99 research outputs found

    NMR Analysis on Microfluidic Devices by Remote Detection

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    We present a novel approach to perform high-sensitivity NMR imaging and spectroscopic analysis on microfluidic devices. The application of NMR, the most information rich spectroscopic technique, to microfluidic devices remains a challenge because the inherently low sensitivity of NMR is aggravated by small fluid volumes leading to low NMR signal, and geometric constraints resulting in poor efficiency for inductive detection. We address the latter by physically separating signal detection from encoding of information with remote detection. Thereby, we use a commercial imaging probe with sufficiently large diameter to encompass the entire device, enabling encoding of NMR information at any location on the chip. Because large-diameter coils are too insensitive for detection, we store the encoded information as longitudinal magnetization and flow it into the outlet capillary. There, we detect the signal with optimal sensitivity using a solenoidal microcoil, and reconstruct the information encoded in the fluid. We present a generally applicable design for a detection-only microcoil probe that can be inserted into the bore of a commercial imaging probe. Using hyperpolarized 129Xe gas, we show that this probe enables sensitive reconstruction of NMR spectroscopic information encoded by the large imaging probe while keeping the flexibility of a large coil

    mycoCLAP, the database for characterized lignocellulose-active proteins of fungal origin: resource and text mining curation support

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    Enzymes active on components of lignocellulosic biomass are used for industrial applications ranging from food processing to biofuels production. These include a diverse array of glycoside hydrolases, carbohydrate esterases, polysaccharide lyases and oxidoreductases. Fungi are prolific producers of these enzymes, spurring fungal genome sequencing efforts to identify and catalogue the genes that encode them. To facilitate the functional annotation of these genes, biochemical data on over 800 fungal lignocellulose-degrading enzymes have been collected from the literature and organized into the searchable database, mycoCLAP (http://mycoclap.fungalgenomics.ca). First implemented in 2011, and updated as described here, mycoCLAP is capable of ranking search results according to closest biochemically characterized homologues: this improves the quality of the annotation, and significantly decreases the time required to annotate novel sequences. The database is freely available to the scientific community, as are the open source applications based on natural language processing developed to support the manual curation of mycoCLAP. Database URL: http://mycoclap.fungalgenomics.ca

    Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder

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    PosterAutism spectrum disorder (ASD) is characterized by impairments in social communication and abnormal repetitive behavior patterns. Recent studies have shown a strong association between ASD and gastrointestinal (GI) symptomatology. Some individuals with ASD show altered reactivity to stress, as well as altered immune markers, particularly stress responsive cytokines including TNF-alpha and IL-6. To assess potential relationships between GI symptoms and stress response, we examined whether GI symptoms are associated with increases in stress-associated endocrine markers and cytokines in ASD. We also conducted exploratory analyses the examine the relationship between IL-6, TNF-alpha, cortisol, and intelligence, as well as the effects of the presence or absence of co-occurring medical conditions on the relationship between IL-6, TNF-alpha, cortisol, and GI symptoms. Given the aforementioned findings, we expected to find positive relationships between GI symptoms and biomarkers of stress, including cortisol levels, IL-6, and TNF-alpha

    Anatomy of STEM Teaching in American Universities: A Snapshot from a Large-Scale Observation Study

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    National and local initiatives focused on the transformation of STEM teaching in higher education have multiplied over the last decade. These initiatives often focus on measuring change in instructional practices, but it is difficult to monitor such change without a national picture of STEM educational practices, especially as characterized by common observational instruments. We characterized a snapshot of this landscape by conducting the first large scale observation-based study. We found that lecturing was prominent throughout the undergraduate STEM curriculum, even in classrooms with infrastructure designed to support active learning, indicating that further work is required to reform STEM education. Additionally, we established that STEM faculty’s instructional practices can vary substantially within a course, invalidating the commonly-used teaching evaluations based on a one-time observation

    Investigation of inter- and intraspecies variation through genome sequencing of Aspergillus section Nigri

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    Aspergillus section Nigri comprises filamentous fungi relevant to biomedicine, bioenergy, health, and biotechnology. To learn more about what genetically sets these species apart, as well as about potential applications in biotechnology and biomedicine, we sequenced 23 genomes de novo, forming a full genome compendium for the section (26 species), as well as 6 Aspergillus niger isolates. This allowed us to quantify both inter-and intraspecies genomic variation. We further predicted 17,903 carbohydrateactive enzymes and 2,717 secondary metabolite gene clusters, which we condensed into 455 distinct families corresponding to compound classes, 49% of which are only found in single species. We performed metabolomics and genetic engineering to correlate genotypes to phenotypes, as demonstrated for the metabolite aurasperone, and by heterologous transfer of citrate production to Aspergillus nidulans. Experimental and computational analyses showed that both secondary metabolism and regulation are key factors that are significant in the delineation of Aspergillus species.Peer reviewe

    Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

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    In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article

    Novel Common Genetic Susceptibility Loci for Colorectal Cancer

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    BACKGROUND: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. METHODS: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. RESULTS: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. CONCLUSIONS: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screenin

    Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases

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    Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤ 6, 7, ≥ 8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69-0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68-0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58-0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54-0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (<4.0 ng/mL) in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness

    A somatic coliphage threshold approach to improve the management of activated sludge wastewater treatment plant effluents in resource-limited regions

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    Versión aceptada para publicaciónEffective wastewater management is crucial to ensure the safety of water reuse projects and 29 effluent discharge into surface waters. Multiple studies have demonstrated that municipal 30 wastewater treatment with conventional activated sludge processes is inefficient for the removal 31 of the wide spectrum of viruses in sewage. In this study, a well-accepted statistical approach was 32 used to investigate the relationship between viral indicators and human enteric viruses during 33 wastewater treatment in a resource-limited region. Influent and effluent samples from five urban 34 wastewater treatment plants (WWTP) in Costa Rica were analyzed for somatic coliphage and 35 human enterovirus, hepatitis A virus, norovirus genotype I and II, and rotavirus. All WWTP 36 provide primary treatment followed by conventional activated sludge treatment prior to 37 discharge into surface waters that are indirectly used for agricultural irrigation. The results 38 revealed a statistically significant relationship between the detection of at least one of the five 39 human enteric viruses and somatic coliphage. Multiple logistic regression and Receiver Operating Characteristic curve analysis identified a threshold of 3.0 ×103 40 (3.5-log10) somatic 41 coliphage plaque forming unit per 100 mL, which corresponded to an increased likelihood of encountering enteric viruses above the limit of detection (>1.83×102 42 virus target/100 mL). 43 Additionally, quantitative microbial risk assessment was executed for famers indirectly reusing 44 WWTP effluent that met the proposed threshold. The resulting estimated median cumulative 45 annual disease burden complied with World Health Organization recommendations. Future 46 studies are needed to validate the proposed threshold for use in Costa Rica and other regions.Universidad de Costa Rica/[]/UCR/Costa RicaNational Science Foundation/[OCE-1566562]/NSF/Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA)UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiologí
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