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Abstract:  According to recent studies, chlorophyll has a potential antioxidant effect, which prevents non-communicable diseases. This study aimed to determine the antioxidant capacity of home-made juice made from a combination of spinach (Spinacia oleracea), chard (Beta vulgaris subsp. cicla) and kiwifruit (Actinidia deliciosa). The aim of this analysis was to elaborate artisanal juice with a high chlorophyll content and antioxidant capacity, suitable for consumption and sensory acceptable, based on spinach, chard and kiwifruit. This was an empirical, simple descriptive, cross-sectional study. The chlorophyll content (Hansmann spectrophotometric method), the total antioxidant capacity (stable radical scavenging (DPPH)) and the fiber (AOAC 985.29) of the juice produced were analyzed. Acceptability was assessed through sensory evaluation using a descriptive test with a hedonic scale to evaluate quality, taking into account the features color, taste, odor and texture. Two samples were produced: one pasteurized and one unpasteurized, so as to determine which one had a higher chlorophyll content and antioxidant capacity. A statistical Z-test with a confidence level of 95 % was used to determine whether the product is sensory acceptable, using Epidat software. The following results were obtained: regarding the unpasteurized juice, a chlorophyll content of 95.81 mg/L (+/- 3.4), antioxidant capacity of 84.56 (% inhibition) (+/- 2.13); concerning the pasteurized juice, 103.22 mg/L (+/- 1.59) of chlorophyll and 96.52 (% inhibition) (+/-0.74) of antioxidant capacity. The fiber content in the pasteurized juice was 1.4 g/ % fiber. According to sensory evaluation, 81 % of untrained judges accepted the product. It was possible to conclude that the beverage prepared, according to its proportions, presents favorable physicochemical and sensory characteristics. In this type of new beverages, the conjugation of the beneficial properties of the mixtures of spinach, chard and kiwifruit, with a higher percentage of absorption and bioavailability due to the absence of inhibitors is interesting, and it can be used as an adjuvant in the effective treatment of non-communicable diseases.Resumen:  Investigaciones actuales refieren que la clorofila tiene un potencial efecto antioxidante, previniendo enfermedades no transmisibles, el presente trabajo pretendió determinar la capacidad antioxidante de un jugo de elaboración artesanal a partir de la combinación de espinaca (Spinaciaoleracea), acelga (Beta vulgaris subespecie cicla) y kiwi (Actinidia deliciosa). Esta investigación tuvo como objetivo elaborar artesanalmente un jugo con alto contenido de clorofila y capacidad antioxidante apto para el consumo y organolépticamente aceptable a base de espinaca, acelga y  kiwi. Estudio empírico, descriptivo simple, corte transversal; se analizó el contenido de clorofila (método espectrofotométrico de Hansmann), capacidad antioxidante total (secuestro del radical estable (DPPH)) y fibra (AOAC 985.29) del jugo elaborado. La aceptabilidad se realizó por evaluación sensorial mediante prueba descriptiva con escala hedónica para valorar la calidad teniendo en cuenta los atributos color, sabor, olor y textura. Se elaboraron dos muestras: una pasteurizada y otra no para conocer cual presentaba mayor contenido de clorofila y capacidad antioxidante.  Se aplicó prueba estadística Z con un nivel de confianza del 95%, para determinar si el producto elaborado es organolépticamente aceptado; software Epidat.  Se obtuvieron los siguientes resultados: en el jugo no pasteurizado, contenido de clorofila de 95,81mg/L (+/- 3,4), capacidad antioxidante de 84,56(% de inhibición) (+/- 2,13); en el jugo pasteurizado, 103,22mg/L (+/- 1,59)  de clorofila y 96,52(% de inhibición) (+/-0,74) de  capacidad antioxidante. El contenido de fibra en el jugo pasteurizado fue de 1,4 g/% de fibra. Según valoración sensorial, el 81% de jueces no entrenados aceptaron el producto.  Se pudo concluir que la bebida elaborada, según sus proporciones, presenta características fisicoquímicas y sensoriales favorables, siendo interesante en este tipo de nuevas bebidas la conjugación de las propiedades benéficas de las mezclas de espinaca, acelga y kiwi, con mayor porcentaje de absorción y biodisponibilidad, por la ausencia de inhibidores, pudiendo emplearse como coadyuvante en el tratamiento eficaz de enfermedades no transmisibles.

