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Conserved components of the macroautophagy machinery in Caenorhabditis elegans

7 months ago
Macroautophagy involves the sequestration of cytoplasmic contents in a double-membrane autophagosome and its subsequent delivery to lysosomes for degradation and recycling. In Caenorhabditis elegans, autophagy participates in diverse processes such as stress resistance, cell fate specification, tissue remodeling, aging, and adaptive immunity. Genetic screens in C. elegans have identified a set of metazoan-specific autophagy genes that form the basis for our molecular understanding of steps...
Hong Zhang

Genome-wide CRISPR screen identifies BUB1 kinase as a druggable vulnerability in malignant pleural mesothelioma

7 months ago
Malignant pleural mesothelioma (MPM) is a rare yet highly aggressive malignancy with a severe prognosis. Compounded by the lack of effective treatment modalities, MPM remains a formidable health challenge. Therefore, the identification of actionable liabilities is critical for advancing precision medicine to combat this lethal disease. Here, we exploit an unbiased genome-wide CRISPR screen, integrating and cross-comparing three MPM cell lines with nonmalignant mesothelial cells, to selectively...
Ece Cakiroglu

Nanopore sensing of protein and peptide conformation for point-of-care applications

7 months ago
The global population's aging and growth will likely result in an increase in chronic aging-related diseases. Early diagnosis could improve the medical care and quality of life. Many diseases are linked to misfolding or conformational changes in biomarker peptides and proteins, which affect their function and binding properties. Current clinical methods struggle to detect and quantify these changes. Therefore, there is a need for sensitive conformational sensors that can detect low-concentration...
Laura Ratinho

A spatiotemporal cell atlas of cardiopulmonary progenitor cell allocation during development

7 months ago
The heart and lung co-orchestrate their development during organogenesis. The mesoderm surrounding both the developing heart and anterior foregut endoderm provides instructive cues guiding cardiopulmonary development. Additionally, it serves as a source of cardiopulmonary progenitor cells (CPPs) expressing Wnt2 that give rise to both cardiac and lung mesodermal cell lineages. Despite the mesoderm's critical importance to both heart and lung development, mechanisms guiding CPP specification are...
Hongbo Wen

Gas1-high quiescent neural stem cells are multipotent and produce oligodendrocytes during aging and after demyelinating injury

7 months ago
Quiescent neural stem cells (qNSCs) in the adult mouse subventricular zone (SVZ) normally have limited capacity to generate glia. Gliogenic domains are present in both dorsal and ventral SVZ, with the ventral region featuring a subpopulation of Gli1+ qNSCs. In dorsal SVZ, however, the molecular identity and developmental origin of oligodendrogenic qNSCs remains elusive. Here, through single-cell analysis and lineage tracing, we identify an undefined subpopulation of Gas1high qNSCs in dorsal SVZ,...
Chaoqiong Ding

Synaptic deregulation of cholinergic projection neurons causes olfactory dysfunction across five fly Parkinsonism models

7 months ago
The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and...
Ulrike Pech

Decoding brain aging trajectory: predictive discrepancies, genetic susceptibilities, and emerging therapeutic strategies

7 months ago
The global extension of human lifespan has intensified the focus on aging, yet its underlying mechanisms remain inadequately understood. The article highlights aspects of genetic susceptibility to impaired brain bioenergetics, trends in age-related gene expression related to neuroinflammation and brain senescence, and the impact of stem cell exhaustion and quiescence on accelerated brain aging. We also review the accumulation of senescent cells, mitochondrial dysfunction, and metabolic...
Yulia Komleva

Harnessing Immune Rejuvenation: Advances in Overcoming T Cell Senescence and Exhaustion in Cancer Immunotherapy

7 months ago
Immunotherapy has transformed the landscape of cancer treatment, with T cell-based strategies at the forefront of this revolution. However, the durability of these responses is frequently undermined by two intertwined phenomena: T cell exhaustion and senescence. While exhaustion is driven by chronic antigen exposure in the immunosuppressive tumor microenvironment, leading to a reversible state of diminished functionality, senescence reflects a more permanent, age- or stress-induced arrest in...
Tesfahun Dessale Admasu

Neuroprotective role of Hippo signaling by microtubule stability control in <em>Caenorhabditis elegans</em>

7 months ago
The evolutionarily conserved Hippo (Hpo) pathway has been shown to impact early development and tumorigenesis by governing cell proliferation and apoptosis. However, its post-developmental roles are relatively unexplored. Here, we demonstrate its roles in post-mitotic cells by showing that defective Hpo signaling accelerates age-associated structural and functional decline of neurons in Caenorhabditis elegans. Loss of wts-1/LATS, the core kinase of the Hpo pathway, resulted in premature...
Hanee Lee

NIA Caenorhabditis Intervention Testing Program: identification of robust and reproducible pharmacological interventions that promote longevity across experimentally accessible, genetically diverse populations

7 months ago
A core facet of the National Institute on Aging's mission is to identify pharmacological interventions that can promote human healthy aging and long life. As part of the comprehensive effort toward that goal, the NIA Division of Biology of Aging established the Caenorhabditis Intervention Testing Program (CITP) in 2013. The C. elegans model (with an ~ 21 day lifespan) has led the field in dissection of longevity genetics and offers features that allow for relatively rapid testing and for the...
Monica Driscoll