Results 81 to 90 of about 34,455 (262)

Near‐Infrared Fluorescent PROTAC Enables Theranostic Imaging and Selective Tau Degradation in Alzheimer's Disease

open access: yesAdvanced Science, EarlyView.
Here, we report a novel NIR fluorescent PROTAC platform that enables real‐time imaging and targeted degradation of Alzheimer's p‐Tau. Our lead compound effectively clears p‐Tau, reduces APP/Aβ, and alleviates cognitive deficits in AD mice. This work demonstrates a theranostic strategy for visualizing degradation and developing next‐generation AD ...
Ziwei Ren   +11 more
wiley   +1 more source

Probing the Energy Landscape of α‐Synuclein Amyloid Fibril Formation by Systematic K‐to‐Q Mutagenesis

open access: yesAdvanced Science, EarlyView.
We use lysine‐to‐glutamine mutations to study the effect of electrostatics on the kinetics and thermodynamics of alpha‐synuclein amyloid fibril formation. We find that mutational effects map on their structural context within fibrils and identify residues that modulate the energy landscape of alpha‐synuclein self‐assembly. Our work outlines a scalable,
Antonin Kunka   +10 more
wiley   +1 more source

Affirmative Action in Brazil: Challenges and Prospects

open access: yesRevista Estudos Feministas, 2008
How do we take stock of affirmative action in Brazil? How should we understand the first initiatives of introduction of a legal framework that institutes affirmative action? What has been the impact of the global agenda on the domestic order?
Flávia Piovesan
doaj  

Palaeoproteomic Deconvolution of Physical and Genetic Collagen Mixtures

open access: yesAdvanced Science, EarlyView.
ClassiCOL_v2 uses a novel “peptide patching” framework that treats any collagen sample as a patchwork of peptide sequences derived from phylogenetically related species. This allows the algorithm to simultaneously resolve two previously intractable problems: multi‐species samples and/or database deficiencies.
Ian Engels   +12 more
wiley   +1 more source

A Gut‐Brain Axis Underlying Succinate‐Associated Compulsive‐Like Behavior

open access: yesAdvanced Science, EarlyView.
Gut‐derived succinate is associated with an excitatory‐inhibitory imbalance in dmPFC glutamatergic neurons, involving microglial SUCNR1 activation and vagal afferent signaling via upregulated gut 5‐HT4 receptors along the DVC‐CeA‐dmPFC circuit, changes that are linked to excessive compulsive‐like behavior.
Yi Li   +12 more
wiley   +1 more source

Persistent Zn2+ Influx‐Mediated Deacetylation of ANXA2 Regulates the “Zn2+‐Autophagic Flux” and Alleviates Intervertebral Disc Degeneration

open access: yesAdvanced Science, EarlyView.
Zinc transporter SLC39A14 sustains intracellular Zn2+ levels to activate SIRT3‑dependent ANXA2 deacetylation at K302. This modification weakens ANXA2‑mTOR binding and releases autophagic‑flux suppression in nucleus pulposus cells. Dysregulated Zn2+ homeostasis disrupts this axis to drive intervertebral disc degeneration.
Yuxin Jin   +23 more
wiley   +1 more source

Engineered Allosteric Biosensor for In Situ DNA Glycosylase Detection in Neuroblastoma Risk Stratification and Drug Resistance Monitoring

open access: yesAdvanced Science, EarlyView.
An engineered allosteric biosensor (UUU‐DZ‐tFNA) was developed, in which UDG specifically recognizes and activates a DNAzyme to achieve signal cycle amplification in a sequentially activatable mode. UUU‐DZ‐tFNA achieves in situ UDG detection across multiple biological levels and facilitates risk stratification and drug resistance monitoring of NB ...
Yaqing Lu   +10 more
wiley   +1 more source

Restores Aβ Clearance by Overcoming PCSK9–LRP1 Dysregulation and TRIB3‐Mediated Autophagy Blockade in Alzheimer's Disease

open access: yesAdvanced Science, EarlyView.
PCSK9 upregulation in cerebrovascular endothelial cells and microglia destabilizes the Aβ transporter LRP1, while TRIB3‐associated autophagy blockade further limits intracellular Aβ degradation. A RAP‐modified tea‐polyphenol nanoparticle co‐delivers siPCSK9 and siTRIB3 to restore LRP1‐mediated Aβ efflux and autophagy‐dependent degradation, reducing Aβ ...
Jie Miao   +8 more
wiley   +1 more source

Neonatal Sevoflurane Exposure Induces Long‐Term Cognitive Impairment via Epigenetically Mediated MMP9 Activation and Perineuronal Net Disruption in the Hippocampal CA2

open access: yesAdvanced Science, EarlyView.
Hippocampal CA2 perineuronal nets ensheathing excitatory pyramidal neurons are selectively vulnerable to repeated neonatal sevoflurane exposure. Epigenetic upregulation of MMP9 via reduced H3K27me3 disrupts PNN integrity, impairs BDNF–TrkB signaling, and causes synaptic protein loss and dendritic spine deficits, leading to persistent social and spatial
Lirong Liang   +11 more
wiley   +1 more source

Clarifying species identity in Aphanopus using wavelet-based otolith shape analysis.

open access: yesPLoS ONE
Accurate species identification is crucial for effective fisheries management, particularly for cryptic species with overlapping ranges and similar morphologies.
Joana Vasconcelos   +8 more
doaj   +1 more source

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