating genome-wide association studies (GWAS) and high-throughput proteomic platforms is a useful strategy to evaluate protein quantitative trait loci (pQTLs) and to detect candidate genes and pathways involved in AD. Due to the novelty of these techniques, the identification of reliable protein measures through a comprehensive quality control is mandatory.

Biomarkers.

Background: Cerebral small vessel disease (cSVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although risk factors for cSVD have been identified, little is known about the biological processes and molecular mediators that influence cSVD development and progression.

Methods: Within the Atherosclerosis Risk in Communities (ARIC) study, we used SomaScan Multiplexed Proteomic technology to relate 4,877 plasma proteins to concurrently measured MRI-defined cSVD characteristics, including WMHs, CMHs, and lacunar infarcts, in late-life (n=1508; mean age: 76).

Biomarkers.

Background: Changes in Amyloid-β (A) and hyperphosphorylated Tau (T) in the brain and cerebrospinal fluid (CSF) precedes AD symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies.

Method: We used the Somascan assay for measuring the protein levels of 7,029 analytes in CSF of 2,286 participants from four different cohorts. We employed a three-stage analytical approach (discovery, replication, and meta-analysis).

Biomarkers.

Background: The identification of novel blood-based biomarkers of small vessel disease of the brain (SVD) may improve pathophysiologic understanding and inform the development of new therapeutic strategies for prevention. We evaluated plasma proteomic associations of white matter fractional anisotropy (WMFA), white matter hyperintensity (WMH) volume, enlarged perivascular space (ePVS) volume, and the presence of microbleeds (MB) on brain magnetic resonance imaging (MRI) in the population-based Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: Eligible MESA participants had 2941 plasma proteins measured from stored blood samples (collected in 2016-2018) using the antibody-based Olink proteomics platform, and completed brain MRI scans in 2018-2019.

Biomarkers.

Background: The research on Alzheimer's disease (AD) has substantially advanced in relation to plasma biomarkers, such as pTau217, for the detection of amyloid (Aβ) pathology which identify, with high accuracy, individuals in the AD biological continuum. However, as these biomarkers become abnormal very early in the disease, biomarkers identifying more advanced disease stages and proxying pathophysiological processes beyond amyloidosis are still needed. Therefore, we have conducted a proteomic study, on plasma and CSF, aiming at identifying proteins reflecting pathological changes in AD.

Biomarkers.

Background: Hypertension is widely prevalent and independently increases the risk of dementia. Advances in high-throughput plasma proteomics analyzed may offer new opportunities to improve risk stratification for these patients.

Method: This study involved a proteomic analysis of plasma samples collected during the baseline recruitment of participants in the UK Biobank.

Biomarkers.

Background: Brain, cerebrospinal fluid (CSF), and plasma metabolomics have been informative in identifying disrupted metabolism pathways in Alzheimer's disease (AD). However, many AD-focused metabolomics studies profiled a relatively small number of individuals and metabolites, especially for CSF. In addition, past studies were limited to one or two tissues.

Biomarkers.

Background: There is growing interest in the role of environmental factors (i.e., exposome) in the pathogenesis of Alzheimer's diseases.

Biomarkers.

Background: Diet has been associated with memory, emotion/stress regulation, structure and function of the hippocampus and amygdala and attenuation of cognitive aging. There is a well-recognized lack of reliability in self-reported dietary intake and great interest in objective metabolic readout of dietary patterns. In this study we constructed dietary profiles from untargeted metabolomics data using a novel metadata-based source annotation method developed at the Dorrestein Lab, also referred to as "foodomics".

Biomarkers.

Background: Alzheimer's disease (AD) pathology occurs in the brain before manifestation of significant cognitive decline. Growing evidence suggests that brain networks such as default mode network (DMN) or salience network, identified through resting-state functional magnetic resonance imaging (MRI), are affected by AD pathology. In this study, we investigated the relationship between network segregation and the key in vivo AD pathologies including beta-amyloid (Aβ) and tau deposition in old adults with no cognitive impairment.

Biomarkers.

Background: Neurodegenerative diseases are a heterogeneous group of illnesses. Differences across patients exist in the underlying biological drivers of disease. Furthermore, cross-diagnostic disease mechanisms exist, and different pathologies often co-occur in the brain.

Biomarkers.

Background: A new pathophysiologic approach to evaluating hyponatremic patients identified the different causes of hyponatremia, including non-hyponatremic patients with renal salt wasting (RSW). RSW was considered a rare to nonexistent syndrome until we found 24 (38%) of 62 hyponatremic patients in a general medical ward to have RSW. We induced RSW in rats by injecting plasma from 18 AD patients suspected to have RSW.

Biomarkers.

Background: It is now widely acknowledged that diet, lifestyle, and environmental exposures largely affect an individual's metabolic state in health and disease, including the brain. Metabolomics has demonstrated its potential to enable exciting discoveries in brain health, facilitated by advances in analytical and informatics techniques. Here, we highlighted the use of MS/MS-based untargeted metabolomics to study the diet and medication exposure of cognitively declined cohorts through the newly developed FoodMASST and DrugMASST tools.

Biomarkers.

Background: Despite age being the primary risk factor for Alzheimer's disease (AD), there remains a necessity for a thorough understanding of the distinct biological pathways affected in the course of healthy aging as opposed to the pathological aging that leads to neurodegeneration. As the genome remains constant throughout one's lifespan, it becomes crucial to unravel the impact of aging on the proteome. Proteins, being key players in various cellular functions, mediate the effects of environmental stimuli and epigenetic alterations.

Biomarkers.

Background: Alzheimer's disease (AD) is a devastating disease at an individual level and for the wider society. Despite huge research efforts the underlaying causes of AD is still not well understood. We know that lipid metabolism is fundamental for maintaining a heathy brain and that some of the strongest risk factors for AD, such as APOE4, affect lipids.