180 research outputs found

    Anti-microbial self-assembling click monolayers utilizing silver nanoparticles for indwelling medical devices

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    The objective of this study was to synthesize and characterize antimicrobial, silver nanoparticles based self-assembling monolayer coatings, for use on chronic indwelling medical devices. The coatings are comprised of novel biomass mediated silver nano particles (SNP) that are biocompatible, highly concentrated, highly pure, cost-effective, polydispersed and compatible for use with existing chronic indwelling medical devices. The HPC SNPs were functionalized with an azide functional group and covalently bound to titanium substrates via ¨Dclick¡¬ chemistry

    Thorough validation of siRNA-induced cell death phenotypes defines new anti-apoptotic protein

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    Loss-of-function by means of RNA interference in cultured human cells enables rapid pathway dissection on a genome-scale. Improved siRNA design and key validation protocols are required to eliminate falsely identified phenotypes resulting from potential off-target consequences. Here, we demonstrate a validation strategy involving several steps for verifying cell death phenotypes revealed during loss-of-function screening. First, from a set of 45 novel human genes we identified gene candidates that, when silenced, induce apoptosis in cultured HeLa cells. For those candidates, we performed more extensive validation with multiple effective siRNAs. In addition, we designed rescue experiments involving candidate genes delivered exogenously and containing silent mutations in the siRNA target regions. Rescue of the observed knockdown phenotype demonstrated an original and more stringent validation of the siRNA's selectivity and the phenotype specificity for the target gene. As a result, our data reveals an anti-apoptotic function for novel human breast adenocarcinoma marker BC-2, adding new depth to BC-2′s description as a putative tumor marker involved in cancer related pathways

    A Combined Approach Exploring Gene Function Based on Worm-Human Orthology

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    Background: Many aspects of the nematode Caenorhabditis elegans biology are conservedbetween invertebrates and vertebrates establishing this particular organism as an excellent geneticmodel. Because of its small size, large populations and self-fertilization of the hermaphrodite,functional predictions carried out by genetic modifications as well as RNAi screens, can be rapidlytested.Results: In order to explore the function of a set of C. elegans genes of unknown function, as wellas their potential functional roles in the human genome, we performed a phylogenetic analysis toselect the most probable worm orthologs. A total of 13 C. elegans genes were subjected to downregulationvia RNAi and characterization of expression profiles using GFP strains. Previouslyunknown distinct expression patterns were observed for four of the analyzed genes, as well as fourvisible RNAi phenotypes. In addition, subcellular protein over-expression profiles of the humanorthologs for seven out of the thirteen genes using human cells were also analyzed.Conclusion: By combining a whole-organism approach using C. elegans with complementaryexperimental work done on human cell lines, this analysis extends currently available informationon the selected set of genes

    An epigenetic memory of pregnancy in the mouse mammary gland.

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    Pregnancy is the major modulator of mammary gland activity. It induces a tremendous expansion of the mammary epithelium and the generation of alveolar structures for milk production. Anecdotal evidence from multiparous humans indicates that the mammary gland may react less strongly to the first pregnancy than it does to subsequent pregnancies. Here, we verify that the mouse mammary gland responds more robustly to a second pregnancy, indicating that the gland retains a long-term memory of pregnancy. A comparison of genome-wide profiles of DNA methylation in isolated mammary cell types reveals substantial and long-lasting alterations. Since these alterations are maintained in the absence of the signal that induced them, we term them epigenetic. The majority of alterations in DNA methylation affect sites occupied by the Stat5a transcription factor and mark specific genes that are upregulated during pregnancy. We postulate that the epigenetic memory of a first pregnancy primes the activation of gene expression networks that promote mammary gland function in subsequent reproductive cycles. More broadly, our data indicate that physiological experience can broadly alter epigenetic states, functionally modifying the capacity of the affected cells to respond to later stimulatory events.We thank Antoine Molaro for helpful discussions. This work was performed with assistance from the CSHL Flow Cytometry Shared Resource and from the CSHL Histology Shared Resource, which are supported by Cancer Center Support Grant 5P30CA045508. This work was supported by the NIH Grand Opportunity award #1 RC2 CA148507 (G.J.H.), P01 award # 2P01CA013106 (G.J.H.), and NIH grant R01 H6005238 (A.D.S.). G.J.H. is an investigator of the Howard Hughes Medical Institute.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.celrep.2015.04.01

    Updates to the RMAP short-read mapping software

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    Summary: We report on a major new version of the RMAP software for mapping reads from short-read sequencing technology. General improvements to accuracy and space requirements are included, along with novel functionality. Included in the RMAP software package are tools for mapping paired-end reads, mapping using more sophisticated use of quality scores, collecting ambiguous mapping locations and mapping bisulfite-treated reads

    Results of a Fall and Spring BioBlitz at Grassy Pond Recreational Area, Lowndes County, Georgia.

