Informing etiological heterogeneity of mild cognitive impairment and risk for progression to dementia with plasma p-tau217.

Background: Mild cognitive impairment (MCI) is a clinical diagnosis representing early symptom changes with preserved functional independence. There are multiple potential etiologies of MCI. While often presumed to be related to Alzheimer's disease (AD), other neurodegenerative and non-neurodegenerative causes are common.

Neuroimaging and biofluid biomarkers across race and ethnicity in older adults across the spectrum of cognition.

Neuroimaging and biofluid biomarkers provide a proxy of pathological changes for Alzheimer's disease (AD) and are useful in improving diagnosis and assessing disease progression. However, it is not clear how race/ethnicity and different prevalence of AD risks impact biomarker levels. In this narrative review, we survey studies focusing on comparing biomarker differences between non-Hispanic White American(s) (NHW), African American(s) (AA), Hispanic/Latino American(s) (HLA), and Asian American(s) with normal cognition, mild cognitive impairment, and dementia.

Functional measures and AD biomarkers among Hispanic and White non-Hispanic older adults.

Introduction: Poorer baseline functioning is associated with long-term cognitive decline among Hispanic older adults, but little is known about associations of these factors with Alzheimer's disease (AD) neuroimaging biomarkers.

Methods: A total of 461 Hispanic and White non-Hispanic (NHW) older adults who are cognitively normal ( = 76), had impaired cognition without mild cognitive impairment (MCI) ( = 41), or carried a diagnosis of MCI ( = 253) or dementia ( = 91) completed neuropsychological and functional assessment, genetic testing, and brain magnetic resonance imaging (MRI). Structural equation modeling (SEM) was used to examine predictive associations between functional and cognitive measures of AD neuroimaging biomarkers.

Dual-Probe Activity-Based Protein Profiling Reveals Site-Specific Differences in Protein Binding of EGFR-Directed Drugs.

Comparative, dose-dependent analysis of interactions between small molecule drugs and their targets, as well as off-target interactions, in complex proteomes is crucial for selecting optimal drug candidates. The affinity of small molecules for targeted proteins is largely dictated by interactions between amino acid side chains and these drugs. Thus, studying drug-protein interactions at an amino acid resolution provides a comprehensive understanding of the drug selectivity and efficacy.

Plasma p-tau217 concordance with amyloid PET among ethnically diverse older adults.

Introduction: Commercially available plasma p-tau217 biomarker tests are not well studied in ethnically diverse samples.

Methods: We evaluated associations between ALZPath plasma p-tau217 and amyloid-beta positron emission tomography (Aβ-PET) in Hispanic/Latino (88% of Cuban or South American ancestry) and non-Hispanic/Latino older adults. One- and two-cutoff ranges were derived and evaluated to assess agreement with Aβ-PET.

The Light-activated Effect of Natural Anthraquinone Parietin against Candida auris and Other Fungal Priority Pathogens.

Antimicrobial photodynamic therapy (aPDT) is an evolving treatment strategy against human pathogenic microbes such as the species, including the emerging pathogen . Using a modified EUCAST protocol, the light-enhanced antifungal activity of the natural compound parietin was explored. The photoactivity was evaluated against three separate strains of five yeasts, and its molecular mode of action was analysed via several techniques, i.

Data center TCP dataset.

In this paper, we would like to introduce a unique dataset that covers thousands of network flow measurements realized through TCP in a data center environment. The TCP protocol is widely used for reliable data transfers and has many different versions. The various versions of TCP are specific in how they deal with link congestion through the congestion control algorithm (CCA).

Structural Characterization of Monoclonal Antibodies and Epitope Mapping by FFAP Footprinting.

Covalent labeling in combination with mass spectrometry is a powerful approach used in structural biology to study protein structures, interactions, and dynamics. Recently, the toolbox of covalent labeling techniques has been expanded with fast fluoroalkylation of proteins (FFAP). FFAP is a novel radical labeling method that utilizes fluoroalkyl radicals generated from hypervalent Togni reagents for targeting aromatic residues.

Protein-Centric Analysis of Personalized Antibody Repertoires Using LC-MS-Based Fab-Profiling on a timsTOF.

Endogenous antibodies, or immunoglobulins (Igs), abundantly present in body fluids, represent some of the most challenging samples to analyze, largely due to the immense variability in their sequences and concentrations. It has been estimated that our body can produce billions of different Ig proteins with different isotypes, making their individual analysis seemingly impossible. However, recent advances in protein-centric proteomics using LC-MS coupled to Orbitrap mass analyzers to profile intact Fab fragments formed by selective cleavage at the IgG-hinge revealed that IgG repertoires may be less diverse, albeit unique for each donor.

The Mediating Effects of Education and Occupational Complexity Between Race and Longitudinal Change in Late Life Cognition in ACTIVE.

This study examined educational and occupational inequality as two aspects of social determinants of health that might mediate the longitudinal relationship between racialization and late life cognitive level and change. Participants were 2371 individuals racialized as Black and White from the ACTIVE study who provided occupational data. Data were analyzed from baseline and five assessments over 10-years using structural equation modeling.

A user DNS fingerprint dataset.

Using a user DNS fingerprint allows one to identify a specific network user regardless of the knowledge of his IP address. This method is proper, for example, when examining the behavior of a monitored network user in more depth. In contrast to other studies, this work introduces a dataset for possible user identification based only on the knowledge of its DNS fingerprint created from the previously sent DNS queries.

Cross-cultural Diagnostic Validity of the Multilingual Naming Test (MINT) in a Sample of Older Adults.

Objective: We aimed to evaluate the psychometric properties and diagnostic accuracy of the 32-item version of the Multilingual Naming Test (MINT) in participants from 2 ethnic groups (European Americans [EA; n = 106] and Hispanic Americans [HA; n = 175]) with 3 diagnostic groups (cognitively normal [CN], n = 94, mild cognitive impairment [MCI], n = 148, and dementia, n = 39).

Method: An Item Response Theory model was used to evaluate items across ethnicity and language groups (Spanish and English), resulting in a 24-item version. We analyzed the MINT discriminant and predictive validity across diagnostic groups.

Fungal Anthraquinone Photoantimicrobials Challenge the Dogma of Cationic Photosensitizers.

The photoantimicrobial potential of four mushroom species (i.e., , , , and ) was explored by studying the minimal inhibitory concentrations (MIC) via a light-modified broth microdilution assay based on the recommended protocols of the European Committee on Antimicrobial Susceptibility Testing (EUCAST).

Plasma Alzheimer's biomarkers and brain amyloid in Hispanic and non-Hispanic older adults.

Introduction: Alzheimer's disease studies often lack ethnic diversity.

Methods: We evaluated associations between plasma biomarkers commonly studied in Alzheimer's (p-tau181, GFAP, and NfL), clinical diagnosis (clinically normal, amnestic MCI, amnestic dementia, or non-amnestic MCI/dementia), and Aβ-PET in Hispanic and non-Hispanic older adults. Hispanics were predominantly of Cuban or South American ancestry.

Molecular structure of soluble vimentin tetramers.

Intermediate filaments (IFs) are essential constituents of the metazoan cytoskeleton. A vast family of cytoplasmic IF proteins are capable of self-assembly from soluble tetrameric species into typical 10-12 nm wide filaments. The primary structure of these proteins includes the signature central 'rod' domain of ~ 300 residues which forms a dimeric α-helical coiled coil composed of three segments (coil1A, coil1B and coil2) interconnected by non-helical, flexible linkers (L1 and L12).

Associations between social determinants of health and 10-year change in everyday functioning within Black/African American and White older adults enrolled in ACTIVE.

Introduction: Given prior work showing racial differences on baseline social determinants of health (SDoH) and 10-year trajectories of everyday functioning, we examined associations between SDoH and longitudinal everyday functioning performance in Black/African American and White older adults.

Methods: Participants were 2505 older adults (M = 73.5; 28% Black/African American) without dementia.

International Consensus Statement on Obstructive Sleep Apnea.

Background: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA).

Methods: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats.

Top-Down Detection of Oxidative Protein Footprinting by Collision-Induced Dissociation, Electron-Transfer Dissociation, and Electron-Capture Dissociation.

Fast photochemical oxidation of proteins (FPOP) footprinting is a structural mass spectrometry method that maps proteins by fast and irreversible chemical reactions. The position of oxidative modification reflects solvent accessibility and site reactivity and thus provides information about protein conformation, structural dynamics, and interactions. Bottom-up mass spectrometry is an established standard method to analyze FPOP samples.

Utilization of Fast Photochemical Oxidation of Proteins and Both Bottom-up and Top-down Mass Spectrometry for Structural Characterization of a Transcription Factor-dsDNA Complex.

A combination of covalent labeling techniques and mass spectrometry (MS) is currently a progressive approach for deriving insights related to the mapping of protein surfaces or protein-ligand interactions. In this study, we mapped an interaction interface between the DNA binding domain (DBD) of FOXO4 protein and the DNA binding element (DAF16) using fast photochemical oxidation of proteins (FPOP). Residues involved in protein-DNA interaction were identified using the bottom-up approach.

The photosensitizer emodin is concentrated in the gills of the fungus Cortinarius rubrophyllus.

The colorful agaricoid fruiting bodies of dermocyboid Cortinarii owe their magnificent hue to a mixture of anthraquinone (AQ) pigments. Recently, it was discovered that some of these fungal anthraquinones have an impressive photopharmacological effect. The question, therefore, arises as to whether these pigments are also of ecological or functional significance.

Xanthoepocin, a photolabile antibiotic of Penicillium ochrochloron CBS 123823 with high activity against multiresistant gram-positive bacteria.

Background: With the steady increase of antibiotic resistance, several strategies have been proposed in the scientific community to overcome the crisis. One of many successful strategies is the re-evaluation of known compounds, which have been early discarded out of the pipeline, with state-of-the-art know-how. Xanthoepocin, a polyketide widespread among the genus Penicillium with an interesting bioactivity spectrum against gram-positive bacteria, is such a discarded antibiotic.

Fast Fluoroalkylation of Proteins Uncovers the Structure and Dynamics of Biological Macromolecules.

Covalent labeling of proteins in combination with mass spectrometry has been established as a complementary technique to classical structural methods, such as X-ray, NMR, or cryogenic electron microscopy (Cryo-EM), used for protein structure determination. Although the current covalent labeling techniques enable the protein solvent accessible areas with sufficient spatial resolution to be monitored, there is still high demand for alternative, less complicated, and inexpensive approaches. Here, we introduce a new covalent labeling method based on fast fluoroalkylation of proteins (FFAP).

2D perovskite-based high spatial resolution X-ray detectors.

X-ray radiography is the most widely used imaging technique with applications encompassing medical and industrial imaging, homeland security, and materials research. Although a significant amount of research and development has gone into improving the spatial resolution of the current state-of-the-art indirect X-ray detectors, it is still limited by the detector thickness and microcolumnar structure quality. This paper demonstrates high spatial resolution X-ray imaging with solution-processable two-dimensional hybrid perovskite single-crystal scintillators grown inside microcapillary channels as small as 20 µm.