66,018 results match your criteria: "Institute of Molecular Systems Biology & Department of Health Sciences and Technology[Affiliation]"

Objectives: The effects of acute physical exercise in patients with resistant hypertension remain largely unexplored compared with hypertensive patients in general. We assessed the short-term effects of acute moderate-intensity (MICE) and high-intensity interval exercise (HIIE) on the clinic (BP) and 24-h ambulatory blood pressure (ABP) of patients with resistant hypertension.

Methods: Using a crossover randomized controlled design, 10 participants (56 ± 7 years) with resistant hypertension performed three experimental sessions: MICE, HIIE, and control.

View Article and Find Full Text PDF

Guest Segregation in Heteromeric Multicage Systems.

J Am Chem Soc

January 2025

Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn Str. 6, 44227 Dortmund, Germany.

Dynamically interconvertible metallo-supramolecular multicomponent assemblies, coexisting orthogonally in solution, serve as simplified mimics for complex networks found in biological systems. Building on recent advances in controlling the nonstatistical self-assembly of heteroleptic coordination cages and heteromeric completive self-sorting, i.e.

View Article and Find Full Text PDF

Oral iron sulfide prevents acute alcohol intoxication by initiating the endogenous multienzymatic antioxidant defense system.

Sci Adv

January 2025

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.

Acute alcohol intoxication could cause multiorgan damage, including nervous, digestive, and cardiovascular systems, and in particular, irreversible damage to the brain and liver. Emerging studies have revealed that the endogenous multienzymatic antioxidant defense system (MEAODS) plays a central role in preventing oxidative stress and other toxicological compounds produced by alcohol. However, few available drugs could quickly regulate MEAODS.

View Article and Find Full Text PDF

Protocol to infer off-target effects of drugs on cellular signaling using interactome-based deep learning.

STAR Protoc

January 2025

Department of Cell and Molecular Biology, SciLifeLab, Karolinska Institutet, 171 77 Stockholm, Sweden. Electronic address:

Drugs that target specific proteins often have off-target effects. We present a protocol using artificial neural networks to model cellular transcriptional responses to drugs, aiming to understand their mechanisms of action. We detail steps for predicting transcriptional activities, inferring drug-target interactions, and explaining the off-target mechanism of action.

View Article and Find Full Text PDF

Anthropogenic carbon dioxide emissions have been increasing rapidly in recent years, driving pH and oxygen levels to record low concentrations in the oceans. Eastern boundary upwelling systems such as the California Current System (CCS) experience exacerbated ocean acidification and hypoxia (OAH) due to the physical and chemical properties of the transported deeper waters. Research efforts have significantly increased in recent years to investigate the deleterious effects of climate change on marine species, but have not focused on the impacts of simultaneous OAH stressor exposure.

View Article and Find Full Text PDF

Large-scale and long-term wildlife research and monitoring using camera traps: a continental synthesis.

Biol Rev Camb Philos Soc

January 2025

Wildlife Observatory of Australia (WildObs), Queensland Cyber Infrastructure Foundation (QCIF), Brisbane, Queensland, 4072, Australia.

Camera traps are widely used in wildlife research and monitoring, so it is imperative to understand their strengths, limitations, and potential for increasing impact. We investigated a decade of use of wildlife cameras (2012-2022) with a case study on Australian terrestrial vertebrates using a multifaceted approach. We (i) synthesised information from a literature review; (ii) conducted an online questionnaire of 132 professionals; (iii) hosted an in-person workshop of 28 leading experts representing academia, non-governmental organisations (NGOs), and government; and (iv) mapped camera trap usage based on all sources.

View Article and Find Full Text PDF

Brain-wide neuronal circuit connectome of human glioblastoma.

Nature

January 2025

Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Glioblastoma (GBM) infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression. Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic. The extent of GBM integration into the brain-wide neuronal circuitry remains unclear.

