Cloning and characterization of xerC gene of Streptococcus suis

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

A cell based high-throughput screening approach for the discovery of new inhibitors of respiratory syncytial virus

Background: Human respiratory syncytial virus (hRSV) is a highly contagious pathogen and is the most common cause of bronchiolitis and pneumonia for infants and children under one year of age. Worldwide, greater than 33 million children under five years of age are affected by hRSV resulting in three million hospitalizations and 200,000 deaths. However, severe lower respiratory tract disease may occur at any age, especially among the elderly or those with compromised cardiac, pulmonary, or immune systems. There is no vaccine commercially available. Existing therapies for the acute infection are ribavirin and the prophylactic humanized monoclonal antibody (Synagis® from MedImmune) that is limited to use in high risk pediatric patients. Thus, the discovery of new inhibitors for hRSV would be clinically beneficial. Results: We have developed and validated a 384-well cell-based, high-throughput assay that measures the cytopathic effect of hRSV (strain Long) in HEp-2 cells using a luminescent-based detection system for signal endpoint (Cell Titer Glo®). The assay is sensitive and robust, with Z factors greater than 0.8, signal to background greater than 35, and signal to noise greater than 24. Utilizing this assay, 313,816 compounds from the Molecular Libraries Small Molecule Repository were screened at 10 μM. We identified 7,583 compounds that showed greater than 22% CPE inhibition in the primary screen. The top 2,500 compounds were selected for confirmation screening and 409 compounds showed at least 50% inhibition of CPE and were considered active. We selected fifty-one compounds, based on potency, selectivity and chemical tractability, for further evaluation in dose response and secondary assays Several compounds had SI50 values greater than 3, while the most active compound displayed an SI50 value of 58.9. Conclusions: A robust automated luminescent-based high throughput screen that measures the inhibition of hRSV-induced cytopathic effect in HEp-2 cells for the rapid identification of potential inhibitors from large compound libraries has been developed, optimized and validated. The active compounds identified in the screen represent different classes of molecules, including aryl sulfonylpyrrolidines which have not been previously identified as having anti-hRSV activity

Meta-analysis of ridge-furrow cultivation effects on maize production and water use efficiency

Ridge-furrow cultivation (RF) is a popular dryland agricultural technique in China, but its effects on maize yield, total water consumption during crop growing stage (ET), and water use efficiency (WUE) have not been systematically analyzed. Here we conducted a meta-analysis of the RF effects on maize yield, ET and WUE based on the data collected from peer-reviewed literature. Yield, ET and WUE varied with climate, soil and mulching management. Averaged across all the geographic locations, RF increased the yield and WUE of maize by 47 % and 39 %, respectively, but no effects on ET. An increase in the yield and WUE occurred under RF in regions regardless of the mean growing season air temperature (MT) or a mean precipitation during the growing season (MP), although there was a trend that RF is more beneficial under low MP. RF also decreased ET in regions with MT>12 °C. RF increased the yield and WUE in regions with medium or fine soil texture. RF increased the yield, ET, and WUE in regions with low soil bulk density (BD) (≤1.3 g cm−3). But in areas where BD is larger than 1.3 g cm−3, RF only increased the yield and WUE. RF increased the yield and WUE with or without mulching, but decreased ET when no mulching was used. Together, optimizing RF effects on the yield, ET and WUE in maize was largely dependent on environmental conditions and management practices

Crop yield and soil organic carbon under ridge–furrow cultivation in China: A meta-analysis

Ridge–furrow cultivation (RF) is a popular emerging technique that can increase crop productivity in dry areas. However, the efficacy of RF on crop yield and soil organic carbon (SOC) remains uncertain under different climate and management conditions. Here, we compiled data from 48 publications to evaluate the response of yield and SOC to RF in China. Overall, our meta-analysis showed that RF increased yield by 30.2%, but it had no effects on SOC. When differentiated based on different categories, yield and SOC varied by crop species, climate, soil textures, mulching management, and ridge–furrow patterns. RF increased the yield of wheat, maize, soybean, rape, linseed, potato, and SOC under soybean cultivation. Yield increase with RF was also consistent across temperature and precipitation. Yield increase was observed in all the soil textures. There were no RF effects on SOC under different soil textures. RF enhanced yields under no mulching, straw mulching and plastic film mulching, but increased SOC only in combination with straw mulching. A higher yield increase was observed under alternating small and large ridges (ASLR) than alternating ridges and furrows (AR). RF decreased SOC by 11.7% under AR, but had no effects on SOC under ASLR. Together, ASLR with straw mulching could increase yield and SOC in coarse soil texture regions with annual mean temperature >10°C and annual mean precipitation > 400 mm. This study showed the importance of considering local environmental conditions with management practices in identifying appropriate RF practices for improving crop productivity and soil carbon sequestration

