Insular Organization of Gene Space in Grass Genomes

Wheat and maize genes were hypothesized to be clustered into islands but the hypothesis was not statistically tested. The hypothesis is statistically tested here in four grass species differing in genome size, Brachypodium distachyon, Oryza sativa, Sorghum bicolor, and Aegilops tauschii. Density functions obtained under a model where gene locations follow a homogeneous Poisson process and thus are not clustered are compared with a model-free situation quantified through a non-parametric density estimate. A simple homogeneous Poisson model for gene locations is not rejected for the small O. sativa and B. distachyon genomes, indicating that genes are distributed largely uniformly in those species, but is rejected for the larger S. bicolor and Ae. tauschii genomes, providing evidence for clustering of genes into islands. It is proposed to call the gene islands “gene insulae” to distinguish them from other types of gene clustering that have been proposed. An average S. bicolor and Ae. tauschii insula is estimated to contain 3.7 and 3.9 genes with an average intergenic distance within an insula of 2.1 and 16.5 kb, respectively. Inter-insular distances are greater than 8 and 81 kb and average 15.1 and 205 kb, in S. bicolor and Ae. tauschii, respectively. A greater gene density observed in the distal regions of the Ae. tauschii chromosomes is shown to be primarily caused by shortening of inter-insular distances. The comparison of the four grass genomes suggests that gene locations are largely a function of a homogeneous Poisson process in small genomes. Nonrandom insertions of LTR retroelements during genome expansion creates gene insulae, which become less dense and further apart with the increase in genome size. High concordance in relative lengths of orthologous intergenic distances among the investigated genomes including the maize genome suggests functional constraints on gene distribution in the grass genomes.     

Shift work,circadian gene variants and risk of breast cancer

Circadian (clock) genes have been linked with several functions relevant to cancer, and epidemiologic research has suggested relationships with breast cancer risk for variants in NPAS2, CLOCK, CRY2 and TIMELESS. Increased breast cancer risk has also been observed among shift workers, suggesting potential interactions in relationships of circadian genes with breast cancer. Relationships with breast cancer of 100 SNPs in 14 clock-related genes, as well as potential interactions with shift work history, were investigated in a case–control study (1042 cases, 1051 controls). Odds ratios in an additive genetic model for European-ancestry participants (645 cases, 806 controls) were calculated, using a two-step correction for multiple testing: within each gene through permutation testing (10,000 permutations), and correcting for the false discovery rate across genes. Interactions of genotypes with ethnicity and shift work (<2 years vs ≥2 years) were evaluated individually. Following permutation analysis, two SNPs (rs3816360 in ARNTL and rs11113179 in CRY1) displayed significant associations with breast cancer and one SNP (rs3027188 in PER1) was marginally significant; however, none were significant following adjustment for the false discovery rate. No significant interaction with shift work history was detected. If shift work causes circadian disruption, this was not reflected in associations between clock gene variants and breast cancer risk in this study. Larger studies are needed to assess interactions with longer durations (>30 years) of shift work that have been associated with breast cancer.     

Increased Cardiac Myocyte PDE5 Levels in Human and Murine Pressure Overload Hypertrophy Contribute to Adverse LV Remodeling

Background

The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC).

Methodology/Principal Findings

In patients with severe aortic stenosis (AS) undergoing valve replacement, we detected greater myocardial PDE5 expression than in control hearts. We observed robust expression in scattered cardiac myocytes of those AS patients with higher LV filling pressures and BNP serum levels. Following TAC, we detected similar, focal PDE5 expression in cardiac myocytes of C57BL/6NTac mice exhibiting the most pronounced LV remodeling. To examine the effect of cell-specific PDE5 expression, we subjected transgenic mice with cardiac myocyte-specific PDE5 overexpression (PDE5-TG) to TAC. LV hypertrophy and fibrosis were similar as in WT, but PDE5-TG had increased cardiac dimensions, and decreased dP/dt_max and dP/dt_min with prolonged tau (P<0.05 for all). Greater cardiac dysfunction in PDE5-TG was associated with reduced myocardial cGMP and SERCA2 levels, and higher passive force in cardiac myocytes in vitro.

Conclusions/Significance

Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload. Increased cardiac myocyte-specific PDE5 expression is a molecular hallmark in hypertrophic hearts with contractile failure, and represents an important therapeutic target.     

The Economic Burden Attributable to a Child’s Inpatient Admission for Diarrheal Disease in Rwanda

Background

Diarrhea is one of the leading causes of childhood morbidity and mortality. Hospitalization for diarrhea can pose a significant burden to health systems and households. The objective of this study was to estimate the economic burden attributable to hospitalization for diarrhea among children less than five years old in Rwanda. These data can be used by decision-makers to assess the impact of interventions that reduce diarrhea morbidity, including rotavirus vaccine introduction.

Methods

This was a prospective costing study where medical records and hospital bills for children admitted with diarrhea at three hospitals were collected to estimate resource use and costs. Hospital length of stay was calculated from medical records. Costs incurred during the hospitalization were abstracted from the hospital bills. Interviews with the child’s caregivers provided data to estimate household costs which included transport costs and lost income. The portion of medical costs borne by insurance and household were reported separately. Annual economic burden before and after rotavirus vaccine introduction was estimated by multiplying the reported number of diarrhea hospitalizations in public health centers and district hospitals by the estimated economic burden per hospitalization. All costs are presented in 2014 US$.

Results

Costs for 203 children were analyzed. Approximately 93% of the children had health insurance coverage. Average hospital length of stay was 5.3 ± 3.9 days. Average medical costs for each child for the illness resulting in a hospitalization were $44.22 ± $23.74 and the total economic burden was $101, of which 65% was borne by the household. For households in the lowest income quintile, the household costs were 110% of their monthly income. The annual economic burden to Rwanda attributable to diarrhea hospitalizations ranged from $1.3 million to $1.7 million before rotavirus vaccine introduction.

