Healthy Aging Metabolomic and Proteomic Signatures Across Multiple Physiological Compartments.

The study of biomarkers in biofluids and tissues expanded our understanding of the biological processes that drive physiological and functional manifestations of aging. However, most of these studies were limited to examining one biological compartment, an approach that fails to recognize that aging pervasively affects the whole body. The simultaneous modeling of hundreds of metabolites and proteins across multiple compartments may provide a more detailed picture of healthy aging and point to differences between chronological and biological aging.

Perturbations in levels of essential metals less severe in Parkinson's disease without dementia than in Parkinson's disease dementia.

It is currently unknown why some individuals with Parkinson's disease (PD) go on to develop dementia [Parkinson's disease dementia (PDD)], whereas others do not. One possibility is differences in susceptibility to metallomic dysregulation. A previous study of the PDD brain identified substantive perturbations in metal levels, including severe multiregional decreases in Cu.

The Society for Immunotherapy of Cancer Perspective on Tissue-Based Technologies for Immuno-Oncology Biomarker Discovery and Application.

With immuno-oncology becoming the standard of care for a variety of cancers, identifying biomarkers that reliably classify patient response, resistance, or toxicity becomes the next critical barrier toward improving care. Multiparametric, multi-omics, and computational platforms generating an unprecedented depth of data are poised to usher in the discovery of increasingly robust biomarkers for enhanced patient selection and personalized treatment approaches. Deciding which developing technologies to implement in clinical settings ultimately, applied either alone or in combination, relies on weighing pros and cons, from minimizing patient sampling to maximizing data outputs, and assessing the reproducibility and representativeness of findings, while lessening data fragmentation toward harmonization.

Evidence of association between higher cardiorespiratory fitness and higher cerebral myelination in aging.

Emerging evidence suggests that altered myelination is an important pathophysiologic correlate of several neurodegenerative diseases, including Alzheimer and Parkinson's diseases. Thus, improving myelin integrity may be an effective intervention to prevent and treat age-associated neurodegenerative pathologies. It has been suggested that cardiorespiratory fitness (CRF) may preserve and enhance cerebral myelination throughout the adult lifespan, but this hypothesis has not been fully tested.

Integrative Multiomic Profiling of Triple-Negative Breast Cancer for Identifying Suitable Therapies.

Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous disease that carries the poorest prognosis of all breast cancers. Although novel TNBC therapies in development are frequently targeted toward tumors carrying a specific genomic, transcriptomic, or protein biomarker, it is poorly understood how these biomarkers are correlated.

Experimental Design: To better understand the molecular features of TNBC and their correlation with one another, we performed multimodal profiling on a cohort of 95 TNBC.

Single-fly genome assemblies fill major phylogenomic gaps across the Drosophilidae Tree of Life.

Long-read sequencing is driving rapid progress in genome assembly across all major groups of life, including species of the family Drosophilidae, a longtime model system for genetics, genomics, and evolution. We previously developed a cost-effective hybrid Oxford Nanopore (ONT) long-read and Illumina short-read sequencing approach and used it to assemble 101 drosophilid genomes from laboratory cultures, greatly increasing the number of genome assemblies for this taxonomic group. The next major challenge is to address the laboratory culture bias in taxon sampling by sequencing genomes of species that cannot easily be reared in the lab.

Metallomic analysis of brain tissues distinguishes between cases of dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease dementia.

Background: Dementia with Lewy bodies (DLB) can be difficult to distinguish from Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) at different stages of its progression due to some overlaps in the clinical and neuropathological presentation of these conditions compared with DLB. Metallomic changes have already been observed in the AD and PDD brain-including widespread decreases in Cu levels and more localised alterations in Na, K, Mn, Fe, Zn, and Se. This study aimed to determine whether these metallomic changes appear in the DLB brain, and how the metallomic profile of the DLB brain appears in comparison to the AD and PDD brain.

Efficiency droop in zincblende InGaN/GaN quantum wells.

The decrease in emission efficiency with increasing drive current density, known as 'droop', of -plane wurtzite InGaN/GaN quantum wells presently limits the use of light-emitting diodes based on them for high brightness lighting applications. InGaN/GaN quantum wells grown in the alternative zincblende phase are free of the strong polarisation fields that exacerbate droop and so were investigated by excitation-dependent photoluminescence and photoreflectance studies. Polarisation-resolved measurements revealed that for all excitation densities studied the emission from such samples largely originates from similar microstructures or combinations of microstructures that form within the quantum well layers.

Spatial multi-omics of human skin reveals KRAS and inflammatory responses to spaceflight.

Spaceflight can change metabolic, immunological, and biological homeostasis and cause skin rashes and irritation, yet the molecular basis remains unclear. To investigate the impact of short-duration spaceflight on the skin, we conducted skin biopsies on the Inspiration4 crew members before (L-44) and after (R + 1) flight. Leveraging multi-omics assays including GeoMx™ Digital Spatial Profiler, single-cell RNA/ATAC-seq, and metagenomics/metatranscriptomics, we assessed spatial gene expressions and associated microbial and immune changes across 95 skin regions in four compartments: outer epidermis, inner epidermis, outer dermis, and vasculature.

The Space Omics and Medical Atlas (SOMA) and international astronaut biobank.

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study, JAXA CFE study, SpaceX Inspiration4 crew, Axiom and Polaris.

Oncogenic signaling in the adult prostate-like accessory gland leads to activation of a conserved pro-tumorigenic program, in the absence of proliferation.

models for tumorigenesis and metastasis have revealed conserved mechanisms of signaling that are also involved in mammalian cancer. Many of these models use the proliferating tissues of the larval stages of development, when tissues are highly mitotically active, or stem cells are abundant. Fewer tumorigenesis models use adult animals to initiate tumor formation when many tissues are largely terminally differentiated and postmitotic.

Localized Pantothenic Acid (Vitamin B5) Reductions Present Throughout the Dementia with Lewy Bodies Brain.

Background: Localized pantothenic acid deficiencies have been observed in several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease dementia (PDD), and Huntington's disease (HD), indicating downstream energetic pathway perturbations. However, no studies have yet been performed to see whether such deficiencies occur across the dementia with Lewy bodies (DLB) brain, or what the pattern of such dysregulation may be.

Objective: Firstly, this study aimed to quantify pantothenic acid levels across ten regions of the brain in order to determine the localization of any pantothenic acid dysregulation in DLB.

Human dementia with Lewy bodies brain shows widespread urea elevations.

Introduction: Several recent studies have uncovered the presence of widespread urea elevations in multiple neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease dementia (PDD), vascular dementia (VaD), and Huntington's disease (HD). However, it is currently unknown whether dementia with Lewy bodies also shows these alterations in urea. This study aimed to investigate if and where urea is perturbed in the DLB brain.

Integrating phylogenies into single-cell RNA sequencing analysis allows comparisons across species, genes, and cells.

Comparisons of single-cell RNA sequencing (scRNA-seq) data across species can reveal links between cellular gene expression and the evolution of cell functions, features, and phenotypes. These comparisons evoke evolutionary histories, as depicted by phylogenetic trees, that define relationships between species, genes, and cells. This Essay considers each of these in turn, laying out challenges and solutions derived from a phylogenetic comparative approach and relating these solutions to previously proposed methods for the pairwise alignment of cellular dimensional maps.

Cell cycle variants during Drosophila male accessory gland development.

The Drosophila melanogaster male accessory gland (AG) is a functional analog of the mammalian prostate and seminal vesicles containing two secretory epithelial cell types, termed main and secondary cells. This tissue is responsible for making and secreting seminal fluid proteins and other molecules that contribute to successful reproduction. The cells of this tissue are binucleate and polyploid, due to variant cell cycles that include endomitosis and endocycling during metamorphosis.

Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis.

The TAM tyrosine kinases, Axl and MerTK, play an important role in rheumatoid arthritis (RA). Here, using a unique synovial tissue bioresource of patients with RA matched for disease stage and treatment exposure, we assessed how Axl and MerTK relate to synovial histopathology and disease activity, and their topographical expression and longitudinal modulation by targeted treatments. We show that in treatment-naive patients, high AXL levels are associated with pauci-immune histology and low disease activity and inversely correlate with the expression levels of pro-inflammatory genes.

Distinct spatial landscapes in clear-cell renal cell carcinoma as revealed by whole transcriptome analysis.

Background: Clear-cell renal cell carcinoma (ccRCC) is the most common and aggressive form of renal cancer and a paradigm of inter- and intratumor heterogeneity. We carried out an exploratory digital spatial profiling of the tumor interior and periphery of two ccRCC tumor specimens and mapped spatially the molecular and cellular composition of their tumor microenvironment and ecosystem.

Materials And Methods: Digital spatial profiling of the whole transcriptome of 19 regions of interest (ROIs) was carried out from two selected highly immunogenic stage pT3a/grade 3 (G3) and stage pT3a/grade 4 (G4) ccRCC.

Normalizing need not be the norm: count-based math for analyzing single-cell data.

Counting transcripts of mRNA are a key method of observation in modern biology. With advances in counting transcripts in single cells (single-cell RNA sequencing or scRNA-seq), these data are routinely used to identify cells by their transcriptional profile, and to identify genes with differential cellular expression. Because the total number of transcripts counted per cell can vary for technical reasons, the first step of many commonly used scRNA-seq workflows is to normalize by sequencing depth, transforming counts into proportional abundances.

Single-fly assemblies fill major phylogenomic gaps across the Drosophilidae Tree of Life.

Long-read sequencing is driving rapid progress in genome assembly across all major groups of life, including species of the family Drosophilidae, a longtime model system for genetics, genomics, and evolution. We previously developed a cost-effective hybrid Oxford Nanopore (ONT) long-read and Illumina short-read sequencing approach and used it to assemble 101 drosophilid genomes from laboratory cultures, greatly increasing the number of genome assemblies for this taxonomic group. The next major challenge is to address the laboratory culture bias in taxon sampling by sequencing genomes of species that cannot easily be reared in the lab.

Tamoxifen-predictive value of gene expression signatures in premenopausal breast cancer: data from the randomized SBII:2 trial.

Background: Gene expression (GEX) signatures in breast cancer provide prognostic information, but little is known about their predictive value for tamoxifen treatment. We examined the tamoxifen-predictive value and prognostic effects of different GEX signatures in premenopausal women with early breast cancer.

Methods: RNA from formalin-fixed paraffin-embedded tumor tissue from premenopausal women randomized between two years of tamoxifen treatment and no systemic treatment was extracted and successfully subjected to GEX profiling (n = 437, NanoString Breast Cancer 360™ panel).

The Effect of the Human Brainstem Myelination on Gait Speed in Normative Aging.

The brainstem functions as a relay and integrative brain center and plays an essential role in motor function. Whether brainstem tissue deterioration, including demyelination, affects motor function has not been studied. Understanding the potential relationship between brainstem demyelination and motor function may be useful for the early diagnosis of neurodegenerative diseases and to understand age-related gait impairments that have no apparent cause.