Mechanisms of Phenytoin‐Induced Toxicity in Freshly Isolated Rat Hepatocytes and the Protective Effects of Taurine and/or Melatonin

Phenytoin is a widely used antiepileptic drug. However, hepatotoxicity is one of its adverse effects reported in some patients. The mechanism(s) by which phenytoin causes hepatotoxicity is not clear yet. This study was designed to evaluate the cytotoxic mechanism(s) of phenytoin toward rat hepatocytes (whose cytochrome P450 enzymes had been induced by Phenobarbital). Furthermore, the effect of taurine and/or melatonin on this toxicity was investigated. Cell death, reactive oxygen species (ROS) formation, lipid peroxidation (LPO), and mitochondrial depolarization were monitored as toxicity markers. Results showed that phenytoin caused an elevation in ROS formation, depletion of intracellular reduced glutathione, increase in cellular oxidized glutathione, enhancement of LPO, and mitochondrial damage. Taurine (1 mM) and/or melatonin (1 mM) administration decreased the intensity of cellular injury caused by phenytoin. This study suggests the protective role of taurine and/or melatonin against phenytoin‐induced cellular damage probably through their reactive radical scavenging properties and their effects on mitochondria.     

Deleterious effects of Bacillus thuringiensis on biological parameters of Habrobracon hebetor parasitizing Helicoverpa armigera

The bacterium Bacillus thuringiensis (Bt) Berliner and the braconid wasp Habrobracon hebetor Say are valuable biocontrol agents attacking larval stages of Helicoverpa armigera (Hübner). Little information is available regarding combination of these biocontrol agents during integrated management of H. armigera. To address this knowledge gap, we document sublethal effects of Bacillus thuringiensis var. kurstaki (Btk) on the H. hebetor attacking H. armigera larvae infected with Btk. The results revealed that the duration of different life stages and fecundity of H. hebetor was significantly affected by sublethal treatments with Btk. We also present data supporting that sublethal concentrations of Btk could adversely affect life table parameters of H. hebetor. Sublethal treatments reduced the net reproductive rate (R ₀) and there were also significant differences among the values of this parameter at all treatments tested. The intrinsic (r _m ) and finite (λ) rates of increase were also significantly lower in parasitoid wasps reared on the treated larvae of H. armigera compared to control. These findings will be useful to develop appropriate strategies for assessing the risks of Btk to the parasitoids and safe deployment of both organisms in integrated pest management programs for sustainable crop production.     

The mzTab Data Exchange Format: Communicating Mass-spectrometry-based Proteomics and Metabolomics Experimental Results to a Wider Audience

