Performance evaluation of the high-throughput quantitative Alinity m Epstein-Barr virus assay.

Unlabelled: Molecular testing for Epstein-Barr virus (EBV) infection is a cornerstone of care to prevent adverse outcomes in immunocompromised patients, including transplant recipients. We evaluated the analytical and clinical performance of the quantitative Alinity m EBV assay for plasma sample testing on the fully automated Alinity m platform. Assay lower limit of detection and precision were determined using commercially available panels in plasma.

Performance evaluation of the high-throughput quantitative Alinity m BK virus assay.

Unlabelled: BK virus (BKV) infection or reactivation in immunocompromised individuals can lead to adverse health consequences including BKV-associated nephropathy (BKVAN) in kidney transplant patients and BKV-associated hemorrhagic cystitis (BKV-HC) in allogeneic hematopoietic stem cell transplant recipients. Monitoring BKV viral load plays an important role in post-transplant patient care. This study evaluates the performance of the Alinity m BKV Investigational Use Only (IUO) assay.

Multi-site performance evaluation of the Alinity m Molecular assay for quantifying Epstein-Barr virus DNA in plasma samples.

Detection and monitoring of acute infection or reactivation of Epstein-Barr virus (EBV) are critical for treatment decision-making and to reduce the risk of EBV-related malignancies and other associated diseases in immunocompromised individuals. The analytical and clinical performance of the Alinity m EBV assay was evaluated at two independent study sites; analytical performance was assessed by evaluating precision with a commercially available 5-member EBV verification panel, while the clinical performance of the Alinity m EBV assay was compared to the RealTi EBV assay and a laboratory-developed test (LDT) as the routine test of record (TOR). Analytical analysis demonstrated standard deviation (SD) between 0.

Functional Common and Rare Germline Variants Cooperate in Familial and Sporadic Cancer Susceptibility.

We investigated a Spanish and Catalan family in which multiple cancer types tracked across three generations, but for which no genetic etiology had been identified. Whole-exome sequencing of germline DNA from multiple affected family members was performed to identify candidate variants to explain this occurrence of familial cancer. We discovered in all cancer-affected family members a single rare heterozygous germline variant (I654V, rs1801201) in , which is located in a transmembrane glycine zipper motif critical for ERBB2-mediated signaling and in complete linkage disequilibrium (' = 1) with a common polymorphism (I655V, rs1136201) previously reported in some populations as associated with cancer risk.

The genetics of breast cancer risk in the post-genome era: thoughts on study design to move past BRCA and towards clinical relevance.

More than 12 % of women will be diagnosed with breast cancer in their lifetime. Although there have been tremendous advances in elucidating genetic risk factors underlying both familial and sporadic breast cancer, much of the genetic contribution to breast cancer etiology remains unknown. The discovery of BRCA1 and BRCA2 over 20 years ago remains the seminal event in the field and has paved the way for the discovery of other high-penetrance susceptibility genes by linkage analysis.

Whole-exome Sequence Analysis Implicates Rare Il17REL Variants in Familial and Sporadic Inflammatory Bowel Disease.

Background: Rare variants (<1%) likely contribute significantly to risk for common diseases such as inflammatory bowel disease (IBD) in specific patient subsets, such as those with high familiality. They are, however, extraordinarily challenging to identify.

Methods: To discover candidate rare variants associated with IBD, we performed whole-exome sequencing on 6 members of a pediatric-onset IBD family with multiple affected individuals.

Integrated genomic analysis suggests MLL3 is a novel candidate susceptibility gene for familial nasopharyngeal carcinoma.

Background: Little is known about genetic factors associated with nasopharyngeal carcinoma (NPC). To gain insight into NPC etiology, we performed whole exome sequencing on germline and tumor DNA from three closely related family members with NPC.

Methods: The family was ascertained through the Pediatric Familial Cancer Clinic at The University of Chicago (Chicago, IL).

edn1 and hand2 Interact in early regulation of pharyngeal arch outgrowth during zebrafish development.

Endothelin-1 (Edn1) signaling provides a critical input to development of the embryonic pharygneal arches and their skeletal derivatives, particularly the articulating joints and the ventral skeleton including the lower jaw. Previous work in zebrafish has mostly focused on the role of Edn1 in dorsal-ventral (DV) patterning, but Edn1 signaling must also regulate tissue size, for with severe loss of the pathway the ventral skeleton is not only mispatterned, but is also prominently hypoplastic--reduced in size. Here we use mutational analyses to show that in the early pharyngeal arches, ventral-specific edn1-mediated proliferation of neural crest derived cells is required for DV expansion and outgrowth, and that this positive regulation is counterbalanced by a negative one exerted through a pivotal, ventrally expressed Edn1-target gene, hand2.

FishFace: interactive atlas of zebrafish craniofacial development at cellular resolution.

Background: The vertebrate craniofacial skeleton may exhibit anatomical complexity and diversity, but its genesis and evolution can be understood through careful dissection of developmental programs at cellular resolution. Resources are lacking that include introductory overviews of skeletal anatomy coupled with descriptions of craniofacial development at cellular resolution. In addition to providing analytical guidelines for other studies, such an atlas would suggest cellular mechanisms underlying development.

Husbandry of Monodelphis domestica in the study of mammalian embryogenesis.

Monodelphis domestica, commonly called the laboratory opossum, is a useful laboratory animal for studying marsupial embryogenesis and mammalian development. Females breed year-round and the animals can be sustainably bred indoors. The authors draw on their own laboratory's experience to supplement previously published research on laboratory opossums.

Regulation of p53 nuclear export through sequential changes in conformation and ubiquitination.

Wild-type p53 is a conformationally labile protein that undergoes nuclear-cytoplasmic shuttling. MDM2-mediated ubiquitination promotes p53 nuclear export by exposing or activating a nuclear export signal (NES) in the C terminus of p53. We observed that cancer-derived p53s with a mutant (primary antibody 1620-/pAb240+) conformation localized in the cytoplasm to a greater extent and displayed increased susceptibility to ubiquitination than p53s with a more wild-type (primary antibody 1620+/pAb240-) conformation.

MDM2 binding induces a conformational change in p53 that is opposed by heat-shock protein 90 and precedes p53 proteasomal degradation.

p53 protein conformation is an important determinant of its localization and activity. Changes in p53 conformation can be monitored by reactivity with wild-type conformation-specific (pAb-1620) or mutant conformation-specific (pAb-240) p53 antibodies. Wild-type p53 accumulated in a mutant (pAb-240 reactive) form when its proteasome-dependent degradation was blocked during recovery from stress treatment and in cells co-expressing p53 and MDM2.