Association of the interaction between daily step counts and frailty with disability in older adults.

The differences in the association of objectively measured physical activity with disability between frail and non-frail older adults remain unclear. We (1) evaluated the dose-dependent relationship between daily steps and disability in older adults with and without frailty and (2) examined the interaction between steps and frailty status in relation to the risk of disability. This prospective study used data from 4065 adults aged ≥ 65 years from the Kyoto-Kameoka Study, Japan.

Longitudinal phosphoproteomics reveals the PI3K-PAK1 axis as a potential target for recurrent colorectal liver metastases.

The resistance of colorectal cancer liver metastases (CRLMs) to 5-fluorouracil (5-FU) chemotherapy remains a significant global health challenge. We investigated the phosphoproteomic dynamics of serial tissue sections obtained from initial metastases and recurrent tumors collected from 24 patients to address this unmet need for innovative therapeutic strategies for patients with CRLM with a poor prognosis. Our analysis revealed the activation of PAK kinase in patients with CRLM with a poor prognosis.

High-Recovery Desalting Tip Columns for a Wide Variety of Peptides in Mass Spectrometry-Based Proteomics.

In mass spectrometry-based proteomics, loss-minimized peptide purification techniques play a key role in improving sensitivity and coverage. We have developed a desalting tip column packed with thermoplastic polymer-coated chromatographic particles, named ChocoTip, to achieve high recoveries in peptide purification by pipet-tip-based LC with centrifugation (tipLC). ChocoTip identified more than twice as many peptides from 20 ng of tryptic peptides from Hela cell lysate compared to a typical StageTip packed with chromatographic particles entangled in a Teflon mesh in tipLC.

Association between Slow and Rapid Weight Gain before 36 Weeks of Corrected Age and 6-Year-Developmental Quotient in Infants Born at <26 Weeks of Gestation.

Objective:  The postnatal growth of preterm infants is influenced by various factors; however, the association between growth and long-term outcomes in extremely preterm infants remains unclear. Therefore, we aimed to determine the association between 6-year development and body weight (BW) at 36 weeks of corrected age (CA) in extremely preterm infants.

Study Design:  We conducted a retrospective observational study including extremely preterm infants born at < 26 weeks of gestation.

jPOST environment accelerates the reuse and reanalysis of public proteome mass spectrometry data.

jPOST (https://jpostdb.org/) comprises jPOSTrepo (https://repository.jpostdb.

Highly sequence-specific, timing-controllable mA demethylation by modulating RNA-binding affinity of mA erasers.

Recent advancements in tools using programmable RNA binding proteins and mA-erasers enable sequence-selective and timing-controllable mA demethylation. However, off-target effects are still a concern. This study addresses the problem by reducing the RNA-binding ability of mA-erasers.

An atlas of the aging mouse proteome reveals the features of age-related post-transcriptional dysregulation.

To what extent and how post-transcriptional dysregulation affects aging proteome remains unclear. Here, we provide proteomic data of whole-tissue lysates (WTL) and low-solubility protein-enriched fractions (LSF) of major tissues collected from mice of 6, 15, 24, and 30 months of age. Low-solubility proteins are preferentially affected by age and the analysis of LSF doubles the number of proteins identified to be differentially expressed with age.

Quantitation of Host Cell Proteins by Capillary LC/IMS/MS/MS in Combination with Rapid Digestion on Immobilized Trypsin Column Under Native Conditions.

Host cell protein (HCP) impurities are considered a critical quality attribute of biopharmaceuticals because of their potential to compromise safety and efficacy, and LC/MS-based analytical methods have been developed to identify and quantify individual proteins instead of employing enzyme-linked immunosorbent assay to assess total HCP levels. Native digestion enables highly sensitive detection of HCPs but requires overnight incubation to generate peptides, limiting the throughput of sample preparation. In this study, we developed an approach employing native digestion on a trypsin-immobilized column to improve the sensitivity and throughput.

Revisiting Protein Reversed-Phase Chromatography for Bottom-Up Proteomics.

We revisited protein reversed-phase chromatography (RP), using state-of-the-art RP columns developed for biopharmaceuticals, such as monoclonal antibodies, in order to evaluate the suitability of this methodology as a prefractionation step for bottom-up proteomics. The protein RP prefractionation (Prot-RP) method was compared with two other widely used prefractionation methods, SDS-PAGE and high-pH peptide RP (Pept-RP) by using cell lysates as samples. The overlap between fractions of Prot-RP was comparable to that of SDS-PAGE, and the protein recovery was approximately 2-fold higher.

Parent-child skin carotenoid level and vegetable intake relationships in users of children's cafeterias in Japan.

