Rewiring of Aminoacyl-tRNA Synthetase Localization and Interactions in Plants With Extensive Mitochondrial tRNA Gene Loss

The number of tRNAs encoded in plant mitochondrial genomes varies considerably. Ongoing loss of bacterial-like mitochondrial tRNA genes in many lineages necessitates the import of nuclear-encoded counterparts that share little sequence similarity. Because tRNAs are involved in highly specific molecular interactions, this replacement process raises questions about the identity and trafficking of enzymes necessary for the maturation and function of newly imported tRNAs. In particular, the aminoacyl-tRNA synthetases (aaRSs) that charge tRNAs are usually divided into distinct classes that specialize on either organellar (mitochondrial and plastid) or nuclear-encoded (cytosolic) tRNAs. Here, we investigate the evolution of aaRS subcellular localization in a plant lineage (Sileneae) that has experienced extensive and rapid mitochondrial tRNA loss. By analyzing full-length mRNA transcripts (PacBio Iso-Seq), we found predicted retargeting of many ancestrally cytosolic aaRSs to the mitochondrion and confirmed these results with colocalization microscopy assays. However, we also found cases where aaRS localization does not appear to change despite functional tRNA replacement, suggesting evolution of novel interactions and charging relationships. Therefore, the history of repeated tRNA replacement in Sileneae mitochondria reveals that differing constraints on tRNA/aaRS interactions may determine which of these alternative coevolutionary paths is used to maintain organellar translation in plant cells

HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014-2015

BACKGROUND: In January 2015, a total of 11 new diagnoses of human immunodeficiency virus (HIV) infection were reported in a small community in Indiana. We investigated the extent and cause of the outbreak and implemented control measures. METHODS: We identified an outbreak-related case as laboratory-confirmed HIV infection newly diagnosed after October 1, 2014, in a person who either resided in Scott County, Indiana, or was named by another case patient as a syringe-sharing or sexual partner. HIV polymerase (pol) sequences from case patients were phylogenetically analyzed, and potential risk factors associated with HIV infection were ascertained. RESULTS: From November 18, 2014, to November 1, 2015, HIV infection was diagnosed in 181 case patients. Most of these patients (87.8%) reported having injected the extended-release formulation of the prescription opioid oxymorphone, and 92.3% were coinfected with hepatitis C virus. Among 159 case patients who had an HIV type 1 pol gene sequence, 157 (98.7%) had sequences that were highly related, as determined by phylogenetic analyses. Contact tracing investigations led to the identification of 536 persons who were named as contacts of case patients; 468 of these contacts (87.3%) were located, assessed for risk, tested for HIV, and, if infected, linked to care. The number of times a contact was named as a syringe-sharing partner by a case patient was significantly associated with the risk of HIV infection (adjusted risk ratio for each time named, 1.9; P<0.001). In response to this outbreak, a public health emergency was declared on March 26, 2015, and a syringe-service program in Indiana was established for the first time. CONCLUSIONS: Injection-drug use of extended-release oxymorphone within a network of persons who inject drugs in Indiana led to the introduction and rapid transmission of HIV. (Funded by the state government of Indiana and others.)

Are Coping Strategies Used by Households During Times of Food Insecurity Associated with Nutritional Status for Children Under 5 in Lao PDR?

Thesis (Master's)--University of Washington, 2014Objectives: To explore associations between frequency and type of coping strategies employed by households and nutritional status (stunting, wasting, underweight) for children under five. Study Design: Cross sectional study conducted in three southern provinces of Lao PDR. Methods: Study universe included 401 households which self-reported as being food insecure in the prior month. Food insecure households selected from the following five coping strategies (strategies were not mutually exclusive) used during times when there was inadequate food for the household: 1. Consumed less preferred, less expensive foods 2. Borrowed food, or help from friend/relative 3. Limited portion size at mealtimes 4. Restricted consumption by adults so small children could eat 5. Reduced number of meals eaten. A coping frequency index was created based on the frequency in which coping strategies were employed during acute food insecurity as follows: daily, 3-6 days a week, 1-2 days a week, less than once a week or never. The frequency coping score was plotted against nutritional outcomes. In addition to the coping index, a relative coping strategy score was calculate for each household to examine the relationship between type of coping strategy and nutritional outcomes. This relative coping score was plotted against nutritional outcomes. Results: Statistically significant (= 10) by income and stunting status. The correlation between nutritional status and both measures of coping: frequency and type of coping strategy was weak. Discussion: This report confirms that residence, income and mother's education are related to food security. Type of coping strategy did not show a relationship with stunting, wasting or underweight status. Frequency of coping showed a relationship with income and stunting. Interventions targeted at improving the nutritional status of children under five in Lao PDR should be broad and aim to influence the many determinants associated with undernutrition

Risk Indicators and Treatment Needs of Children 2–5 Years of Age Receiving Dental Treatment under General Anesthesia in Saskatchewan

Background: When compared to national averages in Canada, Saskatchewan has one of the highest rates of dental treatment under general anesthesia (GA) and average costs per child. Thus, the purpose of this cross-sectional study is to explore the risk indicators and treatment needs of children receiving dental treatment under GA in Saskatchewan. Methods: In this cross-sectional study, we recruited caregivers of children between 24 and 71 months of age in Saskatoon, Canada. Caregivers completed a 40-item questionnaire, which was supplemented with clinical data and then subject to statistical analysis (independent t-tests and one-way ANOVA). Results: A total of 90 caregiver/child dyads were enrolled with the mean age for children being 49.5 ± 12.3 months. The mean age of a child’s first dental visit was 34.7 ± 15.3 months with only 37.9% of children having a dental home. The mean deft index was 11.7 ± 3.4, with an average of 10.9 ± 3.5 teeth receiving treatment. Additionally, location of primary residence (p = 0.03), family income (p = 0.04), family size (p = 0.01), parental education (p = 0.03), dental home (p = 0.04), and body mass index (p = 0.04) had a statistically significant association with a higher mean deft. Conclusions: Our cross-sectional study confirms that children who require dental treatment under GA have a high burden of disease. While individual risk indicators such as diet and oral hygiene play a role in the progression of early childhood caries (ECC), we also demonstrate that children who do not have access to early preventive visits or a dental home are at a higher risk. In addition to improving motivation for oral hygiene at home and nutritional education, improving access to oral health care should be addressed in strategies to reduce ECC

Modifying the health system to maximize voluntary medical male circumcision uptake: a qualitative study in Botswana

Background: In 2007, the World Health Organization and the Joint United Nations Programme on HIV/AIDS endorsed voluntary medical male circumcision (VMMC) as an add-on HIV-prevention strategy. Similar to many other sub-Saharan countries, VMMC uptake in Botswana has been low; as of February 2016, only 42.7% of the program target had been achieved. Previous work has examined how individual-level factors, such as knowledge and attitudes, influence the update of VMMC. This paper examines how factors related to the health system can be leveraged to maximize uptake of circumcision services, with a focus on demand creation, access to services, and service delivery. Methods: Twenty-seven focus group discussions with 238 participants were conducted in four communities in Botswana among men (stratified by circumcision status and age), women (stratified by age), and community leaders. A semi-structured guide was used by a trained same-gender interviewer to facilitate discussions, which were audio recorded, transcribed, translated to English, and analyzed using an inductive analytic approach. Results: Participants felt demand creation activities utilizing age- and gender-appropriate mobilizers and community leaders were more effective than mass media campaigns. Participants felt improved access to VMMC clinics would facilitate service uptake, as would designated men’s clinics with male-friendly providers for VMMC service delivery. Additionally, providing comprehensive pre-procedure counseling and education, outlining the benefits and disadvantages of the surgical procedure, and explaining the differences between the surgical and non-surgical procedures, were suggested by participants to increase understanding and uptake of VMMC. Conclusion: Cultural acceptability of circumcision services can be improved by engaging age- and gender-appropriate community mobilizers. Involving influential community leaders, providing a forum for men to discuss health issues, and bringing services closer to people can increase VMMC utilization. Service delivery can be improved by communicating the pros and cons of the procedure to the clients for informed decision-making

Specificity of a Bacteroides thetaiotaomicron Marker for Human Feces

A bacterial primer set, known to produce a 542-bp amplicon specific for Bacteroides thetaiotaomicron, generated this product in PCR with 1 ng of extracted DNA from 92% of 25 human fecal samples, 100% of 20 sewage samples, and 16% of 31 dog fecal samples. The marker was not detected in 1 ng of fecal DNA from 61 cows, 35 horses, 44 pigs, 24 chickens, 29 turkeys, and 17 geese

Toll-like Receptor and Inflammasome Signals Converge to Amplify the Innate Bactericidal Capacity of T Helper 1 Cells

T cell effector functions can be elicited by noncognate stimuli, but the mechanism and contribution of this pathway to the resolution of intracellular macrophage infections have not been defined. Here, we show that CD4(+) T helper 1 (Th1) cells could be rapidly stimulated by microbe-associated molecular patterns during active infection with Salmonella or Chlamydia. Further, maximal stimulation of Th1 cells by lipopolysaccharide (LPS) did not require T-cell-intrinsic expression of toll-like receptor 4 (TLR4), interleukin-1 receptor (IL-1R), or interferon-γ receptor (IFN-γR) but instead required IL-18R, IL-33R, and adaptor protein MyD88. Innate stimulation of Th1 cells also required host expression of TLR4 and inflammasome components that together increased serum concentrations of IL-18. Finally, the elimination of noncognate Th1 cell stimulation hindered the resolution of primary Salmonella infection. Thus, the in vivo bactericidal capacity of Th1 cells is regulated by the response to noncognate stimuli elicited by multiple innate immune receptors