Expansion and Harvesting of hMSC-TERT

The expansion of human mesenchymal stem cells as suspension culture by means of spinner flasks and microcarriers, compared to the cultivation in tissue culture flasks, offers the advantage of reducing the requirements of large incubator capacities as well as reducing the handling effort during cultivation and harvesting. Nonporous microcarriers are preferable when the cells need to be kept in viable condition for further applications like tissue engineering or cell therapy. In this study, the qualification of Biosilon, Cytodex 1, Cytodex 3, RapidCell and P102-L for expansion of hMSC-TERT with an associated harvesting process using either trypsin, accutase, collagenase or a trypsin-accutase mixture was investigated. A subsequent adipogenic differentiation of harvested hMSC-TERT was performed in order to observe possible negative effects on their (adipogenic) differentiation potential as a result of the cultivation and harvesting method. The cultivated cells showed an average growth rate of 0.52 d-1. The cells cultivated on Biosilon, RapidCell and P102-L were harvested succesfully achieving high cell yield and vitalities near 100%. This was not the case for cells on Cytodex 1 and Cytodex 3. The trypsin-accutase mix was most effective. After spinner expansion and harvesting the cells were successfully differentiated to adipocytes

Deeply virtual and exclusive electroproduction of omega mesons

The exclusive omega electroproduction off the proton was studied in a large kinematical domain above the nucleon resonance region and for the highest possible photon virtuality (Q2) with the 5.75 GeV beam at CEBAF and the CLAS spectrometer. Cross sections were measured up to large values of the four-momentum transfer (-t < 2.7 GeV2) to the proton. The contributions of the interference terms sigma_TT and sigma_TL to the cross sections, as well as an analysis of the omega spin density matrix, indicate that helicity is not conserved in this process. The t-channel pi0 exchange, or more generally the exchange of the associated Regge trajectory, seems to dominate the reaction gamma* p -> omega p, even for Q2 as large as 5 GeV2. Contributions of handbag diagrams, related to Generalized Parton Distributions in the nucleon, are therefore difficult to extract for this process. Remarkably, the high-t behaviour of the cross sections is nearly Q2-independent, which may be interpreted as a coupling of the photon to a point-like object in this kinematical limit.Comment: 15 pages,19 figure

Word Processing differences between dyslexic and control children

BACKGROUND: The aim of this study was to investigate brain responses triggered by different wordclasses in dyslexic and control children. The majority of dyslexic children have difficulties to phonologically assemble a word from sublexical parts following grapheme-to-phoneme correspondences. Therefore, we hypothesised that dyslexic children should mainly differ from controls processing low frequent words that are unfamiliar to the reader. METHODS: We presented different wordclasses (high and low frequent words, pseudowords) in a rapid serial visual word (RSVP) design and performed wavelet analysis on the evoked activity. RESULTS: Dyslexic children had lower evoked power amplitudes and a higher spectral frequency for low frequent words compared to control children. No group differences were found for high frequent words and pseudowords. Control children had higher evoked power amplitudes and a lower spectral frequency for low frequent words compared to high frequent words and pseudowords. This pattern was not present in the dyslexic group. CONCLUSION: Dyslexic children differed from control children only in their brain responses to low frequent words while showing no modulated brain activity in response to the three word types. This might support the hypothesis that dyslexic children are selectively impaired reading words that require sublexical processing. However, the lacking differences between word types raise the question if dyslexic children were able to process the words presented in rapid serial fashion in an adequate way. Therefore the present results should only be interpreted as evidence for a specific sublexical processing deficit with caution

Genome Evolution and the Emergence of Fruiting Body Development in Myxococcus xanthus

BACKGROUND: Lateral gene transfer (LGT) is thought to promote speciation in bacteria, though well-defined examples have not been put forward. METHODOLOGY/PRINCIPLE FINDINGS: We examined the evolutionary history of the genes essential for a trait that defines a phylogenetic order, namely fruiting body development of the Myxococcales. Seventy-eight genes that are essential for Myxococcus xanthus development were examined for LGT. About 73% of the genes exhibit a phylogeny similar to that of the 16S rDNA gene and a codon bias consistent with other M. xanthus genes suggesting vertical transmission. About 22% have an altered codon bias and/or phylogeny suggestive of LGT. The remaining 5% are unique. Genes encoding signal production and sensory transduction were more likely to be transmitted vertically with clear examples of duplication and divergence into multigene families. Genes encoding metabolic enzymes were frequently acquired by LGT. Myxobacteria exhibit aerobic respiration unlike most of the delta Proteobacteria. M. xanthus contains a unique electron transport pathway shaped by LGT of genes for succinate dehydrogenase and three cytochrome oxidase complexes. CONCLUSIONS/SIGNIFICANCE: Fruiting body development depends on genes acquired by LGT, particularly those involved in polysaccharide production. We suggest that aerobic growth fostered innovation necessary for development by allowing myxobacteria access to a different gene pool from anaerobic members of the delta Proteobacteria. Habitat destruction and loss of species diversity could restrict the evolution of new bacterial groups by limiting the size of the prospective gene pool

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The Effects of Amino Acid Supplementation On Hormonal Responses to Resistance Training Overreaching

The purpose of this investigation was to examine the effects of amino acid supplementation on muscular performance and resting hormone concentrations during resistance training overreaching. Seventeen resistance-trained men were randomly assigned to either an amino acid (AA) or a placebo (P) group and under-went 4 weeks of total-body resistance training designed to induce a state of overreaching. The protocol consisted of two 2-week phases (phase 1, 3 sets of 8 exercises performed for 8-12 repetitions-, phase 2, 5 sets of 5 exercises performed for 3-5 repetitions). Muscle strength and resting blood samples were determined before (T1) and at the end of each training week (T2-T5). One-repetition maximum squat and bench press decreased at T2 in the P group but not in the AA group-, both groups showed similar increases in strength at T3 to T5. Significant elevations in serum creatine kinase and uric acid were observed at T2 in the P group; the elevation in creatine kinase correlated highly to reductions in 1 -repetition maximum squat (r = -0.67, r(2) = 0.45). Significant elevations in serum sex honnone-binding globulin were observed during overreaching in the P group from T2 to T5; this response was abolished in the AA group. Significant reductions in total testosterone were observed in the P group at T4 compared with T1, and total testosterone values were higher for the AA group than for the P group from T2 to T4. Serum 22-kd growth hormone concentrations were elevated at T2 to T5 in P group only. No differences were observed in resting cortisol and insulinlike growth factor 1. Hemoglobin concentrations were significantly reduced at T2 to T5 in the P group. These results indicate that the initial impact of high-volume resistance training is muscle strength reduction and hormonal/biochemical alterations. It appears that amino acid supplementation is effective for attenuating muscle strength loss during initial high-volume stress, possibly by reducing muscle damage by maintaining an anabolic environment. (c) 2006 Elsevier Inc. All rights reserved