The emergence of obesity among indigenous Siberians

Once considered a disease of affluence and confined to industrialized nations, obesity is currently emerging as a major health concern in nearly every country in the world. Available data suggest that the prevalence rate of obesity has reached unprecedented levels in most developing countries, and is increasing at a rate that far outpaces that of developed nations. This increase in obesity has also been documented among North American circumpolar populations and is associated with lifestyle changes related to economic development. While obesity has not been well studied among indigenous Siberians, recent anthropological studies indicate that obesity and its associated comorbidities are important health problems.The present study examines recent adult body composition data from four indigenous Siberian populations (Evenki, Ket, Buriat, and Yakut) with two main objectives: 1) to determine the prevalence of overweight and obesity among these groups, and 2) to assess the influence of lifestyle and socioeconomic factors on the development of excess body fat. The results of this study indicate that obesity has emerged as an important health issue among indigenous Siberians, and especially for women, whose obesity rates are considerably higher than those of men (12% vs. 7%). The present study investigated the association between lifestyle and body composition among the Yakut, and documented substantial sex differences in lifestyle correlates of obesity. Yakut men with higher incomes and who owned more luxury consumer goods were more likely to have excess body fat while, among Yakut women, affluence was not strongly associated with overweight and obesity.     

A locus on mouse Chromosome 9 (Adip5) affects the relative weight of the gonadal but not retroperitoneal adipose depot

To identify the gene or genes on mouse Chromosome 9 that contribute to strain differences in fatness, we conducted an expanded mapping analysis to better define the region where suggestive linkage was found, using the F₂ generation of an intercross between the C57BL/6ByJ and 129P3/J mouse strains. Six traits were studied: the summed weight of two adipose depots, the weight of each depot, analyzed individually (the gonadal and retroperitoneal depot), and the weight of each depot (summed and individual) relative to body size. We found significant linkage (LOD = 4.6) that accounted for the relative weight of the summed adipose depots, and another for the relative weight of the gonadal (LOD = 5.3) but not retroperitoneal (LOD = 0.9) adipose depot. This linkage is near marker rs30280752 (61.1 Mb, Build 34) and probably is equivalent to the quantitative trait locus (QTL) Adip5. Because the causal gene is unknown, we identified and evaluated several candidates within the confidence interval with functional significance to the body fatness phenotype (Il18, Acat1, Cyp19a1, Crabp1, Man2c1, Neil1, Mpi1, Csk, Lsm16, Adpgk, Bbs4, Hexa, Thsd4, Dpp8, Anxa2, and Lipc). We conclude that the Adip5 locus is specific to the gonadal adipose depot and that a gene or genes near the linkage peak may account for this QTL. The following sequences have been submitted to the GenBank database: Thsd4: Accession Nos. DQ424862 and DQ517441 and Lsm16: Accession Nos. DQ240818-DQ240819.     

A methodology for centrifuge selection for the separation of high solids density cell broths by visualisation of performance using windows of operation

Expression systems capable of growing to high cell densities are now readily available and are popular due to the benefits of increased product concentration. However, such high solids density cultures pose a major challenge for bioprocess engineers as choosing the right separation equipment and operating it at optimal conditions is crucial for efficient recovery. This study proposes a methodology for the rapid determination of suitable operating conditions for the centrifugal recovery of high cell density fermentation broths. An ultra scale-down (USD) approach for the prediction of clarification and dewatering levels achieved in a range of typical high-speed centrifuges is presented. Together with a visualisation tool, a Window of Operation, this provides for the rapid analysis of separation performance and evaluation of the available operating conditions, as an aid in the selection of the centrifuge equipment most appropriate for a given process duty. A case study examining centrifuge selection for the processing of a high cell density Pichia pastoris culture demonstrates the method. The study examines semi-continuous disc-stack centrifuges and batch-operated machines such as multi-chamber bowls and Carr Powerfuges. Performance is assessed based on the variables of clarification, dewatering and product yield. Inclusion of limits imposed by the centrifuge type and design, and operation itself, serve to constrain the process and to define the Windows of Operation. The insight gained from the case study provides a useful indication of the utility of the methodology presented and illustrates the challenges of centrifuge selection for the demanding case of high solids concentration feed streams.     

NMR studies of ligand binding to P450(eryF) provides insight into the mechanism of cooperativity

Cytochrome P450's (P450's) catalyze the oxidative metabolism of most drugs and toxins. Although extensive studies have proven that some P450's demonstrate both homotropic and heterotropic cooperativity toward a number of substrates, the mechanistic and molecular details of P450 allostery are still not well-established. Here, we use UV/vis and heteronuclear nuclear magnetic resonance (NMR) spectroscopic techniques to study the mechanism and thermodynamics of the binding of two 9-aminophenanthrene (9-AP) and testosterone (TST) molecules to the erythromycin-metabolizing bacterial P450(eryF). UV/vis absorbance spectra of P450(eryF) demonstrated that binding occurs with apparent negative homotropic cooperativity for TST and positive homotropic cooperativity for 9-AP with Hill-equation-derived dissociation constants of K(S) = 4 and 200 microM, respectively. The broadening and shifting observed in the 2D-{1H,15N}-HSQC-monitored titrations of 15N-Phe-labeled P450(eryF) with 9-AP and TST indicated binding on intermediate and fast chemical exchange time scales, respectively, which was consistent with the Hill-equation-derived K(S) values for these two ligands. Regardless of the type of spectral perturbation observed (broadening for 9-AP and shifting for TST), the 15N-Phe NMR resonances most affected were the same in each titration, suggesting that the two ligands "contact" the same phenylalanines within the active site of P450(eryF). This finding is in agreement with X-ray crystal structures of bound P450(eryF) showing different ligands occupying similar active-site niches. Complex spectral behavior was additionally observed for a small collection of resonances in the TST titration, interpreted as multiple binding modes for the low-affinity TST molecule or multiple TST-bound P450(eryF) conformational substates. A structural and energetic model is presented that combines the energetics and structural aspects of 9-AP and TST binding derived from these observations.     

Animals mix it up too: the distribution of self-fertilization among hermaphroditic animals

Excluding insects, hermaphroditism occurs in about one-third of animal species, providing numerous opportunities for the evolution of selfing. Here we provide an overview of reproductive traits in hermaphroditic animal species, review the distribution of selfing rates in animals, and test for ecological correlates of selfing. Our dataset (1342 selfing-rate estimates for 142 species) is 97% based on estimates derived from the analysis of population structure (F(IS)-estimates) using genetic markers. The distribution of selfing is slightly U-shaped and differs significantly from the more strongly U-shaped plant distribution with 47% of animal t-estimates being intermediate (falling between 0.2 and 0.8) compared to 42% for plants. The influence of several factors on the distribution of selfing rates was explored (e.g., number of populations studied per species, habitat, coloniality, sessility, or fertilization type), none of which significantly affect the distribution. Our results suggest that genetic forces might contribute to the evolution of self-fertilization to the same extent in animals and plants, although the high proportion of intermediate outcrossing suggests a significant role of ecological factors (e.g., reproductive assurance) in animals. However, we caution that the distribution of selfing rates in animals is affected by various factors that might bias F(IS)-estimates, including phylogenetic underrepresentation of highly selfing and outcrossing species, various genotyping errors (e.g., null alleles) and inbreeding depression. This highlights the necessity of obtaining better estimates of selfing for hermaphroditic animals, such as genotyping progeny arrays, as in plants.     

Pleistocene rewilding: an optimistic agenda for twenty-first century conservation

Large vertebrates are strong interactors in food webs, yet they were lost from most ecosystems after the dispersal of modern humans from Africa and Eurasia. We call for restoration of missing ecological functions and evolutionary potential of lost North American megafauna using extant conspecifics and related taxa. We refer to this restoration as Pleistocene rewilding; it is conceived as carefully managed ecosystem manipulations whereby costs and benefits are objectively addressed on a case-by-case and locality-by-locality basis. Pleistocene rewilding would deliberately promote large, long-lived species over pest and weed assemblages, facilitate the persistence and ecological effectiveness of megafauna on a global scale, and broaden the underlying premise of conservation from managing extinction to encompass restoring ecological and evolutionary processes. Pleistocene rewilding can begin immediately with species such as Bolson tortoises and feral horses and continue through the coming decades with elephants and Holarctic lions. Our exemplar taxa would contribute biological, economic, and cultural benefits to North America. Owners of large tracts of private land in the central and western United States could be the first to implement this restoration. Risks of Pleistocene rewilding include the possibility of altered disease ecology and associated human health implications, as well as unexpected ecological and sociopolitical consequences of reintroductions. Establishment of programs to monitor suites of species interactions and their consequences for biodiversity and ecosystem health will be a significant challenge. Secure fencing would be a major economic cost, and social challenges will include acceptance of predation as an overriding natural process and the incorporation of pre-Columbian ecological frameworks into conservation strategies.