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991.
Sanne J. Jansen of Lorkeers Johannes M. I. H. Gho Stefan Koudstaal Gerardus P. J. van Hout Peter Paul M. Zwetsloot Joep W. M. van Oorschot Esther C. M. van Eeuwijk Tim Leiner Imo E. Hoefer Marie-José Goumans Pieter A. Doevendans Joost P. G. Sluijter Steven A. J. Chamuleau 《PloS one》2015,10(12)
Background
Recently cardiomyocyte progenitor cells (CMPCs) were successfully isolated from fetal and adult human hearts. Direct intramyocardial injection of human CMPCs (hCMPCs) in experimental mouse models of acute myocardial infarction significantly improved cardiac function compared to controls.Aim
Here, our aim was to investigate whether xenotransplantation via intracoronary infusion of fetal hCMPCs in a pig model of chronic myocardial infarction is safe and efficacious, in view of translation purposes.Methods & Results
We performed a randomized, blinded, placebo controlled trial. Four weeks after ischemia/reperfusion injury by 90 minutes of percutaneous left anterior descending artery occlusion, pigs (n = 16, 68.5 ± 5.4 kg) received intracoronary infusion of 10 million fetal hCMPCs or placebo. All animals were immunosuppressed by cyclosporin (CsA). Four weeks after infusion, endpoint analysis by MRI displayed no difference in left ventricular ejection fraction, left ventricular end diastolic and left ventricular end systolic volumes between both groups. Serial pressure volume (PV-)loop and echocardiography showed no differences in functional parameters between groups at any timepoint. Infarct size at follow-up, measured by late gadolinium enhancement MRI showed no difference between groups. Intracoronary pressure and flow measurements showed no signs of coronary obstruction 30 minutes after cell infusion. No premature death occurred in cell treated animals.Conclusion
Xenotransplantation via intracoronary infusion of hCMPCs is feasible and safe, but not associated with improved left ventricular performance and infarct size compared to placebo in a porcine model of chronic myocardial infarction. 相似文献992.
Doron Kabiri Yael Hants Tom Raz Yarkoni Esther Shaulof Smadar Eventov Friedman Ora Paltiel Ran Nir-Paz Wesam E. Aljamal Yossef Ezra 《PloS one》2015,10(12)
Objective
Stripping of the membranes is an established and widely utilized obstetric procedure associated with higher spontaneous vaginal delivery rates, reduced need for formal induction of labor and a lower likelihood of post-term pregnancy. Due to the theoretical concern of bacterial seeding during the procedure many practitioners choose not to sweep the membranes in Group B Streptococcus (GBS) colonized patients. We conducted ‘the STRIP-G study’ in order to determine whether maternal and neonatal outcomes are affected by GBS carrier status in women undergoing membrane stripping.Study design
We conducted a prospective study in a tertiary referral center, comparing maternal and neonatal outcomes following membrane stripping among GBS-positive, GBS-negative, and GBS-unknown patients. We compared the incidence of composite adverse neonatal outcomes (primary outcome) among the three study groups, while secondary outcome measure was composite adverse maternal outcomes.Results
A total of 542 women were included in the study, of which 135 were GBS-positive, 361 GBS-negative, and 46 GBS-unknown status. Demographic, obstetric, and intra-partum characteristics were similar for all groups. Adverse neonatal outcomes were observed in 8 (5.9%), 31 (8.6%), and 2 (4.3%) in the GBS-positive, GBS-negative, and unknown groups, respectively (P = 0.530), (Odds Ratio between GBS-Positive vs. GBS-Negative groups 0.67 (95%, CI = 0.30–1.50)); while composite adverse maternal outcomes occurred in 9 (6.66%), 31 (8.59%), and 5 (10.87%) in the GBS-positive, GBS-negative, and unknown groups, respectively (P = 0.617).Conclusions
Antepartum membrane stripping in GBS carriers appears to be a safe obstetrical procedure that does not adversely affect maternal or neonatal outcomes. 相似文献993.
Manuel Soto Laura Corvo Esther Garde Laura Ramírez Virginia Iniesta Pedro Bonay Carlos Gómez-Nieto Víctor M. González M. Elena Martín Carlos Alonso Eduardo A. F. Coelho Aldina Barral Manoel Barral-Netto Salvador Iborra 《PLoS neglected tropical diseases》2015,9(5)
Background
Highly conserved intracellular proteins from Leishmania have been described as antigens in natural and experimental infected mammals. The present study aimed to evaluate the antigenicity and prophylactic properties of the Leishmania infantum Poly (A) binding proteins (LiPABPs).Methodology/Principal Findings
Three different members of the LiPABP family have been described. Recombinant tools based on these proteins were constructed: recombinant proteins and DNA vaccines. The three recombinant proteins were employed for coating ELISA plates. Sera from human and canine patients of visceral leishmaniasis and human patients of mucosal leishmaniasis recognized the three LiPABPs. In addition, the protective efficacy of a DNA vaccine based on the combination of the three Leishmania PABPs has been tested in a model of progressive murine leishmaniasis: BALB/c mice infected with Leishmania major. The induction of a Th1-like response against the LiPABP family by genetic vaccination was able to down-regulate the IL-10 predominant responses elicited by parasite LiPABPs after infection in this murine model. This modulation resulted in a partial protection against L. major infection. LiPABP vaccinated mice showed a reduction on the pathology that was accompanied by a decrease in parasite burdens, in antibody titers against Leishmania antigens and in the IL-4 and IL-10 parasite-specific mediated responses in comparison to control mice groups immunized with saline or with the non-recombinant plasmid.Conclusion/Significance
The results presented here demonstrate for the first time the prophylactic properties of a new family of Leishmania antigenic intracellular proteins, the LiPABPs. The redirection of the immune response elicited against the LiPABP family (from IL-10 towards IFN-γ mediated responses) by genetic vaccination was able to induce a partial protection against the development of the disease in a highly susceptible murine model of leishmaniasis. 相似文献994.
Esther J. Lee D. Andrew Merriwether Alexei K. Kasparov Pavel A. Nikolskiy Marina V. Sotnikova Elena Yu Pavlova Vladimir V. Pitulko 《PloS one》2015,10(5)
Modern Arctic Siberia provides a wealth of resources for archaeological, geological, and paleontological research to investigate the population dynamics of faunal communities from the Pleistocene, particularly as the faunal material coming from permafrost has proven suitable for genetic studies. In order to examine the history of the Canid species in the Siberian Arctic, we carried out genetic analysis of fourteen canid remains from various sites, including the well-documented Upper Paleolithic Yana RHS and Early Holocene Zhokhov Island sites. Estimated age of samples range from as recent as 1,700 years before present (YBP) to at least 360,000 YBP for the remains of the extinct wolf, Canis cf. variabilis. In order to examine the genetic affinities of ancient Siberian canids species to the domestic dog and modern wolves, we obtained mitochondrial DNA control region sequences and compared them to published ancient and modern canid sequences. The older canid specimens illustrate affinities with pre-domestic dog/wolf lineages while others appear in the major phylogenetic clades of domestic dogs. Our results suggest a European origin of domestic dog may not be conclusive and illustrates an emerging complexity of genetic contribution of regional wolf breeds to the modern Canis gene pool. 相似文献
995.
Barbara M. Schulte Paul R. Gielen Esther D. Kers-Rebel Gerty Schreibelt Frank J. M. van Kuppeveld Gosse J. Adema 《PloS one》2015,10(3)
Enteroviruses often cause mild disease, yet are also linked to development of autoimmune diabetes. Dendritic cells (DCs) shape both innate and adaptive immune responses, including anti-viral responses. How different human DC subsets shape anti-viral responses, whether they have complementary or overlapping functions and how this relates to autoimmune responses is largely unknown. We used enterovirus-infected β-cells and freshly isolated human myeloid DC (mDC) subsets as a model for autoimmune type 1 diabetes. Our data show that both the BDCA1+ and BDCA3+ mDC subsets engulf mock- as well as virus-infected β-cells, albeit BDCA1+ mDCs are more efficient. Uptake of enterovirus-infected, but not mock-infected cells, activated both DC subsets as indicated by the induction of co-stimulatory molecules and secretion of type I and type III interferons. Both subsets produced similar amounts of interferon-α, yet the BDCA3+ DC were superior in IFN-λ production. The BDCA1+ mDCs more strongly upregulated PD-L1, and were superior in IL-12 and IL-10 production as compared to the BDCA3+ DC. Despite lack of IL-12 production by the BDCA3+ DC, both BDCA1+ and BDCA3+ DCs activated T cells in allogeneic mixed lymphocyte reaction towards a Th1-type reactivity while suppressing Th2-associated cytokines. 相似文献
996.
Petra A. Tsuji Bradley A. Carlson Min-Hyuk Yoo Salvador Naranjo-Suarez Xue-Ming Xu Yiwen He Esther Asaki Harold E. Seifried William C. Reinhold Cindy D. Davis Vadim N. Gladyshev Dolph L. Hatfield 《PloS one》2015,10(4)
Selenoproteins mediate much of the cancer-preventive properties of the essential nutrient selenium, but some of these proteins have been shown to also have cancer-promoting effects. We examined the contributions of the 15kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and formation of experimental metastases of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially interferon-γ-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient, but not in TR1-deficient cells. Interestingly, components of the Wnt/β-catenin signaling pathway were up-regulated in cells lacking both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, our results provide insights into new roles of selenoproteins in cancer. 相似文献
997.
