Malaria in Africa: vector species' niche models and relative risk maps

A central theoretical goal of epidemiology is the construction of spatial models of disease prevalence and risk, including maps for the potential spread of infectious disease. We provide three continent-wide maps representing the relative risk of malaria in Africa based on ecological niche models of vector species and risk analysis at a spatial resolution of 1 arc-minute (9 185 275 cells of approximately 4 sq km). Using a maximum entropy method we construct niche models for 10 malaria vector species based on species occurrence records since 1980, 19 climatic variables, altitude, and land cover data (in 14 classes). For seven vectors (Anopheles coustani, A. funestus, A. melas, A. merus, A. moucheti, A. nili, and A. paludis) these are the first published niche models. We predict that Central Africa has poor habitat for both A. arabiensis and A. gambiae, and that A. quadriannulatus and A. arabiensis have restricted habitats in Southern Africa as claimed by field experts in criticism of previous models. The results of the niche models are incorporated into three relative risk models which assume different ecological interactions between vector species. The "additive" model assumes no interaction; the "minimax" model assumes maximum relative risk due to any vector in a cell; and the "competitive exclusion" model assumes the relative risk that arises from the most suitable vector for a cell. All models include variable anthrophilicity of vectors and spatial variation in human population density. Relative risk maps are produced from these models. All models predict that human population density is the critical factor determining malaria risk. Our method of constructing relative risk maps is equally general. We discuss the limits of the relative risk maps reported here, and the additional data that are required for their improvement. The protocol developed here can be used for any other vector-borne disease.     

Heritability of hyperphagic eating behavior and appetite-related hormones among Hispanic children

Objective: Eating in the absence of hunger (EAH) may be a genetically influenced phenotype of overweight children, but evidence is limited. This research evaluated the heritability (h²) of EAH and its association with overweight among Hispanic children 5 to 18 years old. Genetic and environmental associations of EAH with overweight, fat mass, and key hormonal regulators of food intake were also evaluated. Research Methods and Procedures: A family design was used to study 801 children from 300 Hispanic families. Weighed food intakes were used to measure EAH after an ad libitum dinner providing 50% of estimated energy needs. Fasting ghrelin, amylin, insulin, and leptin were measured by immunoassays. Measured heights, weights, and fat mass (using DXA) were obtained. Total energy expenditure (TEE) was measured by room respiration calorimetry. Results: On average, children consumed 41% of TEE at the dinner meal, followed by an additional 19% of TEE in the absence of hunger. Overweight children consumed 6.5% more energy at dinner (p < 0.001) and 14% more energy in the absence of hunger (p < 0.001) than non‐overweight children. Significant heritabilities were seen for EAH (h² = 0.51) and dinner intake (h² = 0.52) and for fasting levels of ghrelin (h² = 0.67), amylin (h² = 0.37), insulin (h² = 0.37), and leptin (h² = 0.34). Genetic correlations were seen between eating behavior and fasting hormones, suggesting common underlying genes affecting their expression. Discussion: This research provides new evidence that overweight Hispanic children exhibit elevated levels of hyperphagic eating behaviors that are influenced by genetic endowment.     

