Genetic and clinical assessment of 2009 pandemic influenza in southern China

Introduction: South China has a proven role in the global epidemiology of previous influenza outbreaks due to its dual seasonal pattern. We present the virologic, genetic and clinical characterization of pandemic H1N1 influenza infection (pH1N1) in Shantou and Nanchang, cities in southern China, during the second wave of the 2009-2010 pandemic. Methodology: Nasopharyngeal swabs were collected from 165 individuals with influenza-like illness (ILI) who presented to the hospitals in Shantou and Nanchang. Laboratory diagnosis and characterization was performed by real-time PCR, virus isolation in embryonated chicken eggs, and sequencing. Results: pH1N1 activity was sustained in three different temporal patterns throughout the study period. The overall positivity rate of pH1N1 was 50% with major distribution among young adults between the ages of 13 and 30 years. High fever, cough, expectoration, chest pain, myalgia, nasal discharge and efficient viral replication were observed as major clinical markers whereas a substantial number of afebrile cases (17%) was also observed. Rate of hospitalization and disease severity (39%) and recovery (100%) were also high within the region. Furthermore, severe complications were likely to develop in young adults upon pH1N1 infection. Genetic characterization of the HA and NA genes of pH1N1 strains exhibited homogenous spread of pH1N1 strains with 99% identity with prototypic strains; however, minor unique mutations were also observed in the HA gene. Conclusion: The study illustrates the detailed characteristics of 2009 influenza pandemic in southern parts of China that might help to strategize preparedness for future pandemics and subsequent influenza seasons.</br

Cosmological Equation of State and Interacting Energies

In this paper we study a model of cosmic evolution, assuming that the different components of the universe could interact between them any time. An effective equation of state (EOS) for the universe has been used as well. A particular function for w, which gives a good agreement between our results and the experimental data, has been studied. Finally, the model obtained has been applied to different important cases

A hypothalamic-thalamostriatal circuit that controls approach-avoidance conflict in rats

Survival depends on a balance between seeking rewards and avoiding potential threats, but the neural circuits that regulate this motivational conflict remain largely unknown. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited during conflict. Inactivation of aPVTCRF neurons during conflict biases animal’s response toward food, whereas activation of these cells recapitulates the food-seeking suppression observed during conflict. aPVTCRF neurons project densely to the nucleus accumbens (NAc), and activity in this pathway reduces food seeking and increases avoidance. In addition, we identified the ventromedial hypothalamus (VMH) as a critical input to aPVTCRF neurons, and demonstrated that VMH-aPVT neurons mediate defensive behaviors exclusively during conflict. Together, our findings describe a hypothalamic-thalamostriatal circuit that suppresses reward-seeking behavior under the competing demands of avoiding threats.Fil: Engelke, D. S.. The University of Texas Health Science Center; Estados UnidosFil: Zhang, X. O.. The University of Texas Health Science Center; Estados UnidosFil: O’Malley, J. J.. The University of Texas Health Science Center; Estados UnidosFil: Fernandez Leon, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. Sede Olavarría del Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aire. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. Sede Olavarría del Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; ArgentinaFil: Li, S.. University of Manitoba; CanadáFil: Kirouac, G. J.. University of Manitoba; CanadáFil: Beierlein, M.. The University of Texas Health Science Center; Estados UnidosFil: Do Monte, F. H.. The University of Texas Health Science Center; Estados Unido

Induction of Fas mediated caspase-8 independent apoptosis in immune cells by <i>Armigeres subalbatus</i> saliva

Background It is widely recognized that the introduction of saliva of bloodsucking arthropods at the site of pathogen transmission might play a central role in vector-borne infections. However, how the interaction between salivary components and the host immune system takes place and which physiological processes this leads to has yet to be investigated. Armigeres subalbatus is one of the prominent types of mosquitoes involved in the transmission of parasitic and viral diseases in humans and animals. Methodology/Principal Findings Using murine peritoneal macrophages and lymphocytes, and human peripheral mononuclear cells (PBMCs), this study shows that saliva of the female Ar. subalbatus induces apoptosis via interaction with the Fas receptor within a few hours but without activating caspase-8. The process further activates downstream p38 MAPK signaling, a cascade that leads to the induction of apoptosis in capase-3 dependent manner. We further illustrate that Ar. subalbatus saliva suppresses proinflammatory cytokines without changing IL-10 levels, which might happen as a result of apoptosis. Conclusions Our study shows for the first time that saliva-induced apoptosis is the leading phenomenon exerted by Ar. subalbatus that impede immune cells leading to the suppression of their effecter mechanism.</br

