Notch 1-deficient common lymphoid precursors adopt a B cell fate in the thymus.

We have recently reported that Notch 1, a member of the Notch multigene family, is essential for the development of murine T cells. Using a mouse model in which Notch 1 is inactivated in bone marrow (BM) precursors we have shown that B cells instead of T cells are found in the thymus of BM chimeras. However, it is not clear whether these B cells develop by default from a common lymphoid precursor due to the absence of Notch 1 signaling, or whether they arise as a result of perturbed migration of BM-derived B cells and/or altered homeostasis of normal resident thymic B cells. In this report we show that Notch 1-deficient thymic B cells resemble BM B cells in phenotype and turnover kinetics and are located predominantly in the medulla and corticomedullary junction. Peripheral blood lymphocyte analysis shows no evidence of recirculating Notch1(-/)- BM B cells. Furthermore, lack of T cell development is not due to a failure of Notch1(-/)- precursors to home to the thymus, as even after intrathymic reconstitution with BM cells, B cells instead of T cells develop from Notch 1-deficient precursors. Taken together, these results provide evidence for de novo ectopic B cell development in the thymus, and support the hypothesis that in the absence of Notch 1 common lymphoid precursors adopt the default cell fate and develop into B cells instead.

Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.

BACKGROUND: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CAD. OBJECTIVE: We tested whether common genetic polymorphisms associated with variation in tHcy are also associated with CAD. DESIGN: We conducted a meta-analysis of genome-wide association studies (GWAS) on tHcy concentrations in 44,147 individuals of European descent. Polymorphisms associated with tHcy (P < 10(-8)) were tested for association with CAD in 31,400 cases and 92,927 controls. RESULTS: Common variants at 13 loci, explaining 5.9% of the variation in tHcy, were associated with tHcy concentrations, including 6 novel loci in or near MMACHC (2.1 Ã- 10(-9)), SLC17A3 (1.0 Ã- 10(-8)), GTPB10 (1.7 Ã- 10(-8)), CUBN (7.5 Ã- 10(-10)), HNF1A (1.2 Ã- 10(-12)), and FUT2 (6.6 Ã- 10(-9)), and variants previously reported at or near the MTHFR, MTR, CPS1, MUT, NOX4, DPEP1, and CBS genes. Individuals within the highest 10% of the genotype risk score (GRS) had 3-μmol/L higher mean tHcy concentrations than did those within the lowest 10% of the GRS (P = 1 Ã- 10(-36)). The GRS was not associated with risk of CAD (OR: 1.01; 95% CI: 0.98, 1.04; P = 0.49). CONCLUSIONS: We identified several novel loci that influence plasma tHcy concentrations. Overall, common genetic variants that influence plasma tHcy concentrations are not associated with risk of CAD in white populations, which further refutes the causal relevance of moderately elevated tHcy concentrations and tHcy-related pathways for CAD.

Transgene inheritances and genetic similarities of near isogenic lines of genetically modified common beans

The objective of the present work was to determine the inheritance and stability of transgenes of a transgenic bean line expressing the genes rep-trap-ren from Bean golden mosaic virus and the bar gene. Crosses were done between the transgenic line and four commercial bean cultivars, followed by four backcrosses to the commercial cultivars. Progenies from each cross were evaluated for the presence of the transgenes by brushing the leaves with glufosinate ammonium and by polymerase chain reaction using specific oligonucleotides. Advanced generations were rub-inoculated with an isolate of Bean common mosaic necrosis virus (BCMNV). The transgenes were inherited consistently in a Mendelian pattern in the four crosses studied. The analyzed lines recovered close to 80% of the characteristics of the recurrent parent, as determined by the random amplified DNA markers used, besides maintaining important traits such as resistance to BCMNV. The presence of the transgene did not cause any detectable undesirable effect in the evaluated progenies.

Meiotic drive favors Robertsonian metacentric chromosomes in the common shrew (Sorex araneus, Insectivora, mammalia).

Meiotic drive has attracted much interest because it concerns the robustness of Mendelian segregation and its genetic and evolutionary stability. We studied chromosomal meiotic drive in the common shrew (Sorex araneus, Insectivora, Mammalia), which exhibits one of the most remarkable chromosomal polymorphisms within mammalian species. The open question of the evolutionary success of metacentric chromosomes (Robertsonian fusions) versus acrocentrics in the common shrew prompted us to test whether a segregation distortion in favor of metacentrics is present in female and/or male meiosis. Performing crosses under controlled laboratory conditions with animals from natural populations, we found a clear trend toward a segregation distortion in favor of metacentrics during male meiosis, two chromosome combinations (gm and jl) being significantly preferred over their acrocentric homologs. Apart for one Robertsonian fusion (hi), this trend was absent in female meiosis. We propose a model based on recombination events between twin acrocentrics to explain the difference in transmission ratios of the same metacentric in different sexes and unequal drive of particular metacentrics in the same sex. Pooled data for female and male meiosis revealed a trend toward stronger segregation distortion for larger metacentrics. This is partially in agreement with the frequency of metacentrics occurring in natural populations of a chromosome race showing a high degree of chromosomal polymorphism.

Traffic Signal Inventory Project, 2001

The Center for Transportation Research and Education performed a traffic signal inventory study for the Iowa Department of Transportation. The purpose of this study was to determine the level of compliance with the Manual on Uniform Traffic Control Devices (MUTCD) and other industry standards of traffic signals on the state highway system. Signals were randomly selected throughout the State of Iowa. Only signals in cities with a population less than 5,000 were considered. Several intersections need to be addressed immediately to correct clearance timing settings. Red clearance intervals were frequently too short. A handful of intersections had inadequate pedestrian clearance times. Six intersections had at least one yellow clearance interval that did not meet Institute of Transportation Engineers standards. Some of the intersections likely would not meet traffic signal warrants and should be investigated for possible removal. The most common problem found with traffic signals was a lack of maintenance. Many of the signals had at least one of the following problems: burned out lights (signals and/or pedestrian heads), pedestrian lenses in need of replacement, dirty cabinet/missing or poor filter, missing visors, or inoperative pedestrian push buttons. Timing sheets were frequently missing or out of date. Another frequent noncompliance issue was the use of backplates. The MUTCD states that backplates should be used on signals viewed against a bright sky. The majority of signals inventoried did not have backplates on the mast-arm mounted signals. The timing at some intersections could likely be improved by reducing the cycle length. Where there were multiple signals in close proximity rarely was there any attempt at signal coordination. Finally, a number of intersections had equipment that by today’s standards would be considered obsolete.

The Epidemiology of Common Communicable Diseases, January 2016

Chart of common communicable disease, stating incubation, transmission, control measures, and public health response produced by Iowa Department of Public Health.

Phytogeographical origin of Madeiran common beans based on phaseolin patterns

The objective of this work was to determine the geographic origin of the Madeiran common bean (Phaseolus vulgaris) gene pool. Phaseolin patterns of 50 accessions representing the diversity of common bean collected in Madeira, Portugal, and conserved in the ISOPlexis Germplasm Bank, were analysed using the Experion automated electrophoresis system, based on lab-on-a-chip technology. Five common bean standard varieties with typical phaseolin patterns were used to determine the phytogeographical origin of the Madeiran common bean accessions. Ninety two percent of the accessions exhibited a phaseolin pattern consistent with the one of common bean types belonging to the Andean gene pool, while the origin of the remaining 8% of the accessions was indistinguishable. The application of a similarity coefficient of 85%, based on Pearson correlations, increases the number of accessions with uncertain pattern. The analytical approach used permitted the determination of the origin of the common bean gene pool, which is Andean in 98% of the cases, and clustering of the observed variability among the Madeiran common beans.

Overlap Between Common Genetic Polymorphisms Underpinning Kidney Traits and Cardiovascular Disease Phenotypes: The CKDGen Consortium.

BACKGROUND: Chronic kidney disease is associated with cardiovascular disease. We tested for evidence of a shared genetic basis to these traits. STUDY DESIGN: We conducted 2 targeted analyses. First, we examined whether known single-nucleotide polymorphisms (SNPs) underpinning kidney traits were associated with a series of vascular phenotypes. Additionally, we tested whether vascular SNPs were associated with markers of kidney damage. Significance was set to 1.5×10(-4) (0.05/325 tests). SETTING & PARTICIPANTS: Vascular outcomes were analyzed in participants from the AortaGen (20,634), CARDIoGRAM (86,995), CHARGE Eye (15,358), CHARGE IMT (31,181), ICBP (69,395), and NeuroCHARGE (12,385) consortia. Tests for kidney outcomes were conducted in up to 67,093 participants from the CKDGen consortium. PREDICTOR: We used 19 kidney SNPs and 64 vascular SNPs. OUTCOMES & MEASUREMENTS: Vascular outcomes tested were blood pressure, coronary artery disease, carotid intima-media thickness, pulse wave velocity, retinal venular caliber, and brain white matter lesions. Kidney outcomes were estimated glomerular filtration rate and albuminuria. RESULTS: In general, we found that kidney disease variants were not associated with vascular phenotypes (127 of 133 tests were nonsignificant). The one exception was rs653178 near SH2B3 (SH2B adaptor protein 3), which showed direction-consistent association with systolic (P = 9.3 ×10(-10)) and diastolic (P = 1.6 ×10(-14)) blood pressure and coronary artery disease (P = 2.2 ×10(-6)), all previously reported. Similarly, the 64 SNPs associated with vascular phenotypes were not associated with kidney phenotypes (187 of 192 tests were nonsignificant), with the exception of 2 high-correlated SNPs at the SH2B3 locus (P = 1.06 ×10(-07) and P = 7.05 ×10(-08)). LIMITATIONS: The combined effect size of the SNPs for kidney and vascular outcomes may be too low to detect shared genetic associations. CONCLUSIONS: Overall, although we confirmed one locus (SH2B3) as associated with both kidney and cardiovascular disease, our primary findings suggest that there is little overlap between kidney and cardiovascular disease risk variants in the overall population. The reciprocal risks of kidney and cardiovascular disease may not be genetically mediated, but rather a function of the disease milieu itself.

Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations.

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2x10(-201)), ABCG2 (p = 3.1x10(-26)), SLC17A1 (p = 3.0x10(-14)), SLC22A11 (p = 6.7x10(-14)), SLC22A12 (p = 2.0x10(-9)), SLC16A9 (p = 1.1x10(-8)), GCKR (p = 1.4x10(-9)), LRRC16A (p = 8.5x10(-9)), and near PDZK1 (p = 2.7x10(-9)). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0x10(-26)) and propionyl-L-carnitine (p = 5.0x10(-8)) concentrations, which in turn were associated with serum UA levels (p = 1.4x10(-57) and p = 8.1x10(-54), respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels.

Genetic control of potassium content of common bean seeds

The objective of this work was to investigate possible maternal effects on potassium content of common bean seeds, as well as to estimate the heritability and selection gains in early hybrid generations for this character and to evaluate the efficiency of genetic selection to improve the nutritional quality of common bean (Phaseolus vulgaris). Crosses with four cultivars from the Mesoamerican gene pool yielded the reciprocal F1 and F2 generations and the backcrossed populations (BCP1 and BCP2). The potassium content of the progenies was measured via nitric‑perchloric digestion and flame photometry. The potassium content in the tested progenies varied from 6.0 to 14.9 g kg-1 dry matter, and no significant maternal effect was observed. The narrow-sense heritability ranged from low (33.26%) to intermediate (43.05%). Partial dominance was observed for low potassium content in the seeds. No increase in potassium content was obtained through selection. Breeding common bean plants for increasing potassium content in seeds may be difficult because the local environment strongly influences the character.