A new tool for the chemical genetic investigation of the Plasmodium falciparum Pfnek-2 NIMA-related kinase

Background: Examining essential biochemical pathways in Plasmodium falciparum presents serious challenges, as standard molecular techniques such as siRNA cannot be employed in this organism, and generating gene knock-outs of essential proteins requires specialized conditional approaches. In the study of protein kinases, pharmacological inhibition presents a feasible alternative option. However, as in mammalian systems, inhibitors often lack the desired selectivity. Described here is a chemical genetic approach to selectively inhibit Pfnek-2 in P. falciparum, a member of the NIMA-related kinase family that is essential for completion of the sexual development of the parasite. Results: Introduction of a valine to cysteine mutation at position 24 in the glycine rich loop of Pfnek-2 does not affect kinase activity but confers sensitivity to the protein kinase inhibitor 4-(6-ethynyl-9H-purin-2-ylamino) benzene sulfonamide (NCL-00016066). Using a combination of in vitro kinase assays and mass spectrometry, (including phosphoproteomics) the study shows that this compound acts as an irreversible inhibitor to the mutant Pfnek2 likely through a covalent link with the introduced cysteine residue. In particular, this was shown by analysis of total protein mass using mass spectrometry which showed a shift in molecular weight of the mutant kinase in the presence of the inhibitor to be precisely equivalent to the molecular weight of NCL-00016066. A similar molecular weight shift was not observed in the wild type kinase. Importantly, this inhibitor has little activity towards the wild type Pfnek-2 and, therefore, has all the properties of an effective chemical genetic tool that could be employed to determine the cellular targets for Pfnek-2. Conclusions: Allelic replacement of wild-type Pfnek-2 with the mutated kinase will allow for targeted inhibition of Pfnek-2 with NCL-00016066 and hence pave the way for comparative studies aimed at understanding the biological role and transmission-blocking potential of Pfnek-2. © 2016 The Author(s)

Measurement of single electron emission in two-phase xenon

We present the first measurements of the electroluminescence response to the emission of single electrons in a two-phase noble gas detector. Single ionization electrons generated in liquid xenon are detected in a thin gas layer during the 31-day background run of the ZEPLIN-II experiment, a two-phase xenon detector for WIMP dark matter searches. Both the pressure dependence and magnitude of the single-electron response are in agreement with previous measurements of electroluminescence yield in xenon. We discuss different photoionization processes as possible cause for the sample of single electrons studied in this work. This observation may have implications for the design and operation of future large-scale two-phase systems.Comment: 11 pages, 6 figure

SAS6-like protein in Plasmodium indicates that conoid-associated apical complex proteins persist in invasive stages within the mosquito vector

The SAS6-like (SAS6L) protein, a truncated paralogue of the ubiquitous basal body/centriole protein SAS6, has been characterised recently as a flagellum protein in trypanosomatids, but associated with the conoid in apicomplexan Toxoplasma. The conoid has been suggested to derive from flagella parts, but is thought to have been lost from some apicomplexans including the malaria-causing genus Plasmodium. Presence of SAS6L in Plasmodium, therefore, suggested a possible role in flagella assembly in male gametes, the only flagellated stage. Here, we have studied the expression and role of SAS6L throughout the Plasmodium life cycle using the rodent malaria model P. berghei. Contrary to a hypothesised role in flagella, SAS6L was absent during gamete flagellum formation. Instead, SAS6L was restricted to the apical complex in ookinetes and sporozoites, the extracellular invasive stages that develop within the mosquito vector. In these stages SAS6L forms an apical ring, as we show is also the case in Toxoplasma tachyzoites. The SAS6L ring was not apparent in blood-stage invasive merozoites, indicating that the apical complex is differentiated between the different invasive forms. Overall this study indicates that a conoid-associated apical complex protein and ring structure is persistent in Plasmodium in a stage-specific manner

Metabolic Health Has Greater Impact on Diabetes than Simple Overweight/Obesity in Mexican Americans

To compare the risk for diabetes in each of 4 categories of metabolic health and BMI. Methods. Participants were drawn from the Cameron County Hispanic Cohort, a randomly selected Mexican American cohort in Texas on the US-Mexico border. Subjects were divided into 4 phenotypes according to metabolic health and BMI: metabolically healthy normal weight, metabolically healthy overweight/obese, metabolically unhealthy normal weight, and metabolically unhealthy overweight/obese. Metabolic health was defined as having less than 2 metabolic abnormalities. Overweight/obese status was assessed by BMI higher than 25 kg/m2. Diabetes was defined by the 2010 ADA definition or by being on a diabetic medication. Results. The odds ratio for diabetes risk was 2.25 in the metabolically healthy overweight/obese phenotype (95% CI 1.34, 3.79), 3.78 (1.57, 9.09) in the metabolically unhealthy normal weight phenotype, and 5.39 (3.16, 9.20) in metabolically unhealthy overweight/obese phenotype after adjusting for confounding factors compared with the metabolically healthy normal weight phenotype. Conclusions. Metabolic health had a greater effect on the increased risk for diabetes than overweight/obesity. Greater focus on metabolic health might be a more effective target for prevention and control of diabetes than emphasis on weight loss alone

Social Participation and Disaster Risk Reduction Behaviors in Tsunami Prone Areas

This paper examines the relationships between social participation and disaster risk reduction actions. A survey of 557 households in tsunami prone areas in Phang Nga, Thailand was conducted following the 2012 Indian Ocean earthquakes. We use a multivariate probit model to jointly estimate the likelihood of undertaking three responses to earthquake and tsunami hazards (namely, (1) following disaster-related news closely, (2) preparing emergency kits and/or having a family emergency plan, and (3) having an intention to migrate) and community participation.We find that those who experienced losses from the 2004 tsunami are more likely to participate in community activities and respond to earthquake hazards. Compared to men, women are more likely to prepare emergency kits and/or have an emergency plan and have a greater intention to migrate. Living in a community with a higher proportion of women with tertiary education increases the probability of engaging in community activities and carrying out disaster risk reduction measures. Individuals who participate in village-based activities are 5.2% more likely to undertake all three risk reduction actions compared to those not engaging in community activities. This implies that encouraging participation in community activities can have positive externalities in disaster mitigation

Non-communicable diseases and preventive health behaviors: a comparison of Hispanics nationally and those living along the US-Mexico border

Background: Non-communicable diseases (NCDs) are rising among US Hispanics, but few studies have examined the preventive health behaviors for these NCDs among Hispanics. This study compared the preventive health behaviors of smoke-free living, physical activity, fruit and vegetable consumption, and avoidance of heavy alcohol use in Hispanics in the United States and Hispanics living along the US-Mexico border. Methods: Two weighted data sets with information on Hispanic populations were analyzed: 1) the national Behavioral Risk Factor Surveillance Survey (n = 29,942) from 2009; and 2) the Cameron County Hispanic Cohort (n = 1,439) recruited from the US-Mexico border between 2008–2011. To compare the preventive health behaviors of the samples, within a generalized estimating equation framework, weighted univariate and multivariate logistic regression analyses were conducted controlling for age, educational attainment, employment, language, and insurance status. Statistical tests were two-sided with a significance level set at 0.05. Results: Both samples reported low engagement in preventive behaviors. However, Hispanic males and females from the US-Mexico border were significantly less likely than the national sample to meet physical activity and fruit and vegetable consumption guidelines. Also, Hispanic males from the US-Mexico border were more likely to engage in heavy alcohol use. Conclusion: The lack of preventive health behaviors among Hispanics living along the US-Mexico border presents a dire prospect for NCD control in the region. Multipronged approaches to address multiple behaviors should be considered

Anxiety, depression and smoking status among adults of Mexican heritage on the Texas-Mexico Border

The goal of the current analysis is to examine relationships between smoking status and anxiety and depression among adults of Mexican heritage to inform the development of culturally relevant smoking cessations efforts. Mexican heritage residents (N=1,791) of the city of Brownsville, TX, aged 18 years or older, enrolled in the Cameron County Hispanic Cohort, were selected through two stage cluster sampling of randomly selected census tracts from the first and third quartile of SES using Census 2000. Among current smokers, anxiety and depression scores were highest among women who had not completed high school (p\u3c0.05). Former smoking women, but not men, with at least a high school education and former smoking women born in the United States reported higher levels of anxiety and depression than never smoking women. Negative affective states may represent a greater barrier to smoking cessation among women than men

The Cross-Sectional Association Between Lifestyle Behaviors and Breast and Cervical Cancer Screening Among Hispanic Women Along the Texas-Mexico Border

Objective: Lifestyle behaviors may influence timely cancer screening, but their relationship is unknown among Hispanic women who have low cancer screening rates. Methods: We used Cameron County Hispanic Cohort data from 2014 to 2022 to evaluate the relationship between lifestyle and compliance with mammography and Papanicolaou (Pap) screening guidelines ( up-to-date ) among Hispanic women along the Texas-Mexico border. The 2018 World Cancer Research Fund scoring system characterized cancer-preventive lifestyle adherence. Multivariable logistic regression assessed the association between lifestyle behaviors and mammography and, separately, Pap screening. Results: Among 385 age-eligible women for mammography and 412 age-eligible women for Pap test screening, up-to-date mammography and Pap screening were seen in 66.7 % (95 % CI: 58.8-73.7 %) and 71.4 % (95 % CI: 63.6-78.0 %) of women, respectively. Compared to non-adherence, adherence to waist circumference (AOR adjusted odds ratio 9.1, 95 % CI: 1.1-77.9; P = 0.04) and alcohol guidelines (AOR 9.4, 95 % CI: 1.1-81.6; P = 0.04) were associated with up-to-date mammography. Consumption guideline adherence to fruit and vegetable (AOR 4.0, 95 % CI: 1.2-13.4; P = 0.03), ultra-processed foods (AOR 7.5, 95 % CI: 1.6-34.7; P = 0.01), red meat (AOR 6.8, 95 % CI: 1.3-34.8; P = 0.02), and sugary beverages (AOR 16.9, 95 % CI: 2.1-138.4; P = 0.01) were associated with up-to-date Pap screening. Conclusions: Differential factors were associated with increased odds of being up-to-date with mammography versus Pap test screening. Lifestyle behavior promotion complements cancer prevention interventions. Contextual insight into the association between lifestyle and cancer screening provides a foundation for future endeavors to augment these two core components of cancer prevention to address Hispanic women\u27s rising breast and cervical cancer risk

The Precarious Health of Young Mexican American Men in South Texas, Cameron County Hispanic Cohort, 2004–2015

Introduction Hispanic men have higher rates of illness and death from various chronic conditions than do non-Hispanic men. We aimed to characterize the health of Mexican American men living on the US–Mexico border in South Texas and elucidate indications of chronic disease in young men. Methods We sampled all male participants from the Cameron County Hispanic Cohort, an ongoing population-based cohort of Mexican Americans in Brownsville, Texas. We calculated descriptive statistics and stratified the sample into 3 age groups to estimate the prevalence of sociodemographic, behavioral, and clinical factors by age group and evaluated differences between age groups. Results Obesity prevalence was approximately 50% across all age groups (P = .83). Diabetes prevalence was high overall (26.8%), and 16.9% (95% confidence interval [CI], 10.1%–23.8%) of men younger than 35 had diabetes. More than 70% of these young men had elevated liver enzymes, and mean values of aspartate aminotransferase were significantly higher in younger men (45.0 u/L; 95% CI, 39.5–50.6 u/L) than in both older age groups. Less than 20% of young men had any form of health insurance. Current smoking was higher in young men than in men in the other groups, and the rate was higher than the national prevalence of current smoking among Hispanic men. Conclusions We suggest a need for obesity and diabetes prevention programs and smoking cessation programs for men in this region. Opportunities exist to expand current intervention programs and tailor them to better reach this vulnerable population of young Hispanic men. Elevated liver enzymes in men younger than 35 suggest a substantial burden of liver abnormalities, a finding that warrants further study

Real-Time Geospatial analysis Identifies Gaps in Covid-19 Vaccination in a Minority Population

COVID-19 vaccination is being rapidly rolled out in the US and many other countries, and it is crucial to provide fast and accurate assessment of vaccination coverage and vaccination gaps to make strategic adjustments promoting vaccine coverage. We reported the effective use of real-time geospatial analysis to identify barriers and gaps in COVID-19 vaccination in a minority population living in South Texas on the US-Mexico Border, to inform vaccination campaign strategies. We developed 4 rank-based approaches to evaluate the vaccination gap at the census tract level, which considered both population vulnerability and vaccination priority and eligibility. We identified areas with the highest vaccination gaps using different assessment approaches. Real-time geospatial analysis to identify vaccination gaps is critical to rapidly increase vaccination uptake, and to reach herd immunity in the vulnerable and the vaccine hesitant groups. Our results assisted the City of Brownsville Public Health Department in adjusting real-time targeting of vaccination, gathering coverage assessment, and deploying services to areas identified as high vaccination gap. The analyses and responses can be adopted in other locations