Conclusion

Households often bear the largest share of the economic burden attributable to diarrhea hospitalization and the burden can be substantial, especially for households in the lowest income quintile.     

Development and Two-Year Follow-Up Evaluation of a Training Workshop for the Large Preventive Positive Psychology Happy Family Kitchen Project in Hong Kong

Evidence-based practice and capacity-building approaches are essential for large-scale health promotion interventions. However, there are few models in the literature to guide and evaluate training of social service workers in community settings. This paper presents the development and evaluation of the “train-the-trainer” workshop (TTT) for the first large scale, community-based, family intervention projects, entitled “Happy Family Kitchen Project” (HFK) under the FAMILY project, a Hong Kong Jockey Club Initiative for a Harmonious Society. The workshop aimed to enhance social workers’ competence and performance in applying positive psychology constructs in their family interventions under HFK to improve family well-being of the community they served. The two-day TTT was developed and implemented by a multidisciplinary team in partnership with community agencies to 50 social workers (64% women). It focused on the enhancement of knowledge, attitude, and practice of five specific positive psychology themes, which were the basis for the subsequent development of the 23 family interventions for 1419 participants. Acceptability and applicability were enhanced by completing a needs assessment prior to the training. The TTT was evaluated by trainees’ reactions to the training content and design, changes in learners (trainees) and benefits to the service organizations. Focus group interviews to evaluate the workshop at three months after the training, and questionnaire survey at pre-training, immediately after, six months, one year and two years after training were conducted. There were statistically significant increases with large to moderate effect size in perceived knowledge, self-efficacy and practice after training, which sustained to 2-year follow-up. Furthermore, there were statistically significant improvements in family communication and well-being of the participants in the HFK interventions they implemented after training. This paper offers a practical example of development, implementation and model-based evaluation of training programs, which may be helpful to others seeking to develop such programs in diverse communities.     

The right response at the right time: Exploring helminth immune modulation in sticklebacks by experimental coinfection

Parasites are one of the strongest selective agents in nature. They select for hosts that evolve counter‐adaptive strategies to cope with infection. Helminth parasites are special because they can modulate their hosts’ immune responses. This phenomenon is important in epidemiological contexts, where coinfections may be affected. How different types of hosts and helminths interact with each other is insufficiently investigated. We used the three‐spined stickleback (Gasterosteus aculeatus) – Schistocephalus solidus model to study mechanisms and temporal components of helminth immune modulation. Sticklebacks from two contrasting populations with either high resistance (HR) or low resistance (LR) against S. solidus, were individually exposed to S. solidus strains with characteristically high growth (HG) or low growth (LG) in G. aculeatus. We determined the susceptibility to another parasite, the eye fluke Diplostomum pseudospathaceum, and the expression of 23 key immune genes at three time points after S. solidus infection. D. pseudospathaceum infection rates and the gene expression responses depended on host and S. solidus type and changed over time. Whereas the effect of S. solidus type was not significant after three weeks, T regulatory responses and complement components were upregulated at later time points if hosts were infected with HG S. solidus. HR hosts showed a well orchestrated immune response, which was absent in LR hosts. Our results emphasize the role of regulatory T cells and the timing of specific immune responses during helminth infections. This study elucidates the importance to consider different coevolutionary trajectories and ecologies when studying host‐parasite interactions.     

Calorimetry for studying the adsorption of proteins in hydrophobic interaction chromatography

Hydrophobic interaction chromatography is a very popular chromatography method for purification of proteins and plasmids in all scales from analytical to industrial manufacturing. Despite this frequent use, the complex interaction mechanism and the thermodynamic aspects of adsorption in hydrophobic interaction chromatography are still not well understood. Calorimetric methods such as isothermal titration calorimetry and flow calorimetry can help to gain a deeper understanding of the adsorption strength, the influence of salt type and temperature. They can be used to study conformational changes of proteins, which are often associated with the adsorption in hydrophobic interaction chromatography. This review offers a detailed introduction into the thermodynamic fundamentals of adsorption in hydrophobic interaction chromatography with a special focus on the potential applications of isothermal titration calorimetry and flow calorimetry for studying specific problems and relationships of the adsorption behavior of proteins and its various influencing factors. Models for characterizing conformational changes upon adsorption are presented together with methods for assessing this problem for different proteins and stationary phases. All of this knowledge can contribute greatly to forming a sound basis for method development, process optimization and finding modelling strategies in hydrophobic interaction chromatography.     

Elevated Prolactin during Pregnancy Drives a Phenotypic Switch in Mouse Hypothalamic Dopaminergic Neurons

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The Sandfish＇s Skin： Morphology, Chemistry and Reconstruction

The sandfish is a lizard having the remarkable ability to move in desert sand in a swimming-like fashion. The most outstanding adaptations to this mode of life are the low friction behaviour and the extensive abrasion resistance of the sandfish skin against sand, outperforming even steel. We investigated the topography, the composition and the mechanical properties of sandfish scales. These consist of glycosylated keratins with high amount of sulphur but no hard inorganic material, such as silicates or lime. Remarkably, atomic force microscopy shows an almost complete absence of attractive forces between the scale surface and a silicon tip, suggesting that this is responsible for the unusual tribological properties. The unusual glycosylation of the keratins was found to be absolutely necessary for the described phenomenon. The scales were dissolved and reconstituted on a polymer surface resulting in properties similar to the original scale. Thus, we provide a pathway towards exploitation of the reconstituted scale material for future engineering applications.