Laura K. Erdman Valérie D’Acremont Kyla Hayford Nimerta Rajwans Mary Kilowoko Esther Kyungu Philipina Hongoa Leonor Alamo David L. Streiner Blaise Genton Kevin C. Kain 《PloS one》2015,10(9)
Background
Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance.Methods
We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis.Results
Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5–98.8), 80.8% specificity (72.6–87.1), positive likelihood ratio 4.9 (3.4–7.1), negative likelihood ratio 0.083 (0.022–0.32), and misclassification rate 0.20 (standard error 0.038).Conclusions
In Tanzanian children with WHO-defined clinical pneumonia, combinations of host biomarkers distinguished between end-point pneumonia, other infiltrates, and normal chest x-ray, whereas clinical variables did not. These findings generate pathophysiological hypotheses and may have potential research and clinical utility. 相似文献998.
In most animals that have X and Y sex chromosomes, chromosome-wide mechanisms are used to balance X-linked gene expression in males and females. In the fly Drosophila melanogaster, the dosage compensation mechanism also generally extends to X-linked transgenes. Over 70 transgenic lines of the Australian sheep blowfly Lucilia cuprina have been made as part of an effort to develop male-only strains for a genetic control program of this major pest of sheep. All lines carry a constitutively expressed fluorescent protein marker gene. In all 12 X-linked lines, female larvae show brighter fluorescence than male larvae, suggesting the marker gene is not dosage compensated. This has been confirmed by quantitative RT-PCR for selected lines. To determine if endogenous X-linked genes are dosage compensated, we isolated 8 genes that are orthologs of genes that are on the fourth chromosome in D. melanogaster. Recent evidence suggests that the D. melanogaster fourth chromosome, or Muller element F, is the ancestral X chromosome in Diptera that has reverted to an autosome in Drosophila species. We show by quantitative PCR of male and female DNA that 6 of the 8 linkage group F genes reside on the X chromosome in L. cuprina. The other two Muller element F genes were found to be autosomal in L. cuprina, whereas two Muller element B genes were found on the same region of the X chromosome as the L. cuprina orthologs of the D. melanogaster Ephrin and gawky genes. We find that the L. cuprina X chromosome genes are equally expressed in males and females (i.e., fully dosage compensated). Thus, unlike in Drosophila, it appears that the Lucilia dosage compensation system is specific for genes endogenous to the X chromosome and cannot be co-opted by recently arrived transgenes. 相似文献
999.
Victoria L. Ewing Rachel Tolhurst Andrew Kapinda Miguel SanJoaquin Dianne J. Terlouw Esther Richards David G. Lalloo 《PloS one》2015,10(6)
Background
Universal access to, and community uptake of malaria prevention and treatment strategies are critical to achieving current targets for malaria reduction. Each step in the treatment-seeking pathway must be considered in order to establish where opportunities for successful engagement and treatment occur. We describe local classifications of childhood febrile illnesses, present an overview of treatment-seeking, beginning with recognition of illness, and suggest how interventions could be used to target the barriers experienced.Methods
Qualitative data were collected between September 2010 and February 2011. A total of 12 Focus Group Discussions and 22 Critical Incident Interviews were conducted with primary caregivers who had reported a recent febrile episode for one of their children.Findings and Conclusion
The phrase ‘kutentha thupi’, or ‘hot body’ was used to describe fever, the most frequently mentioned causes of which were malungo (translated as ‘malaria’), mauka, nyankhwa and (m)tsempho. Differentiating the cause was challenging because these illnesses were described as having many similar non-specific symptoms, despite considerable differences in the perceived mechanisms of illness. Malungo was widely understood to be caused by mosquitoes. Commonly described symptoms included: fever, weakness, vomiting, diarrhoea and coughing. These symptoms matched well with the biomedical definition of malaria, although they also overlapped with symptoms of other illnesses in both the biomedical model and local illness classifications. In addition, malungo was used interchangeably to describe malaria and fever in general. Caregivers engaged in a three-phased approach to treatment seeking. Phase 1—Assessment; Phase 2—Seeking care outside the home; Phase 3—Evaluation of treatment response. Within this paper, the three-phased approach is explored to identify potential interventions to target barriers to appropriate treatment. Community engagement and health promotion, the provision of antimalarials at community level and better training health workers in the causes and treatment of non-malarial febrile illnesses may improve access to appropriate treatment and outcomes. 相似文献1000.
Joan Martí-Fàbregas Raquel Delgado-Mederos Javier Crespo Esther Pe?a Rebeca Marín Elena Jiménez-Xarrié Ana Fernández-Arcos Jesús Pérez-Pérez Alejandro Martínez-Dome?o Pol Camps-Renom Luís Prats-Sánchez Francesca Casoni Lina Badimon 《PloS one》2015,10(4)