Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Aggression after paediatric traumatic brain injury: A theoretical approach

Primary objective: To examine aggression in adolescent males with and without traumatic brain injury (TBI). Design: Quasi-experimental, matched-participants design. Methods: Thirty-nine adolescents were examined, including a TBI group (n= 11) and a matched, uninjured comparison group (n= 28). Participants with TBI were injured an average of 8.3 years (SD = 4.2 years) prior. Participants and parents completed the Youth Self Report (YSR) and the Child Behavior Checklist (CBCL), both measures of global psychopathology. In addition, the theoretically-driven Reactive and Proactive Aggression Questionnaire (RPQ) and the Form of Aggression Scale (FAS) were completed. Main outcomes and results: When compared using the YSR and CBCL, no group differences were detected. In contrast, using the self-report RPQ, participants with TBI reported more reactive and proactive aggression than non-injured peers. Using the FAS, participants with TBI reported engaging in aggression out of frustration and not to dominate or acquire objects. Conclusion: Aggressive behaviours are a long-term outcome after paediatric TBI. Measures of global psychopathology do not permit detailed examination of specific behaviour problems such as aggression, which may provide inaccurate data from which to derive incidence rates. In contrast, theoretically-driven measures can provide greater insight into post-TBI aggression with important treatment implications

Cytomegalovirus (CMV) IE1- and pp65-specific CD8+ T cell responses broaden over time after primary CMV infection in infants

Cytomegalovirus (CMV) infection remains a significant cause of morbidity and mortality in young children. We have previously shown that CD8+ T cell responses to CMV pp65 or IE1 protein were readily detectable in children with congenital or postnatal CMV infection. Here, we have further characterized the evolution of the peptide specificity of these responses in 7 infants(median, 5 peptides/infant) were targeted, and most (61%) represented sequences not previously reported. Peptide specificity remained stable or broadened over time despite the clearance of CMV viremia. Loss of peptide recognition was not observed. Responses with the highest functional peptide avidity were not necessarily detected earliest. These data provide additional evidence that young infants can generate diverse CMV-specific CD8+ T cell responses but show that early responses may exhibit relatively focused peptide specificity and lower peptide avidity

Reduced frequencies of polyfunctional CMV-specific T cell responses in infants with congenital CMV infection

PURPOSE: CMV infection remains a priority for vaccine development. Vaccination of infants could modify congenital infection and provide lifetime immunity. Properties of CMV-specific T cells associated with control of viral replication in early life have not been fully defined. METHODS: CMV-specific CD4 and CD8 T cell responses were investigated in infants with congenital CMV infection and compared to adults with primary or chronic infection. PBMC were stimulated with UL83 (pp65) or UL122 (IE-2) peptide pools then stained with antibodies to markers of T cell subset (CD4 or CD8), phenotype (CD45RA, CCR7), or function (MIP1beta, CD107, IFNgamma, IL2) for flow cytometry analysis. RESULTS: Detection of CMV pp65-specific CD4 T cells was less common in infants than adults. Responder cells were primarily effector memory (EM, CD45RA-CCR7-) in adults, but mixed memory subsets in infants. Detection of CMV pp65-specific CD8 T cells did not differ between the groups, but infants had lower frequencies of total responding cells and of MIP1beta- or CD107-expressing cells. Responder cells were EM or effector memory RA (CD45RA + CCR7-) in all groups. Polyfunctional T cells were less commonly detected in infants than adults. Responses to IE-2 were detected in adults but not infants. All infants had detectable circulating CMV DNA at initial study (versus 60 % of adults with primary infection) despite longer duration of CMV infection. CONCLUSIONS: Reduced frequencies and altered functional profile of CMV-specific CD4 and CD8 T cell responses were detected in infants compared to adults, and were associated with persistent CMV DNA in peripheral blood

Personal exposure of dairy workers to dust, endotoxin, muramic acid, ergosterol and ammonia on large-scale dairies in the high plains western United States

Dairy workers experience a high degree of bioaerosol exposure, composed of an array of biological and chemical constituents, which have been tied to adverse health effects. A better understanding of the variation in the magnitude and composition of exposures by task is needed to inform worker protection strategies. To characterize the levels and types of exposures, 115 dairy workers grouped into three task categories on nine farms in the high plains western United States underwent personal monitoring for inhalable dust, endotoxin, 3-hydroxy fatty acids (3-OHFA), muramic acid, ergosterol, and ammonia over one work shift. Eighty nine percent of dairy workers were exposed to endotoxin at concentrations exceeding the recommended exposure guidelines (adjusted for a long workshift). The proportion of workers with exposures exceeding recommended guidelines was lower for inhalable dust (12%), and ammonia (1%). Ergosterol exposures were only measurable on 28% of samples, primarily among medical workers and feed handlers. Milking parlor workers were exposed to significantly higher inhalable dust, endotoxin, 3-OHFA, ammonia and muramic acid concentrations compared to workers performing other tasks. Development of large modern dairies has successfully made progress in reducing worker exposures and lung disease prevalence. However, exposure to endotoxin, dust and ammonia continues to present a significant risk to worker health on North American dairies, especially for workers in milking parlors. This study was among the first to concurrently evaluate occupational exposure to assayable endotoxin (lipid A), 3-hydroxy fatty acids or 3-OHFA (a chemical measure of cell bound and non-cell-bound endotoxins), muramic acid, ergosterol, and ammonia among workers on western U.S. dairies. There remains a need for cost-effective, culturally acceptable intervention strategies integrated in OHS Risk Management and production systems to further optimize worker health and farm productivity

Longitudinal predictors of cyber and traditional bullying perpetration in Australian secondary school students

Purpose Cyberbullying perpetration (using communication technology to engage in bullying) is a recent phenomenon that has generated much concern. There are few prospective longitudinal studies of cyberbullying. The current article examines the individual, peer, family, and school risk factors for both cyber and traditional bullying (the latter is bullying that does not use technology) in adolescents. Methods This article draws on a rich data set from the International Youth Development Study, a longitudinal study of students in Victoria, Australia and Washington State, United States, which began in 2002. In this article, data from almost 700 Victorian students recruited in grade 5 are analyzed to examine grade 7 (aged 12–13 years) predictors of traditional and cyberbullying perpetration in grade 9 (aged 14–15 years). Results Fifteen per cent of students engaged in cyberbullying, 21% in traditional bullying, and 7% in both. There are similarities and important differences in the predictors of cyber and traditional bullying. In the fully adjusted model, only prior engagement in relational aggression (a covert form of bullying, such as spreading rumors about another student) predicted cyberbullying perpetration. For traditional bullying, previous relational aggression was also predictive, as was having been a victim and perpetrator of traditional bullying, family conflict, and academic failure. Conclusions The use of evidence-based bullying prevention programs is supported to reduce experiences of all forms of bullying perpetration (cyber, traditional, and relational aggression). In addition, for traditional bullying perpetration, addressing family conflict and student academic support are also important