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Astrocyte-microglia crosstalk through Hevin and Toll-like receptor signaling controls developmental thalamocortical synapse refinement
Astrocyte-microglia crosstalk in thalamocortical synapse refinement.
Both microglia and astrocytes play crucial role in synapse refinement during development but it is not clear how they communicate to balance synapse formation and elimination.
The researchers show that astrocytes instruct this process through the secreted synaptogenic protein Hevin/Sparcl1.
The proteolytically generated C-terminal of Hevin signals to microglia via TLR4, triggering a pro-phagocytic state that promotes refinement of thalamocortical synapses in the developing visual cortex. sciencenewshighlights ScienceMission https://sciencemission.com/Hevin-and-Toll-like-receptor
Microglia are key drivers of synapse refinement during development. Ramirez et al. show that astrocytes instruct this process through the secreted synaptogenic protein Hevin/Sparcl1. The proteolytically generated C-terminal of Hevin signals to microglia via TLR4, triggering a pro-phagocytic state that promotes refinement of thalamocortical synapses in the developing visual cortex.
Plasma proteomic signature of frailty in 50,506 adults
Online now: Jia et al. delineate the most comprehensive plasma proteomic landscape of frailty to date and develop proteomic frailty scores that predict multiple diseases and respond to modifiable risk factors. They identify a biphasic pattern of frailty-related proteomic alterations across the lifespan, revealing critical windows that may inform targeted intervention programs.
Compound amino acid synergizes ceftazidime-avibactam to eradicate extracellular and facultative intracellular MDR pathogens
This study demonstrates that the FDA-approved drug 18AA potently resensitizes multidrug-resistant pathogens to ceftazidime-avibactam. It achieves this by activating two bacterial pathways, the inosine-CusS/R-CusC axis and the proton motive force, to promote antibiotic influx, offering a readily translatable strategy against formidable infections.
RNA barcodes fast-track brain connection mapping
“When engineering a computer, you need to know the circuitry of the central processing unit. If you don’t know how everything is wired together, you can’t understand its function, optimize it or fix it when something breaks. We are approaching the brain the same way,” said study leader Boxuan Zhao, a professor of cell and developmental biology at the University of Illinois Urbana-Champaign.
“Our technology enables simultaneous mapping of thousands of neural connections with single-synapse resolution —a capability that doesn’t exist in any current technology. It is directly applicable to understanding circuit dysfunction in neurodegenerative diseases and could provide a platform for developing circuit-guided therapeutic interventions,” he said.
Abstract: Patients with recurrent kidney stone disease stand to benefit from personalized diagnostics
In this Research Article, Ruxandra Bachmann-Gagescu & team integrate blood and urine biochemistry with genetics to improve interpretation of genetic findings in adults with kidney stone disease—the approach has prognostic value, enabling personalized risk assessment.
3Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
4National Center of Competence in Research (NCCR) Kidney. CH, Bern, Switzerland.
5Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
ADJUVANT Randomized Controlled Trial: Rationale and Design
ADJUVANT: Testing if IV tirofiban is non-inferior to thrombolysis before endovascular thrombectomy for acute ischemic stroke. Read about the upcoming trial.
BackgroundIntravenous thrombolysis followed by endovascular thrombectomy (EVT) is a first‐line recommended strategy for thrombolysis‐eligible patients with stroke due to acute large‐vessel occlusion. Tirofiban, one of the most used glycoprotein IIb/IIIa receptor inhibitors, has been increasingly advocated to counteract different stages of thrombosis mediated by activated platelets. It is unclear whether tirofiban could be used as an alternative to thrombolysis as adjuvant medicine for EVT. This trial aims to assess whether intravenous tirofiban plus EVT is noninferior to intravenous thrombolysis bridging with EVT in patients with acute ischemic stroke due to large‐vessel occlusion who are eligible for thrombolysis.