Telomere Lengths, Pulmonary Fibrosis and Telomerase (<i>TERT</i>) Mutations

Background: Telomerase is an enzyme that catalyzes the addition of nucleotides on the ends of chromosomes. Rare loss of function mutations in the gene that encodes the protein component of telomerase (TERT) have been described in patients with idiopathic pulmonary fibrosis (IPF). Here we examine the telomere lengths and pulmonary fibrosis phenotype seen in multiple kindreds with heterozygous TERT mutations.Methods and Findings: We have identified 134 individuals with heterozygous TERT mutations from 21 unrelated families. Available medical records, surgical lung biopsies and radiographs were evaluated retrospectively. Genomic DNA isolated from circulating leukocytes has been used to measure telomere lengths with a quantitative PCR assay. We find that telomere lengths of TERT mutation carriers decrease in an age-dependent manner and show progressive shortening with successive generations of mutation inheritance. Family members without TERT mutations have a shorter mean telomere length than normal, demonstrating epigenetic inheritance of shortened telomere lengths in the absence of an inherited TERT mutation. Pulmonary fibrosis is an age-dependent phenotype not seen in mutation carriers less than 40 years of age but found in 60% of men 60 years or older; its development is associated with environmental exposures including cigarette smoking. A radiographic CT pattern of usual interstitial pneumonia (UIP), which is consistent with a diagnosis of IPF, is seen in 74% of cases and a pathologic pattern of UIP is seen in 86% of surgical lung biopsies. Pulmonary fibrosis associated with TERT mutations is progressive and lethal with a mean survival of 3 years after diagnosis. Overall, TERT mutation carriers demonstrate reduced life expectancy, with a mean age of death of 58 and 67 years for males and females, respectively.Conclusions: A subset of pulmonary fibrosis, like dyskeratosis congenita, bone marrow failure, and liver disease, represents a “telomeropathy” caused by germline mutations in telomerase and characterized by short telomere lengths. Family members within kindreds who do not inherit the TERT mutation have shorter telomere lengths than controls, demonstrating epigenetic inheritance of a shortened parental telomere length set-point.</p

Challenges associated with biomarker-based classification systems for Alzheimer's disease

Altres ajuts: This work was also supported by research grants from the Carlos III Institute of Health, Spain and the CIBERNED program (Program 1, Alzheimer Disease to Alberto Lleó and SIGNAL study, www.signalstudy.es), partly funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, "Una manera de hacer Europa". This work has also been supported by a "Marató TV3" grant (20141210 to Juan Fortea and 044412 to Rafael Blesa) and by Generalitat de Catalunya and a grant from the Fundació Bancaria La Caixa to Rafael Blesa. I. Illán-Gala is supported by the i-PFIS grant from the FIS, Instituto de Salud Carlos III and the Rio Hortega grant (CM17/00074) from "Acción estratégica en Salud 2013-2016" and the European Social Fund. USPHS NIH grants awarded to M.J.d.L. include: AG13616, AG022374, AG12101, and AG057570.We aimed to evaluate the consistency of the A/T/N classification system. We included healthy controls, mild cognitive impairment, and dementia patients from Alzheimer's disease Neuroimaging Initiative. We assessed subject classification consistency with different biomarker combinations and the agreement and correlation between biomarkers. Subject classification discordance ranged from 12.2% to 44.5% in the whole sample; 17.3%-46.4% in healthy controls; 11.9%-46.5% in mild cognitive impairment, and 1%-35.7% in dementia patients. Amyloid, but not neurodegeneration biomarkers, showed good agreement both in the whole sample and in the clinical subgroups. Amyloid biomarkers were correlated in the whole sample, but not along the Alzheimer's disease continuum (as defined by a positive amyloid positron emission tomography). Neurodegeneration biomarkers were poorly correlated both in the whole sample and along the Alzheimer's disease continuum. The relationship between biomarkers was stage-dependent. Our findings suggest that the current A/T/N classification system does not achieve the required consistency to be used in the clinical setting

