Design, Synthesis, and Pharmacological Evaluation of Nonsteroidal Tricyclic Ligands as Modulators of GABA Receptors.

GABA receptors (GABARs) are the major elements of inhibitory neurotransmission in the central nervous system (CNS). They are established targets for regulation by endogenous brain neuroactive steroids (NASs) such as pregnanolone. However, the complexity of de novo synthesis of NAS derivatives has hindered attempts to circumvent the principal limitations of using endogenous NASs, including selectivity and limited oral bioavailability.

Lesotho's progress towards UNAIDS 95-95-95 targets from 2016 to 2020: comparison of Population-based HIV Impact Assessments.

Background: Lesotho has made substantial efforts to control its HIV epidemic. We aimed to assess progress towards UNAIDS 95-95-95 targets in Lesotho by comparing data from the Lesotho Population-based HIV Impact Assessments conducted in 2016-17 (LePHIA 2016) and 2019-20 (LePHIA 2020).

Methods: The LePHIA surveys used a cross-sectional, two-stage, stratified cluster sampling design to obtain a nationally representative sample of adults aged 15-59 years (LePHIA 2016) or aged 15 years and older (LePHIA 2020) from all ten districts of Lesotho.

Image metric-based multi-observation single-step deep deterministic policy gradient for sensorless adaptive optics.

Sensorless adaptive optics (SAO) has been widely used across diverse fields such as astronomy, microscopy, and ophthalmology. Recent advances have proved the feasibility of using the deep deterministic policy gradient (DDPG) for image metric-based SAO, achieving fast correction speeds compared to the coordinate search Zernike mode hill climbing (ZMHC) method. In this work, we present a multi-observation single-step DDPG (MOSS-DDPG) optimization framework for SAO on a confocal scanning laser ophthalmoscope (SLO) system with particular consideration for applications in preclinical retinal imaging.

GABA receptors and neuroligin 2 synergize to promote synaptic adhesion and inhibitory synaptogenesis.

GABA receptors (γ-aminobutyric acid-gated receptors type A; GABARs), the major structural and functional postsynaptic components of inhibitory synapses in the mammalian brain, belong to a family of GABA-gated Cl/HCO ion channels. They are assembled as heteropentamers from a family of subunits including: α (1-6), β(1-3), γ(1-3), δ, ε, π, θ and ρ(1-3). GABARs together with the postsynaptic adhesion protein Neuroligin 2 (NL2) and many other pre- and post-synaptic proteins guide the initiation and functional maturation of inhibitory GABAergic synapses.

Presynaptic hyperexcitability reversed by positive allosteric modulation of a GABABR epilepsy variant.

GABABRs are key membrane proteins that continually adapt the excitability of the nervous system. These G-protein coupled receptors are activated by the brain's premier inhibitory neurotransmitter GABA. They are obligate heterodimers composed of GABA-binding GABABR1 and G-protein-coupling GABABR2 subunits.