Spontaneous and radiation-induced chromosomal instability and persistence of chromosome aberrations after radiotherapy in lymphocytes from prostate cancer patients

The aim of the study was to compare the spontaneous and ex vivo radiation-induced chromosomal damage in lymphocytes of untreated prostate cancer patients and age-matched healthy donors, and to evaluate the chromosomal damage, induced by radiotherapy, and its persistence. Blood samples from 102 prostate cancer patients were obtained before radiotherapy to investigate the excess acentric fragments and dicentric chromosomes. In addition, in a subgroup of ten patients, simple exchanges in chromosomes 2 and 4 were evaluated by fluorescent in situ hybridization (FISH), before the onset of therapy, in the middle and at the end of therapy, and 1 year later. Data were compared to blood samples from ten age-matched healthy donors. We found that spontaneous yields of acentric chromosome fragments and simple exchanges were significantly increased in lymphocytes of patients before onset of therapy, indicating chromosomal instability in these patients. Ex vivo radiation-induced aberrations were not significantly increased, indicating proficient repair of radiation-induced DNA double-strand breaks in lymphocytes of these patients. As expected, the yields of dicentric and acentric chromosomes, and the partial yields of simple exchanges, were increased after the onset of therapy. Surprisingly, yields after 1 year were comparable to those directly after radiotherapy, indicating persistence of chromosomal instability over this time. Our results indicate that prostate cancer patients are characterized by increased spontaneous chromosomal instability. This instability seems to result from defects other than a deficient repair of radiation-induced DNA double-strand breaks. Radiotherapy-induced chromosomal damage persists 1 year after treatment

Vital capacity evolution in patients treated with the CMCR brace: statistical analysis of 90 scoliotic patients treated with the CMCR brace

<p>Summary</p> <p>Objective</p> <p>To study the evolution of pulmonary capacity during orthopaedic treatment of scoliosis with the CMCR brace.</p> <p>Background</p> <p>Investigating the impact of moderate scoliosis on respiratory capacity and its evolution during CMCR brace treatment with mobile pads.</p> <p>Context</p> <p>Several studies demonstrate the impact of scoliosis on respiratory capacity but few of them focus on the impact of bracing treatment. We studied the evolution of the pulmonary capacity of a cohort of 90 scoliotic patients.</p> <p>Methods</p> <p>This retrospective study included 90 scoliotic patients treated since 1999 with a brace with mobile pads called CMCR (n = 90; mean age: 13 years; 10-16). These patients were diagnosed with an idiopathic scoliosis (mean angulation 20.6°). All patients underwent a radiographic and respiratory evaluation at the beginning, the middle and the end of treatment.</p> <p>Results</p> <p><it>Mean age at treatment start was </it>13. Before treatment, our patients did not have a normal pulmonary capacity: Forced Vital Capacity (FVC) was only 75% of the theoretical value. All curvature types (thoracic, thoraco-lumbar and combined scoliosis) involved this reduced pulmonary capacity, with moderate-angulated scoliosis having a negative impact. At the beginning of brace treatment, the loss of real vital capacity with brace (0.3 litres) was 10% lower than without brace.</p> <p>At CMCR removal, the FVC had increased by 0.4 litre (21% +/- 4.2% compared to the initial value). The theoretical value had increased by 3%. This positive evolution was most important in girls at a low Risser stage (0,1,2), and before 11 years of age.</p> <p>Conclusion</p> <p>These results supported our approach of orthesis conception for adolescent idiopathic scoliosis which uses braces with mobile pads to preserve thorax and spine mobility.</p

Global diversity and biogeography of deep-sea pelagic prokaryotes

The deep-sea is the largest biome of the biosphere, and contains more than half of the whole ocean/'s microbes. Uncovering their general patterns of diversity and community structure at a global scale remains a great challenge, as only fragmentary information of deep-sea microbial diversity exists based on regional-scale studies. Here we report the first globally comprehensive survey of the prokaryotic communities inhabiting the bathypelagic ocean using high-throughput sequencing of the 16S rRNA gene. This work identifies the dominant prokaryotes in the pelagic deep ocean and reveals that 50{\%} of the operational taxonomic units (OTUs) belong to previously unknown prokaryotic taxa, most of which are rare and appear in just a few samples. We show that whereas the local richness of communities is comparable to that observed in previous regional studies, the global pool of prokaryotic taxa detected is modest (\~{}3600 OTUs), as a high proportion of OTUs are shared among samples. The water masses appear to act as clear drivers of the geographical distribution of both particle-attached and free-living prokaryotes. In addition, we show that the deep-oceanic basins in which the bathypelagic realm is divided contain different particle-attached (but not free-living) microbial communities. The combination of the aging of the water masses and a lack of complete dispersal are identified as the main drivers for this biogeographical pattern. All together, we identify the potential of the deep ocean as a reservoir of still unknown biological diversity with a higher degree of spatial complexity than hitherto considered.En prensa8,951

Roles of Electrostatics and Conformation in Protein-Crystal Interactions

In vitro studies have shown that the phosphoprotein osteopontin (OPN) inhibits the nucleation and growth of hydroxyapatite (HA) and other biominerals. In vivo, OPN is believed to prevent the calcification of soft tissues. However, the nature of the interaction between OPN and HA is not understood. In the computational part of the present study, we used molecular dynamics simulations to predict the adsorption of 19 peptides, each 16 amino acids long and collectively covering the entire sequence of OPN, to the {100} face of HA. This analysis showed that there is an inverse relationship between predicted strength of adsorption and peptide isoelectric point (P<0.0001). Analysis of the OPN sequence by PONDR (Predictor of Naturally Disordered Regions) indicated that OPN sequences predicted to adsorb well to HA are highly disordered. In the experimental part of the study, we synthesized phosphorylated and non-phosphorylated peptides corresponding to OPN sequences 65–80 (pSHDHMDDDDDDDDDGD) and 220–235 (pSHEpSTEQSDAIDpSAEK). In agreement with the PONDR analysis, these were shown by circular dichroism spectroscopy to be largely disordered. A constant-composition/seeded growth assay was used to assess the HA-inhibiting potencies of the synthetic peptides. The phosphorylated versions of OPN65-80 (IC50 = 1.93 µg/ml) and OPN220-235 (IC50 = 1.48 µg/ml) are potent inhibitors of HA growth, as is the nonphosphorylated version of OPN65-80 (IC50 = 2.97 µg/ml); the nonphosphorylated version of OPN220-235 has no measurable inhibitory activity. These findings suggest that the adsorption of acidic proteins to Ca2+-rich crystal faces of biominerals is governed by electrostatics and is facilitated by conformational flexibility of the polypeptide chain

A Multi-cell, Multi-scale Model of Vertebrate Segmentation and Somite Formation

Somitogenesis, the formation of the body's primary segmental structure common to all vertebrate development, requires coordination between biological mechanisms at several scales. Explaining how these mechanisms interact across scales and how events are coordinated in space and time is necessary for a complete understanding of somitogenesis and its evolutionary flexibility. So far, mechanisms of somitogenesis have been studied independently. To test the consistency, integrability and combined explanatory power of current prevailing hypotheses, we built an integrated clock-and-wavefront model including submodels of the intracellular segmentation clock, intercellular segmentation-clock coupling via Delta/Notch signaling, an FGF8 determination front, delayed differentiation, clock-wavefront readout, and differential-cell-cell-adhesion-driven cell sorting. We identify inconsistencies between existing submodels and gaps in the current understanding of somitogenesis mechanisms, and propose novel submodels and extensions of existing submodels where necessary. For reasonable initial conditions, 2D simulations of our model robustly generate spatially and temporally regular somites, realistic dynamic morphologies and spontaneous emergence of anterior-traveling stripes of Lfng. We show that these traveling stripes are pseudo-waves rather than true propagating waves. Our model is flexible enough to generate interspecies-like variation in somite size in response to changes in the PSM growth rate and segmentation-clock period, and in the number and width of Lfng stripes in response to changes in the PSM growth rate, segmentation-clock period and PSM length

Mutations in Protein-Binding Hot-Spots on the Hub Protein Smad3 Differentially Affect Its Protein Interactions and Smad3-Regulated Gene Expression

Hub proteins are connected through binding interactions to many other proteins. Smad3, a mediator of signal transduction induced by transforming growth factor beta (TGF-β), serves as a hub protein for over 50 protein-protein interactions. Different cellular responses mediated by Smad3 are the product of cell-type and context dependent Smad3-nucleated protein complexes acting in concert. Our hypothesis is that perturbation of this spectrum of protein complexes by mutation of single protein-binding hot-spots on Smad3 will have distinct consequences on Smad3-mediated responses.We mutated 28 amino acids on the surface of the Smad3 MH2 domain and identified 22 Smad3 variants with reduced binding to subsets of 17 Smad3-binding proteins including Smad4, SARA, Ski, Smurf2 and SIP1. Mutations defective in binding to Smad4, e.g., D408H, or defective in nucleocytoplasmic shuttling, e.g., W406A, were compromised in modulating the expression levels of a Smad3-dependent reporter gene or six endogenous Smad3-responsive genes: Mmp9, IL11, Tnfaip6, Fermt1, Olfm2 and Wnt11. However, the Smad3 mutants Y226A, Y297A, W326A, K341A, and E267A had distinct differences on TGF-β signaling. For example, K341A and Y226A both reduced the Smad3-mediated activation of the reporter gene by ∼50% but K341A only reduced the TGF-β inducibilty of Olfm2 in contrast to Y226A which reduced the TGF-β inducibility of all six endogenous genes as severely as the W406A mutation. E267A had increased protein binding but reduced TGF-β inducibility because it caused higher basal levels of expression. Y297A had increased TGF-β inducibility because it caused lower Smad3-induced basal levels of gene expression.Mutations in protein binding hot-spots on Smad3 reduced the binding to different subsets of interacting proteins and caused a range of quantitative changes in the expression of genes induced by Smad3. This approach should be useful for unraveling which Smad3 protein complexes are critical for specific biological responses

Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood survival