Reference database of total retinal vessel surface area derived from volume-rendered optical coherence tomography angiography

Optical coherence tomography angiography (OCTA) enables three-dimensional, high-resolution, depth-resolved flow to be distinguished from non-vessel tissue signals in the retina. Thus, it enables the quantification of the 3D surface area of the retinal vessel signal. Despite the widespread use of OCTA, no representative spatially rendered reference vessel surface area data are published. In this study, the OCTA vessel surface areas in 203 eyes of 107 healthy participants were measured in the 3D domain. A Generalized Linear Model (GLM) model analysis was performed to investigate the effects of sex, age, spherical equivalent, axial length, and visual acuity on the OCTA vessel surface area. The mean overall vessel surface area was 54.53 mm2 (range from 27.03 to 88.7 mm2). OCTA vessel surface area was slightly negatively correlated with age. However, the GLM model analysis identified axial length as having the strongest effect on OCTA vessel surface area. No significant correlations were found for sex or between left and right eyes. This is the first study to characterize three-dimensional vascular parameters in a population based on OCTA with respect to the vessel surface area

Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect

LRRK2 plays an important role in Parkinson's disease (PD), but its biological functions are largely unknown. Here, we cloned the homolog of human LRRK2, characterized its expression, and investigated its biological functions in zebrafish. The blockage of zebrafish LRRK2 (zLRRK2) protein by morpholinos caused embryonic lethality and severe developmental defects such as growth retardation and loss of neurons. In contrast, the deletion of the WD40 domain of zLRRK2 by morpholinos targeting splicing did not induce severe embryonic developmental defects; rather it caused Parkinsonism-like phenotypes, including loss of dopaminergic neurons in diencephalon and locomotion defects. These neurodegenerative and locomotion defects could be rescued by over-expressing zLRRK2 or hLRRK2 mRNA. The administration of L-dopa could also rescue the locomotion defects, but not the neurodegeneration. Taken together, our results demonstrate that zLRRK2 is an ortholog of hLRRK2 and that the deletion of WD40 domain of zLRRK2 provides a disease model for PD

United States Acculturation and Cancer Patients' End-of-Life Care

Background: Culture shapes how people understand illness and death, but few studies examine whether acculturation influences patients' end-of-life treatment preferences and medical care. Methods and Findings: In this multi-site, prospective, longitudinal cohort study of terminally-ill cancer patients and their caregivers (n = 171 dyads), trained interviewers administered the United States Acculturation Scale (USAS). The USAS is a 19-item scale developed to assess the degree of "Americanization" in first generation or non-US born caregivers of terminally-ill cancer patients. We evaluated the internal consistency, concurrent, criterion, and content validity of the USAS. We also examined whether caregivers' USAS scores predicted patients' communication, treatment preferences, and end-of-life medical care in multivariable models that corrected for significant confounding influences (e.g. education, country of origin, English proficiency). The USAS measure was internally consistent (Cronbach α = 0.98); and significantly associated with US birthplace (r = 0.66, P<0.0001). USAS scores were predictive of patients' preferences for prognostic information (AOR = 1.31, 95% CI:1.00-1.72), but not comfort asking physicians' questions about care (AOR 1.23, 95% CI:0.87-1.73). They predicted patients' preferences for feeding tubes (AOR = 0.68, 95% CI:0.49-0.99) and wish to avoid dying in an intensive care unit (AOR = 1.36, 95% CI:1.05-1.76). Scores indicating greater acculturation were also associated with increased odds of patient participation in clinical trials (AOR = 2.20, 95% CI:1.28-3.78), compared with lower USAS scores, and greater odds of patients receiving chemotherapy (AOR = 1.59, 95% CI:1.20-2.12). Conclusion: The USAS is a reliable and valid measure of "Americanization" associated with advanced cancer patients' end-of-life preferences and care. USAS scores indicating greater caregiver acculturation were associated with increased odds of patient participation in cancer treatment (chemotherapy, clinical trials) compared with lower scores. Future studies should examine the effects of acculturation on end-of-life care to identify patient and provider factors that explain these effects and targets for future interventions to improve care (e.g., by designing more culturally-competent health education materials). © 2013 Wright et al

Identification of QTLs for Arsenic Accumulation in Maize (Zea mays L.) Using a RIL Population

The Arsenic (As) concentration in different tissues of maize was analyzed using a set of RIL populations derived from an elite hybrid, Nongda108. The results showed that the trend of As concentration in the four measured tissues was leaves>stems>bracts>kernels. Eleven QTLs for As concentration were detected in the four tissues. Three QTLs for As concentration in leaves were mapped on chromosomes 1, 5, and 8, respectively. For As concentration in the bracts, two QTLs were identified, with 9.61% and 10.03% phenotypic variance. For As concentration in the stems, three QTLs were detected with 8.24%, 14.86%, and 15.23% phenotypic variance. Three QTLs were identified for kernels on chromosomes 3, 5, and 7, respectively, with 10.73%, 8.52%, and 9.10% phenotypic variance. Only one common chromosomal region between SSR marker bnlg1811 and umc1243 was detected for QTLs qLAV1 and qSAC1. The results implied that the As accumulation in different tissues in maize was controlled by different molecular mechanism. The study demonstrated that maize could be a useful plant for phytoremediation of As-contaminated paddy soil, and the QTLs will be useful for selecting inbred lines and hybrids with low As concentration in their kernels

Linkage mapping of the Phg-1 and Co-14 genes for resistance to angular leaf spot and anthracnose in the common bean cultivar AND 277

The Andean common bean AND 277 has the Co-14 and the Phg-1 alleles that confer resistance to 21 and eight races, respectively, of the anthracnose (ANT) and angular leaf spot (ALS) pathogens. Because of its broad resistance spectrum, Co-14 is one of the main genes used in ANT resistance breeding. Additionally, Phg-1 is used for resistance to ALS. In this study, we elucidate the inheritance of the resistance of AND 277 to both pathogens using F2 populations from the AND 277 × Rudá and AND 277 × Ouro Negro crosses and F2:3 families from the AND 277 × Ouro Negro cross. Rudá and Ouro Negro are susceptible to all of the above races of both pathogens. Co-segregation analysis revealed that a single dominant gene in AND 277 confers resistance to races 65, 73, and 2047 of the ANT and to race 63-23 of the ALS pathogens. Co-14 and Phg-1 are tightly linked (0.0 cM) on linkage group Pv01. Through synteny mapping between common bean and soybean we also identified two new molecular markers, CV542014450 and TGA1.1570, tagging the Co-14 and Phg-1 loci. These markers are linked at 0.7 and 1.3 cM, respectively, from the Co-14/Phg-1 locus in coupling phase. The analysis of allele segregation in the BAT 93/Jalo EEP558 and California Dark Red Kidney/Yolano recombinant populations revealed that CV542014450 and TGA1.1570 segregated in the expected 1:1 ratio. Due to the physical linkage in cis configuration, Co-14 and Phg-1 are inherited together and can be monitored indirectly with the CV542014450 and TGA1.1570 markers. These results illustrate the rapid discovery of new markers through synteny mapping. These markers will reduce the time and costs associated with the pyramiding of these two disease resistance genes

Search for supersymmetric particles in scenarios with a gravitino LSP and stau NLSP

Sleptons, neutralinos and charginos were searched for in the context of scenarios where the lightest supersymmetric particle is the gravitino. It was assumed that the stau is the next-to-lightest supersymmetric particle. Data collected with the DELPHI detector at a centre-of-mass energy near 189 GeV were analysed combining the methods developed in previous searches at lower energies. No evidence for the production of these supersymmetric particles was found. Hence, limits were derived at 95% confidence level.Comment: 31 pages, 14 figure

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Post-Translational Modifications Modulate Ligand Recognition by the Third PDZ Domain of the MAGUK Protein PSD-95

The relative promiscuity of hub proteins such as postsynaptic density protein-95 (PSD-95) can be achieved by alternative splicing, allosteric regulation, and post-translational modifications, the latter of which is the most efficient method of accelerating cellular responses to environmental changes in vivo. Here, a mutational approach was used to determine the impact of phosphorylation and succinimidation post-translational modifications on the binding affinity of the postsynaptic density protein-95/discs large/zonula occludens-1 (PDZ3) domain of PSD-95. Molecular dynamics simulations revealed that the binding affinity of this domain is influenced by an interplay between salt-bridges linking the α3 helix, the β2–β3 loop and the positively charged Lys residues in its high-affinity hexapeptide ligand KKETAV. The α3 helix is an extra structural element that is not present in other PDZ domains, which links PDZ3 with the following SH3 domain in the PSD-95 protein. This regulatory mechanism was confirmed experimentally via thermodynamic and NMR chemical shift perturbation analyses, discarding intra-domain long-range effects. Taken together, the results presented here reveal the molecular basis of the regulatory role of the α3 extra-element and the effects of post-translational modifications of PDZ3 on its binding affinity, both energetically and dynamically.This research was supported by grants CVI-05915, from the Andalusian Regional Government (http://www.juntadeandalucia.es), BIO2009-13261-C02 and BIO2012-39922-C02, from the Spanish Ministry of Science and Innovation (http://www.idi.mineco.gob.es/portal/site​/MICINN/) and FEDER. JMC received a postdoctoral contract from the Spanish Ministry of Science and Innovation. CCV was a recipient of a Formación de Personal Investigador fellowship from the Spanish Ministry of Science and Innovation