Cluster analysis of Iberian, Duroc and crossed pigs

Ponencia publicada en ITEA, vol.104En este estudio se utilizaron datos reales de individuos Ibéricos y Duroc, así como individuos simulados para generar una F1 y los retrocruces respectivos de Ibérico y de Duroc. Se evaluó la capacidad de tres métodos de agrupamiento para distinguir entre estas cinco poblaciones. Los resultados indican que los métodos de agrupamiento evaluados no detectan la partición óptima. En parte el problema se debe a la distinta configuración genética de diferentes variedades (estirpes) de la raza Ibérica que los métodos son capaces de detectar e interfieren en la separación entre individuos puros y cruzados.In this study real data from Iberian and Duroc individuals were used, as well as simulated F1, Iberian and Duroc backcrossed individuals. The ability of three clustering methods to separate the five populations was evaluated. Results indicate that the clustering methods do not detect the optimal partition. The problem is, in part, due to the different genetic configurations of the different strains of Iberian pigs that the methods can detect and, therefore, interfering in the separation between pure and crossed individual

An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis

Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (M. tuberculosis), is a major cause of morbidity and mortality worldwide and efforts to control TB are hampered by difficulties with diagnosis, prevention and treatment 1,2. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease, but current tests cannot identify which individuals will develop disease 3. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines 4,5. We identified a whole blood 393 transcript signature for active TB in intermediate and high burden settings, correlating with radiological extent of disease and reverting to that of healthy controls following treatment. A subset of latent TB patients had signatures similar to those in active TB patients. We also identified a specific 86-transcript signature that discriminated active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-γ and Type I IFNαβ signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis, suggest that this TB signature reflects both changes in cellular composition and altered gene expression. Although an IFN signature was also observed in whole blood of patients with Systemic Lupus Erythematosus (SLE), their complete modular signature differed from TB with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto under-appreciated role of Type I IFNαβ signalling in TB pathogenesis, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series

Background Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. Methods In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms “RSV”, “respiratory syncytial virus”, or “respiratory syncytial viral” combined with “mortality”, “fatality”, “death”, “died”, “deaths”, or “CFR” for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. Findings We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3–11·0) in low-income or lower middle-income countries, 4·0 years (2·0–10·0) in upper middle-income countries, and 7·0 years (3·6–16·8) in high-income countries. Interpretation This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries

Yellowtail flounder, redfish (Sebastes spp.) and witch flounder indices from the Spanish Survey conducted in Divisions 3NO of the NAFO Regulatory Area

Since 1995, Spain carries out a spring stratified random bottom trawl survey in Div. 3NO of the NAFO Regulatory Area. Total mean catches, biomass and mean numbers for yellowtail flounder (Limanda ferruginea) are presented for the period 1995-2017, for redfish (Sebastes spp.) for the period 1997-2017 and for witch flounder (Glyptocephalus cynoglossus) for the period 2002-2017. Detailed indices are presented from 2013. Yellowtail flounder indices do not show a clear trend. Biomass increased from 1997 to 1999 and then remained almost constant throughout all the period, decreasing slightly in 2014-2017. The 2017 value is the lowest since 1998. Redfish indices oscillate greatly over time, probably because the gear does not sample adequately aggregating pelagic species. There was a sharp increase in 2009 and since then until 2015, biomass fluctuated maintaining higher values than before 2009. In 2016 biomass dropped and increase again in 2017 to the 2012 level. The 3N division comprises around the 90% of the total biomass in the last years. Good year classes have not been registered recently. Witch flounder is very scarce and its indices fluctuated throughout the series reaching the minimum value in 2014 and increasing since 2015. 2017 value is among the highest in the series. Recruitment was quite good at the beginning of the series but poor in recent year

Bronchiolitis: an update on management and prophylaxis.

Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children less than 2 years of age in the UK. Respiratory syncytial virus is the most common virus associated with bronchiolitis and has the highest disease severity, mortality and cost. Bronchiolitis is generally a self-limiting condition, but can have serious consequences in infants who are very young, premature, or have underlying comorbidities. Management of bronchiolitis in the UK is guided by the National Institute for Health and Care Excellence (2015) guidance. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Pharmacological interventions including nebulized bronchodilators, steroids and antibiotics generally have limited or no evidence of efficacy and are not advised by National Institute of Health and Care Excellence. Antiviral therapeutics remain in development. As treatments are limited, there have been extensive efforts to develop vaccines, mainly targeting respiratory syncytial virus. At present, the only licensed product is a monoclonal antibody for passive immunisation. Its cost restricts its use to those at highest risk. Vaccines for active immunisation of pregnant women and young infants are also being developed

Motavizumab, A Neutralizing Anti-Respiratory Syncytial Virus (Rsv) Monoclonal Antibody Significantly Modifies The Local And Systemic Cytokine Responses Induced By Rsv In The Mouse Model

Motavizumab (MEDI-524) is a monoclonal antibody with enhanced neutralizing activity against RSV. In mice, motavizumab suppressed RSV replication which resulted in significant reduction of clinical parameters of disease severity. We evaluated the effect of motavizumab on the local and systemic immune response induced by RSV in the mouse model. Balb/c mice were intranasally inoculated with 106.5 PFU RSV A2 or medium. Motavizumab was given once intraperitoneally (1.25 mg/mouse) as prophylaxis, 24 h before virus inoculation. Bronchoalveolar lavage (BAL) and serum samples were obtained at days 1, 5 (acute) and 28 (long-term) post inoculation and analyzed with a multiplex assay (Beadlyte Upstate, NY) for simultaneous quantitation of 18 cytokines: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, KC (similar to human IL-8), IL-10, IL-12p40, IL-12p70, IL-13, IL-17, TNF-α, MCP-1, RANTES, IFN-γ and GM-CSF. Overall, cytokine concentrations were lower in serum than in BAL samples. By day 28, only KC was detected in BAL specimens at low concentrations in all groups. Administration of motavizumab significantly reduced (p < 0.05) BAL concentrations of IL-1α, IL-12p70 and TNF-α on day 1, and concentrations of IFN-γ on days 1 and 5 compared with RSV-infected untreated controls. In the systemic compartment, the concentrations of IL-10, IFN-γ and KC were significantly reduced in the motavizumab-treated mice compared with the untreated controls. In summary, prophylactic administration of motavizumab was associated with significant reductions on RSV replication and concentrations of cytokine and chemokines, which are likely related to the improvement observed in clinical markers of disease severity

Cross-Serotype Immunity Induced by Immunization with a Conserved Rhinovirus Capsid Protein

Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2) capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine

Results for Greenland halibut, American plaice and Atlantic cod of the Spanish survey in NAFO Div. 3NO for the period 1997-2019

Greenland halibut (Reinhardtius hippoglossoides), American plaice (Hippoglossoides platessoides) and Atlantic cod (Gadus morhua) indices from the bottom trawl survey that Spain carries out in Spring since 1995 in Div. 3NO of the NAFO Regulatory Area are presented. Biomass, stratified mean catches and mean number per tow for the three species are presented since 1997, year in which the survey extended the depth strata. Mean catch per tow, length distribution and age distribution (this last except for American plaice) are presented for the last five years (2015-2019). Greenland halibut biomass and abundance estimates presented a decreasing trend since 1999, cut in 2007- 2009 with a high increase. In 2011 the biomass drops under the 2008 value, being stable since then until 2014 with a slight increase in 2015-2019 comprising a big increase in 2017, reaching the maximum of the series. In last years it can be seen a presence of juveniles, mainly in 2004, but the greatest lengths have failed, although in 2009 there is a quite good presence of individuals of ages 6-7 and in 2010 between 5-7. In 2011-2019 the presence of all ages is poor. In 2018 the mode was at 1-2 years, and 2-3 years in 2019, suggesting a fairly strong 2017 cohort. For American plaice we can see a slightly increasing trend from 1999 to 2015, reaching a maximum of mean catch and number in 2006, and a severe decline since 2016, being the 2019 the lowest value of the entire series. The greatest recruitment in the presented series occurred in 2004 and we can follow their mode along the years. No good recruitments were seen since then. In last years the level of all the ages is low. No 2019 age indices are available at this moment. For Atlantic cod, it can be seen a low biomass until 2008, being higher and variable since then, reaching a historical maximum in 2014. From 2015, biomass decreased reaching in 2019 poor values at the level of the 2005 biomass. In 2007-2008 the youngest length classes were much over the rest of the length classes. With the 2006 cohort the series reaches the maximum number of its historical values at five years in 2011. There have been no good recruitments since 2009, although in 2015 and 2016 a discrete presence of individuals of age 1 can be seen

QTL detection for Aeromonas salmonicida resistance related traits in turbot (Scophthalmus maximus)

<p>Abstract</p> <p>Background</p> <p>Interactions between fish and pathogens, that may be harmless under natural conditions, often result in serious diseases in aquaculture systems. This is especially important due to the fact that the strains used in aquaculture are derived from wild strains that may not have had enough time to adapt to new disease pressures. The turbot is one of the most promising European aquaculture species. Furunculosis, caused by the bacterium <it>Aeromonas salmonicida</it>, produces important losses to turbot industry. An appealing solution is to achieve more robust broodstock, which can prevent or diminish the devastating effects of epizooties. Genomics strategies have been developed in turbot to look for candidate genes for resistance to furunculosis and a genetic map with appropriate density to screen for genomic associations has been also constructed. In the present study, a genome scan for QTL affecting resistance and survival to <it>A. salmonicida </it>in four turbot families was carried out. The objectives were to identify consistent QTL using different statistical approaches (linear regression and maximum likelihood) and to locate the tightest associated markers for their application in genetic breeding strategies.</p> <p>Results</p> <p>Significant QTL for resistance were identified by the linear regression method in three linkage groups (LGs 4, 6 and 9) and for survival in two LGs (6 and 9). The maximum likelihood methodology identified QTL in three LGs (5, 6 and 9) for both traits. Significant association between disease traits and genotypes was detected for several markers, some of them explaining up to 17% of the phenotypic variance. We also identified candidate genes located in the detected QTL using data from previously mapped markers.</p> <p>Conclusions</p> <p>Several regions controlling resistance to <it>A. salmonicida </it>in turbot have been detected. The observed concordance between different statistical methods at particular linkage groups gives consistency to our results. The detected associated markers could be useful for genetic breeding strategies. A finer mapping will be necessary at the detected QTL intervals to narrow associations and around the closely associated markers to look for candidate genes through comparative genomics or positional cloning strategies. The identification of associated variants at specific genes will be essential, together with the QTL associations detected in this study, for future marker assisted selection programs.</p