Alternative Strategies to Reduce Maternal Mortality in India: A Cost-Effectiveness Analysis

A cost-effectiveness study by Sue Goldie and colleagues finds that better family planning, provision of safe abortion, and improved intrapartum and emergency obstetrical care could reduce maternal mortality in India by 75% in 5 years

Stochastic analysis of the GAL genetic switch in Saccharomyces cerevisiae: Modeling and experiments reveal hierarchy in glucose repression

<p>Abstract</p> <p>Background</p> <p>Transcriptional regulation involves protein-DNA and protein-protein interactions. Protein-DNA interactions involve reactants that are present in low concentrations, leading to stochastic behavior. In addition, multiple regulatory mechanisms are typically involved in transcriptional regulation. In the <it>GAL </it>regulatory system of <it>Saccharomyces cerevisiae</it>, the inhibition of glucose is accomplished through two regulatory mechanisms: one through the transcriptional repressor Mig1p, and the other through regulating the amount of transcriptional activator Gal4p. However, the impact of stochasticity in gene expression and hierarchy in regulatory mechanisms on the phenotypic level is not clearly understood.</p> <p>Results</p> <p>We address the question of quantifying the effect of stochasticity inherent in these regulatory mechanisms on the performance of various genes under the regulation of Mig1p and Gal4p using a dynamic stochastic model. The stochastic analysis reveals the importance of both the mechanisms of regulation for tight expression of genes in the <it>GAL </it>network. The mechanism involving Gal4p is the dominant mechanism, yielding low variability in the expression of <it>GAL </it>genes. The mechanism involving Mig1p is necessary to maintain the switch-like response of certain <it>GAL </it>genes. The number of binding sites for Mig1p and Gal4p further influences the expression of the genes, with extra binding sites lowering the variability of expression. Our experiments involving growth on various substrates show that the trends predicted in mean expression and its variability are transmitted to the phenotypic level.</p> <p>Conclusion</p> <p>The mechanisms involved in the transcriptional regulation and their variability set up a hierarchy in the phenotypic response to growth on various substrates. Structural motifs, such as the number of binding sites and the mechanism of regulation, determine the level of stochasticity and eventually, the phenotypic response.</p

The genetic legacy of extreme exploitation in a polar vertebrate

Understanding the effects of human exploitation on the genetic composition of wild populations is important for predicting species persistence and adaptive potential. We therefore investigated the genetic legacy of large-scale commercial harvesting by reconstructing, on a global scale, the recent demographic history of the Antarctic fur seal (Arctocephalus gazella), a species that was hunted to the brink of extinction by 18th and 19th century sealers. Molecular genetic data from over 2,000 individuals sampled from all eight major breeding locations across the species’ circumpolar geographic distribution, show that at least four relict populations around Antarctica survived commercial hunting. Coalescent simulations suggest that all of these populations experienced severe bottlenecks down to effective population sizes of around 150–200. Nevertheless, comparably high levels of neutral genetic variability were retained as these declines are unlikely to have been strong enough to deplete allelic richness by more than around 15%. These findings suggest that even dramatic short-term declines need not necessarily result in major losses of diversity, and explain the apparent contradiction between the high genetic diversity of this species and its extreme exploitation history

Postsealing genetic variation and population structure of two species of fur seal (Arctocephalus gazella and A. tropicalis)

Commercial sealing in the 18th and 19th centuries had a major impact on the Antarctic and subantarctic fur seal populations (Arctocephalus gazella and A. tropicalis) in the Southern Ocean. The intensive and unrestricted nature of the industry ensured substantial reductions in population sizes and resulted in both species becoming locally extinct at some sites. However, both species are continuing to recover, through the recolonization of islands across their former range and increasing population size. This study investigated the extent and pattern of genetic variation in each species to examine the hypothesis that higher levels of historic sealing in A. gazella have resulted in a greater loss of genetic variability and population structure compared with A. tropicalis. A 316-bp section of the mitochondrial control region was sequenced and revealed nucleotide diversities of 3.2% and 4.8% for A. gazella and A. tropicalis, respectively. There was no geographical distribution of lineages observed within either species, although the respective ΦST values of 0.074 and 0.19 were significantly greater than zero. These data indicate low levels of population structure in A. gazella and relatively high levels in A. tropicalis. Additional samples screened with restriction endonucleases were incorporated, and the distribution of restriction fragment length polymorphism (RFLP) and sequence haplotypes were examined to identify the main source populations of newly recolonized islands. For A. tropicalis, the data suggest that Macquarie Island and Iles Crozet were probably recolonized by females from Marion Island, and to a lesser extent Ile Amsterdam. Although there was less population structure within A. gazella, there were two geographical regions identified: a western region containing the populations of South Georgia and Bouvetøya, which were the probable sources for populations at Marion, the South Shetland and Heard Islands; and an eastern region containing the panmictic populations of Iles Kerguelen and Macquarie Island. The latter region may be a result of a pronounced founder effect, or represent a remnant population that survived sealing at Iles Kerguelen

Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990.

BACKGROUND: Intrapartum hypoxic events ("birth asphyxia") may result in stillbirth, neonatal or postneonatal mortality, and impairment. Systematic morbidity estimates for the burden of impairment outcomes are currently limited. Neonatal encephalopathy (NE) following an intrapartum hypoxic event is a strong predictor of long-term impairment. METHODS: Linear regression modeling was conducted on data identified through systematic reviews to estimate NE incidence and time trends for 184 countries. Meta-analyses were undertaken to estimate the risk of NE by sex of the newborn, neonatal case fatality rate, and impairment risk. A compartmental model estimated postneonatal survivors of NE, depending on access to care, and then the proportion of survivors with impairment. Separate modeling for the Global Burden of Disease 2010 (GBD2010) study estimated disability adjusted life years (DALYs), years of life with disability (YLDs), and years of life lost (YLLs) attributed to intrapartum-related events. RESULTS: In 2010, 1.15 million babies (uncertainty range: 0.89-1.60 million; 8.5 cases per 1,000 live births) were estimated to have developed NE associated with intrapartum events, with 96% born in low- and middle-income countries, as compared with 1.60 million in 1990 (11.7 cases per 1,000 live births). An estimated 287,000 (181,000-440,000) neonates with NE died in 2010; 233,000 (163,000-342,000) survived with moderate or severe neurodevelopmental impairment; and 181,000 (82,000-319,000) had mild impairment. In GBD2010, intrapartum-related conditions comprised 50.2 million DALYs (2.4% of total) and 6.1 million YLDs. CONCLUSION: Intrapartum-related conditions are a large global burden, mostly due to high mortality in low-income countries. Universal coverage of obstetric care and neonatal resuscitation would prevent most of these deaths and disabilities. Rates of impairment are highest in middle-income countries where neonatal intensive care was more recently introduced, but quality may be poor. In settings without neonatal intensive care, the impairment rate is low due to high mortality, which is relevant for the scale-up of basic neonatal resuscitation

Global threats to pinnipeds

Kovacs KM, Aguilar A, Aurioles D, et al. Global threats to pinnipeds. Marine Mammal Science. 2011;28(2):414-436