Transcranial optogenetic brain modulator for precise bimodal neuromodulation in multiple brain regions.

Transcranial brain stimulation is a promising technology for safe modulation of brain function without invasive procedures. Recent advances in transcranial optogenetic techniques with external light sources, using upconversion particles and highly sensitive opsins, have shown promise for precise neuromodulation with improved spatial resolution in deeper brain regions. However, these methods have not yet been used to selectively excite or inhibit specific neural populations in multiple brain regions.

Efficacy and safety of sofosbuvir-velpatasvir and sofosbuvir-velpatasvir-voxilaprevir for hepatitis C in Korea: a Phase 3b study.

Background/aims: Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir-velpatasvir and sofosbuvir-velpatasvir-voxilaprevir for 12 weeks in HCV-infected Korean adults.

Methods: This Phase 3b, multicenter, open-label study included 2 cohorts.

A neural probe for concurrent real-time measurement of multiple neurochemicals with electrophysiology in multiple brain regions in vivo.

Real-time monitoring of various neurochemicals with high spatial resolution in multiple brain regions in vivo can elucidate neural circuits related to various brain diseases. However, previous systems for monitoring neurochemicals have limitations in observing multiple neurochemicals without crosstalk in real time, and these methods cannot record electrical activity, which is essential for investigating neural circuits. Here, we present a real-time bimodal (RTBM) neural probe that uses monolithically integrated biosensors and multiple shanks to study the connectivity of neural circuits by measuring multiple neurochemicals and electrical neural activity in real time.

Neural mechanism of acute stress regulation by trace aminergic signalling in the lateral habenula in male mice.

Stress management is necessary for vertebrate survival. Chronic stress drives depression by excitation of the lateral habenula (LHb), which silences dopaminergic neurons in the ventral tegmental area (VTA) via GABAergic neuronal projection from the rostromedial tegmental nucleus (RMTg). However, the effect of acute stress on this LHb-RMTg-VTA pathway is not clearly understood.

Gene Expression Profiling of the Habenula in Rats Exposed to Chronic Restraint Stress.

Chronic stress contributes to the risk of developing depression; the habenula, a nucleus in epithalamus, is associated with many neuropsychiatric disorders. Using genome-wide gene expression analysis, we analyzed the transcriptome of the habenula in rats exposed to chronic restraint stress for 14 days. We identified 379 differentially expressed genes (DEGs) that were affected by chronic stress.

Chronic Status of Serum Albumin and Cognitive Function: A Retrospective Cohort Study.

Previous studies have found an association between serum albumin levels and cognitive function. However, the results of this association are inconsistent, and the effect of Apolipoprotein E (APOE) on the association is less clear. Using retrospective cohort data (2008-2020), we investigated whether chronic serum albumin was associated with cognitive performance in older adults.

Down-regulation of habenular calcium-dependent secretion activator 2 induces despair-like behavior.

Calcium-dependent secretion activator 2 (CAPS2) regulates the trafficking and exocytosis of neuropeptide-containing dense-core vesicles (DCVs). CAPS2 is prominently expressed in the medial habenula (MHb), which is related to depressive behavior; however, how MHb neurons cause depressive symptoms and the role of CAPS2 remains unclear. We hypothesized that dysfunction of MHb CAPS neurons might cause defects in neuropeptide secretion and the activity of monoaminergic centers, resulting in depressive-like behaviors.

A DLG2 deficiency in mice leads to reduced sociability and increased repetitive behavior accompanied by aberrant synaptic transmission in the dorsal striatum.

Background: DLG2, also known as postsynaptic density protein-93 (PSD-93) or chapsyn-110, is an excitatory postsynaptic scaffolding protein that interacts with synaptic surface receptors and signaling molecules. A recent study has demonstrated that mutations in the DLG2 promoter region are significantly associated with autism spectrum disorder (ASD). Although DLG2 is well known as a schizophrenia-susceptibility gene, the mechanisms that link DLG2 gene disruption with ASD-like behaviors remain unclear.

Three-Dimensional Analysis of Mouse Habenula Subnuclei Reveals Reduced Volume and Gene Expression in the Lipopolysaccharide-mediated Depression Model.

The habenula (Hb) is small but important brain structure, anatomically and functionally links the forebrain with the midbrain to modulate various neuropsychiatric functions associated with drug addiction and emotion-associated dysfunctions. Several reports suggested that the dysfunction of Hb-related functions affected the Hb structurally and functionally. However, the technical limitation has awaited the solid conclusion of whether Hb change due to depression is likely to occur in certain subnuclei of the Hb.

Multifunctional multi-shank neural probe for investigating and modulating long-range neural circuits in vivo.

Investigation and modulation of neural circuits in vivo at the cellular level are very important for studying functional connectivity in a brain. Recently, neural probes with stimulation capabilities have been introduced, and they provided an opportunity for studying neural activities at a specific region in the brain using various stimuli. However, previous methods have a limitation in dissecting long-range neural circuits due to inherent limitations on their designs.

The Role of the Medial Habenula Cholinergic System in Addiction and Emotion-Associated Behaviors.

The habenula is a complex nucleus composed of lateral and medial subnuclei, which connect between the limbic forebrain and midbrain. Over the past few years, the lateral habenula has received considerable attention because of its potential roles in cognition and in the pathogenesis of various psychiatric disorders. Unlike extensively studied lateral habenula, anatomically and histologically distinct medial habenula remains largely understudied.

Discovery and characterization of conserved binding of eIF4E 1 (CBE1), a eukaryotic translation initiation factor 4E-binding plant protein.

In many eukaryotes, translation initiation is regulated by proteins that bind to the mRNA cap-binding protein eukaryotic translation initiation factor 4E (eIF4E). These proteins commonly prevent association of eIF4E with eIF4G or form repressive messenger ribonucleoproteins that exclude the translation machinery. Such gene-regulatory mechanisms in plants, and even the presence of eIF4E-interacting proteins other than eIF4G (and the plant-specific isoform eIFiso4G, which binds eIFiso4E), are unknown.

Homeodomain Proteins Directly Regulate ATM Kinase Activity.

Ataxia-telangiectasia mutated (ATM) is a serine/threonine kinase that coordinates the response to DNA double-strand breaks and oxidative stress. NKX3.1, a prostate-specific transcription factor, was recently shown to directly stimulate ATM kinase activity through its highly conserved homeodomain.

A case with acute-on-chronic liver failure receiving liver transplantation during daclatasvir and asunaprevir therapy in chronic hepatitis C patient.

We report a case with hepatitis C virus genotype 1 b liver cirrhosis who received liver transplantation because of acute-on-chronic liver failure during daclatasvir (DSV) and asunaprevir (ASV) combination therapy. To our knowledge, this is the first case received liver transplantation during DSV + ASV therapy. Therefore, clinicians should pay particular attention to the possibility of acute liver failure during DSV and ASV combination therapy.

Author Correction: Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior.

A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.

Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior.

Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair.

Mice subjected to uncontrollable electric shocks show depression-like behaviors irrespective of their state of helplessness.

The unpredictable and inescapable electric shock-induced "learned helplessness" paradigm has long been used to produce an animal model of depression to identify the molecules associated with depressive symptoms or to assess the efficacy of pharmacological treatments for depression. After exposure to unpredictable and inescapable shocks (uncontrollable stress), most of mice showed defect in escape behavior in active avoidance test (learned helplessness, LH), while others did not (non-learned helplessness, NLH). Here, we investigated whether mice with LH or NLH exhibited depressive symptoms, including anhedonia, anxiety, and despair.

Single-molecule imaging reveals the mechanism of Exo1 regulation by single-stranded DNA binding proteins.

Exonuclease 1 (Exo1) is a 5'→3' exonuclease and 5'-flap endonuclease that plays a critical role in multiple eukaryotic DNA repair pathways. Exo1 processing at DNA nicks and double-strand breaks creates long stretches of single-stranded DNA, which are rapidly bound by replication protein A (RPA) and other single-stranded DNA binding proteins (SSBs). Here, we use single-molecule fluorescence imaging and quantitative cell biology approaches to reveal the interplay between Exo1 and SSBs.

BRCA1 and CtIP Are Both Required to Recruit Dna2 at Double-Strand Breaks in Homologous Recombination.

Homologous recombination plays a key role in the repair of double-strand breaks (DSBs), and thereby significantly contributes to cellular tolerance to radiotherapy and some chemotherapy. DSB repair by homologous recombination is initiated by 5' to 3' strand resection (DSB resection), with nucleases generating the 3' single-strand DNA (3'ssDNA) at DSB sites. Genetic studies of Saccharomyces cerevisiae demonstrate a two-step DSB resection, wherein CtIP and Mre11 nucleases carry out short-range DSB resection followed by long-range DSB resection done by Dna2 and Exo1 nucleases.

Catalytic and noncatalytic roles of the CtIP endonuclease in double-strand break end resection.

The carboxy-terminal binding protein (CtBP)-interacting protein (CtIP) is known to function in 5' strand resection during homologous recombination, similar to the budding yeast Sae2 protein, but its role in this process is unclear. Here, we characterize recombinant human CtIP and find that it exhibits 5' flap endonuclease activity on branched DNA structures, independent of the MRN complex. Phosphorylation of CtIP at known damage-dependent sites and other sites is essential for its catalytic activity, although the S327 and T847 phosphorylation sites are dispensable.

Visualization of local DNA unwinding by Mre11/Rad50/Nbs1 using single-molecule FRET.

The Mre11/Rad50/Nbs1 (MRN) complex initiates and coordinates DNA repair and signaling events at double-strand breaks. The interaction between MRN and DNA ends is critical for the recruitment of DNA-processing enzymes, end tethering, and activation of the ATM protein kinase. Here we visualized MRN binding to duplex DNA molecules using single-molecule FRET, and found that MRN unwinds 15-20 base pairs at the end of the duplex, holding the branched structure open for minutes at a time in an ATP-dependent reaction.

Detecting hepatocellular carcinoma in gadoxetic-acid-enhanced hepatobiliary-phase MR imaging at 3T: comparing high and low flip angle.

Purpose: We evaluated the diagnostic performance of fat-suppressed 3D T1-weighted gradient-echo magnetic resonance imaging (MRI) sequences for the hepatobiliary phase of gadoxetic-acid-enhanced liver MRI between low and high flip angle (FA) at 3T.

Materials And Methods: Forty-six patients with 62 HCCs were enrolled in this retrospective study from among 267 consecutive patients who underwent 3T MRI with low and high FA (10° and 25°) sequences at the hepatobiliary phase. A radiologist measured signal intensities and standard deviations (SD) of lesion, liver, and spleen and calculated signal-to-noise ratio, liver-spleen contrast, and liver-lesion contrast.