Restriction of Francisella novicida Genetic Diversity during Infection of the Vector Midgut

The genetic diversity of pathogens, and interactions between genotypes, can strongly influence pathogen phenotypes such as transmissibility and virulence. For vector-borne pathogens, both mammalian hosts and arthropod vectors may limit pathogen genotypic diversity (number of unique genotypes circulating in an area) by preventing infection or transmission of particular genotypes. Mammalian hosts often act as “ecological filters” for pathogen diversity, where novel variants are frequently eliminated because of stochastic events or fitness costs. However, whether vectors can serve a similar role in limiting pathogen diversity is less clear. Here we show using Francisella novicida and a natural tick vector of Francisella spp. (Dermacentor andersoni), that the tick vector acted as a stronger ecological filter for pathogen diversity compared to the mammalian host. When both mice and ticks were exposed to mixtures of F. novicida genotypes, significantly fewer genotypes co-colonized ticks compared to mice. In both ticks and mice, increased genotypic diversity negatively affected the recovery of available genotypes. Competition among genotypes contributed to the reduction of diversity during infection of the tick midgut, as genotypes not recovered from tick midguts during mixed genotype infections were recovered from tick midguts during individual genotype infection. Mediated by stochastic and selective forces, pathogen genotype diversity was markedly reduced in the tick. We incorporated our experimental results into a model to demonstrate how vector population dynamics, especially vector-to-host ratio, strongly affected pathogen genotypic diversity in a population over time. Understanding pathogen genotypic population dynamics will aid in identification of the variables that most strongly affect pathogen transmission and disease ecology.     

The Mycobacterium avium subsp. Paratuberculosis protein MAP1305 modulates dendritic cell-mediated T cell proliferation through Toll-like receptor-4

In this study, we show that Mycobacterium avium subsp. Paratuberculosis MAP1305 induces the maturation of bone marrow-derived dendritic cells (BMDCs), a representative antigen presenting cell (APC). MAP1305 protein induces DC maturation and the production of pro-inflammatory cytokines (Interleukin (IL)-6), tumor necrosis factor (TNF)-α, and IL-1β) through Toll like receptor-4 (TLR-4) signaling by directly binding with TLR4. MAP1305 activates the phosphorylation of MAPKs, such as ERK, p38MAPK, and JNK, which is essential for DC maturation. Furthermore, MAP1305-treated DCs transform naïve T cells to polarized CD4⁺ and CD8⁺ T cells, thus indicating a key role for this protein in the Th1 polarization of the resulting immune response. Taken together, M. avium subsp. Paratuberculosis MAP1305 is important for the regulation of innate immune response through DC-mediated proliferation of CD4⁺ and CD8⁺ T cells. [BMB Reports 2014; 47(2): 115-120]     

In Vivo Expression of EphrinA5-Fc in Mice Results in Cephalic Neural Crest Agenesis and Craniofacial Abnormalities

Eph receptors and their ligands ephrins have been implicated in guiding the directed migration of neural crest cells (NCCs). In this study, we found that Wnt1-Cre-mediated expression of ephrinA5-Fc along the dorsal midline of the dien- and mesencephalon resulted in severe craniofacial malformation of mouse embryo. Interestingly, expression of cephalic NCC markers decreased significantly in the frontonasal process and branchial arches 1 and 2, which are target areas for the migratory cephalic NCCs originating in the dien- and mesencephalon. In addition, these craniofacial tissues were much smaller in mutant embryos expressing ephrinA5-Fc. Importantly, EphA7-positive cephalic NCCs were absent along the dorsal dien- and mesencephalon of mutant embryos expressing ephrinA5-Fc, suggesting that the generation of cephalic NCCs is disrupted due to ephrinA5-Fc expression. NCC explant experiments suggested that ephrinA5-Fc perturbed survival of cephalic NCC precursors in the dorsal midline tissue rather than affecting their migratory capacity, which was consistent with our previous report that expression of ephrinA5-Fc in the dorsal midline is responsible for severe neuroepithelial cell apoptotic death. Taken together, our findings strongly suggest that expression of ephrinA5-Fc decreases a population of cephalic NCC precursors in the dorsal midline of the dien- and mesencephalon, thereby disrupting craniofacial development in the mouse embryos.     

Prevalence of and Factors Associated with Lens Opacities in a Korean Adult Population with and without Diabetes: The 2008–2009 Korea National Health and Nutrition Examination Survey

Objective

We examined the prevalence of and factors associated with lens opacities in a Korean adult population with and without diabetes.