Introduction: Studies on the relationship between parental and child dietary intakes are limited in Asian populations. Here, we examined parent-child relationships in skin carotenoid levels and vegetable intake in a Japanese community.

Methods: The study participants were 58 children aged 6-15 years and 39 of their guardians (parents) using children's cafeterias.

Radiographic Knee Osteoarthritis Is a Risk Factor for the Development of Dementia: Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study.

Objective: Osteoarthritis is linked to dementia, but no longitudinal studies have established this connection. This prospective cohort study from the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS) aimed to determine if knee osteoarthritis (KOA) independently predicts dementia in adults aged 65 and above.

Methods: Participants were classified by the Kellgren-Laurence scale into no/minimal KOA (grades 0 and I) and definitive KOA (grade II or higher).

Small extracellular vesicles carrying reovirus, tumor antigens, interferon-β, and damage-associated molecular patterns for efficient tumor treatment.

Small extracellular vesicles (SEV) have attracted much attention both as mediators of intercellular communication and as drug delivery systems. In addition, recent studies have shown that SEV containing virus components and virus particles are released from virus-infected cells. Oncolytic viruses, which efficiently kill tumor cells by tumor cell-specific replication, have been actively studied as novel anticancer agents in clinical and preclinical studies.

One-step N-Terminomics Based on Isolation of Protein N-Terminal Peptides From LysargiNase Digests by Tip-Based Strong Cation Exchange Chromatography.

We have developed a one-step isolation method for protein N-terminal peptides from LysargiNase digests by pipette tip-based strong cation exchange (SCX) chromatography. This CHAMP-N (CHromatographic AMplification of Protein N-terminal peptides) method using disposable and parallel-processable SCX tips instead of conventional HPLC SCX columns facilitates simple, sensitive, reproducible, and high-throughput N-terminomic profiling without sacrificing the high identification numbers and selectivity achieved by the HPLC-based method. By applying the CHAMP-N method to HEK293T cells, we identified novel cleavage sites for signal and transit peptides and non-canonical translation initiation sites.

Systematic Identification of Kinase-Substrate Relationship by Integrated Phosphoproteome and Interactome Analysis.

The sensitivity of phosphorylation site identification by mass spectrometry (MS)-based phosphoproteomics has improved significantly. However, the lack of kinase-substrate relationship (KSR) data has hindered improvement of the range and accuracy of kinase activity prediction using phosphoproteome data. We herein describe the application of a systematic identification of KSR by integrated phosphoproteome and interactome analysis using doxycycline (Dox)-induced target kinase-overexpressing HEK-293 cells.

Skin Carotenoid Levels Are Associated with Demographic Factors, Body Size, and Fruit and Vegetable Intake in the Japanese Population.

This study aimed to determine the association between demographic factors, body size, and fruit and vegetable intake in the general population, focusing on individuals with both low and high skin carotenoid levels. This cross-sectional study was conducted during the 14th National Convention on the Promotion of Food and Nutrition Education (2019) in Yamanashi, Japan (a rural area) and the Open House 2019 at the National Institute of Biomedical Innovation, Health, and Nutrition in Tokyo, Japan (an urban area). Skin carotenoid measurements were conducted, and the participants were asked to fill out a self-administered questionnaire.

Morning physical activity may be more beneficial for blood lipids than afternoon physical activity in older adults: a cross-sectional study.

Background: The effect of differences in daily physical activity patterns on blood lipids has not been determined. This study examines the effects of the differences in free-living daily physical activity patterns (amount and intensity) on blood lipid levels in older adults.

Methods: This cross-sectional study included 51 older participants (71.

Proteomic analysis of serum extracellular vesicles reveals Fibulin-3 as a new marker predicting liver-related events in MASLD.

Background: There is a need for novel noninvasive markers for metabolic dysfunction-associated steatotic liver disease (MASLD) to stratify patients at high risk for liver-related events including liver cancer and decompensation. In the present study, we used proteomic analysis of proteins in extracellular vesicles (EVs) to identify new biomarkers that change with fibrosis progression and can predict the development of liver-related events.

Methods: We analyzed serum EVs from 50 patients with MASLD assessed for liver fibrosis by biopsy and identified proteins that altered with advanced fibrosis.

Long-read sequencing for 29 immune cell subsets reveals disease-linked isoforms.

Alternative splicing events are a major causal mechanism for complex traits, but they have been understudied due to the limitation of short-read sequencing. Here, we generate a full-length isoform annotation of human immune cells from an individual by long-read sequencing for 29 cell subsets. This contains a number of unannotated transcripts and isoforms such as a read-through transcript of TOMM40-APOE in the Alzheimer's disease locus.