Energy imbalance underlying the development of childhood obesity

Objective: To develop a model based on empirical data and human energetics to predict the total energy cost of weight gain and obligatory increase in energy intake and/or decrease in physical activity level associated with weight gain in children and adolescents. Research Methods and Procedures: One‐year changes in weight and body composition and basal metabolic rate (BMR) were measured in 488 Hispanic children and adolescents. Fat‐free mass (FFM) and fat mass (FM) were measured by DXA and BMR by calorimetry. Model specifications include the following: body mass (BM) = FFM + FM, each with a specific energy content, cff (1.07 kcal/g FFM) and cf (9.25 kcal/g FM), basal energy expenditure (EE), kff and kf, and energetic conversion efficiency, eff (0.42) for FFM and ef (0.85) for FM. Total energy cost of weight gain is equal to the sum of energy storage, EE associated with increased BM, conversion energy (CE), and diet‐induced EE (DIEE). Results: Sex‐ and Tanner stage–specific values are indicated for the basal EE of FFM (kff) and the fat fraction in added tissue (fr). Total energy cost of weight gain is partitioned into energy storage (24% to 36%), increase in EE (40% to 57%), CE (8% to 13%), and DIEE (10%). Observed median (10th to 90th percentile) weight gain of 6.1 kg/yr (2.4 to 11.4 kg/yr) corresponds at physical activity level (PAL) = 1.5, 1.75, and 2.0 to a total energy cost of weight gain of 244 (93 to 448 kcal/d), 267 (101 to 485 kcal/d), and 290 kcal/d (110 to 527 kcal/d), respectively, and to a total energy intake of 2695 (1890 to 3730), 3127 (2191 to 4335), and 3551 (2487 to 4930) kcal/d, respectively. If weight gain is caused by a change in PAL alone and PAL₀ = 1.5 at baseline t = 0, the model indicates a drop in PAL of 0.22 (0.08 to 0.34) units, which is equivalent to 60 (18 to 105) min/d of walking at 2.5 mph. Discussion: Halting the development or progression of childhood obesity, as observed in these Hispanic children and adolescents, by counteracting its total energy costs will require a sizable decrease in energy intake and/or reciprocal increase in physical activity.     

Which Obesity Index Best Explains Prevalence Differences in Type 2 Diabetes Mellitus?

Objective: Obesity drives the diabetes epidemic. However, it is not known which obesity index best explains variations in type 2 diabetes mellitus prevalence across populations. Research Methods and Procedures: We analyzed three cross‐sectional studies from San Antonio, TX, (Mexican‐Americans and non‐Hispanic whites, n = 2839), Mexico City (n = 2233), and Spain (n = 2161) (age range, 35 to 64 years). We used the area under the receiver operating characteristic curve (AUC) to assess performance for identifying diabetic subjects and logistic regression analysis to examine differences in diabetes prevalence. Results: AUCs for waist circumference and BMI were similar in white subjects, but the AUC for waist circumference was greater in Mexican‐origin subjects (Mexican men, 0.594 vs. 0.549, p = 0.008; and women, 0.605 vs. 0.557, p = 0.002; Mexican‐American men, 0.648 vs. 0.600, p < 0.001; and women, 0.744 vs. 0.693, p < 0.001). The AUC for waist‐to‐height ratio tended to be greater than that for waist circumference, but statistical significance was demonstrated only in Mexican women (0.628 vs. 0.613, p = 0.044), Mexican‐American women (0.774 vs. 0.758, p < 0.001), and Spanish women (0.734 vs. 0.715, p = 0.039). No obesity index was consistently superior to the others for explaining differences in diabetes prevalence among populations. Conclusions: In white and Mexican‐origin men, waist circumference may be the preferred marker for identifying diabetic subjects on account of its simplicity; in women, waist‐to‐height ratio may be better. Differences in diabetes prevalence among these populations cannot be attributed to a single measure of obesity.     

Deletion of the Bax gene disrupts sexual behavior and modestly impairs motor function in mice

Cell death is a nearly ubiquitous feature of the developing nervous system, and differential death in males and females contributes to several well studied sex differences in neuron number. Nonetheless, the functional importance of neuronal cell death has been subjected to few direct tests. Bax, a pro-apoptotic protein, is required for cell death in many neural regions. Deletion of the Bax gene in mice increases neuron number in several areas and eliminates sex differences in cell number in the brain and spinal cord. Here, sexual and motor behaviors were examined in Bax-/- mice and their wild-type siblings to test the functional consequences of preventing Bax-dependent cell death. Animals were gonadectomized in adulthood and provided with ovarian hormones or with testosterone for tests of feminine and masculine sexual behaviors, respectively. Wild-type mice exhibited a sex difference in feminine sexual behavior, with high lordosis scores in females and low scores in males. This sex difference was eliminated by Bax deletion, with very low receptivity exhibited by both male and female Bax-/- mice. Masculine sexual behavior was not sexually dimorphic among wild-type mice, but mounts and pelvic thrusts were nearly eliminated in Bax-/- mice of both sexes. Motor strength and performance at low speeds on a RotaRod apparatus did not differ by sex or Bax gene status. However, Bax-/- animals exhibited impairments on the RotaRod at higher speeds. Thus, developmental cell death may be required for masculine and feminine sexual behaviors and the fine tuning of motor coordination.     

