Biological effects of power frequency magnetic fields: Neurochemical and toxicological changes in developing chick embryos

BACKGROUND: There are several reports that indicate a linkage between exposure to power frequency (50 – 60 Hz) magnetic fields with abnormalities in the early embryonic development of the chicken. The present study was designed to understand whether power frequency electromagnetic fields could act as an environmental insult and invoke any neurochemical or toxicological changes in developing chick embryo model. METHODS: Fertilized chicken eggs were subjected to continuous exposure to magnetic fields (50 Hz) of varying intensities (5, 50 or 100 μT) for a period of up to 15 days. The embryos were taken out of the eggs on day 5, day 10 and day 15. Neurochemical (norepinephrine and 5-hydroxytryptamine) and amino acid (tyrosine, glutamine and tryptophan) contents were measured, along with an assay of the enzyme glutamine synthetase in the brain. Preliminary toxicological investigations were carried out based on aminotransferases (AST and ALT) and lactate dehydrogenase activities in the whole embryo as well as in the liver. RESULTS: The study revealed that there was a significant increase (p < 0.01 and p < 0.001) in the level of norepinephrine accompanied by a significant decrease (p < 0.01 and p < 0.001) in the tyrosine content in the brain on day 15 following exposure to 5, 50 and 100 μT magnetic fields. There was a significant increase (p < 0.001) in glutamine synthetase activity resulting in the significantly enhanced (p < 0.001) level of glutamine in the brain on day 15 (for 100 μT only). The possible mechanisms for these alterations are discussed. Further, magnetic fields had no effect on the levels of tryptophan and 5-hydroxytryptamine in the brain. Similarly, there was no effect on the activity of either aminotransferases or lactate dehydrogenase in the whole embryo or liver due to magnetic field exposure. CONCLUSIONS: Based on these studies we conclude that magnetic field-induced changes in norepinephrine levels might help explain alterations in the circadian rhythm, observed during magnetic field stress. Also, the enhanced level of glutamine can act as a contributing factor for developmental abnormalities

ASSESSMENT OF EFFICACY AND SAFETY OF ORAL FOSFOMYCIN SINGLE DOSE IN UNCOMPLICATED URINARY TRACT INFECTION AT A TERTIARY CARE HOSPITAL IN SOUTH INDIA

Objectives: Urinary tract infection (UTI) affects 150 million people worldwide each year. The rise in the UTIs is attributed to multidrug-resistant pathogens for which there are minimal treatment options available. This has facilitated the reemergence of certain old antimicrobials such as fosfomycin trometamol (FT). It seems an alternative, but the evidence towards its therapeutic efficiency is scanty. The objective of the study is to evaluate the safety and efficacy of single dose of FT in treating uncomplicated UTI and the resultant variations in the intensity of symptoms after the treatment. Methods: The study is a prospective, observational, and open-label study in the outpatient unit of the Department of General Medicine, RVM institute of Medical Sciences, for 6 months. The study comprises 50 patients among the age group of 18–70 years. Urinary Tract Infection Symptom Assessment questionnaire was used for the evaluation of symptoms pre and post treatment. After the diagnosis of uncomplicated UTI, patients were treated with single-dose of FT. Results: The study comprises 22 males and 28 females. After the treatment, there was a drastic improvement in the condition of patients. The severity level reduced and the quality of life improved post treatment and the results were statistically significant. Among 50 patients treated with the drug, 11 patients reported the side effect of diarrhea. Conclusion: Single dose oral Fosfomycin (3 g) regimen is effective in managing uncomplicated UTI with minimal side effects

Degradation of the insecticidal toxin produced by Bacillus thuringiensis var. kurstaki by extracellular proteases produced by Chrysosporium sp.

Aims:  Some Cry proteins produced by the soil bacterium Bacillus thuringiensis (Bt) or by transgenic Bt plants persist in agricultural soils for an extended period of time, which may pose a hazard for nontarget soil organisms. The aims of our study were to screen for soil fungi capable of degrading the Cry1Ac toxin and to identify the mechanisms that lead to the inactivation of this protein.Methods and Results:  Of the eight fungal strains screened, only one, Chrysosporium sp., was found to produce extracellular proteases capable of degrading the 66-kDa Cry1Ac at the N-terminal end of amino acid 125 (alanine). The proteolytic products of the Cry1Ac toxin did not exhibit any insecticidal activity against Helicoverpa armigera, in contrast to its high toxicity exhibited in the native form.Conclusions:  Proteases elaborated by the Chrysosporium sp. degrade the Cry1Ac toxin in a way that it looses its insecticidal activity against H. armigera.Significance and Impact of the Study: Chrysosporium sp., a specific soil micro-organism capable of producing proteases that degrade the Cry1Ac toxin into inactive products under controlled conditions is being reported for the first time. Application of this observation needs to be further tested in field conditions

Fresolimumab Treatment Decreases Biomarkers and Improves Clinical Symptoms in Systemic Sclerosis Patients

BACKGROUND. TGF-β has potent profibrotic activity in vitro and has long been implicated in systemic sclerosis (SSc), as expression of TGF-β–regulated genes is increased in the skin and lungs of patients with SSc. Therefore, inhibition of TGF-β may benefit these patients. METHODS. Patients with early, diffuse cutaneous SSc were enrolled in an open-label trial of fresolimumab, a high-affinity neutralizing antibody that targets all 3 TGF-β isoforms. Seven patients received two 1 mg/kg doses of fresolimumab, and eight patients received one 5 mg/kg dose of fresolimumab. Serial mid-forearm skin biopsies, performed before and after treatment, were analyzed for expression of the TGF-β–regulated biomarker genes thrombospondin-1 (THBS1) and cartilage oligomeric protein (COMP) and stained for myofibroblasts. Clinical skin disease was assessed using the modified Rodnan skin score (MRSS). RESULTS. In patient skin, THBS1 expression rapidly declined after fresolimumab treatment in both groups (P = 0.0313 at 7 weeks and P = 0.0156 at 3 weeks), and skin expression of COMP exhibited a strong downward trend in both groups. Clinical skin disease dramatically and rapidly decreased (P \u3c 0.001 at all time points). Expression levels of other TGF-β–regulated genes, including SERPINE1 and CTGF, declined (P = 0.049 and P = 0.012, respectively), and a 2-gene, longitudinal pharmacodynamic biomarker of SSc skin disease decreased after fresolimumab treatment (P = 0.0067). Dermal myofibroblast infiltration also declined in patient skin after fresolimumab (P \u3c 0.05). Baseline levels of THBS1 were predictive of reduced THBS1 expression and improved MRSS after fresolimumab treatment. CONCLUSION. The rapid inhibition of TGF-β–regulated gene expression in response to fresolimumab strongly implicates TGF-β in the pathogenesis of fibrosis in SSc. Parallel improvement in the MRSS indicates that fresolimumab rapidly reverses markers of skin fibrosis

CCN2 Is Required for the TGF-β Induced Activation of Smad1 - Erk1/2 Signaling Network

Connective tissue growth factor (CCN2) is a multifunctional matricellular protein, which is frequently overexpressed during organ fibrosis. CCN2 is a mediator of the pro-fibrotic effects of TGF-β in cultured cells, but the specific function of CCN2 in the fibrotic process has not been elucidated. In this study we characterized the CCN2-dependent signaling pathways that are required for the TGF-β induced fibrogenic response. By depleting endogenous CCN2 we show that CCN2 is indispensable for the TGF-β-induced phosphorylation of Smad1 and Erk1/2, but it is unnecessary for the activation of Smad3. TGF-β stimulation triggered formation of the CCN2/β3 integrin protein complexes and activation of Src signaling. Furthermore, we demonstrated that signaling through the αvβ3 integrin receptor and Src was required for the TGF-β induced Smad1 phosphorylation. Recombinant CCN2 activated Src and Erk1/2 signaling, and induced phosphorylation of Fli1, but was unable to stimulate Smad1 or Smad3 phosphorylation. Additional experiments were performed to investigate the role of CCN2 in collagen production. Consistent with the previous studies, blockade of CCN2 abrogated TGF-β-induced collagen mRNA and protein levels. Recombinant CCN2 potently stimulated collagen mRNA levels and upregulated activity of the COL1A2 promoter, however CCN2 was a weak inducer of collagen protein levels. CCN2 stimulation of collagen was dose-dependent with the lower doses (<50 ng/ml) having a stimulatory effect and higher doses having an inhibitory effect on collagen gene expression. In conclusion, our study defines a novel CCN2/αvβ3 integrin/Src/Smad1 axis that contributes to the pro-fibrotic TGF-β signaling and suggests that blockade of this pathway may be beneficial for the treatment of fibrosis

Grapevine rootstocks shape underground bacterial microbiome and networking but not potential functionality

BackgroundThe plant compartments of Vitis vinifera, including the rhizosphere, rhizoplane, root endosphere, phyllosphere and carposphere, provide unique niches that drive specific bacterial microbiome associations. The majority of phyllosphere endophytes originate from the soil and migrate up to the aerial compartments through the root endosphere. Thus, the soil and root endosphere partially define the aerial endosphere in the leaves and berries, contributing to the terroir of the fruit. However, V. vinifera cultivars are invariably grafted onto the rootstocks of other Vitis species and hybrids. It has been hypothesized that the plant species determines the microbiome of the root endosphere and, as a consequence, the aerial endosphere. In this work, we test the first part of this hypothesis. We investigate whether different rootstocks influence the bacteria selected from the surrounding soil, affecting the bacterial diversity and potential functionality of the rhizosphere and root endosphere.MethodsBacterial microbiomes from both the root tissues and the rhizosphere of Barbera cultivars, both ungrafted and grafted on four different rootstocks, cultivated in the same soil from the same vineyard, were characterized by 16S rRNA high-throughput sequencing. To assess the influence of the root genotype on the bacterial communities’ recruitment in the root system, (i) the phylogenetic diversity coupled with the predicted functional profiles and (ii) the co-occurrence bacterial networks were determined. Cultivation-dependent approaches were used to reveal the plant-growth promoting (PGP) potential associated with the grafted and ungrafted root systems.ResultsRichness, diversity and bacterial community networking in the root compartments were significantly influenced by the rootstocks. Complementary to a shared bacterial microbiome, different subsets of soil bacteria, including those endowed with PGP traits, were selected by the root system compartments of different rootstocks. The interaction between the root compartments and the rootstock exerted a unique selective pressure that enhanced niche differentiation, but rootstock-specific bacterial communities were still recruited with conserved PGP traits.ConclusionWhile the rootstock significantly influences the taxonomy, structure and network properties of the bacterial community in grapevine roots, a homeostatic effect on the distribution of the predicted and potential functional PGP traits was found

