SHP-1 Associates with Both Platelet-derived Growth Factor Receptor and the p85 Subunit of Phosphatidylinositol 3-Kinase*

The Src homology 2 (SH2)-containing protein tyrosine phosphatase 1, SHP-1, is highly expressed in all hematopoietic cells as well as in many non-hematopoietic cells, particularly in some malignant epithelial cell lines. In hematopoietic cells, SHP-1 negatively regulates multiple cytokine receptor pathways. The precise function and the targets of SHP-1 in non-hematopoietic cells, however, are largely unknown. Here we demonstrate that SHP-1 associates with both the tyrosine-phosphorylated platelet-derived growth factor (PDGF) receptor and the p85 subunit of phosphatidylinositol 3-kinase in MCF-7 and TRMP cells. Through the use of mutant PDGF receptors and performing peptide competition for immunoprecipitation, it was determined that SHP-1 independently associates with the PDGF receptor and p85 and that its N-terminal SH2 domain is directly responsible for the interactions. Overexpression of SHP-1 in TRMP cells transfected with the PDGF receptor markedly inhibited PDGF-induced c-fos promoter activation, whereas the expression of three catalytically inactive SHP-1 mutants increased the c-fos promoter activation in response to PDGF stimulation. These results indicate that SHP-1 might negatively regulate PDGF receptor-mediated signaling in these cells. Identification of the association of SHP-1 with the PDGF receptor and p85 in MCF-7 and TRMP cells furthers our understanding of the function of SHP-1 in non-hematopoietic cells

Kinetics of thermal degradation of carotenoids related to potential of mixture of wheat, cassava and sweet potato flours in baking products

BACKGROUND The consumption of foods such as sweet potato and cassava with high levels of carotenoids is a possible solution to reduce vitamin A deficiency. In this study, we evaluated the kinetics of thermal degradation of carotenoids. The content of carotenoids was quantified by HPLC, first in fresh material, then in flour, and finally in bakery products using mixtures of wheat, sweet potato and cassava. The degree of acceptance of the bakery products by children was also assessed through a sensory acceptance test. RESULTS The study found that the degradation of carotenoids compounds in sweet potato followed first-order kinetics and fit the Arrhenius equation with correlations of R2>0.9. The retention rates of all-trans-β-carotene were 77%, 56% and 48% at the cooking temperatures of 75°, 85° and 95°C respectively, during a cooking time of 20 min. The concentrations of all trans-β-carotene, after baking, for bread, cookies, and cake were 15, 19 and 14 μg/g db, respectively. In the sensory acceptance test carried out in a school, 47.6% of the boys and 79.2% of the girls rated the cookies made from a mixture of cassava, sweet potato, and wheat flour with the indicator, I like it a lot. CONCLUSION The content of carotenoids compounds was reduced by exposure to high temperatures and long cooking times. The combinations of cooking time and temperature which minimized degradation of all-trans-β-carotene occurred at 75°C-20 min and 95°C-10 min. All trans-β-carotene retentions for bread, cookies and cake were 25%, 15% and 11% respectively. The mixture of wheat-sweet potato-cassava flour can be considered in the development of cookies with positive contributions of all trans-β-carotenes and with a good acceptance by children between 9 and 13 years. This article is protected by copyright. All rights reserved

Clinical factors associated with high glycemic variability defined by coefficient of variation in patients with type 2 diabetes

Antecedentes: La Variabilidad Glucémica Alta (VHG) ha convertirse en un predictor más fuerte de hipoglucemia. Sin embargo, aún se desconocen los factores clínicos asociados con el VHG. Objetivo:Determinar las variables clínicas que se asociaron con un coeficiente de variación (CV) superior al 36% evaluado mediante monitorización continua de glucosa (MCG) en un grupo de pacientes con diabetes mellitus. Métodos: Se evaluó una cohorte de pacientes con diabetes tipo 2 (T2D). Se evaluaron variables demográficas, HbA1c, tasa de filtración glomerular (TFG) y régimen de tratamiento. Se realizó un análisis bivariado, para evaluar la asociación entre la variable resultado (CV > 36%) y cada una de las variables independientes. Se construyó un modelo multivariado para evaluar las asociaciones después de controlar las variables de confusión. Resultados:Se analizaron los datos de MCG de 274 pacientes. CV> 36% estuvo presente en 56 pacientes (20,4%). En el análisis bivariado se incluyeron variables demográficas y clínicas, como tiempo desde el diagnóstico, antecedente de hipoglucemia, A1c, FG y tratamiento instaurado. En el análisis multivariante, FG 9% (OR 2,81; IC 1,05,7,51; p:0,04) y antecedentes de hipoglucemia (OR 2,09; IC 1,02, 4,32; p: 0,04) se asociaron con VHG. El tratamiento con iDPP4 (OR 0,39; IC 0,19, 0,82; p: 0,01) y AGLP1 (OR 0,08; IC 0,01, 0,68; p: 0,02) se asoció inversamente con la VG. Conclusión:Variables clínicas como FG 9% y antecedentes de hipoglucemia se asocian a un VG alto. Nuestros datos sugieren que el uso de tecnología y tratamientos capaces de reducir la variabilidad glucémica podría ser útil en esta población para reducir el riesgo de hipoglucemia y mejorar el control glucémico.Q3Background: High glycemic Variability (HGV) has become a stronger predictor of hypoglycemia. However, clinical factors associate with HGV still are unknown. Objective: To determine clinical variables that were associated with a coefficient of variation (CV) above 36% evaluated by continuous glucose monitoring (CGM) in a group of patients with diabetes mellitus. Methods: A cohort of patients with type 2 diabetes (T2D) was evaluated. Demographic variables, HbA1c, glomerular filtration rate (GFR) and treatment regimen were assessed. A bivariate analysis was performed, to evaluate the association between the outcome variable (CV> 36%) and each of the independent variables. A multivariate model was constructed to evaluate associations after controlling for confounding variables. Results: CGM data from 274 patients were analyzed. CV> 36% was present in 56 patients (20.4%). In the bivariate analysis, demographic and clinical variables were included, such as time since diagnosis, hypoglycemia history, A1c, GFR and treatment established. In the multivariate analysis, GFR 9% (OR 2.81; CI 1.05,7.51; p:0.04) and hypoglycemia history (OR 2.09; CI 1.02,4.32; p:0.04) were associated with HGV. Treatment with iDPP4 (OR 0.39; CI 0.19,0.82; p:0.01) and AGLP1 (OR 0.08; CI 0.01,0.68; p:0.02) was inversely associated with GV. Conclusion: Clinical variables such as GFR 9% and a history of hypoglycemia are associated with a high GV. Our data suggest that the use of technology and treatments able to reduce glycemic variability could be useful in this population to reduce the risk of hypoglycemia and to improve glycemic control.Revista Internacional - Indexad

