Loss of endogenous estrogen alters mitochondrial metabolism and muscle clock-related protein Rbm20 in female mdx mice.

Female carriers of a Duchenne muscular dystrophy (DMD) gene mutation manifest exercise intolerance and metabolic anomalies that may be exacerbated following menopause due to the loss of estrogen, a known regulator of skeletal muscle function and metabolism. Here, we studied the impact of estrogen depletion (via ovariectomy) on exercise tolerance and muscle mitochondrial metabolism in female mdx mice and the potential of estrogen replacement therapy (using estradiol) to protect against functional and metabolic perturbations. We also investigated the effect of estrogen depletion, and replacement, on the skeletal muscle proteome through an untargeted proteomic approach with TMT-labelling. Our study confirms that loss of estrogen in female mdx mice reduces exercise capacity, tricarboxylic acid cycle intermediates, and citrate synthase activity but that these deficits are offset through estrogen replacement therapy. Furthermore, ovariectomy downregulated protein expression of RNA-binding motif factor 20 (Rbm20), a critical regulator of sarcomeric and muscle homeostasis gene splicing, which impacted pathways involving ribosomal and mitochondrial translation. Estrogen replacement modulated Rbm20 protein expression and promoted metabolic processes and the upregulation of proteins involved in mitochondrial dynamics and metabolism. Our data suggest that estrogen mitigates dystrophinopathic features in female mdx mice and that estrogen replacement may be a potential therapy for post-menopausal DMD carriers.

HtrA, fatty acids, and membrane protein interplay in Chlamydia trachomatis to impact stress response and trigger early cellular exit.

Chlamydia trachomatis is an intracellular bacterial pathogen that undergoes a biphasic developmental cycle, consisting of intracellular reticulate bodies and extracellular infectious elementary bodies. A conserved bacterial protease, HtrA, was shown previously to be essential for Chlamydia during the reticulate body phase, using a novel inhibitor (JO146). In this study, isolates selected for the survival of JO146 treatment were found to have polymorphisms in the acyl-acyl carrier protein synthetase gene (aasC). AasC encodes the enzyme responsible for activating fatty acids from the host cell or synthesis to be incorporated into lipid bilayers. The isolates had distinct lipidomes with varied fatty acid compositions. A reduction in the lipid compositions that HtrA prefers to bind to was detected, yet HtrA and MOMP (a key outer membrane protein) were present at higher levels in the variants. Reduced progeny production and an earlier cellular exit were observed. Transcriptome analysis identified that multiple genes were downregulated in the variants especially stress and DNA processing factors. Here, we have shown that the fatty acid composition of chlamydial lipids, HtrA, and membrane proteins interplay and, when disrupted, impact chlamydial stress response that could trigger early cellular exit. IMPORTANCE: Chlamydia trachomatis is an important obligate intracellular pathogen that has a unique biphasic developmental cycle. HtrA is an essential stress or virulence protease in many bacteria, with many different functions. Previously, we demonstrated that HtrA is critical for Chlamydia using a novel inhibitor. In the present study, we characterized genetic variants of Chlamydia trachomatis with reduced susceptibility to the HtrA inhibitor. The variants were changed in membrane fatty acid composition, outer membrane proteins, and transcription of stress genes. Earlier and more synchronous cellular exit was observed. Combined, this links stress response to fatty acids, membrane proteins, and HtrA interplay with the outcome of disrupted timing of chlamydial cellular exit.

