Ancient chloroplast and nuclear genomes provide insights into the evolutionary history of quinoa (chenopodium quinoa willd.)

Quinoa (Chenopodium quinoa), an important crop for the global food security, was domesticated in the Andean highlands of South America about 7,000 years ago, where wild relatives still grow today. Archaeological studies have reported quinoa remains dating back to 4,000 years before present, but the ancient genetic diversity remains uncharacterised. Recent sequencing studies of the quinoa nuclear genome suggested domestication took place independently in highland and coastal environments. However, the origin and exact timing of domestication, and the genomic relationships among the tetraploid relatives (C. hircinumand C. berlandieri) of quinoa are not fully understood. Here, we report the nuclear and chloroplast genome sequences of four ~1,400 years old archaeological samples of C. quinoa from the highlands of northern Argentina. Phylogenetic analyses show thatwild, weedy and cultivated accessions from different species cluster in a monophyletic clade, indicative of historical hybridisation of closely related tetraploid species of Chenopodium. Two of the identified chloroplast haplogroups in the ancient samples appear to be absent from modern quinoa accessions, indicating a genetic bottleneck in the recent past. Further, sequence alignment to the nuclear and chloroplast reference genomes of C. quinoa identified a large number of nucleotide polymorphisms in the ancient specimens, providing resources for further analysis of domestication history as well as genetic changes in loci of breeding value.Fil: Estrada Santamarina, Oscar. University of Adelaide; AustraliaFil: Breen, James. University of Adelaide; AustraliaFil: Mitchell, Kieren J.. University of Adelaide; AustraliaFil: Babot, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucumán. Instituto Superior de Estudios Sociales; ArgentinaFil: Hocsman, Salomón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucumán. Instituto Superior de Estudios Sociales; ArgentinaFil: Jarvis, David. University Brigham Young; Estados UnidosFil: Tester, David. King Abdullah University of Science and Technology; Arabia SauditaFil: Cooper, Alan. University of Adelaide; AustraliaPlant and Animal Genome Conference XXVIISan DiegoEstados UnidosInternational Plant and Animal Genome Conferenc

Detection of Harmful Algal Blooms Using Photopigments and Absorption Signatures: A Case Study of the Florida Red Tide Dinoflagellate, Gymnodinium breve

The utility of photopigments and absorption signatures to detect and enumerate the red tide dinoflagellate, Gymnodinium breve, was evaluated in laboratory cultures and in natural assemblages. The carotenoid, gyroxanthindiester, was an adequate biomarker for G. breve biomass; water‐column concentrations corresponded with cell standing crops and chlorophyll a concentrations during bloom events in Sarasota Bay, Florida. Unlike other carotenoids, the relative abundance of gyroxanthin‐diester did not change throughout a range of physiological states in culture and the gyroxanthin‐diester: chlorophyll a ratio exhibited little variability in a natural assemblage during bloom senescence. Stepwise discriminant analysis indicated that wavelengths indicative of in vivo absorption by accessory chlorophylls and carotenoids could correctly discern spectra of the fucoxanthin‐containing G. breve from spectra of peridinin‐containing dinoflagellates, a diatom, a haptophyte, and a prasinophyte. With the use of a similarity algorithm, the increasing contribution of G. breve was discerned in absorption spectra (and corresponding fourth‐derivative plots) for hypothetical mixed assemblages. However, the absorption properties of chlorophyll c‐containing algae vary little among taxa and it is difficult to discern the contribution of accessory chlorophylls and carotenoids caused by cell packaging. Therefore, the use of absorption spectra alone may not identify the contribution of a chlorophyll c‐containing taxon to the composite spectrum of a mixed assemblage. This difficulty in distinguishing among spectra can be minimized by using the similarity algorithm in conjunction with fourth‐derivative analysis

