Distribution of lipids from the yolk to the tissues during development of the water python (<Emphasis Type="Italic">Liasis fuscus</Emphasis>)

Energy metabolism during embryonic development of snakes differs in several respects from the patterns displayed by other reptiles. There are, however, no previous reports describing the main energy source for development, the yolk lipids, in snake eggs. There is also no information on the distribution of yolk fatty acids to the tissues during snake development. In eggs of the water python (Liasis fuscus), we report that triacylglycerol, phospholipid, cholesteryl ester and free cholesterol, respectively, form 70.3%, 14.1%, 5.7% and 2.1% of the total lipid. The main polyunsaturate of the yolk lipid classes is 18:2n-6. The yolk phospholipid contains 20:4n-6 and 22:6n-3 at 13.0% and 3.6% (w/w), respectively. Approximately 10% and 30% of the initial egg lipids are respectively recovered in the residual yolk and the fat body of the hatchling. A major function of yolk lipid is, therefore, to provision the neonate with large energy reserves. The proportion of 22:6n-3 in brain phospholipid of the hatchling is 11.1% (w/w): this represents only 0.24% of the amount of 22:6n-3 originally present in the egg. This also contrasts with values for free-living avian species where the proportion of DHA in neonatal brain phospholipid is 16–19%. In the liver of the newly hatched python, triacylglycerol, phospholipid and cholesteryl ester, respectively, form 68.2%, 7.7% and 14.3% of total lipid. This contrasts with embryos of birds where cholesteryl ester forms up to 80% of total liver lipid and suggests that the mechanism of lipid transfer in the water python embryo differs in some respects from the avian situation.Abbreviations ARA arachidonic acid - DHA docosahexaenoic acidCommunicated by G. Heldmaier     

Computational and experimental analysis reveals a novel Src family kinase in the C. elegans genome

MOTIVATION: The complete genomes of a number of organisms have already been sequenced. However, the vast majority of annotated genes are derived by gene prediction methods. It is important to not only validate the predicted coding regions but also to identify genes that may have been missed by these programs. METHODS: We searched the entire C.elegans genomic sequence database maintained by the Sanger Center using human c-Src sequence in a TBLASN search. We have confirmed one of the predicted regions by isolation of a cDNA and carried out a phylogenetic analysis of Src kinase family members in the worm, fly and several vertebrate species. RESULTS: Our analysis identified a novel tyrosine kinase in the C.elegans genome that contains functional features typical of the Src family kinases that we have designated as Src-1. The open reading frame contains a conserved N-terminal myristoylation site and a tyrosine residue within the C-terminus that is crucial for regulating the activity of Src kinases. Our phylogenetic analysis of Src family members from C. elegans, Drosophila and other higher organisms revealed a relationship among Src kinases from C. elegans and Drosophila.     

Photoperiodism: the coincidental perception of the season

Many plants use the seasonal change in daylength as a signal for flowering. Daylength sensing in Arabidopsis has now been shown to occur by an external coincidence mechanism, which operates by the circadian and light regulation of CONSTANS.     

National,Regional, and Global Trends in Infertility Prevalence Since 1990: A Systematic Analysis of 277 Health Surveys

Background

Global, regional, and national estimates of prevalence of and tends in infertility are needed to target prevention and treatment efforts. By applying a consistent algorithm to demographic and reproductive surveys available from developed and developing countries, we estimate infertility prevalence and trends, 1990 to 2010, by country and region.

Methods and Findings

We accessed and analyzed household survey data from 277 demographic and reproductive health surveys using a consistent algorithm to calculate infertility. We used a demographic infertility measure with live birth as the outcome and a 5-y exposure period based on union status, contraceptive use, and desire for a child. We corrected for biases arising from the use of incomplete information on past union status and contraceptive use. We used a Bayesian hierarchical model to estimate prevalence of and trends in infertility in 190 countries and territories. In 2010, among women 20–44 y of age who were exposed to the risk of pregnancy, 1.9% (95% uncertainty interval 1.7%, 2.2%) were unable to attain a live birth (primary infertility). Out of women who had had at least one live birth and were exposed to the risk of pregnancy, 10.5% (9.5%, 11.7%) were unable to have another child (secondary infertility). Infertility prevalence was highest in South Asia, Sub-Saharan Africa, North Africa/Middle East, and Central/Eastern Europe and Central Asia. Levels of infertility in 2010 were similar to those in 1990 in most world regions, apart from declines in primary and secondary infertility in Sub-Saharan Africa and primary infertility in South Asia (posterior probability [pp] ≥0.99). Although there were no statistically significant changes in the prevalence of infertility in most regions amongst women who were exposed to the risk of pregnancy, reduced child-seeking behavior resulted in a reduction of primary infertility among all women from 1.6% to 1.5% (pp = 0.90) and a reduction of secondary infertility among all women from 3.9% to 3.0% (pp>0.99) from 1990 to 2010. Due to population growth, however, the absolute number of couples affected by infertility increased from 42.0 million (39.6 million, 44.8 million) in 1990 to 48.5 million (45.0 million, 52.6 million) in 2010. Limitations of the study include gaps in survey data for some countries and the use of proxies to determine exposure to pregnancy.

