Entomopathogenic marine actinomycetes as potential and low-cost biocontrol agents against bloodsucking arthropods

A novel approach to control strategies for integrated blood-feeding parasite management is in high demand, including the use of biological control agents. The present study aims to determine the efficacy of optimized crude extract of actinomycetes strain LK1 as biological control agent against the fourth-instar larvae of Anopheles stephensi and Culex tritaeniorhynchus (Diptera: Culicidae) and adults of Haemaphysalis bispinosa, Rhipicephalus (Boophilus) microplus (Acari: Ixodidae), and Hippobosca maculata (Diptera: Hippoboscidae). Antiparasitic activity was optimized using the Plackett–Burman method, and the design was developed using the software Design-Expert version 8.0.7.1. The production of the optimized crude actinomycetes LK1 strain extract was performed using response surface methodology to optimize the process parameters of protease inhibitor activity of marine actinobacteria for the independent variables like pH, temperature, glucose, casein, and NaCl at two levels (?1 and +1). The potential actinomycetes strain was identified as Saccharomonas spp., and the metamodeling surface simulation procedure was followed. It was studied using a computer-generated experimental design, automatic control of simulation experiments, and sequential optimization of the metamodels fitted to a simulation response surface function. The central composite design (CCD) used for the analysis of treatment showed that a second-order polynomial regression model was in good agreement with the experimental results at R ²?=?0.9829 (p?<?0.05). The optimized values of the variables for antioxidant production were pH 6.00, glucose 1.3 %, casein 0.09 %, temperature 31.23 °C, and NaCl 0.10 %. The LK1 strain-optimized crude extract was purified using reversed-phase high-pressure liquid chromatography, and the isolated protease inhibitor showed antiparasitic activity. The antiparasitic activity of optimized crude extract of LK1 was tested against larvae of A. stephensi (LC₅₀?=?31.82 ppm; r ²?=?0.818) and C. tritaeniorhynchus (LC₅₀?=?26.62 ppm; r ²?=?0.790) and adults of H. bispinosa (LC₅₀?=?106.58 ppm; r ²?=?0.871), R. (B.) microplus (LC₅₀?=?92.96 ppm; r ²?=?0.913), and H. maculata (LC₅₀?=?84.90 ppm; r ²?=?0.857).     

Design,synthesis and biological evaluation of benzo-[d]-imidazo-[2,1-b]-thiazole and imidazo-[2,1-b]-thiazole carboxamide triazole derivatives as antimycobacterial agents

In the search for new anti-mycobacterial agents, we revealed the importance of imidazo-[2,1-b]-thiazole and benzo-[d]-imidazo-[2,1-b]-thiazole carboxamide derivatives. We designed, in silico ADMET predicted and synthesized four series of novel imidazo-[2,1-b]-thiazole and benzo-[d]-imidazo-[2,1-b]-thiazole carboxamide analogues in combination with piperazine and various 1,2,3 triazoles. All the synthesized derivatives were characterized by ¹H NMR, ¹³C NMR, HPLC and MS spectral analysis and evaluated for in vitro antitubercular activity. The most active benzo-[d]-imidazo-[2,1-b]-thiazole derivative IT10, carrying a 4-nitro phenyl moiety, displayed IC₉₀ of 7.05 μM and IC₅₀ of 2.32 μM against Mycobacterium tuberculosis (Mtb) H37Ra, while no acute cellular toxicity was observed (>128 μM) towards the MRC-5 lung fibroblast cell line. Another benzo-[d]-imidazo-[2,1-b]-thiazole compound, IT06, which possesses a 2,4-dichloro phenyl moiety, also showed significant activity with IC₅₀ 2.03 μM and IC₉₀ 15.22 μM against the tested strain of Mtb. Furthermore, the selected hits showed no activity towards a panel of non-tuberculous mycobacteria (NTM), thus suggesting a selective inhibition of Mtb by the tested imidazo-[2,1-b]-thiazole derivatives over the selected panel of NTM. Molecular docking and dynamics studies were also carried out for the most active compounds IT06 and IT10 in order to understand the putative binding pattern, as well as stability of the protein–ligand complex, against the selected target Pantothenate synthetase of Mtb.

In the search for new anti-mycobacterial agents, we revealed the importance of imidazo-[2,1-b]-thiazole and benzo-[d]-imidazo-[2,1-b]-thiazole carboxamide derivatives.     

Post synthetically modified IRMOF-3 for efficient recovery and selective sensing of U(vi) from aqueous medium

A simple and efficient route to develop various novel functionalized MOF materials for rapid and excellent recovery of U(vi) from aqueous medium, along with selective sensing has been demonstrated in the present study. In this connection, a set of four distinct post synthetically modified (PSM) iso-reticular metal organic frameworks were synthesized from IRMOF-3 namely, IRMOF-PC (2-pyridine carboxaldehyde), IRMOF-GA (glutaric anhydride), IRMOF-SMA (sulfamic acid), and IRMOF-DPC (diphenylphosphonic chloride) for the recovery and sensing of U(vi) from aqueous medium. The MOFs were characterized by Fourier transform infrared spectroscopy (FTIR), powder XRD, BET surface area analysis, thermogravimetric analysis (TGA), NMR (¹³C, ¹H and ³¹P), Scanning Electron Microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX). Among all MOFs, post synthetically modified IRMOF-SMA showed enhanced thermal stability of about 420 °C. The MOFs were investigated for U(vi) sorption studies using a batch technique. All the MOFs exhibit excellent sorption capacity towards U(vi) (>90%) and maximum uptake was observed at pH 6. Sorption capacity of MOFs have the following order; IRMOF-3-DPC (300 mg U g⁻¹) > IRMOF-SMA (292 mg U g⁻¹) > IRMOF-PC (289 mg U g⁻¹) > IRMOF-GA (280 mg U g⁻¹) > IRMOF-3 (273 mg U g⁻¹). IRMOF-DPC shows rapid sorption of uranium within 5 min with excellent uptake of U(vi) (>99%). The desorption of U(vi) was examined with different eluents and 0.01 M HNO₃ was found to be most effective. The fluorescence sensing studies of U(vi) via IRMOF-3 and its PSM MOFs revealed high sensitivity and selectivity towards U(vi) over other competing rare earth metal ions (La³⁺, Ce⁴⁺, Sm³⁺, Nd³⁺, Gd³⁺, and Eu³⁺), wherein IRMOF-GA displayed an impressive detection limit of 0.36 mg L⁻¹ for U(vi).

Four IRMOFs following PSM strategy were prepared. The MOFs were characterized by different techniques and were investigated for U(vi) sorption. PSM MOFs displayed impressive fluorescent sensing and selectivity of U(vi) over competing metal ions.     

Physiological lung exclusion — A useful tool in difficult pneumonectomy

Patients with massive haemoptysis with dense fibrosis, a standard pneumonectomy may lead to blood loss with life threatening situation. Physiological Lung exclusion through mid sternotomy is an useful procedure. Four patients had undergone Physiological Lung exclusion. Two patients for massive haemoptysis and two for redo lobectomy. All patients operated through mid sternotomy. The last patient while hilar dissection lost significant blood volume and required cardiopulmonary bypass to complete the procedure. This is an useful procedure when there is anticipation of difficulty in standard pneumonectomy and in sick patients.     

Initial electro-mechanical response to rearward perturbation

The objective of this study was to examine the combined electromyographic (EMG) and mechanical response to a rearward perturbation and to separate the response into three categories: preset properties of the muscle, reflex changes to the muscle, and active changes to the muscle. We hypothesized that an active response is required to maintain balance on a moving platform. Eleven healthy adult subjects stood on a platform oscillating at three frequencies (0.75, 1.0, and 1.25 Hz). Ankle extensor EMG activity and ankle moment were analyzed and compared for initial movement cycles. Timing of events in EMG and moment data were examined to separate observed changes into the three categories. Results showed an initial rise in ankle moment as the platform started to move backwards, followed by a more rapid reflex increase. After a slight drop, ankle moment again rose due to active response. By the third cycle of platform movement, the EMG and moment were synchronized with the platform movement, maintaining the body in a desired posture. Initial preset properties of the ankle extensor muscles combined with reflex activity were not sufficient to maintain balance. Following an initial reflex reaction, further active control was required to match the timing of the ankle moment and the platform motion and avoid a loss of balance. This study provides new insight for the rehabilitation of postural deficits.     

Colorectal cancer incidence, mortality and survival in South-east England between 1972 and 2001.

We report incidence, mortality and survival from colorectal cancer in South-east England using data from 162,022 incident cases and 97,697 deaths collected between 1972 and 2001 at the Thames Cancer Registry, which currently covers 14 million people. Overall, there was an increase in the incidence of colorectal cancer among men aged 50 years and over, and a decrease among the youngest age groups. In women, there was a clear decrease in incidence among those aged less than 60 years but a slight increase among those aged 60-79 years. Furthermore, there has been a steady decrease in mortality for all ages, larger in women than in men, and an increase in the 10-year relative survival for both sexes from just over 30% among those followed-up during 1981-1986 to just over 45% among those followed-up during 1997-2001.     

Optimization of Cultural Conditions for Protease Production by a Fungal Species

Studies were carried out on a paddy soil fungal isolate identified to be a strain of Aspergillus niger from Manipal. The parameters that largely impact enzyme production viz., fermentation time, impeller speed, pH, temperature and nutrient supplements were studied. Optimization of production parameters for production of protease was done by the single-parameter mode. Casein served as substrate and proteolytic activity was estimated using Folin-Ciocalteau method at 660 nm. A maximum yield of 71.3 mg tyrosine/g casein substrate was produced in 96 h on a soluble starch medium at pH 4 in shake flask experiments. Production was carried out on a 3-liter fermenter and 40.7 mg of tyrosine was liberated/g of substrate. The enzyme was extracted with 50% ammonium sulfate and sodium dodecyl sulfate-Polyacrylamide gel electrophoresis showed two bands having mw 45.7 kDa and 38.5 kDa, respectively. The enzyme activity was found to be 147.84 U/ml.