Development of a fingerprinting panel using medically relevant polymorphisms

<p>Abstract</p> <p>Background</p> <p>For population based biorepositories to be of use, rigorous quality control and assurance must be maintained. We have designed and validated a panel of polymorphisms for individual sample identification consisting of 36 common polymorphisms that have been implicated in a wide range of diseases and an additional sex marker. This panel uniquely identifies our biorepository of approximately 20,000 samples and would continue to uniquely identify samples in biorepositories of over 100 million samples.</p> <p>Methods</p> <p>A panel of polymorphisms associated with at least one disease state in multiple populations was constructed using a cut-off of 0.20 or greater confirmed minor allele frequency in a European Caucasian population. The fingerprinting assay was tested using the MALDI-TOF mass spectrometry method of allele determination on a Sequenom platform with a panel of 28 Caucasian HapMap samples; the results were compared with known genotypes to ensure accuracy. The frequencies of the alleles were compared to the expected frequencies from dbSNP and any genotype that did not achieve Hardy Weinberg equilibrium was excluded from the final assay.</p> <p>Results</p> <p>The final assay consisted of the AMG sex marker and 36 medically relevant polymorphisms with representation on each chromosome, encompassing polymorphisms on both the Illumina 550K bead array and the Affymetrix 6.0 chip (with over a million polymorphisms) platform. The validated assay has a P(ID) of 6.132 × 10^-15and a P_sib(ID) of 3.077 × 10^-8. This assay allows unique identification of our biorepository of 20,000 individuals as well and ensures that as we continue to recruit individuals they can be uniquely fingerprinted. In addition, diseases such as cancer, heart disease diabetes, obesity, and respiratory disease are well represented in the fingerprinting assay.</p> <p>Conclusion</p> <p>The polymorphisms in this panel are currently represented on a number of common genotyping platforms making QA/QC flexible enough to accommodate a large number of studies. In addition, this panel can serve as a resource for investigators who are interested in the effects of disease in a population, particularly for common diseases.</p

Antibacterial Metallic Touch Surfaces

Our aim is to present a comprehensive review of the development of modern antibacterial metallic materials as touch surfaces in healthcare settings. Initially we compare Japanese, European and US standards for the assessment of antimicrobial activity. The variations in methodologies defined in these standards are highlighted. Our review will also cover the most relevant factors that define the antimicrobial performance of metals, namely, the effect of humidity, material geometry, chemistry, physical properties and oxidation of the material. The state of the art in contact-killing materials will be described. Finally, the effect of cleaning products, including disinfectants, on the antimicrobial performance, either by direct contact or by altering the touch surface chemistry on which the microbes attach, will be discussed. We offer our outlook, identifying research areas that require further development and an overview of potential future directions of this exciting field

Survival benefits in mimicry: a quantitative framework

Mimicry is a resemblance between species that benefits at least one of the species. It is a ubiquitous evolutionary phenomenon particularly common among prey species, in which case the advantage involves better protection from predation. We formulate a mathematical description of mimicry among prey species, to investigate benefits and disadvantages of mimicry. The basic setup involves differential equations for quantities representing predator behavior, namely, the probabilities for attacking prey at the next encounter. Using this framework, we present new quantitative results, and also provide a unified description of a significant fraction of the quantitative mimicry literature. The new results include `temporary' mutualism between prey species, and an optimal density at which the survival benefit is greatest for the mimic. The formalism leads naturally to extensions in several directions, such as the evolution of mimicry, the interplay of mimicry with population dynamics, etc. We demonstrate this extensibility by presenting some explorations on spatiotemporal pattern dynamics.Comment: 9 pages, 7 figure

Exploring the Educational Involvement of Parents of English Learners

The purpose of the current investigation was to examine the relationships among a range of specific barriers and facilitators of parent involvement and a variety of types of school involvement within a diverse group of immigrant parents of English Learners (ELs) in four elementary school districts. In-home types of educational involvement such as monitoring homework and asking children about their school day were the most commonly reported behaviors, and utilizing community resources was found to be the least common type of parental involvement. Involvement type was predicted by parental demographic factors such as comfort with English language, educational background, and ethnicity, as well as perceptions of barriers and overall school climate. The findings of this study have implications for the design and implementation of interventions (e.g., parent programs, school policy changes) aimed at increasing the parental involvement of EL children

TURNING TEENS INTO FOSSILPHILES: CITIZEN SCIENCE AND ADVANCED VISUALIZATION OF PALEONTOLOGY COLLECTIONS

In 2016, the North Carolina Museum of Natural Sciences (NCMNS) received funding from NSF’s Collections in Support of Biological Research Program to launch a new citizen science initiative—FossilPhiles—aimed at improving publically accessible natural history specimen data. The FossilPhiles project supported NCMNS’ ongoing efforts to digitize paleontology collections and provide STEM opportunities for historically underrepresented student populations by engaging middle and high school students in authentic data collection. Five students were chosen from area schools with underserved populations to digitize highly significant or visually impactful vertebrate, invertebrate, and paleobotanical fossil specimens (e.g., type specimens, rare collections, specimens of high public interest). Students were trained in specimen handling, collections data, and archiving. They collected standard measurement data, photographed specimens in 2D, and constructed 3D photorealistic models using photogrammetry. Over a period of six months, students took over 13,000 photos, documenting 176 specimens in 2D and 137 in 3D. Of these, 124 photos have already been uploaded to the NCMNS’ open-access collections database, accessible through the NCMNS’ website, GBIF, VertNet, and iDigBio. Future project plans include creation of a publicly accessible, interactive portal of the 3D specimen models. Throughout their internships, FossilPhiles students were provided training and opportunities to communicate their experiences with the broader community. The entirety of the FossilPhiles project took place within the glass-walled Paleontology Research Lab (PRL) in the Nature Research Center of the NCMNS, on view to NCMNS’ ~1 million annual visitors. Additionally, students were regularly engaged with communicating about the project in real-time via social media outlets (e.g., Twitter, blogs), sharing photos of fossils they worked on, facts and skills that they learned, and challenges they overcame. FossilPhiles students also partnered with peers engaged in non-STEM museum internships to promote cross-learning. They collaborated with the NCMNS’ Teen Newsroom program to produce a video interview about their evolving impressions on what it means to be a scientist

Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use is the main risk factor for HNSCC, and tobacco-associated HNSCCs have poor prognosis and response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity (≤20%) in HNSCC, highlighting the need to identify new therapeutic options. For this, mouse models that accurately mimic the complexity of the HNSCC mutational landscape and tumor immune environment are urgently needed. Here, we report a mouse HNSCC model system that recapitulates the human tobacco-related HNSCC mutanome, in which tumors grow when implanted in the tongue of immunocompetent mice. These HNSCC lesions have similar immune infiltration and response rates to anti-PD-1 (≤20%) immunotherapy as human HNSCCs. Remarkably, we find that &gt;70% of HNSCC lesions respond to intratumoral anti-CTLA-4. This syngeneic HNSCC mouse model provides a platform to accelerate the development of immunotherapeutic options for HNSCC

The head and neck cancer cell oncogenome: a platform for the development of precision molecular therapies

The recent elucidation of the genomic landscape of head and neck squamous cell carcinoma (HNSCC) has provided a unique opportunity to develop selective cancer treatment options. These efforts will require the establishment of relevant HNSCC models for preclinical testing. Here, we performed full exome and transcriptome sequencing of a large panel of HNSCC-derived cells from different anatomical locations and human papillomavirus (HPV) infection status. These cells exhibit typical mutations in TP53, FAT1, CDK2NA, CASP8, and NOTCH1, and copy number variations (CNVs) and mutations in PIK3CA, HRAS, and PTEN that reflect the widespread activation of the PI3K-mTOR pathway. SMAD4 alterations were observed that may explain the decreased tumor suppressive effect of TGF-β in HNSCC. Surprisingly, we identified HPV+ HNSCC cells harboring TP53 mutations, and documented aberrant TP53 expression in a subset of HPV+ HNSCC cases. This analysis also revealed that most HNSCC cells harbor multiple mutations and CNVs in epigenetic modifiers (e.g., EP300, CREBP, MLL1, MLL2, MLL3, KDM6A, and KDM6B) that may contribute to HNSCC initiation and progression. These genetically-defined experimental HNSCC cellular systems, together with the identification of novel actionable molecular targets, may now facilitate the pre-clinical evaluation of emerging therapeutic agents in tumors exhibiting each precise genomic alteration.Centro de Investigaciones Inmunológicas Básicas y Aplicada