Sex-Dependent Changes to the Intestinal and Hepatic Abundance of Drug Transporters and Metabolizing Enzymes in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is characterized by death and dysfunction of motor neurons that result in a rapidly progressing loss of motor function. While there are some data on alterations at the blood-brain barrier (BBB) in ALS and their potential impact on CNS trafficking of drugs, little is reported on the impact of this disease on the expression of drug-handling proteins in the small intestine and liver. This may impact the dosing of the many medicines that individuals with ALS are prescribed. In the present study, a proteomic evaluation was performed on small intestine and liver samples from postnatal day 120 SOD1G93A mice (a model of familial ALS that harbors a human mutant form of superoxide dismutase 1) and wild-type (WT) littermates (n = 7/genotype/sex). Untargeted, quantitative proteomics was undertaken using either label-based [tandem mass tag (TMT)] or label-free [data-independent acquisition (DIA)] acquisition strategies on high-resolution mass spectrometric instrumentation. Copper chaperone for superoxide dismutase (CCS) was significantly higher in SOD1G93A samples compared to the WT samples for both sexes and tissues, therefore representing a potential biomarker for ALS in this mouse model. Relative to WT mice, male SOD1G93A mice had significantly different proteins (Padj < 0.05, |fold-change|>1.2) in the small intestine (male 22, female 1) and liver (male 140, female 3). This included an up-regulation of intestinal transporters for dietary glucose [solute carrier (SLC) SLC5A1] and cholesterol (Niemann-Pick c1-like 1), as well as for several drugs (e.g., SLC15A1), in the male SOD1G93A mice. There was both an up-regulation (e.g., SLCO2A1) and down-regulation (ammonium transporter rh type b) of transporters in the male SOD1G93A liver. In addition, there was both an up-regulation (e.g., phosphoenolpyruvate carboxykinase) and down-regulation (e.g., carboxylesterase 1) of metabolizing enzymes in the male SOD1G93A liver. This proteomic data set identified male-specific changes to key small intestinal and hepatic transporters and metabolizing enzymes that may have important implications for the bioavailability of nutrients and drugs in individuals with ALS.

Phospho-Analyst: An Interactive, Easy-to-Use Web Platform To Analyze Quantitative Phosphoproteomics Data.

Phosphoproteomics is nowadays the method of choice to comprehensively identify and quantify thousands of phosphorylated peptides and their associated proteins with the goal of interrogating changes in signal transduction pathways and other cellular processes. One of the most popular software suites to analyze phosphoproteomic data sets is MaxQuant, which converts mass spectrometric raw data into quantitative information on phosphopeptides and proteins. However, despite the increased utilization of phosphoproteomics in biomedical research, simple and user-friendly tools supporting downstream statistical analysis and interpretation of these highly complex outputs are still lacking. We have therefore developed Phospho-Analyst, which─similar to its sibling LFQ-Analyst─is an easy-to-use, interactive web application specifically designed to reproducibly perform differential expression analyses with "one click" and to visualize phosphoproteomic results in a meaningful and practical manner. Furthermore, if quantitative total proteomic information is available for the same samples, Phospho-Analyst automatically normalizes all phosphoproteomic results to underlying protein abundance levels, thereby ensuring that only genuine changes in phosphorylation events are considered. As such, Phospho-Analyst can not only be used by experienced proteomic veterans but also by researchers without any prior knowledge in (phospho)proteomics, statistics, or bioinformatics. Phospho-Analyst, including a detailed manual, is freely available at https://analyst-suites.org/apps/phospho-analyst/.

Brain health is independently impaired by E-vaping and high-fat diet.

Tobacco smoking and high-fat diet (HFD) independently impair short-term memory. E-cigarettes produce e-vapour containing flavourings and nicotine. Here, we investigated whether e-vapour inhalation interacts with HFD to affect short-term memory and neural integrity. Balb/c mice (7 weeks, male) were fed a HFD (43% fat, 20 kJ/g) for 16 weeks. In the last 6 weeks, half of the mice were exposed to tobacco-flavoured e-vapour from nicotine-containing (18 mg/L) or nicotine-free (0 mg/L) e-fluids twice daily. Short-term memory function was measured in week 15. HFD alone did not impair memory function, but increased brain phosphorylated (p)-Tau and astrogliosis marker, while neuron and microglia levels were decreased. E-vapour exposure significantly impaired short-term memory function independent of diet and nicotine. Nicotine free e-vapour induced greater changes compared to the nicotine e-vapour and included, increased systemic cytokines, increased brain p-Tau and decreased postsynaptic density protein (PSD)-95 levels in chow-fed mice, and decreased astrogliosis marker, increased microglia and increased glycogen synthase kinase levels in HFD-fed mice. Increased hippocampal apoptosis was also differentially observed in chow and HFD mice. In conclusion, E-vapour exposure impaired short-term memory independent of diet and nicotine, and was correlated to increased systemic inflammation, reduced PSD-95 level and increased astrogliosis in chow-fed mice, but decreased gliosis and increased microglia in HFD-fed mice, indicating the inflammatory nature of e-vapour leading to short term memory impairment.

