Charge-Dependence of the Nucleon-Nucleon Interaction

Based upon the Bonn meson-exchange-model for the nucleon-nucleon ($NN$) interaction, we calculate the charge-independence breaking (CIB) of the $NN$ interaction due to pion-mass splitting. Besides the one-pion-exchange (OPE), we take into account the $2\pi$-exchange model and contributions from three and four irreducible pion exchanges. We calculate the CIB differences in the $^1S_0$ effective range parameters as well as phase shift differences for partial waves up to total angular momentum J=4 and laboratory energies below 300 MeV. We find that the CIB effect from OPE dominates in all partial waves. However, the CIB effects from the $2\pi$ model are noticable up to D-waves and amount to about 40% of the OPE CIB-contribution in some partial waves, at 300 MeV. The effects from 3$\pi$ and 4$\pi$ contributions are negligible except in $^1S_0$ and $^3P_2$.Comment: 12 pages, RevTex, 14 figure

Gigwa v2—Extended and improved genotype investigator

The study of genetic variations is the basis of many research domains in biology. From genome structure to population dynamics, many applications involve the use of genetic variants. The advent of next-generation sequencing technologies led to such a flood of data that the daily work of scientists is often more focused on data management than data analysis. This mass of genotyping data poses several computational challenges in terms of storage, search, sharing, analysis, and visualization. While existing tools try to solve these challenges, few of them offer a comprehensive and scalable solution. Gigwa v2 is an easy-to-use, species-agnostic web application for managing and exploring high-density genotyping data. It can handle multiple databases and may be installed on a local computer or deployed as an online data portal. It supports various standard import and export formats, provides advanced filtering options, and offers means to visualize density charts or push selected data into various stand-alone or online tools. It implements 2 standard RESTful application programming interfaces, GA4GH, which is health-oriented, and BrAPI, which is breeding-oriented, thus offering wide possibilities of interaction with third-party applications. The project home page provides a list of live instances allowing users to test the system on public data (or reasonably sized user-provided data). This new version of Gigwa provides a more intuitive and more powerful way to explore large amounts of genotyping data by offering a scalable solution to search for genotype patterns, functional annotations, or more complex filtering. Furthermore, its user-friendliness and interoperability make it widely accessible to the life science community

Homeolog expression analysis in an allotriploid non-model crop via integration of transcriptomics and proteomics

Open Access Journal; Published online: 22 Jan 2018The fate of doubled genes, from allopolyploid or autopolyploid origin, is controlled at multiple levels, resulting in the modern day cultivars. We studied the root growth of 3 different triploid banana cultivars under control and osmotic stress conditions. The root growth of the allopolyploid ABB cultivar was 42% higher under control and 61% higher under osmotic stress. By integrating transcriptomics and proteomics, we studied the gene expression of all 3 cultivars, resulting in 2,749 identified root proteins. 383 gene loci displayed genotype specific differential expression whereof 252 showed at least one Single Amino Acid Polymorphism (SAAP). In the ABB cultivar, allele expressions supposedly follow a 1/3 and 2/3 pattern for respectively the A and the B allele. Using transcriptome read alignment to assess the homeoallelic contribution we found that 63% of the allele specific genes deviated from this expectation. 32 gene loci even did not express the A allele. The identified ABB allele- specific proteins correlate well with the observed growth phenotype as they are enriched in energy related functions such as ATP metabolic processes, nicotinamide nucleotide metabolic processes, and glycolysis

Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-alpha co-expression, but little interleukin-22 and interleukin-23R expression

Introduction\ud Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to systematically analyse the phenotype, cytokine profile and frequency of interleukin-17 (IL-17) producing CD4-positive T cells in mononuclear cells isolated from peripheral blood, synovial fluid and synovial tissue of RA patients with established disease, and to correlate cell frequencies with disease activity. \ud \ud Methods\ud Flow cytometry was used to analyse the phenotype and cytokine production of mononuclear cells isolated from peripheral blood (PBMC) (n = 44), synovial fluid (SFMC) (n = 14) and synovium (SVMC) (n = 10) of RA patients and PBMC of healthy controls (n = 13). \ud \ud Results\ud The frequency of IL-17-producing CD4 T cells was elevated in RA SFMC compared with RA PBMC (P = 0.04). However, the frequency of this population in RA SVMC was comparable to that in paired RA PBMC. The percentage of IL-17-producing CD4 T cells coexpressing tumor necrosis factor alpha (TNFα) was significantly increased in SFMC (P = 0.0068). The frequency of IFNγ-producing CD4 T cells was also significantly higher in SFMC than paired PBMC (P = 0.042). The majority of IL-17-producing CD4 T cells coexpressed IFNγ. IL-17-producing CD4 T cells in RA PBMC and SFMC exhibited very little IL-22 or IL-23R coexpression. \ud \ud Conclusions\ud These findings demonstrate a modest enrichment of IL-17-producing CD4 T cells in RA SFMC compared to PBMC. Th17 cells in SFMC produce more TNFα than their PBMC counterparts, but are not a significant source of IL-22 and do not express IL-23R. However, the percentage of CD4 T cells which produce IL-17 in the rheumatoid joint is low, suggesting that other cells may be alternative sources of IL-17 within the joints of RA patients. \ud \u

Baricitinib inhibits structural joint damage progression in patients with rheumatoid arthritis – a comprehensive review

Baricitinib is an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 that has proved effective and well tolerated in the treatment of rheumatoid arthritis (RA) in an extensive programme of clinical studies of patients with moderate-to-severe disease. In a phase 2b dose-ranging study of baricitinib in combination with traditional disease-modifyingantirheumatic drugs (DMARDs) in RA patients, magnetic resonance imaging showed that baricitinib 2 mg or 4 mgonce daily provided dose-dependent suppression of synovitis, osteitis, erosion and cartilage loss at weeks 12 and 24versus placebo. These findings correlated with clinical outcomes and were confirmed in three phase 3 studies (RA-BEGIN, RA-BEAM and RA-BUILD) using X-rays to assess structural joint damage. In patients naïve to DMARDs (RA-BEGINstudy), baricitinib 4 mg once daily as monotherapy or combined with methotrexate produced smaller mean changesin structural joint damage than methotrexate monotherapy at week 24. Differences versus methotrexate werestatistically significant for combined therapy. In patients responding inadequately to methotrexate (RA-BEAM study),baricitinib 4 mg plus background methotrexate significantly inhibited structural joint damage at week 24 versus placebo, and the results were comparable to those observed with adalimumab plus background methotrexate. Inpatients responding inadequately to conventional synthetic DMARDs (csDMARDs; RA-BUILD study), baricitinib 4 mgagain significantly inhibited radiographic progression compared with placebo at week 24. Benefits were also observedwith baricitinib 2 mg once daily, but the effects of baricitinib 4 mg were more robust. The positive effects of baricitinib4 mg on radiographic progression continued over 1 and 2 years in the long-term extension study RA-BEYOND, withsimilar effects to adalimumab and significantly greater effects than placebo. Findings from the phase 3 studies ofpatients with RA were supported by preclinical studies, which showed that baricitinib has an osteoprotective effect, increasing mineralisation in bone-forming cells. In conclusion, baricitinib 4 mg once daily inhibits radiographic jointdamage progression in patients with moderate-to-severe RA who are naïve to DMARDs or respond inadequately to csDMARDs, including methotrexate, and the beneficial effects are similar to those observed with adalimumab

Effect of paleopolyploidy and allopolyploidy on gene expression in banana

Open Access JournalBananas (Musa spp.) are an important crop worldwide. Most modern cultivars resulted from a complex polyploidization history that comprised three whole genome duplications (WGDs) shaping the haploid Musa genome, followed by inter- and intra-specific crosses between Musa acuminata and M. balbisiana (A and B genome, respectively). Unresolved hybridizations finally led to banana diversification into several autotriploid (AAA) and allotriploid cultivars (AAB and ABB). Using transcriptomic data, we investigated the impact of the genome structure on gene expression patterns in roots of 12 different triploid genotypes covering AAA, AAB and ABB subgenome constitutions

Directed Neural Differentiation of Mouse Embryonic Stem Cells Is a Sensitive System for the Identification of Novel Hox Gene Effectors

The evolutionarily conserved Hox family of homeodomain transcription factors plays fundamental roles in regulating cell specification along the anterior posterior axis during development of all bilaterian animals by controlling cell fate choices in a highly localized, extracellular signal and cell context dependent manner. Some studies have established downstream target genes in specific systems but their identification is insufficient to explain either the ability of Hox genes to direct homeotic transformations or the breadth of their patterning potential. To begin delineating Hox gene function in neural development we used a mouse ES cell based system that combines efficient neural differentiation with inducible Hoxb1 expression. Gene expression profiling suggested that Hoxb1 acted as both activator and repressor in the short term but predominantly as a repressor in the long run. Activated and repressed genes segregated in distinct processes suggesting that, in the context examined, Hoxb1 blocked differentiation while activating genes related to early developmental processes, wnt and cell surface receptor linked signal transduction and cell-to-cell communication. To further elucidate aspects of Hoxb1 function we used loss and gain of function approaches in the mouse and chick embryos. We show that Hoxb1 acts as an activator to establish the full expression domain of CRABPI and II in rhombomere 4 and as a repressor to restrict expression of Lhx5 and Lhx9. Thus the Hoxb1 patterning activity includes the regulation of the cellular response to retinoic acid and the delay of the expression of genes that commit cells to neural differentiation. The results of this study show that ES neural differentiation and inducible Hox gene expression can be used as a sensitive model system to systematically identify Hox novel target genes, delineate their interactions with signaling pathways in dictating cell fate and define the extent of functional overlap among different Hox genes