Spaceflight Standard Measures

The main goal is to ensure that a minimal set of measures is consistently captured from all ISS crewmembers until the end of ISS to characterize the effects of space. The data from these measures will placed in an archive managed by HRP and can be made available to studies via data sharing agreements

CD1b-restricted GEM T cell responses are modulated by Mycobacterium tuberculosis mycolic acid meromycolate chains

Tuberculosis, caused by Mycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in tuberculosis granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs. Computational simulations suggest that meromycolate chain dynamics regulate mycolate head group movement, thereby modulating GEM-TCR activity. Our findings have significant implications for the design of future vaccines that target GEM T cells

Testing and Validation of High Density Resequencing Microarray for Broad Range Biothreat Agents Detection

Rapid and effective detection and identification of emerging microbiological threats and potential biowarfare agents is very challenging when using traditional culture-based methods. Contemporary molecular techniques, relying upon reverse transcription and/or polymerase chain reaction (RT-PCR/PCR) provide a rapid and effective alternative, however, such assays are generally designed and optimized to detect only a limited number of targets, and seldom are capable of differentiation among variants of detected targets. To meet these challenges, we have designed a broad-range resequencing pathogen microarray (RPM) for detection of tropical and emerging infectious agents (TEI) including biothreat agents: RPM-TEI v 1.0 (RPM-TEI). The scope of the RPM-TEI assay enables detection and differential identification of 84 types of pathogens and 13 toxin genes, including most of the class A, B and C select agents as defined by the Centers for Disease Control and Prevention (CDC, Atlanta, GA). Due to the high risks associated with handling these particular target pathogens, the sensitivity validation of the RPM-TEI has been performed using an innovative approach, in which synthetic DNA fragments are used as templates for testing the assay's limit of detection (LOD). Assay specificity and sensitivity was subsequently confirmed by testing with full-length genomic nucleic acids of selected agents. The LOD for a majority of the agents detected by RPM-TEI was determined to be at least 104 copies per test. Our results also show that the RPM-TEI assay not only detects and identifies agents, but is also able to differentiate near neighbors of the same agent types, such as closely related strains of filoviruses of the Ebola Zaire group, or the Machupo and Lassa arenaviruses. Furthermore, each RPM-TEI assay results in specimen-specific agent gene sequence information that can be used to assess pathogenicity, mutations, and virulence markers, results that are not generally available from multiplexed RT-PCR/PCR-based detection assays

Metagenomic analysis of viruses associated with maize lethal necrosis in Kenya

Background: Maize lethal necrosis is caused by a synergistic co-infection of Maize chlorotic mottle virus (MCMV) and a specific member of the Potyviridae, such as Sugarcane mosaic virus (SCMV), Wheat streak mosaic virus (WSMV) or Johnson grass mosaic virus (JGMV). Typical maize lethal necrosis symptoms include severe yellowing and leaf drying from the edges. In Kenya, we detected plants showing typical and atypical symptoms. Both groups of plants often tested negative for SCMV by ELISA. Methods: We used next-generation sequencing to identify viruses associated to maize lethal necrosis in Kenya through a metagenomics analysis. Symptomatic and asymptomatic leaf samples were collected from maize and sorghum representing sixteen counties. Results: Complete and partial genomes were assembled for MCMV, SCMV, Maize streak virus (MSV) and Maize yellow dwarf virus-RMV (MYDV-RMV). These four viruses (MCMV, SCMV, MSV and MYDV-RMV) were found together in 30 of 68 samples. A geographic analysis showed that these viruses are widely distributed in Kenya. Phylogenetic analyses of nucleotide sequences showed that MCMV, MYDV-RMV and MSV are similar to isolates from East Africa and other parts of the world. Single nucleotide polymorphism, nucleotide and polyprotein sequence alignments identified three genetically distinct groups of SCMV in Kenya. Variation mapped to sequences at the border of NIb and the coat protein. Partial genome sequences were obtained for other four potyviruses and one polerovirus. Conclusion: Our results uncover the complexity of the maize lethal necrosis epidemic in Kenya. MCMV, SCMV, MSV and MYDV-RMV are widely distributed and infect both maize and sorghum. SCMV population in Kenya is diverse and consists of numerous strains that are genetically different to isolates from other parts of the world. Several potyviruses, and possibly poleroviruses, are also involved

Chromosomal Inversions between Human and Chimpanzee Lineages Caused by Retrotransposons

The long interspersed element-1 (LINE-1 or L1) and Alu elements are the most abundant mobile elements comprising 21% and 11% of the human genome, respectively. Since the divergence of human and chimpanzee lineages, these elements have vigorously created chromosomal rearrangements causing genomic difference between humans and chimpanzees by either increasing or decreasing the size of genome. Here, we report an exotic mechanism, retrotransposon recombination-mediated inversion (RRMI), that usually does not alter the amount of genomic material present. Through the comparison of the human and chimpanzee draft genome sequences, we identified 252 inversions whose respective inversion junctions can clearly be characterized. Our results suggest that L1 and Alu elements cause chromosomal inversions by either forming a secondary structure or providing a fragile site for double-strand breaks. The detailed analysis of the inversion breakpoints showed that L1 and Alu elements are responsible for at least 44% of the 252 inversion loci between human and chimpanzee lineages, including 49 RRMI loci. Among them, three RRMI loci inverted exonic regions in known genes, which implicates this mechanism in generating the genomic and phenotypic differences between human and chimpanzee lineages. This study is the first comprehensive analysis of mobile element bases inversion breakpoints between human and chimpanzee lineages, and highlights their role in primate genome evolution

Error Bounded Approximate Reparametrization Of Non-Uniform Rational B-Spline Curves

In designing free-form curves and surfaces, the user of a geometric modeler generally wishes to concentrate on shape. Geometric constructions using parametrically defined representations, however, often lead to unwanted or surprising effects due to curve and surface parametrizations. Reparametrizing curve or surface representations is an important approach to minimizing these effects. Reparametrization also can be viewed as a means for transforming curves and surfaces into representations that are better suited to establishing important properties or exploring the design space. This research explores the use of curve reparametrization in modeling tools for NURBS (Non-Uniform Rational B-Spline) based CAD systems. There are many practical applications of such tools including establishing and exploring correspondence in geometry, creating related speed profiles along motion curves for animation, specifying speeds along tool paths, and identifying geometrically equivalent, or nearly equiv..

Uptake and Population-Level Impact of Expedited Partner Therapy (EPT) on <i>Chlamydia trachomatis</i> and <i>Neisseria gonorrhoeae</i>: The Washington State Community-Level Randomized Trial of EPT

<div><p>Background</p><p>Expedited partner therapy (EPT), the practice of treating the sex partners of persons with sexually transmitted infections without their medical evaluation, increases partner treatment and decreases gonorrhea and chlamydia reinfection rates. We conducted a stepped-wedge, community-level randomized trial to determine whether a public health intervention promoting EPT could increase its use and decrease chlamydia test positivity and gonorrhea incidence in women.</p><p>Methods and Findings</p><p>The trial randomly assigned local health jurisdictions (LHJs) in Washington State, US, into four study waves. Waves instituted the intervention in randomly assigned order at intervals of 6–8 mo. Of the state’s 25 LHJs, 24 were eligible and 23 participated. Heterosexual individuals with gonorrhea or chlamydial infection were eligible for the intervention. The study made free patient-delivered partner therapy (PDPT) available to clinicians, and provided public health partner services based on clinician referral. The main study outcomes were chlamydia test positivity among women ages 14–25 y in 219 sentinel clinics, and incidence of reported gonorrhea in women, both measured at the community level. Receipt of PDPT from clinicians was evaluated among randomly selected patients. 23 and 22 LHJs provided data on gonorrhea and chlamydia outcomes, respectively. The intervention increased the percentage of persons receiving PDPT from clinicians (from 18% to 34%, <i>p</i> < 0.001) and the percentage receiving partner services (from 25% to 45%, <i>p</i> < 0.001). Chlamydia test positivity and gonorrhea incidence in women decreased over the study period, from 8.2% to 6.5% and from 59.6 to 26.4 per 100,000, respectively. After adjusting for temporal trends, the intervention was associated with an approximately 10% reduction in both chlamydia positivity and gonorrhea incidence, though the confidence bounds on these outcomes both crossed one (chlamydia positivity prevalence ratio = 0.89, 95% CI 0.77–1.04, <i>p</i> = 0.15; gonorrhea incidence rate ratio = 0.91, 95% CI .71–1.16, <i>p</i> = 0.45). Study findings were potentially limited by inadequate statistical power, by the institution of some aspects of the study intervention outside of the research randomization sequence, and by the fact that LHJs did not constitute truly isolated sexual networks.</p><p>Conclusions</p><p>A public health intervention promoting the use of free PDPT substantially increased its use and may have resulted in decreased chlamydial and gonococcal infections at the population level.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01665690" target="_blank">NCT01665690</a></p></div