Novel Timothy Syndrome Mutation Leading to Increase in CACNA1C Window Current

Background Timothy syndrome (TS) is a rare multisystem genetic disorder characterized by a myriad of abnormalities, including QT prolongation, syndactyly, and neurologic symptoms. The predominant genetic causes are recurrent de novo missense mutations in exon 8/8A of the CACNA1C-encoded L-type calcium channel; however, some cases remain genetically elusive. Objective The purpose of this study was to identify the genetic cause of TS in a patient who did not harbor a CACNA1C mutation in exon 8/A, and was negative for all other plausible genetic substrates. Methods Diagnostic exome sequencing was used to identify the genetic substrate responsible for our case of TS. The identified mutation was characterized using whole-cell patch-clamp technique, and the results of these analyses were modeled using a modified Luo–Rudy dynamic model to determine the effects on the cardiac action potential. Results Whole exome sequencing revealed a novel CACNA1C mutation, p.Ile1166Thr, in a young male with diagnosed TS. Functional electrophysiologic analysis identified a novel mechanism of TS-mediated disease, with an overall loss of current density and a gain-of-function shift in activation, leading to an increased window current. Modeling studies of this variant predicted prolongation of the action potential as well as the development of spontaneous early afterdepolarizations. Conclusion Through expanded whole exome sequencing, we identified a novel genetic substrate for TS, p.Ile1166Thr-CACNA1C. Electrophysiologic experiments combined with modeling studies have identified a novel TS mechanism through increased window current. Therefore, expanded genetic testing in cases of TS to the entire CACNA1C coding region, if initial targeted testing is negative, may be warranted

Identification of larval sea basses (Centropristis spp.) using ribosomal DNA-specific molecular assays

This paper is not subject to U.S. copyright. The definitive version was published in Fishery Bulletin 106 (2008): 183-193.The identification of sea bass (Centropristis) larvae to species is difficult because of similar morphological characters, spawning times, and overlapping species ranges. Black sea bass (Centropristis striata) is an important fishery species and is currently considered to be overfished south of Cape Hatteras, North Carolina. We describe methods for identifying three species of sea bass larvae using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays based on species-specific amplification of rDNA internal transcribed spacer reg ions. The assays were tested against DNA of ten other cooccurring reef fish species to ensure the assay’s specificity. Centropristis larvae were collected on three cruises during cross-shelf transects and were used to validate the assays. Seventysix Centropristis larvae were assayed and 69 (91%) were identified successfully. DNA was not amplified from 5% of the larvae and identification was inconclusive for 3% of the larvae. These assays can be used to identify sea bass eggs and larvae and will help to assess spawning locations, spawning times, and larval dispersal.Collection of larvae at sea was supported by funding from the National Science Foundation through OCE 9876565 to C. Jones, S. Thorrold, A. Valle-Levinson, and J. Hare. Additional funding for this project was provided by Office of National Marine Sanctuaries and by Grays Reef National Marine Sanctuary

Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.

BackgroundAdjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC.MethodsWe did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805.FindingsBetween June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment.InterpretationAddition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC.FundingNational Cancer Institute of the National Institutes of Health

Localization and functional consequences of a direct interaction between TRIOBP-1 and hERG/KCNH2 proteins in the heart

Reduced levels of hERG protein and the corresponding repolarizing current IKr can cause arrhythmia and sudden cardiac death, but the underlying cellular mechanisms controlling hERG surface expression are not well understood. We identified TRIOBP-1, an F-actin binding protein previously associated with actin polymerization, as a putative hERG-interacting protein in a yeast-two hybrid screen of a cardiac library. We corroborated this interaction using Forster resonance energy transfer (FRET) in HEK293 cells and co-immunoprecipitation in HEK293 cells and native cardiac tissue. TRIOBP-1 overexpression reduced hERG surface expression and current density, whereas reducing TRIOBP-1 expression via shRNA knockdown resulted in increased hERG protein levels. Immunolabeling in rat cardiomyocytes showed that native TRIOBP-1 overlapped predominantly with myosin binding protein C and secondarily with rat ERG. In human stem cell-derived cardiomyocytes, TRIOBP-1 overexpression caused intracellular co-sequestration of hERG signal, reduced native IKr, and disrupted action potential repolarization. Calcium currents were also reduced to a lesser degree and cell capacitance was increased. These findings establish that TRIOBP-1 interacts directly with hERG and can affect protein levels, IKr magnitude, and cardiac membrane excitability

International criteria for electrocardiographic interpretation in athletes: Consensus statement.

Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly, advanced by a growing body of scientific data and investigations that both examine proposed criteria sets and establish new evidence to guide refinements. On 26-27 February 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington (USA), to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Quinoa phenotyping methodologies: An international consensus

Quinoa is a crop originating in the Andes but grown more widely and with the genetic potential for significant further expansion. Due to the phenotypic plasticity of quinoa, varieties need to be assessed across years and multiple locations. To improve comparability among field trials across the globe and to facilitate collaborations, components of the trials need to be kept consistent, including the type and methods of data collected. Here, an internationally open-access framework for phenotyping a wide range of quinoa features is proposed to facilitate the systematic agronomic, physiological and genetic characterization of quinoa for crop adaptation and improvement. Mature plant phenotyping is a central aspect of this paper, including detailed descriptions and the provision of phenotyping cards to facilitate consistency in data collection. High-throughput methods for multi-temporal phenotyping based on remote sensing technologies are described. Tools for higher-throughput post-harvest phenotyping of seeds are presented. A guideline for approaching quinoa field trials including the collection of environmental data and designing layouts with statistical robustness is suggested. To move towards developing resources for quinoa in line with major cereal crops, a database was created. The Quinoa Germinate Platform will serve as a central repository of data for quinoa researchers globally.Fil: Stanschewski, Clara S.. King Abdullah University of Science and Technology; Arabia SauditaFil: Rey, Elodie. King Abdullah University of Science and Technology; Arabia SauditaFil: Fiene, Gabriele. King Abdullah University of Science and Technology; Arabia SauditaFil: Craine, Evan B.. Washington State University; Estados UnidosFil: Wellman, Gordon. King Abdullah University of Science and Technology; Arabia SauditaFil: Melino, Vanessa J.. King Abdullah University of Science and Technology; Arabia SauditaFil: Patiranage, Dilan S. R.. King Abdullah University of Science and Technology; Arabia SauditaFil: Johansen, Kasper. King Abdullah University of Science and Technology; Arabia SauditaFil: Schmöckel, Sandra M.. King Abdullah University of Science and Technology; Arabia SauditaFil: Bertero, Hector Daniel. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Vegetal. Cátedra de Producción Vegetal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Oakey, Helena. University of Adelaide; AustraliaFil: Colque Little, Carla. Universidad de Copenhagen; DinamarcaFil: Afzal, Irfan. University of Agriculture; PakistánFil: Raubach, Sebastian. The James Hutton Institute; Reino UnidoFil: Miller, Nathan. University of Wisconsin; Estados UnidosFil: Streich, Jared. Oak Ridge National Laboratory; Estados UnidosFil: Amby, Daniel Buchvaldt. Universidad de Copenhagen; DinamarcaFil: Emrani, Nazgol. Christian-albrechts-universität Zu Kiel; AlemaniaFil: Warmington, Mark. Agriculture And Food; AustraliaFil: Mousa, Magdi A. A.. Assiut University; Arabia Saudita. King Abdullah University of Science and Technology; Arabia SauditaFil: Wu, David. Shanxi Jiaqi Agri-Tech Co.; ChinaFil: Jacobson, Daniel. Oak Ridge National Laboratory; Estados UnidosFil: Andreasen, Christian. Universidad de Copenhagen; DinamarcaFil: Jung, Christian. Christian-albrechts-universität Zu Kiel; AlemaniaFil: Murphy, Kevin. Washington State University; Estados UnidosFil: Bazile, Didier. Savoirs, Environnement, Sociétés; Francia. Universite Paul-valery Montpellier Iii; FranciaFil: Tester, Mark. King Abdullah University of Science and Technology; Arabia Saudit

Noncardiac genetic predisposition in sudden infant death syndrome.

PURPOSE: Sudden infant death syndrome (SIDS) is the commonest cause of sudden death of an infant; however, the genetic basis remains poorly understood. We aimed to identify noncardiac genes underpinning SIDS and determine their prevalence compared with ethnically matched controls. METHODS: Using exome sequencing we assessed the yield of ultrarare nonsynonymous variants (minor allele frequency [MAF] ≤0.00005, dominant model; MAF ≤0.01, recessive model) in 278 European SIDS cases (62% male; average age =2.7 ± 2 months) versus 973 European controls across 61 noncardiac SIDS-susceptibility genes. The variants were classified according to American College of Medical Genetics and Genomics criteria. Case-control, gene-collapsing analysis was performed in eight candidate biological pathways previously implicated in SIDS pathogenesis. RESULTS: Overall 43/278 SIDS cases harbored an ultrarare single-nucleotide variant compared with 114/973 controls (15.5 vs. 11.7%, p=0.10). Only 2/61 noncardiac genes were significantly overrepresented in cases compared with controls (ECE1, 3/278 [1%] vs. 1/973 [0.1%] p=0.036; SLC6A4, 2/278 [0.7%] vs. 1/973 [0.1%] p=0.049). There was no difference in yield of pathogenic or likely pathogenic variants between cases and controls (1/278 [0.36%] vs. 4/973 [0.41%]; p=1.0). Gene-collapsing analysis did not identify any specific biological pathways to be significantly associated with SIDS. CONCLUSIONS: A monogenic basis for SIDS amongst the previously implicated noncardiac genes and their encoded biological pathways is negligible