Not Available

Not AvailableA simple, sensitive and indirect spectrophotometric method for the determination of protein precipitable polyphenols (tannins) has been developed, based on the ability of the polyphenols to precipitate the synthetic, brown coloured azo-pro- tein, bovine serum albumin±benzidine conjugate (BSA±benzidine, mole ratio 1:7), which shows an absorption maxima at 405 nm. The amount of unprecipita- ted BSA±benzidine is measured directly at 405 nm, which is inversely related to the polyphenol concentration. Tannic acid was used as a reference standard. The microassay was performed in citrate/phosphate bu er (0.1 m), pH 4.8. The method was found to be linear in the range of 5±150 g (3±88 nmol) of tannic acid (y=1.0+(ÿ0.007)x; r=ÿ0.989). Spiking studies carried out with various levels of tannic acid (0.01, 0.1 and 1.0%) indicated a recovery in the range of 94± 101% and 94±98% in rice and sorghum samples, respectively. Free phenolics, when added in the range of 50±150 g (catechin, chlorogenic acid, ferulic acid, ca eic acid and p-coumaric acid) had no in¯uence on the protein precipitation in the microassay. Also spectral analysis of free phenolics and acid-methanolic sor- ghum extracts showed no interference in the present method. The conjugate was found to be stable over a period of 24 weeks in a freeze-dried condition and at 4 C, with <5% deterioration in aqueous condition. The microassay method developed has been used for the quantitation of protein precipitable polyphenols in various sorghum (Sorghum bicolor L. Moench) genotypes and compared with the widely used Folin±Denis chemical method of analysis.Not Availabl

Mineral phosphate solubilization by rhizosphere bacteria and scope for manipulation of the direct oxidation pathway involving glucose dehydrogenase

Microbial biodiversity in the soil plays a significant role in metabolism of complex molecules, helps in plant nutrition and offers countless new genes, biochemical pathways, antibiotics and other metabolites, useful molecules for agronomic productivity. Phosphorus being the second most important macro-nutrient required by the plants, next to nitrogen, its availability in soluble form in the soils is of great importance in agriculture. Microbes present in the soil employ different strategies to make use of unavailable forms of phosphate and in turn also help plants making phosphate available for plant use. Azotobacter, a free-living nitrogen fixer, is known to increase the fertility of the soil and in turn the productivity of different crops. The glucose dehydrogenase gene, the first enzyme in the direct oxidation pathway, contributes significantly to mineral phosphate solubilization ability in several Gram-negative bacteria. It is possible to enhance further the biofertilizer potential of plant growth-promoting rhizobacteria by introducing the genes involved mineral phosphate solubilization without affecting their ability to fix nitrogen or produce phytohormones for dual benefit to agricultural crops. Glucose dehydrogenases from Gram-negative bacteria can be engineered to improve their ability to use different substrates, function at higher temperatures and EDTA tolerance, etc., through site-directed mutagenesis

Bioremediation of industrial toxic metals with gum kondagogu (<i>Cochlospermum gossypium</i>): A natural carbohydrate biopolymer

113-120The ability of gum kondagogu [Cochlospermum gossypium (L.) DC.], a natural carbohydrate biopolymer, was investigated for adsorptive removal of toxic metal ions Cd2+, Cu2+, Fe2+, Pb2+, Ni2+, Zn2+, Hg2+ and total Cr present in industrial effluents. Various physico-chemical parameters, such as, pH, temperature, equilibrium contact time, % biosorption and adsorption capacity, were investigated. Metal biosorption (%) and adsorption capacity of the biopolymer was determined by ICP-MS. Gum kondagogu was capable of competitively biosorb 8 toxic metal ions from the samples of industrial effluents tested. The adsorption capacity was observed to be in the following order, Cd2+ > Cu2+ > Fe2+ > Pb2+ > Hg2+ > total Cr > Ni2+ > Zn2+. The maximum adsorption capacity of metals by gum kondagogu varied in the range of 31-37 mg g-1 for Fe2+ and minimum of 5.5-9.3 mg g-1 for Hg2+ in the effluent samples tested. The equilibrium adsorption data were fitted to Langmuir isotherm models for all the metal ions adsorbed. FT-IR studies were carried out to understand the type of functional groups in gum kondagogu responsible for metal biosorption process. Desorption studies on biosorbed metal ions showed that HCl was a good eluant for all metals tested. The re-adsorption capacity of the recycled gum kondagogu biopolymer sustained its biosorption property at 90% level, even after 3 cycle of desorption. Gum kondagogu biopolymer has the potential to be used as an effective, non-toxic, economical and an efficient biosorbent clean-up matrix for removal of toxic metals from industrial effluents