Acute kidney injury in stable COPD and at exacerbation.

BACKGROUND: While acute kidney injury (AKI) alone is associated with increased mortality, the incidence of hospital admission with AKI among stable and exacerbating COPD patients and the effect of concurrent AKI at COPD exacerbation on mortality is not known. METHODS: A total of 189,561 individuals with COPD were identified from the Clinical Practice Research Datalink. Using Poisson and logistic regressions, we explored which factors predicted admission for AKI (identified in Hospital Episode Statistics) in this COPD cohort and concomitant AKI at a hospitalization for COPD exacerbation. Using survival analysis, we investigated the effect of concurrent AKI at exacerbation on mortality (n=36,107) and identified confounding factors. RESULTS: The incidence of AKI in the total COPD cohort was 128/100,000 person-years. The prevalence of concomitant AKI at exacerbation was 1.9%, and the mortality rate in patients with AKI at exacerbation was 521/1,000 person-years. Male sex, older age, and lower glomerular filtration rate predicted higher risk of AKI or death. There was a 1.80 fold (95% confidence interval: 1.61, 2.03) increase in adjusted mortality within the first 6 months post COPD exacerbation in patients suffering from AKI and COPD exacerbation compared to those who were AKI free. CONCLUSION: In comparison to previous studies on general populations and hospitalizations, the incidence and prevalence of AKI is relatively high in COPD patients. Coexisting AKI at exacerbation is prognostic of poor outcome

RNF12 Activates Xist and Is Essential for X Chromosome Inactivation

In somatic cells of female placental mammals, one of the two X chromosomes is transcriptionally silenced to accomplish an equal dose of X-encoded gene products in males and females. Initiation of random X chromosome inactivation (XCI) is thought to be regulated by X-encoded activators and autosomally encoded suppressors controlling Xist. Spreading of Xist RNA leads to silencing of the X chromosome in cis. Here, we demonstrate that the dose dependent X-encoded XCI activator RNF12/RLIM acts in trans and activates Xist. We did not find evidence for RNF12-mediated regulation of XCI through Tsix or the Xist intron 1 region, which are both known to be involved in inhibition of Xist. In addition, we found that Xist intron 1, which contains a pluripotency factor binding site, is not required for suppression of Xist in undifferentiated ES cells. Analysis of female Rnf12−/− knockout ES cells showed that RNF12 is essential for initiation of XCI and is mainly involved in the regulation of Xist. We conclude that RNF12 is an indispensable factor in up-regulation of Xist transcription, thereby leading to initiation of random XCI

Functional divergence in the role of N-linked glycosylation in smoothened signaling

The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice

The X-inactivation trans-activator Rnf12 is negatively regulated by pluripotency factors in embryonic stem cells

X-inactivation, the molecular mechanism enabling dosage compensation in mammals, is tightly controlled during mouse early embryogenesis. In the morula, X-inactivation is imprinted with exclusive silencing of the paternally inherited X-chromosome. In contrast, in the post-implantation epiblast, X-inactivation affects randomly either the paternal or the maternal X-chromosome. The transition from imprinted to random X-inactivation takes place in the inner cell mass (ICM) of the blastocyst from which embryonic stem (ES) cells are derived. The trigger of X-inactivation, Xist, is specifically downregulated in the pluripotent cells of the ICM, thereby ensuring the reactivation of the inactive paternal X-chromosome and the transient presence of two active X-chromosomes. Moreover, Tsix, a critical cis-repressor of Xist, is upregulated in the ICM and in ES cells where it imposes a particular chromatin state at the Xist promoter that ensures the establishment of random X-inactivation upon differentiation. Recently, we have shown that key transcription factors supporting pluripotency directly repress Xist and activate Tsix and thus couple Xist/Tsix control to pluripotency. In this manuscript, we report that Rnf12, a third X-linked gene critical for the regulation of X-inactivation, is under the control of Nanog, Oct4 and Sox2, the three factors lying at the heart of the pluripotency network. We conclude that in mouse ES cells the pluripotency-associated machinery exerts an exhaustive control of X-inactivation by taking over the regulation of all three major regulators of X-inactivation: Xist, Tsix, and Rnf12

Knowledge, attitude and practice of women in Campinas, São Paulo, Brazil with respect to physical exercise in pregnancy: a descriptive study

<p>Abstract</p> <p>Background</p> <p>Pregnancy is a good time to develop healthy lifestyle habits including regular exercise and good nutrition. Programs of physical exercise for pregnant women have been recommended; however, there are few references on this subject in the literature. The objective of this study was to evaluate the knowledge, attitude and practice of pregnant women with respect to appropriate physical exercise during pregnancy, and also to investigate why some women do not exercise during pregnancy.</p> <p>Methods</p> <p>A descriptive study was conducted in which 161 women of 18 to 45 years of age were interviewed in the third trimester of pregnancy. These women were receiving prenatal care at National Health Service (SUS) primary healthcare units and had no pathologies for which physical exercise would constitute a risk. The women were selected at an ultrasonography clinic accredited to the SUS in Campinas, São Paulo. A previously elaborated knowledge, attitude and practice (KAP) questionnaire was used to collect data, which were then stored in an Epinfo database. Statistical analysis was conducted using Pearson's chi-square test and Fisher's exact test to evaluate the association between the study variables (p < 0.05).</p> <p>Results</p> <p>Almost two-thirds (65.6%) of the women were sufficiently informed about the practice of physical exercise during pregnancy and the vast majority (93.8%) was in favor of it. Nevertheless, only just over 20% of the women in this sample exercised adequately. Significant associations were found between an adequate knowledge of physical exercise during pregnancy and education level (p = 0.0014) and between the adequate practice of physical exercise during pregnancy and having had fewer pregnancies (p = 0.0001). Lack of time and feeling tired and uncomfortable were the principal reasons given by the women for not exercising.</p> <p>Conclusion</p> <p>These results suggest that women's knowledge concerning the practice of physical exercise during pregnancy is reasonable and their attitude is favorable; however, relatively few actually exercise during pregnancy.</p

Cancer during Adolescence: Negative and Positive Consequences Reported Three and Four Years after Diagnosis

Persons diagnosed with cancer during adolescence have reported negative and positive cancer-related consequences two years after diagnosis. The overall aim was to longitudinally describe negative and positive cancer-related consequences reported by the same persons three and four years after diagnosis. A secondary aim was to explore whether reports of using vs. not using certain coping strategies shortly after diagnosis are related to reporting or not reporting certain consequences four years after diagnosis. Thirty-two participants answered questions about coping strategies shortly after diagnosis and negative and positive consequences three and four years after diagnosis. Answers about consequences were analysed with content analysis, potential relations between coping strategies and consequences were analysed by Fisher's exact test. The great majority reported negative and positive consequences three and four years after diagnosis and the findings indicate stability over time with regard to perceived consequences during the extended phase of survival. Findings reveal a potential relation between seeking information shortly after diagnosis and reporting a more positive view of life four years after diagnosis and not using fighting spirit shortly after diagnosis and not reporting good self-esteem and good relations four years after diagnosis. It is concluded that concomitant negative and positive cancer-related consequences appear stable over time in the extended phase of survival and that dialectical forces of negative and positive as well as distress and growth often go hand-in-hand after a trauma such as cancer during adolescence

Identification of miRNA from Porphyra yezoensis by High-Throughput Sequencing and Bioinformatics Analysis

BACKGROUND: miRNAs are a class of non-coding, small RNAs that are approximately 22 nucleotides long and play important roles in the translational level regulation of gene expression by either directly binding or cleaving target mRNAs. The red alga, Porphyra yezoensis is one of the most important marine economic crops worldwide. To date, only a few miRNAs have been identified in green unicellar alga and there is no report about Porphyra miRNAs. METHODOLOGY/PRINCIPAL FINDINGS: To identify miRNAs in Porphyra yezoensis, a small RNA library was constructed. Solexa technology was used to perform high throughput sequencing of the library and subsequent bioinformatics analysis to identify novel miRNAs. Specifically, 180,557,942 reads produced 13,324 unique miRNAs representing 224 conserved miRNA families that have been identified in other plants species. In addition, seven novel putative miRNAs were predicted from a limited number of ESTs. The potential targets of these putative miRNAs were also predicted based on sequence homology search. CONCLUSIONS/SIGNIFICANCE: This study provides a first large scale cloning and characterization of Porphyra miRNAs and their potential targets. These miRNAs belong to 224 conserved miRNA families and 7 miRNAs are novel in Porphyra. These miRNAs add to the growing database of new miRNA and lay the foundation for further understanding of miRNA function in the regulation of Porphyra yezoensis development