Research Design and Methods

Among the 11,163 adults (≥19 years old) from the fourth Korea National Health and Nutrition Examination Survey in 2008–2009, the data from laboratory tests, nutritional surveys, and slit-lamp examinations of 10,248 persons (4,397 men, 5,851 women) were examined. Cataract was defined as the presence of any nuclear, cortical, subcapsular, or mixed cataract in at least one eye, using the Lens Opacities Classification System III.

Results

The weighted prevalence of cataracts were 23.5% [95% confidence interval (CI), 21.7–25.4] in a Korean adult population (19–39 years old, 1.8% [1.3–2.5], 40–64 years old, 25.2% [22.5–28.1],≥65 years old, 87.8% [85.4–89.9])and 54.7% [50.1–59.2] in a diabetic population(19–39 years old, 11.6% [4.5–26.5], 40–64 years old, 41.1% [35.4–47.0], ≥65 years old, 88.3% [83.5–91.8]). In a logistic regression analysis, age, myopia, and the presence of diabetes were independent risk factors. For young (age 19–39 years) and middle aged (age 40–65 years) adults with diabetes, the OR of having a lens opacity is 5.04 [1.41–17.98] and 1.47 [1.11–1.94], respectively, as those without diabetes, whereas for adults aged 65 and older, there was no difference in the prevalence of cataract.

Conclusions

According to these national survey data, ∼ 24% of Korean adults and ∼ 55% of people with diabetes have cataracts. The presence of diabetes was independently associated with cataracts in young and middle aged adults.     

Psychological Factors as Predictors of Suicidal Ideation among Adolescents in Malaysia

Background

There has been a drastic increase in the rate of suicides over the past 45 years in Malaysia. The statistics show that adolescents aged between 16 and 19 years old are at high risk of committing suicide. This could be attributed to issues relating to the developmental stage of adolescents. During this stage, adolescents face challenges and are exposed to various stressful experiences and risk factors relating to suicide.

Method

The present study examined psychological factors (i.e., depression, anxiety and stress) as predictors for suicidal ideation among adolescents. A cross-sectional study was conducted on 190 students (103 males and 87 females), aged 15 to 19 years old from two different schools in Kuala Lumpur. The Depression Anxiety Stress Scale 21-item version (DASS-21) was used to measure depression, anxiety and stress among the students, and the Beck Scale for Suicide Ideation (BSS) to measure suicidal ideation. The data were analysed using Pearson''s correlation and multiple regression analysis.

Results

The results show that 11.10%, 10.00%, and 9.50% of the students reported that they were experiencing severe depression, anxiety and stress, respectively. There were significant correlations between depression, anxiety, and stress with suicidal ideation. However, only depression was identified as a predictor for suicidal ideation.

Conclusion

Hence, this study extends the role of depression in predicting suicidal ideation among adolescents in the Malaysian context. The findings imply that teenagers should be assisted in strengthening their positive coping strategies in managing distress to reduce depression and suicidal ideation.     

Gender Differences and Socioeconomic Status in Relation to Overweight among Older Korean People

Background

The ever-increasing older population and its association with serious overweight problems have garnered much attention. The correlation between being overweight and socioeconomic status factors could be helpful for understanding the inequalities among the overweight population. We examined the correlation between being overweight and some key variables, such as demographics, socioeconomic status, general health status, and health behavior in a large sample of older individuals, by each gender.

Methods

We used data from the 2008 Korean Longitudinal Study of Aging and it included 8,157 participants who were 45 years or older. To understand the relationship between the overweight participants in accordance to demographic and socioeconomic characteristics, health status, and health behaviors, a weighted chi-square test and logistic regression analysis were conducted by separating variables related to overweight, according to the genders.

Results

The number of people in the normal group was 6,347 (77.8%), while the people who were considered overweight were 1,810 (22.2%). Women (n = 4,583) constituted 52.7% of the subject, 24.9% of whom were classified as overweight. Meanwhile, 20.6% of the 47.3% (n = 3,574) of the sample who were men were classified as overweight. Participants between the ages of 45 and 64 with chronic diseases were more likely to be overweight. Men in the 4th quartile of household income were more likely to be overweight than those who were in the 1st quartile, in contrast, while unemployed women with lower education levels and urban residents were at greater risk for being overweight.

Conclusions

Among the men, health status and health behavior appeared to show a correlation with being overweight; however, among women, socioeconomic status factors were strongly related to being overweight. These findings appear to support the association of gender-specifics with the prevalence of being overweight.