Adaptation of water resources systems to changing society and environment: a statement by the International Association of Hydrological Sciences

Hydrol. Sci. J.-J. Sci. Hydrol.ISI Document Delivery No.: EB2CDTimes Cited: 0Cited Reference Count: 153Ceola, Serena Montanari, Alberto Krueger, Tobias Dyer, Fiona Kreibich, Heidi Westerberg, Ida Carr, Gemma Cudennec, Christophe Elshorbagy, Amin Savenije, Hubert Van der Zaag, Pieter Rosbjerg, Dan Aksoy, Hafzullah Viola, Francesco Petrucci, Guido MacLeod, Kit Croke, Barry Ganora, Daniele Hermans, Leon Polo, Maria J. Xu, Zongxue Borga, Marco Helmschrot, Jorg Toth, Elena Ranzi, Roberto Castellarin, Attilio Hurford, Anthony Brilly, Mitija Viglione, Alberto Bloeschl, Guenter Sivapalan, Murugesu Domeneghetti, Alessio Marinelli, Alberto Di Baldassarre, GiulianoPeople Programme (Marie Curie Actions) of the European Union [329762]; IRI THESys; German Excellence Initiative; EU [603587]IW acknowledges the support of the People Programme (Marie Curie Actions) of the European Union's 7th Framework Programme FP7/2007-2013/(grant agreement no. 329762). TK is funded, through IRI THESys, by the German Excellence Initiative. SC, AM, AC, and ET acknowledge financial support from the EU funded project SWITCHON (603587).Taylor & francis ltdAbingdonWe explore how to address the challenges of adaptation of water resources systems under changing conditions by supporting flexible, resilient and low-regret solutions, coupled with on-going monitoring and evaluation. This will require improved understanding of the linkages between biophysical and social aspects in order to better anticipate the possible future co-evolution of water systems and society. We also present a call to enhance the dialogue and foster the actions of governments, the international scientific community, research funding agencies and additional stakeholders in order to develop effective solutions to support water resources systems adaptation. Finally, we call the scientific community to a renewed and unified effort to deliver an innovative message to stakeholders. Water science is essential to resolve the water crisis, but the effectiveness of solutions depends, inter alia, on the capability of scientists to deliver a new, coherent and technical vision for the future development of water systems

Heterogeneous virulence of pandemic 2009 influenza H1N1 virus in mice

Background Understanding the pathogenesis of influenza infection is a key factor leading to the prevention and control of future outbreaks. Pandemic 2009 Influenza H1N1 infection, although frequently mild, led to a severe and fatal form of disease in certain cases that make its virulence nature debatable. Much effort has been made toward explaining the determinants of disease severity; however, no absolute reason has been established. Results This study presents the heterogeneous virulence of clinically similar strains of pandemic 2009 influenza virus in human alveolar adenocarcinoma cells and mice. The viruses were obtained from patients who were admitted in a local hospital in China with a similar course of infection and recovered. The A/Nanchang/8002/2009 and /Nanchang/8011/2009 viruses showed efficient replication and high lethality in mice while infection with A/Nanchang/8008/2009 was not lethal with impaired viral replication, minimal pathology and modest proinflammatory activity in lungs. Sequence analysis displayed prominent differences between polymerase subunits (PB2 and PA) of viral genomes that might correlate with their different phenotypic behavior. Conclusions The study confirms that biological heterogeneity, linked with the extent of viral replication, exists among pandemic H1N1 strains that may serve as a benchmark for future investigations on influenza pathogenesis.</br

Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza

Abstract Introduction Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. Methods We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. Results Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. Conclusions While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness