Zika virus (ZIKV) infections occur in areas where dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), and other viruses of the genus
cocirculate. The envelope (E) proteins of these ...closely related flaviviruses induce specific long-term immunity, yet subsequent infections are associated with cross-reactive antibody responses that may enhance disease susceptibility and severity. To gain a better understanding of ZIKV infections against a background of similar viral diseases, we examined serological immune responses to ZIKV, WNV, DENV, and YFV infections of humans and nonhuman primates (NHPs). Using printed microarrays, we detected very specific antibody responses to primary infections with probes of recombinant E proteins from 15 species and lineages of flaviviruses pathogenic to humans, while high cross-reactivity between ZIKV and DENV was observed with 11 printed native viruses. Notably, antibodies from human primary ZIKV or secondary DENV infections that occurred in areas where flavivirus is endemic broadly recognized E proteins from many flaviviruses, especially DENV, indicating a strong influence of infection history on immune responses. A predictive algorithm was used to tentatively identify previous encounters with specific flaviviruses based on serum antibody interactions with the multispecies panel of E proteins. These results illustrate the potential impact of exposure to related viruses on the outcome of ZIKV infection and offer considerations for development of vaccines and diagnostics.
The recombinant dengue virus type-4 vaccine candidate 2AA30 was attenuated in rhesus monkeys due to an engineered 30-nucleotide deletion in the 3'-untranslated region of the viral genome. A clinical ...trial to evaluate the safety and immunogenicity of a single dose of 2Adelta30 was conducted with 20 adult human volunteers. The vaccine candidate was well tolerated and did not cause systemic illness in any of the 20 volunteers. Viremia was detectable in 14 volunteers at a mean level of 1.6 log10 plaque-forming units/ml of serum, although all 20 volunteers seroconverted with a seven-fold or greater increase in serum neutralizing antibody titer on day 28 post-vaccination (mean titer = 1:580). A mild, asymptomatic, macular rash developed in 10 volunteers, and a transient elevation in the serum level of alanine aminotransferase was noted in five volunteers. The low level of reactogenicity and high degree of immunogenicity of this vaccine candidate warrant its further evaluation and its use to create chimeric vaccine viruses expressing the structural genes of dengue virus types 1, 2, and 3.
Age constitutes a salient feature of a face and signals group membership. There is evidence of greater attention to and better memory for own-age than other-age faces. However, little is known about ...the neural and behavioral mechanisms underlying processing differences for own-age vs. other-age faces. Even less is known about the impact of emotion expressed in faces on such own-age effects. Using fMRI, the present study examined brain activity while young and older adult participants identified expressions of neutral, happy, and angry young and older faces. Across facial expressions, medial prefrontal cortex, insula, and (for older participants) amygdala showed greater activity to own-age than other-age faces. These own-age effects in ventral medial prefrontal cortex and insula held for neutral and happy faces, but not for angry faces. This novel and intriguing finding suggests that processing of negative facial emotions under some conditions overrides age-of-face effects.
•fMRI study of mechanisms of own-age face processing and effects of emotion.•Greater activity for own-age than other-age faces in mPFC, insula, and amygdala.•Processing of negative expressions overrides age-of-face effects.•Effects of familiarity, motivational salience, affective evaluation are discussed.
Over the past several years, there has been increased interest in reformulated and alternative diesel fuels to control emissions and provide energy independence. In the following study, a California ...diesel fuel was compared with neat biodiesel, an 80% California diesel/20% biodiesel blend, and a synthetic diesel fuel to examine the effects on emissions. Chassis dynamometer tests were performed on four light heavy-duty diesel trucks using each of the four fuels. The results of this study showed that biodiesel, the biodiesel blends, and the synthetic diesel produced generally lower THC and CO emissions than California diesel. NO x emissions were comparable over most of the fuel/vehicle combinations, with slightly higher NO x emissions found for the two noncatalyst vehicles on 100% biodiesel. Particulate emissions were slightly higher for two test vehicles and significantly higher for a third test vehicle on the biodiesel fuels. Chemical analyses showed elemental and organic carbon to be the primary constituents of the diesel particulate, accounting for 73−80% of the total mass for the four vehicles. Neat biodiesel had the highest organic carbon fractions for each of the test vehicles. PAH emissions for all fuel combinations were relatively low, probably due to the low fuel PAH levels.
Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all ...genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.
Currently, many states are upgrading their child restraint laws to include provisions for the use of age-appropriate restraints through 6 to 8 years of age, with some also requiring rear seating for ...children, enabling the laws to be in closer alignment with best-practice recommendations.
To evaluate the relationships of seating position and restraint status to the risk of injury among children in passenger vehicle crashes.
This was a cross-sectional study of children <16 years of age who were involved in crashes of insured vehicles in 15 states, with data collected via insurance claims records and a telephone survey. A probability sample of 17980 children in 11506 crashes, representing 229106 children in 146613 crashes, was collected between December 1, 1998, and November 30, 2002. Parent reports were used to define restraint status, seating position, and occurrence of clinically significant injuries, with the use of a previously validated instrument.
Approximately 62% of the children used seat belts, 35% used child restraints, and 3% used no restraint. Nearly 4 of 5 children sat in the rear seat, with one half of all children being restrained appropriately for their age in the rear, although this varied according to the age of the child. Overall, 1.6% of children suffered serious injuries, 13.5% had minor injuries, and 84.9% did not have any injury. Unrestrained children in the front were at the highest risk of injury and appropriately restrained children in the rear were at the lowest risk, for all age groups. Inappropriately restrained children were at nearly twice the risk of injury, compared with appropriately restrained children (odds ratio OR: 1.8; 95% confidence interval CI: 1.4-2.3), whereas unrestrained children were at >3 times the risk (OR: 3.2; 95% CI: 2.5-4.1). The effect of seating row was smaller than the effect of restraint status; children in the front seat were at 40% greater risk of injury, compared with children in the rear seat (OR: 1.4; 95% CI: 1.2-1.7). Had all children in the study population been appropriately restrained in the rear seat, 1014 serious injuries (95% CI: 675-1353 injuries) would have been prevented (with the assumption that restraint effectiveness does not depend on a variety of other driver-related, child-related, crash-related, vehicle-related, and environmental factors).
Age-appropriate restraint confers relatively more safety benefit than rear seating, but the 2 work synergistically to provide the best protection for children in crashes. These results support the current focus on age-appropriate restraint in recently upgraded state child restraint laws. However, it is important to note that considerable added benefit would be realized with additional requirements for rear seating.
The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and ...five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.
Objective To determine the prevalence and nature of residual cognitive disability after inpatient rehabilitation for children aged 7-18 years with traumatic injuries. Study design This retrospective ...cohort study included children aged 7-18 years in the Uniform Data System for Medical Rehabilitation who underwent inpatient rehabilitation for traumatic injuries in 523 facilities from 2002-2011. Traumatic injuries were identified by standardized Medicare Inpatient Rehabilitation Facility–Patient Assessment Instrument codes. Cognitive outcomes were measured by the Functional Independence Measure instrument. A validated, categorical staging system derived from responses to the items in the cognitive domain of the functional independence measure was used and consisted of clinically relevant levels of cognitive achievement from stage 1 (total cognitive disability) to stage 7 (completely independent cognitive function). Results There were 13 798 injured children who completed inpatient rehabilitation during the 10-year period. On admission to inpatient rehabilitation, patients with traumatic brain injury (TBI) had more cognitive disability (median stage 2) than those with spinal cord injury or other injuries (median stage 5). Cognitive functioning improved for all patients, but children with TBI still tended to have significant residual cognitive disability (median stage on discharge, 4). Conclusions Injured children gained cognitive functionality throughout inpatient rehabilitation. Those with TBI had more severe cognitive disability on admission and more residual disability on discharge. This is important not only for patient and family expectation setting but also for resource and service planning, as discharge from inpatient rehabilitation is a critical milestone for reintegration into society for children with serious injury.
Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide ...resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.
Interpreting variants, especially noncoding ones, in the increasing number of personal genomes is challenging. We used patterns of polymorphisms in functionally annotated regions in 1092 humans to ...identify deleterious variants; then we experimentally validated candidates. We analyzed both coding and noncoding regions, with the former corroborating the latter. We found regions particularly sensitive to mutations ("ultrasensitive") and variants that are disruptive because of mechanistic effects on transcription-factor binding (that is, "motif-breakers"). We also found variants in regions with higher network centrality tend to be deleterious. Insertions and deletions followed a similar pattern to single-nucleotide variants, with some notable exceptions (e.g., certain deletions and enhancers). On the basis of these patterns, we developed a computational tool (FunSeq), whose application to ~90 cancer genomes reveals nearly a hundred candidate noncoding drivers.
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