High flavonoid accompanied with high starch accumulation triggered by nutrient starvation in bioenergy crop duckweed (Landoltia punctata)

Background: As the fastest growing plant, duckweed can thrive on anthropogenic wastewater. The purple-backed duckweed, Landoltia punctata, is rich in starch and flavonoids. However, the molecular biological basis of high flavonoid and low lignin content remains largely unknown, as does the best method to combine nutrients removed from sewage and the utilization value improvement of duckweed biomass. Results: A combined omics study was performed to investigate the biosynthesis of flavonoid and the metabolic flux changes in L. punctata grown in different culture medium. Phenylalanine metabolism related transcripts were identified and carefully analyzed. Expression quantification results showed that most of the flavonoid biosynthetic transcripts were relatively highly expressed, while most lignin-related transcripts were poorly expressed or failed to be detected by iTRAQ based proteomic analyses. This explains why duckweed has a much lower lignin percentage and higher flavonoid content than most other plants. Growing in distilled water, expression of most flavonoid-related transcripts were increased, while most were decreased in uniconazole treated L. punctata (1/6 x Hoagland + 800 mg center dot L-1 uniconazole). When L. punctata was cultivated in full nutrient medium (1/6 x Hoagland), more than half of these transcripts were increased, however others were suppressed. Metabolome results showed that a total of 20 flavonoid compounds were separated by HPLC in L. punctata grown in uniconazole and full nutrient medium. The quantities of all 20 compounds were decreased by uniconazole, while 11 were increased and 6 decreased when grown in full nutrient medium. Nutrient starvation resulted in an obvious purple accumulation on the underside of each frond. Conclusions: The high flavonoid and low lignin content of L. punctata appears to be predominantly caused by the flavonoid-directed metabolic flux. Nutrient starvation is the best option to obtain high starch and flavonoid accumulation simultaneously in a short time for biofuels fermentation and natural products isolation

Molecular basis of FAAH-OUT-associated human pain insensitivity

Chronic pain affects millions of people worldwide and new treatments are needed urgently. One way to identify novel analgesic strategies is to understand the biological dysfunctions that lead to human inherited pain insensitivity disorders. Here we report how the recently discovered brain and dorsal root ganglia-expressed FAAH-OUT long non-coding RNA (lncRNA) gene, which was found from studying a pain-insensitive patient with reduced anxiety and fast wound healing, regulates the adjacent key endocannabinoid system gene FAAH, which encodes the anandamide-degrading fatty acid amide hydrolase enzyme. We demonstrate that the disruption in FAAH-OUT lncRNA transcription leads to DNMT1-dependent DNA methylation within the FAAH promoter. In addition, FAAH-OUT contains a conserved regulatory element, FAAH-AMP, that acts as an enhancer for FAAH expression. Furthermore, using transcriptomic analyses in patient-derived cells we have uncovered a network of genes that are dysregulated from disruption of the FAAH-FAAH-OUT axis, thus providing a coherent mechanistic basis to understand the human phenotype observed. Given that FAAH is a potential target for the treatment of pain, anxiety, depression and other neurological disorders, this new understanding of the regulatory role of the FAAH-OUT gene provides a platform for the development of future gene and small molecule therapies

Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing

Diagnostic whole genome sequencing (WGS) is increasingly used in rare diseases. However, standard, semi-automated WGS analysis may overlook diagnoses in complex disorders. Here, we show that specialist multidisciplinary analysis of WGS, following an initial 'no primary findings' (NPF) report, improves diagnostic rates and alters management. We undertook WGS in 102 adults with diagnostically challenging primary mitochondrial disease phenotypes. NPF cases were reviewed by a genomic medicine team, thus enabling bespoke informatic approaches, co-ordinated phenotypic validation, and functional work. We enhanced the diagnostic rate from 16.7% to 31.4%, with management implications for all new diagnoses, and detected strong candidate disease-causing variants in a further 3.9% of patients. This approach presents a standardised model of care that supports mainstream clinicians and enhances diagnostic equity for complex disorders, thereby facilitating access to the potential benefits of genomic healthcare. This research was made possible through access to the data and findings generated by the 100,000 Genomes Project: http://www.genomicsengland.co.uk

Molecular basis of FAAH-OUT-associated human pain insensitivity.

Chronic pain affects millions of people worldwide and new treatments are needed urgently. One way to identify novel analgesic strategies is to understand the biological dysfunctions that lead to human inherited pain insensitivity disorders. Here we report how the recently discovered brain and dorsal root ganglia-expressed FAAH-OUT long non-coding RNA (lncRNA) gene, which was found from studying a pain-insensitive patient with reduced anxiety and fast wound healing, regulates the adjacent key endocannabinoid system gene FAAH, which encodes the anandamide-degrading fatty acid amide hydrolase enzyme. We demonstrate that the disruption in FAAH-OUT lncRNA transcription leads to DNMT1-dependent DNA methylation within the FAAH promoter. In addition, FAAH-OUT contains a conserved regulatory element, FAAH-AMP, that acts as an enhancer for FAAH expression. Furthermore, using transcriptomic analyses in patient-derived cells we have uncovered a network of genes that are dysregulated from disruption of the FAAH-FAAH-OUT axis, thus providing a coherent mechanistic basis to understand the human phenotype observed. Given that FAAH is a potential target for the treatment of pain, anxiety, depression and other neurological disorders, this new understanding of the regulatory role of the FAAH-OUT gene provides a platform for the development of future gene and small molecule therapies.- Medical Research Council/United Kingdom - grant No. [G1100340/MRC_]. - Medical Research Council/United Kingdom - grant No. [MR/R011737/1/MRC_]. - Versus Arthritis/United Kingdom [20200/VAC_]. - Medical Research Council grant [G1100340]. - Medical Research Council grant [MR/R011737/1]. - Qatar University grants [QUSD-CMED-2018/9-3] and [QUCG-CMED-19/20-4]. - Qatar National Research Fund [NPRP13S-0209-200315]. - Versus Arthritis grant [20200]. - Wellcome grant [200183/Z/15/Z]

Search for the Higgs boson in events with missing transverse energy and b quark jets produced in proton-antiproton collisions at s**(1/2)=1.96 TeV

We search for the standard model Higgs boson produced in association with an electroweak vector boson in events with no identified charged leptons, large imbalance in transverse momentum, and two jets where at least one contains a secondary vertex consistent with the decay of b hadrons. We use ~1 fb-1 integrated luminosity of proton-antiproton collisions at s**(1/2)=1.96 TeV recorded by the CDF II experiment at the Tevatron. We find 268 (16) single (double) b-tagged candidate events, where 248 +/- 43 (14.4 +/- 2.7) are expected from standard model background processes. We place 95% confidence level upper limits on the Higgs boson production cross section for several Higgs boson masses ranging from 110 GeV/c2 to 140 GeV/c2. For a mass of 115 GeV/c2 the observed (expected) limit is 20.4 (14.2) times the standard model prediction.Comment: 8 pages, 2 figures, submitted to Phys. Rev. Let

Measurement of WγW\gamma and ZγZ\gamma Production in ppˉp\bar{p} Collisions at s\sqrt{s} = 1.96 TeV

The Standard Model predictions for $W\gamma$ and $Z\gamma$ production are tested using an integrated luminosity of 200 pb$^{-1}$ of \ppbar collision data collected at the Collider Detector at Fermilab. The cross sections are measured selecting leptonic decays of the $W$ and $Z$ bosons, and photons with transverse energy $E_T>7$ GeV that are well separated from leptons. The production cross sections and kinematic distributions for the $W\gamma$ and $Z\gamma$ are compared to SM predictions.Comment: 7 pages, 4 figures, submitted to PR

Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron

We study the underlying event in proton-antiproton collisions by examining the behavior of charged particles (transverse momentum pT > 0.5 GeV/c, pseudorapidity |\eta| < 1) produced in association with large transverse momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan production) or the leading jet (in high-pT jet production) in each event to define three regions of \eta-\phi space; toward, away, and transverse, where \phi is the azimuthal scattering angle. For Drell-Yan production (excluding the leptons) both the toward and transverse regions are very sensitive to the underlying event. In high-pT jet production the transverse region is very sensitive to the underlying event and is separated into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The data are corrected to the particle level to remove detector effects and are then compared with several QCD Monte-Carlo models. The goal of this analysis is to provide data that can be used to test and improve the QCD Monte-Carlo models of the underlying event that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.

Measurement of the Helicity Fractions of W Bosons from Top Quark Decays Using Fully Reconstructed top-antitop Events with CDF II

We present a measurement of the fractions F_0 and F_+ of longitudinally polarized and right-handed W bosons in top quark decays using data collected with the CDF II detector. The data set used in the analysis corresponds to an integrated luminosity of approximately 318 pb -1. We select ttbar candidate events with one lepton, at least four jets, and missing transverse energy. Our helicity measurement uses the decay angle theta*, which is defined as the angle between the momentum of the charged lepton in the W boson rest frame and the W momentum in the top quark rest frame. The cos(theta*) distribution in the data is determined by full kinematic reconstruction of the ttbar candidates. We find F_0 = 0.85 +0.15 -0.22 (stat) +- 0.06 (syst) and F_+ = 0.05 +0.11 -0.05 (stat) +- 0.03 (syst), which is consistent with the standard model prediction. We set an upper limit on the fraction of right-handed W bosons of F_+ < 0.26 at the 95% confidence level.Comment: 11 pages, 2 figures, submitted to Phys. Rev.

Search for a Higgs Boson Produced in Association with a W Boson in pbar-p Collisions at sqrt{s} = 1.96 TeV

We present a search for a standard model Higgs boson produced in association with a W boson using 2.7 1/fb of integrated luminosity of pbar-p collision data taken at sqrt{s} = 1.96 TeV. Limits on the Higgs boson production rate are obtained for masses between 100 GeV and 150 GeV. Through the use of multivariate techniques, the analysis achieves an observed (expected) 95% confidence level upper limit of 5.6 (4.8) times the theoretically expected production cross section for a standard model Higgs boson with a mass of 115 GeV.Comment: submitted to Phys. Rev. Let

Measurement of Ratios of Fragmentation Fractions for Bottom Hadrons in p-pbar Collisions at sqrt{s}=1.96 TeV

This paper describes the first measurement of b-quark fragmentation fractions into bottom hadrons in Run II of the Tevatron Collider at Fermilab. The result is based on a 360 pb-1 sample of data collected with the CDF II detector in p-pbar collisions at sqrt{s}=1.96 TeV. Semileptonic decays of B0, B+, and B_s mesons, as well as Lambda_b baryons, are reconstructed. For an effective bottom hadron p_T threshold of 7 GeV/c, the fragmentation fractions are measured to be f_u/f_d=1.054 +/- 0.018 (stat) +0.025-0.045(sys) +/- 0.058 (Br), f_s/(f_u+f_d)=0.160 +/- 0.005 (stat) +0.011-0.010 (sys) +0.057-0.034 (Br), and f_{Lambda_b}/(f_u+f_d)=0.281\pm0.012 (stat) +0.058-0.056 (sys) +0.128-0.086 (Br), where the uncertainty (Br) is due to uncertainties on measured branching ratios. The value of f_s/(f_u+f_d) agrees within one standard deviation with previous CDF measurements and the world average of this quantity, which is dominated by LEP measurements. However, the ratio f_{Lambda_b}/(f_u+f_d) is approximately twice the value previously measured at LEP. The approximately 2 sigma discrepancy is examined in terms of kinematic differences between the two production environments.Comment: Submitted to PRD, 54 pages, 53 plot