View Article and Find Full Text PDF

A Guide to Breast Cancer Research: An Introduction.

Adv Exp Med Biol

January 2025

Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

"A Guide to Breast Cancer Research: From Cells and Molecular Mechanisms to Therapy" is designed as a comprehensive reference for early career investigators and postgraduate students. This book aims to provide a broad overview of contemporary breast cancer research. It covers key areas including development and cancer, metastasis and immunology, subtypes, signalling, therapy, and resistance.

View Article and Find Full Text PDF

The complex nature of the immunosuppressive tumor microenvironment (TME) requires multi-agent combinations for optimal immunotherapy. Here we describe multiplex universal combinatorial immunotherapy via gene silencing (MUCIG), which uses CRISPR-Cas13d to silence multiple endogenous immunosuppressive genes in the TME, promoting TME remodeling and enhancing antitumor immunity. MUCIG vectors targeting four genes delivered by adeno-associated virus (AAV) (Cd274/Pdl1, Lgals9/Galectin9, Lgals3/Galectin3 and Cd47; AAV-Cas13d-PGGC) demonstrate significant antitumor efficacy across multiple syngeneic tumor models, remodeling the TME by increasing CD8 T-cell infiltration while reducing neutrophils.

View Article and Find Full Text PDF

Single-cell proteomics (SCP) promises to revolutionize biomedicine by providing an unparalleled view of the proteome in individual cells. Here, we present a high-sensitivity SCP workflow named Chip-Tip, identifying >5,000 proteins in individual HeLa cells. It also facilitated direct detection of post-translational modifications in single cells, making the need for specific post-translational modification-enrichment unnecessary.

View Article and Find Full Text PDF

Intercellular mitochondria transfer is an evolutionarily conserved process in which one cell delivers some of their mitochondria to another cell in the absence of cell division. This process has diverse functions depending on the cell types involved and physiological or disease context. Although mitochondria transfer was first shown to provide metabolic support to acceptor cells, recent studies have revealed diverse functions of mitochondria transfer, including, but not limited to, the maintenance of mitochondria quality of the donor cell and the regulation of tissue homeostasis and remodelling.

View Article and Find Full Text PDF

Occurrence of degenerative interactions is thought to serve as a mechanism underlying hybrid unfitness in most animal systems. However, the molecular mechanisms underpinning the genetic interaction and how they contribute to overall hybrid incompatibilities are limited to only a handful of examples. A vertebrate model organism, Xiphophorus, is used to study hybrid dysfunction, and it has been shown from this model that diseases, such as melanoma, can occur in certain interspecies hybrids.

View Article and Find Full Text PDF

Although rare non-coding variants (RVs) play crucial roles in complex traits and diseases, understanding their mechanisms and identifying disease-associated RVs continue to be major challenges. Here we constructed a comprehensive atlas of alternative polyadenylation (APA) outliers (aOutliers), including 1334 3' UTR and 200 intronic aOutliers, from 15,201 samples across 49 human tissues. These aOutliers exhibit unique characteristics from transcription or splicing outliers, with a pronounced RV enrichment.

View Article and Find Full Text PDF

Background: Molecular tumor boards (MTBs) play a pivotal role in personalized oncology, leveraging complex data sets to tailor therapy for cancer patients. The integration of digital support and visualization tools is essential in this rapidly evolving field facing fast-growing data and changing clinical processes. This study addresses the gap in understanding the evolution of software and visualization needs within MTBs and evaluates the current state of digital support.

View Article and Find Full Text PDF

Systems Biology of Streptophyte Cell Evolution.

Annu Rev Plant Biol

January 2025

1Department of Applied Bioinformatics, Institute for Microbiology and Genetics, University of Göttingen, Göttingen, Germany; email:

More than 500 million years ago, a streptophyte algal population established a foothold on land and started terraforming Earth through an unprecedented radiation. This event is called plant terrestrialization and yielded the Embryophyta. Recent advancements in the field of plant evolutionary developmental biology (evo-devo) have propelled our knowledge of the closest algal relatives of land plants, the zygnematophytes, highlighting that several aspects of plant cell biology are shared between embryophytes and their sister lineage.

View Article and Find Full Text PDF

Sugars are ubiquitous in biology; they occur in all kingdoms of life. Despite their prevalence, they have often been somewhat neglected in studies of structure-dynamics-function relationships of macromolecules to which they are attached, with the exception of nucleic acids. This is largely due to the inherent difficulties of not only studying the conformational dynamics of sugars using experimental methods but indeed also resolving their static structures.

View Article and Find Full Text PDF

A widespread and ancient bacterial machinery assembles cytochrome OmcS nanowires essential for extracellular electron transfer.

Cell Chem Biol

January 2025

Microbial Sciences Institute, Yale University, West Haven, CT 06516, USA; Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06511, USA. Electronic address:

Microbial extracellular electron transfer (EET) drives various globally important environmental phenomena and has biotechnology applications. Diverse prokaryotes have been proposed to perform EET via surface-displayed "nanowires" composed of multi-heme cytochromes. However, the mechanism that enables only a few cytochromes to polymerize into nanowires is unclear.

View Article and Find Full Text PDF

Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy.

Cell Rep

January 2025

Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Pharmacology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation of p38 mitogen-activated protein kinase (MAPK) is implicated in ALS.

View Article and Find Full Text PDF

Macrolide resistance due to (55).

Microbiol Spectr

January 2025

Institute for Microbial Systems and Society, Faculty of Science, University of Regina, Regina, Saskatchewan, Canada.

Unlabelled: Antimicrobial resistance (AMR) is a global threat. The identification and characterization of novel resistance genes is integral to AMR surveillance. The (55) gene was originally identified through whole genome sequencing of macrolide-resistant strains of .

View Article and Find Full Text PDF

The impact of heteroresistance on tuberculosis (TB) treatment outcomes is unclear, as is the role of different rifampin and isoniazid exposures on developing resistance mutations. Hollow fiber system model of TB (HFS-TB) units were inoculated with drug-susceptible () and treated with isoniazid and rifampin exposure identified in a clinical trial as leading to treatment failure and acquired drug resistance. Systems were sampled for drug concentration measurements, estimation of total and drug-resistant , and small molecule overlapping reads (SMOR) analysis for the detection of heteroresistance.

View Article and Find Full Text PDF

Discovery of a heparan sulfate binding domain in monkeypox virus H3 as an anti-poxviral drug target combining AI and MD simulations.

Elife

January 2025

State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.

Viral adhesion to host cells is a critical step in infection for many viruses, including monkeypox virus (MPXV). In MPXV, the H3 protein mediates viral adhesion through its interaction with heparan sulfate (HS), yet the structural details of this interaction have remained elusive. Using AI-based structural prediction tools and molecular dynamics (MD) simulations, we identified a novel, positively charged α-helical domain in H3 that is essential for HS binding.

View Article and Find Full Text PDF

Modular organization of enhancer network provides transcriptional robustness in mammalian development.

Nucleic Acids Res

January 2025

State Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, No. 4221, Xiang'an South Road, Xiamen, Fujian 361102, China.

Enhancer clusters, pivotal in mammalian development and diseases, can organize as enhancer networks to control cell identity and disease genes; however, the underlying mechanism remains largely unexplored. Here, we introduce eNet 2.0, a comprehensive tool for enhancer networks analysis during development and diseases based on single-cell chromatin accessibility data.

View Article and Find Full Text PDF

Heritable fragile bone disorders (FBDs), ranging from multifactorial to rare monogenic conditions, are characterized by an elevated fracture risk. Validating causative genes and understanding their mechanisms remain challenging. We assessed a semi-high throughput zebrafish screening platform for rapid in vivo functional testing of candidate FBD genes.

View Article and Find Full Text PDF