6 research outputs found

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Diabetes is associated with impairment of uterine contractility and high Caesarean section rate

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    Aims/hypothesis The prevalence of births worldwide complicated by diabetes mellitus is increasing. In the UK, for example, <25% of diabetic women have a non-instrumental vaginal delivery. Strikingly, more than half the Caesarean sections (CS) in these patients are non-elective, but the reasons for this are not understood. We have tested the hypothesis that poor myometrial contractility as a consequence of the disease contributes to this high CS rate. Methods We compared spontaneous, high K depolarisation and oxytocin-induced contractions from diabetic and matched control patients having an elective CS. To investigate the mechanism of any differences we measured intracellular Ca, and performed western blotting and compared the tissues histologically. Results There was significantly decreased contraction amplitude and duration in uteri from diabetic compared with control patients, even when possible confounders such as BMI were analysed. Reduced intracellular calcium signals and expression of calcium entry channels were found in uteruses from diabetic patients, which, along with a reduction in muscle content found on histological examination, could explain the reduced force. Myometrium from diabetic patients was responsive to oxytocin, but still did not reach the levels found in non-diabetic patients. Conclusions/interpretations These are the first data investigating myometrium in diabetic patients and they support the hypothesis that there is poorer contractility even in the presence of oxytocin. The underlying mechanism is related to reduced Ca channel expression and intracellular calcium signals and a decrease in muscle mass. We conclude that these factors significantly contribute to the increased emergency CS rate in diabetic patients

    Expression and distribution of Na, K-ATPase isoforms in the human uterus

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    Na, K-ATPase activity relies on the composition of its catalytic α, β, and FXYD constituents, all of which are expressed as multiple isoforms (4α, 4β, and 7 FXYD). We used reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry to study Na, K-ATPase expression in uterine samples from nonlaboring elective and laboring emergency caesarean sections (CSs). Transcripts of α1 to 3, β1 to 3, and FXYD1 isoforms were detected in all samples, but FXYD2 was only present in hysterectomy samples. Abundant immunoreactivity of α1 and moderate α2 was localized in myometrial smooth muscle and secretory glands of all groups. Smooth muscle and gland epithelia showed diffuse cytoplasmic α3 immunoreactivity. β isoforms were detected in all groups but β3 showed much denser immunoreactivity in myometrial samples taken from women in labor. In pregnancy, there was a switch in isoform expression, resulting in increased β3 and decreased FXYD2 at the protein and messenger RNA (mRNA) levels. Na, K-ATPase isoform alterations may modulate uterine contractility during labor
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