Proteotoxic stress is a common challenge for all organisms. Among various mechanisms involved in defending such stress, the evolutionarily conserved unfolded protein responses (UPRs) play a key role across species. Interestingly, UPRs can occur in different subcellular compartments including the endoplasmic reticulum (UPR ), mitochondria (UPR ), and cytoplasm (UPR ) through distinct mechanisms. While previous studies have shown that the UPRs are intuitively linked to organismal aging, a systematic assay on the temporal regulation of different type of UPRs during aging is still lacking. Here, using Caenorhabditis elegans (C. elegans) as the model system, we found that the endogenous UPRs (UPR , UPR , and UPR ) elevate with age, but their inducibility exhibits an age-dependent decline. Moreover, we revealed that the temporal requirements to induce different types of UPRs are distinct. Namely, while the UPR can only be induced during the larval stage, the UPR can be induced until early adulthood and the inducibility of UPR is well maintained until mid-late stage of life. Furthermore, we showed that different tissues may exhibit distinct temporal profiles of UPR inducibility during aging. Collectively, our findings demonstrate that UPRs of different subcellular compartments may have distinct temporal mechanisms during aging.
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http://dx.doi.org/10.1002/jcp.30215 | DOI Listing |
ACS Appl Mater Interfaces
January 2025
Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
Combination therapies using checkpoint inhibitors with immunostimulatory agonists have attracted great attention due to their synergistic therapeutic effects for cancer treatment. However, such combination immunotherapies require specific timing of doses to show sufficient antitumor efficacy. Sequential treatment usually requires multiple administrations of the individual drugs at specific time points, thus increasing the complexity of the drug regimen and compromising patient compliance.
View Article and Find Full Text PDFCell Rep
January 2025
Nash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:
Temporal lobe epilepsy (TLE) causes pervasive and progressive memory impairments, yet the specific circuit changes that drive these deficits remain unclear. To investigate how hippocampal-entorhinal dysfunction contributes to progressive memory deficits in epilepsy, we performed simultaneous in vivo electrophysiology in the hippocampus (HPC) and medial entorhinal cortex (MEC) of control and epileptic mice 3 or 8 weeks after pilocarpine-induced status epilepticus (Pilo-SE). We found that HPC synchronization deficits (including reduced theta power, coherence, and altered interneuron spike timing) emerged within 3 weeks of Pilo-SE, aligning with early-onset, relatively subtle memory deficits.
View Article and Find Full Text PDFOpen Res Eur
October 2024
Univ. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369 - URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, F-59000 Lille, France, University of Lille, Lille, Hauts-de-France, France.
Background: France (FR) and New Caledonia (NC) are both French territories, one in Western Europe, the other as part of the Pacific Island Countries and Territories (PICTs). Despite schooling in similar educational systems, FR and NC adolescents develop distinct relationships with physical activity, which is influenced by the geographical-cultural and symbolic structures of their respective societies. This study explored the distribution of physical activity according to geographical culture and opportunity-temporal dimensions.
View Article and Find Full Text PDFFront Microbiol
January 2025
USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE, United States.
Introduction: Probiotics are a promising intervention for modulating the microbiome and the immune system, promoting health benefits in cattle. While studies have characterized the calf lung bacterial profile with and without oral probiotics, simultaneous probiotic effects on the bacterial populations of multiple sites along the respiratory tract have not been characterized.
Methods: This study utilized the same pre-weaning diary calf group from our previous studies to characterize the bacterial populations present in the nostril and tonsil across control and treatment groups and nine sampling time points.
Commun Biol
January 2025
Western Institute for Neuroscience, Western University, London, ON, Canada.
Our brain seamlessly integrates distinct sensory information to form a coherent percept. However, when real-world audiovisual events are perceived, the specific brain regions and timings for processing different levels of information remain less investigated. To address that, we curated naturalistic videos and recorded functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) data when participants viewed videos with accompanying sounds.
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