2,254 research outputs found
Pregnancy postponement and childlessness leads to chronic hypervascularity of the breasts and cancer risk
Epidemiologists have established that women with small families, and particularly nulliparae, are prone to develop breast cancer later in life. We report that physiological mammary hypervascularity may be an intermediate reason against the background that breast-core vascularity is normal in pregnancy but pathological in the vascularisation of cancer. We examined breast ‘core’ vascularity in nulliparae during their potential reproductive life and in parous women after their last birth but before their menopause. Fifty clinically normal pre-menopausal non-pregnant women (100 breasts) were studied daily for one ‘luteal positive’ menstrual cycle. Their parity history varied from zero to five babies. Under controlled domestic conditions each wore a special electronic thermometric bra to automatically record breast ‘core’ temperature changes as a measure of mammary tissue blood flow. In the nulliparae there was a rise of breast vascularity throughout reproductive life. In the parous women, a year or so after each birth, breast vascularity was reset at a lower level than before the pregnancy; thereafter, as in nulliparae, there was progressive increase in mammary vascularity until the menopause
Improved annotation of 3' untranslated regions and complex loci by combination of strand-specific direct RNA sequencing, RNA-seq and ESTs
The reference annotations made for a genome sequence provide the framework
for all subsequent analyses of the genome. Correct annotation is particularly
important when interpreting the results of RNA-seq experiments where short
sequence reads are mapped against the genome and assigned to genes according to
the annotation. Inconsistencies in annotations between the reference and the
experimental system can lead to incorrect interpretation of the effect on RNA
expression of an experimental treatment or mutation in the system under study.
Until recently, the genome-wide annotation of 3-prime untranslated regions
received less attention than coding regions and the delineation of intron/exon
boundaries. In this paper, data produced for samples in Human, Chicken and A.
thaliana by the novel single-molecule, strand-specific, Direct RNA Sequencing
technology from Helicos Biosciences which locates 3-prime polyadenylation sites
to within +/- 2 nt, were combined with archival EST and RNA-Seq data. Nine
examples are illustrated where this combination of data allowed: (1) gene and
3-prime UTR re-annotation (including extension of one 3-prime UTR by 5.9 kb);
(2) disentangling of gene expression in complex regions; (3) clearer
interpretation of small RNA expression and (4) identification of novel genes.
While the specific examples displayed here may become obsolete as genome
sequences and their annotations are refined, the principles laid out in this
paper will be of general use both to those annotating genomes and those seeking
to interpret existing publically available annotations in the context of their
own experimental dataComment: 44 pages, 9 figure
Aromatase gene and its effects on growth, reproductive and maternal ability traits in a multibreed sheep population from Brazil
We determined the polymorphism C242T of the aromatase gene (Cyp19) and its allelic frequency, as well as the effect of the variants on productive and reproductive traits in 71 purebred Santa Inês sheep, 13 purebred Brazilian Somali sheep, nine purebred Poll Dorset sheep, and 18 crossbred 1/2 Dorper sheep. The animals were genotyped using the PCR-RFLP technique. The influence of the animal's genotype on its performance or on the performance of its lambs was analyzed by the least square method. Another factor assessed was the importance of the animal's genotype in analysis models for quantitative breeding value estimates, and whether there were differences among the averages of breeding values of animals with different genotypes for this gene. In the sample studied, no AA individuals were observed; the AB and BB frequencies were 0.64 and 0.36, respectively. All Brazilian Somali sheep were of genotype BB. All 1/2 Dorper BB animals presented a lower age at first lambing, and the Santa Inês BB ewes presented a lower lambing interval. In these same genetic groups, AB ewes presented higher litter weight at weaning. This is evidence that BB ewes have a better reproductive performance phenotype, whereas AB ewes present a better maternal ability phenotype. However, in general, animals with genotype AB presented better average breeding values than those with genotype BB
Robust estimation of microbial diversity in theory and in practice
Quantifying diversity is of central importance for the study of structure,
function and evolution of microbial communities. The estimation of microbial
diversity has received renewed attention with the advent of large-scale
metagenomic studies. Here, we consider what the diversity observed in a sample
tells us about the diversity of the community being sampled. First, we argue
that one cannot reliably estimate the absolute and relative number of microbial
species present in a community without making unsupported assumptions about
species abundance distributions. The reason for this is that sample data do not
contain information about the number of rare species in the tail of species
abundance distributions. We illustrate the difficulty in comparing species
richness estimates by applying Chao's estimator of species richness to a set of
in silico communities: they are ranked incorrectly in the presence of large
numbers of rare species. Next, we extend our analysis to a general family of
diversity metrics ("Hill diversities"), and construct lower and upper estimates
of diversity values consistent with the sample data. The theory generalizes
Chao's estimator, which we retrieve as the lower estimate of species richness.
We show that Shannon and Simpson diversity can be robustly estimated for the in
silico communities. We analyze nine metagenomic data sets from a wide range of
environments, and show that our findings are relevant for empirically-sampled
communities. Hence, we recommend the use of Shannon and Simpson diversity
rather than species richness in efforts to quantify and compare microbial
diversity.Comment: To be published in The ISME Journal. Main text: 16 pages, 5 figures.
Supplement: 16 pages, 4 figure
The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes
Many cases of non-standard genetic codes are known in mitochondrial genomes.
We carry out analysis of phylogeny and codon usage of organisms for which the
complete mitochondrial genome is available, and we determine the most likely
mechanism for codon reassignment in each case. Reassignment events can be
classified according to the gain-loss framework. The gain represents the
appearance of a new tRNA for the reassigned codon or the change of an existing
tRNA such that it gains the ability to pair with the codon. The loss represents
the deletion of a tRNA or the change in a tRNA so that it no longer translates
the codon. One possible mechanism is Codon Disappearance, where the codon
disappears from the genome prior to the gain and loss events. In the
alternative mechanisms the codon does not disappear. In the Unassigned Codon
mechanism, the loss occurs first, whereas in the Ambiguous Intermediate
mechanism, the gain occurs first. Codon usage analysis gives clear evidence of
cases where the codon disappeared at the point of the reassignment and also
cases where it did not disappear. Codon disappearance is the probable
explanation for stop to sense reassignments and a small number of reassignments
of sense codons. However, the majority of sense to sense reassignments cannot
be explained by codon disappearance. In the latter cases, by analysis of the
presence or absence of tRNAs in the genome and of the changes in tRNA
sequences, it is sometimes possible to distinguish between the Unassigned Codon
and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments
follow the same scenario and that it is necessary to consider the details of
each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary
information). To appear in J.Mol.Evo
Microbial ligand costimulation drives neutrophilic steroid-refractory asthma
Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD
Complementary and alternative medicines (CAMs) and adherence to mental health medications
BACKGROUND: Medication regimes are often poorly adhered to, and the negative consequences of this are well recognised. The dynamics underlying non-adherence are less understood. This paper examines adherence to prescription medications for mental health difficulties in relation to the use of complementary and alternative medicines (CAMs). This was based on suggestions that within medical pluralism, CAMs may reduce adherence to conventional prescription medications for reasons such as their further complicating the medication regime or their being perceived as a substitute with less adverse side effects than conventional prescription medications. METHODS: Data used was from the National Comorbidity Study Replication (NCS-R), specifically those 1396 individuals who reported taking a prescription drug for mental health difficulties within the last 12 months and under the supervision of a health professional. This subsample was selected due to their being the only subgroup questioned regarding their medication adherence. Other demographic and health factors were also considered. RESULTS: The use of complementary medicines alongside the conventional medicines bore no significant relation to odds of reporting adherence versus non adherence. Ethnicity and medication count were significant predictors of adherence versus non-adherence. CONCLUSIONS: The above findings are discussed from the point of both promoting the use of CAMs and increasing health professionals’ understanding of the dynamics underlying adherence, or the lack thereof, and subsequently informing interventions to reduce the problems associated with this issue in terms of increased health care needs and reduced quality of life
Metal backed versus all-polyethylene unicompartmental knee arthroplasty: the effect of implant thickness on proximal tibial strain in an experimentally validated finite element model
Objectives Up to 40% of unicompartmental knee arthroplasty (UKA) revisions are performed for unexplained pain which may be caused by elevated proximal tibial bone strain. This study investigates the effect of tibial component metal backing and polyethylene thickness on bone strain in a cemented fixed-bearing medial UKA using a finite element model (FEM) validated experimentally by digital image correlation (DIC) and acoustic emission (AE). Materials and Methods A total of ten composite tibias implanted with all-polyethylene (AP) and metal-backed (MB) tibial components were loaded to 2500 N. Cortical strain was measured using DIC and cancellous microdamage using AE. FEMs were created and validated and polyethylene thickness varied from 6 mm to 10 mm. The volume of cancellous bone exposed to 3000 µε and > 7000 µε maximum principal (tensile) microstrain was computed. Results Experimental AE data and the FEM volume of cancellous bone with compressive strain < -3000 µε correlated strongly: R = 0.947, R2 = 0.847, percentage error 12.5% (p < 0.001). DIC and FEM data correlated: R = 0.838, R2 = 0.702, percentage error 4.5% (p < 0.001). FEM strain patterns included MB lateral edge concentrations; AP concentrations at keel, peg and at the region of load application. Cancellous strains were higher in AP implants at all loads: 2.2- (10 mm) to 3.2-times (6 mm) the volume of cancellous bone compressively strained < -7000 µε. Conclusion AP tibial components display greater volumes of pathologically overstrained cancellous bone than MB implants of the same geometry. Increasing AP thickness does not overcome these pathological forces and comes at the cost of greater bone resection
Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory
Data from the Sudbury Neutrino Observatory have been used to constrain the
lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The
analysis was based on a search for gamma-rays from the de-excitation of the
residual nucleus that would result from the disappearance of either a proton or
neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90%
confidence for either neutron or proton decay modes. This is about an order of
magnitude more stringent than previous constraints on invisible proton decay
modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of
2) Submitted to Physical Review Letter
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