elaboracion de papel vegetal que cumpla las normas tappi para el diseno e impresion a partir de la fibra de la cascara del platano verde

En la presente investigación se elaborará un manual para la elaboración de papel vegetal que cumpla las normas TAPPI para el diseño e impresión a partir de la fibra de la cascara del plátano verde ya que estas técnicas antiguas que inusualmente se usan para la elaboración de papel artesanal han funcionado bien debido a que ha sido destinado para impresión serigrafía o manual que no demanden mayor calidad ni parámetros técnicos de su constitución. Hay que tener en ceunta que la fabricación del papel a mano es una técnica que a pesar de tener miles de años de antigüedad no ha sido explotada adecuadamente y no se consigue papel de buena calidad que pueda reemplazar a los que usamos normalmente. Muchos artesanos hacen papel a mano sin una técnica científica que permita conocer las propiedades de las fibras a utilizar para elaborar papel para imprenta o impresoras comunes. En nuestro caso elaboraremos papel vegetal a partir de la fibra de la cascara del plátano verde que presente las mejores propiedades de formación física y óptica.</p

Growth kinetics and atomistic mechanisms of native oxidation of ZrSx_xSe2−x_{2-x} and MoS2_2 crystals

A thorough understanding of native oxides is essential for designing semiconductor devices. Here we report a study of the rate and mechanisms of spontaneous oxidation of bulk single crystals of ZrS$_x$Se$_{2-x}$ alloys and MoS$_2$. ZrS$_x$Se$_{2-x}$ alloys oxidize rapidly, and the oxidation rate increases with Se content. Oxidation of basal surfaces is initiated by favorable O$_2$ adsorption and proceeds by a mechanism of Zr-O bond switching, that collapses the van der Waals gaps, and is facilitated by progressive redox transitions of the chalcogen. The rate-limiting process is the formation and out-diffusion of SO$_2$. In contrast, MoS$_2$ basal surfaces are stable due to unfavorable oxygen adsorption. Our results provide insight and quantitative guidance for designing and processing semiconductor devices based on ZrS$_x$Se$_{2-x}$ and MoS$_2$, and identify the atomistic-scale mechanisms of bonding and phase transformations in layered materials with competing anions

Differential tumor-targeting abilities of three single-domain antibody formats

The large molecular size of antibody drugs is considered one major factor preventing them from becoming more efficient therapeutics. Variable regions of heavy chain antibodies (HCAbs), or single-domain antibodies (sdAbs), are ideal building blocks for smaller antibodies due to their molecular size and enhanced stability. In the search for better antibody formats for in vivo imaging and/or therapy of cancer, three types of sdAb-based molecules directed against epidermal growth factor receptor (EGFR) were constructed, characterized and tested. Eleven sdAbs were isolated from a phage display library constructed from the sdAb repertoire of a llama immunized with a variant of EGFR. A pentameric sdAb, or pentabody, V2C-EG2 was constructed by fusing one of the sdAbs, EG2, to a pentamerization protein domain. A chimeric HCAb (cHCAb), EG2-hFc, was constructed by fusing EG2 to the fragment crystallizable (Fc) of human IgG1. Whereas EG2 and V2C-EG2 localized mainly in the kidneys after i.v. injection, EG2-hFc exhibited excellent tumor accumulation, and this was largely attributed to its long serum half life, which is comparable to that of IgGs. The moderate size (~80 kDa) and intact human Fc make HCAbs a unique antibody format which may outperform whole IgGs as imaging and therapeutic reagents.Peer reviewed: YesNRC publication: Ye

SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus

Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=462 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples; pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/494 (0%, 95%CI 0-0.7%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19