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Laurence Ris

Bio: Laurence Ris is an academic researcher from University of Mons. The author has contributed to research in topics: Long-term potentiation & Synaptic plasticity. The author has an hindex of 26, co-authored 73 publications receiving 3676 citations. Previous affiliations of Laurence Ris include University College London & Centre national de la recherche scientifique.


Papers
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Journal ArticleDOI
TL;DR: Olfactory and gustatory disorders are prevalent symptoms in European CO VID-19 patients, who may not have nasal symptoms, and the sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection.
Abstract: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection.

2,030 citations

Journal ArticleDOI
TL;DR: The findings demonstrate the critical involvement of amyloid peptides in defective LTP in APP transgenic mice and highlight the complex functional relation of APP and PS1 to cognition and neuronal plasticity in adult and aging brain.
Abstract: In the brain of Alzheimer's disease (AD) patients, neurotoxic amyloid peptides accumulate and are deposited as senile plaques. A major therapeutic strategy aims to decrease production of amyloid peptides by inhibition of gamma-secretase. Presenilins are polytopic transmembrane proteins that are essential for gamma-secretase activity during development and in amyloid production. By loxP/Cre-recombinase-mediated deletion, we generated mice with postnatal, neuron-specific presenilin-1 (PS1) deficiency, denoted PS1(n-/-), that were viable and fertile, with normal brain morphology. In adult PS1(n-/-) mice, levels of endogenous brain amyloid peptides were strongly decreased, concomitant with accumulation of amyloid precursor protein (APP) C-terminal fragments. In the cross of APP[V717I]xPS1 (n-/-) double transgenic mice, the neuronal absence of PS1 effectively prevented amyloid pathology, even in mice that were 18 months old. This contrasted sharply with APP[V717I] single transgenic mice that all develop amyloid pathology at the age of 10-12 months. In APP[V717I]xPS1 (n-/-) mice, long-term potentiation (LTP) was practically rescued at the end of the 2 hr observation period, again contrasting sharply with the strongly impaired LTP in APP[V717I] mice. The findings demonstrate the critical involvement of amyloid peptides in defective LTP in APP transgenic mice. Although these data open perspectives for therapy of AD by gamma-secretase inhibition, the neuronal absence of PS1 failed to rescue the cognitive defect, assessed by the object recognition test, of the parent APP[V717I] transgenic mice. This points to potentially detrimental effects of accumulating APP C99 fragments and demands further study of the consequences of inhibition of gamma-secretase activity. In addition, our data highlight the complex functional relation of APP and PS1 to cognition and neuronal plasticity in adult and aging brain.

267 citations

Journal ArticleDOI
TL;DR: The slight recovery of sensitivity to head rotation was due only to units behaving as type II neurons, and in the absence of statistically significant difference between the characteristics of the neuronal discharge of the second-order vestibular neurons recorded in the SVN, LVN, and rostral MVN, the data were pooled.
Abstract: 1 Neuronal activity was investigated in the left superior vestibular nucleus (SVN), lateral vestibular nucleus (LVN), and rostral part of the medial vestibular nucleus (MVN) in the alert guinea pig after a unilateral (left) labyrinthectomy was performed Vestibular neurons were recorded either immediately (just-postoperative group, n = 6) or 1 wk after labyrinthectomy (1-wk-postoperative group, n = 6) and compared with the activity recorded in intact animals (control group, n = 6) 2 Animals were prepared for extracellular recording of single-unit activity and for eye movement recording (scleral search coil technique) To enable stimulation of the left vestibular nerve, bipolar silver ball electrodes were chronically implanted either in contact with the bony labyrinth in the control group or close to the stump of the vestibular nerve after labyrinthectomy Complete labyrinthectomy was performed under halothane anesthesia 3 The criterion used to select vestibular neurons for analysis was their recruitment by an electric shock on the vestibular nerve Of the 589 recorded neurons, 424, defined as second-order vestibular neurons, were recruited at monosynaptic latencies (085-115 ms) and 165 were recruited at polysynaptic latencies One hundred three second-order vestibular neurons were recorded in the control group, 173 in the just-postoperative group, and 148 in the 1-wk-postoperative group 4 The activity of the electrically recruited neurons was recorded during sinusoidal horizontal head rotation in the dark (03 Hz, 40 degrees/s peak velocity) The behavior of the neurons was analyzed by plotting their firing rate against head velocity The Y-intercept of the regression line was used to express spontaneous firing rate (resting discharge), and its slope was used to express the sensitivity of the neuron-to-head velocity 5 In the absence of statistically significant difference between the characteristics of the neuronal discharge of the second-order vestibular neurons recorded in the SVN, LVN, and rostral MVN, the data were pooled The Resting discharge of these cells amounted to 410 +/- 247 (SD) spikes/s in the control state, fell to 72 +/- 139 spikes/s just after labyrinthectomy, and completely returned to normal values 1 wk after surgery (425 +/- 216 spikes/s) Among the monosynaptically recruited neurons, the percentage of silent units was 0% in the control group, 69% in the just-postoperative group, and 0% in the 1-wk-postoperative group 6 By contrast, the sensitivity to head velocity of the second-order vestibular neurons, which was 069 +/- 048 (SD) spikess-1/degs-1 in the control state and which fell to 003 +/- 011 spikess-1/degs-1 just after labyrinthectomy, remained low 1 wk after injury (021 +/- 026 spikess-1/degs-1) Moreover, the slight recovery of sensitivity to head rotation was due only to units behaving as type II neurons 7 The mean resting discharge of the polysynaptically recruited neurons (pooled from the 3 explored nuclei) was 316 +/- 193 spikes/s in the control group It decreased to 116 +/- 121 spikes/s in the just-postoperative group and recovered to 398 +/- 202 spikes/s in the 1-wk-postoperative group No neuron was silent at rest either in the control group or in the 1-wk-postoperative group Just after labyrinthectomy, 35% of the neurons had a null resting activity The mean sensitivity to head velocity of these neurons was 055 +/- 042 spikess-1/degs-1 in the control group It decreased to 005 +/- 012 spikess-1/degs-1 in the just-postoperative group and recovered to 022 +/- 017 spikess-1/degs-1 in the 1-wk-postoperative group 8 We conclude that, at least in the guinea pig, the restoration of the spontaneous activity of the deafferented neurons is complete 1 wk after a unilateral labyrinthectomy and thus probably plays an important role in vestibular compensation

189 citations

Journal ArticleDOI
TL;DR: The spiking behavior of the neurons in the vestibular nuclei in the alert guinea pig after a bilateral labyrinthectomy was studied to address the relative contributions of the loss of the excitatory influence from the ipsilateral labyrinth (destroyed) and of the persistence of the inhibitory Influence from the contralateral labyrinth (intact).
Abstract: Ris, Laurence and Emile Godaux. Neuronal activity in the vestibular nuclei after contralateral or bilateral labyrinthectomy in the alert guinea pig. J. Neurophysiol. 80: 2352–2367, 1998. In the gui...

139 citations

Journal ArticleDOI
TL;DR: The lowered excitotoxic threshold for kainic acid was also observed in mice transgenic for mutant human PS2[N141I] and was prevented by dantrolene, an inhibitor of Ca2+ release from the endoplasmic reticulum.

132 citations


Cited by
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Journal ArticleDOI
25 Oct 2002-Science
TL;DR: Mounting evidence suggests that this syndrome begins with subtle alterations of hippocampal synaptic efficacy prior to frank neuronal degeneration, and that the synaptic dysfunction is caused by diffusible oligomeric assemblies of the amyloid β protein.
Abstract: In its earliest clinical phase, Alzheimer's disease characteristically produces a remarkably pure impairment of memory. Mounting evidence suggests that this syndrome begins with subtle alterations of hippocampal synaptic efficacy prior to frank neuronal degeneration, and that the synaptic dysfunction is caused by diffusible oligomeric assemblies of the amyloid β protein.

3,941 citations

Journal ArticleDOI
25 Aug 2020-JAMA
TL;DR: This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19, the novel severe acute respiratory syndrome coronavirus 2 pandemic that has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease.
Abstract: Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

3,371 citations

Journal ArticleDOI
TL;DR: The extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 are reviewed to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
Abstract: Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

2,113 citations

Journal ArticleDOI
Carly G. K. Ziegler, Samuel J. Allon, Sarah K. Nyquist, Ian M. Mbano1, Vincent N. Miao, Constantine N. Tzouanas, Yuming Cao2, Ashraf S. Yousif3, Julia Bals3, Blake M. Hauser3, Blake M. Hauser4, Jared Feldman4, Jared Feldman3, Christoph Muus4, Christoph Muus5, Marc H. Wadsworth, Samuel W. Kazer, Travis K. Hughes, Benjamin Doran, G. James Gatter3, G. James Gatter6, G. James Gatter5, Marko Vukovic, Faith Taliaferro5, Faith Taliaferro7, Benjamin E. Mead, Zhiru Guo2, Jennifer P. Wang2, Delphine Gras8, Magali Plaisant9, Meshal Ansari, Ilias Angelidis, Heiko Adler, Jennifer M.S. Sucre10, Chase J. Taylor10, Brian M. Lin4, Avinash Waghray4, Vanessa Mitsialis7, Vanessa Mitsialis11, Daniel F. Dwyer11, Kathleen M. Buchheit11, Joshua A. Boyce11, Nora A. Barrett11, Tanya M. Laidlaw11, Shaina L. Carroll12, Lucrezia Colonna13, Victor Tkachev4, Victor Tkachev7, Christopher W. Peterson13, Christopher W. Peterson14, Alison Yu15, Alison Yu7, Hengqi Betty Zheng15, Hengqi Betty Zheng13, Hannah P. Gideon16, Caylin G. Winchell16, Philana Ling Lin16, Philana Ling Lin7, Colin D. Bingle17, Scott B. Snapper7, Scott B. Snapper11, Jonathan A. Kropski10, Jonathan A. Kropski18, Fabian J. Theis, Herbert B. Schiller, Laure-Emmanuelle Zaragosi9, Pascal Barbry9, Alasdair Leslie1, Alasdair Leslie19, Hans-Peter Kiem14, Hans-Peter Kiem13, JoAnne L. Flynn16, Sarah M. Fortune3, Sarah M. Fortune5, Sarah M. Fortune4, Bonnie Berger6, Robert W. Finberg2, Leslie S. Kean4, Leslie S. Kean7, Manuel Garber2, Aaron G. Schmidt4, Aaron G. Schmidt3, Daniel Lingwood3, Alex K. Shalek, Jose Ordovas-Montanes, Nicholas E. Banovich, Alvis Brazma, Tushar J. Desai, Thu Elizabeth Duong, Oliver Eickelberg, Christine S. Falk, Michael Farzan20, Ian A. Glass, Muzlifah Haniffa, Peter Horvath, Deborah T. Hung, Naftali Kaminski, Mark A. Krasnow, Malte Kühnemund, Robert Lafyatis, Haeock Lee, Sylvie Leroy, Sten Linnarson, Joakim Lundeberg, Kerstin B. Meyer, Alexander V. Misharin, Martijn C. Nawijn, Marko Nikolic, Dana Pe'er, Joseph E. Powell, Stephen R. Quake, Jay Rajagopal, Purushothama Rao Tata, Emma L. Rawlins, Aviv Regev, Paul A. Reyfman, Mauricio Rojas, Orit Rosen, Kourosh Saeb-Parsy, Christos Samakovlis, Herbert B. Schiller, Joachim L. Schultze, Max A. Seibold, Douglas P. Shepherd, Jason R. Spence, Avrum Spira, Xin Sun, Sarah A. Teichmann, Fabian J. Theis, Alexander M. Tsankov, Maarten van den Berge, Michael von Papen, Jeffrey A. Whitsett, Ramnik J. Xavier, Yan Xu, Kun Zhang 
28 May 2020-Cell
TL;DR: The data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.

1,911 citations

Journal ArticleDOI
TL;DR: Intriguingly, most organelle-specific death responses finally lead to either MMP or caspase activation, both of which might function as central integrators of the death pathway, thereby streamlining lysosome-, Golgi- or ER-elicited responses into a common pathway.
Abstract: Nuclear DNA damage and ligation of plasma-membrane death receptors have long been recognized as initial triggers of apoptosis that induce mitochondrial membrane permeabilization (MMP) and/or the direct activation of caspases. Accumulating evidence suggests that other organelles, including the endoplasmic reticulum (ER), lysosomes and the Golgi apparatus, are also major points of integration of pro-apoptotic signalling or damage sensing. Each organelle possesses sensors that detect specific alterations, locally activates signal transduction pathways and emits signals that ensure inter-organellar cross-talk. The ER senses local stress through chaperones, Ca2+-binding proteins and Ca2+ release channels, which might transmit ER Ca2+ responses to mitochondria. The ER also contains several Bcl-2-binding proteins, and Bcl-2 has been reported to exert part of its cytoprotective effect within the ER. Upon membrane destabilization, lysosomes release cathepsins that are endowed with the capacity of triggering MMP. The Golgi apparatus constitutes a privileged site for the generation of the pro-apoptotic mediator ganglioside GD3, facilitates local caspase-2 activation and might serve as a storage organelle for latent death receptors. Intriguingly, most organelle-specific death responses finally lead to either MMP or caspase activation, both of which might function as central integrators of the death pathway, thereby streamlining lysosome-, Golgi- or ER-elicited responses into a common pathway.

1,443 citations