The HUPO Proteomics Standards Initiative has developed several standardized data formats to facilitate data sharing in mass spectrometry (MS)-based proteomics. These allow researchers to report their complete results in a unified way. However, at present, there is no format to describe the final qualitative and quantitative results for proteomics and metabolomics experiments in a simple tabular format. Many downstream analysis use cases are only concerned with the final results of an experiment and require an easily accessible format, compatible with tools such as Microsoft Excel or R.We developed the mzTab file format for MS-based proteomics and metabolomics results to meet this need. mzTab is intended as a lightweight supplement to the existing standard XML-based file formats (mzML, mzIdentML, mzQuantML), providing a comprehensive summary, similar in concept to the supplemental material of a scientific publication. mzTab files can contain protein, peptide, and small molecule identifications together with experimental metadata and basic quantitative information. The format is not intended to store the complete experimental evidence but provides mechanisms to report results at different levels of detail. These range from a simple summary of the final results to a representation of the results including the experimental design. This format is ideally suited to make MS-based proteomics and metabolomics results available to a wider biological community outside the field of MS. Several software tools for proteomics and metabolomics have already adapted the format as an output format. The comprehensive mzTab specification document and extensive additional documentation can be found online.Mass spectrometry (MS)¹ has become a major analysis tool in the life sciences (1). It is currently used in different modes for several “omics” approaches, proteomics and metabolomics being the most prominent. In both disciplines, one major burden in the exchange, communication, and large-scale (re-) analysis of MS-based data is the significant number of software pipelines and, consequently, heterogeneous file formats used to process, analyze, and store these experimental results, including both identification and quantification data. Publication guidelines from scientific journals and funding agencies'' requirements for public data availability have led to an increasing amount of MS-based proteomics and metabolomics data being submitted to public repositories, such as those of the ProteomeXchange consortium (2) or, in the case of metabolomics, the resources from the nascent COSMOS (Coordination of Standards in Metabolomics) initiative (3).In the past few years, the Human Proteome Organization Proteomics Standards Initiative (PSI) has developed several vendor-neutral standard data formats to overcome the representation heterogeneity. The Human Proteome Organization PSI promotes the usage of three XML file formats to fully report the data coming from MS-based proteomics experiments (including related metadata): mzML (4) to store the “primary” MS data (the spectra and chromatograms), mzIdentML (5) to report peptide identifications and inferred protein identifications, and mzQuantML (6) to store quantitative information associated with these results.Even though the existence of the PSI standard data formats represents a huge step forward, these formats cannot address all use cases related to proteomics and metabolomics data exchange and sharing equally well. During the development of mzML, mzIdentML, and mzQuantML, the main focus lay on providing an exact and comprehensive representation of the gathered results. All three formats can be used within analysis pipelines and as interchange formats between independent analysis tools. It is thus vital that these formats be capable of storing the full data and analysis that led to the results. Therefore, all three formats result in relatively complex schemas, a clear necessity for adequate representation of the complexity found in MS-based data.An inevitable drawback of this approach is that data consumers can find it difficult to quickly retrieve the required information. Several application programming interfaces (APIs) have been developed to simplify software development based on these formats (7–9), but profound proteomics and bioinformatics knowledge still is required in order to use them efficiently and take full advantage of the comprehensive information contained.The new file format presented here, mzTab, aims to describe the qualitative and quantitative results for MS-based proteomics and metabolomics experiments in a consistent, simpler tabular format, abstracting from the mass spectrometry details. The format contains identifications, basic quantitative information, and related metadata. With mzTab''s flexible design, it is possible to report results at different levels ranging from a simple summary or subset of the complete information (e.g. the final results) to fairly comprehensive representation of the results including the experimental design. Many downstream analysis use cases are only concerned with the final results of an experiment in an easily accessible format that is compatible with tools such as Microsoft Excel® or R (10) and can easily be adapted by existing bioinformatics tools. Therefore, mzTab is ideally suited to make MS proteomics and metabolomics results available to the wider biological community, beyond the field of MS.mzTab follows a similar philosophy as the other tab-delimited format recently developed by the PSI to represent molecular interaction data, MITAB (11). MITAB is a simpler tab-delimited format, whereas PSI-MI XML (12), the more detailed XML-based format, holds the complete evidence. The microarray community makes wide use of the format MAGE-TAB (13), another example of such a solution that can cover the main use cases and, for the sake of simplicity, is often preferred to the XML standard format MAGE-ML (14). Additionally, in MS-based proteomics, several software packages, such as Mascot (15), OMSSA (16), MaxQuant (17), OpenMS/TOPP (18, 19), and SpectraST (20), also support the export of their results in a tab-delimited format next to a more complete and complex default format. These simple formats do not contain the complete information but are nevertheless sufficient for the most frequent use cases.mzTab has been designed with the same purpose in mind. It can be used alone or in conjunction with mzML (or other related MS data formats such as mzXML (21) or text-based peak list formats such as MGF), mzIdentML, and/or mzQuantML. Several highly successful concepts taken from the development process of mzIdentML and mzQuantML were adapted to the text-based nature of mzTab.In addition, there is a trend to perform more integrated experimental workflows involving both proteomics and metabolomics data. Thus, we developed a standard format that can represent both types of information in a single file.     

