Good spaced seeds for homology search

MOTIVATION: Filtration is an important technique used to speed up local alignment as exemplified in the BLAST programs. Recently, Ma et al. discovered that better filtering can be achieved by spacing out the matching positions according to a certain pattern, instead of contiguous positions to trigger a local alignment in their PatternHunter program. Such a match pattern is called a spaced seed. RESULTS: Our numerical computation shows that the ranks of spaced seeds (based on sensitivity) change with the sequences similarity. Since homologous sequences may have diverse similarity, we assess the sensitivity of spaced seeds over a range of similarity levels and present a list of good spaced seeds for facilitating homology search in DNA genomic sequences. We validate that the listed spaced seeds are indeed more sensitive using three arbitrarily chosen pairs of DNA genomic sequences.     

Beta 57-Asp plays an essential role in the unique SDS stability of HLA-DQA1*0102/DQB1*0602 alpha beta protein dimer, the class II MHC allele associated with protection from insulin-dependent diabetes mellitus

Studies of the stability of HLA-DQ have revealed a correlation between SDS stability of MHC class II alphabeta dimers and insulin-dependent diabetes mellitus (IDDM) susceptibility. The MHC class II alphabeta dimer encoded by HLA-DQA1*0102/DQB1*0602 (DQ0602), which is a dominant protective allele in IDDM, exhibits the greatest SDS stability among HLA-DQ molecules in EBV-transformed B-lymphoblastoid cells and PBLs. DQ0602 is also uniquely SDS stable in the HLA-DM-deficient cell line, BLS-1. We addressed the molecular mechanism of the stability of DQ0602 in BLS-1. A panel of mutants based on the polymorphic differences between HLA-DQA1*0102/DQB1*0602 and HLA-DQA1*0102/DQB1*0604 were generated and expressed in BLS-1. An Asp at beta57 was found to be critical for SDS stability, whereas Tyr at beta30, Gly at beta70, and Ala at beta86 played secondary roles. Furthermore, the level of class II-associated invariant chain peptide bound to HLA-DQ did not correlate with SDS stability, suggesting that class II-associated invariant chain peptide does not play a direct role in the unique SDS stability of DQ0602. These results support a role for DQB1 codon 57 in HLA-DQ alphabeta dimer stability and IDDM susceptibility.     

Low molecular weight disulfide cross-linking peptides as nonviral gene delivery carriers

Cross-linking peptides have been developed by inserting multiple Cys residues into a 20 amino acid condensing peptide that polymerizes through disulfide bond formation when bound to DNA resulting in small, highly stable DNA condensates that mediate efficient in vitro gene transfer [McKenzie et al. (2000) J. Biol. Chem. 275, 9970-9977]. In the present study, a minimal peptide of four Lys and two terminal Cys residues was found to substitute for Cys-Trp-(Lys)(17)-Cys, resulting in DNA condensates with similar particle size and gene expression in HepG2 cells. Substitution of His for Lys residues resulted in an optimal peptide of Cys-His-(Lys)(6)-His-Cys that, in addition to the attributes described above, also provided buffering capacity to enhance in vitro gene expression in the absence of chloroquine. The reported structure-activity relationships systematically explore peptides with combinations of Lys, Cys, and His residues resulting in low molecular weight peptides with improved gene transfer properties.     

Effect of an injury awareness education program on risk-taking behaviors and injuries in juvenile justice offenders: a retrospective cohort study

Background

Risk-taking behavior is a leading cause of injury and death amongst young people.

Methodology and Principal Findings

This was a retrospective cohort study on the effectiveness of a 1-day youth injury awareness education program (Prevent Alcohol and Risk-related Trauma in Youth, P.A.R.T.Y.) program in reducing risk taking behaviors and injuries of juvenille justice offenders in Western Australia. Of the 3659 juvenile justice offenders convicted by the court magistrates between 2006 and 2010, 225 were referred to the P.A.R.T.Y. education program. In a before and after survey of these 225 participants, a significant proportion of them stated that they were more receptive to modifying their risk-taking behavior (21% before vs. 57% after). Using data from the Western Australia Police and Department of Health, the incidence of subsequent offences and injuries of all juvenile justice offenders was assessed. The incidence of subsequent traffic or violence-related offences was significantly lower for those who had attended the program compared to those who did not (3.6% vs. 26.8%; absolute risk reduction [ARR] = 23.2%, 95% confidence interval [CI] 19.9%–25.8%; number needed to benefit = 4.3, 95%CI 3.9–5.1; p = 0.001), as were injuries leading to hospitalization (0% vs. 1.6% including 0.2% fatality; ARR = 1.6%, 95%CI 1.2%–2.1%) and alcohol or drug-related offences (0% vs. 2.4%; ARR 2.4%, 95%CI 1.9%–2.9%). In the multivariate analysis, only P.A.R.T.Y. education program attendance (odds ratio [OR] 0.10, 95%CI 0.05–0.21) and a higher socioeconomic background (OR 0.97 per decile increment in Index of Relative Socioeconomic Advantage and Disadvantage, 95%CI 0.93–0.99) were associated with a lower risk of subsequent traffic or violence-related offences.

Significance

Participation in an injury education program involving real-life trauma scenarios was associated with a reduced subsequent risk of committing violence- or traffic-related offences, injuries, and death for juvenille justice offenders.     

Access to reliable information about long-term prognosis influences clinical opinion on use of lifesaving intervention

Background

Decompressive craniectomy has been traditionally used as a lifesaving rescue treatment in severe traumatic brain injury (TBI). This study assessed whether objective information on long-term prognosis would influence healthcare workers'' opinion about using decompressive craniectomy as a lifesaving procedure for patients with severe TBI.

Method

A two-part structured interview was used to assess the participants'' opinion to perform decompressive craniectomy for three patients who had very severe TBI. Their opinion was assessed before and after knowing the predicted and observed risks of an unfavourable long-term neurological outcome in various scenarios.

Results

Five hundred healthcare workers with a wide variety of clinical backgrounds participated. The participants were significantly more likely to recommend decompressive craniectomy for their patients than for themselves (mean difference in visual analogue scale [VAS] −1.5, 95% confidence interval −1.3 to −1.6), especially when the next of kin of the patients requested intervention. Patients'' preferences were more similar to patients who had advance directives. The participants'' preferences to perform the procedure for themselves and their patients both significantly reduced after knowing the predicted risks of unfavourable outcomes, and the changes in attitude were consistent across different specialties, amount of experience in caring for similar patients, religious backgrounds, and positions in the specialty of the participants.

Conclusions

Access to objective information on risk of an unfavourable long-term outcome influenced healthcare workers'' decision to recommend decompressive craniectomy, considered as a lifesaving procedure, for patients with very severe TBI.     

Airflow dynamics of coughing in healthy human volunteers by shadowgraph imaging: an aid to aerosol infection control

Cough airflow dynamics have been previously studied using a variety of experimental methods. In this study, real-time, non-invasive shadowgraph imaging was applied to obtain additional analyses of cough airflows produced by healthy volunteers. Twenty healthy volunteers (10 women, mean age 32.2±12.9 years; 10 men, mean age 25.3±2.5 years) were asked to cough freely, then into their sleeves (as per current US CDC recommendations) in this study to analyze cough airflow dynamics. For the 10 females (cases 1-10), their maximum detectable cough propagation distances ranged from 0.16-0.55 m, with maximum derived velocities of 2.2-5.0 m/s, and their maximum detectable 2-D projected areas ranged from 0.010-0.11 m(2), with maximum derived expansion rates of 0.15-0.55 m(2)/s. For the 10 males (cases 11-20), their maximum detectable cough propagation distances ranged from 0.31-0.64 m, with maximum derived velocities of 3.2-14 m/s, and their maximum detectable 2-D projected areas ranged from 0.04-0.14 m(2), with maximum derived expansion rates of 0.25-1.4 m(2)/s. These peak velocities were measured when the visibility of the exhaled airflows was optimal and compare favorably with those reported previously using other methods, and may be seen as a validation of these previous approaches in a more natural setting. However, the propagation distances can only represent a lower limit due to the inability of the shadowgraph method to visualize these cough airflows once their temperature cools to that of the ambient air, which is an important limitation of this methodology. The qualitative high-speed video footage of these volunteers coughing into their sleeves demonstrates that although this method rarely completely blocks the cough airflow, it decelerates, splits and redirects the airflow, eventually reducing its propagation. The effectiveness of this intervention depends on optimum positioning of the arm over the nose and mouth during coughing, though unsightly stains on sleeves may make it unacceptable to some.     

Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes

Although human induced pluripotent stem cells (hiPSCs) have enormous potential in regenerative medicine, their epigenetic variability suggests that some lines may not be suitable for human therapy. There are currently few benchmarks for assessing quality. Here we show that X-inactivation markers can be used to separate hiPSC lines into distinct epigenetic classes and that the classes are phenotypically distinct. Loss of XIST expression is strongly correlated with upregulation of X-linked oncogenes, accelerated growth rate in?vitro, and poorer differentiation in?vivo. Whereas differences in X-inactivation potential result in epigenetic variability of female hiPSC lines, male hiPSC lines generally resemble each other and do not overexpress the oncogenes. Neither physiological oxygen levels nor HDAC inhibitors offer advantages to culturing female hiPSC lines. We conclude that female hiPSCs may be epigenetically less stable in culture and caution that loss of?XIST may result in qualitatively less desirable stem cell lines.     

Multifunctional protein particles with dual analytical channels for colorimetric enzymatic bioassays and fluorescent immunoassays

Advanced multifunctional protein particles encapsulated enzymes and antibodies were developed for enzymatic bioassays and immunoassays with colorimetric and fluorescent channels. A colorimetric channel based on color-substrate precipitation was assigned for enzymatic bioassays for the measurement of hydrogen peroxide with the lowest detectable concentration of 10 μM. A fluorescent channel based on fluorescent labeled antibodies was assigned for immunoassays for the measurement of mouse immunoglobulin G (M IgG) with the lowest detectable concentration of 1.25 μgL(-1). The protein microparticles were fabricated with a template-assisted self-assembly technique termed "Protein Activation Spontaneous Self-assemble" (PASS). The multifunctional protein particles prepared with the PASS method have the advantages of high loading of analytical biomolecules, integrated biological functions, porous structure, and more importantly, they are optically transparent and fluorescence inactive. These unique features make our protein particles a new generation of bead-based platforms to perform enzyme bioassays and immunoassays.     

Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas

Cathepsin S is a lysosomal cysteine protease implicated in tumourigenesis with key roles in invasion and angiogenesis. We have previously shown that the specific inhibition of Cathepsin S using a monoclonal antibody (Fsn0503) blocks colorectal carcinoma tumour growth and angiogenesis in vivo.