•Nedd4 expression is abundant in the hippocampus.•Nedd4 heterozygous mice show significant decrease in long-term spatial learning and memory.•A significant decrease in long-term potentiation (LTP) ...was observed in the Nedd4 heterozygous mice.
The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4+/− mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4+/+ and Nedd4+/− mice in terms of short-term spatial memory in a Y-maze test. Nedd4+/− mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes.
Existing research concerning the development of generativity, the capacity to provide care and guidance to future generations, has primarily focused on the role of sociodemographic variables. ...However, one important feature that might be of importance for the study of generativity is insecure romantic attachment, given its influence on how people establish relationships with others. Still, the role of the two dimensions of insecure romantic attachment (i.e., anxiety and avoidance) on the most studied aspects of generativity (i.e., generative concern and generative acts) remains largely underexplored. Therefore, the present study investigates what contributes to generativity by exploring the role of sociodemographic features (i.e., age, gender, having children, years of education) and above all the two dimensions of insecure romantic attachment on generative concern and acts. A sample of 427 adults (age range: 25–65 years old) completed an online survey including romantic attachment and generativity measures. Afterwards, correlational and regression analyses were conducted to explore the data. Results showed that years of education positively predicted generative concern, whereas both anxiety and avoidance negatively predicted it. Yet, no sociodemographic feature nor dimension of insecure romantic attachment predicted generative acts. Thus, insecure romantic attachment could be a useful key to understanding generative concern.
Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is associated with disorders affecting the peripheral and the central nervous system. A high number of patients develop ...post-COVID-19 syndrome with the persistence of a large spectrum of symptoms, including neurological, beyond 4 weeks after infection. Several potential mechanisms in the acute phase have been hypothesized, including damage of the blood-brain-barrier (BBB). We tested weather markers of BBB damage in association with markers of brain injury and systemic inflammation may help in identifying a blood signature for disease severity and neurological complications.
Blood biomarkers of BBB disruption (MMP-9, GFAP), neuronal damage (NFL) and systemic inflammation (PPIA, IL-10, TNFα) were measured in two COVID-19 patient cohorts with high disease severity (ICUCovid; n=79) and with neurological complications (NeuroCovid; n=78), and in two control groups free from COVID-19 history, healthy subjects (n=20) and patients with amyotrophic lateral sclerosis (ALS; n=51). Samples from COVID-19 patients were collected during the first and the second wave of COVID-19 pandemic in Lombardy, Italy. Evaluations were done at acute and chronic phases of the COVID-19 infection.
Blood biomarkers of BBB disruption and neuronal damage are high in COVID-19 patients with levels similar to or higher than ALS. NeuroCovid patients display lower levels of the cytokine storm inducer PPIA but higher levels of MMP-9 than ICUCovid patients. There was evidence of different temporal dynamics in ICUCovid compared to NeuroCovid patients with PPIA and IL-10 showing the highest levels in ICUCovid patients at acute phase. On the contrary, MMP-9 was higher at acute phase in NeuroCovid patients, with a severity dependency in the long-term. We also found a clear severity dependency of NFL and GFAP levels, with deceased patients showing the highest levels.
The overall picture points to an increased risk for neurological complications in association with high levels of biomarkers of BBB disruption. Our observations may provide hints for therapeutic approaches mitigating BBB disruption to reduce the neurological damage in the acute phase and potential dysfunction in the long-term.
High circulating levels of proprotein convertase subtilisin/kexin 9 (PCSK9) were shown to be predictive of cardiovascular events in patients with atrial fibrillation and in those with acute coronary ...syndrome (1,2). Because high PCSK9 plasma levels were significantly correlated with 11-dehydro-thromboxane B2 (11-dh-TxB2) (1) and with platelet reactivity (2), it is conceivable to hypothesize a direct effect of PCSK9 on platelet activation. Contribution of PCSK9 to arterial thrombosis was evaluated in a FeCl3-induced carotid artery injury model in adult PCSK9+/+ and PCSK9−/− mice (n = 7/group). hrPCSK9 added to platelet-rich plasma samples significantly enhanced platelet aggregation induced by subthreshold concentration of epinephrine (0.3 and 0.6 μM), reducing the lag time (∼40%) (Figure 1A) and increasing the area under the curve (∼15%). By contrast, 57% of PCSK9+/+ mice displayed a total occlusion with stable thrombi within 15.8 ± 7.4 min after application of FeCl3 (Figure 1B). ...platelet activation, assessed by flow cytometry in terms of activated GP IIb/IIIa and P-selectin expression and of platelet–leukocyte aggregates, was reduced by approximately 60% in the mutant mice compared to the rate in PCSK9+/+ mice in response to injury (data not shown).
The Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America clinical practice guideline is intended to guide clinicians ...caring for solid-organ transplant (SOT) donors, candidates and recipients regarding infectious diseases (ID) issues related to this geographical region, mostly located in the tropics. These recommendations are based on both systematic reviews of relevant literature and expert opinion from both transplant ID and travel medicine specialists. The guidelines provide recommendations for risk evaluation and laboratory investigation, as well as management and prevention of infection of the most relevant endemic diseases of Latin America. This summary includes a brief description of the guideline recommendations but does not include the complete rationale and references for each recommendation, which is available in the online version of the article, published in this journal as a supplement. The supplement contains 10 reviews referring to endemic or travel diseases (eg, tuberculosis, Chagas disease ChD, leishmaniasis, malaria, strongyloidiasis and schistosomiasis, travelers diarrhea, arboviruses, endemic fungal infections, viral hepatitis, and vaccines) and an illustrative section with maps (http://www.pmourao.com/map/). Contributors included experts from 13 countries (Brazil, Canada, Chile, Denmark, France, Italy, Peru, Spain, Switzerland, Turkey, United Kingdom, United States, and Uruguay) representing four continents (Asia, the Americas and Europe), along with scientific and medical societies.
Collaborative learning is a teaching method that brings together students to discuss a topic important for a given course or curriculum and solve a related problem or create a product. By doing this, ...learners create knowledge together and gain 21st –century skills such as communication, critical thinking, decision making, leadership and conflict management. Universities had to close their campuses and turn their education fully online in 2020 due to the COVID-19 pandemic, which created a forced step in the evolution of the digitalisation of collaborative teaching. How did TU Delft face this challenge? How did the students experience the online version of collaborative learning? How did distant learning affect their motivation? This article presents four student team projects investigating these questions from the collaborative learning perspective. One of the significant findings of these projects is the lack of socio-emotional interactions during online collaborative work. We present a few guidelines on how to enable these interactions when designing online or blended collaborative education.
Online and blended education, COVID-19 outbreak, Higher education, Collaborative learning, Student experience, Collaboration.
Transcription factors ensure skin homeostasis via tight regulation of distinct resident stem cells. Here we report that JunB, a member of the AP-1 transcription factor family, regulates epidermal ...stem cells and sebaceous glands through balancing proliferation and differentiation of progenitors and by suppressing lineage infidelity. JunB deficiency in basal progenitors results in a dermatitis-like syndrome resembling seborrheic dermatitis harboring structurally and functionally impaired sebaceous glands with a globally altered lipid profile. A fate switch occurs in a subset of JunB deficient epidermal progenitors during wound healing resulting in de novo formation of sebaceous glands. Dysregulated Notch signaling is identified to be causal for this phenotype. In fact, pharmacological inhibition of Notch signaling can efficiently restore the lineage drift, impaired epidermal differentiation and disrupted barrier function in JunB conditional knockout mice. These findings define an unprecedented role for JunB in epidermal-pilosebaceous stem cell homeostasis and its pathology.
Abstract Mounting ambitions and capabilities for public and private, non-government sector crewed space exploration bring with them an increasingly diverse set of space travelers, raising new and ...nontrivial ethical, legal, and medical policy and practice concerns which are still relatively underexplored. In this piece, we lay out several pressing issues related to ethical considerations for selecting space travelers and conducting human subject research on them, especially in the context of non-governmental and commercial/private space operations.
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