Ribosome engineering and fermentation optimization leads to overproduction of tiancimycin A,a new enediyne natural product from <Emphasis Type="Italic">Streptomyces</Emphasis> sp. CB03234

Tiancimycin (TNM) A, a recently discovered enediyne natural product from Streptomyces sp. CB03234, showed rapid and complete killing of cancer cells and could be used as a payload in antibody drug conjugates. The low yield of TNM A in the wild-type strain promoted us to use ribosome engineering and fermentation optimization for its yield improvement. The Streptomyces sp. CB03234-R-16 mutant strain with a L422P mutation in RpoB, the RNA polymerase β-subunit, was obtained from the rifamycin-resistant screening. After fermentation optimization, the titers of TNM A in Streptomyces sp. CB03234-R-16 reached to 22.5 ± 3.1 mg L^?1 in shaking flasks, and 13 ± 1 mg L^?1 in 15 L fermentors, which were at least 40-fold higher than that in the wild-type strain (~ 0.3 mg L^?1). Quantitative real-time RT-PCR revealed markedly enhanced expression of key genes encoding TNM A biosynthetic enzymes and regulators in Streptomyces sp. CB03234-R-16. Our study should greatly facilitate the future efforts to develop TNM A into a clinical anticancer drug.     

Interactions among stressors may be weak: Implications for management of freshwater macroinvertebrate communities

Aim

Ecological models that do not account for interactions among stressors, if interactions are important, could be inaccurate and lead to inefficient conservation strategies. Conversely, if interactions are not important (i.e., stressors operate largely independently), then actions concentrating on a stressor‐by‐stressor basis would be warranted. Here, we investigated whether interactions among multiple stressors affected widely used indices of freshwater macroinvertebrate biodiversity, which are sensitive to environmental change at management‐relevant scales (i.e., reaches and catchments).

Location

State of Victoria, south‐eastern Australia.

Methods

We used a 7,418‐sample dataset for stream macroinvertebrates from 2,165 sites distributed over 237,630 km² for 20 years. We calculated the interactive effects on stream macroinvertebrates of stressors operating at different scales, namely vegetation loss at the catchment and reach scales and hydrological change and salinization at the local scale. The importance of interactions among multiple stressors was assessed by comparing the cross‐validated predictive performance of models with and without multiple stressor interaction terms.

Results

Cross‐validated models explained 31%–63% of the variation in the macroinvertebrate responses. The most important stressors were catchment vegetation loss (the proportion of remaining native vegetation cover) and salinity. The inclusion of interaction terms did not increase cross‐validated predictive performance, which indicates that there was little evidence that interactions among stressors were important for explaining variation in commonly used freshwater macroinvertebrate condition indices.

Main conclusions

Interactions among vegetation, salinity and hydrological change stressors may not always be of importance for determining patterns of stream macroinvertebrate biodiversity, so that such interactions may not necessarily be critical considerations for catchment and reach scale management, at least if based on these or comparable condition indices. The mitigation of the impacts of vegetation loss, salinization and hydrological change stressors one‐by‐one probably is sufficient to guide conservation activities and might be advantageous if socio‐political contexts make it difficult to address interactions among stressors.

     

A novel task scheduling approach based on dynamic queues and hybrid meta-heuristic algorithms for cloud computing environment

Task scheduling is one of the most challenging aspects to improve the overall performance of cloud computing and optimize cloud utilization and Quality of Service (QoS). This paper focuses on Task Scheduling optimization using a novel approach based on Dynamic dispatch Queues (TSDQ) and hybrid meta-heuristic algorithms. We propose two hybrid meta-heuristic algorithms, the first one using Fuzzy Logic with Particle Swarm Optimization algorithm (TSDQ-FLPSO), the second one using Simulated Annealing with Particle Swarm Optimization algorithm (TSDQ-SAPSO). Several experiments have been carried out based on an open source simulator (CloudSim) using synthetic and real data sets from real systems. The experimental results demonstrate the effectiveness of the proposed approach and the optimal results is provided using TSDQ-FLPSO compared to TSDQ-SAPSO and other existing scheduling algorithms especially in a high dimensional problem. The TSDQ-FLPSO algorithm shows a great advantage in terms of waiting time, queue length, makespan, cost, resource utilization, degree of imbalance, and load balancing.     

Evaluation of site availability exploitation towards performance optimization in data grids

Data in distributed systems are often replicated into different storage elements in order to facilitate their access. This allows optimizing execution time and bandwidth consumption, ensures load balancing and increases data availability and quality of service. Several replication strategies have then been proposed in the literature. In this work, a new evaluation metric for replication strategies is introduced and experimentally evaluated. This metric, called SAvE, serves to tackle a key feature, although neglected in the literature, which is the ability of a replication strategy to exploit the most available sites in the system. The design of such a metric requires an accurate determination of the availability degree of each site. A new measurement of site availability, denoted SA, is then designed to be integrated into SAvE while overcoming the drawbacks experienced by existing measurements. Extensive experiments are performed using the OptorSim simulator to show the accuracy and the effectiveness of our contributions.     

Nanoantenna-Enhanced Radiative and Anisotropic Decay Rates in Monolayer-Quantum Dots

Plasmonics - Nanoantenna-enhanced ultrafast emission from colloidal quantum dots as quantum emitters is required for fast quantum communications. On-chip integration of such devices requires a...     

Co-Processed Excipients for Dispersible Tablets–Part 1: Manufacturability

Co-processed excipients may enhance functionality and reduce drawbacks of traditional excipients for the manufacture of tablets on a commercial scale. The following study aimed to characterise a range of co-processed excipients that may prove suitable for dispersible tablet formulations prepared by direct compression. Co-processed excipients were lubricated and compressed into 10.5-mm convex tablets using a Phoenix compaction simulator. Compression profiles were generated by varying the compression force applied to the formulation and the prepared tablets were characterised for hardness, friability, disintegration and fineness of dispersion. Our data indicates that CombiLac, F-Melt type C and SmartEx QD100 were the top 3 most suitable out of 16 co-processed excipients under the conditions evaluated. They exhibited good flow properties (Carr’s index ? 20), excellent tabletability (tensile strength >?3.0 MPa at 0.85 solid fraction), very low friability (<?1% after 15 min), rapid disintegration times (27–49 s) and produced dispersions of ideal fineness (<?250 μm). Other co-processed excipients (including F-Melt type M, Ludiflash, MicroceLac, Pharmaburst 500 and Avicel HFE-102) may be appropriate for dispersible tablets produced by direct compression providing the identified disintegration and dispersion risks were mitigated prior to commercialisation. This indicates that robust dispersible tablets which disintegrate rapidly could be manufactured from a range of co-processed excipients.     

In Toto Imaging of Dynamic Osteoblast Behaviors in Regenerating Skeletal Bone

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Husbandry protocols for the Band‐tailed pigeon,Patagioenas fasciata albilinea,at the WCS,Bronx Zoo for future conservation management programs

From 2015 to 2016 we determined the husbandry protocols involved in the captive rearing of the Band‐tailed Pigeon (BTPI), Patagioenas fascinate albilinea, for use as a tool in the future management of like extant and extinct avian taxa. Current and historical ex‐situ conservation management of BTPIs and the closely related Passenger Pigeon, Ectopistes migratorius, is limited in scope and required further examination. Focus on the BTPI within zoos and private aviculture facilities is currently lacking. New pressures on the wild populations and future examination of the parameters involved in the possible restoration of the Passenger Pigeon may rely on a complete understanding of these conservation management techniques. Here we report on the establishment of a colony of BTPIs, at the Wildlife Conservation Society (WCS), and detail the progress attained. A confiscated group of BTPIs was presented to WCS and allowed us to set up the colony, document the husbandry involved, and monitor neonatal development and the factors that influence that development. The information has provided a better understanding of the BTPI and has implications for the future conservation management of this and like species.     

Soil C:N:P stoichiometry responds to vegetation change from grassland to woodland

Woody encroachment has been a major land cover change in dryland ecosystems during the past century. While numerous studies have demonstrated strong effects of woody encroachment on soil carbon (C), nitrogen (N), and phosphorus (P) storage, far less is known about the plasticity of soil C:N:P stoichiometry in response to woody encroachment. We assessed landscape-scale patterns of spatial heterogeneity in soil C:N:P ratios throughout a 1.2 m soil profile in a region where grassland is being replaced by a diverse assemblage of subtropical woody plants dominated by Prosopis glandulosa, an N₂-fixing tree. Woody species had leaf and fine root C:N:P ratios significantly different from grasses. Variation in soil C:N ratios in both horizontal and vertical planes was remarkably smaller than that of soil N:P and C:P ratios. Spatial patterns of soil C:N ratio throughout the profile were not strongly related to vegetation cover. In contrast, spatial patterns of soil N:P and C:P ratios displayed a strong resemblance to that of vegetation cover throughout the soil profile. Within the uppermost soil layer (0–5 cm), soil N:P and C:P ratios were higher underneath woody patches while lower within the grassland; however, this pattern was reversed in subsurface soils (15–120 cm). These results indicate a complex response of soil C:N:P stoichiometry to vegetation change, which could have important implications for understanding C, N, and P interactions and nutrient limitations in dryland ecosystems.