Publications by authors named "Uri Manor"

The maturation and stabilization of appropriate synaptic connections is a vital step in neural circuit development; however, the molecular signals underlying these processes are not fully understood. We show that astrocytes, through production of glypican 5 (GPC5), are required for maturation and refinement of synapses in the mouse cortex during the critical period. In the absence of astrocyte GPC5, thalamocortical synapses show structural immaturity, including smaller presynaptic terminals, decreased postsynaptic density area, and presence of more postsynaptic partners at multisynaptic connections.

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Mitochondria are crucial for cellular metabolism and signalling. Mitochondrial activity is modulated by mitochondrial fission and fusion, which are required to properly balance metabolic functions, transfer material between mitochondria, and remove defective mitochondria. Mitochondrial fission occurs at mitochondria-endoplasmic reticulum (ER) contact sites, and requires the formation of actin filaments that drive mitochondrial constriction and the recruitment of the fission protein DRP1.

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Mitochondria are dynamic organelles essential for cellular homeostasis, undergoing continuous fission and fusion processes that regulate their morphology, distribution, and function. Disruptions in these dynamics are linked to numerous diseases, including neurodegenerative disorders and cancer. Understanding these processes is vital for developing therapeutic strategies aimed at mitigating mitochondrial dysfunction.

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Hearing loss can profoundly impact an individual's quality of life, affecting communication, social interactions, and overall well-being. Many people with hearing impairment report feelings of isolation, frustration, and decreased confidence in social settings, which can lead to withdrawal from activities they once enjoyed. Genetics plays a significant role in congenital hearing loss, accounting for approximately half of all cases.

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Little is known about experiences of physicians when deciding on initiating life support during medical crises of mass casualties and undersupply. We performed a qualitative analysis of interviews with 14 physicians about their decision-making experience when considering initiating mechanical ventilation in patients with severe COVID-19 during the early pandemic. Three themes were revealed: (a) The accumulating clinical experience with invasive ventilation, and the physicians' perception of ventilation as effective or futile in these patients; (b) Preferences of patients and their families regarding mechanical ventilation; and (c) Economic, logistic, and organizational considerations of the undersupplied healthcare system.

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Article Synopsis
  • - Producing accurate 3D models from biological images, especially of complex brain structures, requires extensive human effort to annotate data, which is time-consuming and typically done by experts.
  • - The authors developed a new deep learning method that allows for quick 3D segmentations using minimal 2D annotations, dramatically reducing the time required to create training data.
  • - This innovative approach enables non-experts to generate necessary annotations efficiently, making it easier to study brain circuits and their connections across larger datasets.
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The Israeli health system is experiencing an ongoing manpower crisis that will deepen soon with the increase in the number of patients and the overcrowding in clinics and hospitals. The core of the crisis is the need to staff the hospitalization departments and clinics with quality manpower. Alongside the initial staffing, there is an obligation to ensure the survivability of the professional personnel in the system over the years, and this must be done while constantly preventing the process of professional burnout.

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Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered 55 RNA-binding proteins (RBPs) that influence CHMP7 localization, including SmD1, a survival of motor neuron (SMN) complex component.

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Article Synopsis
  • * The researchers found that dark microglia interact with blood vessels and synapses and engage in trogocytosis, meaning they take pieces of pre-synaptic axon terminals.
  • * They discovered that dark microglia express specific proteins like CLEC7a, LPL, and TREM2, and that TREM2 is crucial for their function, indicating their important role in synaptic pruning and brain development.
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Proper regulation of organelle dynamics and inter-organelle contacts is critical for cellular health and function. Both the endoplasmic reticulum (ER) and actin cytoskeleton are known to regulate organelle dynamics, but how, when, and where these two subcellular components are coordinated to control organelle dynamics remains unclear. Here, we show that ER-associated actin consistently marks mitochondrial, endosomal, and lysosomal fission sites.

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Proper regulation of organelle dynamics is critical for cellular function, but the mechanisms coordinating multiple organelles remain poorly understood. Here we show that actin polymerization mediated by the endoplasmic reticulum (ER)-anchored formin INF2 acts as a master regulator of organelle morphology and movement. Using high-resolution imaging, we demonstrate that INF2-polymerized actin filaments assemble at ER contact sites on mitochondria, endosomes, and lysosomes just prior to their fission.

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In this paper, we introduce a new, open-source software developed in Python for analyzing Auditory Brainstem Response (ABR) waveforms. ABRs are a far-field recording of synchronous neural activity generated by the auditory fibers in the ear in response to sound, and used to study acoustic neural information traveling along the ascending auditory pathway. Common ABR data analysis practices are subject to human interpretation and are labor-intensive, requiring manual annotations and visual estimation of hearing thresholds.

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Article Synopsis
  • Cochlear hair cell stereocilia bundles are essential for hearing, and mutations causing deafness can alter their structure, leading to challenges in quantifying these changes using traditional methods.
  • Current techniques, like using phalloidin for labeling, result in non-specific tissue labeling, making it hard to segment stereocilia from other structures, often requiring significant manual effort and time.
  • VASCilia is a new Napari plugin that automates the process of 3D instance segmentation for cochlear stereocilia analysis, offering user-friendly controls and advanced deep learning features to streamline measurements and enhance research efficiency.
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PSSR2 improves and expands on the previously established PSSR (Point-Scanning Super-Resolution) workflow for simultaneous super-resolution and denoising of undersampled microscopy data. PSSR2 is designed to put state-of-the-art technology into the hands of the general microscopy and biology research community, enabling user-friendly implementation of PSSR workflows with little to no programming experience required, especially through its integrated CLI and Napari plugin.

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Article Synopsis
  • Producing dense 3D reconstructions from biological imaging is tough and usually needs a lot of precise training data for deep learning models.
  • The brain's neuropil, with its complex structure of various cellular processes, is particularly challenging to annotate with traditional methods.
  • We created a new deep learning approach that allows for quick 3D segmentations from minimal 2D annotations, reducing human annotation time significantly and enabling non-experts to contribute effectively.
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Background: Age and sex can be estimated using artificial intelligence on the basis of various sources. The aims of this study were to test whether convolutional neural networks could be trained to estimate age and predict sex using standard transthoracic echocardiography and to evaluate the prognostic implications.

Methods: The algorithm was trained on 76,342 patients, validated in 22,825 patients, and tested in 20,960 patients.

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Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment.

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Article Synopsis
  • Researchers are investigating the link between sensory deficiencies, particularly hearing loss, and the development of Alzheimer's disease (AD), which remains poorly understood.
  • In a study with two AD mouse models, early-onset hearing loss was found to occur at a young age, before any cognitive changes, indicating that hearing impairment may be an early sign of AD.
  • The study suggests that DNA damage in the cochlea could be a contributing factor to this hearing dysfunction in AD, as evidenced by specific markers indicating mitochondrial impairment and reduced synaptic function in auditory cells.
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Age-related hearing loss (ARHL) is a common sensory impairment with complex underlying mechanisms. In our previous study, we performed a meta-analysis of genome-wide association studies (GWAS) in mice and identified a novel locus on chromosome 18 associated with ARHL specifically linked to a 32 kHz tone burst stimulus. Consequently, we investigated the role of Formin Homology 2 Domain Containing 3 (Fhod3), a newly discovered candidate gene for ARHL based on the GWAS results.

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Astrocytes, the most abundant glial cell type in the brain, are underrepresented in traditional cortical organoid models due to the delayed onset of cortical gliogenesis. Here we introduce a new glia-enriched cortical organoid model that exhibits accelerated astrogliogenesis. We demonstrated that induction of a gliogenic switch in a subset of progenitors enabled the rapid derivation of astroglial cells, which account for 25-31% of the cell population within 8-10 weeks of differentiation.

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  • Mitochondrial DNA (mtDNA) plays a crucial role in energy production and acts as a damage-associated molecular pattern (DAMP), which triggers immune responses and contributes to inflammation during various diseases.
  • When cells experience mtDNA stress, such as during herpes simplex virus-1 infection, changes occur in mitochondrial structure and function, leading to the release of mtDNA into the cytoplasm and activation of the cGAS-STING immune pathway.
  • The study suggests that mtDNA undergoing replication stress is selectively removed through a quality control mechanism involving endosomes, and this process could be a potential target for therapies aimed at reducing mtDNA-related inflammation during infections.
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The development of high-resolution microscopes has made it possible to investigate cellular processes in 3D and over time. However, observing fast cellular dynamics remains challenging because of photobleaching and phototoxicity. Here we report the implementation of two content-aware frame interpolation (CAFI) deep learning networks, Zooming SlowMo and Depth-Aware Video Frame Interpolation, that are highly suited for accurately predicting images in between image pairs, therefore improving the temporal resolution of image series post-acquisition.

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Myelin is essential for rapid nerve signaling and is increasingly found to play important roles in learning and in diverse diseases of the CNS. Morphological parameters of myelin such as sheath length are thought to precisely tune conduction velocity, but the mechanisms controlling sheath morphology are poorly understood. Local calcium signaling has been observed in nascent myelin sheaths and can be modulated by neuronal activity.

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Age-related hearing loss (ARHL) is the most common cause of hearing loss and one of the most prevalent conditions affecting the elderly worldwide. Despite evidence from our lab and others about its polygenic nature, little is known about the specific genes, cell types, and pathways involved in ARHL, impeding the development of therapeutic interventions. In this manuscript, we describe, for the first time, the complete cell-type specific transcriptome of the aging mouse cochlea using snRNA-seq in an outbred mouse model in relation to auditory threshold variation.

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Biallelic mutations in the gene that encodes the enzyme N-glycanase 1 (NGLY1) cause a rare disease with multi-symptomatic features including developmental delay, intellectual disability, neuropathy, and seizures. NGLY1's activity in human neural cells is currently not well understood. To understand how NGLY1 gene loss leads to the specific phenotypes of NGLY1 deficiency, we employed direct conversion of NGLY1 patient-derived induced pluripotent stem cells (iPSCs) to functional cortical neurons.

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