Serum contents of immunoreactive pancreatic secretory trypsin inhibitor and seminal plasma acrosin-trypsin inhibitor in polytraumatized patients

2 pag

Accelerated HIV testing for PMTCT in maternity and labour wards is vital to capture mothers at a critical point in the programme at district level

TORONTO AIDS Conference 200

Transcriptome analysis of Brachypodium during fungal pathogen infection reveals both shared and distinct defense responses with wheat

© 2017 The Author(s). Fusarium crown rot (FCR) of wheat and barley, predominantly caused by the fungal pathogen Fusarium pseudograminearum, is a disease of economic significance. The quantitative nature of FCR resistance within cultivated wheat germplasm has significantly limited breeding efforts to enhanced FCR resistance in wheat. In this study, we characterized the molecular responses of Brachypodium distachyon (Brachypodium hereafter) to F. pseudograminearum infection using RNA-seq to determine whether Brachypodium can be exploited as a model system towards better understanding of F. pseudograminearum-wheat interaction. The transcriptional response to infection in Brachypodium was strikingly similar to that previously reported in wheat, both in shared expression patterns of wheat homologs of Brachypodium genes and functional overlap revealed through comparative gene ontology analysis in both species. Metabolites produced by various biosynthetic pathways induced in both wheat and Brachypodium were quantified, revealing a high degree of overlap between these two species in metabolic response to infection but also showed Brachypodium does not produce certain defence-related metabolites found in wheat. Functional analyses of candidate genes identified in this study will improve our understanding of resistance mechanisms and may lead to the development of new strategies to protect cereal crops from pathogen infection

The trajectory taken by dimeric Cu/Zn superoxide dismutase through the protein unfolding and dissociation landscape is modulated by salt-bridge formation

Native mass spectrometry (MS) is a powerful means for studying macromolecular protein assemblies, including accessing activated states. However, much remains to be understood about what governs which regions of the protein (un)folding funnel are explored by activation of protein ions in vacuum. Here we examine the trajectory that Cu/Zn superoxide dismutase (SOD1) dimers take over the unfolding and dissociation free energy landscape in vacuum. We examined wild-type SOD1 and six disease-related point-mutants by using tandem MS and ion-mobility MS as a function of collisional activation. For six of the seven SOD1 variants, increasing activation prompted dimers to transition through two unfolding events and dissociate symmetrically into monomers with (as near as possible) equal charges. The exception was G37R, which proceeded only through the first unfolding transition, and displayed a much higher abundance of asymmetric products. Supported by the observation that ejected asymmetric G37R monomers were more compact than symmetric G37R ones, we localised this effect to the formation of a gas-phase salt-bridge in the first activated conformation. To examine the data quantitatively, we applied Arrhenius-type analysis to estimate the barriers on the corresponding free energy landscape. This reveals a heightening of the barrier to unfolding in G37R >5 kJmol-1 over the other variants, consistent with expectations for the strength of a salt-bridge. Our work demonstrates weaknesses in the simple general framework for understanding protein complex dissociation in vacuum, and highlights the importance of individual residues, their local environment, and specific interactions in governing product formation

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Chronic multichannel neural recordings from soft regenerative microchannel electrodes during gait

Reliably interfacing a nerve with an electrode array is one of the approaches to restore motor and sensory functions after an injury to the peripheral nerve. Accomplishing this with current technologies is challenging as the electrode-neuron interface often degrades over time, and surrounding myoelectric signals contaminate the neuro-signals in awake, moving animals. The purpose of this study was to evaluate the potential of microchannel electrode implants to monitor over time and in freely moving animals, neural activity from regenerating nerves. We designed and fabricated implants with silicone rubber and elastic thin-film metallization. Each implant carries an eight-by-twelve matrix of parallel microchannels (of 120\u2009 7\u2009110\u2009\u3bcm2 cross-section and 4\u2009mm length) and gold thin-film electrodes embedded in the floor of ten of the microchannels. After sterilization, the soft, multi-lumen electrode implant is sutured between the stumps of the sciatic nerve. Over a period of three months and in four rats, the microchannel electrodes recorded spike activity from the regenerating sciatic nerve. Histology indicates mini-nerves formed of axons and supporting cells regenerate robustly in the implants. Analysis of the recorded spikes and gait kinematics over the ten-week period suggests firing patterns collected with the microchannel electrode implant can be associated with different phases of gait

Feed intake and production parameters of lactating crossbred cows fed maize-based diets of stover, silage or quality protein silage

Thirty-six Boran × Friesian dairy cows (392 ± 12 kg; mean ± SD) in early parity were used in a randomised complete block design. Cows were blocked by parity into three blocks of 12 animals and offered normal maize (NM) stover (T1), NM silage (T2) or quality protein maize (QPM) silage (T3) basal diets supplemented with a similar concentrate mix. Feed intake, body weight and condition changes and milk yield and composition were assessed. The daily intake of DM, OM, NDF and ADF for cows fed the NM stover-based diet was higher (P < 0.05) than for the cows fed the NM silage and QPM silage-based diets. However, the daily intake of DOM (9.3 kg) and ME (140.8 MJ) for cows on QPM silage-based diet was higher (P < 0.05) than for cows on NM stover-based diet (8.4 kg and 124.2 MJ) and NM silage-based diet (7.9 kg and 119.1 MJ). Body weight of cows was affected (P < 0.05) by the diet, but diet had no effect (P > 0.05) on body condition score, milk yield and milk composition. The digestible organic matter in the NM stover-based diet (724 g/kg DM) was lower (P < 0.05) than that in the NM (770 g/kg DM) and QPM silage-based diet (762 g/kg DM). It was concluded that the performances of the cows on the NM silage and QPM silage diets were similar and were not superior to that of the NM stover-based diet