Battling for Ribosomes: Translational Control at the Forefront of the Antiviral Response

In the early stages of infection, gaining control of the cellular protein synthesis machinery including its ribosomes is the ultimate combat objective for a virus. To successfully replicate, viruses unequivocally need to usurp and redeploy this machinery for translation of their own mRNA. In response, the host triggers global shutdown of translation while paradoxically allowing swift synthesis of antiviral proteins as a strategy to limit collateral damage. This fundamental conflict at the level of translational control defines the outcome of infection. As part of this special issue on molecular mechanisms of early virus–host cell interactions, we review the current state of knowledge regarding translational control during viral infection with specific emphasis on protein kinase RNA-activated and mammalian target of rapamycin-mediated mechanisms. We also describe recent technological advances that will allow unprecedented insight into how viruses and host cells battle for ribosomes.     

Synthesis and pharmacological investigation of new N-hydroxyalkyl-2-aminophenothiazines exhibiting marked MDR inhibitory effect

Novel N-hydroxyalkyl-2-aminophenothiazines implying a tetrazole moiety at the alkyl chain have been synthesized by hydroboration–oxidation of dienes followed by Buchwald–Hartwig cross-coupling reaction. Also, some sulfoxide and sulfone derivatives have been prepared by selective oxidations. MDR inhibition studies on rat hepatocyte cell culture revealed that some derivatives exhibit marked biological efficacy exceeding that of the standard verapamil (e.g., 3h, 4h, 16). Selected derivatives were subjected to chemical resolution to provide both enantiomers which were shown of similar activity on P-gp interaction measurements. The new compounds exhibited no toxicity.     

5-Bromo-2-aryl benzimidazole derivatives as non-cytotoxic potential dual inhibitors of α-glucosidase and urease enzymes

On the basis of previous report on promising α-glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC₅₀ = 8.15 ± 0.03–354.67 ± 0.19 μM) as compared to standard thiourea (IC₅₀ = 21.25 ± 0.15 μM). It is worth mentioning that derivatives 7 (IC₅₀ = 12.07 ± 0.05 μM), 8 (IC₅₀ = 10.57 ± 0.12 μM), 11 (IC₅₀ = 13.76 ± 0.02 μM), 14 (IC₅₀ = 15.70 ± 0.12 μM) and 22 (IC₅₀ = 8.15 ± 0.03 μM) were found to be more potent inhibitors than standard. All compounds were also evaluated for cytotoxicity towards 3T3 mouse fibroblast cell line and found to be completely non-toxic. Previously benzimidazole 1–25 were also showed α-glucosidase inhibitory potential. In silico studies were performed on the lead molecules i.e. 2, 7, 8, 11, 14, and 22, in order to rationalize the binding interaction of compounds with the active site of urease enzyme.     

Microphytobenthos assemblage mapping by spatial visible-infrared remote sensing in a shellfish ecosystem

The aim of this work is to assess the use of (SPOT) multispectral visible infrared remote sensing to study microphytobentos assemblages in a shellfish ecosystem (Bay of Bourgneuf, France). SPOT satellite images (acquired at low tide in spring or autumn between 1986 and 1998) were calibrated using in situ radiometric data, and the normalised vegetation index (NDVI) obtained from these images showed microphytobenthos on bay mudflats. Proliferation was mainly along a north-south strip, essentially localised around the +2 m isobath and covering a surface area of 19 to 25% of the total mudflat area studied (420 to 550 ha). Three factors seem to be responsible for the spatial structure of the assemblages: bathymetry, nutrient input from the Falleron River and its channel, and the location of oyster-farming areas. Although spatial and spectral resolutions of multispectral remote sensing data have certain limitations, this approach opens up a new field of application for hyperspectral remote sensing, particularly for synoptic mapping of biomass distribution.     

Proteomics of human prostate cancer biospecimens: the global,systems-wide perspective for Protein markers with potential clinical utility

Despite intense global efforts, no new clinical and/or viable biomarkers have been established to overcome the limitation of the prostate specific antigen in the early diagnosis and prognosis of prostate cancer (PCa). The current proteomic approaches to PCa biomarker discovery, each have distinct advantages and disadvantages, yet when combined hold real promise in the coming years. One key approach to this effort is the development of non-targeted, depletion-free and quantitative liquid chromatography–ultra high resolution tandem mass spectrometry (LC–MS) pipelines for the systems-wide interrogation of the diverse proteomes encompassed in whole tissue and blood serum or plasma. Derived quantitative proteomes can be decoded for their biomedical relevance with advanced bioinformatics and bibliographic mining to yield promising ‘molecular portraits’ that can gauge prostatic disease at the serological level. Their functional annotation, although potentially useful, is beyond our current level of biological understanding and should not be requisite for their effective use in the clinical monitoring of prostatic disease.     

