Neurite-Enriched MicroRNA-218 Stimulates Translation of the GluA2 Subunit and Increases Excitatory Synaptic Strength

Local control of protein translation is a fundamental process for the regulation of synaptic plasticity. It has been demonstrated that the local protein synthesis occurring in axons and dendrites can be shaped by numerous mechanisms, including miRNA-mediated regulation. However, several aspects underlying this regulatory process have not been elucidated yet. Here, we analyze the differential miRNA profile in cell bodies and neurites of primary hippocampal neurons and find an enrichment of the precursor and mature forms of miR-218 in the neuritic projections. We show that miR-218 abundance is regulated during hippocampal development and by chronic silencing or activation of neuronal network. Overexpression and knockdown of miR-218 demonstrated that miR-218 targets the mRNA encoding the GluA2 subunit of AMPA receptors and modulates its expression. At the functional level, miR-218 overexpression increases glutamatergic synaptic transmission at both single neuron and network levels. Our data demonstrate that miR-218 may play a key role in the regulation of AMPA-mediated excitatory transmission and in the homeostatic regulation of synaptic plasticity

Evaluation of Two-Month Antibody Levels after Heterologous ChAdOx1-S/BNT162b2 Vaccination Compared to Homologous ChAdOx1-S or BNT162b2 Vaccination

none11noWe evaluated the post-vaccination humoral response of three real-world cohorts. Vaccinated subjects primed with ChAdOx1-S and boosted with BNT162b2 mRNA vaccine were compared to homologous dosing (BNT162b2/BNT162b2 and ChAdOx1-S/ChAdOx1-S). Serum samples were collected two months after vaccination from a total of 1248 subjects. The results showed that the heterologous vaccine schedule induced a significantly higher humoral response followed by homologous BNT162b2/BNT162b2 and ChAdOx1-S/ChAdOx1-S vaccines (p < 0.0001). Moreover, analyzing factors (i.e., vaccine schedule, sex, age, BMI, smoking, diabetes, cardiovascular diseases, respiratory tract diseases, COVID-19 diagnosis, vaccine side effects) influencing the IgG anti-S response, we found that only the type of vaccine affected the antibody titer (p < 0.0001). Only mild vaccine reactions resolved within few days (40% of subjects) and no severe side effects for either homologous groups or the heterologous group were reported. Our data support the use of heterologous vaccination as an effective and safe alternative to increase humoral immunity against COVID-19.openBarocci, Simone; Orlandi, Chiara; Diotallevi, Aurora; Buffi, Gloria; Ceccarelli, Marcello; Vandini, Daniela; Carlotti, Eugenio; Galluzzi, Luca; Rocchi, Marco Bruno Luigi; Magnani, Mauro; Casabianca, AnnaBarocci, Simone; Orlandi, Chiara; Diotallevi, Aurora; Buffi, Gloria; Ceccarelli, Marcello; Vandini, Daniela; Carlotti, Eugenio; Galluzzi, Luca; Rocchi, Marco Bruno Luigi; Magnani, Mauro; Casabianca, Ann

Dilated-Hypokinetic Evolution of Hypertrophic Cardiomyopathy Prevalence, Incidence, Risk Factors, and Prognostic Implications in Pediatric and Adult Patients

ObjectivesThis study sought to investigate the incidence, risk factors, and prognosis of dilated-hypokinetic evolution in a large cohort of patients with hypertrophic cardiomyopathy (HCM) followed up at a cardiology center serving both the pediatric and the adult population.BackgroundThe available data on this evolution of HCM mainly regards prevalence (rather than incidence) in adults, with very little being known about the pediatric population.MethodsA total of 222 consecutive HCM patients (65% men, 19% ≤18 years old) were prospectively evaluated for a mean follow-up of 11 ± 9 years.ResultsA diagnosis of dilated-hypokinetic HCM was made in 12 patients at first evaluation (11 without previous septal myectomy surgery; prevalence, 4.9%). Twelve of the 210 patients with classic HCM at first evaluation underwent dilated-hypokinetic evolution (incidence, 5.3/1,000 patient-years). Patients with prevalent/incident dilated-hypokinetic evolution were younger at first evaluation (32 ± 14 years vs. 41 ± 21 years, p = 0.04) and more often had a family history of HCM (61% vs. 26%, p = 0.002) or sudden death (43% vs. 19%, p = 0.01) with respect to patients who maintained classic HCM. Moreover, they showed greater interventricular septum (23 ± 3 mm vs. 19 ± 6 mm, p = 0.004) and posterior wall (15 ± 3 mm vs. 13 ± 4 mm, p = 0.006) thickness. Cardiovascular death-free survival was lower among patients with dilated-hypokinetic HCM (p < 0.04). Cox proportional hazards regression analysis identified left ventricular wall thickness (hazard ratio [HR] = 1.07; 95% confidence interval [CI], 1.01 to 1.14; p = 0.03) and end-diastolic diameter (HR = 1.08; 95% CI 1.04 to 1.11; p = 0.0001) as independent predictors of cardiovascular death.ConclusionsDilated-hypokinetic evolution is rare but not exceptional in HCM. Young age at diagnosis, family history of HCM, and greater wall thickness are incremental risk factors for dilated-hypokinetic HCM, which carries an ominous prognosis

Bright light exposure reduces TH-positive dopamine neurons: Implications of light pollution in Parkinson\u27s disease epidemiology

This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra. Twenty-one days after birth, Sprague–Dawley albino rats were divided into groups and raised under different conditions of light exposure. At the end of the irradiation period, rats were sacrificed and assayed for neuromelanin formation and number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. The rats exposed to bright light for 20 days or 90 days showed a relatively greater number of neuromelanin-positive neurons. Surprisingly, TH-positive neurons decreased progressively in the substantia nigra reaching a significant 29% reduction after 90 days of continuous bright light exposure. This decrease was paralleled by a diminution of dopamine and its metabolite in the striatum. Remarkably, in preliminary analysis that accounted for population density, the age and race adjusted Parkinson's disease prevalence significantly correlated with average satellite-observed sky light pollution

Bright light exposure reduces TH-positive dopamine neurons: implications of light pollution in Parkinson's disease epidemiology.

This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra. Twenty-one days after birth, Sprague-Dawley albino rats were divided into groups and raised under different conditions of light exposure. At the end of the irradiation period, rats were sacrificed and assayed for neuromelanin formation and number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. The rats exposed to bright light for 20 days or 90 days showed a relatively greater number of neuromelanin-positive neurons. Surprisingly, TH-positive neurons decreased progressively in the substantia nigra reaching a significant 29% reduction after 90 days of continuous bright light exposure. This decrease was paralleled by a diminution of dopamine and its metabolite in the striatum. Remarkably, in preliminary analysis that accounted for population density, the age and race adjusted Parkinson's disease prevalence significantly correlated with average satellite-observed sky light pollution

Eyes as Gateways for Environmental Light to the Substantia Nigra: Relevance in Parkinson’s Disease

Recent data indicates that prolonged bright light exposure of rats induces production of neuromelanin and reduction of tyrosine hydroxylase positive neurons in the substantia nigra. This effect was the result of direct light reaching the substantia nigra and not due to alteration of circadian rhythms. Here, we measured the spectrum of light reaching the substantia nigra in rats and analysed the pathway that light may take to reach this deep brain structure in humans. Wavelength range and light intensity, emitted from a fluorescent tube, were measured, using a stereotaxically implanted optical fibre in the rat mesencephalon. The hypothetical path of environmental light from the eye to the substantia nigra in humans was investigated by computed tomography and magnetic resonance imaging. Light with wavelengths greater than 600 nm reached the rat substantia nigra, with a peak at 709 nm. Eyes appear to be the gateway for light to the mesencephalon since covering the eyes with aluminum foil reduced light intensity by half. Using computed tomography and magnetic resonance imaging of a human head, we identified the eye and the superior orbital fissure as possible gateways for environmental light to reach the mesencephalon

Do neuroticism and efficacy beliefs moderate the relationship between climate change worry and mental wellbeing?

BackgroundResearch on the nature and prevalence of phenomena like climate anxiety (or eco-anxiety) is increasing rapidly but there is little understanding of the conditions under which climate change worry becomes more or less likely to significantly impact mental wellbeing. Here, we considered two plausible moderators of the relationship between climate change worry and mental wellbeing: neuroticism and efficacy beliefs.MethodsAnalysis was conducted with survey data gathered in six European countries in autumn 2019. Participants were recruited from universities in the participating countries using opportunity sampling.ResultsWe found that climate change worry is negatively related to mental wellbeing at any level of perceived efficacy. In contrast, climate change worry is only significantly related to mental wellbeing at low and average levels of neuroticism. High neuroticism appears to have a masking, rather than amplifying, role in the relationship between climate change worry and mental wellbeing.LimitationsThe cross-sectional design of the study precludes verification of causal relationships among variables. The brief measure of neuroticism employed also did not allow for nuanced analysis of how different facets of neuroticism contribute to the observed interaction with climate change worry. Findings cannot be indiscriminately generalised to less privileged groups facing the worst impacts of the climate crisis.ConclusionOur findings lend to a view that harmful impacts of climate change worry on mental wellbeing cannot simply be ascribed to dispositional traits like neuroticism. We advocate for interventions that tackle negative climate-related emotions as unique psychological stressors

Detección y caracterización preliminar de Escherichia coli O174 productor de toxina

El síndrome urémico hemolítico (SUH), una en­fermedad transmitida por alimentos, es la principal causa de insuficiencia renal aguda y la segunda causa de insuficiencia renal crónica y de trasplante renal en niños en la Argentina, con 400 a 500 notificaciones anuales de casos. Este síndrome origina los costos más elevados para el Sistema Nacional de Salud. Se considera que Escherichia coli productora de toxina Shiga (STEC) es el agente etiológico más frecuente del SUH. Dentro de este patotipo STEC asociado a SUH, se destaca el serotipo STEC O157:H7 que representa el 60 % de dichos aislamientos. Otros serogrupos STEC no-O157 representan el 40 % de los aislamientos de STEC provenientes de SUH. La preva­lencia de cada serotipo depende de cada país. Se informó que los cuatro serogrupos preva­lentes en la Argentina dentro de los no-O157 son O145, O121, O26 y O174. De ellos, el serogrupo O174 se destaca como proble­mática local y no está cubierto por protocolos de diag­nóstico europeos ni americanos. Las infecciones por STEC en la Argentina, por su naturaleza endémica, su alta incidencia y la presentación de brotes difusos, di­fieren de las de otras regiones referenciales en materia normativa. Para asegurar la calidad e inocuidad agroalimentaria, podría ser incluido el diagnóstico de O174 en alimentos. El objetivo de este proyecto es evaluar técnicas diagnósticas específicas de este serogrupo.Hemolytic uremic syndrome (HUS), a foodborne disease, is the main cause of acute renal failure and the second cause of chronic renal failure and kidney transplant in children in Argentina, with 400-500 cases each year. This syndrome provokes the highest costs to the National Health System. Shiga toxinproducing Escherichia coli (STEC) is considered the most frequent etiological agent of HUS. Among STEC serotypes associated with HUS, O157:H7 represents 60% of the isolates. Other non-O157 STEC serogroups account for the remaining 40%. The prevalence of each serotype varies from one country to other. It was reported that the four prevalent non-O157 serogroups in Argentina are O145, O121, O26 and O174. Among these, serogroup O174 stands out as a local problem and is not included in european or american diagnostic protocols. STEC infections in Argentina, due to their endemic nature, high incidence and occurrence of diffuse outbreaks differ from those taking place in countries whose regulatory standards serve for reference purposes. In order to ensure food quality and safety, diagnosis of O174 in food should be included. The aim of this study is to assess specific diagnostic techniques for this serogroup

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects