Biology subjects

Falach, R.

Publications and source records attributed to Falach, R..

5 recordsLinked to original sources

bioRxiv2023

SleepEEGpy: a Python-based package for the preprocessing, analysis, and visualization of sleep EEG data

Sleep research uses electroencephalography (EEG) to infer brain activity in health and disease. Beyond standard sleep scoring, there is increased interest in advanced EEG analysis that require extensive preprocessing to improve the signal-to-noise ratio, and dedicated analysis algorithms. While many EEG software packages exist, sleep research has specific needs that require dedicated tools (e.g. particular artifacts, event detection). Currently, sleep investigators use different libraries for specific tasks in a fragmented configuration that is inefficient, prone to errors, and requires the learning of multiple software environments. This leads to a high initial complexity, creating a crucial barrier for beginners in sleep research. Here, we present SleepEEGpy, an open-source Python software "wrapper" package to facilitate sleep EEG data preprocessing and analysis. SleepEEGpy builds upon MNE-Python, YASA, and SpecParam tools to provide an all-in-one, beginner-friendly package for comprehensive yet straightforward sleep EEG research including (i) cleaning, (ii) independent component analysis, (iii) detection of sleep events, (iv) analysis of spectral features, and associated visualization tools. A dashboard visualization tool provides an overview to evaluate data and its preprocessing, which can be useful as an initial step prior to detailed analysis. We demonstrate the SleepEEGpy pipeline and its functionalities by applying it to overnight high-density EEG data in healthy participants, revealing multiple characteristic activity signatures typical of each vigilance state. These include alpha oscillations in wakefulness, sleep spindle and slow wave activities in NREM sleep, and theta activity in REM sleep. We hope that this software will be embraced and further developed by the sleep research community, and constitute a useful entry point tool for beginners in sleep EEG research.

neuroscience↗

bioRxiv2023

A visual paired associate learning (vPAL) paradigm to study memory consolidation during sleep

The hippocampus helps transform an experience into an enduring memory by associating its multiple aspects. Sleep improves the consolidation of the newly formed associations, leading to stable long-term memory. Most research on human declarative memory and its consolidation during sleep uses word-pair associations requiring exhaustive learning. Here we present the visual paired association learning (vPAL) paradigm, in which participants learn new associations between images of celebrities and animals. vPAL associations are based on a one-shot exposure that resembles learning in natural conditions. We tested if vPAL can reveal a role for sleep in memory consolidation by assessing the specificity of memory recognition, and the cued recall performance, before and after sleep. We found that a daytime nap improved the stability of recognition memory and discrimination abilities compared to identical intervals of wakefulness. By contrast, cued recall of associations did not exhibit significant sleep-dependent effects. High-density EEG during naps further revealed an association between sleep spindle density and stability of recognition memory. Thus, the vPAL paradigm opens new avenues for future research on sleep and memory consolidation across ages and heterogeneous populations in health and disease.

neuroscience↗

bioRxiv2021

Therapeutic antibodies, targeting the SARS-CoV-2 spike N-terminal domain, protect lethally infected K18-hACE2 mice

Since the onset of the current COVID-19 pandemic, high priority is given to the development of neutralizing antibodies, as a key approach for the design of therapeutic strategies to countermeasure and eradicate the disease. Previously, we reported the development of human therapeutic monoclonal antibodies (mAbs) exhibiting very high protective ability. These mAbs recognize epitopes on the spike receptor binding domain (RBD) of SARS-CoV-2 that is considered to represent the main rout of receptor engagement by the SARS-CoV-2 virus. The recent emergence of viral variants emphasizes the notion that efficient antibody treatments need to rely on mAbs against several distinct key epitopes in order to circumvent the occurrence of therapy escape-mutants. Here we report the isolation and characterization of 12 neutralizing mAbs, identified by screening a phage-display library constructed from lymphatic cells collected from severe COVID-19 patients. The antibodies target three distinct epitopes on the spike N-terminal domain (NTD) of SARS-CoV-2, one of them defining a major site of vulnerability of the virus. Extensive characterization of these mAbs suggests a neutralization mechanism which relies both on amino-acid and N-glycan recognition on the virus, and involvement of receptors other than the hACE2 on the target cell. Two of the selected mAbs, which demonstrated superior neutralization potency in vitro, were further evaluated in vivo, demonstrating their ability to fully protect K18-hACE2 transgenic mice even when administered at low doses and late after infection. The study demonstrates the high potential of the mAbs for therapy of SARS-CoV-2 infection and underlines the possible role of the NTD in mediating infection of host cells via alternative cellular portals other than the canonical ACE2 receptor.

immunology↗

bioRxiv2020

Induced pulmonary comorbidities render CD-1 mice sensitive to SARS-CoV-2

Severe manifestations of COVID-19 are mostly restricted to people with comorbidities. Here we report that induced mild pulmonary morbidities render SARS-CoV-2-refractive CD-1 mice to be susceptible to this virus. Specifically, SARS-CoV-2 infection after application of low-doses of the acute-lung-injury stimulants bleomycin or ricin caused a severe disease in CD-1 mice, manifested by sustained body weight loss and mortality rates of >50%. Further studies revealed markedly higher levels of viral RNA in the lungs, heart and serum of low-dose-ricin pretreated, as compared to non-pretreated mice. Notably, the deleterious effects of SARS-CoV-2 infection were effectively alleviated by passive transfer of polyclonal or monoclonal antibodies generated against SARS-CoV-2 RBD. Thus, viral cell entry in the sensitized mice seems to involve viral RBD binding, albeit by a mechanism other than the canonical ACE2-mediated uptake route. In summary, we present a novel mice-based animal model for the study of comorbidity-dependent severe COVID-19.

pathology↗

bioRxiv2020

Post-exposure protection of SARS-CoV-2 lethal infected K18-hACE2 transgenic mice by neutralizing human monoclonal antibody

Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits high levels of mortality and morbidity and has dramatic consequences on human life, sociality and global economy. Neutralizing antibodies constitute a highly promising approach for treating and preventing infection by this novel pathogen. In the present study, we characterized and further evaluated the recently identified human monoclonal MD65 antibody for its ability to provide protection against a lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice. Eighty percent of the untreated mice succumbed 6-9 days post-infection while administration of the MD65 antibody as late as 3 days after exposure, rescued all infected animals. In addition, the efficiency of the treatment is supported by prevention of morbidity and ablation of the load of infective virions in the lungs of treated animals. The data unprecedentedly demonstrate, the therapeutic value of human monoclonal antibodies as a life-saving treatment of severe COVID-19 infection.

immunology↗