Creation of an international registry to support discovery in schwannomatosis.

Schwannomatosis is a tumor suppressor syndrome that causes multiple tumors along peripheral nerves. Formal diagnostic criteria were first published in 2005. Variability in clinical presentation and a relative lack of awareness of the syndrome have contributed to difficulty recognizing affected individuals and accurately describing the natural history of the disorder. Many critical questions such as the mutations underlying schwannomatosis, genotype-phenotype correlations, inheritance patterns, pathologic diagnosis of schwannomatosis-associated schwannomas, tumor burden in schwannomatosis, the incidence of malignancy, and the effectiveness of current, or new treatments remain unanswered. A well-curated registry of schwannomatosis patients is needed to facilitate research in field. An international consortium of clinicians and scientists across multiple disciplines with expertise in schwannomatosis was established and charged with the task of designing and populating a schwannomatosis patient registry. The International Schwannomatosis Registry (ISR) was built around key data points that allow confirmation of the diagnosis and identification of potential research subjects to advance research to further the knowledge base for schwannomatosis. A registry with 389 participants enrolled to date has been established. Twenty-three additional subjects are pending review. A formal process has been established for scientific investigators to propose research projects, identify eligible subjects, and seek collaborators from ISR sites. Research collaborations have been created using the information collected by the registry and are currently being conducted. The ISR is a platform from which multiple research endeavors can be launched, facilitating connections between affected individuals interested in participating in research and researchers actively investigating a variety of aspects of schwannomatosis. © 2016 Wiley Periodicals, Inc.

25-OH-vitamin D deficiency and cellular alloimmunity as measured by panel of reactive T cell testing in dialysis patients.

Primed antidonor alloreactive T cells are detrimental to transplant outcome, but factors that impact the strength of this immune response prior to transplantation are unknown. We tested peripheral blood mononuclear cells from dialysis patients, against panels of allogeneic, primary B-cell lines in a newly standardized IFNγ ELISPOT panel of reactive T cell (PRT) assay. Results were correlated with known alloantibody-sensitizing events and other clinical parameters. As 25-OH-vitamin D deficiency is associated with enhanced cellular immunity, is common in dialysis patients and is correctable, we assessed the relationship between serum 25-OH-vitamin D and the PRT. Using independent test and validation cohorts we found that low serum levels of 25-OH-vitamin D (<26 ng/mL) correlated with high-PRT values (in the upper 50th percentile, OR 0.02, p = 0.01) independent of age, sex, race, previous transplant, transfusion, pregnancy, time on dialysis, panel of reactive antibody, iPTH, and treatment with 1,25-OH-vitamin D. The data provide a potential mechanism for the possible relationship between vitamin D deficiency and poor posttransplant outcome, and support studies to test the impact of 25-OH-vitamin D repletion on alloimmunity and allograft injury in kidney transplant candidates.

Genetic and Phenotypic Variation of the Pepper golden mosaic virus Complex.

ABSTRACT Three isolates of the bipartite begomovirus Pepper golden mosaic virus (PepGMV) were characterized for genomic and biological properties. The complete nucleotide sequences of the DNA-A and DNA-B components were determined from infectious clones of PepGMV-Serrano (PepGMV-Ser), PepGMV-Mosaic (PepGMV-Mo), and PepGMV-Distortion (PepGMV-D). Nucleotide sequence identity among PepGMV components ranged from 91 to 96% for DNA-A and from 84 to 99% for DNA-B, with each PepGMV component most closely related to the corresponding component of Cabbage leaf curl virus (CaLCV). However, phylogenetic relationships among begomovirus components were incongruent because DNA-A of PepGMV and CaLCV share an inferred evolutionary history distinct from that of DNA-B. The cloned components of PepGMV-Ser, -Mo, and -D were infectious by biolistic inoculation to pepper but differed in symptom expression: PepGMV-Ser exhibited a bright golden mosaic, PepGMV-Mo produced a yellow-green mosaic, and PepGMV-D caused only a mild mosaic and foliar distortion followed by a "recovery" phenotype in which leaves developing after initial symptom expression appeared normal. Differences in symptoms also were observed on tomato, tobacco, and Datura stramonium. Progeny virus derived from clones of PepGMV-Ser and -Mo were transmitted from pepper to pepper by the B biotype of Bemisia tabaci; progeny virus derived from PepGMV-D clones was not transmissible by the B biotype. Reassortant genomes derived from heterologous DNA components of the three isolates were infectious in all possible pairwise combinations, with symptom phenotype in pepper determined by the DNA-B component. Collectively, these results indicate that the three virus isolates examined may be considered distinct strains of PepGMV that have the capacity to exchange genetic material.

A paradigm for computer-assisted radiology resident rotation scheduling.

RATIONALE AND OBJECTIVES: The scheduling of radiology residents remains a major annual undertaking of chief residents. In this article, we describe a paradigm to implement interactive computer programs to reduce the inefficiencies and inequities of planning the yearly schedule. METHODS: We used the programming language, Prolog, to develop a compact program that provides faster and more flexible performance than those reported in the literature. This interactive program stores scheduling requirements in data files separated from the control program and runs on a Macintosh computer. RESULTS: The schedule of any residency year is generated within 3-7 sec. The fast computation and query capabilities of this scheduling program have helped chief residents to identify conflicting requirements that were previously overlooked. CONCLUSION: Using our programming paradigm, we have developed a portable Prolog-based scheduling program that is quick and easy to use.

Chino del tomate virus:Relationships to Other Begomoviruses and Identification of A-Component Variants that Affect Symptom Expression.

Phylogenetic and distance analyses place Chino del tomate virus (CdTV) in the New World clade of begomoviruses and indicate that CdTV and Tomato leaf crumple virus (TLCrV) are closely related strains of the same virus. One cloned CdTV A component (pCdTV-H6), when inoculated to tomato with the B component (pCdTV-B52), produced mild symptoms and low DNA titers. Another cloned CdTV A component (pCdTV-H8), when coinoculated to tomato with the B component, produced moderate leaf curling and veinal chlorosis similar to that of TLCrV. Coinoculation of both CdTV A components and the B component to tomato produced wild-type chino del tomate (CdT) disease symptoms consisting of severe leaf curling, veinal and interveinal chlorosis, and stunting. The two CdTV A components were nearly identical, except at nucleotide positions 1,722 and 2,324. The polymorphism at nucleotide 1,722 resulted in a change at Rep amino acid 261. The second polymorphism at nucleotide 2,324 resulted in changes at Rep amino acid 60 and AC4 amino acid 10. Two chimeric A components constructed by reciprocal exchange of a fragment bearing the polymorphic site at nucleotide 1,722 were evaluated for symptom phenotype. One chimeric A component (pCdTV-H86) produced wild-type CdT symptoms when coinoculated to tomato with the B component. The reciprocal chimeric A component (pCdTV-H68), when coin-oculated to tomato with the B component, also produced severe leaf curling, veinal chlorosis, and stunting. However, pCdTV-H68 induced less obvious interveinal chlorosis than wild-type or pCdTV-H86. Examination of A component genotypes recovered from tomato coinoculated with pCdTV-H6 and pCdTV-H8 indicated that recombination occurred to produce a genotype identical to pCdTV-H86. These results indicate that subtle genotypic variation has significant effects on symptom expression and may explain phenotypic differences observed among isolates and cloned DNAs of CdTV and TLCrV.

Biotic, molecular, and phylogenetic characterization of bean calico mosaic virus, a distinct begomovirus species with affiliation in the squash leaf curl virus cluster.

ABSTRACT Bean calico mosaic virus (BCMoV), a whitefly-transmitted geminivirus from Sonora, Mexico, was purified, and the genome components were cloned and sequenced. Purified viral fractions and cloned genome components were infectious by biolistic inoculation to bean, completing Koch's postulates for both. The B biotype of the whitefly Bemisia tabaci efficiently transmitted both native virus and progeny virus derived from cloned DNA inoculum. Host ranges of native virus and of progeny virus derived from cloned DNA were identical based upon whitefly and biolistic mediated transmission, respectively. BCMoV has a relatively wide experimental host range among begomoviruses known to infect bean, encompassing genera and species within the Fabaceae, Malvaceae, and Solanaceae. BCMoV has a bipartite genome, as do other New World begomoviruses. BCMoV DNA-A shared highest nucleotide sequence identities with squash leaf curl virus-E strain (SLCV-E) and cabbage leaf curl virus (CaLCV) at 80.1 and 80.7%, respectively. BCMoV DNA-B shared highest nucleotide sequence identity with SLCV-E at 70.7%. The common region (CR) sequences of BCMoV and SLCV-E are 73 to 76% identical; however, modular cis-acting elements within the CR involved in replication origin function and recognition are 100% conserved. Phy-logenetic analysis indicated that BCMoV DNA-A shares a most recent common ancestor with the DNA-A of two viruses that also occur in the Sonoran Desert, SLCV-E and Texas pepper virus (TPV-TAM), and CaLCV from Florida. In contrast, a phylogenetic analysis indicated that BCMoV DNA-B shares a most recent common ancestor with SLCV-E; whereas DNA-B of CaLCV clustered in a separate clade with pepper hausteco virus. Collectively, biological and molecular characteristics indicate that BCMoV is a distinct begomovirus species with the northernmost distribution of any begomovirus isolated from bean in the Americas. Furthermore, the phylogenetic relationships of begomovirus cognate components are not necessarily identical, suggesting that DNA-A and DNA-B of some begomoviruses may have different evolutionary histories.

cis-acting sites required for osmoregulation of ompF expression in Escherichia coli K-12.

OmpF and OmpC are major outer membrane proteins which form passive diffusion pores in Escherichia coli K-12. The expression of the structural genes for these proteins, ompF and ompC, is influenced by medium osmotic strength and requires the products of two regulatory genes, ompR and envZ. We have constructed a series of ompF-lacZ fusions containing different regions of ompF to determine sites involved with osmoregulation. These fusions were crossed onto a specialized transducing phage and integrated into the bacterial chromosome in unit copy. By measuring the fluctuations of beta-galactosidase activity in lysogens grown in high versus low osmolarity, we have identified three regions which are necessary. Furthermore, we have determined that, although the OmpR activation site is not sufficient, OmpR is probably essential for ompF osmoregulation.

Relation of contraceptive and reproductive history to ovarian cancer risk in carriers and noncarriers of BRCA1 gene mutations.

In the general population, ovarian cancer risk is inversely associated with oral contraceptive use, tubal ligation, and childbearing. Among carriers of BRCA1 gene mutations, the data are conflicting. The authors identified women diagnosed with incident invasive epithelial ovarian cancer in the San Francisco Bay Area of California from March 1997 through July 2001. They compared the contraceptive and reproductive histories of 36 carrier cases and 381 noncarrier cases with those of 568 controls identified by random digit dialing who were frequency matched to cases on age and race/ethnicity. In both carriers and noncarriers, reduced risk was associated with ever use of oral contraceptives (odds ratio = 0.54 (95% confidence interval (CI): 0.26, 1.13) for carriers and 0.55 (95% CI: 0.41, 0.73) for noncarriers), duration of oral contraceptive use (risk reduction per year = 13% (p = 0.01) for carriers and 6% (p < 0.001) for noncarriers), history of tubal ligation (odds ratio = 0.68 (95% CI: 0.25, 1.90) for carriers and 0.65 (95% CI: 0.45, 0.95) for noncarriers), and increasing parity (risk reduction per childbirth = 16% (p = 0.26) for carriers and 24% (p < 0.001) for noncarriers). These data suggest that BRCA1 mutation carriers and noncarriers have similar risk reductions associated with oral contraceptive use, tubal ligation, and parity.