Genetic diversity and geographical differentiation of Iranian landrace,cultivars, and exotic chickpea lines as revealed by morphological and microsatellite markers

Assessment of the extent of genetic variability within chickpea is fundamental for chickpea breeding and conservation of genetic resources and is particularly useful as a general guide in the choice of parents for breeding hybrids. To establish genetic diversity among 60 accessions of chickpea comprising landraces, internationally developed improved lines, and cultivars, genetic distances were evaluated using 14 simple sequence repeat markers. These markers showed a high level of polymorphism; a total of 59 different alleles were detected, with a mean of 4.2 alleles per locus. The polymorphic information content (PIC) value ranged from 0.31 to 0.89. All the markers, with the exception of TAA170, TA110, GA34, and Ts35, were considered to be informative (PIC > 0.5), indicating their potential usefulness for cultivar identification. Based on the UNJ clustering method, all accessions were clustered in five groups, which indicated the probable origin and region similarity of Iranian landraces over the other cultivars. It also represents a wide diversity among available germplasm. The result has firmly established that introduction of genetic materials from exotic sources has broadened the genetic base of the national chickpea breeding program. As further implications of the findings, this study can be useful for selective breeding for specific traits and in enhancing the genetic base of breeding programs.     

Predicted structure model of Bungarotoxin from Bungarus fasciatus snake

Snake venoms are cocktails comprising combinations of different proteins, peptides, enzymes and toxins. Snake toxins have diverse characteristics having different molecular configuration, structure and mode of action. Many toxins derived from snake venom have distinct pharmacological activities. Venom from Bungarus fasciatus (commonly known as banded krait) is a species of elapid snake found on the South East Asia and Indian sub-continent, mainly contains neurotoxins. Beta bungartotoxin is the major fraction of Bungarus venom and particularly act pre-synaptically by obstructing neurotransmitter release. This toxin in other snake species functionally forms a heterodimer containing two different subunits (A and B). Dimerization of these two chains is a pre-requisite for the proper functionality of this protein. However, B. fasciatus bungartotoxin contains only B chain and their structural orientation in yet to be resolved. Therefore, it is of interest to describe the predicted structure model of the toxin for functional insights. In this work we analyzed the neurotoxic nature, their alignments, secondary and three dimensional structures, functions, active sites and stability with the help of different bioinformatical tools. A comprehensive analysis of the predicted model provides approaching to the functional interpretation of its molecular action.     

A comparative in silico characterization of functional and physicochemical properties of 3FTx (three finger toxin) proteins from four venomous snakes

Snake venom is an abundant resource of diverse pharmacologically bioactive proteins and peptides and a good natural source of drug lead compounds and used as important research tools in the field of toxicology, pharmacology and neuroscience. Three finger toxins (3FTx) is an important super-family of snake venom proteins which has a conserved three finger like appearance in three dimensional structures. Members of 3FTx family show a wide array of pharmacological effects by targeting different receptors and ion channels with high specificity and many of them are being investigated as potential drug target. Therefore, with a vision to verdict a new edge and attempt we determined the amino acid compositional (%) profile, physiochemical properties, secondary structural and functional analysis and phylogenetic relationship of three finger toxins present in four different elapid snake species namely, Naja naja, Astrotia stokesii, Hydrophis cyanocintus and Pelamis platura using different bioinformatics tools. From the outcome of the current studies, it will be possible to know about a range of biological functions which are responsible mainly for the glowing amino acid composition profile of these proteins. Amino acid composition (%) profile although represents differential amount of different amino acid residues which encompasses a family precise model but all the protein sequence have a conserved amount of cysteine. The analysis of physicochemical properties can be used as a basic approach to contribute in developing rational drug through protein engineering and understanding different physiological function which will be beneficial for the welfare of human being.     

