Skip to main content

Aggregator

Structural basis of oligomerization-modulated activation and autoinhibition of orphan receptor GPR3

4 days ago
G protein-coupled receptor 3 (GPR3) is a class A orphan receptor characterized by high constitutive activity in the G(s) signaling pathway. GPR3 has been implicated in Alzheimer's disease and the regulation of thermogenesis in human adipocytes, yet the molecular mechanisms underlying its self-activation and potential endogenous modulators remain unclear. In this study, we present cryo-electron microscopy (cryo-EM) structures of GPR3 in different oligomerization states, both in the absence and...
Hao Chang

Cryo-TEM structure of β-glucocerebrosidase in complex with its transporter LIMP-2

4 days ago
Targeting proteins to their final cellular destination requires transport mechanisms and nearly all lysosomal enzymes reach the lysosome via the mannose-6-phosphate receptor pathway. One of the few known exceptions is the enzyme β-glucocerebrosidase (GCase) that requires the lysosomal integral membrane protein type-2 (LIMP-2) as a proprietary lysosomal transporter. Genetic variations in the GCase encoding gene GBA1 cause Gaucher's disease (GD) and present the highest genetic risk factor to...
Jan Philipp Dobert

Senescence-associated lineage-aberrant plasticity evokes T-cell-mediated tumor control

4 days ago
Cellular senescence is a stress-inducible state switch relevant in aging, tumorigenesis and cancer therapy. Beyond a lasting arrest, senescent cells are characterized by profound chromatin remodeling and transcriptional reprogramming. We show here myeloid-skewed aberrant lineage plasticity and its immunological ramifications in therapy-induced senescence (TIS) of primary human and murine B-cell lymphoma. We find myeloid transcription factor (TF) networks, specifically AP-1-, C/EBPβ- and...
Dimitri Belenki

Ovarian vascular aging: a hidden driver of mid-age female fertility decline

4 days ago
Although ovarian reserve remains sufficient, ovarian function declines in mid-age, leading to reduced fertility around age 35, with the causes remaining unclear. Recent studies highlight vascular aging as a key factor in this decline, with age-related reductions in ovarian vascular remodeling disrupting oocyte development. Salidroside, a natural compound that reverses ovarian vascular aging and promotes ovarian angiogenesis, presents a promising strategy to rejuvenate ovarian health and enhance...
Ge Wang

Quantitative PET imaging and modeling of molecular blood-brain barrier permeability

4 days ago
Neuroimaging of blood-brain barrier permeability has been instrumental in identifying its broad involvement in neurological and systemic diseases. However, current methods evaluate the blood-brain barrier mainly as a structural barrier. Here we developed a non-invasive positron emission tomography method in humans to measure the blood-brain barrier permeability of molecular radiotracers that cross the blood-brain barrier through its molecule-specific transport mechanism. Our method uses...
Kevin J Chung

Pan-PTM profiling identifies post-translational modifications associated with exceptional longevity and preservation of skeletal muscle function in Drosophila

4 days ago
Skeletal muscle weakness is a major component of age-associated frailty, but the underlying mechanisms are not completely understood. Drosophila has emerged as a useful model for studying skeletal muscle aging. In this organism, previous lab-based selection established strains with increased longevity and reduced age-associated muscle functional decline compared to a parental strain. Here, we have applied a computational pipeline (JUMPptm) for retrieving information on 8 post-translational...
Suresh Poudel

Exploring new markers for biological aging from bioimpedance analysis and cognitive functions in older adults

4 days ago
Aging is a complex process that affects human health and lifespan. While chronological age (CA) is a significant risk factor for many diseases, it does not fully capture biological changes that influence health span. This study explores cognitive measures using the Seoul Neuropsychological Screening Battery and body composition profiles as potential biological age (BA) markers in the older population. Multiple linear regression, principal component analysis (PCA), and the Klemera-Doubal (KDM)...
Dieu Ni Thi Doan