(S)-N-(2,5-Dimethylphenyl)-1-(quinoline-8-ylsulfonyl)pyrrolidine-2-carboxamide as a Small Molecule Inhibitor Probe for the Study of Respiratory Syncytial Virus Infection

A high-throughput, cell-based screen was used to identify chemotypes as inhibitors for human respiratory syncytial virus (hRSV). Optimization of a sulfonylpyrrolidine scaffold resulted in compound 5o that inhibited a virus-induced cytopathic effect in the entry stage of infection (EC50 = 2.3 ± 0.8 µM) with marginal cytotoxicity (CC50 = 30.9 ± 1.1 µM) and reduced viral titer by 100-fold. Compared to ribavirin, sulfonylpyrrolidine 5o demonstrated an improved in vitro potency and selectivity index

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Quaternary folding in the south piedmont of central segment of Tianshan Mountains

The Tianshan Mountains are an important active structural belt in the interior of Eurasia. By integrated methods of surface geology survey and interpretation of seismic profiles, we distinguish fold scarps located at the south limb of the Kuqatawu anticline and the north limb of the Dongqiulitag anticline in the Kuqa rejuvenation foreland thrust belt, south piedmont of central segment of the Tian- shan Mountains. Fold scarp is a newly found structural phenomenon. Because of the bend of thrust plane and the movement of hanging wall above the thrust plane, the origi- nal horizontal deposits of hanging wall and their surface become a monocline structure, resulting from the separating and migration of the active and fixed axial surfaces. Meas- uring the geometry of fold scarp and using the data of age of the deformed deposits, the crustal shortening rate resulting from the deeply seated subsurface thrust is calculated. The crustal shortening rate reflected by the fold scarp located at the north limb of the Dngqiulitag anticline is (1␣0.1) mm/a. The fold scarps of the Dongqiulitag anticline and the Ku- qatawu anticline identify that the deformation process of the crustal compressive structures in the Kuqa area extends into the Late Quaternary

The Quaternary fault in Jiamu area, the Xinjiang Uygur Autonomous Region

peer reviewedThe Quaternary Tailan River fault has been found in the Tianshan foothills area, the Xinjiang Uygur Autonomous Region. It is the recent boundary fault of the Tarim Basin coupling with the West Tianshan Mountains. In the light of measurement data of the slip which cuts the Quaternary deposits of different ages, the Quaternary kine- matic figures of the Tailan River fault are estimated as fol- lows: crustal shortening 3.7 km and shortening rate 1.59 mm/a, uplift of Tianshan Mountains 1.34 km and uplift rate 0.56 mm/a, and additional relief of 900 m. Considering the contribution of the Gumubiezi anticline close to the south of the Tailan River fault, the Quaternary crustal shortening and shortening rate of the Jiamu area are 4.8 km and 2 mm/a respectively. The above-mentioned data coincide with the crustal shortening rate calculated from the growth strata in the Kuqa area, as well as the GPS measurements in the Lake Issyk area and the Korla-Urumqi area, reflecting the fast thrusting period within the shortening tectonic processes of the rejuvenation foreland basin in front of the southern foothill of the West Tianshan Mountains since Neogene

Adaptive monitoring method for batch processes based on phase dissimilarity updating with limited modeling data

A monitoring method is proposed for batch processes, starting with limited reference batches and then updating model data structure with accumulation of new normal batches. On the basis of analysis of the unfolded matrix ((time × batch) × variable), a generalized moving window method is introduced for exploring local covariance structure, phase division, and the development of monitoring models. Then, an adaptive updating algorithm, based on phase-specific dissimilarity analysis, is developed for model updating to accommodate additional information from the accumulation of new batch data and to explore time-varying behaviors from batch to batch. The proposed method is illustrated with two processes, an industrial scale experimental injection molding and a simulated fed-batch penicillin fermentation. Both results show that the proposed method is effective. © 2007 American Chemical Society