Intracellular interferons in fish : a unique means to combat viral infection

Peer reviewedPublisher PD

Multifield Dynamics in Higgs-otic Inflation

In Higgs-otic inflation a complex neutral scalar combination of the $h^0$ and $H^0$ MSSM Higgs fields plays the role of inflaton in a chaotic fashion. The potential is protected from large trans-Planckian corrections at large inflaton if the system is embedded in string theory so that the Higgs fields parametrize a D-brane position. The inflaton potential is then given by a DBI+CS D-brane action yielding an approximate linear behaviour at large field. The inflaton scalar potential is a 2-field model with specific non-canonical kinetic terms. Previous computations of the cosmological parameters (i.e. scalar and tensor perturbations) did not take into account the full 2-field character of the model, ignoring in particular the presence of isocurvature perturbations and their coupling to the adiabatic modes. It is well known that for generic 2-field potentials such effects may significantly alter the observational signatures of a given model. We perform a full analysis of adiabatic and isocurvature perturbations in the Higgs-otic 2-field model. We show that the predictivity of the model is increased compared to the adiabatic approximation. Isocurvature perturbations moderately feed back into adiabatic fluctuations. However, the isocurvature component is exponentially damped by the end of inflation. The tensor to scalar ratio varies in a region $r=0.08-0.12$, consistent with combined Planck/BICEP results.Comment: 35 pages, 11 figure

A first generation BAC-based physical map of the rainbow trout genome

Background: Rainbow trout (Oncorhynchus mykiss) are the most-widely cultivated cold freshwater fish in the world and an important model species for many research areas. Coupling great interest in this species as a research model with the need for genetic improvement of aquaculture production efficiency traits justifies the continued development of genomics research resources. Many quantitative trait loci (QTL) have been identified for production and life-history traits in rainbow trout. A bacterial artificial chromosome (BAC) physical map is needed to facilitate fine mapping of QTL and the selection of positional candidate genes for incorporation in marker-assisted selection (MAS) for improving rainbow trout aquaculture production. This resource will also facilitate efforts to obtain and assemble a whole-genome reference sequence for this species.[br/] Results: The physical map was constructed from DNA fingerprinting of 192,096 BAC clones using the 4-color high-information content fingerprinting (HICF) method. The clones were assembled into physical map contigs using the finger-printing contig (FPC) program. The map is composed of 4,173 contigs and 9,379 singletons. The total number of unique fingerprinting fragments (consensus bands) in contigs is 1,185,157, which corresponds to an estimated physical length of 2.0 Gb. The map assembly was validated by 1) comparison with probe hybridization results and agarose gel fingerprinting contigs; and 2) anchoring large contigs to the microsatellite-based genetic linkage map.[br/] Conclusion: The production and validation of the first BAC physical map of the rainbow trout genome is described in this paper. We are currently integrating this map with the NCCCWA genetic map using more than 200 microsatellites isolated from BAC end sequences and by identifying BACs that harbor more than 300 previously mapped markers. The availability of an integrated physical and genetic map will enable detailed comparative genome analyses, fine mapping of QTL, positional cloning, selection of positional candidate genes for economically important traits and the incorporation of MAS into rainbow trout breeding programs

Transplanckian axions !?

We discuss quantum gravitational effects in Einstein theory coupled to periodic axion scalars to analyze the viability of several proposals to achieve superplanckian axion periods (aka decay constants) and their possible application to large field inflation models. The effects we study correspond to the nucleation of euclidean gravitational instantons charged under the axion, and our results are essentially compatible with (but independent of) the Weak Gravity Conjecture, as follows: Single axion theories with superplanckian periods contain gravitational instantons inducing sizable higher harmonics in the axion potential, which spoil superplanckian inflaton field range. A similar result holds for multi-axion models with lattice alignment (like the Kim-Nilles-Peloso model). Finally, theories with $N$ axions can still achieve a moderately superplanckian periodicity (by a $\sqrt{N}$ factor) with no higher harmonics in the axion potential. The Weak Gravity Conjecture fails to hold in this case due to the absence of some instantons, which are forbidden by a discrete $\mathbf{Z}_N$ gauge symmetry. Finally we discuss the realization of these instantons as euclidean D-branes in string compactifications.Comment: 46 pages, 6 figures. Added references, clarifications, and missing factor of 1/2 to instanton action. Conclusions unchange

Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial.

IMPORTANCE: Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Most patients die within 1 to 2 years of diagnosis. Tumor-treating fields (TTFields) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly. OBJECTIVE: To evaluate the efficacy and safety of TTFields used in combination with temozolomide maintenance treatment after chemoradiation therapy for patients with glioblastoma. DESIGN, SETTING, AND PARTICIPANTS: After completion of chemoradiotherapy, patients with glioblastoma were randomized (2:1) to receive maintenance treatment with either TTFields plus temozolomide (n = 466) or temozolomide alone (n = 229) (median time from diagnosis to randomization, 3.8 months in both groups). The study enrolled 695 of the planned 700 patients between July 2009 and November 2014 at 83 centers in the United States, Canada, Europe, Israel, and South Korea. The trial was terminated based on the results of this planned interim analysis. INTERVENTIONS: Treatment with TTFields was delivered continuously (>18 hours/day) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device. Temozolomide (150-200 mg/m2/d) was given for 5 days of each 28-day cycle. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival in the intent-to-treat population (significance threshold of .01) with overall survival in the per-protocol population (n = 280) as a powered secondary end point (significance threshold of .006). This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up. RESULTS: The interim analysis included 210 patients randomized to TTFields plus temozolomide and 105 randomized to temozolomide alone, and was conducted at a median follow-up of 38 months (range, 18-60 months). Median progression-free survival in the intent-to-treat population was 7.1 months (95% CI, 5.9-8.2 months) in the TTFields plus temozolomide group and 4.0 months (95% CI, 3.3-5.2 months) in the temozolomide alone group (hazard ratio [HR], 0.62 [98.7% CI, 0.43-0.89]; P = .001). Median overall survival in the per-protocol population was 20.5 months (95% CI, 16.7-25.0 months) in the TTFields plus temozolomide group (n = 196) and 15.6 months (95% CI, 13.3-19.1 months) in the temozolomide alone group (n = 84) (HR, 0.64 [99.4% CI, 0.42-0.98]; P = .004). CONCLUSIONS AND RELEVANCE: In this interim analysis of 315 patients with glioblastoma who had completed standard chemoradiation therapy, adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00916409

Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial.

Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor. To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system. In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis. Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz frequency, alternating electric fields, was delivered (≥ 18 hours/d) via 4 transducer arrays on the shaved scalp and connected to a portable device. Temozolomide was administered to both groups (150-200 mg/m2) for 5 days per 28-day cycle (6-12 cycles). Progression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group. Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P < .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P < .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone. In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis. clinicaltrials.gov Identifier: NCT00916409

A First Generation BAC-Based Physical Map of the Asian Seabass (Lates calcarifer)

BACKGROUND: The Asian seabass (Lates calcarifer) is an important marine foodfish species in Southeast Asia and Australia. Genetic improvement of this species has been achieved to some extent through selective breeding programs since 1990s. Several genomic tools such as DNA markers, a linkage map, cDNA and BAC libraries have been developed to assist selective breeding. A physical map is still lacking, although it is essential for positional cloning of genes located in quantitative trait loci (QTL) and assembly of whole genome sequences. METHODOLOGY/PRINCIPAL FINDINGS: A genome-wide physical map of the Asian seabass was constructed by restriction fingerprinting of 38,208 BAC clones with SNaPshot HICF FPC technique. A total of 30,454 were assembled into 2,865 contigs. The physical length of the assembled contigs summed up to 665 Mb. Analyses of some contigs using different methods demonstrated the reliability of the assembly. CONCLUSIONS/SIGNIFICANCE: The present physical map is the first physical map for Asian seabass. This physical map will facilitate the fine mapping of QTL for economically important traits and the positional cloning of genes located in QTL. It will also be useful for the whole genome sequencing and assembly. Detailed information about BAC-contigs and BAC clones are available upon request

An association between Helicobacter pylori infection and cognitive function in children at early school age: a community-based study

<p>Abstract</p> <p>Background</p> <p><it>H. pylori </it>infection has been linked to iron deficiency anemia, a risk factor of diminished cognitive development. The hypothesis on an association between <it>H. pylori </it>infection and cognitive function was examined in healthy children, independently of socioeconomic and nutritional factors.</p> <p>Methods</p> <p>A community-based study was conducted among 200 children aged 6-9 years, from different socioeconomic background. <it>H. pylori </it>infection was examined by an ELISA kit for detection of <it>H. pylori </it>antigen in stool samples. Cognitive function of the children was blindly assessed using Stanford-Benit test 5^thedition, yielding IQ scores. Data on socioeconomic factors and nutritional covariates were collected through maternal interviews and from medical records. Multivariate linear regression analysis was performed to obtain adjusted beta coefficients.</p> <p>Results</p> <p><it>H. pylori </it>infection was associated with lower IQ scores only in children from a relatively higher socioeconomic community; adjusted beta coefficient -6.1 (95% CI -11.4, -0.8) (P = 0.02) for full-scale IQ score, -6.0 (95% CI -11.1, -0.2) (P = 0.04) for non-verbal IQ score and -5.7 (95% CI -10.8, -0.6) (P = 0.02) for verbal IQ score, after controlling for potential confounders.</p> <p>Conclusions</p> <p><it>H. pylori </it>infection might be negatively involved in cognitive development at early school age. Further studies in other populations with larger samples are needed to confirm this novel finding.</p

A genetically anchored physical framework for Theobroma cacao cv. Matina 1-6

<p>Abstract</p> <p>Background</p> <p>The fermented dried seeds of <it>Theobroma cacao </it>(cacao tree) are the main ingredient in chocolate. World cocoa production was estimated to be 3 million tons in 2010 with an annual estimated average growth rate of 2.2%. The cacao bean production industry is currently under threat from a rise in fungal diseases including black pod, frosty pod, and witches' broom. In order to address these issues, genome-sequencing efforts have been initiated recently to facilitate identification of genetic markers and genes that could be utilized to accelerate the release of robust <it>T. cacao </it>cultivars. However, problems inherent with assembly and resolution of distal regions of complex eukaryotic genomes, such as gaps, chimeric joins, and unresolvable repeat-induced compressions, have been unavoidably encountered with the sequencing strategies selected.</p> <p>Results</p> <p>Here, we describe the construction of a BAC-based integrated genetic-physical map of the <it>T. cacao </it>cultivar Matina 1-6 which is designed to augment and enhance these sequencing efforts. Three BAC libraries, each comprised of 10× coverage, were constructed and fingerprinted. 230 genetic markers from a high-resolution genetic recombination map and 96 Arabidopsis-derived conserved ortholog set (COS) II markers were anchored using pooled overgo hybridization. A dense tile path consisting of 29,383 BACs was selected and end-sequenced. The physical map consists of 154 contigs and 4,268 singletons. Forty-nine contigs are genetically anchored and ordered to chromosomes for a total span of 307.2 Mbp. The unanchored contigs (105) span 67.4 Mbp and therefore the estimated genome size of <it>T. cacao </it>is 374.6 Mbp. A comparative analysis with <it>A. thaliana, V. vinifera</it>, and <it>P. trichocarpa </it>suggests that comparisons of the genome assemblies of these distantly related species could provide insights into genome structure, evolutionary history, conservation of functional sites, and improvements in physical map assembly. A comparison between the two <it>T. cacao </it>cultivars Matina 1-6 and Criollo indicates a high degree of collinearity in their genomes, yet rearrangements were also observed.</p> <p>Conclusions</p> <p>The results presented in this study are a stand-alone resource for functional exploitation and enhancement of <it>Theobroma cacao </it>but are also expected to complement and augment ongoing genome-sequencing efforts. This resource will serve as a template for refinement of the <it>T. cacao </it>genome through gap-filling, targeted re-sequencing, and resolution of repetitive DNA arrays.</p

Single nucleotide polymorphism discovery in rainbow trout by deep sequencing of a reduced representation library

<p>Abstract</p> <p>Background</p> <p>To enhance capabilities for genomic analyses in rainbow trout, such as genomic selection, a large suite of polymorphic markers that are amenable to high-throughput genotyping protocols must be identified. Expressed Sequence Tags (ESTs) have been used for single nucleotide polymorphism (SNP) discovery in salmonids. In those strategies, the salmonid semi-tetraploid genomes often led to assemblies of paralogous sequences and therefore resulted in a high rate of false positive SNP identification. Sequencing genomic DNA using primers identified from ESTs proved to be an effective but time consuming methodology of SNP identification in rainbow trout, therefore not suitable for high throughput SNP discovery. In this study, we employed a high-throughput strategy that used pyrosequencing technology to generate data from a reduced representation library constructed with genomic DNA pooled from 96 unrelated rainbow trout that represent the National Center for Cool and Cold Water Aquaculture (NCCCWA) broodstock population.</p> <p>Results</p> <p>The reduced representation library consisted of 440 bp fragments resulting from complete digestion with the restriction enzyme <it>Hae</it>III; sequencing produced 2,000,000 reads providing an average 6 fold coverage of the estimated 150,000 unique genomic restriction fragments (300,000 fragment ends). Three independent data analyses identified 22,022 to 47,128 putative SNPs on 13,140 to 24,627 independent contigs. A set of 384 putative SNPs, randomly selected from the sets produced by the three analyses were genotyped on individual fish to determine the validation rate of putative SNPs among analyses, distinguish apparent SNPs that actually represent paralogous loci in the tetraploid genome, examine Mendelian segregation, and place the validated SNPs on the rainbow trout linkage map. Approximately 48% (183) of the putative SNPs were validated; 167 markers were successfully incorporated into the rainbow trout linkage map. In addition, 2% of the sequences from the validated markers were associated with rainbow trout transcripts.</p> <p>Conclusion</p> <p>The use of reduced representation libraries and pyrosequencing technology proved to be an effective strategy for the discovery of a high number of putative SNPs in rainbow trout; however, modifications to the technique to decrease the false discovery rate resulting from the evolutionary recent genome duplication would be desirable.</p