Gap suppression at a Lifshitz transition in a multi-condensate superconductor.

In multi-orbital materials, superconductivity can exhibit several coupled condensates. In this context, quantum confinement in two-dimensional superconducting oxide interfaces offers new degrees of freedom to engineer the band structure and selectively control the occupancy of 3d orbitals by electrostatic doping. Here, we use resonant microwave transport to extract the superfluid stiffness of the (110)-oriented LaAlO3/SrTiO3 interface in the entire phase diagram. We provide evidence of a transition from single-condensate to two-condensate superconductivity driven by continuous and reversible electrostatic doping, which we relate to the Lifshitz transition between 3d bands based on numerical simulations of the quantum well. We find that the superconducting gap is suppressed while the second band is populated, challenging Bardeen-Cooper-Schrieffer theory. We ascribe this behaviour to the existence of superconducting order parameters with opposite signs in the two condensates due to repulsive coupling. Our findings offer an innovative perspective on the possibility to tune and control multiple-orbital physics in superconducting interfaces.

Competition between electron pairing and phase coherence in superconducting interfaces.

In LaAlO3/SrTiO3 heterostructures, a gate tunable superconducting electron gas is confined in a quantum well at the interface between two insulating oxides. Remarkably, the gas coexists with both magnetism and strong Rashba spin-orbit coupling. However, both the origin of superconductivity and the nature of the transition to the normal state over the whole doping range remain elusive. Here we use resonant microwave transport to extract the superfluid stiffness and the superconducting gap energy of the LaAlO3/SrTiO3 interface as a function of carrier density. We show that the superconducting phase diagram of this system is controlled by the competition between electron pairing and phase coherence. The analysis of the superfluid density reveals that only a very small fraction of the electrons condenses into the superconducting state. We propose that this corresponds to the weak filling of high-energy dxz/dyz bands in the quantum well, more apt to host superconductivity.

Field-effect control of superconductivity and Rashba spin-orbit coupling in top-gated LaAlO3/SrTiO3 devices.

The recent development in the fabrication of artificial oxide heterostructures opens new avenues in the field of quantum materials by enabling the manipulation of the charge, spin and orbital degrees of freedom. In this context, the discovery of two-dimensional electron gases (2-DEGs) at LaAlO3/SrTiO3 interfaces, which exhibit both superconductivity and strong Rashba spin-orbit coupling (SOC), represents a major breakthrough. Here, we report on the realisation of a field-effect LaAlO3/SrTiO3 device, whose physical properties, including superconductivity and SOC, can be tuned over a wide range by a top-gate voltage. We derive a phase diagram, which emphasises a field-effect-induced superconductor-to-insulator quantum phase transition. Magneto-transport measurements show that the Rashba coupling constant increases linearly with the interfacial electric field. Our results pave the way for the realisation of mesoscopic devices, where these two properties can be manipulated on a local scale by means of top-gates.

In vitro inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: synergistic effect of interferon-alpha and ribavirin combination.

Chikungunya virus (CHIKV) and Semliki Forest virus (SFV) were used in our laboratory to screen active antiviral compounds against viruses of the Alphavirus genus. Antiviral activity was estimated by the reduction of the cytopathic effect of each alphavirus on infected Vero cells and by virus titer reduction. Cytotoxicity was evaluated by determining the inhibition of Trypan blue exclusion in confluent cell cultures and by the evaluation of the inhibitory effect on cell growth. With CHIKV and SFV, the selectivity indices of human recombinant interferon-alpha and iota-carrageenan were much higher than that of ribavirin, which has been previously investigated for its inhibitory effect on alphavirus infections. Compared to ribavirin, 6-azauridine was more effective against CHIKV and showed a similar antiviral activity against SFV. IFN-alpha2b, glycyrrhizin, 6-azauridine, and ribavirin caused a concentration-dependent reduction in the virus yield with CHIKV and SFV. Moreover, the combination of IFN-alpha2b and ribavirin had a subsynergistic antiviral effect on these two alphaviruses and should be evaluated for the treatment of these infections.

Gulf war syndrome: could it be triggered by biological warfare-vaccines using pertussis as an adjuvant?

Several recent epidemiological studies have shown that vaccinations against biological warfare using pertussis as an adjuvant were associated with the Gulf war syndrome. If such epidemiological findings are confirmed, we propose that the use of pertussis as an adjuvant could trigger neurodegeneration through induction of interleukin-1beta secretion in the brain. In turn, neuronal lesions may be sustained by stress or neurotoxic chemical combinations. Particular susceptibility for IL-1beta secretion and potential distant neuronal damage could provide an explanation for the diversity of the symptoms observed on veterans.

[The Gulf war syndrome]. / Le syndrome de la guerre du Golfe.

SPARSE DATA: The Gulf war syndrome remains a little know entity since its first appearance 10 years ago. The objective of our work was to synthesize the data published on the subject in the scientific literature. We analysed the results of American and English epidemiological surveys, from which it was difficult to distinguish the existence of a univocal syndrome. IMPRECISE DEFINITION: It is difficult to give a clear clinical definition of the syndrome, the signs of which fluctuate depending on the studies. Chronic fatigue is frequently associated with the Gulf war syndrome, although some studies have described electrophysiological neurological lesions. NUMEROUS HYPOTHESES: The role of stress, vaccinations and their adjuvants, exposition to neurotoxic substances and weak uranium have been incriminated. We propose that multiple factors be integrated in the research for the genesis of this atypic syndrome.

Quantitative real-time PCR detection of Rift Valley fever virus and its application to evaluation of antiviral compounds.

The Rift Valley fever virus (RVFV), a member of the genus Phlebovirus (family Bunyaviridae) is an enveloped negative-strand RNA virus with a tripartite genome. Until 2000, RVFV circulation was limited to the African continent, but the recent deadly outbreak in the Arabian Peninsula dramatically illustrated the need for rapid diagnostic methods, effective treatments, and prophylaxis. A method for quantifying the small RNA segment by a real-time detection reverse transcription (RT)-PCR using TaqMan technology and targeting the nonstructural protein-coding region was developed, and primers and a probe were designed. After optimization of the amplification reaction and establishment of a calibration curve with synthetic RNA transcribed in vitro from a plasmid containing the gene of interest, real-time RT-PCR was assessed with samples consisting of RVFV from infected Vero cells. The method was found to be specific for RVFV, and it was successfully applied to the detection of the RVFV genome in animal sera infected with RVFV as well as to the assessment of the efficiency of various drugs (ribavirin, alpha interferon, 6-azauridine, and glycyrrhizin) for antiviral activity. Altogether, the results indicated a strong correlation between the infectious virus titer and the amount of viral genome assayed by real time RT-PCR. This novel method could be of great interest for the rapid diagnosis and screening of new antiviral compounds, as it is sensitive and time saving and does not require manipulation of infectious material.

Highly sensitive Taqman PCR detection of Puumala hantavirus.

An increasing number of clinical cases of Hantavirus infections have been reported from various regions in Asia, Europe and North America. Hantaviruses (family Bunyaviridae, genus Hantavirus) are enveloped and possess a single-stranded trisegmented RNA genome of negative polarity. Rodents or insectivores are natural hosts of hantaviruses and transmit the virus to humans chiefly by aerosolisation. These viruses are the causative agents of haemorrhagic fever with renal and pulmonary syndromes. In the northeast of France, Puumala hantavirus causes, every year, more than 150 mild forms of haemorrhagic fever with a renal syndrome known as nephropathia epidemica. Serological tests may lack sensitivity for diagnosing early stages of infection and virus isolation is limited because it grows poorly in cell culture. Since reverse transcription (RT)-PCR amplification is an efficient method for detecting viral genomes in patient specimens, we developed an assay using a Taqman probe and compared it with the classical RT-PCR amplification. To achieve this goal, a Puumala strain was grown in Vero E6 cells and RNA extracted from the culture supernatant. We found that the semi-nested RT-PCR detected a minimal amount of 300 TCID(50) mL(-1), while the Taqman PCR allowed detection of less than 10 TCID(50) mL(-1 )and provided a quantitative analysis.

Mosquito cells bind and replicate hepatitis C virus.

Several studies have demonstrated some hepatitis C virus (HCV) replication in lymphocyte and hepatocyte cell lines such as in African green monkey Vero cells. The aim of the present study was to select other cell lines able to bind and replicate HCV. Human hepatoma PLC/PRF/5 cells, human lymphoma Namalwa cells, Vero and mosquito AP61 cells were inoculated with HCV-positive plasma, washed six times and examined for the presence of the viral genome at different times post infection, using an RT-PCR method. Binding of HCV to cells was estimated by HCV RNA detection in cells 2 hr after inoculation and in the last wash of these cells. Successive virus passages in cells were carried out. All the cells studied were able to bind HCV but only AP61 and Vero cells provided evidence of replication and production of infectious virus: virus RNA was detected during 28 days post-infection in four successive virus passages. CD81 molecules, a putative HCV receptor, were detected by cytofluorometric analysis. Vero cells express CD81 molecules whereas these molecules were not detected on AP61 cells. It is suggested that other receptors are involved in HCV binding to Vero and AP61 cells.

Comparison of flavivirus universal primer pairs and development of a rapid, highly sensitive heminested reverse transcription-PCR assay for detection of flaviviruses targeted to a conserved region of the NS5 gene sequences.

Arthropod-transmitted flaviviruses are responsible for considerable morbidity and mortality, causing severe encephalitic, hemorrhagic, and febrile illnesses in humans. Because there are no specific clinical symptoms for infection by a determined virus and because different arboviruses could be present in the same area, a genus diagnosis by PCR would be a useful first-line diagnostic method. The six published Flavivirus genus primer pairs localized in the NS1, NS3, NS5, and 3' NC regions were evaluated in terms of specificity and sensitivity with flaviviruses (including the main viruses pathogenic for humans) at a titer of 10(5) 50% tissue culture infectious doses (TCID(50)s) ml(-1) with a common identification step by agarose gel electrophoresis. Only one NS5 primer pair allowed the detection of all tested flaviviruses with the sensitivity limit of 10(5) TCID(50)s ml(-1). Using a heminested PCR with new primers designed in the same region after an alignment of 30 different flaviviruses, the sensitivity of reverse transcription-PCR was improved and allowed the detection of about 200 infectious doses ml(-1) with all of the tick- and mosquito-borne flaviviruses tested. It was confirmed that the sequenced amplified products in the NS5 region allowed predictability of flavivirus species by dendrogram, including the New York 99 West Nile strain. This technique was successfully performed with a cerebrospinal fluid sample from a patient hospitalized with West Nile virus encephalitis.

Chronic restraint stress induces severe disruption of the T-cell specific response to tetanus toxin vaccine.

Chronic stress is known to induce immunological disorders. In the present study we examined the consequences of chronic restraint stress on the immune response to tetanus toxin in mice. We investigated the repartition of subsets of lymphoid cells in blood and spleen, the functional ability of lymphocytes to proliferate and to produce cytokines, and antibody titres against tetanus toxin following stress. We report discordance of the stimulation index of lymphocytes in the restraint group: the proliferating rate severely decreased following stimulation with a relevant antigen, whereas it increased with mitogen. Thus, we report a decrease in cytokine production with relevant antigen (interferon-gamma and interleukin-10), without a T helper type 1 and 2 secretion imbalance. Moreover, we observed an alteration in the humoral response, including a delay in isotype maturation and an immunoglobulin G1/G2a imbalance.

A recombinant Fab neutralizes dengue virus in vitro.

A recombinant Fab that recognizes a neutralizing epitope located in the (296-400) region of protein E of dengue virus was obtained from cloned hybridoma cells secreting the mouse monoclonal antibody (mAb) 4E11. The Fd and light chain antibody genes were amplified by polymerase chain reaction, cloned into the phagemid vector pMad, expressed in bacteria to produce Fab fragments and sequenced. The mAb 4E11, in particular its light chain complementary-determining regions, shared homologies with two other anti-viral mAbs. The affinity of the parental mAb and the cloned Fab to the MalE-E(296-400) fusion protein were shown to be of the same magnitude, i.e. nanomolar. Fab 4E11 neutralization capacity was found between 8 and 4-times or less lower than that of mAb 4E11, depending on serotypes, thus the Fab could have a smaller antiviral activity than the mAb in vitro.

Inhibition of sandfly fever Sicilian virus (Phlebovirus) replication in vitro by antiviral compounds.

Sandfly fever Sicilian virus (SFSV) was used in our laboratory to screen antiviral substances active toward viruses of the Bunyaviridae family. Antiviral activity was estimated by the reduction of the cytopathic effect of SFSV on infected Vero cells. Cytotoxicity was evaluated by determining the inhibition of Trypan blue exclusion. The specificity of action of each tested compound was estimated by the selectivity index (CD50/ED50). Selectivity indices of human recombinant interferon-alpha (IFN alpha) (Roferon and Introna), iota-, kappa- and lambda- carrageenans, fucoidan and 6-azauridine were much higher than that of ribavirin, the only antiviral substance which has been previously investigated for its inhibitory effects on Phlebovirus infections. Other compounds showed significant antiviral activity: glycyrrhizin, suramin sodium, dextran sulphate and pentosan polysulphate. All these compounds caused a concentration-dependent reduction in the virus yield. Ribavirin, 6-azauridine and IFN alpha have been shown to inhibit a late step of the virus replicative cycle, whereas glycyrrhizin and suramin sodium were active at an early step and the sulphated polysaccharides inhibited adsorption of SFSV on the cells. The antiviral compounds selected in this study as specific inhibitors of in vitro replication of SFSV are promising candidates for the chemotherapy of haemorrhagic fevers caused by viruses of the Bunyaviridae family. The combination of IFN alpha and ribavirin, which showed a synergistic antiviral effect, should be evaluated for the treatment of these infections.

[Arbovirus infections. From virus, mosquitoes, animals and humans]. / Arboviroses. Des virus, des moustiques, des animaux et des hommes.

Arboviruses occur throughout the world in plants and animals: reptiles, birds and mammals including man. These relatively recent RNA-containing viruses have great evolutionary potential and are a major cause of epidemics. Arboviruses exhibit a dual life cycle involving continual transmission to and from the vertebrate host and arthropod vector which ingests or inoculates the agent during blood meals. Agents belong to many different viral families and represent an important source of emerging diseases. Because of the mode of transmission is vectorial, spread can enhanced by man-made changes in the ecosystem. This risk is often underestimated. The population explosion provides a great opportunity for the progression of these arboviruses.

Inhibition of the expression of hepatitis A and B viruses (HAV and HBV) proteins by interferon in a human hepatocarcinoma cell line (PLC/PRF/5).

AIMS/METHODS: PLC/PRF/5 is a continuous human hepatocarcinoma cell line whose genome contains integrated HBV DNA and which secretes two of the hepatitis B virus envelope proteins (HBs and PreS2). This line is also susceptible to infection by hepatitis A virus and was therefore used to compare the effects of interferon on protein synthesis of these two viruses and to assess the interactions which occur between them during infection. RESULTS: Results showed that recombinant interferon alpha 2-a inhibited the expression of the two hepatitis B virus envelope antigens (HBs and PreS2) and of the only hepatitis A virus antigen in a dose-dependent fashion. Comparison of the effect of interferon on antigenic protein production of these two viruses, showed stronger inhibition of hepatitis A virus capsid antigen than of hepatitis B virus envelope antigens. Infection with hepatitis A virus also downregulates the expression of the two hepatitis B virus proteins. CONCLUSIONS: Considering the absence of cytotoxic effects from the doses used, this study confirms the relevance of this cellular model for the study of antiviral cytokines in vitro. It also provides a further rationale for the clinical evaluation of the therapeutic potential of interferons in severe hepatitis cases due either to hepatitis A virus alone or to superinfection of hepatitis B virus carriers by hepatitis A virus.

[Multicenter study on the efficacy of Zyrtec (Cetirizine) in the treatment of perennial allergic rhinitis in 875 adolescents]. / Etude multicentrique sur l'efficacité de Zyrtec (Cétirizine) dans le traitement des rhinites allergiques perannuelles de 875 adolescents.

875 adolescents of both sexes, aged between 12 and 15 years, who had presented with a perennial allergic rhinitis, were included in an open study that was conducted by pediatricians and allergologists on the efficacy of ZYRTEC (CETIRIZINE). There were four evaluations in the study, at Day-10, D 0, D15 and D30 and it was conducted according to the following plan: A first period (D-10 to D 0) to establish the eligibility of the subjects to be tested, and to establish the clinical allergic history, before definitive inclusion at D 0. A second period, of therapy, of 30 days, during which the subjects took a 10 mg tablet of ZYRTEC as a daily dose. Efficacy was evaluated at each visit by scores of intensity of major symptoms (sneezing, nasal discharge, nasal obstruction, nasal pruritus) and secondary symptoms (ocular score ... ) of rhinitis, as well as anterior rhinoscopy. The patients made an auto-evaluation of symptoms at different times. Analysis of the different parameters showed a real efficacy of ZYRTEC, for 30 days of treatment, in young patients. Furthermore, the tolerance of the product is excellent. This study has shown an overall improvement in the symptoms of perennial allergic rhinitis in patients who were treated with ZYRTEC in conditions similar to those of usual medical practice by pediatricians and allergologists.

[Fever of unknown origin (FUO) in the camps of Rwandan refugees in the Goma region of in Zaire (September 1994)]. / Les fièvres d'origine indéterminée (FOI) dans les camps de réfugiés rwandais de la région de Goma au Zaïre (septembre 1994).

After the outbreaks of cholera, dysenteriae, meningitidis of which the rwandese refugees have been the victims in August and September 1994 in the camps of the Goma's area (Zaïre), the medical teams were confronted with a great number of fevers of unknown origin. In order to explore the possible etiologies, we have conducted a cases/controls study (n = 96). Clinically, the cases occur more frequently than controls headache (p < 0.001), splenomegaly (p = 0.02) and neutropeny (p < 0.001) Serologically, it has been constated non significantly difference between cases and controls, but prevalence of HIV-1 infections (19 and 6%) and arbovirus (23 and 10%) infections are very high. Arbovirosis could explain, partially or associated with HIV and tuberculosis, the presence of these fevers undeterminated more than malaria or typhus epidemic.

[Multicenter hospital study on the efficacy of Zyrtec (R) (cetirizine) compared to a placebo, in the treatment of perennial allergic rhinitis in 254 adolescents aged 12-15]. / Etude multicentrique hospitalière sur l'efficacité de Zyrtec (cétirizine) comparé à un placebo, dans le traitement des rhinites allergiques perannuelles de 254 adolescents de 12 à 15 ans.

In this multicenter parallel group randomized trial 254 teenagers, aged 12-15, suffering from perennial allergic rhinitis were investigated. Four evaluations (D-10, D0, D15, D30) were performed according to the following design: a 10-day run-in period (D-10, D0) to determine/establish the patient eligibility and to perform an allergologic checkup. The decision to include the patient was made at D0 according to selection criteria. a 30-day treatment period (D0 to D30). The patient received either cetirizine 10 mg once a day or placebo given in a double blind way according to randomization. Efficacy was assessed at each visit with a nasal symptom score (sneezing, rhinorrhea, obstruction, pruritus) and an ocular symptom score (watery eyes, conjunctival pruritus, red eyes). In addition, an objective evaluation was performed by means of anterior rhinoscopy. Global evaluations by the investigator and the patient on visual analog scales were assessed. Side effects were recorded. At baseline there was no significant difference between the two groups. At day 15 and day 30, all symptoms, subjective as well as objective, were significantly improved in the cetirizine group. Tolerance was good with no significant difference between cetirizine and placebo.