Characterization of Hessian fly from Israel

Mayetiola destructor Say, the Hessian fly, is a gall midge and a member of the Dipteran family Cecidomyiidae. It is a common pest of wheat found throughout all of the major wheat growing areas of the world and poses a serious economic threat to the United States (US), particularly in the Southeast winter wheat region. Damage to wheat is done solely by feeding first and second in-star larvae. Hessian fly (Hf) infestations result in a loss in grain yield by the stunting and/or killing of seedling wheat plants in the winter and by causing breakage at the nodes of the plant in the spring. Feeding begins as the larvae settles at the base of the plant and establishes a feeding site by creating a layer nutritive tissue. Control of Hf in the US is primarily performed through avoidance by planting after the bulk emergence of the fly and through planting resistant wheat cultivars which contain a Hf-specific R gene. In Israel, Hf is found throughout the primary agricultural region but is not considered an economic threat. No cultural practices are used to control the insect, and Hf resistant wheat cultivars are not deployed in commercial agriculture. Native grasses and wild wheat progenitors that can serve as alternative hosts are readily available in non-cultivated areas. The sampling Hf in Israel will provide information from a Mediterranean population which is as close to Fertile Crescent, the center of origin to both Hf and the domestication of wheat, as can be currently sampled. This will allow the examination of population structure in Israel, of differential expression of effector proteins, of virulence to Hf R genes when resistant wheat cultivars are not deployed, and of the genetic inheritance of avirulence genes (Avr) in virulent Hf. This will allow advancement in the understanding of the Hf-wheat interaction that can be used to create more effective and long-lasting control of Hf in US. Samples of a dipteran pest of wheat from multiple locations in the agricultural area of Israel were tested to confirm identity, describe local populations and suggest the use of deploying resistance (R) genes in wheat cultivars for control of Hf. Morphological evaluation of adults and a free-choice oviposition preference test documenting that females overwhelmingly preferred to oviposit on wheat instead of barley supported the identification of the Israeli samples as Hf. Using the cytochrome c oxidase subunit I (coxI), the Barcoding Region, nine haplotypes were revealed. These results supported the identification of Hf as all nine haplotypes fell within a single clade that was significantly separated from other gall midge species including Mayetiola hordei. A greenhouse culture was established for one of the sampling locations, Magen, and it was evaluated for virulence to 19 different R genes. .Magen was significantly virulent to 11 of the 19 R genes tested, and complementation analysis documented that, for four of the R genes tested, the Israeli Hf shared loci for virulence with Hf from the US. Levels of Hf infestation at seven Israeli fields were at least at the 5-8% level, which historically has indicated a significant yield loss. Microsatellite genotyping of the five Hf collections from Israel revealed two mixed populations in Israel that are distinctly separate from the single population in Syria. Evidence is emerging that some proteins secreted by gall forming plant-parasites act as effectors responsible for systemic changes in the host plant, such as galling and nutrient tissue formation. A large number of secreted salivary gland proteins (SSGPs), the putative effectors responsible for the physiological changes elicited in susceptible seedling wheat by Hf larvae, have been documented. However, how the genes encoding these candidate effectors might respond under field conditions is unknown. Microarray analysis was performed to investigate variation in SSGP transcript abundance among field collections from different geographic regions (southeastern US, central US, and the Mediterranean). Results revealed significant variation in SSGP transcript abundance among the field collections studied. The field collections separated into three distinct groups that corresponded to the wheat classes grown in the different geographic regions as well as to recently described Hessian fly populations. These data support previous reports correlating Hessian fly population structure with micropopulation differences due to agro-ecosystem parameters such as cultivation of regionally adapted wheat varieties, deployment of resistance genes, and variation in climatic conditions. Hf larvae produce a large number of secreted salivary effector proteins involved in effector triggered immunity that elicit systemic changes in susceptible wheat as well as trigger the defense response in resistant wheat. One of the avirulence effectors responsible for the interaction between Hf larvae and resistance gene H13 in wheat has recently been cloned and characterized using Hf populations from the US. Within the US, virulence is a sex-linked, recessive trait and was shown to be associated with three independent insertions that resulted in a loss of expression of the avirulence gene. Genetic crosses testing for the inheritance of virulence to H13 in Hf from Israel revealed that it is controlled by a sex-linked, recessive trait at a single loci. Additionally, no complementation occurred between crosses of virulent US and virulent Israeli Hf, supporting the hypothesis that virulence resides at the same locus in both populations. However, no insertions were identified in the coding region nor upstream or downstream of the coding region. Further, no single nucleotide polymorphisms or frame shifts corresponding to virulence were identified. These data suggest the molecular basis of virulence in the Israeli population to resistance gene H13 in wheat is not the same as in the US. As the most effective form of Hf control employs the planting of resistant wheat cultivars containing one or more H genes, frequent Hf sampling is required to monitor the level of virulence present in locally adapted populations. A novel assay for detecting virulence in the field was created by sampling Hf males using sticky traps baited with Hf sex pheromone and the molecular marker for virulence to H13. The Hf gene that controls virulence in Hf to resistance gene H13 in wheat has recently been cloned and characterized, and diagnostic molecular markers for the alleles controlling avirulence and virulence are now available. Utilizing two separate PCR reactions, the six alleles for avirulence and virulence can be scored based on band size on a 2% agarose gel. The results support the most recent survey of virulence to H13 as scored through the testing of live insects infesting H13 wheat in the greenhouse. Throughout the southeast, all three avirulence alleles can be identified while the most frequently identified allele for virulence corresponded to a 5kb insertion into exon 1 of vH13. In South Carolina, the PCR assay is sensitive enough to detect the spread of virulence into two counties previously documented as 100% susceptible to H13

Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease

Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of Aβ plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with Aβ plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than Aβ and tau measures. Our results highlight the multifaceted landscape of AD pathophysiology and its temporal evolution. Such knowledge will be critical for developing precision therapeutic interventions and biomarkers for AD beyond those associated with Aβ and tau.Fil: Johnson, Erik C. B.. University of Emory; Estados UnidosFil: Bian, Shijia. University of Emory; Estados UnidosFil: Haque, Rafi U.. University of Emory; Estados UnidosFil: Carter, E. Kathleen. University of Emory; Estados UnidosFil: Watson, Caroline M.. University of Emory; Estados UnidosFil: Gordon, Brian A.. Washington University in St. Louis; Estados UnidosFil: Ping, Lingyan. University of Emory; Estados UnidosFil: Duong, Duc M.. University of Emory; Estados UnidosFil: Epstein, Michael P.. University of Emory; Estados UnidosFil: McDade, Eric. Washington University in St. Louis; Estados UnidosFil: Barthélemy, Nicolas R.. Washington University in St. Louis; Estados UnidosFil: Karch, Celeste M.. Washington University in St. Louis; Estados UnidosFil: Xiong, Chengjie. Washington University in St. Louis; Estados UnidosFil: Cruchaga, Carlos. Washington University in St. Louis; Estados UnidosFil: Perrin, Richard J.. Washington University in St. Louis; Estados UnidosFil: Wingo, Aliza P.. Washington University in St. Louis; Estados UnidosFil: Wingo, Thomas S.. University of Emory; Estados UnidosFil: Chhatwal, Jasmeer P.. Harvard Medical School; Estados UnidosFil: Day, Gregory S.. University of Emory; Estados UnidosFil: Noble, James M.. Harvard Medical School; Estados UnidosFil: Berman, Sarah B.. Mayo Clinic; Estados UnidosFil: Martins, Ralph. Edith Cowan University; AustraliaFil: Graff Radford, Neill R.. Univeristy of Pittsburgh. School of Medicine; Estados Unidos. Mayo Clinic; Estados UnidosFil: Surace, Ezequiel Ignacio. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ortiz, Ana Luisa Sosa. Washington University in St. Louis; Estados UnidosFil: Daniels, Alisha. Washington University in St. Louis; Estados UnidosFil: Courtney, Laura. Washington University in St. Louis; Estados UnidosFil: Supnet Bell, Charlene. Washington University in St. Louis; Estados UnidosFil: Xu, Jinbin. No especifíca;Fil: Ringman, John. No especifíca

Genes Expressed in Specific Areas of the Human Fetal Cerebral Cortex Display Distinct Patterns of Evolution

The developmental mechanisms through which the cerebral cortex increased in size and complexity during primate evolution are essentially unknown. To uncover genetic networks active in the developing cerebral cortex, we combined three-dimensional reconstruction of human fetal brains at midgestation and whole genome expression profiling. This novel approach enabled transcriptional characterization of neurons from accurately defined cortical regions containing presumptive Broca and Wernicke language areas, as well as surrounding associative areas. We identified hundreds of genes displaying differential expression between the two regions, but no significant difference in gene expression between left and right hemispheres. Validation by qRTPCR and in situ hybridization confirmed the robustness of our approach and revealed novel patterns of area- and layer-specific expression throughout the developing cortex. Genes differentially expressed between cortical areas were significantly associated with fast-evolving non-coding sequences harboring human-specific substitutions that could lead to divergence in their repertoires of transcription factor binding sites. Strikingly, while some of these sequences were accelerated in the human lineage only, many others were accelerated in chimpanzee and/or mouse lineages, indicating that genes important for cortical development may be particularly prone to changes in transcriptional regulation across mammals. Genes differentially expressed between cortical regions were also enriched for transcriptional targets of FoxP2, a key gene for the acquisition of language abilities in humans. Our findings point to a subset of genes with a unique combination of cortical areal expression and evolutionary patterns, suggesting that they play important roles in the transcriptional network underlying human-specific neural traits

Ensemble Analysis of Angiogenic Growth in Three-Dimensional Microfluidic Cell Cultures

We demonstrate ensemble three-dimensional cell cultures and quantitative analysis of angiogenic growth from uniform endothelial monolayers. Our approach combines two key elements: a micro-fluidic assay that enables parallelized angiogenic growth instances subject to common extracellular conditions, and an automated image acquisition and processing scheme enabling high-throughput, unbiased quantification of angiogenic growth. Because of the increased throughput of the assay in comparison to existing three-dimensional morphogenic assays, statistical properties of angiogenic growth can be reliably estimated. We used the assay to evaluate the combined effects of vascular endothelial growth factor (VEGF) and the signaling lipid sphingoshine-1-phosphate (S1P). Our results show the importance of S1P in amplifying the angiogenic response in the presence of VEGF gradients. Furthermore, the application of S1P with VEGF gradients resulted in angiogenic sprouts with higher aspect ratio than S1P with background levels of VEGF, despite reduced total migratory activity. This implies a synergistic effect between the growth factors in promoting angiogenic activity. Finally, the variance in the computed angiogenic metrics (as measured by ensemble standard deviation) was found to increase linearly with the ensemble mean. This finding is consistent with stochastic agent-based mathematical models of angiogenesis that represent angiogenic growth as a series of independent stochastic cell-level decisions

VERITAS discovery of very high energy gamma-ray emission from S3 1227+25 and multiwavelength observations

We report the detection of very high energy gamma-ray emission from the blazar S3 1227+25 (VER J1230+253) with the Very Energetic Radiation Imaging Telescope Array System (VERITAS). VERITAS observations of the source were triggered by the detection of a hard-spectrum GeV flare on May 15, 2015 with the Fermi-Large Area Telescope (LAT). A combined five-hour VERITAS exposure on May 16th and May 18th resulted in a strong 13$\sigma$ detection with a differential photon spectral index, $\Gamma$ = 3.8 $\pm$ 0.4, and a flux level at 9% of the Crab Nebula above 120 GeV. This also triggered target of opportunity observations with Swift, optical photometry, polarimetry and radio measurements, also presented in this work, in addition to the VERITAS and Fermi-LAT data. A temporal analysis of the gamma-ray flux during this period finds evidence of a shortest variability timescale of $\tau_{obs}$ = 6.2 $\pm$ 0.9 hours, indicating emission from compact regions within the jet, and the combined gamma-ray spectrum shows no strong evidence of a spectral cut-off. An investigation into correlations between the multiwavelength observations found evidence of optical and gamma-ray correlations, suggesting a single-zone model of emission. Finally, the multiwavelength spectral energy distribution is well described by a simple one-zone leptonic synchrotron self-Compton radiation model.Comment: 18 pages, 6 figures. Accepted for publication in the Astrophysical Journal (ApJ

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Characteristics of Adults in the Hepatitis B Research Network in North America Reflect Their Country of Origin and Hepatitis B Virus Genotype

Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the US and Canada might be disproportionately affected. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant