161 research outputs found
Syk and Zap-70 function redundantly to promote angioblast migration
AbstractSpleen tyrosine kinase (Syk) plays critical roles in B-cell and T-cell development, the maintenance of vascular integrity, and proper partitioning of the blood vascular and lymphatic vascular system. Here, we utilize the zebrafish as an in vivo system to demonstrate novel roles for Syk and the related kinase Zeta associated protein (Zap-70) in promoting angioblast migration. Partial knockdown of either gene results in early angiogenic delay of the intersegmental vessels, dorsal intersegmental vessel patterning defects, and partial loss of the thoracic duct. Higher dose knockdown of both genes results in little to no angiogenic sprouting of the intersegmental vessels, a phenotype which resembles knockdown of vegfa. Di-phosphorylated ERK, an effector of the vegfa pathway, is also downregulated in the aorta of syk:zap double morphants. Over-expression of syk under the control of a blood-specific or vascular-specific promoter rescues sprouting defects after loss of vegfa. Together these results suggest that syk and zap-70 function redundantly in an early progenitor to promote the migration of intersegmental vessel angioblasts and lymphangioblasts that contribute to the thoracic duct, either downstream of, or in parallel to vegfa
Feminizing political parties: womenâs party member organizations within European parliamentary parties
Party member womenâs organizations were early features of party development. While some contemporary studies maintain these are important sites for the substantive representation of women, there is also a claim that they are in decline. Our primary purpose here is to establish the existence of party member womenâs organizations â as one test of the first dimension of party feminization: the inclusion of women. We draw on new survey data of 17 European countries provided by Scarrow, Poguntke and Webb. We establish that almost half have a party member womenâs organization. The new data also permits analysis of relationships between party member womenâs organization and gender quotas for the top party leadership body (National Executive Committee (NEC)), womenâs presence among the party leadership and candidate quota rules. Together we see these (i) as a means to establish whether women are marginalized within the party, thereby limiting descriptive representation and (ii) as surrogate measures for womenâs substantive representation. We importantly find that the presence of a party member womenâs organization does not come at the cost of womenâs presence on the NEC. In the final section, we turn our attention to building a new comparative research agenda that more fully addresses substantive representation
Re-gendering the UK House of Commons: the academic critical actor and her âFeminist in Residenceâ
Phylogenetic Analysis of the MS4A and TMEM176 Gene Families
The MS4A gene family in humans includes CD20 (MS4A1), FcRbeta (MS4A2), Htm4 (MS4A3), and at least 13 other syntenic genes encoding membrane proteins, most having characteristic tetraspanning topology. Expression of MS4A genes is variable in tissues throughout the body; however, several are limited to cells in the hematopoietic system where they have known roles in immune cell functions. Genes in the small TMEM176 group share significant sequence similarity with MS4A genes and there is evidence of immune function of at least one of the encoded proteins. In this study, we examined the evolutionary history of the MS4A/TMEM176 families as well as tissue expression of the phylogenetically earliest members, in order to investigate their possible origins in immune cells.Orthologs of human MS4A genes were found only in mammals; however, MS4A gene homologs were found in most jawed vertebrates. TMEM176 genes were found only in mammals and bony fish. Several unusual MS4A genes having 2 or more tandem MS4A sequences were identified in the chicken (Gallus gallus) and early mammals (opossum, Monodelphis domestica and platypus, Ornithorhyncus anatinus). A large number of highly conserved MS4A and TMEM176 genes was found in zebrafish (Danio rerio). The most primitive organism identified to have MS4A genes was spiny dogfish (Squalus acanthus). Tissue expression of MS4A genes in S. acanthias and D. rerio showed no evidence of expression restricted to the hematopoietic system.Our findings suggest that MS4A genes first appeared in cartilaginous fish with expression outside of the immune system, and have since diversified in many species into their modern forms with expression and function in both immune and nonimmune cells
IL-17 Signaling triggers degradation of the constitutive NF-ÎșB inhibitor ABIN-1
IL-17 activates NF-ÎșB and induces expression of proinflammatory genes. IL-17 drives disease in autoimmune conditions, and antiâIL-17 Abs have shown impressive success in the clinic. Although produced by lymphocytes, IL-17 predominantly signals in fibroblasts and epithelial cells. IL-17âdriven inflammation is kept in check by negative feedback signaling molecules, including the ubiquitin editing enzyme A20, whose gene TNFAIP3 is linked to autoimmune disease susceptibility. The A20 binding inhibitor of NF-ÎșB activation 1 (ABIN-1) is an A20-binding protein encoded by the TNIP1 gene, which is also linked to autoimmune disease susceptibility including psoriasis. Accordingly, we hypothesized that ABIN-1 might play a role in negatively regulating IL-17 signaling activity. Indeed, ABIN-1 enhanced both tonic and IL-17âdependent NF-ÎșB signaling in IL-17âresponsive fibroblast cells. Interestingly, the inhibitory activities of ABIN-1 on IL-17 signaling were independent of A20. ABIN-1 is a known NF-ÎșB target gene, and we found that IL-17âinduced activation of NF-ÎșB led to enhanced ABIN-1 mRNA expression and promoter activity. Surprisingly, however, the ABIN-1 protein was inducibly degraded following IL-17 signaling in a proteasome-dependent manner. Thus, ABIN-1, acting independently of A20, restricts both baseline and IL-17âinduced inflammatory gene expression. We conclude that IL-17âinduced signals lead to degradation of ABIN-1, thereby releasing a constitutive cellular brake on NF-ÎșB activation
Using Abbreviated Injury Scale (AIS) codes to classify Computed Tomography (CT) features in the Marshall System
<p>Abstract</p> <p>Background</p> <p>The purpose of Abbreviated Injury Scale (AIS) is to code various types of Traumatic Brain Injuries (TBI) based on their anatomical location and severity. The Marshall CT Classification is used to identify those subgroups of brain injured patients at higher risk of deterioration or mortality. The purpose of this study is to determine whether and how AIS coding can be translated to the Marshall Classification</p> <p>Methods</p> <p>Initially, a Marshall Class was allocated to each AIS code through cross-tabulation. This was agreed upon through several discussion meetings with experts from both fields (clinicians and AIS coders). Furthermore, in order to make this translation possible, some necessary assumptions with regards to coding and classification of mass lesions and brain swelling were essential which were all approved and made explicit.</p> <p>Results</p> <p>The proposed method involves two stages: firstly to determine all possible Marshall Classes which a given patient can attract based on allocated AIS codes; via cross-tabulation and secondly to assign one Marshall Class to each patient through an algorithm.</p> <p>Conclusion</p> <p>This method can be easily programmed in computer softwares and it would enable future important TBI research programs using trauma registry data.</p
Transcriptomics Identifies Modules of Differentially Expressed Genes and Novel Cyclotides in Viola pubescens
Viola is a large genus with worldwide distribution and many traits not currently exemplified in model plants including unique breeding systems and the production of cyclotides. Here we report de novo genome assembly and transcriptomic analyses of the non-model species Viola pubescens using short-read DNA sequencing data and RNA-Seq from eight diverse tissues. First, V. pubescens genome size was estimated through flow cytometry, resulting in an approximate haploid genome of 455 Mbp. Next, the draft V. pubescens genome was sequenced and assembled resulting in 264,035,065 read pairs and 161,038 contigs with an N50 length of 3,455 base pairs (bp). RNA-Seq data were then assembled into tissue-specific transcripts. Together, the DNA and transcript data generated 38,081 ab initio gene models which were functionally annotated based on homology to Arabidopsis thaliana genes and Pfam domains. Gene expression was visualized for each tissue via principal component analysis and hierarchical clustering, and gene co-expression analysis identified 20 modules of tissue-specific transcriptional networks. Some of these modules highlight genetic differences between chasmogamous and cleistogamous flowers and may provide insight into V. pubescensâ mixed breeding system. Orthologous clustering with the proteomes of A. thaliana and Populus trichocarpa revealed 8,531 sequences unique to V. pubescens, including 81 novel cyclotide precursor sequences. Cyclotides are plant peptides characterized by a stable, cyclic cystine knot motif, making them strong candidates for drug scaffolding and protein engineering. Analysis of the RNA-Seq data for these cyclotide transcripts revealed diverse expression patterns both between transcripts and tissues. The diversity of these cyclotides was also highlighted in a maximum likelihood protein cladogram containing V. pubescens cyclotides and published cyclotide sequences from other Violaceae and Rubiaceae species. Collectively, this work provides the most comprehensive sequence resource for Viola, offers valuable transcriptomic insight into V. pubescens, and will facilitate future functional genomics research in Viola and other diverse plant groups
Corrigendum: Transcriptomics Identifies Modules of Differentially Expressed Genes and Novel Cyclotides in Viola pubescens
IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis
Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17ra(ÎK13)). Following oral Candida infection, Il17ra(ÎK13) mice exhibited fungal loads and weight loss indistinguishable from Il17ra(â/â) mice. Susceptibility in Il17ra(ÎK13) mice correlated with expression of the antimicrobial peptide ÎČ-defensin 3 (BD3, Defb3). Consistently, Defb3(â/â) mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3expression
ć¶șćéèš Lingnan Newsletter (珏63æ)
https://commons.ln.edu.hk/lingnan_newsletter/1062/thumbnail.jp
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