Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits.

Chronic methamphetamine (METH) use, a prevalent psychostimulant, is known to impair attention, yet the cellular mechanisms driving these deficits remain poorly understood. Here, we employed a rat model of repeated passive METH injections and evaluated attentional performance using the 5-choice serial reaction time task (5-CSRTT). Using single-nucleus RNA sequencing, immunofluorescence and in situ hybridization, we characterized the response of neurons in the reticulotegmental nucleus (RtTg) to METH exposure.

Heterozygous Variants in KCNJ10 Cause Paroxysmal Kinesigenic Dyskinesia Via Haploinsufficiency.

Objective: Most paroxysmal kinesigenic dyskinesia (PKD) cases are hereditary, yet approximately 60% of patients remain genetically undiagnosed. We undertook the present study to uncover the genetic basis for undiagnosed PKD patients.

Methods: Whole-exome sequencing was performed for 106 PRRT2-negative PKD probands.

An oligopeptide permease, OppABCD, requires an iron-sulfur cluster domain for functionality.

Oligopeptide permease, OppABCD, belongs to the type I ABC transporter family. Its role is to import oligopeptides into bacteria for nutrient uptake and to modulate the host immune response. OppABCD consists of a cluster C substrate-binding protein (SBP), OppA, membrane-spanning OppB and OppC subunits, and an ATPase, OppD, that contains two nucleotide-binding domains (NBDs).

Molecular basis for substrate transport of ABC importer DppABCD.

The type I adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter DppABCD is believed to be responsible for the import of exogenous heme as an iron source into the cytoplasm of the human pathogen (). Additionally, this system is also known to be involved in the acquisition of tri- or tetra-peptides. Here, we report the cryo-electron microscopy structures of the dual-function DppABCD transporter in three forms, namely, the , substrate-bound, and ATP-bound states.

Rhesus monkeys exhibiting spontaneous ritualistic behaviors resembling obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric disorder that affects ∼2%-3% of the population globally. Studying spontaneous OCD-like behaviors in non-human primates may improve our understanding of the disorder. In large rhesus monkey colonies, we found 10 monkeys spontaneously exhibiting persistent sequential motor behaviors (SMBs) in individual-specific sequences that were repetitive, time-consuming and stable over prolonged periods.

A potential broad-spectrum neutralizing antibody against Betacoronavirus.

Three pandemics caused by human Betacoronavirus had broken out in the past two decades. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was one of the novel epidemic strains which caused the third pandemic, coronavirus disease 2019 (COVID-19), a global public health crisis. So far, more than millions of people have been infected.

Repeated methamphetamine exposure decreases plasma brain-derived neurotrophic factor levels in rhesus monkeys.

Background: Brain-derived neurotrophic factor (BDNF) is known to prevent methamphetamine (METH)-induced neurotoxicity and plays a role in various stages of METH addiction. However, there is a lack of research with longitudinal design on changes in plasma BDNF levels in active METH-dependent individuals.

Aims: The aim of the study was to investigate changes in BDNF levels during METH self-administration in monkeys.

Molecular recognition of trehalose and trehalose analogues by LpqY-SugABC.

Trehalose plays a crucial role in the survival and virulence of the deadly human pathogen (). The type I ATP-binding cassette (ABC) transporter LpqY-SugABC is the sole pathway for trehalose to enter . The substrate-binding protein, LpqY, which forms a stable complex with the translocator SugABC, recognizes and captures trehalose and its analogues in the periplasmic space, but the precise molecular mechanism for this process is still not well understood.

Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB.

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.

A high-fidelity RNA-targeting Cas13 restores paternal Ube3a expression and improves motor functions in Angelman syndrome mice.

Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by loss of function mutations in maternally expressed UBE3A. No gene-specific treatment is available for patients so far. Although intact and transcriptionally active, paternally inherited UBE3A is silenced by elongation of antisense long noncoding RNA UBE3A-ATS in neurons.

The Pathology of Primary Familial Brain Calcification: Implications for Treatment.

Primary familial brain calcification (PFBC) is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain, accompanied by various symptoms, such as dystonia, ataxia, parkinsonism, dementia, depression, headaches, and epilepsy. Currently, the etiology of PFBC is largely unknown, and no specific prevention or treatment is available. During the past 10 years, six causative genes (SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, and JAM2) have been identified in PFBC.

Loss of function of CMPK2 causes mitochondria deficiency and brain calcification.

Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions.

Structure-based design of anti-mycobacterial drug leads that target the mycolic acid transporter MmpL3.

New anti-tubercular agents are urgently needed to address the emerging threat of drug resistance to human tuberculosis. Here, we have used structure-assisted methods to develop compounds that target mycobacterial membrane protein large 3 (MmpL3). MmpL3 is essential for the transport of mycolic acids, an important cell-wall component of mycobacteria.

Base-edited cynomolgus monkeys mimic core symptoms of STXBP1 encephalopathy.

Presynaptic syntaxin binding protein 1 (STXBP1) is essential for neurotransmitter release. Heterozygous mutations in this protein cause STXBP1 encephalopathy (STXBP1-E), which is characterized by intellectual disabilities and epilepsies. Since nonhuman primates closely resemble humans, monkey models may advance studies on the pathogenesis and therapeutic treatments of STXBP1-E.