Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes

In situ hybridization experiments were carried out with two clones, YACG 35 and 2.8, which had been selected from two genomic libraries strongly enriched for the human Y chromosome. Besides the human Y chromosome, both sequences strongly hybridized to the human X chromosome, with few minor binding sites on autosomes. In particular, on the X chromosome DNA from clone YACG 35 hybridized to the centromeric region and the distal part of the short arm (Xp2.2). On the Y chromosome, the sequence was assigned to one site situated in the border region between Yq1.1 and Yq1.2. DNA from clone 2.8 also hybridized to the centromeric region of the X and the distal part of the short arm (Xq2.2). On the Y, however, two binding sites were observed (Yp1.1 and Yq1.2). The findings indicate that sex chromosomal sequences may be localized in homologous regions (as suggested from meiotic pairing) but also at ectopic sites

The writing on the wall: the concealed communities of the East Yorkshire horselads

This paper examines the graffiti found within late nineteenth and early-twentieth century farm buildings in the Wolds of East Yorkshire. It suggests that the graffiti were created by a group of young men at the bottom of the social hierarchy - the horselads – and was one of the ways in which they constructed a distinctive sense of communal identity, at a particular stage in their lives. Whilst it tells us much about changing agricultural regimes and social structures, it also informs us about experiences and attitudes often hidden from official histories and biographies. In this way, the graffiti are argued to inform our understanding, not only of a concealed community, but also about their hidden histor

Exploring local knowledge and perceptions on zoonoses among pastoralists in northern and eastern Tanzania

Background: Zoonoses account for the most commonly reported emerging and re-emerging infectious diseases in Sub-Saharan Africa. However, there is limited knowledge on how pastoral communities perceive zoonoses in relation to their livelihoods, culture and their wider ecology. This study was carried out to explore local knowledge and perceptions on zoonoses among pastoralists in Tanzania. Methodology and principal findings: This study involved pastoralists in Ngorongoro district in northern Tanzania and Kibaha and Bagamoyo districts in eastern Tanzania. Qualitative methods of focus group discussions, participatory epidemiology and interviews were used. A total of 223 people were involved in the study. Among the pastoralists, there was no specific term in their local language that describes zoonosis. Pastoralists from northern Tanzania possessed a higher understanding on the existence of a number of zoonoses than their eastern districts' counterparts. Understanding of zoonoses could be categorized into two broad groups: a local syndromic framework, whereby specific symptoms of a particular illness in humans concurred with symptoms in animals, and the biomedical framework, where a case definition is supported by diagnostic tests. Some pastoralists understand the possibility of some infections that could cross over to humans from animals but harm from these are generally tolerated and are not considered as threats. A number of social and cultural practices aimed at maintaining specific cultural functions including social cohesion and rites of passage involve animal products, which present zoonotic risk. Conclusions: These findings show how zoonoses are locally understood, and how epidemiology and biomedicine are shaping pastoralists perceptions to zoonoses. Evidence is needed to understand better the true burden and impact of zoonoses in these communities. More studies are needed that seek to clarify the common understanding of zoonoses that could be used to guide effective and locally relevant interventions. Such studies should consider in their approaches the pastoralists' wider social, cultural and economic set up

A randomised control trial of low glycaemic index carbohydrate diet versus no dietary intervention in the prevention of recurrence of macrosomia

<p>Abstract</p> <p>Background</p> <p>Maternal weight and maternal weight gain during pregnancy exert a significant influence on infant birth weight and the incidence of macrosomia. Fetal macrosomia is associated with an increase in both adverse obstetric and neonatal outcome, and also confers a future risk of childhood obesity. Studies have shown that a low glycaemic diet is associated with lower birth weights, however these studies have been small and not randomised <abbrgrp><abbr bid="B1">1</abbr><abbr bid="B2">2</abbr></abbrgrp>. Fetal macrosomia recurs in a second pregnancy in one third of women, and maternal weight influences this recurrence risk <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>.</p> <p>Methods/Design</p> <p>We propose a randomised control trial of low glycaemic index carbohydrate diet vs. no dietary intervention in the prevention of recurrence of fetal macrosomia.</p> <p>Secundigravid women whose first baby was macrosomic, defined as a birth weight greater than 4000 g will be recruited at their first antenatal visit.</p> <p>Patients will be randomised into two arms, a control arm which will receive no dietary intervention and a diet arm which will be commenced on a low glycaemic index diet.</p> <p>The primary outcome measure will be the mean birth weight centiles and ponderal indices in each group.</p> <p>Discussion</p> <p>Altering the source of maternal dietary carbohydrate may prove to be valuable in the management of pregnancies where there has been a history of fetal macrosomia. Fetal macrosomia recurs in a second pregnancy in one third of women. This randomised control trial will investigate whether or not a low glycaemic index diet can affect this recurrence risk.</p> <p>Current Controlled Trials Registration Number</p> <p>ISRCTN54392969</p

Surprisingly low compliance to local guidelines for risk factor based screening for gestational diabetes mellitus - A population-based study

BACKGROUND: Screening for gestational diabetes mellitus (GDM) is routine during pregnancy in many countries in the world. The screening programs are either based on general screening offered to all pregnant women or risk factor based screening stipulated in local clinical guidelines. The aims of this study were to investigate: 1) the compliance with local guidelines of screening for GDM and 2) the outcomes of pregnancy and birth in relation to risk factors of GDM and whether or not exposed to oral glucose tolerance test (OGTT).METHODS: This study design was a population-based retrospective cross-sectional study of 822 women. A combination of questionnaire data and data collected from medical records was applied. Compliance to the local guidelines of risk factor based screening for GDM was examined and a comparison of outcomes of pregnancy and delivery in relation to risk factor groups for GDM was performed.RESULTS: Of the 822 participants, 257 (31.3%) women fulfilled at least one criterion for being exposed to screening for GDM according to the local clinical guidelines. However, only 79 (30.7%) of these women were actually exposed to OGTT and of those correctly exposed for screening, seven women were diagnosed with GDM. Women developing risk factors for GDM during pregnancy had a substantially increased risk of giving birth to an infant with macrosomia.CONCLUSION: Surprisingly low compliance with the local clinical guidelines for screening for GDM during pregnancy was found. Furthermore, the prevalence of the risk factors of GDM in our study was almost doubled compared to previous Swedish studies. Pregnant women developing risk factors of GDM during pregnancy were found to be at substantially increased risk of giving birth to an infant with macrosomia. There is a need of actions improving compliance to the local guidelines.</p

Careers of an elite cohort of U.S. basic life science postdoctoral fellows and the influence of their mentor's citation record

<p>Abstract</p> <p>Background</p> <p>There is general agreement that the number of U.S. science PhDs being trained far exceeds the number of future academic positions. One suggested approach to this problem is to significantly reduce the number of PhD positions. A counter argument is that students are aware of the limited academic positions but have chosen a PhD track because it opens other, non-academic, opportunities. The latter view requires that students have objective information about what careers options will be available for them.</p> <p>Methods</p> <p>The scientific careers of the 1992-94 cohort of NIH National Institute of General Medical Sciences (NIGMS) Kirchstein-NRSA F32 postdoctoral fellows (PD) was determined by following their publications (PubMed), grants (NIH and NSF), and faculty and industry positions through 2009. These basic life science PDs receive support through individual grant applications and represent the most successful class of NIH PDs as judged by academic careers and grants. The sex dependence of the career and grant success and the influence of the PD mentor's citation record were also determined</p> <p>Results</p> <p>Of the 439 1992-94 NIGMS F32 fellows, the careers of 417 could be determined. Although females had significantly higher rates of dropping out of science (22% females, 9% males) there was no significant difference in the fraction of females that ended up as associate or full professors at research universities (22.8% females, 29.1% for males). More males then females ended up in industry (34% males, 22% females). Although there was no significant correlation between male grant success and their mentor's publication record (h index, citations, publications), there was a significant correlation for females. Females whose mentor's h index was in the top quartile were nearly 3 times as likely to receive a major grant as those whose mentors were in the bottom quartile (38.7% versus 13.3%).</p> <p>Conclusions</p> <p>Sixteen years after starting their PD, only 9% of males had dropped out of science. More females (28%) have dropped out of science, primarily because fewer went into industry positions. The mentor's publication record does not affect the future grant success of males but it has a dramatic effect on female grant success.</p

CSMET: Comparative Genomic Motif Detection via Multi-Resolution Phylogenetic Shadowing

Functional turnover of transcription factor binding sites (TFBSs), such as whole-motif loss or gain, are common events during genome evolution. Conventional probabilistic phylogenetic shadowing methods model the evolution of genomes only at nucleotide level, and lack the ability to capture the evolutionary dynamics of functional turnover of aligned sequence entities. As a result, comparative genomic search of non-conserved motifs across evolutionarily related taxa remains a difficult challenge, especially in higher eukaryotes, where the cis-regulatory regions containing motifs can be long and divergent; existing methods rely heavily on specialized pattern-driven heuristic search or sampling algorithms, which can be difficult to generalize and hard to interpret based on phylogenetic principles. We propose a new method: Conditional Shadowing via Multi-resolution Evolutionary Trees, or CSMET, which uses a context-dependent probabilistic graphical model that allows aligned sites from different taxa in a multiple alignment to be modeled by either a background or an appropriate motif phylogeny conditioning on the functional specifications of each taxon. The functional specifications themselves are the output of a phylogeny which models the evolution not of individual nucleotides, but of the overall functionality (e.g., functional retention or loss) of the aligned sequence segments over lineages. Combining this method with a hidden Markov model that autocorrelates evolutionary rates on successive sites in the genome, CSMET offers a principled way to take into consideration lineage-specific evolution of TFBSs during motif detection, and a readily computable analytical form of the posterior distribution of motifs under TFBS turnover. On both simulated and real Drosophila cis-regulatory modules, CSMET outperforms other state-of-the-art comparative genomic motif finders

Industrial energy use and the human life history

The demographic rates of most organisms are supported by the consumption of food energy, which is used to produce new biomass and fuel physiological processes. Unlike other species, modern humans use ‘extra-metabolic' energy sources acquired independent of physiology, which also influence demographics. We ask whether the amount of extra-metabolic energy added to the energy budget affects demographic and life history traits in a predictable way. Currently it is not known how human demographics respond to energy use, and we characterize this response using an allometric approach. All of the human life history traits we examine are significant functions of per capita energy use across industrialized populations. We find a continuum of traits from those that respond strongly to the amount of extra-metabolic energy used, to those that respond with shallow slopes. We also show that the differences in plasticity across traits can drive the net reproductive rate to below-replacement levels

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

Clinical studies of the treatment of glioma and cutaneous melanoma using boron neutron capture therapy (BNCT) are currently taking place in the USA, Europe and Japan. New BNCT clinical facilities are under construction in Finland, Sweden, England and California. The observation of transient acute effects in the oral mucosa of a number of glioma patients involved in the American clinical trials, suggests that radiation damage of the oral mucosa could be a potential complication in future BNCT clinical protocols, involving higher doses and larger irradiation field sizes. The present investigation is the first to use a high resolution surface analytical technique to relate the microdistribution of boron-10 (10B) in the oral mucosa to the biological effectiveness of the 10B(n,α)7Li neutron capture reaction in this tissue. The two boron delivery agents used clinically in Europe/Japan and the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respectively, were evaluated using a rat ventral tongue model. 10B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of 10B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood 10B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The 10B content of the lamina propria was higher than that measured in the epithelium for both BSH and BPA. The difference was most marked for BSH, where 10B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of 10B was also measured in blood vessel walls where relatively low levels of accumulation of BSH, as compared with BPA, was demonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood 10B partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively. Evaluation of tongue mucosal response (ulceration) to BNC irradiation indicated a considerably reduced radiation sensitivity using BSH as the boron delivery agent relative to BPA. The compound biological effectiveness (CBE) factor for BSH was estimated at 0.29 ± 0.02. This compares with a previously published CBE factor for BPA of 4.87 ± 0.16. It was concluded that variations in the microdistribution profile of 10B, using the two boron delivery agents, had a significant effect on the response of oral mucosa to BNC irradiation. From a clinical perspective, based on the findings of the present study, it is probable that potential radiation-induced oral mucositis will be restricted to BNCT protocols involving BPA. However, a thorough high resolution analysis of 10B microdistribution in human oral mucosal tissue, using a technique such as ion microscopy, is a prerequisite for the use of experimentally derived CBE factors in clinical BNCT. © 2000 Cancer Research Campaig