Afferent Neurons of the Zebrafish Lateral Line Are Strict Selectors of Hair-Cell Orientation

Hair cells in the inner ear display a characteristic polarization of their apical stereocilia across the plane of the sensory epithelium. This planar orientation allows coherent transduction of mechanical stimuli because the axis of morphological polarity of the stereocilia corresponds to the direction of excitability of the hair cells. Neuromasts of the lateral line in fishes and amphibians form two intermingled populations of hair cells oriented at 180° relative to each other, however, creating a stimulus-polarity ambiguity. Therefore, it is unknown how these animals resolve the vectorial component of a mechanical stimulus. Using genetic mosaics and live imaging in transgenic zebrafish to visualize hair cells and neurons at single-cell resolution, we show that lateral-line afferents can recognize the planar polarization of hair cells. Each neuron forms synapses with hair cells of identical orientation to divide the neuromast into functional planar-polarity compartments. We also show that afferent neurons are strict selectors of polarity that can re-establish synapses with identically oriented targets during hair-cell regeneration. Our results provide the anatomical bases for the physiological models of signal-polarity resolution by the lateral line

Aprendizaje flexible y personalizado para atender la diversidad en el aula, mediante la gamificación, a través del uso integrado de un sistema virtual de respuesta en el aula para dispositivos móviles con acceso a internet y una aplicación de screencasting

Sección Deptal. de Farmacología y Toxicología (Veterinaria)Fac. de VeterinariaFALSEsubmitte

ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization

BackgroundWhole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts.MethodsWe developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient's standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA).ResultsClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes.ConclusionsClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Neural map organization and development in the lateral-line system

Les neurones sensorials projecten al sistema nerviós central seguint una distribució espacial ordenada, formant mapes neuronals que representen propietats dels estímuls sensorials i que són considerats essencials per a la interpretació del món extern. He utilitzat la línia lateral de la larva del peix zebra com a model per a l’estudi de l’organització i el desenvolupament dels mapes neuronals sensorials. Les neurones sensorials de la línia lateral formen un mapa neuronal topogràfic, anomenat somatotopia, que representa la posició de l’estímul sensorial. He demostrat que l’ordre de neurogènesi defineix la somatotopia. A més, he identificat dues subclasses de neurones sensorials de la línia lateral que presenten diferències en els seus patrons de projecció central i en els contactes amb una neurona central: la cèl·lula de Mauthner. Proposo que aquest dimorfisme és important per a donar lloc a reaccions comportamentals adients al context sensorial. També he demostrat una contribució per part de l’ordre de neurogènesi a la formació del mapa neuronal dimòrfic de la línia lateral. Finalment, he obtingut resultats que mostren que la diversitat neuronal i la topologia del mapa observades ocorren amb normalitat en l’absència d’activitat sensorial. Pag

Shape analysis of subcortical structures in obsessive-compulsive disorder and the relationship with comorbid anxiety, depression, and medication use: a meta-analysis by the OCD Brain Imaging Consortium

Objective: neuroimaging studies of obsessive-compulsive disorder (OCD) patients have highlighted the important role of deep gray matter structures. Less work has however focused on subcortical shape in OCD patients. Methods: here we pooled brain MRI scans from 412 OCD patients and 368 controls to perform a meta-analysis utilizing the ENIGMA-Shape protocol. In addition, we investigated modulating effects of medication status, comorbid anxiety or depression, and disease duration on subcortical shape. Results: there was no significant difference in shape thickness or surface area between OCD patients and healthy controls. For the subgroup analyses, OCD patients with comorbid depression or anxiety had lower thickness of the hippocampus and caudate nucleus and higher thickness of the putamen and pallidum compared to controls. OCD patients with comorbid depression had lower shape surface area in the thalamus, caudate nucleus, putamen, hippocampus, and nucleus accumbens and higher shape surface area in the pallidum. OCD patients with comorbid anxiety had lower shape surface area in the putamen and the left caudate nucleus and higher shape surface area in the pallidum and the right caudate nucleus. Further, OCD patients on medication had lower shape thickness of the putamen, thalamus, and hippocampus and higher thickness of the pallidum and caudate nucleus, as well as lower shape surface area in the hippocampus and amygdala and higher surface area in the putamen, pallidum, and caudate nucleus compared to controls. There were no significant differences between OCD patients without co-morbid anxiety and/or depression and healthy controls on shape measures. In addition, there were also no significant differences between OCD patients not using medication and healthy controls. Conclusions: the findings here are partly consistent with prior work on brain volumes in OCD, insofar as they emphasize that alterations in subcortical brain morphology are associated with comorbidity and medication status. Further work is needed to understand the biological processes contributing to subcortical shape

Brain activity during traditional textbook and audiovisual-3D learning

INTRODUCTION: Audiovisual educational tools have increasingly been used during the past years to complement and compete with traditional textbooks. However, little is known as to how the brain processes didactic information presented in different formats. We directly assessed brain activity during learning using both traditional textbook and audiovisual-3D material. METHODS: A homogeneous sample of 30 young adults with active study habits was assessed. Educational material on the subject of Cardiology was adapted to be presented during the acquisition of functional MRI. RESULTS: When tested after image acquisition, participants obtained similar examination scores for both formats. Evoked brain activity was robust during both traditional textbook and audiovisual-3D lessons, but a greater number of brain systems were implicated in the processing of audiovisual-3D information, consistent with its multisource sensory nature. However, learning was not associated with group mean brain activations, but was instead predicted by distinct functional MRI signal changes in the frontal lobes and showed distinct cognitive correlates. In the audiovisual-3D version, examination scores were positively correlated with late-evoked prefrontal cortex activity and working memory, and negatively correlated with language-related frontal areas and verbal memory. As for the traditional textbook version, the fewer results obtained suggested the opposite pattern, with examination scores negatively correlating with prefrontal cortex activity evoked during the lesson. CONCLUSIONS: Overall, the results indicate that a similar level of knowledge may be achieved via different cognitive strategies. In our experiment, audiovisual learning appeared to benefit from prefrontal executive resources (as opposed to memorizing verbal information) more than traditional textbook learning

The Effects of Air Pollution on the Brain: a Review of Studies Interfacing Environmental Epidemiology and Neuroimaging

PURPOSE OF REVIEW: An emerging body of evidence has raised concern regarding the potentially harmful effects of inhaled pollutants on the central nervous system during the last decade. In the general population, traffic-related air pollution (TRAP) exposure has been associated with adverse effects on cognitive, behavior, and psychomotor development in children, and with cognitive decline and higher risk of dementia in the elderly. Recently, studies have interfaced environmental epidemiology with magnetic resonance imaging to investigate in vivo the effects of TRAP on the human brain. The aim of this systematic review was to describe and synthesize the findings from these studies. The bibliographic search was carried out in PubMed with ad hoc keywords. RECENT FINDINGS: The selected studies revealed that cerebral white matter, cortical gray matter, and basal ganglia might be the targets of TRAP. The detected brain damages could be involved in cognition changes. The effect of TRAP on cognition appears to be biologically plausible. Interfacing environmental epidemiology and neuroimaging is an emerging field with room for improvement. Future studies, together with inputs from experimental findings, should provide more relevant and detailed knowledge about the nature of the relationship between TRAP exposure and cognitive, behavior, and psychomotor disorders observed in the general population.Marion Mortamais is supported by a Marie Skłodowska-Curie Individual Fellowship (H2020-MSCA-IF-2014; EU project 656294)

Nosocomial Bacteremia Due to an As Yet Unclassified Acinetobacter Genomic Species 17-Like Strain

We describe a case of bacteremia due to an as yet unclassified Acinetobacter genomic species 17-like strain. The recognition of this microorganism as non-Acinetobacter baumannii may have important epidemiological implications, as it relieves the hospital of the implementation of barrier precautions for patients infected or colonized as may be necessary with a multiresistant A. baumannii epidemic