Diabetes mellitus in the Pima Indians: genetic and evolutionary considerations

Non-insulin-dependent diabetes mellitus is a common disease in the Pima Indians. It is familial and strongly related to obesity. Neel (1962) suggested that the introduction of a steady food supply to people who have evolved a "thrifty genotype" leads to obesity, insulin resistance, and diabetes. Our findings in the Pimas of differences in insulin sensitivity in different metabolic pathways suggest that the thrifty genotype involves the ability of insulin to maintain fat stores despite resistance to glucose disposal. The recent increase in diabetes incidence following the availability of an abundant food supply suggests that the ability to store energy efficiently during cycles of feast and famine may now lead to obesity, insulin resistance, and diabetes.     

Art and the Middle-to-Upper Paleolithic transition in Europe: comments on the archaeological arguments for an early Upper Paleolithic antiquity of the Grotte Chauvet art

The spectacular art of the Grotte Chauvet stands out among all other examples of Aurignacian art, which are restricted to a handful of sites in other regions of western and Central Europe, which take the form of sophisticated carvings on organic materials and of simple engravings on rockshelter walls. Given its sophistication, Chauvet has understandably come to feature prominently in debates as to the nature of human symbolic origins, the behavioral capacities of Homo sapiens, the nature of the dispersal of modern humans across Europe, and the possibly contemporary extinction of Homo neanderthalensis. Significant objections to such an antiquity have, however, been made in recent years on the grounds of the style, themes, and technical practice of the art itself, and on the grounds of the AMS radiocarbon dating program that was first seen to suggest an early Upper Paleolithic age. To date, no attention has been paid to claims for an Aurignacian age on specifically archaeological grounds. Here, I undertake a critical examination of the archaeology of the cave and its wider region, as well as attempts to verify the antiquity of the art on the basis of comparison with well-dated Aurignacian art elsewhere. I conclude that none of the archaeological arguments withstand scrutiny and that many can be rejected as they are either incorrect or tautologous. By contrast, hypotheses that the art is of Gravettian-Magdalenian age have not been successfully eliminated. The age of the art of the Grotte Chauvet should be seen as a scientific problem, not an established fact. While it may prove impossible to prove an Aurignacian age for some of the Chauvet art I suggest a set of expectations that would, in combination, strengthen the robusticity of the ‘long chronology’ argument. The onus is upon Chauvet long chronologists to do this, and until they do, we must conclude that the art of the Grotte Chauvet is not dated, and very possibly much younger than claimed.     

A stochastic mathematical model of methicillin resistant Staphylococcus aureus transmission in an intensive care unit: predicting the impact of interventions

OBJECTIVES: To estimate the transmission rate of MRSA in an intensive care unit (ICU) in an 800 bed Australian teaching hospital and predict the impact of infection control interventions. METHODS: A mathematical model was developed which consisted of four compartments: colonised and uncolonised patients and contaminated and uncontaminated health-care workers (HCWs). Patient movements, MRSA acquisition and daily prevalence data were collected from an ICU over 939 days. Hand hygiene compliance and the probability of MRSA transmission from patient to HCW per discordant contact were measured during the study. Attack rate and reproduction ratio were estimated using Bayesian methods. The impact of a number of interventions on attack rate was estimated using both stochastic and deterministic versions of the model. RESULTS: The mean number of secondary cases arising from the ICU admission of colonised patients, also called the ward reproduction ratio, R(w), was estimated to be 0.50 (95% CI 0.39-0.62). The attack rate was one MRSA transmission per 160 (95% CI 130-210) uncolonised-patient days. Results were not sensitive to uncertainty in measured model parameters (hand hygiene rate and transmission probability per contact). Hand hygiene was predicted to be the most effective intervention. Decolonisation was predicted to be relatively ineffective. Increasing HCW numbers was predicted to increase MRSA transmission, in the absence of patient cohorting. The predictions of the stochastic model differed from those of the deterministic model, with lower levels of colonisation predicted by the stochastic model. CONCLUSIONS: The number of secondary cases of MRSA colonisation within the ICU in this study was below unity. Transmission of MRSA was sustained through admission of colonised patients. Stochastic model simulations give more realistic predictions in hospital ward settings than deterministic models. Increasing staff does not necessarily lead to reduced transmission of nosocomial pathogens.     

Molecular dynamics simulations of Trichomonas vaginalis ferredoxin show a loop-cap transition

The crystal structure of the oxidized Trichomonas vaginalis ferredoxin (Tvfd) showed a unique crevice that exposed the redox center. Here we have examined the dynamics and solvation of the active site of Tvfd using molecular dynamics simulations of both the reduced and oxidized states. The oxidized simulation stays true to the crystal form with a heavy atom root mean-squared deviation of 2 A. However, within the reduced simulation of Tvfd a profound loop-cap transition into the redox center occurred within 6-ns of the start of the simulation and remained open throughout the rest of the 20-ns simulation. This large opening seen in the simulations supports the hypothesis that the exceptionally fast electron transfer rate between Tvfd and the drug metronidazole is due to the increased access of the antibiotic to the redox center of the protein and not due to the reduction potential.     

Birth weight and non-insulin dependent diabetes: thrifty genotype,thrifty phenotype,or surviving small baby genotype?

OBJECTIVE--To determine the prevalence of diabetes in relation to birth weight in Pima Indians. DESIGN--Follow up study of infants born during 1940-72 who had undergone a glucose tolerance test at ages 20-39 years. SETTING--Gila River Indian community, Arizona. SUBJECTS--1179 American Indians. MAIN OUTCOME MEASURE--Prevalence of non-insulin dependent diabetes mellitus (plasma glucose concentration > or = 11.1 mmol/l two hours after ingestion of carbohydrate). RESULTS--The prevalence was greatest in those with the lowest and highest birth weights. The age adjusted prevalences for birth weights < 2500 g, 2500-4499 g, and > or = 4500 g were 30%, 17%, and 32%, respectively. When age, sex, body mass index, maternal diabetes during pregnancy, and birth year were controlled for, subjects with birth weights < 2500 g had a higher rate than those with weights 2500-4499 g (odds ratio 3.81; 95% confidence interval 1.70 to 8.52). The risk for subsequent diabetes among higher birthweight infants (> or = 4500 g) was associated with maternal diabetes during pregnancy. Most diabetes, however, occurred in subjects with intermediate birth weights (2500-4500 g). CONCLUSIONS--The relation of the prevalence of diabetes to birth weight in the Pima Indians is U shaped and is related to parental diabetes. Low birth weight is associated with non-insulin dependent diabetes. Given the high mortality of low birthweight infants selective survival in infancy of those genetically predisposed to insulin resistance and diabetes provides an explanation for the observed relation between low birth weight and diabetes and the high prevalence of diabetes in many populations.     

Bullied no more: when and how DNA shoves proteins around

The predominant protein-centric perspective in protein-DNA-binding studies assumes that the protein drives the interaction. Research focuses on protein structural motifs, electrostatic surfaces and contact potentials, while DNA is often ignored as a passive polymer to be manipulated. Recent studies of DNA topology, the supercoiling, knotting, and linking of the helices, have shown that DNA has the capability to be an active participant in its transactions. DNA topology-induced structural and geometric changes can drive, or at least strongly influence, the interactions between protein and DNA. Deformations of the B-form structure arise from both the considerable elastic energy arising from supercoiling and from the electrostatic energy. Here, we discuss how these energies are harnessed for topology-driven, sequence-specific deformations that can allow DNA to direct its own metabolism.     

Differences in Microbial Activity and Microbial Populations of Peat Associated with Suppression of Damping-Off Disease Caused by Pythium sylvaticum

The microbiological characteristics associated with disease-suppressive peats are unclear. We used a bioassay for Pythium sylvaticum-induced damping-off of cress seedlings to identify conducive and suppressive peats. Microbial activity in unconditioned peats was negatively correlated with the counts of P. sylvaticum at the end of the bioassay. Denaturing gradient gel electrophoresis (DGGE) profiling and clone library analyses of small-subunit rRNA gene sequences from two suppressive and two conducive peats differed in the bacterial profiles generated and the diversity of sequence populations. There were also significant differences between bacterial sequence populations from suppressive and conducive peats. The frequencies of a number of microbial groups, including the Rhizobium-Agrobacterium group (specifically sequences similar to those for the genera Ochrobactrum and Zoogloea) and the Acidobacteria, increased specifically in the suppressive peats, although no single bacterial group was associated with disease suppression. Fungal DGGE profiles varied little over the course of the bioassay; however, two bands associated specifically with suppressive samples were detected. Sequences from these bands corresponded to Basidiomycete yeast genera. Although the DGGE profiles were similar, fungal sequence diversity also increased during the bioassay. Sequences highly similar to those of Cryptococcus increased in relative abundance during the bioassay, particularly in the suppressive samples. This study highlights the importance of using complementary approaches to molecular profiling of complex populations and provides the first report that basidiomycetous yeasts may be associated with the suppression of Pythium-induced diseases in peats.     

Bayesian modelling of an epidemic of severe acute respiratory syndrome

This paper analyses data arising from a SARS epidemic in Shanxi province of China involving a total of 354 people infected with SARS-CoV between late February and late May 2003. Using Bayesian inference, we have estimated critical epidemiological determinants. The estimated mean incubation period was 5.3 days (95% CI 4.2–6.8 days), mean time to hospitalisation was 3.5 days (95% CI 2.8–3.6 days), mean time from symptom onset to recovery was 26 days (95% CI 25–27 days) and mean time from symptom onset to death was 21 days (95% CI 16–26 days). The reproduction ratio was estimated to be 4.8 (95% CI 2.2–8.8) in the early part of the epidemic (February and March 2003) reducing to 0.75 (95% CI 0.65–0.85) in the later part of the epidemic (April and May 2003). The infectivity of symptomatic SARS cases in hospital and in the community was estimated. Community SARS cases caused transmission to others at an estimated rate of 0.4 per infective per day during the early part of the epidemic, reducing to 0.2 in the later part of the epidemic. For hospitalised patients, the daily infectivity was approximately 0.15 early in the epidemic, but fell to 0.0006 in the later part of the epidemic. Despite the lower daily infectivity level for hospitalised patients, the long duration of the hospitalisation led to a greater number of transmissions within hospitals compared with the community in the early part of the epidemic, as estimated by this study. This study investigated the individual infectivity profile during the symptomatic period, with an estimated peak infectivity on the ninth symptomatic day.