ICAM-1 nanoclusters regulate hepatic epithelial cell polarity by leukocyte adhesion-independent control of apical actomyosin

Epithelial intercellular adhesion molecule (ICAM)-1 is apically polarized, interacts with, and guides leukocytes across epithelial barriers. Polarized hepatic epithelia organize their apical membrane domain into bile canaliculi and ducts, which are not accessible to circulating immune cells but that nevertheless confine most of ICAM-1. Here, by analyzing ICAM-1_KO human hepatic cells, liver organoids from ICAM-1_KO mice and rescue-of-function experiments, we show that ICAM-1 regulates epithelial apicobasal polarity in a leukocyte adhesion-independent manner. ICAM-1 signals to an actomyosin network at the base of canalicular microvilli, thereby controlling the dynamics and size of bile canalicular-like structures. We identified the scaffolding protein EBP50/NHERF1/SLC9A3R1, which connects membrane proteins with the underlying actin cytoskeleton, in the proximity interactome of ICAM-1. EBP50 and ICAM-1 form nano-scale domains that overlap in microvilli, from which ICAM-1 regulates EBP50 nano-organization. Indeed, EBP50 expression is required for ICAM-1-mediated control of BC morphogenesis and actomyosin. Our findings indicate that ICAM-1 regulates the dynamics of epithelial apical membrane domains beyond its role as a heterotypic cell–cell adhesion molecule and reveal potential therapeutic strategies for preserving epithelial architecture during inflammatory stress

Estudio controlado del ritmo del habla en la enfermedad de Parkinson

Resumen: Introducción: Las alteraciones en el habla aparecen en la mayoría de los pacientes con la enfermedad de Parkinson (EP) en el curso del trastorno. Su origen y gravedad son de interés clínico y diagnóstico. Objetivo: Evaluar los patrones de deterioro en el habla en pacientes con la EP, e identificar diferencias en la velocidad de elocución y articulación en comparación con sujetos de control, empleando un método de análisis automático en una tarea de lectura. Pacientes: Participaron 39 pacientes con la EP y 45 controles asintomáticos igualados en sexo y edad. Los pacientes con la EP, en estado on, no presentaban fluctuaciones motoras ni discinesias durante la evaluación del habla. Resultados: El grupo de pacientes con la EP muestran una significativa reducción de la velocidad de elocución y articulación. No se encontraron correlaciones significativas entre los parámetros del habla estudiados y las características de los pacientes, tales como la dosis de L-dopa, duración del trastorno, edad, ni en las puntuaciones en las escalas UPDRS III o Hoehn y Yahr. Conclusiones: Los pacientes con la EP muestran un patrón característico de deterioro del ritmo del habla. Estos resultados indican que las disfluencias en la EP son el resultado de la alteración del movimiento que afecta a la fisiología de los sistemas de producción del habla. Abstract: Introduction: Speech disturbances will affect most patients with Parkinson's disease (PD) over the course of the disease. The origin and severity of these symptoms are of clinical and diagnostic interest. Purpose: To evaluate the clinical pattern of speech impairment in PD patients and identify significant differences in speech rate and articulation compared to control subjects. Speech rate and articulation in a reading task were measured using an automatic analytical method. Patients: A total of 39 PD patients in the ‘on’ state and 45 age-and sex-matched asymptomatic controls participated in the study. None of the patients experienced dyskinesias or motor fluctuations during the test. Results: The patients with PD displayed a significant reduction in speech and articulation rates; there were no significant correlations between the studied speech parameters and patient characteristics such as L-dopa dose, duration of the disorder, age, and UPDRS III scores and Hoehn & Yahr scales. Conclusion: Patients with PD show a characteristic pattern of declining speech rate. These results suggest that in PD, disfluencies are the result of the movement disorder affecting the physiology of speech production systems. Palabras clave: Enfermedad de Parkinson, Habla, Voz, Velocidad de elocución, Velocidad articulatoria, L-dopa, Keywords: Parkinson's disease, Speech, Voice, Speech rate, Articulation rate, L-dop

Evidence of conditioned behavior in amoebae

Associative memory is the main type of learning by which complex organisms endowed with evolved nervous systems respond efficiently to certain environmental stimuli. It has been found in different multicellular species, from cephalopods to humans, but never in individual cells. Here we describe a motility pattern consistent with associative conditioned behavior in the microorganism Amoeba proteus. We use a controlled direct-current electric field as the conditioned stimulus, and a specific chemotactic peptide as the unconditioned stimulus. The amoebae are capable of linking two independent past events, generating persistent locomotion movements that can prevail for 44 min on average. We confirm a similar behavior in a related species, Metamoeba leningradensis. Thus, our results indicate that unicellular organisms can modify their behavior during migration by associative conditioning.We would like to thank Dr. Andrew Goodkov from the Institute of Cytology (Russian Academy of Science) St. Petersburg, Russia, for valuable advices related to Amoeba organisms, Laura Pérez Gómez and Luis Rojo García for their assistance designing Fig. 1 and the AutoCAD 3D model, A-M Pérez Biedermann for her valuable contribution in our study, José González Romero and José Miguel Pérez Pérez from the Institute of Parasitology and Biomedicine “Lopez-Neyra” for their technical assistance. In addition, we thank María Calleja-Felipe for her valuable help in the peptide gradient experiments. This work was supported by a grant of the University of Basque Country (UPV/EHU), GIU17/066, the Basque Government grant IT974-16, and by the UPV/EHU and Basque Center of Applied Mathematics, grant US18/21”

Patients awaiting surgery for neurosurgical diseases during the first wave of the COVID-19 pandemic in Spain: a multicentre cohort study.

The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery. This was an observational retrospective study. A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020. A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease. The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection. More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p Patients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures