Evolutionary divergence and limits of conserved non-coding sequence detection in plant genomes

The discovery of regulatory motifs embedded in upstream regions of plants is a particularly challenging bioinformatics task. Previous studies have shown that motifs in plants are short compared with those found in vertebrates. Furthermore, plant genomes have undergone several diversification mechanisms such as genome duplication events which impact the evolution of regulatory motifs. In this article, a systematic phylogenomic comparison of upstream regions is conducted to further identify features of the plant regulatory genomes, the component of genomes regulating gene expression, to enable future de novo discoveries. The findings highlight differences in upstream region properties between major plant groups and the effects of divergence times and duplication events. First, clear differences in upstream region evolution can be detected between monocots and dicots, thus suggesting that a separation of these groups should be made when searching for novel regulatory motifs, particularly since universal motifs such as the TATA box are rare. Second, investigating the decay rate of significantly aligned regions suggests that a divergence time of 100 mya sets a limit for reliable conserved non-coding sequence (CNS) detection. Insights presented here will set a framework to help identify embedded motifs of functional relevance by understanding the limits of bioinformatics detection for CNSs.</p

The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat

The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC(0-24h) were significantly reduced by PCN pre-treatment. Biliary digoxin clearance increased 2-fold following PCN treatment. PCN significantly increased net digoxin secretion (2.05- and 4.5-fold respectively) in ileum and colon but not in duodenum or jejunum. This increased secretion correlated with increased Pgp protein expression in ileum and colon. Both intestinal and biliary excretion therefore contribute to altered digoxin disposition following PCN

Transcriptome analysis of Aspergillus niger xlnR and xkiA mutants grown on corn Stover and soybean hulls reveals a highly complex regulatory network.

BACKGROUND:Enzymatic plant biomass degradation by fungi is a highly complex process and one of the leading challenges in developing a biobased economy. Some industrial fungi (e.g. Aspergillus niger) have a long history of use with respect to plant biomass degradation and for that reason have become 'model' species for this topic. A. niger is a major industrial enzyme producer that has a broad ability to degrade plant based polysaccharides. A. niger wild-type, the (hemi-)cellulolytic regulator (xlnR) and xylulokinase (xkiA1) mutant strains were grown on a monocot (corn stover, CS) and dicot (soybean hulls, SBH) substrate. The xkiA1 mutant is unable to utilize the pentoses D-xylose and L-arabinose and the polysaccharide xylan, and was previously shown to accumulate inducers for the (hemi-)cellulolytic transcriptional activator XlnR and the arabinanolytic transcriptional activator AraR in the presence of pentoses, resulting in overexpression of their target genes. The xlnR mutant has reduced growth on xylan and down-regulation of its target genes. The mutants therefore have a similar phenotype on xylan, but an opposite transcriptional effect. D-xylose and L-arabinose are the most abundant monosaccharides after D-glucose in nearly all plant-derived biomass materials. In this study we evaluated the effect of the xlnR and xkiA1 mutation during growth on two pentose-rich substrates by transcriptome analysis. RESULTS:Particular attention was given to CAZymes, metabolic pathways and transcription factors related to the plant biomass degradation. Genes coding for the main enzymes involved in plant biomass degradation were down-regulated at the beginning of the growth on CS and SBH. However, at a later time point, significant differences were found in the expression profiles of both mutants on CS compared to SBH. CONCLUSION:This study demonstrates the high complexity of the plant biomass degradation process by fungi, by showing that mutant strains with fairly straightforward phenotypes on pure mono- and polysaccharides, have much less clear-cut phenotypes and transcriptomes on crude plant biomass

Ai Chi: aquatic relaxing effects on functional performance and quality of life in elderly

OBJETIVO: Este estudo avaliou os efeitos da técnica de relaxamento aquático Ai Chi em um grupo de idosos, em relação ao equilíbrio, qualidade de vida e funcionalidade. MÉTODOS: Foram selecionados 20 idosos de ambos os sexos, com média de idade de 68,95 (± 7,42) anos, que foram submetidas à técnica Ai Chi. Os idosos foram avaliados antes e depois do programa de exercícios, que teve duração de 12 semanas, com sessões de 45 minutos, duas vezes por semana, pelas seguintes escalas: Medida de Independência Funcional (MIF), que avalia a funcionalidade; Escala de Berg, que avalia o equilíbrio; e SF36, que mensura a qualidade de vida. Para o desenvolvimento da pesquisa, utilizamos uma piscina aquecida, numa temperatura de 33-34° C. RESULTADOS: Houve melhora significante no equilíbrio pré e pós aplicação da técnica (p < 0,003), não houve melhora significante em relação às medidas de independência funcional (p < 0,10) e a qualidade de vida (p < 0,38). CONCLUSÃO: A técnica de relaxamento aquático Ai Chi proporcionou melhora do equilíbrio, porém não houve mudanças em relação à qualidade de vida e à funcionalidade em idosos independentes.OBJECTIVE: This study evaluated the effects of Ai Chi in one group of elderly people in relation to balance, quality of life and functionality. METHODS: We selected 20 elderly people, mean age 68,95 (±7,42) years, that were submitted to Ai Chi technique. The elderly were evaluation after and before exercises program, for 12 weeks, 45 minutes each section, twice a week, by the following scales: Independence Function Measure (IFM), Berg Scale (Brazilian version), and SF-36, for quality of life. The study was made at Ibirapuera University warm pool (33-34° C). RESULTS: There was increase in balance before and after Ai Chi application (p < 0,003), but there was not increase of measure of functional independence (p < 0,10) and quality of life (p < 0,38). CONCLUSION: The Ai Chi technique when applied to elderly people provided an increase on balance. The other evaluations did not show statistic results

The views of women and pharmacists on the desirability of a progestogen-only pill over the counter. Results of a survey in Germany, Italy and Spain

Purpose To explore the perceived need and enthusiasm for over the counter (OTC) progestogen-only pills (POP). Materials and Methods A web-based survey of 1000 sexually active women (16-45) and 100 pharmacists in Germany, Italy and Spain. Results Despite not wanting to conceive, 5-6% of women in each country were not using contraception and 8-20% were using methods less effective than condoms. At least 74% of respondents felt knowledgeable about the different contraceptives available but at least 1/3 had experienced difficulty accessing oral contraceptive (OCs) in the past two years. The cost of contraceptives, the need to see a doctor and long waits for appointments were cited as barriers for not using OCs. The majority agreed they would discuss with their doctor the decision to buy the POP, consult about side effects and other reproductive health issues. Over 2/3 of pharmacists in each country would be very, or fairly, likely to recommend the POP, agreeing that the benefits included improved access for women, and offered them more independence. Conclusions Asked directly, women in Germany, Spain and Italy currently using contraception are positive about a POP OTC. Pharmacists are also positive, with the overwhelming majority in favour of providing POPs

Do Genetic Variants Modify the Effect of Smoking on Risk of Preeclampsia in Pregnancy?

Under embargo until: 2022-11-28Objective Maternal smoking is associated with as much as a 50% reduced risk of preeclampsia, despite increasing risk of other poor pregnancy outcomes that often co-occur with preeclampsia, such as preterm birth and fetal growth restriction. Researchers have long sought to understand whether this perplexing association is biologically based, or a result of noncausal mechanisms. We examined whether smoking-response genes modify the smoking-preeclampsia association to investigate potential biological explanations. Study Design We conducted a nested case–control study within the Norwegian Mother, Father and Child Birth Cohort (1999–2008) of 2,596 mother–child dyads. We used family-based log-linear Poisson regression to examine modification of the maternal smoking-preeclampsia relationship by maternal and fetal single nucleotide polymorphisms involved in cellular processes related to components of cigarette smoke (n = 1,915 with minor allele frequency ≥10%). We further investigated the influence of smoking cessation during pregnancy. Results Three polymorphisms showed overall (p < 0.001) multiplicative interaction between smoking and maternal genotype. For rs3765692 (TP73) and rs10770343 (PIK3C2G), protection associated with smoking was reduced with two maternal copies of the risk allele and was stronger in continuers than quitters (interaction p = 0.02 for both loci, based on testing 3-level smoking by 3-level genotype). For rs2278361 (APAF1) the inverse smoking-preeclampsia association was eliminated by the presence of a single risk allele, and again the trend was stronger in continuers than in quitters (interaction p = 0.01). Conclusion Evidence for gene–smoking interaction was limited, but differences by smoking cessation warrant further investigation. We demonstrate the potential utility of expanded dyad methods and gene–environment interaction analyses for outcomes with complex relationships between maternal and fetal genotypes and exposures.acceptedVersio

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.

Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires

Seed dispersal potential of Asian elephants

This research article published by Elsevier, 2016Elephants, the largest terrestrial mega-herbivores, play an important ecological role in maintaining forest ecosystem diversity. While several plant species strongly rely on African elephants (Loxodonta africana; L. cyclotis) as seed dispersers, little is known about the dispersal potential of Asian elephants (Elephas maximus). We examined the effects of elephant fruit consumption on potential seed dispersal using the example of a tree species with mega-faunal characteristics, Dillenia indica L., in Thailand. We conducted feeding trials with Asian elephants to quantify seed survival and gut passage times (GPT). In total, 1200 ingested and non-ingested control seeds were planted in soil and in elephant dung to quantify differences in germination rates in terms of GPT and dung treatment. We used survival analysis as a novel approach to account for the right-censored nature of the data obtained from germination experiments. The average seed survival rate was 79% and the mean GPT was 35 h. The minimum and maximum GPT were 20 h and 72 h, respectively. Ingested seeds were significantly more likely to germinate and to do so earlier than non-ingested control seeds (P = 0.0002). Seeds with the longest GPT displayed the highest germination success over time. Unexpectedly, seeds planted with dung had longer germination times than those planted without. We conclude that D. indica does not solely depend on but benefits from dispersal by elephants. The declining numbers of these mega-faunal seed dispersers might, therefore, have long-term negative consequences for the recruitment and dispersal dynamics of populations of certain tree species

Opposing MMP-9 Expression in Mesenchymal Stromal Cells and Head and Neck Tumor Cells after Direct 2D and 3D Co-Culture

Bone marrow-derived mesenchymal stromal cells (BMSCs) respond to a variety of tumor cell-derived signals, such as inflammatory cytokines and growth factors. As a result, the inflammatory tumor microenvironment may lead to the recruitment of BMSCs. Whether BMSCs in the tumor environment are more likely to promote tumor growth or tumor suppression is still controversial. In our experiments, direct 3D co-culture of BMSCs with tumor cells from the head and neck region (HNSCC) results in strong expression and secretion of MMP-9. The observed MMP-9 secretion mainly originates from BMSCs, leading to increased invasiveness. In addition to our in vitro data, we show in vivo data based on the chorioallantoic membrane (CAM) model. Our results demonstrate that MMP-9 induces hemorrhage and increased perfusion in BMSC/HNSCC co-culture. While we had previously outlined that MMP-9 expression and secretion originate from BMSCs, our data showed a strong downregulation of MMP-9 promoter activity in HNSCC cells upon direct contact with BMSCs using the luciferase activity assay. Interestingly, the 2D and 3D models of direct co-culture suggest different drivers for the downregulation of MMP-9 promoter activity. Whereas the 3D model depicts a BMSC-dependent downregulation, the 2D model shows cell density-dependent downregulation. In summary, our data suggest that the direct interaction of HNSCC cells and BMSCs promotes tumor progression by significantly facilitating angiogenesis via MMP-9 expression. On the other hand, data from 3D and 2D co-culture models indicate opposing regulation of the MMP-9 promoter in tumor cells once stromal cells are involved