Browse Articles

Bidirectional cohort study protocol to construct and validate a prediction model for perioperative pulmonary complications in elderly hip fracture patients

Enabling Selective Mechanochemical Scission of Network Crosslinks by Exchanging Single Carbon Atoms for Silicon

Towards realistic simulation of disease progression in the visual cortex with CNNs

Daily briefing: Meet the scientists who edit Wikipedia

Electrocatalytic Alkene Hydrogenation/Deuteration

Identifying chickpea (Cicer arietinum L.) genotypes rich in ascorbic acid as a source of drought tolerance

Bespoke vaccines can elicit long-lived immune activity against pancreatic cancer

Author Correction: Estimating global geographical distribution and ecological niche dynamics of Ammannia coccinea under climate change based on Biomod2

High-Energy, High-Power Sodium-Ion Batteries from a Layered Organic Cathode

Assessment of hydrological loading displacement from GNSS and GRACE data using deep learning algorithms

Ion Irradiation-Induced Coordinatively Unsaturated Zn Sites for Enhanced CO Hydrogenation

Synaptic Vesicle Glycoprotein 2A Knockout in Parvalbumin and Somatostatin Interneurons Drives Seizures in the Postnatal Mouse Brain

Synaptic vesicle glycoprotein 2A (SV2A) is a presynaptic protein targeted by the antiseizure drug levetiracetam. One or more of the three SV2 genes is expressed in all neurons and is essential to normal neurotransmission. Loss of SV2A results in a seizure phenotype in mice and mutations in humans are also linked to congenital seizures. How SV2A action impacts the epileptic phenotype remains unclear, especially among the diverse neuronal populations that regulate network excitability. This study explored how brain structure and function are affected by SV2A conditional knock-out (SV2A-cKO) in specific neural cell subtypes. We show that SV2A-cKO in all neurons of the postnatal brain triggers lethal seizures, suggesting that the seizures observed in earlier knock-out models were not due to aberrant brain development. Similar lethal seizures are detected in mice in which the loss of SV2A is limited to GABAergic neurons, whereas loss in excitatory neurons produces no noticeable phenotype. No apparent gender difference was ever observed. Further investigation revealed that SV2A-cKO in different GABAergic interneuron populations induces seizure, with variable timescales and severity. Most notably SV2A-cKO in parvalbumin interneurons (PV+) leads to lethal seizures in young animals, while SV2A-cKO in somatostatin (SST) inhibitory neurons results in seizures that were scarcely observed only in adult mice. These results support the crucial role SV2A plays in PV and SST interneurons and suggest that the action of levetiracetam may be due largely to effects on a subset of GABAergic interneurons.

AI-enabled diagnosis and localization of myocardial ischemia and coronary artery stenosis from magnetocardiographic recordings

Vibrationally Assisted Tunneling through the Bread of a Proton Sandwich─Connections to Dynamic Matching

Metformin inhibits the growth of SCLC cells by inducing autophagy and apoptosis via the suppression of EGFR and AKT signalling

High-Pressure Effects on an Octa-Hydrated Curium Complex: An Experimental and Theoretical Investigation

Microvascular Dysfunction, Mitochondrial Reprogramming, and Inflammasome Activation as Critical Regulators of Ischemic Stroke Severity Induced by Chronic Exposure to Prescription Opioids

The opioid epidemic endangers not only public health but also social and economic welfare. Growing clinical evidence indicates that chronic use of prescription opioids may contribute to an elevated risk of ischemic stroke and negatively impact poststroke recovery. In addition, NLRP3 inflammasome activation has been related to several cerebrovascular diseases, including ischemic stroke. Interestingly, an increase in NLRP3 inflammasome activation has also been reported in chronic opioid exposure. Given the pivotal roles of the blood–brain barrier (BBB) and oxidative stress in ischemic stroke pathophysiology, this study focuses on the impact of chronic exposure to prescription opioids on the integrity of cerebrovascular microvasculature, endothelial mitochondrial homeostasis, and the outcomes of ischemic stroke in male wild-type and NLRP3-deficient mice. Our results demonstrate that chronic opioid exposure can compromise the integrity of the BBB and elevate the generation of reactive oxygen species (ROS), resulting in endothelial mitochondrial dysfunction and apoptosis activation. We also provide evidence that opioid exposure enhances inflammasome activation and inflammatory responses and increases the severity of an ischemic stroke. The antioxidantN-acetylcysteine ameliorated these opioid-induced alterations and accelerated the poststroke tissue restoration and functional recovery processes in opioid-exposed mice. Importantly, there was also a significant decrease in ischemic stroke damage in the NLRP3-deficient mice with chronic opioid exposure as compared with wild-type controls. These findings indicate that chronic exposure to prescription opioids impacts the outcome of ischemic stroke by damaging microvascular cerebral integrity through inflammasome activation and mitochondrial dysfunction.

Advancing triple-negative breast cancer treatment through peptide decorated solid lipid nanoparticles for paclitaxel delivery

Comparison of a Nonheme Iron Cyclopropanase with a Homologous Hydroxylase Reveals Mechanistic Features Associated with Distinct Reaction Outcomes

Development of Differential Sublaminar Feedforward Inhibitory Circuits in CA1 Hippocampus Requires <i>Satb2</i>

Pyramidal cells (PCs) in CA1 hippocampus can be classified by their radial position as deep or superficial and organize into subtype-specific circuits necessary for differential information processing. Specifically, superficial PCs receive fewer inhibitory synapses from parvalbumin (PV)-expressing interneurons than deep PCs, resulting in weaker feedforward inhibition of input from CA3 Schaffer collaterals. Using mice, we investigated mechanisms underlying CA1 PC differentiation and the development of this inhibitory circuit motif. We found that the transcriptional regulator SATB2, which is necessary for pyramidal cell differentiation in the neocortex, is selectively expressed in superficial PCs during early postnatal development. To investigate its role in CA1, we conditionally knocked out Satb2 from pyramidal cells during embryonic development using both male and female Emx1 IRES-Cre ; Satb2 flox/flox mice. Loss of Satb2 resulted in increased feedforward inhibition of CA3 Schaffer collateral input to superficial PCs, which matched that observed to deep PCs in control mice. Using paired whole-cell recordings between PCs and PV+ interneurons, we found this was due to an increase in the strength of unitary inhibitory synaptic connections from PV+ interneurons to mutant superficial PCs. Regulation of synapse strength was restricted to inhibitory synapses; excitatory synaptic connections from CA3 to CA1 PCs and CA1 PCs to PV+ interneurons were not affected by loss of Satb2 . Finally, we show that SATB2 expression in superficial PCs is necessary to suppress the formation of synapses from PV+ interneurons during synaptogenesis. Thus, early postnatal expression of SATB2 in superficial PCs is necessary for the development of biased feedforward inhibition in CA1.