Modeling cancer metabolism on a genome scale

Cancer cells have fundamentally altered cellular metabolism that is associated with their tumorigenicity and malignancy. In addition to the widely studied Warburg effect, several new key metabolic alterations in cancer have been established over the last decade, leading to the recognition that altered tumor metabolism is one of the hallmarks of cancer. Deciphering the full scope and functional implications of the dysregulated metabolism in cancer requires both the advancement of a variety of omics measurements and the advancement of computational approaches for the analysis and contextualization of the accumulated data. Encouragingly, while the metabolic network is highly interconnected and complex, it is at the same time probably the best characterized cellular network. Following, this review discusses the challenges that genome‐scale modeling of cancer metabolism has been facing. We survey several recent studies demonstrating the first strides that have been done, testifying to the value of this approach in portraying a network‐level view of the cancer metabolism and in identifying novel drug targets and biomarkers. Finally, we outline a few new steps that may further advance this field

Application of genomic and quantitative genetic tools to identify candidate resistance genes for brown rot resistance in peach.

The availability of a complete peach genome assembly and three different peach genome sequences created by our group provide new opportunities for application of genomic data and can improve the power of the classical Quantitative Trait Loci (QTL) approaches to identify candidate genes for peach disease resistance. Brown rot caused by Monilinia spp., is the most important fungal disease of stone fruits worldwide. Improved levels of peach fruit rot resistance have been identified in some cultivars and advanced selections developed in the UC Davis and USDA breeding programs. Whole genome sequencing of the Pop-DF parents lead to discovery of high-quality SNP markers for QTL genome scanning in this experimental population. Pop-DF created by crossing a brown rot moderately resistant cultivar 'Dr. Davis' and a brown rot resistant introgression line, 'F8,1-42', derived from an initial almond × peach interspecific hybrid, was evaluated for brown rot resistance in fruit of harvest maturity over three seasons. Using the SNP linkage map of Pop-DF and phenotypic data collected with inoculated fruit, a genome scan for QTL identified several SNP markers associated with brown rot resistance. Two of these QTLs were placed on linkage group 1, covering a large (physical) region on chromosome 1. The genome scan for QTL and SNP effects predicted several candidate genes associated with disease resistance responses in other host-pathogen systems. Two potential candidate genes, ppa011763m and ppa026453m, may be the genes primarily responsible for M. fructicola recognition in peach, activating both PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI) responses. Our results provide a foundation for further genetic dissection, marker assisted breeding for brown rot resistance, and development of peach cultivars resistant to brown rot

Comunicación corta. Diferenciación de cepas vacunales del virus del síndrome reproductor y respiratorio porcino de tipo I y cepas de campo por análisis de polimorfismos en la longitud de fragmentos de restricción

The use of modified live virus (MLV) vaccines is a common procedure to control porcine reproductive and respiratory syndrome virus (PRRSV) infection in the great majority of countries from America, Asia and Europe, including Spain. Current discriminatory techniques allow the detection of different MLV type-II vaccine strains. Herein we report a rapid and accurate technique aimed to discriminate between MLV type-I vaccine strains and Spanish field strains. This technique comprises a reverse transcription (RT) and nested polymerase chain reaction (nPCR) amplification of PRRSV ORF5 followed by a digestion of RT-nPCR products with two specific endonucleases, ItaI and AccI. Combined utilization of ItaI and AccI generates restriction fragments length polymorphisms (RFLP) patterns adequate for the differentiation of 30 Spanish field isolates, of which 12 were isolated between 1991 and 1995 and 18 between 2000 and 2003. These different RFLP patterns can be used to distinguish unequivocally between Spanish field strains of PRRSV and the three MLV type-I vaccines used in Spain: AmervacPRRS®, Pyrsvac-183® and PorcilisPRRS®.Para controlar la infección por el virus del síndrome reproductor y respiratorio porcino (PRRSV), en la gran mayoría de países de América, Asia y Europa, incluyendo España, se usan frecuentemente vacunas basadas en virus vivos modificados (MLV). En la actualidad existen técnicas discriminatorias que permiten detectar cepas vacunales del PRRSV de tipo II. El presente trabajo describe una técnica precisa y rápida para la diferenciación de cepas vacunales de tipo I del PRRSV y cepas de campo españolas. Esta técnica se basa en la transcripción reversa y posterior amplificación de la ORF5 del genoma del PRRSV utilizando la reacción en cadena de la polimerasa anidada, seguida de la digestión de los amplicones generados con dos endonucleasas específicas: ItaI y AccI. La utilización combinada de ambas enzimas genera patrones de polimorfismos en la longitud de fragmentos de restricción (RFLP), adecuados para la distinción de las 30 cepas de campo usadas, de las cuales 12 fueron aisladas entre 1991 y 1995 y 18 entre 2000 y 2003. Estos diferentes patrones pueden ser utilizados para distinguir entre cepas de campo españolas del PRRSV y las tres cepas vacunales de tipo I usadas en España: AmervacPRRS®, Pyrsvac-183® y PorcilisPRRS®

Observation of a New Excited Ds+ Meson in B0 →d-D+K+π-Decays

Using pp collision data corresponding to an integrated luminosity of 5.4 fb−1 collected with the LHCb detector at a center-of-mass energy of 13 TeV, the B0 → D−DþKþπ− decay is studied. A new excited Dþ s meson is observed decaying into the DþKþπ− final state with large statistical significance. The pole mass and width, and the spin parity of the new state are measured with an amplitude analysis to be mR ¼ 2591 6 7 MeV, ΓR ¼ 89 16 12 MeV, and JP ¼ 0−, where the first uncertainty is statistical and the second systematic. Fit fractions for all components in the amplitude analysis are also reported. The new resonance, denoted as Ds0ð2590Þþ, is a strong candidate to be the Dsð21 S0Þþ state, the radial excitation of the pseudoscalar ground-state Dþ s meson

Observation of Multiplicity Dependent Prompt χc1 (3872) and ψ (2S) Production in pp Collisions

The production of χc1(3872) and ψ(2S) hadrons is studied as a function of charged particle multiplicity in pp collisions at a center-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 2 fb−1 . For both states, the fraction that is produced promptly at the collision vertex is found to decrease as charged particle multiplicity increases. The ratio of χc1(3872) to ψ(2S) cross-sections for promptly produced particles is also found to decrease with multiplicity, while no significant dependence on multiplicity is observed for the equivalent ratio of particles produced away from the collision vertex in b-hadron decays. This behavior is consistent with a calculation that models the χc1(3872) structure as a compact tetraquark. Implications for the binding energy of the χc1(3872) state are discussed

Measurement of CP observables in B± → D(*)K± and B± → D(*) π ± decays using two-body D final states

Measurements of CP observables in B± → D(∗)K± and B± → D(∗)π ± decays are presented, where D(∗) indicates a neutral D or D∗ meson that is an admixture of meson and anti-meson states. Decays of the D(∗) meson to the Dπ0 and Dγ final states are partially reconstructed without inclusion of the neutral pion or photon. Decays of the D meson are reconstructed in the K±π ∓, K+K−, and π +π − final states. The analysis uses a sample of charged B mesons produced in proton-proton collisions and collected with the LHCb experiment, corresponding to integrated luminosities of 2.0, 1.0, and 5.7 fb−1 taken at centre-of-mass energies of 7, 8, and 13 TeV, respectively. The measurements of partially reconstructed B± → D(∗)K± and B± → D(∗)π ± with D → K∓π ± decays are the first of their kind, and a first observation of the B± → (Dπ0 )D∗ π ± decay is made with a significance of 6.1 standard deviations. All CP observables are measured with world-best precision, and in combination with other LHCb results will provide strong constraints on the CKM angle

Search for CP violation in D(s)+→h+π0 and D(s)+→h+η decays

Searches for CP violation in the two-body decays D + (s) → h +π 0 and D + (s) → h +η (where h + denotes a π + or K+ meson) are performed using pp collision data collected by the LHCb experiment corresponding to either 9 fb−1 or 6 fb−1 of integrated luminosity. The π 0 and η mesons are reconstructed using the e +e −γ final state, which can proceed as three-body decays π 0 → e +e −γ and η → e +e −γ, or via the two-body decays π 0 → γγ and η → γγ followed by a photon conversion. The measurements are made relative to the control modes D + (s)→ K0 S h + to cancel the production and detection asymmetries. The CP asymmetries are measured to b

Observation of the decay Λb0 → χc1pπ−

The Cabibbo-suppressed decay Λ 0 b → χc1pπ − is observed for the first time using data from proton-proton collisions corresponding to an integrated luminosity of 6 fb−1 , collected with the LHCb detector at a centre-of-mass energy of 13 TeV. Evidence for the Λ 0 b → χc2pπ − decay is also found. Using the Λ 0 b → χc1pK− decay as normalisation channel, the ratios of branching fractions are measured to be B Λ 0 b → χc1pπ − B Λ0 b → χc1pK− = (6.59 ± 1.01 ± 0.22) × 10−2 , B Λ 0 b → χc2pπ − B Λ0 b → χc1pπ− = 0.95 ± 0.30 ± 0.04 ± 0.04 , B Λ 0 b → χc2pK− B Λ0 b → χc1pK− = 1.06 ± 0.05 ± 0.04 ± 0.04 , where the first uncertainty is statistical, the second is systematic and the third is due to the uncertainties in the branching fractions of χc1,2 → J/ψγ decays. Keywords: B physics, Branching fraction, Hadron-Hadron scattering (experiments), QCD, Qua

Angular analysis of B0→D∗−D∗+s with D∗+s→D+sγ decays

The first full angular analysis of the B0 → D∗−D∗+ s decay is performed using 6 fb−1 of pp collision data collected with the LHCb experiment at a centre-of-mass energy of 13 TeV. The D∗+ s → D+ s γ and D∗− → D 0 π − vector meson decays are used with the subsequent D+ s → K+K−π + and D 0 → K+π − decays. All helicity amplitudes and phases are measured, and the longitudinal polarisation fraction is determined to be fL = 0.578±0.010±0.011 with world-best precision, where the first uncertainty is statistical and the second is systematic. The pattern of helicity amplitude magnitudes is found to align with expectations from quark-helicity conservation in B decays. The ratio of branching fractions [B(B0 → D∗−D∗+ s ) × B(D∗+ s → D+ s γ)]/B(B0 → D∗−D+ s ) is measured to be 2.045 ± 0.022 ± 0.071 with world-best precision. In addition, the first observation of the Cabibbo-suppressed Bs → D∗−D+ s decay is made with a significance of seven standard deviations. The branching fraction ratio B(Bs → D∗−D+ s )/B(B0 → D∗−D+ s ) is measured to be 0.049 ± 0.006 ± 0.003 ± 0.002, where the third uncertainty is due to limited knowledge of the ratio of fragmentation fractions

Study of Bs0 → J/ψπ+π−K+K− decays

The decays Bs0 → J/ψπ+π−K+K− are studied using a data set corresponding to an integrated luminosity of 9 fb−1, collected with the LHCb detector in proton-proton collisions at centre-of-mass energies of 7, 8 and 13 TeV. The decays Bs0 → J / ψK∗ 0K ¯ ∗ 0 and Bs0 → χc1(3872)K+K−, where the K+K−pair does not originate from a ϕ meson, are observed for the first time. Precise measurements of the ratios of branching fractions between intermediate χc1(3872)ϕ, J / ψK∗ 0K ¯ ∗ 0, ψ(2S)ϕ and χc1(3872)K+K− states are reported. A structure, denoted as X(4740), is observed in the J/ψϕ mass spectrum and, assuming a Breit-Wigner parameterisation, its mass and width are determined to be mX(4740)=4741±6±6MeV/c2,ΓX(4740)=53±15±11MeV, where the first uncertainty is statistical and the second is systematic. In addition, the most precise single measurement of the mass of the Bs0 meson is performed and gives a value of mBs0=5366.98±0.07±0.13MeV/c