1,551 research outputs found
Partonic description of a supersymmetric p-brane
We consider supersymmetric extensions of a recently proposed partonic
description of a bosonic p-brane which reformulates the Nambu-Goto action as an
interacting multi-particle action with Filippov-Lie algebra gauge symmetry. We
construct a worldline supersymmetric action by postulating, among others, a
p-form fermion. Demanding a local worldline supersymmetry rather than the full
worldvolume supersymmetry, we circumvent a known no-go theorem against the
construction of a Ramond-Neveu-Schwarz supersymmetric action for a p-brane of
p>1. We also derive a spacetime supersymmetric Green-Schwarz extension from the
preexisting kappa-symmetric action.Comment: 1+16 pages, no figure; References added and Concluding section
expanded. Final version to appear in JHE
Engineering the Salmonella type III secretion system to export spider silk monomers
The type III secretion system (T3SS) exports proteins from the cytoplasm, through both the inner and outer membranes, to the external environment. Here, a system is constructed to harness the T3SS encoded within Salmonella Pathogeneity Island 1 to export proteins of biotechnological interest. The system is composed of an operon containing the target protein fused to an N-terminal secretion tag and its cognate chaperone. Transcription is controlled by a genetic circuit that only turns on when the cell is actively secreting protein. The system is refined using a small human protein (DH domain) and demonstrated by exporting three silk monomers (ADF-1, -2, and -3), representative of different types of spider silk. Synthetic genes encoding silk monomers were designed to enhance genetic stability and codon usage, constructed by automated DNA synthesis, and cloned into the secretion control system. Secretion rates up to 1.8 mg l−1 h−1 are demonstrated with up to 14% of expressed protein secreted. This work introduces new parts to control protein secretion in Gram-negative bacteria, which will be broadly applicable to problems in biotechnology
Built environment and physical activity: domain- and activity-specific associations among Brazilian adolescents
RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus
Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions
Does a SLAP lesion affect shoulder muscle recruitment as measured by EMG activity during a rugby tackle?
Background: The study objective was to assess the influence of a SLAP lesion on onset of EMG activity in shoulder muscles during a front on rugby football tackle within professional rugby players.
Methods: Mixed cross-sectional study evaluating between and within group differences in EMG onset times. Testing was carried out within the physiotherapy department of a university sports medicine clinic. The test group consisted of 7 players with clinically diagnosed SLAP lesions, later verified on arthroscopy. The reference group consisted of 15 uninjured and full time professional rugby players from within the same playing squad. Controlled tackles were performed against a tackle dummy. Onset of EMG activity was assessed from surface EMG of Pectorialis Major, Biceps Brachii, Latissimus Dorsi, Serratus Anterior and Infraspinatus muscles relative to time of impact. Analysis of differences in activation timing between muscles and limbs (injured versus non-injured side and non injured side versus matched reference group).
Results: Serratus Anterior was activated prior to all other muscles in all (P = 0.001-0.03) subjects. In the SLAP
injured shoulder Biceps was activated later than in the non-injured side. Onset times of all muscles of the noninjured shoulder in the injured player were consistently earlier compared with the reference group. Whereas, within
the injured shoulder, all muscle activation timings were later than in the reference group.
Conclusions: This study shows that in shoulders with a SLAP lesion there is a trend towards delay in activation time of Biceps and other muscles with the exception of an associated earlier onset of activation of Serratus anterior, possibly due to a coping strategy to protect glenohumeral stability and thoraco-scapular stability. This
trend was not statistically significant in all cases
Fabrication and vibration characterization of curcumin extracted from turmeric (Curcuma longa) rhizomes of the northern Vietnam
A formative study exploring perceptions of physical activity and physical activity monitoring among children and young people with cystic fibrosis and health care professionals
Background: Physical activity (PA) is associated with reduced hospitalisations and maintenance of lung function in patients with Cystic Fibrosis (CF). PA is therefore recommended as part of standard care. Despite this, there is no consensus for monitoring of PA and little is known about perceptions of PA monitoring among children and young people with CF. Therefore, the research aimed to explore patients’ perceptions of PA and the acceptability of using PA monitoring devices with children and young people with CF.
Methods: An action research approach was utilised, whereby findings from earlier research phases informed subsequent phases. Four phases were utilised, including patient interviews, PA monitoring, follow-up patient interviews and health care professional (HCP) interviews. Subsequently, an expert panel discussed the study to develop recommendations for practice and future research.
Results: Findings suggest that experiences of PA in children and young people with CF are largely comparable to their non-CF peers, with individuals engaging in a variety of activities. CF was not perceived as a barrier per se, although participants acknowledged that they could be limited by their symptoms. Maintenance of health emerged as a key facilitator, in some cases PA offered patients the opportunity to ‘normalise’ their condition.
Participants reported enjoying wearing the monitoring devices and had good compliance. Wrist-worn devices and devices providing feedback were preferred. HCPs recognised the potential benefits of the devices in clinical practice.
Recommendations based on these findings are that interventions to promote PA in children and young people with CF should be individualised and involve families to promote PA as part of an active lifestyle. Patients should receive support alongside the PA data obtained from monitoring devices.
Conclusions: PA monitoring devices appear to be an acceptable method for objective assessment of PA among children and young people with CF and their clinicians. Wrist-worn devices, which are unobtrusive and can display feedback, were perceived as most acceptable. By understanding the factors impacting PA, CF health professionals will be better placed to support patients and improve health outcomes
Gene-Boosted Assembly of a Novel Bacterial Genome from Very Short Reads
Recent improvements in technology have made DNA sequencing dramatically faster and more efficient than ever before. The new technologies produce highly accurate sequences, but one drawback is that the most efficient technology produces the shortest read lengths. Short-read sequencing has been applied successfully to resequence the human genome and those of other species but not to whole-genome sequencing of novel organisms. Here we describe the sequencing and assembly of a novel clinical isolate of Pseudomonas aeruginosa, strain PAb1, using very short read technology. From 8,627,900 reads, each 33 nucleotides in length, we assembled the genome into one scaffold of 76 ordered contiguous sequences containing 6,290,005 nucleotides, including one contig spanning 512,638 nucleotides, plus an additional 436 unordered contigs containing 416,897 nucleotides. Our method includes a novel gene-boosting algorithm that uses amino acid sequences from predicted proteins to build a better assembly. This study demonstrates the feasibility of very short read sequencing for the sequencing of bacterial genomes, particularly those for which a related species has been sequenced previously, and expands the potential application of this new technology to most known prokaryotic species
Incorporation of albumin fusion proteins into fibrin clots in vitro and in vivo: comparison of different fusion motifs recognized by factor XIIIa
<p>Abstract</p> <p>Background</p> <p>The transglutaminase activated factor XIII (FXIIIa) acts to strengthen pathological fibrin clots and to slow their dissolution, in part by crosslinking active α<sub>2</sub>-antiplasmin (α<sub>2</sub>AP) to fibrin. We previously reported that a yeast-derived recombinant fusion protein comprising α<sub>2</sub>AP residues 13-42 linked to human serum albumin (HSA) weakened <it>in vitro </it>clots but failed to become specifically incorporated into <it>in vivo </it>clots. In this study, our aims were to improve both the stability and clot localization of the HSA fusion protein by replacing α<sub>2</sub>AP residues 13-42 with shorter sequences recognized more effectively by FXIIIa.</p> <p>Results</p> <p>Expression plasmids were prepared encoding recombinant HSA with the following N-terminal 23 residue extensions: H<sub>6</sub>NQEQVSPLTLLAG<sub>4</sub>Y (designated XL1); H<sub>6</sub>DQMMLPWAVTLG<sub>4</sub>Y (XL2); H<sub>6</sub>WQHKIDLPYNGAG<sub>4</sub>Y (XL3); and their 17 residue non-His-tagged equivalents (XL4, XL5, and XL6). The HSA moiety of XL4- to XL6-HSA proteins was C-terminally His-tagged. All chimerae were efficiently secreted from transformed <it>Pichia pastoris </it>yeast except XL3-HSA, and following nickel chelate affinity purification were found to be intact by amino acid sequencing, as was an N-terminally His-tagged version of α<sub>2</sub>AP(13-42)-HSA. Of the proteins tested, XL5-HSA was cross-linked to biotin pentylamine (BPA) most rapidly by FXIIIa, and was the most effective competitor of α<sub>2</sub>AP crosslinking not only to BPA but also to plasma fibrin clots. In the mouse ferric chloride <it>vena cava </it>thrombosis model, radiolabeled XL5-HSA was retained in the clot to a greater extent than recombinant HSA. In the rabbit jugular vein stasis thrombosis model, XL5-HSA was also retained in the clot, in a urea-insensitive manner indicative of crosslinking to fibrin, to a greater extent than recombinant HSA.</p> <p>Conclusions</p> <p>Fusion protein XL5-HSA (DQMMLPWAVTLG<sub>4</sub>Y-HSAH<sub>6</sub>) was found to be more active as a substrate for FXIIIa-mediated transamidation than seven other candidate fusion proteins <it>in vitro</it>. The improved stability and reactivity of this chimeric protein was further evidenced by its incorporation into <it>in vivo </it>clots formed in thrombosis models in both mice and rabbits.</p
IL-2 Regulates SEB Induced Toxic Shock Syndrome in BALB/c Mice
BACKGROUND:Toxic Shock Syndrome (TSS) is characterized by fever, rash, hypotension, constitutional symptoms, and multi-organ involvement and is caused by Staphylococcus aureus enterotoxins such as Staphylococcal Enterotoxin B (SEB). SEB binds to the MHC-IIalpha chain and is recognized by the TCRbeta chain of the Vbeta8 TCR(+) T cells. The binding of SEB to Vbeta chain results in rapid activation of T cells and production of inflammatory cytokines, such as Interleukin-2 (IL-2), Interferon-gamma and Tumor Necrosis Factor-alpha which mediate TSS. Although IL2 was originally identified as the T cell growth factor and was proposed to contribute to T cell differentiation, its role in TSS remains unexplored. METHODOLOGY/PRINCIPAL FINDINGS:Mice were injected with D-Gal (25 mg/mouse). One hour after D-Galactosamine (D-Gal) injection each mouse was injected with SEB (20 microg/mouse. Mice were then observed for 72 hrs and death was recorded at different times. We tested Interleukin-12, IFNgamma, and IL-2 deficient mice (IL-2(-/-)), but only the IL-2 deficient mice were resistant to SEB induced toxic shock syndrome. More importantly reconstitution of IL-2 in IL-2 deficient mice restored the shock. Interestingly, SEB induced IL-2 production from T cells was dependent on p38MAPK activation in macrophages as inhibition of it in macrophages significantly inhibited IL-2 production from T cells. CONCLUSION:This study shows the importance of IL -2 in TSS which has not been previously explored and it also shows that regulating macrophages function can regulate T cells and TSS
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