Kilgoreengberg2016
The walking ability of many broilers is characterised by slight or definite defects categorised as gait scores (GS) 1 and 2. The present study aimed to examine potential relationships between GSs and indicators of body morphology, leg pathology, tibia strength and wooden breast in Ross 308 broilers assessed as GS ≤ 2.
At 38 days of age, GS and live body weight of 179 birds was recorded. Each bird was examined post-mortem for signs of wooden breast, contact dermatitis and a range of leg pathologies. Weights of different body parts and tibia strength were quantified.
Within sex, GS increased with increasing live body weight (p=0.020). There was a tendency for an effect of GS on prevalence of footpad dermatitis (p=0.086) and dislocated femoral joint cartilage (p=0.059) where both pathologies increased in frequency with increasing GS. Greater load was required to fracture tibia from GS2 than GS0 birds (p=0.040).
Within this relatively small data set, no strong relationships between GS ≤ 2 and indicators of body morphology, leg pathology, tibia strength and wooden breast in Ross 308 broilers were found, except for the live terminal body weight. Further studies, involving larger data sets are required for full clarification.
Within this relatively small data set, no strong relationships between GS ≤ 2 and indicators of body morphology, leg pathology, tibia strength and wooden breast in Ross 308 broilers were found, except for the live terminal body weight. Further studies, involving larger data sets are required for full clarification.
Implementing effective interventions for hepatitis C virus (HCV) requires detailed understanding of local transmission dynamics and geospatial spread. Little is known about HCV phylodynamics, particularly among high-burden populations such as people who inject drugs (PWID).
We used 483 HCV sequences and detailed individual-level data from PWID across four Indian cities. Bayesian phylogeographic analyses were used to evaluate transmission hotspots and geospatial diffusion of virus. Phylogenetic cluster analysis was performed to infer epidemiologic links and factors associated with clustering. A total of 492 HIV sequences were used to draw comparisons within the same population, and in the case of co-infections, evaluate molecular evidence for shared transmission pathways. Overall, 139/483 (28.8%) of HCV sequences clustered with a median cluster size of three individuals. Genetically linked participants with HCV were significantly younger and more likely to be infected with HCV subtype 3b, as well as live and inject close to one another. Phylogenetic evidence suggests likely ongoing HCV infection/reinfection with limited support for shared HIV/HCV transmission pathways. Phylogeographic analyses trace historic HCV spread back to Northeastern India and show diffusion patterns consistent with drug trafficking routes.
This study is among the first to characterize HCV phylodynamics among PWID in a low-and middle-income country setting. Heterogeneity and recent genetic linkage of HCV across geographically disparate Indian states suggest that targeted interventions could help prevent reimportation of virus via drug trafficking routes.
This study is among the first to characterize HCV phylodynamics among PWID in a low-and middle-income country setting. Heterogeneity and recent genetic linkage of HCV across geographically disparate Indian states suggest that targeted interventions could help prevent reimportation of virus via drug trafficking routes.Dinitrotoluene (DNT) has been extensively used in manufacturing munitions, polyurethane foams and other important chemical products. PMX-53 However, it is highly toxic and mutagenic to most organisms. Here, we synthesized a codon-optimized bacterial nitroreductase gene, NfsI, for plant expression. The kinetic analysis indicates that the recombinant NfsI can detoxify both 2,4-DNT and its sulfonate (DNTS), while it has a 97.6-fold higher catalytic efficiency for 2,4-DNT than DNTS. Furthermore, we overexpressed NfsI in switchgrass (Panicum virgatum L.), which is a multiple-purpose crop used for fodder and biofuel production as well as phytoremediation. The 2,4-DNT treatment inhibited root elongation of wild-type switchgrass plants and promoted reactive oxygen species (ROS) accumulation in roots. In contrast, overexpression of NfsI in switchgrass significantly alleviated 2,4-DNT-induced root growth inhibition and ROS overproduction. Thus, the NfsI overexpressing transgenic switchgrass plant removed 94.1% 2,4-DNT after 6 days, whose efficiency was 1.7-fold higher than control plants. Moreover, the comparative transcriptome analysis suggests that 22.9% of differentially expressed genes induced by 2,4-DNT may participate in NfsI-mediated 2,4-DNT detoxification in switchgrass. Our work sheds light on the function of NfsI during DNT phytoremediation for the first time, revealing the application potential of switchgrass plants engineered with NfsI.
Antigen-binding fragment (F
) reversal agents were developed to reverse, in bleeding emergency, the long-acting anticoagulant effect of JNJ-64179375 (JNJ-9375), a monoclonal antibody that binds exosite-1 on thrombin.
The pharmacokinetic and pharmacodynamic (PK/PD) activities of three reversal agents of varying in vitro binding affinities to JNJ-9375 were characterised in cynomolgus monkeys. The time course of JNJ-9375 anticoagulant activity and reversal effects of each agent were evaluated. A mechanism-based PK/PD model, which integrated free serum concentrations of reversal agent, total and free serum concentrations of JNJ-9375, and thrombin time, was developed to quantitatively relate JNJ-9375 neutralisation to reversal of induced thrombin time prolongation. Model-based allometric scale-up of the lead reversal agent and the PK/PD relationship of JNJ-9375 in healthy volunteers were utilised to predict clinical dosing regimens.
Lowering of free JNJ-9375 by the reversal agents corresponded with reversal of thrombin time prolongation. Total JNJ-9375 displayed typical mAb clearance at 2.75 ml·day
·kg
, whereas reversal agents cleared faster between 1400 and 2400 ml·day
·kg
. The model-estimated in vivo K
values for JNJ-9375 reversal agents were 9nM (ICHB-256), 0.4nM (ICHB-281) and 13.7 pM (ICHB-164), in rank-ordered agreement of their K
values determined in vitro. The three reversal agents exhibited different neutralisation characteristics in vivo, governed primarily by their binding kinetics to JNJ-9375. The model predicted a priori free JNJ-9375 kinetics after dosing ICHB-164 (JNJ-67842125) and JNJ-9375 under a different regimen.
The results enabled selection of JNJ-67842125 as the reversal agent for JNJ-9375.
The results enabled selection of JNJ-67842125 as the reversal agent for JNJ-9375.
