Gene content evolution in the arthropods

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

Selective inhibition of the human tie-1 promoter with triplex-forming oligonucleotides targeted to ets binding sites

The Tie receptors (Tie-1 and Tie-2/Tek) are essential for angiogenesis and vascular remodeling/integrity. Tie receptors are up-regulated in tumor-associated endothelium, and their inhibition disrupts angiogenesis and can prevent tumor growth as a consequence. To investigate the potential of anti-gene approaches to inhibit tie gene expression for anti-angiogenic therapy, we have examined triple-helical (triplex) DNA formation at 2 tandem Ets transcription factor binding motifs (designated E-1 and E-2) in the human tie-1 promoter. Various tie-1 promoter deletion/mutation luciferase reporter constructs were generated and transfected into endothelial cells to examine the relative activities of E-1 and E-2. The binding of antiparallel and parallel (control) purine motif oligonucleotides (21-22 bp) targeted to E-1 and E-2 was assessed by plasmid DNA fragment binding and electrophoretic mobility shift assays. Triplex-forming oligonucleotides were incubated with tie-1 reporter constructs and transfected into endothelial cells to determine their activity. The Ets binding motifs in the E-1 sequence were essential for human tie-1 promoter activity in endothelial cells, whereas the deletion of E-2 had no effect. Antiparallel purine motif oligonucleotides targeted at E-1 or E-2 selectively formed strong triplex DNA (K(d) approximately 10(-7) M) at 37 degrees C. Transfection of tie-1 reporter constructs with triplex DNA at E-1, but not E-2, specifically inhibited tie-1 promoter activity by up to 75% compared with control oligonucleotides in endothelial cells. As similar multiple Ets binding sites are important for the regulation of several endothelial-restricted genes, this approach may have broad therapeutic potential for cancer and other pathologies involving endothelial proliferation/dysfunction

Evaluation of viral co-infections among patients with community-associated Clostridioides difficile infection.

We assessed viral co-infections in 155 patients with community-associated Clostridioides difficile infection in five U.S. sites during December 2012-February 2013. Eighteen patients (12%) tested positive for norovirus (n = 10), adenovirus (n = 4), rotavirus (n = 3), or sapovirus (n = 1). Co-infected patients were more likely than non-co-infected patients to have nausea or vomiting (56% vs 31%; p = 0.04), suggesting that viral co-pathogens contributed to symptoms in some patients. There were no significant differences in prior healthcare or medication exposures or in CDI complications

Cost-effectiveness of Increasing Access to Contraception during the Zika Virus Outbreak, Puerto Rico, 2016

We modeled the potential cost-effectiveness of increasing access to contraception in Puerto Rico during a Zika virus outbreak. The intervention is projected to cost an additional $33.5 million in family planning services and is likely to be cost-saving for the healthcare system overall. It could reduce Zika virus–related costs by$65.2 million ($2.8 million from less Zika virus testing and monitoring and$62.3 million from avoided costs of Zika virus–associated microcephaly [ZAM]). The estimates are influenced by the contraception methods used, the frequency of ZAM, and the lifetime incremental cost of ZAM. Accounting for unwanted pregnancies that are prevented, irrespective of Zika virus infection, an additional $40.4 million in medical costs would be avoided through the intervention. Increasing contraceptive access for women who want to delay or avoid pregnancy in Puerto Rico during a Zika virus outbreak can substantially reduce the number of cases of ZAM and healthcare costs

Child mental health and maternal depression history in Pakistan

Purpose We address the significant gaps in knowledge of prevalence and correlates of child mental health (CMH) problems outside of high income countries. We describe the prevalence of CMH problems and their correlates with a focus on the association with maternal depression in a sample of seven-year-old children in rural Pakistan. Methods This study was nested in a long-term follow-up of a perinatal depression intervention together with a reference group of non-depressed women, yielding a population representative sample. The Total Difficulties (TD) and component scores of the Strength and Difficulties Questionnaire (SDQ) were used to measure emotional and behavioral difficulties. Results The mean SDQ TD score was 10.6 (standard deviation = 8.3), with 12.5 % of children categorized as ?abnormal? using standard cutoffs. Boys had a roughly 1 point higher (worse) SDQ TD score than girls (p value = 0.04). Children of mothers who were depressed prenatally as well as currently had SDQ TD scores 2.87 points higher than children whose mothers were not depressed at either time point (p value < 0.01). This association was stronger for boys. There was no evidence of elevated SDQ TD score among children whose mothers were depressed only prenatally or only currently. Some deviations from this pattern were observed with specific components of the SDQ. Conclusions In this low resource, South Asian setting, we found evidence of elevated levels of emotional and behavioral problems, highlighting the need for effective interventions. Given the strong association of CMH with maternal depression, any intervention efforts should give strong consideration to maternal mental health