ß-Methylamino-L-alanine-induced protein aggregation in vitro and protection by L-serine.

The cyanobacterial non-protein amino acid α-amino-ß-methylaminopropionic acid, more commonly known as BMAA, was first discovered in the seeds of the ancient gymnosperm Cycad circinalis (now Cycas micronesica Hill). BMAA was linked to the high incidence of neurological disorders on the island of Guam first reported in the 1950s. BMAA still attracts interest as a possible causative factor in amyotrophic lateral sclerosis (ALS) following the identification of ALS disease clusters associated with living in proximity to lakes with regular cyanobacterial blooms. Since its discovery, BMAA toxicity has been the subject of many in vivo and in vitro studies. A number of mechanisms of toxicity have been proposed including an agonist effect at glutamate receptors, competition with cysteine for transport system xc_ and other mechanisms capable of generating cellular oxidative stress. In addition, a wide range of studies have reported effects related to disturbances in proteostasis including endoplasmic reticulum stress and activation of the unfolded protein response. In the present studies we examine the effects of BMAA on the ubiquitin-proteasome system (UPS) and on chaperone-mediated autophagy (CMA) by measuring levels of ubiquitinated proteins and lamp2a protein levels in a differentiated neuronal cell line exposed to BMAA. The BMAA induced increases in oxidised proteins and the increase in CMA activity reported could be prevented by co-administration of L-serine but not by the two antioxidants examined. These data provide further evidence of a protective role for L-serine against the deleterious effects of BMAA.

Toxicity and bioaccumulation of two non-protein amino acids synthesised by cyanobacteria, ß-N-Methylamino-L-alanine (BMAA) and 2,4-diaminobutyric acid (DAB), on a crop plant.

In order to study the toxicity of the cyanobacterial non-protein amino acids (NPAAs) L-ß-N-methylamino-L-alanine (BMAA) and its structural isomer L-2,4-diaminobutyric acid (DAB) in the forage crop plant alfalfa (Medicago sativa), seedlings were exposed to NPAA-containing media for four days. Root growth was significantly inhibited by both treatments. The content of derivatised free and protein-bound BMAA and DAB in seedlings was then analysed by LC-MS/MS. Both NPAAs were detected in free and protein-bound fractions with higher levels detected in free fractions. Compared to shoots, there was approximately tenfold more BMAA and DAB in alfalfa roots. These results suggest that NPAAs might be taken up into crop plants from contaminated irrigation water and enter the food chain. This may present an exposure pathway for NPAAs in humans.

Formylated N-terminal methionine is absent from the Mycoplasma hyopneumoniae proteome: Implications for translation initiation.

N-terminal methionine excision (NME) is a proteolytic pathway that cleaves the N-termini of proteins, a process that influences where proteins localise in the cell and their turnover rates. In bacteria, protein biosynthesis is initiated by formylated methionine start tRNA (fMet-tRNAfMet). The formyl group is attached by formyltransferase (FMT) and is subsequently removed by peptide deformylase (PDF) in most but not all proteins. Methionine aminopeptidase then cleaves deformylated methionine to complete the process. Components of NME, particularly PDF, are promising therapeutic targets for bacterial pathogens. In Mycoplasma hyopneumoniae, a genome-reduced, major respiratory pathogen of swine, pdf and fmt are absent from its genome. Our bioinformatic analysis uncovered additional enzymes involved in formylated N-terminal methionine (fnMet) processing missing in fourteen mycoplasma species, including M. hyopneumoniae but not in Mycoplasma pneumoniae, a major respiratory pathogen of humans. Consistent with our bioinformatic studies, an analysis of in-house tryptic peptide libraries confirmed the absence of fnMet in M. hyopneumoniae proteins but, as expected fnMet peptides were detected in the proteome of M. pneumoniae. Additionally, computational molecular modelling of M. hyopneumoniae translation initiation factors reveal structural and sequence differences in areas known to interact with fMet-tRNAfMet. Our data suggests that some mycoplasmas have evolved a translation process that does not require fnMet.

