Features and distribution of CD8 T cells with human leukocyte antigen class I-specific receptor expression in chronic hepatitis C.: NKRs+ CD8 T cells in chronic Hepatitis C.

CD8(+) T cells represent a sizable component of the liver inflammatory infiltrate in chronic hepatitis C and are thought to contribute to immune-mediated tissue injury. Because chronic stimulation may promote the expression by CD8(+) T cells of distinct human leukocyte antigen class I-specific natural killer cell receptors (NKRs) susceptible to both inhibiting effector functions and promoting cell survival, we examined the distribution and characteristics of CD8(+) T cells with such receptors in chronic hepatitis C patients. NKR CD8(+) T cells were detectable in liver and peripheral blood from hepatitis C virus (HCV)-infected patients but were not major subsets. However, the frequency of NKG2A(+) CD8(+) in the liver and in a lesser extent in the peripheral blood was positively correlated to histological activity in HCV-infected patients. No such correlation was found with KIR(+) T cells in liver in HCV-infected patients and with the both NKR CD8(+) T cells in hepatitis B virus (HBV) infected patients. Circulating CD8(+) T cells expressing KIRs exhibited phenotypic features of memory T cells with exacerbated expression of the senescence marker CD57 in patients. NKG2A(+)CD8(+) T cells were committed T cells that appeared less differentiated than KIR(+)CD8(+) T cells. In HCV-infected patients, their content in perforin was low and similar to that observed in NKG2A(-)CD8(+) T cells; this scenario was not observed in healthy subjects and HBV-infected patients. Both NKG2A and KIRs could inhibit the response of HCV-specific CD8(+) T cells ex vivo. CONCLUSION: These results support the concept that an accumulation in the liver parenchyma of NKR(+)CD8(+) T cells that have functional alterations could be responsible for liver lesions. They provide novel insights into the complexity of liver-infiltrating CD8(+) T cells in chronic hepatitis C and reveal that distinct subsets of antigen-experienced CD8(+) T cells are differentially sensitive to the pervasive influence of HCV

The Gaia satellite: a tool for Emission Line Stars and Hot Stars

The Gaia satellite will be launched at the end of 2011. It will observe at least 1 billion stars, and among them several million emission line stars and hot stars. Gaia will provide parallaxes for each star and spectra for stars till V magnitude equal to 17. After a general description of Gaia, we present the codes and methods, which are currently developed by our team. They will provide automatically the astrophysical parameters and spectral classification for the hot and emission line stars in the Milky Way and other close Local Group galaxies such as the Magellanic Clouds.Comment: SF2A2008, session GAIA, invited tal

AGATHE: A tool for personalized rehabilitation of cognitive functions

Stroke, traumatic brain injury, multiple sclerosis, Parkinson's disease, Alzheimer's... Every year in France, tens of thousands of people fall victim to one of those neurological pathologies. Acquired brain injury leads to cognitive impairment and heavy loss of autonomy. Rehabilitation interventions are needed to enable people to recover capacity and return to Activities of Daily Living (ADL), such as grocery shopping. Unfortunately, the resources made available in cognitive rehabilitation are insufficient for the growing needs of victims of brain damage. The assets of virtual reality to address this big problem of public health are today scientifically recognized [Rizzo and Kim 2005; Klinger, et al. 2010]. In this context, we designed the AGATHE tool (Adaptable, configurable and upgradable tool for the generation of personalized therapeutic applications in cognitive rehabilitation) (AGATHE project, ANR-09-TECS-002).French National Research Agency (ANR) Laval Agglomération et Conseil Général de la Mayenn

AGATHE: A tool for personalized rehabilitation of cognitive functions

Stroke, traumatic brain injury, multiple sclerosis, Parkinson's disease, Alzheimer's... Every year in France, tens of thousands of people fall victim to one of those neurological pathologies. Acquired brain injury leads to cognitive impairment and heavy loss of autonomy. Rehabilitation interventions are needed to enable people to recover capacity and return to Activities of Daily Living (ADL), such as grocery shopping. Unfortunately, the resources made available in cognitive rehabilitation are insufficient for the growing needs of victims of brain damage. The assets of virtual reality to address this big problem of public health are today scientifically recognized [Rizzo and Kim 2005; Klinger, et al. 2010]. In this context, we designed the AGATHE tool (Adaptable, configurable and upgradable tool for the generation of personalized therapeutic applications in cognitive rehabilitation) (AGATHE project, ANR-09-TECS-002).French National Research Agency (ANR) Laval Agglomération et Conseil Général de la Mayenn

OVX033, a nucleocapsid-based vaccine candidate, provides broad-spectrum protection against SARS-CoV-2 variants in a hamster challenge model

Spike-based COVID-19 vaccines induce potent neutralizing antibodies but their efficacy against SARS-CoV-2 variants decreases. OVX033 is a recombinant protein composed of the full-length nucleocapsid (N) protein of SARS-CoV-2 genetically fused to oligoDOM®, a self-assembling domain which improves antigen immunogenicity. OVX033 including N as an antigenic target is proposed as new vaccine candidate providing broad-spectrum protection against sarbecoviruses. OVX033 demonstrated its ability to trigger cross-reactive T cell responses and cross-protection against three variants of SARS-CoV-2 (B.1 Europe, Delta B.1.617.2, and Omicron B.1.1.529) in a hamster challenge model, as evidenced by lower weight loss, lower lung viral loads, and reduced lung histopathological lesions

Assessment of dietary diversity and nutritional support for children living with HIV in the IeDEA pediatric West African cohort: a non-comparative, feasibility study

BACKGROUND: Nutritional care is not optimally integrated into pediatric HIV care in sub-Saharan Africa. We assessed the 6-month effect of a nutritional support provided to children living with HIV, followed in a multicentric cohort in West Africa. METHODS: In 2014-2016, a nutritional intervention was carried out for children living with HIV, aged under 10 years, receiving antiretroviral therapy (ART) or not, in five HIV pediatric cohorts, in Benin, Togo and Côte d'Ivoire. Weight deficiency was assessed using two definitions: wasting (Weight for Height Z-score [WHZ] for children<5 years old or Body-Mass-Index for Age [BAZ] for ≥5 years) and underweight (Weight for Age Z-score [WAZ]) (WHO child growth standards). Combining these indicators, three categories of nutritional support were defined: 1/ children with severe malnutrition (WAZ and/or WHZ/BAZ <-3 Standard Deviations [SD]) were supported with Ready-To-Use Therapeutic Food (RUTF), 2/ those with moderate malnutrition (WAZ and/or WHZ/BAZ = [-3;-2[ SD) were supported with fortified blended flours produced locally in each country, 3/ those non malnourished (WAZ and WHZ/BAZ ≥-2 SD) received nutritional counselling only. Children were followed monthly over 6 months. Dietary Diversity Score (DDS) using a 24h recall was measured at the first and last visit of the intervention. RESULTS: Overall, 326 children were included, 48% were girls. At baseline, 66% were aged 5-10 years, 91% were on ART, and 17% were severely immunodeficient (CD4 <250 cells/mL or CD4%<15). Twenty-nine (9%) were severely malnourished, 63 (19%) moderately malnourished and 234 (72%) non-malnourished. After 6 months, 9/29 (31%) and 31/63 (48%) recovered from severe and moderate malnutrition respectively. The median DDS was 8 (IQR 7-9) in Côte d'Ivoire and Togo, 6 (IQR 6-7) in Benin. Mean DDS was 4.3/9 (sd 1.2) at first visit, with a lower score in Benin, but with no difference between first and last visit (p=0.907), nor by intervention groups (p-value=0.767). CONCLUSIONS: This intervention had a limited effect on nutritional recovery and dietary diversity improvement. Questions remain on determining appropriate nutritional products, in terms of adherence, proper use for families and adequate energy needs coverage for children living with HIV. TRIAL REGISTRATION: PACTR202001816232398 , June 01, 2020, retrospectively registered

Evaluation des populations lymphocytaires T intra-hépatiques au cours de l'hépatite virale chronique C

Le but de ce travail était d'évaluer le rôle des LIH au cours de l'HCC. méthodes: Les LIH étaient évalués par cytométrie de flux, immunohistochimie et par RT-PCR en temps réel. La diversité des récepteurs à l'antigène (TCR) était étudiée par analyse moléculaire de la région CDR3 (technique "immunoscope"). résultats: La distribution des LIH est modifiée au cours de l'HCC (augmentation des lymphocytes T conventionels, diminution des lymphocytes T[gamma][delta], NK et TNK). Une corrélation était observée entre le nombre de lymphocytes T CD8 exprimant des marqueurs de cytoxicité et la sévérité de la maladie. L'analyse moléculaire de leur TCR retrouvait un répertoire divers, typique d'une population polyclonale. Conclusion: Nos résultats montrent que les lymphocytes T CD8 sont les principaux effecteurs des lésions hépatiques au cours de l'HCC. Leur caractère polyclonal et leur absence d'efficacité antivirale suggère qu'il s'agit en majorité de lymphocytes non spécifiques recrutés dans le foie.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Ceftriaxone preserves glutamate transporters and prevents intermittent hypoxia-induced vulnerability to brain excitotoxic injury.

Hypoxia alters cellular metabolism and although the effects of sustained hypoxia (SH) have been extensively studied, less is known about chronic intermittent hypoxia (IH), commonly associated with cardiovascular morbidity and stroke. We hypothesize that impaired glutamate homeostasis after chronic IH may underlie vulnerability to stroke-induced excitotoxicity. P16 organotypic hippocampal slices, cultured for 7 days were exposed for 7 days to IH (alternating 2 min 5% O2-15 min 21% O2), SH (5% O2) or RA (21% O2), then 3 glutamate challenges. The first and last exposures were intended as a metabolic stimulus (200 µM glutamate, 15 min); the second emulated excitotoxicity (10 mM glutamate, 10 min). GFAP, MAP2, and EAAT1, EAAT2 glutamate transporters expression were assessed after exposure to each hypoxic protocol. Additionally, cell viability was determined at baseline and after each glutamate challenge, in presence or absence of ceftriaxone that increases glutamate transporter expression. GFAP and MAP2 decreased after 7 days IH and SH. Long-term IH but not SH decreased EAAT1 and EAAT2. Excitotoxic glutamate challenge decreased cell viability and the following 200 µM exposure further increased cell death, particularly in IH-exposed slices. Ceftriaxone prevented glutamate transporter decrease and improved cell viability after IH and excitotoxicity. We conclude that IH is more detrimental to cell survival and glutamate homeostasis than SH. These findings suggest that impaired regulation of extracellular glutamate levels is implicated in the increased brain susceptibility to excitotoxic insult after long-term IH