Anti-fungal resistance in candida isolated from oral and diaper rash candidiasis in neonates

The purpose of the present study is to evaluate the sensitivity of Candida species isolated from oral candidiasis and diaper dermatitis infections in children. The children referring to private and public clinics in Ilam, Iran were exmined for oral candidiasis and diaper dermatitis. In this study, 248 oral candidiasis and diaper dermatitis samples were collected and cultured.Candida species were identified by using standard methods. Resistance and sensitivity to amphotericin B, nystatin, ketoconazole, fluconazole, itraconazole, clotrimazole, and posaconazole were determined using the CLSI M44-A standard disk diffusion method. From the 248 studied samples, 149 were positive for Candida, among which the Candida albicans was the most prevalent (64.4%). The resistance of different Candida species to nystatin, itraconazole, fluconazole, ketoconazole, clotrimazole, voriconazole, and posaconazole were 4, 43, 34.2, 34.9, 21.5, 6, and 6.7%, respectively. No resistance to amphotericin B was observed. Considering rather low resistance to nystatin, this drug is the best choice for oral candidiasis and diaper dermatitis.     

Study of the inhibitory effect of Quercus Coccifera's aqueous extract on Staphylococcus aureus and Pseudomonas aeruginosa In vitro

The use of therapeutic herbs has become of great importance these days due to the increase in drug resistance. From a long time ago the Venus'' navel plant has been used to treat infections. In this study the antibacterial effect of the aqueous extract from the Quercus coccifera (jaft) herb, under laboratory conditions. This study was carried out experimentally. After collecting the Venus navel herb, it was dried in a warm dry environment away from direct sunlight in the shade. The alcoholic extract was prepared using a standard method. Clinical samples of staphylococcus aureus and pseudomonas aeruginosa were acquired from Ilam''s health care institutes. The inhibitory effect of the extracts was analysed in the Mueller Hinton using the disk diffusion method for both bacteria. Then MIC and MBC of the extracts was determined using the Macro broth dilution method. At its highest concentration the aqueous extract had an inhibition zone of 27.2 and 23.7 mm on staphylococcus aureus and pseudomonas aeruginosa consecutively. The MIC and MBC for staphylococcus aureus were 10 and 12.5 µg/ml and for pseudomonas aeruginosa they were 10 and 17.5 µg/m consecutively. The results of this study show the strong antimicrobial effect of jaft''s aqueous extract on staphylococcus aureus and pseudomonas aeruginosa and if more studies are based on this topic it could be a substitute for common antibiotics.     

Network Scale-Up Correction Factors for Population Size Estimation of People Who Inject Drugs and Female Sex Workers in Iran

Introduction

The results of the network scale-up (NSU) method in estimating the size of key populations for HIV might be biased if the recruited subjects are not fully informed of the risky behaviors of people in their networks (low visibility), or key populations have a smaller social network (low popularity). We aimed to measure such biases in the size estimation of people who inject drugs (PWIDs), and female sex workers (FSWs) in Iran.

Methods

We interviewed 163 male PWIDs, 76 FSWs (known as egos) and 600 subjects from the general population. We selected twenty first-names (ten males and ten females) and asked the study subjects separately how many people they knew with one of these names (known as alters). Visibility Factor (VF) was defined as the percentage of FSW or PWID alters that were aware of their behavior. In addition, the popularity factor (PF) was calculated by dividing the number of alters reported by FSWs and PWIDs into that of the general population. The 95% uncertainty intervals (UI) were calculated using bootstrap technique.

Results

The VF was estimated at 54% (95% UI: 52%–56%) for PWID and 45% (95% UI: 42%– 48%) for FSW. The VF among the peer alters was significantly higher than non-peer ones. The PF for PWID and FSW was 69% (95% UI: 66%–73%) and 77% (95% UI: 72%–83%), respectively. The cross-validation and name splitting analysis showed that our estimates were not influenced by any single name.

Conclusions

Both correction factors, particularly VF were far from one, and NSU results without correction, could lead to up to 4 times underestimation of the sizes. Therefore, applying these coefficients is necessary in NSU projects.