Conclusions

We analyzed demographic and reproductive household survey data to reveal global patterns and trends in infertility. Independent from population growth and worldwide declines in the preferred number of children, we found little evidence of changes in infertility over two decades, apart from in the regions of Sub-Saharan Africa and South Asia. Further research is needed to identify the etiological causes of these patterns and trends. Please see later in the article for the Editors'' Summary     

BRCA1-directed,enhanced and aberrant homologous recombination: Mechanism and potential treatment strategies

Despite intense studies, questions still remain regarding the molecular mechanisms leading to the development of hereditary breast and ovarian cancers. Research focused on elucidating the role of the breast cancer susceptibility gene 1 (BRCA1) in the DNA damage response may be of the most critical importance to understanding these processes. The BRCA1 protein has an N-terminal RING domain possessing E3 ubiquitin-ligase activity and a C-terminal BRCT domain involved in binding specific phosphoproteins. These domains are involved directly or indirectly in DNA double-strand break (DSB) repair. As the two terminal domains of BRCA1 represent two separate entities, understanding how these domains communicate and are functionally altered in regards to DSB repair is critical for understanding the development of BRCA1-related breast and ovarian cancers and for developing novel therapeutics. Herein, we review recent findings of how altered functions of these domains might lead to cancer through a mechanism of increased aberrant homologous recombination and possible implications for the development of BRCA1 inhibitors.Key words: BRCT, DNA repair, peptide, radiation, RING, ubiquitylation     

Lumican is a major proteoglycan component of the bone matrix.

MC3T3-E1 mouse calvaria cells are a clonal population of committed osteoprogenitors that in the presence of appropriate supplements form a mineralized bone matrix. The development of the MC3T3-E1 cells can be divided into three major stages, namely, proliferation, differentiation, and mineralization. Recently, using the cDNA microarray technology we found lumican to be abundantly expressed during the mineralization and differentiation stages of the MC3T3-E1 development and not during the proliferation stage. Lumican has been shown to play essential roles in regulating collagen fibril formation in different extracellular matrices but its expression in the developing bone matrix remains elusive. By examining the expression profile of this gene during the different stages of MC3T3-E1 development, utilizing the 'real-time' PCR technology, we observed that the expression of lumican increases as the osteoblast culture differentiates and matures, suggesting that lumican may be involved in regulating collagen fibrillogenesis in bone matrices. Using immunostaining, we observed that during the early embryonic development of mouse (E11 to E13), lumican is mainly expressed in the cartilaginous matrices. However, in the older embryos (E14 to E16), the expression of lumican is more prominent in the developing bone matrices. Our data suggest that lumican is a significant proteoglycan component of bone matrix, which is secreted by differentiating and mature osteoblasts only and therefore it can be used as a marker to distinguish proliferating pre-osteoblasts from the differentiating osteoblasts.     

Validation of a spatial agent-based model for Taenia solium transmission (“CystiAgent”) against a large prospective trial of control strategies in northern Peru

BackgroundThe pork tapeworm (Taenia solium) is a parasitic helminth that imposes a major health and economic burden on poor rural populations around the world. As recognized by the World Health Organization, a key barrier for achieving control of T. solium is the lack of an accurate and validated simulation model with which to study transmission and evaluate available control and elimination strategies. CystiAgent is a spatially-explicit agent based model for T. solium that is unique among T. solium models in its ability to represent key spatial and environmental features of transmission and simulate spatially targeted interventions, such as ring strategy.Methods/Principal findingsWe validated CystiAgent against results from the Ring Strategy Trial (RST)–a large cluster-randomized trial conducted in northern Peru that evaluated six unique interventions for T. solium control in 23 villages. For the validation, each intervention strategy was replicated in CystiAgent, and the simulated prevalences of human taeniasis, porcine cysticercosis, and porcine seroincidence were compared against prevalence estimates from the trial. Results showed that CystiAgent produced declines in transmission in response to each of the six intervention strategies, but overestimated the effect of interventions in the majority of villages; simulated prevalences for human taenasis and porcine cysticercosis at the end of the trial were a median of 0.53 and 5.0 percentages points less than prevalence observed at the end of the trial, respectively.Conclusions/SignificanceThe validation of CystiAgent represented an important step towards developing an accurate and reliable T. solium transmission model that can be deployed to fill critical gaps in our understanding of T. solium transmission and control. To improve model accuracy, future versions would benefit from improved data on pig immunity and resistance, field effectiveness of anti-helminthic treatment, and factors driving spatial clustering of T. solium infections including dispersion and contact with T. solium eggs in the environment.     

Major histocompatibility complex based resistance to a common bacterial pathogen of amphibians

Given their well-developed systems of innate and adaptive immunity, global population declines of amphibians are particularly perplexing. To investigate the role of the major histocompatibility complex (MHC) in conferring pathogen resistance, we challenged Xenopus laevis tadpoles bearing different combinations of four MHC haplotypes (f, g, j, and r) with the bacterial pathogen Aeromonas hydrophila in two experiments. In the first, we exposed ff, fg, gg, gj, and jj tadpoles, obtained from breeding MHC homozygous parents, to one of three doses of A. hydrophila or heat-killed bacteria as a control. In the second, we exposed ff, fg, fr, gg, rg, and rr tadpoles, obtained from breeding MHC heterozygous parents and subsequently genotyped by PCR, to A. hydrophila, heat-killed bacteria or media alone as controls. We thereby determined whether the same patterns of MHC resistance emerged within as among families, independent of non-MHC heritable differences. Tadpoles with r or g MHC haplotypes were more likely to die than were those with f or j haplotypes. Growth rates varied among MHC types, independent of exposure dose. Heterozygous individuals with both susceptible and resistant haplotypes were intermediate to either homozygous genotype in both size and survival. The effect of the MHC on growth and survival was consistent between experiments and across families. MHC alleles differentially confer resistance to, or tolerance of, the bacterial pathogen, which affects tadpoles' growth and survival.