Association between MUC1 gene polymorphism and expected progeny differences in Nelore cattle (Bos primigenius indicus)

MUC1 is a heavily glycosylated mammalian transmembrane protein expressed by mucosal secretory tissues for both protection against microbial infection and lubrication. An important characteristic of MUC1 is its variable number of tandem repeats (VNTR) containing several sites for O-glycosylation. VNTR length has been associated with many human diseases and with certain economically important traits in domestic ruminants. The aim of the present study was to correlate the length of MUC1 gene VNTR with expected progeny differences (EPDs) obtained for growth, fertility and carcass traits. Five alleles were identified, with alleles containing short VNTRs being more frequent than those with long, thereby demonstrating that Brazilian Nelore cattle are characterized by high frequencies in short MUC1 VNTRs. Statistical analyses revealed there to be no significant association between VNTR length and EPDs for weight at 120 days (W120 ), scrotal circumference at 365 (SC 365 ) and 450 (SC 450 ) days, age at first calving (AFC), and rib eye area (REA)

North African Influences and Potential Bias in Case-Control Association Studies in the Spanish Population

BACKGROUND: Despite the limited genetic heterogeneity of Spanish populations, substantial evidences support that historical African influences have not affected them uniformly. Accounting for such population differences might be essential to reduce spurious results in association studies of genetic factors with disease. Using ancestry informative markers (AIMs), we aimed to measure the African influences in Spanish populations and to explore whether these might introduce statistical bias in population-based association studies. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 93 AIMs in Spanish (from the Canary Islands and the Iberian Peninsula) and Northwest Africans, and conducted population and individual-based clustering analyses along with reference data from the HapMap, HGDP-CEPH, and other sources. We found significant differences for the Northwest African influence among Spanish populations from as low as ≈ 5% in Spanish from the Iberian Peninsula to as much as ≈ 17% in Canary Islanders, whereas the sub-Saharan African influence was negligible. Strikingly, the Northwest African ancestry showed a wide inter-individual variation in Canary Islanders ranging from 0% to 96%, reflecting the violent way the Islands were conquered and colonized by the Spanish in the XV century. As a consequence, a comparison of allele frequencies between Spanish samples from the Iberian Peninsula and the Canary Islands evidenced an excess of markers with significant differences. However, the inflation of p-values for the differences was adequately controlled by correcting for genetic ancestry estimates derived from a reduced number of AIMs. CONCLUSIONS/SIGNIFICANCE: Although the African influences estimated might be biased due to marker ascertainment, these results confirm that Northwest African genetic footprints are recognizable nowadays in the Spanish populations, particularly in Canary Islanders, and that the uneven African influences existing in these populations might increase the risk for false positives in association studies. Adjusting for population stratification assessed with a few dozen AIMs would be sufficient to control this effect

Treatment of isoniazid-resistant pulmonary tuberculosis

<p>Abstract</p> <p>Background</p> <p>Although resistance to isoniazid (INH) is the most common form of drug resistance seen among <it>Mycobacterium tuberculosis </it>isolates, there have been few studies on the efficacy and optimal duration of treatment for patients with INH-resistant tuberculosis (TB).</p> <p>Methods</p> <p>We evaluated retrospectively the treatment outcomes of 39 patients who were treated for INH-resistant pulmonary TB. The treatment regimens consisted of a 12-month regimen of rifampin (RIF) and ethambutol (EMB), with pyrazinamide (PZA) given during the first 2 months (2HREZ/10RE) (<it>n </it>= 21), a 9-month regimen of RIF and EMB with PZA during the first 2 months (2HREZ/7RE) (<it>n </it>= 5), and a 6-month regimen of RIF, EMB, and PZA (2HREZ/4REZ) (<it>n </it>= 13). After drug susceptibility testing confirmed the INH-resistance of the isolated <it>M. tuberculosis </it>strains, INH was discontinued for all the patients.</p> <p>Results</p> <p>Among the 39 patients, treatment was successfully completed by 36 patients (92%). However, treatment failure occurred, and acquired resistance to other first-line drugs, such as RIF, developed in three patients (8%). Cavitary and bilateral extensive lesions were commonly found in the chest radiographs of the patients who exhibited treatment failure.</p> <p>Conclusion</p> <p>These findings underline the seriousness of concerns regarding treatment failure and the development of multidrug-resistant TB in patients with INH-resistant TB following treatment with recommended regimens.</p

Assessment of nutritional risk among in-school adolescents from Cantabria

Seminario “Promoción de hábitos saludables en adolescentes desde el ámbito educativo”.Objetivo: Evaluar el riesgo nutricional, por edad y sexo, que presentan los adolescentes escolarizados en la Comunidad Autónoma de Cantabria. Sujetos: Se realizó un estudio transversal, analizando una muestra de 1101 adolescentes, de los que 51,6% eran varones y 48,4% fueron mujeres de edades comprendidas entre los 10 y los 17 años, escolarizados en centros de enseñanza pública, mediante el cuestionario Krece Plus. Resultados: Se observa un elevado porcentaje de ado- lescentes que presentan un riesgo nutricional elevado (35%). Los varones presentan un riesgo nutricional alto en un porcentaje ligeramente superior a las mujeres (37,8 % vs 32,1%). Además, el riesgo nutricional alto sufre un notable incremento a medida que la edad de los jóvenes aumenta. Se aprecian diferencias estadísticamente signi- ficativas tanto en los grupos de edad de los varones (p = 0,024), de las mujeres (p < 0,001) como en el grupo global (p = 0,001). En los tres casos, la distribución del riego nutricional en los grupos de menor edad es muy similar (entre 35,2 y 35,8% en los h , entre 27,9 y 29,7% en las m , y entre 31,7 y 32,7% en el grupo total). Mientras que en el grupo de mayor edad estos valores prácticamente se duplican (57,1% en los h , 69,0% en las m , y 62,2 % en el grupo total). Conclusión: Los resultados obtenidos muestran una realidad preocupante debido, principalmente, al elevado porcentaje de adolescentes que presentan un riesgo nutri- cional elevado. Siendo los varones y los adolescentes de mayor edad los sectores en los que este riesgo nutricional elevado es superior.Objective: To analyse nutritional risk, by age and sex, among primary and secondary education adolescents from Cantabria. Methodology: a cross-sectional study was carried out, analysing a sample of 1101 adolescents: 568 (51.6%) were men and 533 (48.4%) were women, aged 12 to 17, attending 16 different primary and secondary education centres in Cantabria, by means of a Krece Plus questionnaire. Results: A high percentage of adolescents with a high nutritional risk (35%) can be observed. Men show a high nutritional risk slightly higher than women (37.8% h vs 32.1% m ). Moreover, the high nutritional risk expe riences a notable increase as young people get older. Significant statistical differences can be seen both in male and female groups, and as a global group. In all three cases, the nutritional risk distribution in the youngest group is very similar (35.2-35.8% in h , 27.9-29.7% in m , 31.7-32.7% in the global group); whereas in elder adolescents, those values are practically doubled (57.1% in h , 69.0% in m , y 62.2% in the global group). Conclusions: Results are alarming mainly given the high percentage of adolescents with a high nutritional risk. Men and older adolescents are the groups in which high nutritional risk is more evident

A Molecular Study on the Prevalence and Virulence Potential of Aeromonas spp. Recovered from Patients Suffering from Diarrhea in Israel

Background: Species of the genus Aeromonas are native inhabitants of aquatic environments and have recently been considered emerging human pathogens. Although the gastrointestinal tract is by far the most common anatomic site from which aeromonads are recovered, their role as etiologic agents of bacterial diarrhea is still disputed. Aeromonas-associated diarrhea is a phenomenon occurring worldwide; however, the exact prevalence of Aeromonas infections on a global scale is unknown. Methodology/Principal Findings: The prevalence and virulence potential of Aeromonas in patients suffering from diarrhea in Israel was studied using molecular methods. 1,033 diarrheal stools were sampled between April and September 2010 and Aeromonas species were identified in 17 (,2%) patients by sequencing the rpoD gene. Aeromonas species identity and abundance was: A. caviae (65%), A. veronii (29%) and Aeromonas taiwanensis (6%). This is the first clinical record of A. taiwanensis as a diarrheal causative since its recent discovery from a wound infection in a patient in Taiwan. Most of the patients (77%) from which Aeromonas species were isolated were negative for any other pathogens. The patients ranged from 1 to 92 years in age. Aeromonas isolates were found to possess different virulence-associated genes: ahpB (88%), pla/ lip/lipH3/apl-1 (71%), act/hlyA/aerA (35%), alt (18%), ast (6%), fla (65%), lafA (41%), TTSS ascV (12%), TTSS ascF-ascG (12%), TTSS-dependent ADP-ribosylating toxins aexU (41%) and aexT (6%) in various combinations. Most of the identified strain

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9–RAGE–NF-κB–JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.We thank all members of the Brain Metastasis Group and A. Chalmers, E. Wagner, O. Fernández-Capetillo, R. Ciérvide and A. Hidalgo for critical discussion of the manuscript; the CNIO Core Facilities for their excellent assistance; and Fox Chase Cancer Center Transgenic Facility for generation of S100A9 mice. We thank EuCOMM repository for providing S100A9 targeted embryonic stem cells. We also thank J. Massagué (MSKCC) for some of the BrM cell lines and M. Bosenberg (Yale) for the YUMM1.1 cell line. Samples from patients included in this study that provided by the Girona Biomedical Research Institute (IDIBGI) (Biobanc IDIBGI, B.0000872) are integrated into the Spanish National Biobanks Network and in the Xarxa de Bancs de Tumors de Catalunya (XBTC) financed by the Pla Director d’Oncologia de Catalunya. All patients consented to the storage of these samples in the biobank and for their use in research projects. This study was funded by MINECO (SAF2017-89643-R) (M.V.), Fundació La Marató de TV3 (201906-30-31-32) (J.B.-B., M.V. and A.C.), Fundación Ramón Areces (CIVP19S8163) (M.V.) and CIVP20S10662 (E.O.P.), Worldwide Cancer Research (19-0177) (M.V. and E.C.-J.M.), Cancer Research Institute (Clinic and Laboratory Integration Program CRI Award 2018 (54545) (M.V.), AECC (Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.), LAB AECC 2019 (LABAE19002VALI) (M.V.), ERC CoG (864759) (M.V.), Portuguese Foundation for Science and Technology (SFRH/bd/100089/2014) (C.M.), Boehringer-Ingelheim Fonds MD Fellowship (L.M.), La Caixa International PhD Program Fellowship-Marie Skłodowska-Curie (LCF/BQ/DI17/11620028) (P.G.-G.), La Caixa INPhINIT Fellowship (LCF/BQ/DI19/11730044) (A.P.-A.), MINECO-Severo Ochoa PhD Fellowship (BES-2017-081995) (L.A.-E.) and an AECC postdoctoral fellowship (POSTD19016PRIE) (N.P.). M.V. is an EMBO YIP member (4053). Additional support was provided by Gertrud and Erich Roggenbuck Stiftung (M.M.), Science Foundation Ireland Frontiers for the Future Award (19/FFP/6443) (L.Y.), Science Foundation Ireland Strategic Partnership Programme, Precision Oncology Ireland (18/SPP/3522) (L.Y.), Breast Cancer Now Fellowship Award with the generous support of Walk the Walk (2019AugSF1310) (D.V.), Science Foundation Ireland (20/FFP-P/8597) (D.V.), Paradifference Foundation (C.F.-T.), “la Caixa” Foundation (ID 100010434) (A.I.), European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement 847648 (CF/BQ/PI20/11760029) (A.I.), Champalimaud Centre for the Unknown (N.S.), Lisboa Regional Operational Programme (Lisboa 2020) (LISBOA01-0145-FEDER-022170) (N.S.), NCI (R01 CA227629; R01 CA218133) (S.I.G.), Fundació Roses Contra el Càncer (J.B.-B.), Ministerio de Universidades FPU Fellowship (FPU 18/00069) (P.T.), MICIN-Agencia Estatal de Investigación Fellowships (PRE2020-093032 and BES-2017-080415) (P.M. and E. Cintado, respectively), Ministerio de Ciencia, Innovación y Universidades-E050251 (PID2019-110292RB-I00) (J.L.T.), FCT (PTDC/MED-ONC/32222/2017) (C.C.F.), Fundação Millennium bcp (C.C.F.), private donations (C.C.F.) and the Foundation for Applied Cancer Research in Zurich (E.L.R. and M.W.)

Prácticas alimentarias de los adolescentes de Cantabria

Objetivo. Analizar determinadas prácticas alimentarias en adolescentes escolarizados en centros de educación pública de Cantabria, participantes en el Proyecto "Promoción de Hábitos Saludables en Adolescentes desde el Ámbito Educativo". Sujetos. Se realizó un estudio transversal, analizando una muestra de 1.101 adolescentes: 568 (51,6%) varones y 533 (48,4%) mujeres, de edades comprendidas entre los 10 y los 17 años, escolarizados en dieciséis centros de enseñanza primaria y secundaria, mediante un cuestionario autocumplimentado. Resultados. Los adolescentes suelen realizar entre cuatro (41,5%) y cinco (31,6%) ingestas diarias. Durante los días de colegio, el 34% emplea entre diez y quince minutos en desayunar, y entre 30 y 35 minutos en comer (33,5%) y cenar (23%). Un elevado porcentaje (49,4%) de adolescentes desayunaba en soledad durante los días lectivos. Las principales ingestas alimenticias se realizan en el hogar. Las bebidas no alcohólicas (53,6%) y los dulces (42%) son los principales destinos de su dinero de bolsillo. En la casi totalidad de los hogares, es la madre la que se encarga de la compra de los alimentos, de la preparación de las comidas y de decidir tanto el almuerzo como la merienda. La pizza (72,6%) y las patatas fritas (70,8%) son los alimentos considerados más ricos entre los analizados, mientras que el perrito caliente (49,4%) y la hamburguesa (48,5%) son considerados como los menos sanos. El 58,6% de los encuestados cena viendo la televisión. Conclusión. En el estudio del comportamiento alimentario es necesario analizar la influencia de otros factores que, en muchas ocasiones, están detrás de las recomendaciones dietéticas y que casi siempre son ignorados. Prácticas alimentarias como las analizadas en el presente estudio, permiten, cuando estas se desarrollan de forma adecuada, una mejora sustancial en la salud alimentaria y nutricional de las personas

Model for screening of resonant magnetic perturbations by plasma in a realistic tokamak geometry and its impact on divertor strike points

This work addresses the question of the relation between strike-point splitting and magnetic stochasticity at the edge of a poloidally diverted tokamak in the presence of externally imposed magnetic perturbations. More specifically, ad-hoc helical current sheets are introduced in order to mimic a hypothetical screening of the external resonant magnetic perturbations by the plasma. These current sheets, which suppress magnetic islands, are found to reduce the amount of splitting expected at the target, which suggests that screening effects should be observable experimentally. Multiple screening current sheets reinforce each other, i.e. less current relative to the case of only one current sheet is required to screen the perturbation.Comment: Accepted in the Proceedings of the 19th International Conference on Plasma Surface Interactions, to be published in Journal of Nuclear Materials. Version 2: minor formatting and text improvements, more results mentioned in the conclusion and abstrac

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate