Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids

Multicellular tumor spheroids are an important {\it in vitro} model of the pre-vascular phase of solid tumors, for sizes well below the diagnostic limit: therefore a biophysical model of spheroids has the ability to shed light on the internal workings and organization of tumors at a critical phase of their development. To this end, we have developed a computer program that integrates the behavior of individual cells and their interactions with other cells and the surrounding environment. It is based on a quantitative description of metabolism, growth, proliferation and death of single tumor cells, and on equations that model biochemical and mechanical cell-cell and cell-environment interactions. The program reproduces existing experimental data on spheroids, and yields unique views of their microenvironment. Simulations show complex internal flows and motions of nutrients, metabolites and cells, that are otherwise unobservable with current experimental techniques, and give novel clues on tumor development and strong hints for future therapies.Comment: 20 pages, 10 figures. Accepted for publication in PLOS One. The published version contains links to a supplementary text and three video file

Accretion of Planetary Material onto Host Stars

Accretion of planetary material onto host stars may occur throughout a star's life. Especially prone to accretion, extrasolar planets in short-period orbits, while relatively rare, constitute a significant fraction of the known population, and these planets are subject to dynamical and atmospheric influences that can drive significant mass loss. Theoretical models frame expectations regarding the rates and extent of this planetary accretion. For instance, tidal interactions between planets and stars may drive complete orbital decay during the main sequence. Many planets that survive their stars' main sequence lifetime will still be engulfed when the host stars become red giant stars. There is some observational evidence supporting these predictions, such as a dearth of close-in planets around fast stellar rotators, which is consistent with tidal spin-up and planet accretion. There remains no clear chemical evidence for pollution of the atmospheres of main sequence or red giant stars by planetary materials, but a wealth of evidence points to active accretion by white dwarfs. In this article, we review the current understanding of accretion of planetary material, from the pre- to the post-main sequence and beyond. The review begins with the astrophysical framework for that process and then considers accretion during various phases of a host star's life, during which the details of accretion vary, and the observational evidence for accretion during these phases.Comment: 18 pages, 5 figures (with some redacted), invited revie

Radiografia simples e tomografia computadorizada do crânio em crianças e adolescentes vítimas de traumatismo craniano leve

OBJECTIVE: To identify which pediatric patients with mild head trauma are candidates for skull radiographs or cranial computed tomography (CCT) scans. METHOD: Patients with mild head trauma aged from 0 to 19 years presenting to the Emergency Department of a trauma centre from Salvador City, Brazil, between May 2007 and May 2008. RESULTS: A total of 1888 mild head trauma patients were admitted; mean age was 7.4 (±5.5) years. A total of 1956 skull radiographs and 734 CCT scans were performed. About 44.4% patients with Glasgow coma score (GCS) 13 and 55.4% with GCS 14 had abnormal CCT scans. In patients with multiple traumas, 16% had abnormal findings on CCT scans. CONCLUSION: We strongly recommend routine CCT studies to patients with GCS of 13 and 14 or to multiple trauma victims, independently of score. Routine screening skull radiographs were not useful in the evaluation of mild head trauma patients in this study.OBJETIVO: Identificar quais os pacientes na faixa pediátrica com trauma craniencefálico leve são candidatos para a realização de radiografia simples ou tomografia computadorizada do crânio (TCC). MÉTODO: Pacientes com trauma craniano leve, entre 0 e 19 anos, admitidos em um centro de referência em traumatologia, na cidade do Salvador, Brasil, entre maio 2007 e maio 2008. RESULTADOS: Foram atendidos 1888 pacientes com trauma craniano leve, com idade média de 7,4 (±5,5) anos. Um total de 1956 radiografias simples e 734 TCC foram realizadas. Em 44,4% dos pacientes com escala de coma de Glasgow (GCS) 13 e 55.4% com GCS 14, tiveram TCC com achados anormais. Em pacientes com múltiplos traumas, 16% possuíam alterações na TCC. CONCLUSÃO: Recomendamos TCC em pacientes com GCS 13 e 14 ou naqueles com traumas múltiplos, independente do GCS. Radiografias simples do crânio como rotina, não foram identificadas como úteis, no presente estudo

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

Differential physiological changes following internet exposure in higher and lower problematic internet users

Problematic internet use (PIU) has been suggested as in need of further research with a view to being included as a disorder in future Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association, but lack of knowledge about the impact of internet cessation on physiological function remains a major gap in knowledge and a barrier to PIU classification. One hundred and forty-four participants were assessed for physiological (blood pressure and heart rate) and psychological (mood and state anxiety) function before and after an internet session. Individuals also completed a psychometric examination relating to their usage of the internet, as well as their levels of depression and trait anxiety. Individuals who identified themselves as having PIU displayed increases in heart rate and systolic blood pressure, as well as reduced mood and increased state of anxiety, following cessation of internet session. There were no such changes in individuals with no self-reported PIU. These changes were independent of levels of depression and trait anxiety. These changes after cessation of internet use are similar to those seen in individuals who have ceased using sedative or opiate drugs, and suggest PIU deserves further investigation and serious consideration as a disorder

Identification, isolation and in vitro expansion of human and nonhuman primate T stem cell memory cell

The T cell compartment is phenotypically and functionally heterogeneous; subsets of naive and memory cells have different functional properties, and also differ with respect to homeostatic potential and the ability to persist in vivo. Human stem cell memory T (TSCM) cells, which possess superior immune reconstitution and antitumor response capabilities, can be identified by polychromatic flow cytometry on the basis of the simultaneous expression of several naive markers together with the memory marker CD95. We describe here a protocol based on the minimum set of markers required for optimal identification of human and nonhuman primate (NHP) TSCM cells with commonly available flow cytometers. By using flow sorters, TSCM cells can thereby be isolated efficiently at high yield and purity. With the use of the 5.5-h isolation procedure, depending on the number of cells needed, the sorting procedure can last for 2-15 h. We also indicate multiple strategies for their efficient expansion in vitro at consistent numbers for functional characterization or adoptive transfer experiments

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Adaptabilidade e estabilidade de populações de cenoura

No processo de desenvolvimento de novas cultivares de cenoura, é imprescindível o conhecimento do comportamento das populações em fase final de melhoramento, frente aos possíveis ambientes para os quais elas possam vir a ser indicadas. Isso pode ser verificado por meio de análises de adaptabilidade e estabilidade. O objetivo desse estudo foi quantificar a adaptabilidade e estabilidade de populações de cenoura do grupo Brasilia. O trabalho foi conduzido nos anos agrícolas de 2007/2008, 2008/2009 e 2009/2010 em cinco locais: três com cultivo convencional em São Gotardo (MG); Irecê (BA) e Gama (DF); e dois com cultivo orgânico no Programa de Assentamento Dirigido do Distrito Federal (PAD-DF) e em Gama (DF). O delineamento experimental utilizado foi de blocos ao acaso com três repetições e parcelas de 1 m². Foram avaliadas quatro populações de cenoura do grupo Brasília: 0912532, 0912520, BRS Planalto e Brasília. Aos 100 dias após a semeadura, foi determinada em cada parcela, em gramas, a massa fresca das raízes com padrão comercial. Foi utilizada a metodologia REML/BLUP para a avaliação da adaptabilidade e estabilidade. Pôde-se verificar que as populações com melhor adaptabilidade e estabilidade foram BRS Planalto e 0912520. BRS Planalto destacou-se principalmente na safra de 2009/2010; enquanto a população 0912520 destacou-se em 2007/2008 e 2008/2009; Brasília teve o pior desempenho na maioria dos locais, porém apresentou bom desempenho ou adaptabilidade específica para Irecê (BA).In the process of developing new cultivars, it is imperative to know the performance of carrot populations in final breeding phase for the possible environments to which they may be indicated; this can be verified testing the adaptability and stability. In this study the adaptability and stability of carrot genotypes from the Brasilia group were verified. The experiment was carried out during the 2007/2008, 2008/2009 and 2009/2010 crop years at five different places, three being in conventional growing at Sao Gotardo (Minas Gerais state), Irece (Bahia state) and Gama (Federal District), and two in organic growing at Managed Settlement Program of the Federal District (PAD-DF) and Gama. A randomized block design with three replications with 1 m² plots was used. Four carrot genotypes from the Brasilia group: 0912532, 0912520, BRS Planalto and Brasilia were evaluated. 100 days following sowing, fresh mass of commercial root value was determined in grams, in each plot. Regarding adaptability and stability assessment, the REML/BLUP methodology was applied. BRS Planalto and 0912520 were the genotypes with better adaptability and stability; BRS Planalto was preeminent mainly in 2009-2010 crop years; and 0912520 was preeminent in 2007/2008 and 2008/2009. Brasilia had the worst performance in most places, but good performance and specific adaptability to Irece

Genome wide scan for quantitative trait loci affecting tick resistance in cattle (Bos taurus × Bos indicus)

<p><b>Abstract</b></p> <p><b>Background</b></p> <p>In tropical countries, losses caused by bovine tick <it>Rhipicephalus (Boophilus) microplus</it> infestation have a tremendous economic impact on cattle production systems. Genetic variation between <it>Bos taurus</it> and <it>Bos indicus</it> to tick resistance and molecular biology tools might allow for the identification of molecular markers linked to resistance traits that could be used as an auxiliary tool in selection programs. The objective of this work was to identify QTL associated with tick resistance/susceptibility in a bovine F2 population derived from the Gyr (<it>Bos indicus</it>) × Holstein (<it>Bos taurus</it>) cross.</p> <p>Results</p> <p>Through a whole genome scan with microsatellite markers, we were able to map six genomic regions associated with bovine tick resistance. For most QTL, we have found that depending on the tick evaluation season (dry and rainy) different sets of genes could be involved in the resistance mechanism. We identified dry season specific QTL on BTA 2 and 10, rainy season specific QTL on BTA 5, 11 and 27. We also found a highly significant genome wide QTL for both dry and rainy seasons in the central region of BTA 23.</p> <p>Conclusions</p> <p>The experimental F2 population derived from Gyr × Holstein cross successfully allowed the identification of six highly significant QTL associated with tick resistance in cattle. QTL located on BTA 23 might be related with the bovine histocompatibility complex. Further investigation of these QTL will help to isolate candidate genes involved with tick resistance in cattle.</p