How suspect race affects police use of force in an interaction over time.

Although studies often find racial disparities in policing outcomes, less is known about how suspect race biases police interactions as they unfold. This study examines what is differentially occurring during police-suspect interactions for White, Black, and Latino suspects across time. It is hypothesized that racial bias may be more evident earlier in interactions, when less information about the situation is available. One hundred thirty-nine (62 White, 42 Black, and 35 Latino) use-of-force case files and associated written narratives from a medium to large size urban police department in the United States were analyzed. Trained coders broke down the interaction narratives into discrete "sequences," or dyadic action-reaction steps involving a suspect action (level of resistance) and an officer response (level of force). A linear mixed-effects model was run on amount of police use of force by suspect race and time, with suspect resistance and suspect actions toward third-party/self as controls. Results demonstrated that Black and Latino suspects receive more force in the beginning stages of the interaction, whereas Whites escalated in level of force faster after initial levels. By breaking down police-suspect interactions into discrete sequences, the current study reveals a better understanding of when bias originates in police use of force and informs how to focus policing interventions. (PsycINFO Database Record

The application of terminomics for the identification of protein start sites and proteoforms in bacteria.

Protein terminomics, or the study of amino acids sequences at the protein amino or carboxyl terminus has rapidly evolved as a proteomic discipline due to significant methodological improvements in the labelling and recovery of terminal peptides as well as the increased speed and sensitivity of current mass spectrometry instrumentation. The most significant beneficiaries of these developments include an increased awareness and understanding of complex proteolytic cascades that regulate key biological processes and in genome annotation. Most terminomics research to date has focused on gaining insight into important biological processes such as inflammation, wound healing and cancer. The application of terminomics to the study of important biological questions in prokaryotes is gaining traction. Here we review current applications and progress of terminomics in prokaryotes, discuss the significance of protease research in bacterial pathogenesis and protein maturation, and suggest novel applications of terminomics in the study of infectious disease.

Cognitive Impairment and Social Determinants of Health Among Indigenous Women.

BACKGROUND AND OBJECTIVES: Cognitive impairment and Alzheimer's disease and related dementias (ADRD) pose significant challenges for Indigenous populations, necessitating urgent research. Limited evidence suggests that high rates of ADRD among Indigenous peoples are associated with social determinants of health (SDOH), such as education, income, health literacy, religion, and social engagement. RESEARCH DESIGN AND METHODS: Collaborating with a Northern Plains tribe, participants were recruited 123 self-identified Indigenous women aged 40-70 through a comprehensive recruitment strategy. Employing the SDOH framework, the research assessed cognitive impairment and Alzheimer's disease knowledge (ADK), utilizing the Ascertain Dementia 8 and Alzheimer's disease knowledge scales (ADK-30). The investigation examined the relationships between selected SDOH variables and cognitive impairment status. RESULTS: More than half of the participants showed signs of cognitive impairment, which correlated with lower income and education levels. Increased knowledge about Alzheimer's disease, particularly in terms of treatment management and its life impact subscales, was associated with lower odds of cognitive impairment. Conversely, higher levels of depressive symptoms and participation in religious activities were linked to increased odds of cognitive impairment. DISCUSSION AND IMPLICATIONS: The findings underscore the importance of culturally grounded tools and SDOH frameworks tailored to Indigenous contexts in addressing ADRD disparities. Future research should integrate historical and cultural factors to advance health equity within Indigenous communities, ultimately mitigating the impact of ADRD and promoting overall well-being.

Analysis and visualization of quantitative proteomics data using FragPipe-Analyst.

The FragPipe computational proteomics platform is gaining widespread popularity among the proteomics research community because of its fast processing speed and user-friendly graphical interface. Although FragPipe produces well-formatted output tables that are ready for analysis, there is still a need for an easy-to-use and user-friendly downstream statistical analysis and visualization tool. FragPipe-Analyst addresses this need by providing an R shiny web server to assist FragPipe users in conducting downstream analyses of the resulting quantitative proteomics data. It supports major quantification workflows including label-free quantification, tandem mass tags, and data-independent acquisition. FragPipe-Analyst offers a range of useful functionalities, such as various missing value imputation options, data quality control, unsupervised clustering, differential expression (DE) analysis using Limma, and gene ontology and pathway enrichment analysis using Enrichr. To support advanced analysis and customized visualizations, we also developed FragPipeAnalystR, an R package encompassing all FragPipe-Analyst functionalities that is extended to support site-specific analysis of post-translational modifications (PTMs). FragPipe-Analyst and FragPipeAnalystR are both open-source and freely available.

A Semiautomated Proteomics and Phosphoproteomics Protocol for the Identification of Novel Therapeutic Targets and Predictive Biomarkers in In Vivo Xenograft Models of Pediatric Cancers.

Genomic profiling has identified therapeutic targets for precision treatment of certain cancers, but many patients lack actionable mutations. Additional omics approaches, like proteomics and phosphoproteomics, are essential for comprehensive mapping of cancer-associated molecular phenotypes. In vivo models, such as cell line and patient-derived xenografts (PDX), offer valuable insights into cancer biology and treatment strategies.This chapter presents a semiautomated high-throughput workflow for integrated proteomics and phosphoproteomics analysis on the Kingfish platform coupled with MagReSyn® Zr-IMAC HP. It enhances protein extraction from in vivo xenograft samples and provides better insights into cancers with poor prognosis. The approach successfully identified over 11,000 unique phosphosites and ~6000 proteins in SJSA-1 pediatric osteosarcoma xenografts, demonstrating its efficacy. This workflow is a valuable tool for studying tumor biology and developing precision oncology strategies.

Mapping the IMiD-dependent cereblon interactome using BioID-proximity labelling.

Immunomodulatory imide drugs (IMiDs) are central components of therapy for multiple myeloma (MM). IMiDs bind cereblon (CRBN), an adaptor for the CUL4-DDB1-RBX1 E3 ligase to change its substrate specificity and induce degradation of 'neosubstrate' transcription factors that are essential to MM cells. Mechanistic studies to date have largely focussed on mediators of therapeutic activity and insight into clinical IMiD toxicities is less developed. We adopted BioID2-dependent proximity labelling (BioID2-CRBN) to characterise the CRBN interactome in the presence and absence of various IMiDs and the proteasome inhibitor, bortezomib. We aimed to leverage this technology to further map CRBN interactions beyond what has been achieved by conventional proteomic techniques. In support of this approach, analysis of cells expressing BioID2-CRBN following IMiD treatment displayed biotinylation of known CRBN interactors and neosubstrates. We observed that bortezomib alone significantly modifies the CRBN interactome. Proximity labelling also suggested that IMiDs augment the interaction between CRBN and proteins that are not degraded, thus designating 'neointeractors' distinct from previously disclosed 'neosubstrates'. Here we identify Non-Muscle Myosin Heavy Chain IIA (MYH9) as a putative CRBN neointeractor that may contribute to the haematological toxicity of IMiDs. These studies provide proof of concept for proximity labelling technologies in the mechanistic profiling of IMiDs and related E3-ligase-modulating drugs.

White matter maturation supports the development of reasoning ability through its influence on processing speed.

The structure of the human brain changes in several ways throughout childhood and adolescence. Perhaps the most salient of these changes is the strengthening of white matter tracts that enable distal brain regions to communicate with one another more quickly and efficiently. Here, we sought to understand whether and how white matter changes contribute to improved reasoning ability over development. In particular, we sought to understand whether previously reported relationships between white matter microstructure and reasoning are mediated by processing speed. To this end, we analyzed diffusion tensor imaging data as well as data from standard psychometric tests of cognitive abilities from 103 individuals between the ages of 6 and 18. We used structural equation modeling to investigate the network of relationships between brain and behavior variables. Our analyses provide support for the hypothesis that white matter maturation (as indexed either by microstructural organization or volume) supports improved processing speed, which, in turn, supports improved reasoning ability.

Effects of e-vapour and high-fat diet on the immunohistochemical staining of nicotinic acetylcholine receptors, apoptosis, microglia and astrocytes in the adult male mouse hippocampus.

The use of e-cigarettes/e-vapour, and the consumption of a high-fat diet (HFD), are two popular lifestyle choices associated with alterations in the hippocampus. This study, using a mouse model, investigated the effects of exposure to e-vapour (± nicotine) and HFD (43% fat) consumption, on the expression of nicotinic acetylcholine receptor (nAChR) subunits α3, α4, α7 and ß2, apoptosis markers caspase-3 and TUNEL, microglial marker Iba-1, and astrocyte marker GFAP, in hippocampal subregions of dentate gyrus (DG) and cornu ammonis (CA) 1-3. The major findings included: (1) HFD alone had minimal effect with no consistent pattern or interaction between the markers, (2) E-vapour (± nicotine) predominantly affected the CA2 subregion, decreasing α7 and ß2 nAChR subunits and Iba-1, (3) Nicotine e-vapour increased TUNEL across all subregions, and (4) HFD, in the presence of nicotine-free e-vapour, decreased caspase-3 and increased TUNEL across all regions, and decreased Iba-1 in the CA subregions, while HFD and nicotine-containing e-vapour, subregion specifically affected the α3, α4 and α7 nAChR subunits, with a protective effect against change in GFAP in the DG and Iba-1 in the CA1 and CA3. These findings highlight that e-vapour itself alters nAChRs, particularly in the CA2 subregion, associated with a decrease in neuroinflammatory response (Iba-1) across the whole hippocampus, and the addition of nicotine increases cell apoptosis across the whole hippocampus. HFD alone was not detrimental in our model, but in the presence of nicotine-free e-vapour, it differentially affected apoptosis, while the addition of nicotine increased nAChR subunits.

A new isolation method for bacterial extracellular vesicles providing greater purity and improved proteomic detection of vesicle proteins.

Contaminants within cell culture media often co-isolate with eukaryotic extracellular vesicles (EVs) thus affecting their biological properties. It has yet to be investigated if this is also true for bacterial EVs (BEVs), especially for organisms grown in complex culture media containing animal-derived products. To address this question, we isolated BEVs from the fastidious bacterium Helicobacter pylori grown in either standard Brain Heart Infusion (BHI) medium or BHI depleted of animal-derived products (D-BHI). We show that BEVs prepared from bacteria grown in D-BHI medium have similar morphologies, size ranges and yields to those prepared from standard medium. Similarly, no differences were found in the ability of H. pylori BEVs to induce IL-8 responses in epithelial cells. However, H. pylori BEVs prepared from D-BHI medium were of higher purity than those prepared from standard medium. Importantly, proteomic analyses detected 3.4-fold more H. pylori proteins and 10-fold fewer bovine-derived proteins in BEV samples prepared from D-BHI rather than the standard method. Fifty-seven H. pylori proteins were uniquely detected in BEV samples prepared from D-BHI. In conclusion, we have described an improved method for BEV isolation. Furthermore, we demonstrate how animal-derived products in bacteriological culture media may adversely affect proteomic analyses of BEVs.

SAPrIm, a semi-automated protocol for mid-throughput immunopeptidomics.

Human leukocyte antigen (HLA) molecules play a crucial role in directing adaptive immune responses based on the nature of their peptide ligands, collectively coined the immunopeptidome. As such, the study of HLA molecules has been of major interest in the development of cancer immunotherapies such as vaccines and T-cell therapies. Hence, a comprehensive understanding and profiling of the immunopeptidome is required to foster the growth of these personalised solutions. We herein describe SAPrIm, an Immunopeptidomics tool for the Mid-Throughput era. This is a semi-automated workflow involving the KingFisher platform to isolate immunopeptidomes using anti-HLA antibodies coupled to a hyper-porous magnetic protein A microbead, a variable window data independent acquisition (DIA) method and the ability to run up to 12 samples in parallel. Using this workflow, we were able to concordantly identify and quantify ~400 - 13000 unique peptides from 5e5 - 5e7 cells, respectively. Overall, we propose that the application of this workflow will be crucial for the future of immunopeptidome profiling, especially for mid-size cohorts and comparative immunopeptidomics studies.

Explainable machine learning identifies multi-omics signatures of muscle response to spaceflight in mice.

The adverse effects of microgravity exposure on mammalian physiology during spaceflight necessitate a deep understanding of the underlying mechanisms to develop effective countermeasures. One such concern is muscle atrophy, which is partly attributed to the dysregulation of calcium levels due to abnormalities in SERCA pump functioning. To identify potential biomarkers for this condition, multi-omics data and physiological data available on the NASA Open Science Data Repository (osdr.nasa.gov) were used, and machine learning methods were employed. Specifically, we used multi-omics (transcriptomic, proteomic, and DNA methylation) data and calcium reuptake data collected from C57BL/6 J mouse soleus and tibialis anterior tissues during several 30+ day-long missions on the international space station. The QLattice symbolic regression algorithm was introduced to generate highly explainable models that predict either experimental conditions or calcium reuptake levels based on multi-omics features. The list of candidate models established by QLattice was used to identify key features contributing to the predictive capability of these models, with Acyp1 and Rps7 proteins found to be the most predictive biomarkers related to the resilience of the tibialis anterior muscle in space. These findings could serve as targets for future interventions aiming to reduce the extent of muscle atrophy during space travel.

Differences in Life Space Activity Patterns Between Older Adults With Mild Cognitive Impairment Living Alone or as a Couple: Cohort Study Using Passive Activity Sensing.

BACKGROUND: Measuring function with passive in-home sensors has the advantages of real-world, objective, continuous, and unobtrusive measurement. However, previous studies have focused on 1-person homes only, which limits their generalizability. OBJECTIVE: This study aimed to compare the life space activity patterns of participants living alone with those of participants living as a couple and to compare people with mild cognitive impairment (MCI) with cognitively normal participants in both 1- and 2-person homes. METHODS: Passive infrared motion sensors and door contact sensors were installed in 1- and 2-person homes with cognitively normal residents or residents with MCI. A home was classified as an MCI home if at least 1 person in the home had MCI. Time out of home (TOOH), independent life space activity (ILSA), and use of the living room, kitchen, bathroom, and bedroom were calculated. Data were analyzed using the following methods: (1) daily averages over 4 weeks, (2) hourly averages (time of day) over 4 weeks, or (3) longitudinal day-to-day changes. RESULTS: In total, 129 homes with people living alone (n=27, 20.9%, MCI and n=102, 79.1%, no-MCI homes) and 52 homes with people living as a couple (n=24, 46.2%, MCI and n=28, 53.8%, no-MCI homes) were included with a mean follow-up of 719 (SD 308) days. Using all 3 analysis methods, we found that 2-person homes showed a shorter TOOH, a longer ILSA, and shorter living room and kitchen use. In MCI homes, ILSA was higher in 2-person homes but lower in 1-person homes. The effects of MCI status on other outcomes were only found when using the hourly averages or longitudinal day-to-day changes over time, and they depended on the household type (alone vs residing as a couple). CONCLUSIONS: This study shows that in-home behavior is different when a participant is living alone compared to when they are living as a couple, meaning that the household type should be considered when studying in-home behavior. The effects of MCI status can be detected with in-home sensors, even in 2-person homes, but data should be analyzed on an hour-to-hour basis or longitudinally.