Development of a Model For Estimating the Size and Dynamics of the Pet Dog Population

Abstract

A conceptual model was developed to describe the dynamics of the pet dog population. The model synthesizes existing data collected for a variety of purposes to estimate the size of the various components of the pet dog population in Washington and Iowa during 1991. The total population mortality rate was estimated as 12.4% per year. Animal shelters in Washington and Iowa handled 7.6% and euthanized 4.0% of the dog population in those two states. When these estimates were extrapolated to the entire U.S. dog population, the model predicted that the total annual turnover in owned dogs was 14.7%, or 7.71 million dogs, that 4 million dogs were handled by animal shelters, and that 2.1 million were euthanized. It was also estimated that 79% of all female dogs were spayed, that household breeding could be attributed to less than one-fifth (18.7%) of the female dogs in the reproductive pool, and that the number of owners contributing to total dog population turnover through failure to retain their dog (103,453) was approximately three times the number of owners who allowed their female dogs to be bred (32,513).     

Looking After Chronically III Dogs: Impacts on the Caregiver's Life

ABSTRACT

Studies in human medicine show that care of chronically ill family members can affect the caregiver's life in several ways and cause “caregiver burden.” Companion animals are offered increasingly advanced veterinary treatments, sometimes involving home care. Owners choosing such treatments could thus face similar challenges when caring for their animals. This qualitative study uncovers impacts on an owner's life, when attending to the care of an aged or chronically ill dog and reflects on the differing roles of caregivers with animal and human patients. Twelve dog owners were selected for in-depth interviews based on the dogs' diagnoses, and the choice of treatments and care expected to affect the owner's life. Interviews were recorded, transcribed, and analyzed qualitatively. The dog owners reported several changes in their lives due to their dog's condition: practicalities like extra care, changes in use of the home, and restrictions relating to work, social life, and finances. These were time-consuming, tough, and annoying, but could often be dealt with through planning and prioritizing. Changes in the human–dog relationship and activities caused sadness and frustration, which in turn led to feelings of guilt, and in some cases created a feeling of loss. Also, concerns about the progress of the dog's condition, it's welfare, and euthanasia brought emotional distress and many doubts. The owners did, however, respond to the changes differently and as a result experienced different effects on their own life. This study confirms that the situations of caregivers with human and animal patients are in some ways similar, yet the study also identifies and reflects on some of the differences. These include the caregiver role and the options of assistance as well as euthanasia. Veterinary staff are urged to inform owners about possible impacts on their lives when considering careconsuming treatments, and to be aware of the need for support during treatment as well as in decisions about euthanasia.     

Aromatic and aliphatic mono- and bis-nitroxides: A study on their radical scavenging abilities

Nitroxide radicals are an emerging class of interesting compounds with versatile antioxidant and radioprotective properties. All literature studies have so far concentrated on compounds bearing only one nitroxide function. Here, we now investigate and compare the radical scavenging behaviour and antioxidant activity of aromatic indolinonic and aliphatic piperidine bis-nitroxides, i.e compounds bearing two nitroxide functions. Their corresponding mono-derivatives were also studied for comparison. Radical scavenging activity was investigated using EPR and UV–Vis spectroscopy by following spectral changes in acetonitrile of the nitroxides in the presence of alkyl and peroxyl radicals generated, respectively, under anoxic or aerobic conditions from thermal decomposition of AMVN [2,2′-azobis(2,4-di-methylvaleronitrile)]. Antioxidant activity of the nitroxides was evaluated by monitoring conjugated dienes (CD) formation during methyl linoleate micelles peroxidation and by measuring carbonyl content in oxidized bovine serum albumin (BSA). The results show that: (a) each nitroxide moiety in bis-nitroxides scavenges radicals independent of each other; (b) aliphatic nitroxides do not scavenge peroxyl radicals, at least under the experimental conditions used here, whereas indolinonic aromatic ones do: their stoichiometric number is 1.14 and 2.17, respectively, for mono- and bis-derivatives; (c) bis-nitroxides are roughly twice more efficient at inhibiting lipid peroxidation compared to their corresponding mono-derivatives. Although this study provides only comparative information on the relative radical-scavenging abilities of mono- and bis-nitroxides, it helps in understanding further the interesting reactivity of these compounds especially with regards to peroxyl radicals where many controversies in the literature exist.     

Evaluating the physiological effect of strobilurin-based fungicide (Opera 183 g/L SE) against Sclerotium rolfsii and Aspergillus niger pathogens of Arachis hypogaea L.

Abstract

The present study was designed to investigate the effect of fungicide Opera 183?g/L SE on groundnut crop (either as seed or foliar treatment) to control damages and losses incurred especially by the soil borne pathogens Sclerotium rolfsii and Aspergillus niger. The results revealed that 0.15% Opera-treated seeds showed early germination, high percentage of germination, less mortality rate in S. rolfsii and A. niger-infested soil. Enhanced activities of defence-related enzymes, protein, carbohydrate and chlorophyll content up to 2–4 d were observed in Opera-treated plants as compared with untreated plants. Moreover, the application of Opera had a positive effect on yield up to 22%, green fodder at the time of harvest and no disease incidence. From the present study, it is recommended that application of Opera at 750?ml/hectare in the form of foliar treatment to groundnut plants could help in inducing resistance towards opportunistic pathogens and also could enhance the yield.