Genes flanking Xist in mouse and human are separated on the X chromosome in American marsupials

X inactivation, the transcriptional silencing of one of the two X chromosomes in female mammals, achieves dosage compensation of X-linked genes relative to XY males. In eutherian mammals X inactivation is regulated by the X-inactive specific transcript (Xist), a cis-acting non-coding RNA that triggers silencing of the chromosome from which it is transcribed. Marsupial mammals also undergo X inactivation but the mechanism is relatively poorly understood. We set out to analyse the X chromosome in Monodelphis domestica and Didelphis virginiana, focusing on characterizing the interval defined by the Chic1 and Slc16a2 genes that in eutherians flank the Xist locus. The synteny of this region is retained on chicken chromosome 4 where other loci belonging to the evolutionarily ancient stratum of the human X chromosome, the so-called X conserved region (XCR), are also located. We show that in both M. domestica and D. virginiana an evolutionary breakpoint has separated the Chic1 and Slc16a2 loci. Detailed analysis of opossum genomic sequences revealed linkage of Chic1 with the Lnx3 gene, recently proposed to be the evolutionary precursor of Xist, and Fip1, the evolutionary precursor of Tsx, a gene located immediately downstream of Xist in eutherians. We discuss these findings in relation to the evolution of Xist and X inactivation in mammals

The effect of beta-alanine supplementation on neuromuscular fatigue in elderly (55–92 Years): a double-blind randomized study

<p>Abstract</p> <p>Background</p> <p>Ageing is associated with a significant reduction in skeletal muscle carnosine which has been linked with a reduction in the buffering capacity of muscle and in theory, may increase the rate of fatigue during exercise. Supplementing beta-alanine has been shown to significantly increase skeletal muscle carnosine. The purpose of this study, therefore, was to examine the effects of ninety days of beta-alanine supplementation on the physical working capacity at the fatigue threshold (PWC_FT) in elderly men and women.</p> <p>Methods</p> <p>Using a double-blind placebo controlled design, twenty-six men (n = 9) and women (n = 17) (age ± SD = 72.8 ± 11.1 yrs) were randomly assigned to either beta-alanine (BA: 800 mg × 3 per day; n = 12; CarnoSyn™) or Placebo (PL; n = 14) group. Before (pre) and after (post) the supplementation period, participants performed a discontinuous cycle ergometry test to determine the PWC_FT.</p> <p>Results</p> <p>Significant increases in PWC_FT(28.6%) from pre- to post-supplementation were found for the BA treatment group (p < 0.05), but no change was observed with PL treatment. These findings suggest that ninety days of BA supplementation may increase physical working capacity by delaying the onset of neuromuscular fatigue in elderly men and women.</p> <p>Conclusion</p> <p>We suggest that BA supplementation, by improving intracellular pH control, improves muscle endurance in the elderly. This, we believe, could have importance in the prevention of falls, and the maintenance of health and independent living in elderly men and women.</p

Burst of Young Retrogenes and Independent Retrogene Formation in Mammals

Retroposition and retrogenes gain increasing attention as recent studies show that they play an important role in human new gene formation. Here we examined the patterns of retrogene distribution in 8 mammalian genomes using 4 non-mammalian genomes as a contrast. There has been a burst of young retrogenes not only in primate lineages as suggested in a recent study, but also in other mammalian lineages. In mammals, most of the retrofamilies (the gene families that have retrogenes) are shared between species. In these shared retrofamilies, 14%–18% of functional retrogenes may have originated independently in multiple mammalian species. Notably, in the independently originated retrogenes, there is an enrichment of ribosome related gene function. In sharp contrast, none of these patterns hold in non-mammals. Our results suggest that the recruitment of the specific L1 retrotransposons in mammals might have been an important evolutionary event for the split of mammals and non-mammals and retroposition continues to be an important active process in shaping the dynamics of mammalian genomes, as compared to being rather inert in non-mammals

The role of micro-organisms (Staphylococcus aureus and Candida albicans) in the pathogenesis of breast pain and infection in lactating women: study protocol

Background: The CASTLE (Candida and Staphylococcus Transmission: Longitudinal Evaluation) study will investigate the micro-organisms involved in the development of mastitis and &ldquo;breast thrush&rdquo; among breastfeeding women. To date, the organism(s) associated with the development of breast thrush have not been identified. The CASTLE study will also investigate the impact of physical health problems and breastfeeding problems on maternal psychological health in the early postpartum period.Methods/Design: The CASTLE study is a longitudinal descriptive study designed to investigate the role of Staphylococcus spp (species) and Candida spp in breast pain and infection among lactating women, and to describe the transmission dynamics of S. aureus and Candida spp between mother and infant. The relationship between breastfeeding and postpartum health problems as well as maternal psychological well-being is also being investigated. A prospective cohort of four hundred nulliparous women who are at least thirty six weeks gestation pregnant are being recruited from two hospitals in Melbourne, Australia (November 2009 to June 2011). At recruitment, nasal, nipple (both breasts) and vaginal swabs are taken and participants complete a questionnaire asking about previous known staphylococcal and candidal infections. Following the birth, participants are followed-up six times: in hospital and then at home weekly until four weeks postpartum. Participants complete a questionnaire at each time points to collect information about breastfeeding problems and postpartum health problems. Nasal and nipple swabs and breast milk samples are collected from the mother. Oral and nasal swabs are collected from the baby. A telephone interview is conducted at eight weeks postpartum to collect information about postpartum health problems and breastfeeding problems, such as mastitis and nipple and breast pain.Discussion: This study is the first longitudinal study of the role of both staphylococcal and candidal colonisation in breast infections and will help to resolve the current controversy about which is the primary organism in the condition known as breast thrush. This study will also document transmission dynamics of S. aureus and Candida spp between mother and infant. In addition, CASTLE will investigate the impact of common maternal physical health symptoms and the effect of breastfeeding problems on maternal psychological well-being.<br /

Estimating food production in an urban landscape

There is increasing interest in urban food production for reasons of food security, environmental sustainability, social and health benefits. In developed nations urban food growing is largely informal and localised, in gardens, allotments and public spaces, but we know little about the magnitude of this production. Here we couple own-grown crop yield data with garden and allotment areal surveys and urban fruit tree occurrence to provide one of the first estimates for current and potential food production in a UK urban setting. Current production is estimated to be sufficient to supply the urban population with fruit and vegetables for about 30 days per year, while the most optimistic model results suggest that existing land cultivated for food could supply over half of the annual demand. Our findings provide a baseline for current production whilst highlighting the potential for change under the scaling up of cultivation on existing land

Genetic Transformation of an Obligate Anaerobe, P. gingivalis for FMN-Green Fluorescent Protein Expression in Studying Host-Microbe Interaction

The recent introduction of “oxygen-independent” flavin mononucleotide (FMN)-based fluorescent proteins (FbFPs) is of major interest to both eukaryotic and prokaryotic microbial biologists. Accordingly, we demonstrate for the first time that an obligate anaerobe, the successful opportunistic pathogen of the oral cavity, Porphyromonas gingivalis, can be genetically engineered for expression of the non-toxic green FbFP. The resulting transformants are functional for studying dynamic bacterial processes in living host cells. The visualization of the transformed P. gingivalis (PgFbFP) revealed strong fluorescence that reached a maximum emission at 495 nm as determined by fluorescence microscopy and spectrofluorometry. Human primary gingival epithelial cells (GECs) were infected with PgFbFP and the bacterial invasion of host cells was analyzed by a quantitative fluorescence microscopy and antibiotic protection assays. The results showed similar levels of intracellular bacteria for both wild type and PgFbFP strains. In conjunction with organelle specific fluorescent dyes, utilization of the transformed strain provided direct and accurate determination of the live/metabolically active P. gingivalis' trafficking in the GECs over time. Furthermore, the GECs were co-infected with PgFbFP and the ATP-dependent Clp serine protease-deficient mutant (ClpP-) to study the differential fates of the two strains within the same host cells. Quantitative co-localization analyses displayed the intracellular PgFbFP significantly associated with the endoplasmic reticulum network, whereas the majority of ClpP- organisms trafficked into the lysosomes. Hence, we have developed a novel and reliable method to characterize live host cell-microbe interactions and demonstrated the adaptability of FMN-green fluorescent protein for studying persistent host infections induced by obligate anaerobic organisms

Lack of EGF receptor contributes to drug sensitivity of human germline cells

Germline mutations have been associated with generation of various types of tumour. In this study, we investigated genetic alteration of germline tumours that affect the drug sensitivity of cells. Although all germline tumour cells we tested were hypersensitive to DNA-damaging drugs, no significant alteration was observed in their DNA repair activity or the expression of DNA repair proteins. In contrast, germline tumours expressed very low level of epidermal growth factor receptor (EGFR) compared to drug-resistant ovarian cancer cells. An immunohistochemical analysis indicated that most of the primary germline tumours we tested expressed very low level of EGFR. In accordance with this, overexpression of EGFR in germline tumour cells showed an increase in drug resistance, suggesting that a lack of EGFR, at least in part, contributes to the drug sensitivity of germline tumours

A Gene Catalogue of the Euchromatic Male-Specific Region of the Horse Y Chromosome: Comparison with Human and Other Mammals

Studies of the Y chromosome in primates, rodents and carnivores provide compelling evidence that the male specific region of Y (MSY) contains functional genes, many of which have specialized roles in spermatogenesis and male-fertility. Little similarity, however, has been found between the gene content and sequence of MSY in different species. This hinders the discovery of species-specific male fertility genes and limits our understanding about MSY evolution in mammals. Here, a detailed MSY gene catalogue was developed for the horse – an odd-toed ungulate. Using direct cDNA selection from horse testis, and sequence analysis of Y-specific BAC clones, 37 horse MSY genes/transcripts were identified. The genes were mapped to the MSY BAC contig map, characterized for copy number, analyzed for transcriptional profiles by RT-PCR, examined for the presence of ORFs, and compared to other mammalian orthologs. We demonstrate that the horse MSY harbors 20 X-degenerate genes with known orthologs in other eutherian species. The remaining 17 genes are acquired or novel and have so far been identified only in the horse or donkey Y chromosomes. Notably, 3 transcripts were found in the heterochromatic part of the Y. We show that despite substantial differences between the sequence, gene content and organization of horse and other mammalian Y chromosomes, the functions of MSY genes are predominantly related to testis and spermatogenesis. Altogether, 10 multicopy genes with testis-specific expression were identified in the horse MSY, and considered likely candidate genes for stallion fertility. The findings establish an important foundation for the study of Y-linked genetic factors governing fertility in stallions, and improve our knowledge about the evolutionary processes that have shaped Y chromosomes in different mammalian lineages

Observations of Magnetic Fields Surrounding LkH alpha 101 Taken by the BISTRO Survey with JCMT-POL-2

We report the first high spatial resolution measurement of magnetic fields surrounding LkHα 101, part of the Auriga–California molecular cloud. The observations were taken with the POL-2 polarimeter on the James Clerk Maxwell Telescope within the framework of the B-fields In Star-forming Region Observations (BISTRO) survey. Observed polarization of thermal dust emission at 850 μm is found to be mostly associated with the redshifted gas component of the cloud. The magnetic field displays a relatively complex morphology. Two variants of the Davis–Chandrasekhar–Fermi method, unsharp masking and structure function, are used to calculate the strength of magnetic fields in the plane of the sky, yielding a similar result of BPOS ~ 115 μG. The mass-to-magnetic-flux ratio in critical value units, λ ~ 0.3, is the smallest among the values obtained for other regions surveyed by POL-2. This implies that the LkHα 101 region is subcritical, and the magnetic field is strong enough to prevent gravitational collapse. The inferred δB/B0 ~ 0.3 implies that the large-scale component of the magnetic field dominates the turbulent one. The variation of the polarization fraction with total emission intensity can be fitted by a power law with an index of α = 0.82 ± 0.03, which lies in the range previously reported for molecular clouds. We find that the polarization fraction decreases rapidly with proximity to the only early B star (LkHα 101) in the region. Magnetic field tangling and the joint effect of grain alignment and rotational disruption by radiative torques can potentially explain such a decreasing trend

Revealing the diverse magnetic field morphologies in Taurus dense cores with sensitive sub-millimeter polarimetry

We have obtained sensitive dust continuum polarization observations at 850 μm in the B213 region of Taurus using POL-2 on SCUBA-2 at the James Clerk Maxwell Telescope (JCMT), as part of the BISTRO (B-fields in STar-forming Region Observations) survey. These observations allow us to probe magnetic field (B-field) at high spatial resolution (∼2000 au or ∼0.01 pc at 140 pc) in two protostellar cores (K04166 and K04169) and one prestellar core (Miz-8b) that lie within the B213 filament. Using the Davis-Chandrasekhar-Fermi method, we estimate the B-field strengths in K04166, K04169, and Miz-8b to be 38±14 μG, 44±16 μG, and 12±5 μG, respectively. These cores show distinct mean B-field orientations. B-field in K04166 is well ordered and aligned parallel to the orientations of the core minor axis, outflows, core rotation axis, and large-scale uniform B-field, in accordance with magnetically regulated star formation via ambipolar diffusion taking place in K04166. B-field in K04169 is found to be ordered but oriented nearly perpendicular to the core minor axis and large-scale B-field, and not well-correlated with other axes. In contrast, Miz-8b exhibits disordered B-field which show no preferred alignment with the core minor axis or large-scale field. We found that only one core, K04166, retains a memory of the large-scale uniform B-field. The other two cores, K04169 and Miz-8b, are decoupled from the large-scale field. Such a complex B-field configuration could be caused by gas inflow onto the filament, even in the presence of a substantial magnetic flux