Online interoperable resources for building hippocampal neuron models via the Hippocampus Hub.

To build biophysically detailed models of brain cells, circuits, and regions, a data-driven approach is increasingly being adopted. This helps to obtain a simulated activity that reproduces the experimentally recorded neural dynamics as faithfully as possible, and to turn the model into a useful framework for making predictions based on the principles governing the nature of neural cells. In such a context, the access to existing neural models and data outstandingly facilitates the work of computational neuroscientists and fosters its novelty, as the scientific community grows wider and neural models progressively increase in type, size, and number.

The EBRAINS Hodgkin-Huxley Neuron Builder: An online resource for building data-driven neuron models.

In the last decades, brain modeling has been established as a fundamental tool for understanding neural mechanisms and information processing in individual cells and circuits at different scales of observation. Building data-driven brain models requires the availability of experimental data and analysis tools as well as neural simulation environments and, often, large scale computing facilities. All these components are rarely found in a comprehensive framework and usually require programming.

EBRAINS Live Papers - Interactive Resource Sheets for Computational Studies in Neuroscience.

We present here an online platform for sharing resources underlying publications in neuroscience. It enables authors to easily upload and distribute digital resources, such as data, code, and notebooks, in a structured and systematic way. Interactivity is a prominent feature of the Live Papers, with features to download, visualise or simulate data, models and results presented in the corresponding publications.

The EBRAINS NeuroFeatureExtract: An Online Resource for the Extraction of Neural Activity Features From Electrophysiological Data.

The description of neural dynamics, in terms of precise characterizations of action potential timings and shape and voltage related measures, is fundamental for a deeper understanding of the neural code and its information content. Not only such measures serve the scientific questions posed by experimentalists but are increasingly being used by computational neuroscientists for the construction of biophysically detailed data-driven models. Nonetheless, online resources enabling users to perform such feature extraction operation are lacking.

HippoUnit: A software tool for the automated testing and systematic comparison of detailed models of hippocampal neurons based on electrophysiological data.

Anatomically and biophysically detailed data-driven neuronal models have become widely used tools for understanding and predicting the behavior and function of neurons. Due to the increasing availability of experimental data from anatomical and electrophysiological measurements as well as the growing number of computational and software tools that enable accurate neuronal modeling, there are now a large number of different models of many cell types available in the literature. These models were usually built to capture a few important or interesting properties of the given neuron type, and it is often unknown how they would behave outside their original context.

Why Communities Should Be the Focus to Reduce Stigma Attached to COVID-19.

Since 1999, the CORE Group Polio Project (CGPP) has developed, refined, and deployed effective strategies to mobilize communities to improve vaccine uptake for polio (and other vaccine-preventable diseases such as measles) and conduct surveillance for infectious disease threats in high-risk, border, and hard-to-reach locations. CORE Group Polio Project teams have been called upon to address the COVID-19 pandemic, and, like with polio, the pandemic response is impacted by stigma in all areas of response, from health education, testing, contact tracing, and even treatment for infected individuals. The CGPP has reached back into its polio experience and is redeploying successful community engagement activities to address stigma as part of the COVID-19 response.

Platelet protein S limits venous but not arterial thrombosis propensity by controlling coagulation in the thrombus.

Anticoagulant protein S (PS) in platelets (PSplt) resembles plasma PS and is released on platelet activation, but its role in thrombosis has not been elucidated. Here we report that inactivation of PSplt expression using the Platelet factor 4 (Pf4)-Cre transgene (Pros1lox/loxPf4-Cre+) in mice promotes thrombus propensity in the vena cava, where shear rates are low, but not in the carotid artery, where shear rates are high. At a low shear rate, PSplt functions as a cofactor for both activated protein C and tissue factor pathway inhibitor, thereby limiting factor X activation and thrombin generation within the growing thrombus and ensuring that highly activated platelets and fibrin remain localized at the injury site.

Preventing Importation of Poliovirus in the Horn of Africa: The Success of the Cross-Border Health Initiative in Kenya and Somalia.

In 2013, the outbreak of wild poliovirus (WPV) in the Horn of Africa (HOA) triggered an aggressive, coordinated national and regional response to interrupt continued transmission. Kenya, Somalia, Ethiopia, South Sudan, and other HOA countries share a range of complex factors that enabled the outbreak: porous and sparsely populated borders, insecurity due to armed conflicts, and weak health systems with persistently under-resourced health facilities resulting in low-quality care and low levels of immunization coverage in mobile populations. Consequently, the continued risk of WPV importation demanded cross-border and intersectoral collaboration.

Trust, Communication, and Community Networks: How the CORE Group Polio Project Community Volunteers Led the Fight against Polio in Ethiopia's Most At-Risk Areas.

The last case of wild poliovirus in Ethiopia was reported in 2014. Until the disease is eradicated globally, the risk of reimportation remains high. In 1999, the CORE Group Polio Project (CGPP) began its community-centered polio eradication efforts in Ethiopia, using community volunteers (CVs) to ensure that no child has missed polio vaccine.

The CORE Group Partners Project in North East Nigeria: Community Engagement Strategies to Combat Skepticism and Build Trust for Vaccine Acceptance.

In North East Nigeria, anti-immunization rumors and sentiments have negatively impacted the country's polio eradication efforts. Since 2014, the CORE Group Partners Project (CGPP) has leveraged local-level strategies to help change prevailing attitudes and behaviors by improving immunization acceptability in some of the most difficult settlements in Nigeria's states at highest risk for polio. The CGPP's communication model in Nigeria, in part, emphasizes the need to counter suspicion and address myths and misunderstandings by convening community dialogs and compound meetings, both of which serve as safe spaces for open discussion primarily aimed at addressing non-compliance.

Contributions of Volunteer Community Mobilizers to Polio Eradication in Nigeria: The Experiences of Non-governmental and Civil Society Organizations.

The Northern states were the epicenter of the wild poliovirus outbreak in Nigeria in 2016. To raise immunization coverage, particularly of polio, the Polio Eradication Initiative (PEI) in Nigeria introduced the use of nongovernmental organizations and volunteer community mobilizers (VCMs) through the CORE Group Polio Project (CGPP). The CGPP has been contributing to Nigeria's polio eradication efforts since 2013.

Age-related preference for geometric spatial cues during real-world navigation.

Ageing effects on spatial navigation are characterized mainly in terms of impaired allocentric strategies. However, an alternative hypothesis is that navigation difficulties in aged people are associated with deficits in processing and encoding spatial cues. We tested this hypothesis by studying how geometry and landmark cues control navigation in young and older adults in a real, ecological environment.

The physiological variability of channel density in hippocampal CA1 pyramidal cells and interneurons explored using a unified data-driven modeling workflow.

Every neuron is part of a network, exerting its function by transforming multiple spatiotemporal synaptic input patterns into a single spiking output. This function is specified by the particular shape and passive electrical properties of the neuronal membrane, and the composition and spatial distribution of ion channels across its processes. For a variety of physiological or pathological reasons, the intrinsic input/output function may change during a neuron's lifetime.

Targeting anticoagulant protein S to improve hemostasis in hemophilia.

Improved treatments are needed for hemophilia A and B, bleeding disorders affecting 400 000 people worldwide. We investigated whether targeting protein S could promote hemostasis in hemophilia by rebalancing coagulation. Protein S (PS) is an anticoagulant acting as cofactor for activated protein C and tissue factor pathway inhibitor (TFPI).

A Synthetic Factor XIIa Inhibitor Blocks Selectively Intrinsic Coagulation Initiation.

Coagulation factor XII (FXII) inhibitors are of interest for the study of the protease in the intrinsic coagulation pathway, for the suppression of contact activation in blood coagulation assays, and they have potential application in antithrombotic therapy. However, synthetic FXII inhibitors developed to date have weak binding affinity and/or poor selectivity. Herein, we developed a peptide macrocycle that inhibits activated FXII (FXIIa) with an inhibitory constant Ki of 22 nM and a selectivity of >2000-fold over other proteases.

Modulation of network activity and induction of homeostatic synaptic plasticity by enzymatic removal of heparan sulfates.

Heparan sulfates (HSs) are complex and highly active molecules that are required for synaptogenesis and long-term potentiation. A deficit in HSs leads to autistic phenotype in mice. Here, we investigated the long-term effect of heparinase I, which digests highly sulfated HSs, on the spontaneous bioelectrical activity of neuronal networks in developing primary hippocampal cultures.

A closed-loop neurobotic system for fine touch sensing.

Objective: Fine touch sensing relies on peripheral-to-central neurotransmission of somesthetic percepts, as well as on active motion policies shaping tactile exploration. This paper presents a novel neuroengineering framework for robotic applications based on the multistage processing of fine tactile information in the closed action-perception loop.

Approach: The integrated system modules focus on (i) neural coding principles of spatiotemporal spiking patterns at the periphery of the somatosensory pathway, (ii) probabilistic decoding mechanisms mediating cortical-like tactile recognition and (iii) decision-making and low-level motor adaptation underlying active touch sensing.

Ofatumumab is more efficient than rituximab in lysing B chronic lymphocytic leukemia cells in whole blood and in combination with chemotherapy.

Ofatumumab (OFA) is a human anti-CD20 Ab approved for treatment of fludarabine-refractory B chronic lymphocytic leukemia (B-CLL). The efficacy of different immunotherapeutic strategies is best investigated in conditions that are as physiologic as possible. We have therefore compared the activity OFA and rituximab (RTX), alone or in combination with chemotherapeutic agents in unmanipulated whole blood assays, using flow cytometry.

Encoding/decoding of first and second order tactile afferents in a neurorobotic application.

We present a neurorobotic framework to investigate tactile information processing at the early stages of the somatosensory pathway. We focus on spatiotemporal coding of first and second order responses to Braille stimulation, which offers a suitable protocol to investigate the neural bases of fine touch discrimination. First, we model Slow Adaptive type I fingertip mechanoreceptor responses to Braille characters sensed both statically and dynamically.

Antitumour effects of single or combined monoclonal antibodies directed against membrane antigens expressed by human B cells leukaemia.

Background: The increasing availability of different monoclonal antibodies (mAbs) opens the way to more specific biologic therapy of cancer patients. However, despite the significant success of therapy in breast and ovarian carcinomas with anti-HER2 mAbs as well as in non-Hodkin B cell lymphomas with anti-CD20 mAbs, certain B cell malignancies such as B chronic lymphocytic leukaemia (B-CLL) respond poorly to anti-CD20 mAb, due to the low surface expression of this molecule. Thus, new mAbs adapted to each types of tumour will help to develop personalised mAb treatment.

Mechanism of action of type II, glycoengineered, anti-CD20 monoclonal antibody GA101 in B-chronic lymphocytic leukemia whole blood assays in comparison with rituximab and alemtuzumab.

We analyzed in B-chronic lymphocytic leukemia (B-CLL) whole blood assays the activity of therapeutic mAbs alemtuzumab, rituximab, and type II glycoengineered anti-CD20 mAb GA101. Whole blood samples were treated with Abs, and death of CD19(+) B-CLL was measured by flow cytometry. Alemtuzumab efficiently lysed B-CLL targets with maximal lysis at 1-4 h (62%).

Investigating neuronal activity by SPYCODE multi-channel data analyzer.

Multi-channel acquisition from neuronal networks, either in vivo or in vitro, is becoming a standard in modern neuroscience in order to infer how cell assemblies communicate. In spite of the large diffusion of micro-electrode-array-based systems, researchers usually find it difficult to manage the huge quantity of data routinely recorded during the experimental sessions. In fact, many of the available open-source toolboxes still lack two fundamental requirements for treating multi-channel recordings: (i) a rich repertoire of algorithms for extracting information both at a single channel and at the whole network level; (ii) the capability of autonomously repeating the same set of computational operations to 'multiple' recording streams (also from different experiments) and without a manual intervention.

Low-frequency stimulation enhances burst activity in cortical cultures during development.

The intact brain is continuously targeted by a wealth of stimuli with distinct spatio-temporal patterns which modify, since the very beginning of development, the activity and the connectivity of neuronal networks. In this paper, we used dissociated neuronal cultures coupled to microelectrode arrays (MEAs) to study the response of cortical neuron assemblies to low-frequency stimuli constantly delivered over weeks in vitro. We monitored the spontaneous activity of the cultures before and after the stimulation sessions, as well as their evoked response to the stimulus.