209 research outputs found

    miR-125b Acts as a Tumor Suppressor in Breast Tumorigenesis via Its Novel Direct Targets ENPEP, CK2-α, CCNJ, and MEGF9

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    MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. To explore the dysregulation of miRNAs in breast cancer, a genome-wide expression profiling of 939 miRNAs was performed in 50 breast cancer patients. A total of 35 miRNAs were aberrantly expressed between breast cancer tissue and adjacent normal breast tissue and several novel miRNAs were identified as potential oncogenes or tumor suppressor miRNAs in breast tumorigenesis. miR-125b exhibited the largest decrease in expression. Enforced miR-125b expression in mammary cells decreased cell proliferation by inducing G2/M cell cycle arrest and reduced anchorage-independent cell growth of cells of mammary origin. miR-125b was found to perform its tumor suppressor function via the direct targeting of the 3'-UTRs of ENPEP, CK2-alpha, CCNJ, and MEGF9 mRNAs. Silencing these miR-125b targets mimicked the biological effects of miR-125b overexpression, confirming that they are modulated by miR-125b. Analysis of ENPEP, CK2-alpha, CCNJ, and MEGF9 protein expression in breast cancer patients revealed that they were overexpressed in 56%, 40-56%, 20%, and 32% of the tumors, respectively. The expression of ENPEP and CK2-alpha was inversely correlated with miR-125b expression in breast tumors, indicating the relevance of these potential oncogenic proteins in breast cancer patients. Our results support a prognostic role for CK2-alpha, whose expression may help clinicians predict breast tumor aggressiveness. In particular, our results show that restoration of miR-125b expression or knockdown of ENPEP, CK2-alpha, CCNJ, or MEGF9 may provide novel approaches for the treatment of breast cancer

    Placental Hypoxia during Placental Malaria

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    Placental malaria causes fetal growth retardation (FGR), which has been linked epidemiologically to placental monocyte infiltrates. We investigated whether parasite or monocyte infiltrates were associated with placental hypoxia, as a potential mechanism underlying malarial FGR

    A Randomized Placebo-Controlled Trial of Intermittent Preventive Treatment in Pregnant Women in the Context of Insecticide Treated Nets Delivered through the Antenatal Clinic

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    Background:Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets(ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of theircombined use.Methods:1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC)visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess thesafety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight.Findings:Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence atdelivery (RR, 0.92 [95% CI, 0.79-1.08]), low birth weight (RR, 0.99 [95% CI, 0.70-1.39]), or overall placental infection(p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40-61.20]; p = 0.020) in the incidence of clinicalmalaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p,0.001), and ofactively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderlinestatistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITN's use was morethan 90% in both groups.Conclusions:Two-dose SP was associated with a reduction in some indicators, but these were not translated to significantimprovement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administerIPTp. ITNs should be part of the ANC package in sub-Saharan Afric

    Divergent Serpentoviruses in Free-Ranging Invasive Pythons and Native Colubrids in Southern Florida, United States

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    Burmese python (Python bivittatus) is an invasive snake that has significantly affected ecosystems in southern Florida, United States. Aside from direct predation and competition, invasive species can also introduce nonnative pathogens that can adversely affect native species. The subfamily Serpentovirinae (order Nidovirales) is composed of positive-sense RNA viruses primarily found in reptiles. Some serpentoviruses, such as shingleback nidovirus, are associated with mortalities in wild populations, while others, including ball python nidovirus and green tree python nidovirus can be a major cause of disease and mortality in captive animals. To determine if serpentoviruses were present in invasive Burmese pythons in southern Florida, oral swabs were collected from both free-ranging and long-term captive snakes. Swabs were screened for the presence of serpentovirus by reverse transcription PCR and sequenced. A total serpentovirus prevalence of 27.8% was detected in 318 python samples. Of the initial swabs from 172 free-ranging pythons, 42 (24.4%) were positive for multiple divergent viral sequences comprising four clades across the sampling range. Both sex and snout-vent length were statistically significant factors in virus prevalence, with larger male snakes having the highest prevalence. Sampling location was statistically significant in circulating virus sequence. Mild clinical signs and lesions consistent with serpentovirus infection were observed in a subset of sampled pythons. Testing of native snakes (n = 219, 18 species) in part of the python range found no evidence of python virus spillover; however, five individual native snakes (2.3%) representing three species were PCR positive for unique, divergent serpentoviruses. Calculated pairwise uncorrected distance analysis indicated the newly discovered virus sequences likely represent three novel genera in the subfamily Serpentovirinae. This study is the first to characterize serpentovirus in wild free-ranging pythons or in any free-ranging North America reptile. Though the risk these viruses pose to the invasive and native species is unknown, the potential for spillover to native herpetofauna warrants further investigation

    Identifying invasive species threats, pathways, and impacts to improve biosecurity

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    Managing invasive species with prevention and early-detection strategies can avert severe ecological and economic impacts. Horizon scanning, an evidence-based process combining risk screening and consensus building to identify threats, has become a valuable tool for prioritizing invasive species management and prevention. We assembled a working group of experts from academic, government, and nonprofit agencies and organizations, and conducted a multi-taxa horizon scan for Florida, USA, the first of its kind in North America. Our primary objectives were to identify high-risk species and their introduction pathways, to detail the magnitude and mechanism of potential impacts, and, more broadly, to demonstrate the utility of horizon scanning. As a means to facilitate future horizon scans, we document the process used to generate the list of taxa for screening. We evaluated 460 taxa for their potential to arrive, establish, and cause negative ecological and socioeconomic impacts, and identified 40 potential invaders, including alewife, zebra mussel, crab-eating macaque, and red swamp crayfish. Vertebrates and aquatic invertebrates posed the greatest invasion threat, over half of the high-risk taxa were omnivores, and there was high confidence in the scoring of high-risk taxa. Common arrival pathways were ballast water, biofouling of vessels, and escape from the pet/aquarium/horticulture trade. Competition, predation, and damage to agriculture/forestry/aquaculture were common impact mechanisms. We recommend full risk analysis for the high-risk taxa; increased surveillance at Florida's ports, state borders, and high-risk pathways; and periodic review and revision of the list. Few horizon scans detail the comprehensive methodology (including list-building), certainty estimates for all scoring categories and the final score, detailed pathways, and the magnitude and mechanism of impact. Providing this information can further inform prevention efforts and can be efficiently replicated in other regions. Moreover, harmonizing methodology can facilitate data sharing and enhance interpretation of results for stakeholders and the general public.</p
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