Designed to Fail: Why Most Commonly Used Designs Will Fail and How to Fix Them

https://digitalcommons.usm.maine.edu/cbep-presentations/1069/thumbnail.jp

Adenosine and Autism: A Spectrum of Opportunities [post-print]

In rodents, insufficient adenosine produces behavioral and physiological symptoms consistent with several comorbidities of autism. In rodents and humans, stimuli postulated to increase adenosine can ameliorate these comorbidities. Because adenosine is a broad homeostatic regulator of cell function and nervous system activity, increasing adenosine\u27s influence might be a new therapeutic target for autism with multiple beneficial effects

The Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring

The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays

Comparative genomics of two super-shedder isolates of Escherichia coli O157:H7

Shiga toxin-producing Escherichia coli O157:H7 (O157) are zoonotic foodborne pathogens and of major public health concern that cause considerable intestinal and extra-intestinal illnesses in humans. O157 colonize the recto-anal junction (RAJ) of asymptomatic cattle who shed the bacterium into the environment through fecal matter. A small subset of cattle, termed super-shedders (SS), excrete O157 at a rate (104 CFU/g of feces) that is several orders of magnitude greater than other colonized cattle and play a major role in the prevalence and transmission of O157. To better understand microbial factors contributing to super-shedding we have recently sequenced two SS isolates, SS17 (GenBank accession no. CP008805) and SS52 (GenBank accession no. CP010304) and shown that SS isolates display a distinctive strongly adherent phenotype on bovine rectal squamous epithelial cells. Here we present a detailed comparative genomics analysis of SS17 and SS52 with other previously characterized O157 strains (EC4115, EDL933, Sakai, TW14359). The results highlight specific polymorphisms and genomic features shared amongst SS strains, and reveal several SNPs that are shared amongst SS isolates, including in genes involved in motility, adherence, and metabolism. Finally, our analyses reveal distinctive patterns of distribution of phage-associated genes amongst the two SS and other isolates. Together, the results of our comparative genomics studies suggest that while SS17 and SS52 share genomic features with other lineage I/II isolates, they likely have distinct recent evolutionary histories. Future comparative and functional genomic studies are needed to decipher the precise molecular basis for super shedding in O157

Complete Genome Sequence of Mycobacterium avium subsp. paratuberculosis, Isolated from Human Breast Milk

Mycobacterium avium subsp. paratuberculosis causes Johne’s disease (JD) in cattle, sheep, goats, and other ruminant animals. JD presents as a chronic granulomatous intestinal infection with a worldwide distribution and imposes a significant economic toll on livestock industries (1). M. avium subsp. paratuberculosis has a complex cell wall structure containing mycolic acids and several lipids similar to those of other members of this genus, yet it is the most slowly growing member. This bacterium often requires 8 to 16 weeks before colonies are visible in culture, which is a major hurdle in diagnostics and therefore in the implementation of optimal JD control measures. Although a well-established domestic and wild animal pathogen, it has also been implicated as a causative agent in human Crohn’s disease (2), and even though this link is controversial (3), M. avium subsp. paratuberculosis isolates have been obtained from humans. For instance, M. avium subsp. paratuberculosis 4, the isolate whose sequence we report here, was originally isolated from the breast milk of a Crohn’s disease patient in 2000 (4)

Complete Genome Sequence of Mycobacterium avium subsp. paratuberculosis, Isolated from Human Breast Milk

Mycobacterium avium subsp. paratuberculosis causes Johne’s disease (JD) in cattle, sheep, goats, and other ruminant animals. JD presents as a chronic granulomatous intestinal infection with a worldwide distribution and imposes a significant economic toll on livestock industries (1). M. avium subsp. paratuberculosis has a complex cell wall structure containing mycolic acids and several lipids similar to those of other members of this genus, yet it is the most slowly growing member. This bacterium often requires 8 to 16 weeks before colonies are visible in culture, which is a major hurdle in diagnostics and therefore in the implementation of optimal JD control measures. Although a well-established domestic and wild animal pathogen, it has also been implicated as a causative agent in human Crohn’s disease (2), and even though this link is controversial (3), M. avium subsp. paratuberculosis isolates have been obtained from humans. For instance, M. avium subsp. paratuberculosis 4, the isolate whose sequence we report here, was originally isolated from the breast milk of a Crohn’s disease patient in 2000 (4)

Evolución del diseño de interiores en los grandes Centros Comerciales de Lima Central Sur en las últimas tres décadas

La investigación responde a una problemática que se evidencia a través de una serie de debilidades que repercuten en el diseño de dichos centros comerciales. El conocimiento de nuevas tecnologías para el diseño interior era escaso, no había conocimientos de enchapes, acabados finos, iluminación decorativa y diseño interior en general. Los materiales tampoco eran de gran ayuda, solo se conocían las estructuras comunes, como el cemento y el acero. Tampoco había conocimientos sobre técnicas constructivas

Automatic detection of circulating tumor cells and cancer associated fibroblasts using deep learning

Circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) from whole blood are emerging as important biomarkers that potentially aid in cancer diagnosis and prognosis. The microfilter technology provides an efficient capture platform for them but is confounded by two challenges. First, uneven microfilter surfaces makes it hard for commercial scanners to obtain images with all cells in-focus. Second, current analysis is labor-intensive with long turnaround time and user-to-user variability. Here we addressed the first challenge through developing a customized imaging system and data pre-processing algorithms. Utilizing cultured cancer and CAF cells captured by microfilters, we showed that images from our custom system are 99.3% in-focus compared to 89.9% from a top-of-the-line commercial scanner. Then we developed a deep-learning-based method to automatically identify tumor cells serving to mimic CTC (mCTC) and CAFs. Our deep learning method achieved precision and recall of 94% (± 0.2%) and 96% (± 0.2%) for mCTC detection, and 93% (± 1.7%) and 84% (± 3.1%) for CAF detection, significantly better than a conventional computer vision method, whose numbers are 92% (± 0.2%) and 78% (± 0.3%) for mCTC and 58% (± 3.9%) and 56% (± 3.5%) for CAF. Our custom imaging system combined with deep learning cell identification method represents an important advance on CTC and CAF analysis

Characterization of a Bacillus anthracis spore coat-surface protein that influences coat-surface morphology

Bacterial spores are encased in a multilayered proteinaceous shell, called the coat. In many Bacillus spp., the coat protects against environmental assault and facilitates germination. In Bacillus anthracis , the spore is the etiological agent of anthrax, and the functions of the coat likely contribute to virulence. Here, we characterize a B. anthracis spore protein, called CotΒ, which is encoded only in the genomes of the Bacillus cereus group. We found that CotΒ is synthesized specifically during sporulation and is assembled onto the spore coat surface. Our analysis of a cotΒ null mutant in the Sterne strain reveals that CotΒ has a role in determining coat-surface morphology but does not detectably affect germination. In the fully virulent Ames strain, a cotΒ null mutation has no effect on virulence in a murine model of B. anthracis infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72138/1/j.1574-6968.2008.01380.x.pd