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Academic leadership in uncertain times
Science, Volume 389, Issue 6763, Page 882-882, August 2025.
Playing Possum: How Animals Understand Death
Science, Volume 389, Issue 6763, Page 883-883, August 2025.
Mars mania and the making of scientific authority
Science, Volume 389, Issue 6763, Page 883-883, August 2025.
Attempt to oust CDC director sparks key resignations by agency officials
Susan Monarez, who clashed with the U.S. health secretary over vaccine policy, refuses to step down
Mammoths in Mexico? Huge bone trove reveals giant beasts thrived in warmth, too
Fossils found while building airport contain first mammoth DNA from tropical location
Glow-in-the-dark particles let succulents shine in the dark
New technique lets popular houseplants glow for a little while—without genetic engineering
Study shows how the human pelvis was reshaped for upright walking
Comparisons of pelvic development in human and primate embryos reveals key steps in human evolution
Here’s how the first proteins might have assembled, sparking life
RNA could have helped amino acids join up without preexisting protein machinery, lab study suggests
Amyloid-β oligomers, curvilinear and annular assemblies, imaged by cryo-ET, cryo-EM, and AFM
Prefibrillar structures of the amyloid-β (Aβ) peptide are central to cytotoxicity in Alzheimer's disease. Time-resolved imaging of oligomers has enabled quantification of their extension. A snapshot of these prefibrillar assemblies has been characterized using a combination of cryo-electron tomography (cryo-ET), cryo-electron microscopy (cryo-EM) single-particle analysis, and atomic force microscopy (AFM). A highly consistent diameter for all curvilinear protofibrils and oligomers of 2.8...
Gut-brain nexus: Mapping multimodal links to neurodegeneration at biobank scale
Alzheimer's disease (AD) and Parkinson's disease (PD) are influenced by genetic and environmental factors. We conducted a biobank-scale study to (i) identify endocrine, nutritional, metabolic, and digestive disorders with potential causal or temporal associations with AD/PD risk before diagnosis; (ii) assess plasma biomarkers' specificity for AD/PD in the context of co-occurring gut related traits and disorders; and (iii) integrate multimodal datasets to enhance AD/PD prediction. Our findings...
Putative PINK1/Parkin activators lower the threshold for mitophagy by sensitizing cells to mitochondrial stress
The PINK1/Parkin pathway targets damaged mitochondria for degradation via mitophagy. Genetic evidence implicates impaired mitophagy in Parkinson's disease, making its pharmacological enhancement a promising therapeutic strategy. Here, we characterize two mitophagy activators: a novel Parkin activator, FB231, and the reported PINK1 activator MTK458. Both compounds lower the threshold for mitochondrial toxins to induce PINK1/Parkin-mediated mitophagy. However, global proteomics revealed that FB231...
Structural insights into the activation of TMEM175 by small molecule
The upregulation of transmembrane protein 175 (TMEM175) has the potential to improve Parkinson's disease (PD) by aiding in the removal of α-synuclein aggregates. Understanding the structural basis of TMEM175 agonisms is crucial for uncovering its therapeutic potential for PD. Here, we have identified the first cryo-electron microscopy (cryo-EM) structure of human TMEM175 complexes with three agonists: DCY1020, DCY1040, and TUG-891. An open state of TMEM175 is unequivocally captured, laying the...
Biomolecular phase separation of microtubule-associated protein Tau and its role in the genesis of Brain Disorders
Microtubule-associated tau (MAP) is a crucial component for cellular cytoskeleton stability. However, upon hyperphosphorylation, these tau proteins detach from microtubules, leading to the genesis of clumpy fibrillar-rich β or paired helical filamental structures known as amyloids. Such deposits predispose a multitude of fatal disorders, including Alzheimer's Disease. The initial event behind such genesis is still a mystery. Today, numerous research studies try to untangle the initial events...
Breaking shackles of molecular weight and emission for NIR-II fluorophores by regulating Columb attraction interaction
The second near-infrared (NIR-II) dyes provide advantages for in vivo imaging, but challenges persist. A primary issue is the lack of practicable strategies to balance emission wavelength and molecular weight, particularly for low-molecular-weight (<500 Da) NIR-II (λ(em) > 1000 nm) dyes. Here, we propose a strategy that tunes NIR-II emissions by reducing Coulomb attraction interaction, contrasting with traditional approaches that redshift absorption wavelengths through energy gap reduction....
Periadventitial delivery of mesenchymal stem cells improves vascular remodeling and maturation in arteriovenous fistulas
Worldwide, more than 4 million patients with end-stage kidney disease require hemodialysis through an arteriovenous fistula (AVF). AVFs fail because of venous neointimal hyperplasia (VNH) resulting in venous stenosis formation. A phase 1 randomized trial in patients undergoing upper extremity AVF placement was performed to evaluate the safety and efficacy of autologous adipose-derived mesenchymal stem cells (MSCs) in improving AVF function. The mechanism of action by which MSCs exert their...
Dietary L-3,4-dihydroxyphenylalanine (L-DOPA) augments cuticular melanization in Anopheles mosquitos reducing their lifespan and malaria burden
L-3,4-dihydroxyphenylalanine (L-DOPA), a naturally occurring tyrosine derivative, is prevalent in environments that include mosquito habitats, potentially serving as part of their diet. Given its role as a precursor for melanin synthesis we investigate the effect of dietary L-DOPA on mosquito physiology and immunity to Plasmodium falciparum and Cryptococcus neoformans infection. Dietary L-DOPA is incorporated into mosquito melanin via a non-canonical pathway and has a profound transcriptional...
Remodeling adipocytes' lipid metabolism with a polycation loaded enzyme-active framework reverses osteoporotic bone marrow
The function of osteoporosis-induced bone marrow adipocyte (BMAds) accumulation remains inadequately understood. Here, we analyze bone marrow lipidomic data and reveal that BMAds deteriorate the skeletal microenvironment by secreting large amounts of lipids, altering the senescence status of neighboring cells by affecting their mitochondrial function. To specifically target BMAds under osteoporotic conditions, we design a polycation-loaded biomimetic dual-site framework (CZP@LC) that interferes...
A chaperone-proteasome-based fragmentation machinery is essential for aggrephagy
Perturbations in protein quality control lead to the accumulation of misfolded proteins and protein aggregates, which can compromise health and lifespan. One key mechanism eliminating protein aggregates is aggrephagy, a selective type of autophagy. Here we reveal that fragmentation is required before autophagic clearance of various types of amorphous aggregates. This fragmentation requires both the 19S proteasomal regulatory particle and the DNAJB6-HSP70-HSP110 chaperone module. These two...
Oxidative stress response protein delays ovarian aging by promoting stress granule clearance
No abstract
The interplay between circadian rhythms and aging: molecular mechanisms and therapeutic strategies
Circadian rhythms are essential biological systems operating on a 24-h cycle, playing a crucial role in regulating sleep, cognitive function, immune responses, and hormone secretion. This review explores the intricate relationship between circadian rhythms and aging, with a focus on the underlying molecular mechanisms. It discusses age-related changes in sleep patterns and the role of circadian disruption in the progression of neurodegenerative diseases such as Parkinson's and Alzheimer's....