Análise composicional da pupa do bicho-da-seda (Bombyx mori L.)

The sericulture in Cauca department is a constant dynamic looking for strengthening different tiers of its productive chain. In the process of winding the cocoon, the pupa of the silkworm is generated as a by-product, which has not been accurately exploited. In order to evaluate the pupa and silkworm meal, as alternative sources to include in diets for animal nutrition, the compositional analysis was made from dry matter (%MSA), humidity (%HR), ash (%CNZ), crude protein (%PB), ether extract (%EE), chitin (%QTN) and in vitro digestibility of dry matter (% DivMS). For this purpose, we used fresh pupae (PGS) and pupal meal (PGSh), supplied by CORSEDA's farmers. The dry base results showed values of PB 50,05 and 51,73%; EE 41,36 and 37,62%; QTN 2,47 and 5,49%, for pupa and meal respectively. In terms of the digestibility of the dry matter, the pupa had a better performance with 84,73 against 77,45% corresponding to meal. The nutritional profile of the fresh pupa and meal allowed to determine that they are potential raw materials to be used in the formulation of balanced food for the animal industry.La sericultura en el Departamento del Cauca se encuentra en una dinámica constante que busca fortalecer distintos eslabones de su cadena productiva. En el proceso de devanado del capullo se genera la pupa de gusano de seda como subproducto, el cual no es aprovechado de manera eficiente. Con el objeto de evaluar la pupa y harina de gusano de seda, como fuentes alternativas de inclusión en dietas para la nutrición animal, se realizó el análisis composicional de materia seca (%MSA), humedad (%HR), cenizas (%CNZ), proteína bruta (%PB), extracto etéreo (%EE), quitina (%QTN) y la digestibilidad in vitro de la materia seca (%DivMS). Para ello, se utilizaron pupas frescas (PGS) y harina de pupa (PGSh), suministradas por sericultores asociados a CORSEDA. Los resultados efectuados en base seca arrojaron valores de PB de 50,05 y 51,73%; EE  41,36 y 37,62%; QTN 2,47 y 5,49%, para pupa y harina respectivamente. En términos de la digestibilidad de la materia seca, la pupa tuvo un mejor comportamiento con 84,73 contra 77,45% respecto a la harina. El perfil nutricional de la pupa fresca y la harina permitió determinar que son materias primas potenciales para ser utilizadas en la formulación de balanceados para la industria animal.A sericultura no Departamento de Cauca, está em constante dinâmica em busca do fortalecimento de diferentes elos de sua cadeia produtiva. No processo de enrolamento do casulo, a pupa do bicho-da-seda é gerada como um subproduto, que não é usado de forma eficiente. A fim de avaliar a pupa de bicho da seda e farinha, como fontes alternativas para inclusão em dietas de alimentos para animais, a análise da composição foi realizada: matéria seca (%MSA), humidade (%HR), cinzas (%CNZ), proteína bruta (%PB), extrato etéreo (%EE), quitina (%QTN) e digestibilidade in vitro da matéria seca (%DivMS). Para este propósito, pupas frescas (PGS) e farelo de pupa (PGSh) foram usadas, fornecidas pelos agricultores da CORSEDA. Os resultados da base seca mostraram valores de PB de 50,05 e 51,73%; EE 41,36 e 37,62%; QTN 2,47 e 5,49%, para pupa e farinha, respectivamente. Em termos de digestibilidade da matéria seca, a pupa teve um melhor desempenho com 84,73 contra 77,45% com relação à farinha. O perfil nutricional das pupas e farinhas frescas, permite determinar que são matérias-primas potenciais, a serem utilizadas na formulação de balanceamento para a indústria animal

IGF1R signaling induces epithelial-mesenchymal plasticity via ITGAV in cutaneous carcinoma

BackgroundEarly cutaneous squamous cell carcinomas (cSCCs) generally show epithelial differentiation features and good prognosis, whereas advanced cSCCs present mesenchymal traits associated with tumor relapse, metastasis, and poor survival. Currently, the mechanisms involved in cSCC progression are unclear, and the established markers are suboptimal for accurately predicting the clinical course of the disease.MethodsUsing a mouse model of cSCC progression, expression microarray analysis, immunofluorescence and flow cytometry assays, we have identified a prognostic biomarker of tumor relapse, which has been evaluated in a cohort of cSCC patient samples. Phosphoproteomic analysis have revealed signaling pathways induced in epithelial plastic cancer cells that promote epithelial-mesenchymal plasticity (EMP) and tumor progression. These pathways have been validated by genetic and pharmacological inhibition assays.ResultsWe show that the emergence of epithelial cancer cells expressing integrin alpha V (ITGAV) promotes cSCC progression to a mesenchymal state. Consistently, ITGAV expression allows the identification of patients at risk of cSCC relapse above the currently employed clinical histopathological parameters. We also demonstrate that activation of insulin-like growth factor-1 receptor (IGF1R) pathway in epithelial cancer cells is necessary to induce EMP and mesenchymal state acquisition in response to tumor microenvironment-derived factors, while promoting ITGAV expression. Likewise, ITGAV knockdown in epithelial plastic cancer cells also blocks EMP acquisition, generating epithelial tumors.ConclusionsOur results demonstrate that ITGAV is a prognostic biomarker of relapse in cSCCs that would allow improved patient stratification. ITGAV also collaborates with IGF1R to induce EMP in epithelial cancer cells and promotes cSCC progression, revealing a potential therapeutic strategy to block the generation of advanced mesenchymal cSCCs.Graphical AbstractDuring cSCC progression, cancer cells evolve from the epithelial to the mesenchymal state, which is associated with poor prognosis. The current investigation reveals that, at intermediate cSCC stages (MD/PD-SCC), epithelial cancer cells activate IGF1R and ITGAV signaling to acquire EMP and progress to the aggressive mesenchymal state in response to TME-derived factors. In addition, ITGAV allows the identification of these epithelial plastic cancer cells and functions as a prognostic biomarker of tumor relapse

Genetic Ancestry, Social Classification, and Racial Inequalities in Blood Pressure in Southeastern Puerto Rico

The role of race in human genetics and biomedical research is among the most contested issues in science. Much debate centers on the relative importance of genetic versus sociocultural factors in explaining racial inequalities in health. However, few studies integrate genetic and sociocultural data to test competing explanations directly.We draw on ethnographic, epidemiologic, and genetic data collected in Southeastern Puerto Rico to isolate two distinct variables for which race is often used as a proxy: genetic ancestry versus social classification. We show that color, an aspect of social classification based on the culturally defined meaning of race in Puerto Rico, better predicts blood pressure than does a genetic-based estimate of continental ancestry. We also find that incorporating sociocultural variables reveals a new and significant association between a candidate gene polymorphism for hypertension (alpha(2C) adrenergic receptor deletion) and blood pressure.This study addresses the recognized need to measure both genetic and sociocultural factors in research on racial inequalities in health. Our preliminary results provide the most direct evidence to date that previously reported associations between genetic ancestry and health may be attributable to sociocultural factors related to race and racism, rather than to functional genetic differences between racially defined groups. Our results also imply that including sociocultural variables in future research may improve our ability to detect significant allele-phenotype associations. Thus, measuring sociocultural factors related to race may both empower future genetic association studies and help to clarify the biological consequences of social inequalities

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Genome-wide association of multiple complex traits in outbred mice by ultra low-coverage sequencing

The authors wish to acknowledge excellent technical assistance from A. Kurioka, L. Swadling, C. de Lara, J. Ussher, R. Townsend, S. Lionikaite, A.S. Lionikiene, R. Wolswinkel and I. van der Made. We would like to thank T.M. Keane and A.G. Doran for their help in annotating variants and adding the FVB/NJ strain to the MGP. We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics and the Wellcome Trust Sanger Institute for the generation of the sequencing data. This work was funded by Wellcome Trust grant 090532/Z/09/Z (J.F.). Primary phenotyping of the mice was supported by the Mary Lyon Centre and Mammalian Genetics Unit (Medical Research Council, UK Hub grant G0900747 91070 and Medical Research Council, UK grant MC U142684172). D.A.B. acknowledges support from NIH R01AR056280. The sleep work was supported by the state of Vaud (Switzerland) and the Swiss National Science Foundation (SNF 14694 and 136201 to P.F.). The ECG work was supported by the Netherlands CardioVascular Research Initiative (Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organization for Health Research and Development and the Royal Netherlands Academy of Sciences) PREDICT project, InterUniversity Cardiology Institute of the Netherlands (ICIN; 061.02; C.A.R. and C.R.B.). N.C. is supported by the Agency of Science, Technology and Research (A*STAR) Graduate Academy. R.W.D. is supported by a grant from the Wellcome Trust (097308/Z/11/Z).Peer reviewedPostprin

Análisis composicional de la pupa de gusano de seda (Bombyx mori L.)

La sericultura en el Departamento del Cauca se encuentra en una dinámica constante que busca fortalecer distintos eslabones de su cadena productiva. En el proceso de devanado del capullo se genera la pupa de gusano de seda como subproducto, el cual no es aprovechado de manera eficiente. Con el objeto de evaluar la pupa y harina de gusano de seda, como fuentes alternativas de inclusión en dietas para la nutrición animal, se realizó el análisis composicional de materia seca (%MSA), humedad (%HR), cenizas (%CNZ), proteína bruta (%PB), extracto etéreo (%EE), quitina (%QTN) y la digestibilidad in vitro de la materia seca (%DivMS). Para ello, se utilizaron pupas frescas (PGS) y harina de pupa (PGSh), suministradas por sericultores asociados a CORSEDA. Los resultados efectuados en base seca arrojaron valores de PB de 50,05 y 51,73%; EE 41,36 y 37,62%; QTN 2,47 y 5,49%, para pupa y harina respectivamente. En términos de la digestibilidad de la materia seca, la pupa tuvo un mejor comportamiento con 84,73 contra 77,45% respecto a la harina. El perfil nutricional de la pupa fresca y la harina permitió determinar que son materias primas potenciales para ser utilizadas en la formulación de balanceados para la industria anima

Oxidation of commercial (a-type) zein with hydrogen peroxide improves its hydration and dramatically increases dough extensibility even below its glass transition temperature

To improve the rheological properties of zein doughs, a-type zein and zein-starch doughs were prepared with the oxidising agents, hydrogen peroxide and peroxidase, which strengthen gluten-based doughs by cross-linking. Hydrogen peroxide and peroxidase increased zein dough extensibility compared to preparation with water. Hydrogen peroxide prepared zein doughs were extensible and cohesive below zein's glass transition temperature. The doughs did not exude water and maintained flexibility when stored. Confocal laser scanning microscopy revealed that in zein-starch doughs prepared with hydrogen peroxide a thin continuous zein matrix was formed around the starch granules, whereas doughs prepared with water exhibited clumps of granules. SDS-PAGE of zein doughs and films treated with the oxidising agents showed no evidence of zein polymerisation, nor did Fourier transform infrared spectrometry reveal any significant changes in secondary structure. Further, hydrogen peroxide treatment did not increase zein film glass transition temperature, but it did increase transition enthalpy, and film water uptake increased with hydrogen peroxide concentration. The greatly increased extensibility of hydrogen peroxide prepared zein doughs and their improved water-holding are not due to oxidative cross-linking. It is proposed that the effects are primarily due to hydroxylation of amino acid aliphatic side chains, improving hydration through hydrogen bonding

Discovery and validation of a personalised risk predictor for incident tuberculosis in low transmission settings

The risk of tuberculosis (TB) is variable among individuals with latent Mycobacterium tuberculosis infection (LTBI), but validated estimates of personalized risk are lacking. In pooled data from 18 systematically identified cohort studies from 20 countries, including 80,468 individuals tested for LTBI, 5-year cumulative incident TB risk among people with untreated LTBI was 15.6% (95% confidence interval (CI), 8.0–29.2%) among child contacts, 4.8% (95% CI, 3.0–7.7%) among adult contacts, 5.0% (95% CI, 1.6–14.5%) among migrants and 4.8% (95% CI, 1.5–14.3%) among immunocompromised groups. We confirmed highly variable estimates within risk groups, necessitating an individualized approach to risk stratification. Therefore, we developed a personalized risk predictor for incident TB (PERISKOPE-TB) that combines a quantitative measure of T cell sensitization and clinical covariates. Internal–external cross-validation of the model demonstrated a random effects meta-analysis C-statistic of 0.88 (95% CI, 0.82–0.93) for incident TB. In decision curve analysis, the model demonstrated clinical utility for targeting preventative treatment, compared to treating all, or no, people with LTBI. We challenge the current crude approach to TB risk estimation among people with LTBI in favor of our evidence-based and patient-centered method, in settings aiming for pre-elimination worldwide