Effect of Ankle-Foot Orthosis on Paretic Gastrocnemius and Tibialis Anterior Muscle Contraction of Stroke Survivors During Walking: A Pilot Study.

Ankle-foot orthoses (AFOs) have been commonly prescribed for stroke survivors with foot drop, but their impact on the contractions of paretic tibialis anterior (TA) and medial gastrocnemius (MG) has remained inconclusive. This study thus investigated the effect of AFOs on these muscle contractions in stroke survivors. The contractions of paretic TA and MG muscles were assessed in twenty stroke patients and compared between walking with and without AFOs, using a novel wearable dynamic ultrasound imaging and sensing system.

Recurrent disruption of tumour suppressor genes in cancer by somatic mutations in cleavage and polyadenylation signals.

The expression of eukaryotic genes relies on the precise 3'-terminal cleavage and polyadenylation of newly synthesized pre-mRNA transcripts. Defects in these processes have been associated with various diseases, including cancer. While cancer-focused sequencing studies have identified numerous driver mutations in protein-coding sequences, noncoding drivers - particularly those affecting the cis-elements required for pre-mRNA cleavage and polyadenylation - have received less attention.

Housing and Husbandry Factors Affecting Zebrafish () Novel Tank Test Responses: A Global Multi-Laboratory Study.

The reproducibility crisis in bioscience, characterized by inconsistent study results, impedes our understanding of biological processes and global collaborative studies offer a unique solution. This study is the first global collaboration using the zebrafish () novel tank test, a behavioral assay for anxiety-like responses. We analyzed data from 20 laboratories worldwide, focusing on housing conditions and experimental setups.

Reprogramming astroglia into neurons with hallmarks of fast-spiking parvalbumin-positive interneurons by phospho-site-deficient Ascl1.

Cellular reprogramming of mammalian glia to an induced neuronal fate holds the potential for restoring diseased brain circuits. While the proneural factor () is widely used for neuronal reprogramming, in the early postnatal mouse cortex, fails to induce the glia-to-neuron conversion, instead promoting the proliferation of oligodendrocyte progenitor cells (OPC). Since Ascl1 activity is posttranslationally regulated, here, we investigated the consequences of mutating six serine phospho-acceptor sites to alanine (Ascl1SA6) on lineage reprogramming in vivo.

Structure of the RNA-dependent RNA polymerase P2 from the cystovirus φ8.

The replication of RNA viruses relies on the activity of RNA-dependent RNA polymerases (RdRps). Despite large variations in their genomic sequences, viral RdRps share a common architecture generally known as a closed right hand. The P2 polymerase of cystovirus φ6 is currently among the best characterized viral RdRps.

RNA in axons, dendrites, synapses and beyond.

In neurons, a diverse range of coding and non-coding RNAs localize to axons, dendrites, and synapses, where they facilitate rapid responses to local needs, such as axon and dendrite extension and branching, synapse formation, and synaptic plasticity. Here, we review the extent of our current understanding of RNA subclass diversity in these functionally demanding subcellular compartments. We discuss the similarities and differences identified between axonal, dendritic and synaptic local transcriptomes, and discuss the reported and hypothesized fates and functions of localized RNAs.

Human TDP43 is required for ALS‑related annexin A11 toxicity in .

Genomics allows identification of genes and mutations associated with amyotrophic lateral sclerosis (ALS). Mutations in annexin A11 (ANXA11) are responsible for ~1% of all familial ALS and fronto-temporal dementia cases. The present study used the fruit fly, , to assess the mechanism of toxicity of ANXA11 mutants in residues that are conserved in the fly ANXB11 protein, the closest homolog to human ANXA11.

The heart is a resident tissue for hematopoietic stem and progenitor cells in zebrafish.

The contribution of endocardial cells (EdCs) to the hematopoietic lineages has been strongly debated. Here, we provide evidence that in zebrafish, the endocardium gives rise to and maintains a stable population of hematopoietic cells. Using single-cell sequencing, we identify an endocardial subpopulation expressing enriched levels of hematopoietic-promoting genes.

Prediction-error signals in anterior cingulate cortex drive task-switching.

Task-switching is a fundamental cognitive ability that allows animals to update their knowledge of current rules or contexts. Detecting discrepancies between predicted and observed events is essential for this process. However, little is known about how the brain computes cognitive prediction-errors and whether neural prediction-error signals are causally related to task-switching behaviours.

Transmembrane and coiled-coil 2 associates with Alzheimer's disease pathology in the human brain.

Transmembrane and coiled-coil 2 (TMCC2) is a human orthologue of the Drosophila gene dementin, mutant alleles of which cause neurodegeneration with features of Alzheimer's disease (AD). TMCC2 and Dementin further have an evolutionarily conserved interaction with the amyloid protein precursor (APP), a protein central to AD pathogenesis. To investigate if human TMCC2 might also participate in mechanisms of neurodegeneration, we examined TMCC2 expression in late onset AD human brain and age-matched controls, familial AD cases bearing a mutation in APP Val717, and Down syndrome AD.

Poised PABP-RNA hubs implement signal-dependent mRNA decay in development.

Signaling pathways drive cell fate transitions largely by changing gene expression. However, the mechanisms for rapid and selective transcriptome rewiring in response to signaling cues remain elusive. Here we use deep learning to deconvolve both the sequence determinants and the trans-acting regulators that trigger extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase kinase (MEK)-induced decay of the naive pluripotency mRNAs.

Annexin A11 mutations are associated with nuclear envelope dysfunction in vivo and in human tissue.

Annexin A11 mutations are a rare cause of amyotrophic lateral sclerosis (ALS), wherein replicated protein variants P36R, G38R, D40G and D40Y are located in a small-alpha helix within the long, disordered N-terminus. To elucidate disease mechanisms, we characterised the phenotypes induced by a genetic loss of function (LoF) and by misexpression of G38R and D40G in vivo. Loss of Annexin A11 results in a low-penetrant behavioural phenotype and aberrant axonal morphology in zebrafish homozygous knockout larvae, which is rescued by human WT Annexin A11.

Alternative splicing coupled to nonsense-mediated decay coordinates downregulation of non-neuronal genes in developing mouse neurons.

Background: The functional coupling between alternative pre-mRNA splicing (AS) and the mRNA quality control mechanism called nonsense-mediated decay (NMD) can modulate transcript abundance. Previous studies have identified several examples of such a regulation in developing neurons. However, the systems-level effects of AS-NMD in this context are poorly understood.

Excitatory and inhibitory synapses show a tight subcellular correlation that weakens over development.

Neurons receive correlated levels of excitation and inhibition, a feature that is important for proper brain function. However, how this relationship between excitatory and inhibitory inputs is established during the dynamic period of circuit wiring remains unexplored. Using multiple techniques, including in utero electroporation, electron microscopy, and electrophysiology, we reveal a tight correlation in the distribution of excitatory and inhibitory synapses along the dendrites of developing CA1 hippocampal neurons.

Breakthroughs in choroid plexus and CSF biology from the first European Choroid plexus Scientific Forum (ECSF).

The European Choroid plexus Scientific Forum (ECSF), held in Heidelberg, Germany between the 7th and 9th of November 2023, involved 21 speakers from eight countries. ECSF focused on discussing cutting-edge fundamental and medical research related to the development and functions of the choroid plexus and its implications for health, aging, and disease, including choroid plexus tumors. In addition to new findings in this expanding field, innovative approaches, animal models and 3D in vitro models were showcased to encourage further investigation into choroid plexus and cerebrospinal fluid roles.

Alternative splicing controls teneurin-3 compact dimer formation for neuronal recognition.

Neuronal network formation is facilitated by recognition between synaptic cell adhesion molecules at the cell surface. Alternative splicing of cell adhesion molecules provides additional specificity in forming neuronal connections. For the teneurin family of cell adhesion molecules, alternative splicing of the EGF-repeats and NHL domain controls synaptic protein-protein interactions.

Somatostatin interneurons control the timing of developmental desynchronization in cortical networks.

Synchronous neuronal activity is a hallmark of the developing brain. In the mouse cerebral cortex, activity decorrelates during the second week of postnatal development, progressively acquiring the characteristic sparse pattern underlying the integration of sensory information. The maturation of inhibition seems critical for this process, but the interneurons involved in this crucial transition of network activity in the developing cortex remain unknown.

Male-Dominant Effects of Chd8 Haploinsufficiency on Synaptic Phenotypes during Development in Mouse Prefrontal Cortex.

is a high penetrance, high confidence risk gene for autism spectrum disorder (ASD), a neurodevelopmental disorder that is substantially more prevalent among males than among females. Recent studies have demonstrated variable sex differences in the behaviors and synaptic phenotypes of mice carrying different heterozygous ASD-associated mutations in . We examined functional and structural cellular phenotypes linked to synaptic transmission in deep layer pyramidal neurons of the prefrontal cortex in male and female mice carrying a heterozygous, loss-of-function mutation in the C57BL/6J strain across development from postnatal day 2 to adulthood.

The growth factor EPIREGULIN promotes basal progenitor cell proliferation in the developing neocortex.

Neocortex expansion during evolution is linked to higher numbers of neurons, which are thought to result from increased proliferative capacity and neurogenic potential of basal progenitor cells during development. Here, we show that EREG, encoding the growth factor EPIREGULIN, is expressed in the human developing neocortex and in gorilla cerebral organoids, but not in the mouse neocortex. Addition of EPIREGULIN to the mouse neocortex increases proliferation of basal progenitor cells, whereas EREG ablation in human cortical organoids reduces proliferation in the subventricular zone.

Parvalbumin interneuron deficits in schizophrenia.

Parvalbumin-expressing (PV+) interneurons represent one of the most abundant subclasses of cortical interneurons. Owing to their specific electrophysiological and synaptic properties, PV+ interneurons are essential for gating and pacing the activity of excitatory neurons. In particular, PV+ interneurons are critically involved in generating and maintaining cortical rhythms in the gamma frequency, which are essential for complex cognitive functions.

Beyond a Transmission Cable-New Technologies to Reveal the Richness in Axonal Electrophysiology.

The axon is a neuronal structure capable of processing, encoding, and transmitting information. This assessment contrasts with a limiting, but deeply rooted, perspective where the axon functions solely as a transmission cable of somatodendritic activity, sending signals in the form of stereotypical action potentials. This perspective arose, at least partially, because of the technical difficulties in probing axons: their extreme length-to-diameter ratio and intricate growth paths preclude the study of their dynamics through traditional techniques.

Telencephalic eversion in embryos and early larvae of four teleost species.

The telencephalon of ray-finned fishes undergoes eversion, which is very different to the evagination that occurs in most other vertebrates. Ventricle morphogenesis is key to build an everted telencephalon. Thus, here we use the apical marker zona occludens 1 to understand ventricle morphology, extension of the tela choroidea and the eversion process during early telencephalon development of four teleost species: giant danio (Devario aequipinnatus), blind cavefish (Astyanax mexicanus), medaka (Oryzias latipes), and paradise fish (Macroposus opercularis).