Secondary chemicals protect mould from fungivory

The vast repertoire of toxic fungal secondary metabolites has long been assumed to have an evolved protective role against fungivory. It still remains elusive, however, whether fungi contain these compounds as an anti-predator adaptation. We demonstrate that loss of secondary metabolites in the soil mould Aspergillus nidulans causes, under the attack of the fungivorous springtail Folsomia candida, a disadvantage to the fungus. Springtails exhibited a distinct preference for feeding on a mutant deleted for LaeA, a global regulator of Aspergillus secondary metabolites. Consumption of the mutant yielded a reproductive advantage to the arthropod but detrimental effects on fungal biomass compared with a wild-type fungus capable of producing the entire arsenal of secondary metabolites. Our results demonstrate that fungal secondary metabolites shape food choice behaviour, can affect population dynamics of fungivores, and suggest that fungivores may provide a selective force favouring secondary metabolites synthesis in fungi.     

The frequency of occurrence and discriminatory power of compounds found in human scent across a population determined by SPME-GC/MS

The composition of human scent collected from the hands is of interest to the medical community as a mechanism to diagnose disease and the forensic community as a means to investigate canine scent discriminations. An extensive survey of the volatile organic compounds (VOCs) identified in the headspace of hand odor samples utilizing solid phase micro-extraction gas chromatography/mass spectrometry (SPME-GC/MS) has been conducted to determine the constituents of the human base odor profile. Sixty-three compounds were extracted from the collected odor samples. The composition included acids, alcohols, aldehydes, hydrocarbons, esters, ketones and nitrogen-containing compounds. The majority of the compounds detected (79.4%) were present in less than one third of the individuals sampled. Spearman correlation coefficient comparisons at a match/no-match threshold of 0.9 produced a distinguish ability of 99.67% across the population.     

Proteomic patterns for classification of ovarian cancer and CTCL serum samples utilizing peak pairs indicative of post-translational modifications

Proteomic patterns as a potential diagnostic technology has been well established for several cancer conditions and other diseases. The use of machine learning techniques such as decision trees, neural networks, genetic algorithms, and other methods has been the basis for pattern determination. Cancer is known to involve signaling pathways that are regulated through PTM of proteins. These modifications are also detectable with high confidence using high-resolution MS. We generated data using a prOTOF mass spectrometer on two sets of patient samples: ovarian cancer and cutaneous t-cell lymphoma (CTCL) with matched normal samples for each disease. Using the knowledge of mass shifts caused by common modifications, we built models using peak pairs and compared this to a conventional technique using individual peaks. The results for each disease showed that a small number of peak pairs gave classification equal to or better than the conventional technique that used multiple individual peaks. This simple peak picking technique could be used to guide identification of important peak pairs involved in the disease process.     

A role for Alström syndrome protein, alms1, in kidney ciliogenesis and cellular quiescence

Premature truncation alleles in the ALMS1 gene are a frequent cause of human Alstr?m syndrome. Alstr?m syndrome is a rare disorder characterized by early obesity and sensory impairment, symptoms shared with other genetic diseases affecting proteins of the primary cilium. ALMS1 localizes to centrosomes and ciliary basal bodies, but truncation mutations in Alms1/ALMS1 do not preclude formation of cilia. Here, we show that in vitro knockdown of Alms1 in mice causes stunted cilia on kidney epithelial cells and prevents these cells from increasing calcium influx in response to mechanical stimuli. The stunted-cilium phenotype can be rescued with a 5' fragment of the Alms1 cDNA, which resembles disease-associated alleles. In a mouse model of Alstr?m syndrome, Alms1 protein can be stably expressed from the mutant allele and is required for cilia formation in primary cells. Aged mice developed specific loss of cilia from the kidney proximal tubules, which is associated with foci of apoptosis or proliferation. As renal failure is a common cause of mortality in Alstr?m syndrome patients, we conclude that this disease should be considered as a further example of the class of renal ciliopathies: wild-type or mutant alleles of the Alstr?m syndrome gene can support normal kidney ciliogenesis in vitro and in vivo, but mutant alleles are associated with age-dependent loss of kidney primary cilia.