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    Two 24 h BioBlitzes were conducted in September, 2018, and April, 2019, at Grassy Pond Recreational Area in Lowndes County, Georgia. Teams of scientists, students, and public participants surveyed plants, insects, amphibians and reptiles, birds, mammals, fungi, lichens, and aquatic microorganisms. Both events included educational programs with informational walks and activities targeted to youth. In the fall, 654 species and 55 additional genera were recorded. In the spring, there were 581 species and 54 additional genera recorded. Two fungi and 38 lichens were first reports for Lowndes County; one fungus was a first for Georgia. One lichen may be a first for North America. One snake and 5 bat species were notably first reports for Grassy Pond Recreational Area

    Top-Ranked Priority Research Questions for Soil Science in the 21st Century

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    Soils provide critical support essential for life on earth, regulate processes across diverse terrestrial and aquatic ecosystems, and interact with the atmosphere. However, soil science is constrained by a variety of challenges including decreasing funding prospects and a declining number of new students and young professionals. Hence, there is a crucial need to revitalize the impact, relevance, and recognition of soil science as well as promote collaboration beyond traditionally defined soil science research disciplines. Such revitalization and collaboration may be fostered by a shift from discipline-focused soil science research to cross-disciplinary research approaches and issue-driven research. In this paper, we present the outcomes of an initiative to identify priority research questions as a tool for guiding future soil science research. The collaborative approach involved four stages including (i) survey-based solicitation of questions; (ii) criteria-based screening of submitted candidate questions, (iii) criteria-based ranking of screened questions, and (iv) final revision of top ranked questions. The 25 top ranked research questions emerged from 140 submitted candidate questions within five predetermined thematic areas that represent current and emerging research areas. We expect that the identified questions will inspire both existing and prospective researchers, enhance multi-disciplinary collaboration both within and outside soil science, draw the attention of grant-awarding bodies, and guide soil science research to address pressing societal, agricultural, and environmental challenges. Furthermore, we hope that the approach and findings presented in this paper will advance soil sciences by fostering improved collaboration among soil science practitioners and researchers, as well as with other sciences, policy experts, and emerging professionals (including students) to meet societal needs

    The relationship between pitch discrimination and acoustic voice measures in a cohort of female speakers

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    Background. Evidence across a range of musically trained, hearing disordered and voice disordered populations present conflicting results regarding the relationship between pitch discrimination (PD) and voice quality. PD characteristics of female speakers with and without a musical training background and no selfreported voice disorder, and the relationship between PD and voice quality in this particular population, have not been investigated. Aims. To evaluate PD characteristics in a cohort of female participants without a self-reported voice disorder and the relationship between PD and acoustic voice measures. Method. One hundred fourteen female participants were studied, all of whom self-reported as being non-voice disordered. All completed the Newcastle Assessment of Pitch Discrimination which involved a two-tone PD task. Their voices were recorded producing standardized vocal tasks. Voice samples were acoustically analyzed for frequency-domain measures (fundamental frequency and its standard deviation, and harmonics-to-noise ratio) and spectral-domain measures (cepstral peak prominence and the Cepstral/Spectral Index of Dysphonia). Data were analyzed for the whole cohort and for musical and non-musical training backgrounds. Results. In the whole cohort, there were no significant correlations between PD and acoustic voice measures. PD accuracy in musically trained speakers was better than in non-trained speakers and correlated with fundamental frequency standard deviation in prolonged vowel tasks. Vocalists demonstrated superior PD accuracy and fundamental frequency standard deviation in prolonged vowels compared to instrumentalists but did not show significant correlations between PD and acoustic measures. The Newcastle Assessment of Pitch Discrimination was a reliable tool, showing moderate-good prediction value in differentiating musical background. Conclusions. There was little evidence of a relationship between PD and acoustic measures of voice quality, regardless of musical training background and superior PD accuracy among the musically trained. These data do not support ideas concerning the co-development of perception and action among individuals identified as having voice quality measures within normal ranges. Numerous measures of voice quality, including measures sensitive to pitch, did not distinguish across musically and non-musically trained individuals, despite individual differences in pitch discrimination

    Deep Sequencing of Target Linkage Assay-Identified Regions in Familial Breast Cancer: Methods, Analysis Pipeline and Troubleshooting

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    Background: The classical candidate-gene approach has failed to identify novel breast cancer susceptibility genes. Nowadays, massive parallel sequencing technology allows the development of studies unaffordable a few years ago. However, analysis protocols are not yet sufficiently developed to extract all information from the huge amount of data obtained. Methodology/Principal Findings: In this study, we performed high throughput sequencing in two regions located on chromosomes 3 and 6, recently identified by linkage studies by our group as candidate regions for harbouring breast cancer susceptibility genes. In order to enrich for the coding regions of all described genes located in both candidate regions, a hybrid-selection method on tiling microarrays was performed. Conclusions/Significance: We developed an analysis pipeline based on SOAP aligner to identify candidate variants with a high real positive confirmation rate (0.89), with which we identified eight variants considered candidates for functiona
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