Basolateral amygdala hyperexcitability is associated with precocious developmental emergence of fear-learning in Fragile X Syndrome.

Fragile X Syndrome (FXS) is a neurodevelopmental disorder and the most common monogenic cause of intellectual disability, autism spectrum disorders (ASDs) and anxiety disorders. Loss of fragile x mental retardation protein (FMRP) results in disruptions of synaptic development during a critical period (CP) of circuit formation in the basolateral amygdala (BLA). However, it is unknown how these alterations impact microcircuit development and function. Using a combination of electrophysiologic and behavioral approaches in both male (Fmr1-/y) and female (Fmr1-/-) mice, we demonstrate that principal neurons (PNs) in the Fmr1KO BLA exhibit hyperexcitability during a sensitive period in amygdala development. This hyperexcitability contributes to increased excitatory gain in fear-learning circuits. Further, synaptic plasticity is enhanced in the BLA of Fmr1KO mice. Behavioral correlation demonstrates that fear-learning emerges precociously in the Fmr1KO mouse. Early life THIP intervention ameliorates fear-learning in Fmr1KO mice. These results suggest that CP plasticity in the amygdala of the Fmr1KO mouse may be shifted to earlier developmental timepoints.SIGNIFICANCE STATEMENTIn these studies we identify early developmental alterations in principal neurons in the FXS BLA. We show that as early as P14, excitability and feed-forward excitation, and synaptic plasticity is enhanced in Fmr1KO lateral amygdala. This correlates with precocious emergence of fear-learning in the Fmr1KO mouse. Early life THIP intervention restores CP plasticity in WT mice and ameliorates fear-learning in the Fmr1KO mouse.

Absent hyperdense middle cerebral artery sign is associated with poor functional outcome after mechanical thrombectomy.

BACKGROUND: The hyperdense middle cerebral artery sign on computed tomography indicates proximal middle cerebral artery occlusion. Recent reports suggest an association between the hyperdense sign and successful reperfusion. The prognostic value of the hyperdense middle cerebral artery sign in patients receiving mechanical thrombectomy has not been extensively studied. AIMS: Our study aims to evaluate the association between the hyperdense middle cerebral artery sign and functional outcome in patients with M1 occlusions that had undergone mechanical thrombectomy. METHODS: We conducted a single-center retrospective observational cohort study of 102 consecutive patients presenting with acute M1 occlusions that had undergone mechanical thrombectomy. Patients were stratified into cohorts based on the presence of hyperdense middle cerebral artery sign visually assessed on computed tomography by two readers. The outcomes of interests were functional disability measured by the ordinal Modified Rankin Scale (mRS) at 90 days, mortality, reperfusion status and hemorrhagic conversion. RESULTS: Out of the 102 patients with M1 occlusions, 71 had hyperdense middle cerebral artery sign. There was no significant difference between the cohorts in age, baseline mRS, NIHSS, ASPECTS, and time to reperfusion. The absence of hyperdense middle cerebral artery sign was associated with increased odds of being dependent or dying (higher mRS) (OR: 3.24, 95% CI: 1.30-8.06, p = 0.011) after adjusting for other significant predictors, including age, female sex, hypertension, presenting serum glucose, ASPECTS, CTA collateral score, and successful reperfusion. CONCLUSION: The absence of hyperdense middle cerebral artery sign is associated with worse functional outcome in patients presenting with M1 occlusions undergoing thrombectomy.

Aluminium-Catalyzed C(sp)-H Borylation of Alkynes.

Historically used in stoichiometric hydroalumination chemistry, recent advances have transformed aluminium hydrides into versatile catalysts for the hydroboration of unsaturated multiple bonds. This catalytic ability is founded on the defining reactivity of aluminium hydrides with alkynes and alkenes: 1,2-hydroalumination of the unsaturated π-system. This manuscript reports the aluminium hydride catalyzed dehydroborylation of terminal alkynes. A tethered intramolecular amine ligand controls reactivity at the aluminium hydride centre, switching off hydroalumination and instead enabling selective reactions at the alkyne C-H σ-bond. Chemoselective C-H borylation was observed across a series of aryl- and alkyl-substituted alkynes (21 examples). On the basis of kinetic and density functional theory studies, a mechanism in which C-H borylation proceeds by σ-bond metathesis between pinacolborane (HBpin) and alkynyl aluminium intermediates is proposed.

Expanding the Entamoeba Universe: New Hosts Yield Novel Ribosomal Lineages.

Removing the requirement for cell culture has led to a substantial increase in the number of lineages of Entamoeba recognized as distinct. Surveying the range of potential host species for this parasite genus has barely been started and it is clear that additional sampling of the same host in different locations often identifies additional diversity. In this study, using small subunit ribosomal RNA gene sequencing, we identify four new lineages of Entamoeba, including the first report of Entamoeba from an elephant, and extend the host range of some previously described lineages. In addition, examination of microbiome data from a number of host animals suggests that substantial Entamoeba diversity remains to be uncovered.