The WAVE complex in developmental and adulthood brain disorders.

Actin polymerization and depolymerization are fundamental cellular processes required not only for the embryonic and postnatal development of the brain but also for the maintenance of neuronal plasticity and survival in the adult and aging brain. The orchestrated organization of actin filaments is controlled by various actin regulatory proteins. Wiskott‒Aldrich syndrome protein-family verprolin-homologous protein (WAVE) members are key activators of ARP2/3 complex-mediated actin polymerization.

Genetic Variant Analyses Identify Novel Candidate Autism Risk Genes from a Highly Consanguineous Cohort of 104 Families from Oman.

Deficits in social communication, restricted interests, and repetitive behaviours are hallmarks of autism spectrum disorder (ASD). Despite high genetic heritability, the majority of clinically diagnosed ASD cases have unknown genetic origins. We performed genome sequencing on mothers, fathers, and affected individuals from 104 families with ASD in Oman, a Middle Eastern country underrepresented in international genetic studies.

Novel Digital Anomalies, Hippocampal Atrophy, and Mutations Expand the Genotypic and Phenotypic Spectra of CNKSR2 in the Houge Type of X-Linked Syndromic Intellectual Development Disorder (MRXSHG).

The Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2, a gene located at Xp22.12.

Nonlinear parameter estimation with physics-constrained spectral-spatial priors for highly accelerated chemical exchange saturation transfer MRI.

To develop a nonlinear, model-based parameter estimation method directly from incomplete measurements in - space for robust spectral analysis in highly accelerated chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI).. A CEST-specific, separable nonlinear model, which describes spectral decomposition using multi-pool Lorentzian functions (conventional magnetization transfer (MT), direct saturation of water signals (DS), amide, amine, and nuclear Overhauser effect) derived from the steady-state Bloch McConnel equation, is incorporated into a measurement model in CEST MRI.

Genome Sequencing Identifies 13 Novel Candidate Risk Genes for Autism Spectrum Disorder in a Qatari Cohort.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted interests, and repetitive behaviors. Despite considerable research efforts, the genetic complexity of ASD remains poorly understood, complicating diagnosis and treatment, especially in the Arab population, with its genetic diversity linked to migration, tribal structures, and high consanguinity. To address the scarcity of ASD genetic data in the Middle East, we conducted genome sequencing (GS) on 50 ASD subjects and their unaffected parents.

A normative framework dissociates need and motivation in hypothalamic neurons.

Physiological needs evoke motivational drives that produce natural behaviors for survival. In previous studies, the temporally intertwined dynamics of need and motivation have made it challenging to differentiate these two components. On the basis of classic homeostatic theories, we established a normative framework to derive computational models for need-encoding and motivation-encoding neurons.

Exome sequencing reveals neurodevelopmental genes in simplex consanguineous Iranian families with syndromic autism.

Background And Objective: Autosomal recessive genetic disorders pose significant health challenges in regions where consanguineous marriages are prevalent. The utilization of exome sequencing as a frequently employed methodology has enabled a clear delineation of diagnostic efficacy and mode of inheritance within multiplex consanguineous families. However, these aspects remain less elucidated within simplex families.

Identification of rare genetic variants in the PCDH genetic family in a cohort of transgender women.

Objective: To study the identification of rare genetic variants in the PCDH genetic family in a cohort of transgender women (TGW) and their potential role in gender identity.

Design: Exome sequencing and functional ontology analysis.

Setting: Outpatient gender health and reproductive endocrinology clinics.

Heterozygous ZNHIT3 variants within the 17q12 recurrent deletion region are associated with Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome.

The molecular basis of mullerian aplasia, also known as Mayer-Rokitansky-Kuster Hauser (MRKH) or congenital absence of the uterus and vagina, is largely unknown. We applied a multifaceted genetic approach to studying the pathogenesis of MRKH including exome sequencing of trios and duos, genome sequencing of families, qPCR, RT-PCR, and Sanger sequencing to detect intragenic deletions, insertions, splice variants, single nucleotide variants, and rearrangements in 132 persons with MRKH. We identified two heterozygous variants in ZNHIT3 localized to a commonly involved CNV region at chromosome 17q12 in two different families with MRKH.

Autosomal recessive non-syndromic hearing loss genes in Pakistan during the previous three decades.

Hearing loss is a clinically and genetically heterogeneous disorder, with over 148 genes and 170 loci associated with its pathogenesis. The spectrum and frequency of causal variants vary across different genetic ancestries and are more prevalent in populations that practice consanguineous marriages. Pakistan has a rich history of autosomal recessive gene discovery related to non-syndromic hearing loss.

Identification of two novel autism genes, and , in Qatar simplex families through exome sequencing.

This study investigated the genetic underpinnings of autism spectrum disorder (ASD) in a Middle Eastern cohort in Qatar using exome sequencing. The study identified six candidate autism genes in independent simplex families, including both four known and two novel autosomal dominant and autosomal recessive genes associated with ASD. The variants consisted primarily of and homozygous missense and splice variants.

Multi-timescale reinforcement learning in the brain.

To thrive in complex environments, animals and artificial agents must learn to act adaptively to maximize fitness and rewards. Such adaptive behavior can be learned through reinforcement learning, a class of algorithms that has been successful at training artificial agents and at characterizing the firing of dopamine neurons in the midbrain. In classical reinforcement learning, agents discount future rewards exponentially according to a single time scale, controlled by the discount factor.

Bi-allelic truncating variants in CASP2 underlie a neurodevelopmental disorder with lissencephaly.

Lissencephaly (LIS) is a malformation of cortical development due to deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. Thirty-one LIS-associated genes have been previously described. Recently, biallelic pathogenic variants in CRADD and PIDD1, have associated with LIS impacting the previously established role of the PIDDosome in activating caspase-2.

Competitive integration of time and reward explains value-sensitive foraging decisions and frontal cortex ramping dynamics.

Patch foraging presents a ubiquitous decision-making process in which animals decide when to abandon a resource patch of diminishing value to pursue an alternative. We developed a virtual foraging task in which mouse behavior varied systematically with patch value. Mouse behavior could be explained by a model integrating time and rewards antagonistically, scaled by a latent patience state.

Distinct roles of the orbitofrontal cortex, ventral striatum, and dopamine neurons in counterfactual thinking of decision outcomes.

Individuals often assess past decisions by comparing what was gained with what would have been gained had they acted differently. Thoughts of past alternatives that counter what actually happened are called "counterfactuals." Recent theories emphasize the role of the prefrontal cortex in processing counterfactual outcomes in decision-making, although how subcortical regions contribute to this process remains to be elucidated.

Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell development.

WDR11, a gene associated with Kallmann syndrome, is important in reproductive system development but molecular understanding of its action remains incomplete. We previously reported that Wdr11-deficient embryos exhibit defective ciliogenesis and developmental defects associated with Hedgehog (HH) signalling. Here we demonstrate that WDR11 is required for primordial germ cell (PGC) development, regulating canonical and noncanonical HH signalling in parallel.

Prior expectation enhances sensorimotor behavior by modulating population tuning and subspace activity in sensory cortex.

Prior knowledge facilitates our perception and goal-directed behaviors, particularly when sensory input is lacking or noisy. However, the neural mechanisms underlying the improvement in sensorimotor behavior by prior expectations remain unknown. In this study, we examine the neural activity in the middle temporal (MT) area of visual cortex while monkeys perform a smooth pursuit eye movement task with prior expectation of the visual target's motion direction.

Editorial for the Special Issue on "Molecular Genetics of Autism and Intellectual Disability".

Autism spectrum disorder (ASD), a neurodevelopmental illness that affects children at an early age with a global prevalence of 1%, is diagnosed based on clinical features such as social impairment, repetitive behaviors, and restricted interests [...