Drug Target Identification and Prioritization for Treatment of Ovine Foot Rot: An In Silico

Ovine foot rot is an infection of the feet of sheep, mainly caused by Dichelobacter nodosus. In its virulent form, it is highly contagious and debilitating, causing significant losses in the form of decline in wool growth and quality and poor fertility. Current methods of treatment are ineffective in complete eradication. Effective antibiotic treatment of foot rot is hence necessary to ensure better outcomes during control phases by reduction in culling count and the possibility of carriers of the infection. Using computational approaches, we have identified a set of 297 proteins that are essential to the D. nodosus and nonhomologous with sheep proteins. These proteins may be considered as potential vaccine candidates or drug targets for designing antibiotics against the bacterium. This core set of drug targets have been analyzed for pathway annotation to identify 67 proteins involved in unique bacterial pathways. Choke-point analysis on the drug targets identified 138 choke-point proteins, 29 involved in unique bacterial pathways. Subcellular localization was also predicted for each target to identify the ones that are membrane associated or secreted extracellularly. In addition, a total of 13 targets were identified that are common in at least 10 pathogenic bacterial species

Ekspresija gena za imunološki odgovor nakon izazivačke infekcije u indijskih šarana rohu (Labeo rohita) cijepljenih modificiranom formulacijom proteina R vanjske membrane bakterije Aeromonas hydrophila

Although vaccination and post-vaccination studies have gained considerable importance in the field of aquaculture diseases, little is understood about the mechanism of immune-protection in vaccinated fish following infection. In the present study, an attempt was made to discover the mechanism of protection rendered by a modified adjuvant-based recombinant outer membrane protein R (rOmpR) vaccine, in rohu, Labeo rohita (an important Indian major carp species) following a challenge with Aeromonas hydrophila. For this, expression analysis of an array of immune molecules (IgM, complement factor 3, interleukin 1β, interleukin 6, tumor necrosis factor α, interleukin 15, MHC I and MHC II) was carried out in the anterior kidney tissues of vaccinated fish, at 0, 12, 24, 48, 72 and 120 h post-challenge. Higher transcript levels of IgM, MHC I and MHC II were evident in the mineral oil-based OmpR vaccinated and modified adjuvant-based OmpR-vaccinated groups, at different time points post-challenge, including the non-challenged fish. Early onset of pro-inflammatory cytokines and expression of most of the immune genes was more pronounced in vaccinated fish at different time points post-challenge, thus indicating a better immune response in these fish. This study indicated the activation of both humoral and cell mediated immunity in vaccinated rohu following a challenge with A. hydrophila.Iako su cijepljenje i istraživanja nakon cijepljenja znatno dobila na važnosti u borbi protiv bolesti u akvakulturi, malo se zna o mehanizmu imunološke zaštite u cijepljenih riba nakon izazivačke infekcije. U ovom se istraživanju pokušalo rasvijetliti mehanizam zaštite nakon cijepljenja modificiranim cjepivom pripravljenim od rekombinantnog proteina R (rOmpR) vezanog na adjuvans u vrste Labeo rohita (za Indiju važne vrste šarana) i izazivačke infekcije vrstom Aeromonas hydrophila. U tu svrhu analizirana je ekspresija niza imunosnih molekula (IgM, faktor 3 komplementa, interleukin 1β, interleukin 6, faktor tumorske nekroze α, interleukin 15, MHC I and MHC II) u bubrežnim tkivima cijepljenih riba 0, 12, 24, 48, 72 i 120 h nakon izazivačke infekcije. Više razine transkripata IgM, MHC I i MHC II bile su očite u skupina cijepljenih OmpR-om s mineralnim uljem kao adjuvansom i modificiranim OmpR-om s mineralnim uljem u različitim vremenskim razmacima nakon izazivačke infekcije kao i onih koje nisu bile podvrgnute izazivačkoj infekciji. Rana pojava proupalnih citokina i ekspresije većine imunosnih gena bila je više izražena u cijepljenih riba u različitim vremenskim točkama nakon izazivačke infekcije što upućuje na bolji imunosni odgovor u tih riba. Ovo istraživanje naznačuje aktivaciju i humoralne i stanične imunosti u cijepljenih rohu riba nakon izazivačke infekcije bakterijom A. hydrophila

Measurements of the pp → ZZ production cross section and the Z → 4ℓ branching fraction, and constraints on anomalous triple gauge couplings at √s = 13 TeV

Four-lepton production in proton-proton collisions, pp -> (Z/gamma*)(Z/gamma*) -> 4l, where l = e or mu, is studied at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb(-1). The ZZ production cross section, sigma(pp -> ZZ) = 17.2 +/- 0.5 (stat) +/- 0.7 (syst) +/- 0.4 (theo) +/- 0.4 (lumi) pb, measured using events with two opposite-sign, same-flavor lepton pairs produced in the mass region 60 4l) = 4.83(-0.22)(+0.23) (stat)(-0.29)(+0.32) (syst) +/- 0.08 (theo) +/- 0.12(lumi) x 10(-6) for events with a four-lepton invariant mass in the range 80 4GeV for all opposite-sign, same-flavor lepton pairs. The results agree with standard model predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ. couplings at 95% confidence level: -0.0012 < f(4)(Z) < 0.0010, -0.0010 < f(5)(Z) < 0.0013, -0.0012 < f(4)(gamma) < 0.0013, -0.0012 < f(5)(gamma) < 0.0013

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV