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In this study, the Sr22 gene was isolated and prepared for transformation in disease-susceptible commercial high-yielding wheat ( Triticum aestivum L.) cultivar Lasani-2008. The Sr22 fragment was initially inserted in plasmid pUC57 for sequence confirmation before performing further experiments. After confirmation, Sr22 was subcloned in pGreen0029 which helped in further cloning and ligation. pUC57- Sr22 was restricted with Nru 1 and Bam H1, while pGreen0029 was restricted with Eco RV and Bam H1 and ligated. From pGreen0029, Sr22 was eluted and ligated in pJIT163 to insert the 2 × 35S promoter and CaMV terminator using Xho 1 and Bam H1 and Sal 1. At this stage, the expression cassette was completed. The 2 × 35Sp- Sr22 -CaMVt was then ligated in pGreen0029 and transferred to Agrobacterium along with pSOUP. pSOUP helped pGreen0029 to insert 2X35Sp- Sr22 -CaMVt in the callus of Lasani-2008, along with kanamycin-resistant gene. Transgenic callus was used for regeneration of the whole plant by tissue culture. Transgenic plants were further tested by PCR, qPCR and SDS-PAGE. The transgenic Lasani-2008 showed substantial resistance against stem rust in both seedling and adult plant stages. The results also showed that transgenic Lasani-2008 has increased average yield of grains (i.e., 4893 ± 148 kg/ha) as compared to non-transgenic Lasani-2008 (i.e., with average yield of gains 4762 ± 103 kg/ha). Sr22 containing lines and the transgenic developed in this study can be used in breeding systems. Transgenic seeds developed will be shared with breeding institutes and breeders should use this information to develop new varieties., Competing Interests: Conflict of interestAuthors declare that no conflict of interest exists., (© King Abdulaziz City for Science and Technology 2020.)

A recent spike in demand for chemical preservative free food has derived the scientific community to develop natural ways of food preservation. Therefore, bio-preservation could be considered as the great alternative over chemical ones owing to its potential to increase shelf-life and nutritional values of foodstuffs. In the present study, lactic acid producing bacterial species were isolated from rice rinsed water and identified by 16S rRNA gene sequencing as Lactobacillus plantarum BCH-1 (KX388380) and Lactobacillus coryniformis BCH-4 (KX388387). Antifungal metabolites from both Lactobacillus species were extracted by polarity-based solvents in which ethyl acetate showed remarkable antifungal activity against Aspergillus flavus and Aspergillus fumigatus by disc diffusion assay. Different organic acids and fatty acids have been identified by reversed-phase high-performance liquid chromatography (RP-HPLC) and gas chromatography-mass spectrometry (GC-MS) analysis, respectively. Lactic acid and citric acid were the major organic acids found in ethyl acetate fractions of L. plantarum and L. coryniformis, respectively. Similarly, 9,12-otadecadienoic acid (Z,Z)-methyl ester and hexadecanoic acid, methyl ester were the major fatty acids found in n-hexane fractions of L. plantarum and L. coryniformis respectively. Moreover, the isolation of novel antifungal metabolites from locally isolated Lactobacillus species was focused and it was revealed that organic acids are important contributors towards antifungal potential. A novel fatty acid (i.e. 12-hydroxydodecanoic acid) has also been explored and found as potential metabolite against filamentous fungi. Conclusively, various metabolites isolated from non-dairy source showed antifungal activity especially against Aspergillus species. Hence, these metabolites have been considered as a good choice for bio-preservation.

Crop pollination by the western honey bee Apis mellifera is vital to agriculture but threatened by alarmingly high levels of colony mortality, especially in Europe and North America. Colony loss is due, in part, to the high viral loads of Deformed wing virus (DWV), transmitted by the ectoparasitic mite Varroa destructor, especially throughout the overwintering period of a honey bee colony. Covert DWV infection is commonplace and has been causally linked to precocious foraging, which itself has been linked to colony loss. Taking advantage of four brain transcriptome studies that unexpectedly revealed evidence of covert DWV-A infection, we set out to explore whether this effect is due to DWV-A mimicking naturally occurring changes in brain gene expression that are associated with behavioral maturation. Consistent with this hypothesis, we found that brain gene expression profiles of DWV-A infected bees resembled those of foragers, even in individuals that were much younger than typical foragers. In addition, brain transcriptional regulatory network analysis revealed a positive association between DWV-A infection and transcription factors previously associated with honey bee foraging behavior. Surprisingly, single-cell RNA-Sequencing implicated glia, not neurons, in this effect; there are relatively few glial cells in the insect brain and they are rarely associated with behavioral plasticity. Covert DWV-A infection also has been linked to impaired learning, which together with precocious foraging can lead to increased occurrence of infected bees from one colony mistakenly entering another colony, especially under crowded modern apiary conditions. These findings provide new insights into the mechanisms by which DWV-A affects honey bee health and colony survival.

Background: The implementation of the Electronic Medical Record (EMR) system initiated a significant transition in the healthcare system from traditional paper-based medical records to a digital version. Though EMR offers several benefits compared to Paper Medical Records (PMR), patient satisfaction with the EMR has been an area of concern. The objective of this study is to explore patient satisfaction with the EMR compared to the PMR of patients attending five Primary Healthcare Centers in the Western Region of Saudi Arabia., Methods: A cross-sectional survey was conducted with patients who attended five Primary Health Care centers (PHCs) in the Western Region during 2018. A sample of 377 participants was invited to complete a self-developed structured questionnaire with multiple choice and Likert Scale questions. The questionnaire was distributed to participants in the PHC waiting areas., Results: The sample size realized as (n = 377) participants, the majority (65.0%) were female. The overall patient satisfaction was 3.708. Patient satisfaction with the EMR was statistically significant compared to the PMR (3.7241 vs. 3.6919, p < 0.001). Several factors provided evidence of the overall satisfaction with the implementation of the EMR, including an increase in physician attention during the clinical consultation (82.3%), increased explanation of tests and medication (85.8%), increased time spent with the patient during the consultation (80.4%) and increased active listening by the physician (77.3%). Besides, the patients felt confident to ask the physician question related to health during clinical consultation (84.0%)., Conclusion: Patient satisfaction during the clinical consultation and overall satisfaction with various PHC services improved with the implementation of EMR.

The present study was conducted to examine the effect of exogenously applied ascorbic acid (AsA) on osmoprotectants and the oxidative defense system in four cultivars (16171, 16183, 16207 and 16246) of safflower under well-watered and water deficit conditions. Water stress (60% field capacity) significantly decreased the shoot and root fresh and dry weights, shoot and root lengths and chlorophyll contents in all four safflower cultivars, while it increased the leaf free proline, total phenolics, total soluble proteins, hydrogen peroxide content and activities of catalase, superoxide dismutase and peroxidase enzymes. Foliar-applied (100 mg L -1 and 150 mg L - 1 ) ascorbic acid caused a marked improvement in shoot and root fresh and dry weights, plant height, chlorophyll and AsA contents as well as the activity of peroxidase (POD) enzyme particularly under water deficit conditions. It also increased the accumulation of leaf proline, total phenolics, total soluble proteins and glycine betaine (GB) content in all four cultivars. Exogenously applied AsA lowered the contents of MDA and H 2 O 2, and the activities of CAT and SOD enzymes. Overall, exogenously applied AsA had a positive effect on the growth of safflower plants under water deficit conditions which could be related to AsA-induced enhanced osmoprotection and regulation of antioxidant defense system., Competing Interests: The authors declare no conflict of interest.

The complicated clinical picture and biomolecular pattern of human autoimmune diseases (ADs) make knowledge on their etiology still fragmentary. The diagnostic approaches for ADs require improvement both for clinical and research effort to progress. Synthetic biomolecular antigens find growing applications for diagnosis and investigation of ADs. The main goal of this work is to detect interaction between synthetic antigens and autoantibodies in systemic lupus erythematosus within a combined, high-throughput assay. A panel of synthetic antigens has been prepared from DNA, RNA, locked nucleic acids and apolipoprotein H. The binding of synthetic antigens to autoantibodies has been confirmed in sera samples from those with active systemic lupus erythematosus (SLE) by indirect enzyme linked immunosorbent assay. Our study provides an efficient methodology for combined autoantibody profiling in SLE.

Hearing loss is a genetically heterogeneous disorder affecting approximately 360 million people worldwide and is among the most common sensorineural disorders. Here, we report a genetic analysis of seven large consanguineous families segregating prelingual sensorineural hearing loss. Whole-exome sequencing (WES) revealed seven different pathogenic variants segregating with hearing loss in these families, three novel variants (c.1204G>A, c.322G>T, and c.5587C>T) in TMPRSS3, ESRRB, and OTOF , and four previously reported variants (c.208C>T, c.6371G>A, c.226G>A, and c.494C>T) in LRTOMT , MYO15A , KCNE1 , and LHFPL5 , respectively . All identified variants had very low frequencies in the control databases and were predicted to have pathogenic effects on the encoded proteins. In addition to being familial, we also found intersibship locus heterogeneity in the evaluated families. The known pathogenic c.226C>T variant identified in KCNE1 only segregates with the hearing loss phenotype in a subset of affected members of the family GCNF21. This study further highlights the challenges of identifying disease-causing variants for highly heterogeneous disorders and reports the identification of three novel and four previously reported variants in seven known deafness genes., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Secreted frizzled-related protein 4 (SFRP4) is a member of secreted protein family with sequence similarity to frizzled receptors of wingless-related integration site (Wnt) signaling pathways. These proteins control diverse functions from embryonic development to adults in many organisms including humans. Initially, SFRPs were recognized as antagonists of Wnt signaling and supposed to interact with Wnts. Further research demonstrated their interactions to frizzled receptors and a functional diversity was related to these proteins, Wnt signaling potentiation in addition to modulation. SFRP4 is the largest member of SFRP family and is implicated in many diseases including obesity, type 2 diabetes (T2D), and cancer. SFRP4 acts as a biomarker for T2D and was expressed several years before clinical diagnosis of disease. This review mainly focusses on the role of SFRP4 in obesity and how it can lead to β-cell failure and ultimately to T2D. The role of SFRP4 in adipose tissues causing increased production of adipokines lead to the oxidative stress in pancreas that particularly have low amount of antioxidant enzymes in pancreatic β-cells leading to failure in exocytosis of insulin containing granules causing T2D. Obesity-induced inflammation is a principal factor in pathogenesis of insulin resistance as well as metabolic syndrome. Pro-inflammatory cytokines have potential to cause insulin resistance in skeletal muscles, adipose tissue, and liver via inhibition of insulin signal transduction. Secretion of SFRP4 is mediated by interleukin 1-β (IL1-β). This review highlights the molecular mechanisms by which SFRP4 leads to T2D. Understanding of molecular mechanism and targeting SFRP4 could help to eradicate or reduce chances of developing T2D., (© 2019 International Union of Biochemistry and Molecular Biology.)

Alzheimer's disease (AD) differentially and specifically affects brain regions and neuronal cell types in a predictable pattern. Damage to the brain appears to spread and worsens with time, taking over more regions and activating multiple stressors that can converge to promote vulnerability of certain cell types. At the same time, other cell types and brain regions remain intact in the face of this onslaught of neuropathology. Although neuropathologic descriptions of AD have been extensively expanded and mapped over the last several decades, our understanding of the mechanisms underlying how certain regions and cell populations are specifically vulnerable or resistant has lagged behind. In this review, we detail what is known about the selectivity of local initiation of AD pathology in the hippocampus, its proposed spread via synaptic connections, and the diversity of clinical phenotypes and brain atrophy patterns that may arise from different fibrillar strains of pathologic proteins or genetic predispositions. We summarize accumulated and emerging knowledge of the cellular and molecular basis for neuroanatomic selectivity, consider potential disease-relevant differences between vulnerable and resistant neuronal cell types and isolate molecular markers to identify them.

Altered enzymatic machineries are a substantial biochemical characteristic of tumor cell metabolism that switch metabolic profile from oxidative phosphorylation to amplified glycolysis as well as increased lactate production under hypoxia conditions. Reprogrammed metabolic profile is an emerging hallmark of cancer. Overexpression of several glycolytic enzymes and glucose transporters has been reported in 24 different types of cancers that represent approximately 70% of all the cancer cases around the globe. Thus, targeting glycolytic enzymes could serve as tempting avenue for drug design against cancer. Phosphoglycerate mutase 1 (PGAM1) is an important glycolytic enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate. Recent investigations have revealed the overexpression of PGAM1 in several human cancers that is linked with tumor growth, survival, and invasion. The aim of this review is to update scientific research network with cancer-specific role of PGAM1 to elucidate its capability as bonafide therapeutic target for cancer therapy. Moreover, we have also summarized the reported genetic and pharmacological inhibitors of PGAM1. This study suggests that further investigations on PGAM1 should focus on the exploration of molecular mechanisms of PGAM1 overexpression in development of cancer, assessment of biosafety profiles of known inhibitors of PGAM1, and utilization of PGAM1 inhibitors in combinatorial therapies. These future studies will surely support the unbiased strategies for the development of novel PGAM1 inhibitors for cancer therapies., (© 2019 International Union of Biochemistry and Molecular Biology.)

Motherhood is characterized by dramatic changes in brain and behavior, but less is known about fatherhood. Here we report that male sticklebacks-a small fish in which fathers provide care-experience dramatic changes in neurogenomic state as they become fathers. Some genes are unique to different stages of paternal care, some genes are shared across stages, and some genes are added to the previously acquired neurogenomic state. Comparative genomic analysis suggests that some of these neurogenomic dynamics resemble changes associated with pregnancy and reproduction in mammalian mothers. Moreover, gene regulatory analysis identifies transcription factors that are regulated in opposite directions in response to a territorial challenge versus during paternal care. Altogether these results show that some of the molecular mechanisms of parental care might be deeply conserved and might not be sex-specific, and suggest that tradeoffs between opposing social behaviors are managed at the gene regulatory level.

The aim of the present study was to purify, hydrolyze and modify the Cordia myxa gum to document its binder potential in pharmaceutical tablets formulation. The hydrolysis and modification was carried out to remove impurities, roughness, increase thermal stability and to improve the functional properties of biopolymers. Physiochemical properties such as pH, solubility, viscosity, swelling index, bulk and tapped density was performed prior to investigate binder potential. The binder potential of Cordia myxa gum was studied in its different forms such as crude, purified, modified and hydrolyzed in paracetamol tablets and was compared with standard hydroxypropyl methylcellulose (HPMC) being used as synthetic binder. Tablets were prepared by direct compression method and evaluated for weight uniformity, hardness, friability, disintegration time and dissolution analysis. Prepared tablets with selected gums exhibit faster and slower dissolution profile in the same dissolution system. The crude gum has high dissolution rate whereas the hydrolyzed and modified gums showed less dissolution rate. The hydrolyzed and modified gums having faster release rate and it could be helpful in conventional tablet formulations efficiently as compared to synthetic HPMC binder.

The need for some economic strategies for increased growth and nutraceuticals of medicinal plants is well acknowledged now. It was hypothesized that external magnetic field treatment (MFT) of seeds affecting internal magnet of cells may affect growth and metabolism. In this study, seeds were subjected to pre-sowing magnetic field (50 mT at 5 mm for 5 s). At vegetative stage, the leaf growth, chlorophyll content, catalase (CAT), peroxidase (POD), amino acids, proteins, flavonoids, soluble sugars, total soluble phenolics, carotenoids, anthocyanins, phenolic profile (HPLC based), and antimicrobial activity of leaves (in terms of the minimum inhibitory concentration against Staphylococcus aureus and Pseudomonas aeruginosa) were studied. Yield was evaluated for nutritive components in fruit (peel+pulp) and peel. MFT improved germination percentage, growth, leaf chlorophyll, antimicrobial activity, peel amino acids, phenolics, and POD with negligible effect on fruit nutritive value. Moreover, photosynthetic pigments and cinnamic acid exhibited direct correlation with antimicrobial potential against both pathogens. However, sinapic acid showed positive correlation against Staphylococcus aureus only. Cinnamic acid, coumaric acid, syringic acid, and quercetin were in direct correlation against Pseudomonas aeruginosa; it was directly correlated with total flavonoids too. In conclusion, magnetic field can be used to manipulate plant cell metabolism promising improvement of growth, antimicrobial activity, and phenolics of interest.

Pathogenic agents cause an increased risk of various fatal diseases and there is a need to reduce this risk using medicinal plants and their seeds. The present research work was designed to study the efficacy of different sunflower seed hybrid varieties (i.e. FH622, FH620, FH615, FH613 and FH545) chemically primed with potassium nitrate as natural antioxidant and antimicrobial agent. Antioxidant potential was determined using DPPH test, reducing power, TPC and TFC. Antibacterial activity was determined against Gram positive and Gram negative bacterial species. After one week, the germination data including mean germination and percentage of final emergence was calculated. It was found that seed varieties FH620 and FH615 have higher values of mean germination as compared to FH545 while FH615 has higher percentage of final emergence as compared to FH620 and FH545. High phenolic and flavonoid contents were observed in FH620 and FH615 as compared to FH545 variety. It was also observed that seed variety FH615 when treated with KNO3 solution had significantly high germination as well as antioxidant parameters and antibacterial activity as compared to other varieties. Similarly FH615 showed high antibacterial activities against Gram positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria. This study showed that all selected sunflower hybrids have good antioxidant and antibacterial potentials that would further be used for different trials to cure different pathogen related diseases, and these are natural sources of antioxidants for commercial and therapeutic applications.

A technique is presented where a custom milled impression coping is used to replicate the clinically established anterior incisal guidance to the definitive prosthesis when multiple implants are restored in the esthetic zone. A conventional impression is initially made, then the stone cast is scanned, and a digitally designed custom screw-retained, implant-supported interim prosthesis is milled from a polymethylmethacrylate (PMMA) billet. This is aimed to digitally design the pontic areas, contour the gingival soft tissue, and establish an anterior incisal guidance. A custom milled impression coping (CMIC) is then fabricated. The CMIC has contours similar to the contours of the interim prosthesis and is fabricated from a PMMA billet. Titanium inserts are placed in the interim prosthesis and the CMIC. The CMIC is inserted intraorally and used for the final impression by using a custom tray and by following the open tray impression protocol. With the proposed technique, the exact contours of the digitally designed and clinically verified interim prosthesis are used to fabricate the definitive restoration., (© 2019 by the American College of Prosthodontists.)

Purpose: Primary congenital glaucoma (PCG) is a clinically and genetically heterogeneous disease. The present study was undertaken to find the genetic causes of PCG segregating in 36 large consanguineous Pakistani families., Methods: Ophthalmic examination including fundoscopy, or slit-lamp microscopy was performed to clinically characterize the PCG phenotype. Genomic nucleotide sequences of the CYP1B1 and LTBP2 genes were analyzed with either Sanger or whole exome sequencing. In silico prediction programs were used to assess the pathogenicity of identified alleles. ClustalW alignments were performed to determine evolutionary conservation, and three-dimensional (3D) modeling was performed using HOPE and Phyre2 software., Results: Among the known loci, mutations in CYP1B1 and LTBP2 are the common causes of PCG. Therefore, we analyzed the genomic nucleotide sequences of CYP1B1 and LTBP2 , and detected probable pathogenic variants cosegregating with PCG in 14 families. These included the three novel (c.542T>A, c.1436A>G, and c.1325delC) and five known (c.868dupC, c.1168C>T, c.1169G>A, c.1209InsTCATGCCACC, and c.1310C>T) variants in CYP1B1 . Two of the novel variants are missense substitutions [p.(Leu181Gln), p.(Gln479Arg)], which replaced evolutionary conserved amino acids, and are predicted to be pathogenic by various in silico programs, while the third variant (c.1325delC) is predicted to cause reading frameshift and premature truncation of the protein. A single mutation, p.(Arg390His), causes PCG in six (~43%) of the 14 CYP1B1 mutations harboring families, and thus, is the most common variant in this cohort. Surprisingly, we did not find any LTBP2 pathogenic variants in the families, which further supports the genetic heterogeneity of PCG in the Pakistani population., Conclusions: In conclusion, results of the present study enhance our understanding of the genetic basis of PCG, support the notion of a genetic modifier of CYP1B1 , and contribute to the development of genetic testing protocols and genetic counseling for PCG in Pakistani families.

Social challenges like territorial intrusions evoke behavioral responses in widely diverging species. Recent work has showed that evolutionary "toolkits"-genes and modules with lineage-specific variations but deep conservation of function-participate in the behavioral response to social challenge. Here, we develop a multispecies computational-experimental approach to characterize such a toolkit at a systems level. Brain transcriptomic responses to social challenge was probed via RNA-seq profiling in three diverged species-honey bees, mice and three-spined stickleback fish-following a common methodology, allowing fair comparisons across species. Data were collected from multiple brain regions and multiple time points after social challenge exposure, achieving anatomical and temporal resolution substantially greater than previous work. We developed statistically rigorous analyses equipped to find homologous functional groups among these species at the levels of individual genes, functional and coexpressed gene modules, and transcription factor subnetworks. We identified six orthogroups involved in response to social challenge, including groups represented by mouse genes Npas4 and Nr4a1, as well as common modulation of systems such as transcriptional regulators, ion channels, G-protein-coupled receptors and synaptic proteins. We also identified conserved coexpression modules enriched for mitochondrial fatty acid metabolism and heat shock that constitute the shared neurogenomic response. Our analysis suggests a toolkit wherein nuclear receptors, interacting with chaperones, induce transcriptional changes in mitochondrial activity, neural cytoarchitecture and synaptic transmission after social challenge. It shows systems-level mechanisms that have been repeatedly co-opted during evolution of analogous behaviors, thus advancing the genetic toolkit concept beyond individual genes., (© 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

The increasing risk of variety of fatal diseases including diabetes mellitus is imposing serious challenge to chemist, biologists and clinicians. Due to the side effects of the chemotherapy, worldwide it is thinking that phyto-medicine are more effective to cope continuously increasing risk of fatal diseases without any side effect. Seed priming is a strategic pre-sowing semi-bioengineering technique which has ability to improve the growth rate and biologically active compounds in short time. Among seed priming techniques, tyrosine seed priming most frequently used because amino acids provide best growth media for nutritional food crops. Seeds of Momordica charantia were subjected to the pre-sowing tyrosine solution. Different growth parameters including growth emergence rate, seedling vigor, growth and weight of root, shoot and leaf were studied. The results showed positive effect on Momordica charantia seed growth and phenolic acids production i.e. ferulic acid - 43.95 ppm and sinapic acid - 18.39 ppm. The antiglycation assay showed 23.45±1.23% antiglycation activity of primed-seed fruit extract as compare to control seed fruit extract (0.87±0.03%). On the basis of the results, it is concluded that tyrosine primed seed fruit extract could effectively be further tested for pre-clinical and clinical studies to manage diabetes mellitus disease.

A technique is described where the tooth's natural crown is used as part of the interim implant supported prosthesis in clinical situations where a tooth with poor prognosis is extracted and an implant is placed immediately after tooth extraction. A preliminary impression is made before tooth extraction, and the exact tooth positioning is assessed in the laboratory as part of the treatment plan. An acrylic resin repositioning jig is fabricated that will guide the clinician in seating and orienting the crown intraorally after implant placement is completed. After the natural tooth is extracted and an implant is immediately placed via guided approach, the extracted natural crown is hollowed and placed on top of an interim abutment. The natural crown is positioned intraorally by using the acrylic resin repositioning jig. The crown is then internally relined and placed as part of the interim implant supported prosthesis. After osseointegration has been confirmed, a definitive prosthesis is placed.

Growing evidence points to a disruption of cortico-thalamo-cortical circuits in schizophrenia (SZ) and bipolar disorder (BD). Clues for a specific involvement of the thalamic reticular nucleus (TRN) come from its unique neuronal characteristics and neural connectivity, allowing it to shape the thalamo-cortical information flow. A direct involvement of the TRN in SZ and BD has not been tested thus far. We used a combination of human postmortem and rodent studies to test the hypothesis that neurons expressing parvalbumin (PV neurons), a main TRN neuronal population, and associated Wisteria floribunda agglutinin-labeled perineuronal nets (WFA/PNNs) are altered in SZ and BD, and that these changes may occur early in the course of the disease as a consequence of oxidative stress. In both disease groups, marked decreases of PV neurons (immunoreactive for PV) and WFA/PNNs were observed in the TRN, with no effects of duration of illness or age at onset. Similarly, in transgenic mice with redox dysregulation, numbers of PV neurons and WFA/PNN+PV neurons were decreased in transgenic compared with wild-type mice; these changes were present at postnatal day (P) 20 for PV neurons and P40 for WFA/PNN+PV neurons, accompanied by alterations of their firing properties. These results show profound abnormalities of PV neurons in the TRN of subjects with SZ and BD, and offer support for the hypothesis that oxidative stress may play a key role in impacting TRN PV neurons at early stages of these disorders. We put forth that these TRN abnormalities may contribute to disruptions of sleep spindles, focused attention and emotion processing in these disorders.

Organisms can gain information about their environment from their ancestors, their parents or their own personal experience. 'Cue integration' models often start with the simplifying assumption that information from different sources is additive. Here, we test key assumptions and predictions of cue integration theory at both the phenotypic and molecular level in threespined sticklebacks (Gasterosteus aculeatus). We show that regardless of whether cues about predation risk were provided by their father or acquired through personal experience, sticklebacks produced the same set of predator-adapted phenotypes. Moreover, there were nonadditive effects of personal and paternal experience: animals that received cues from both sources resembled animals that received cues from a single source. A similar pattern was detected at the molecular level: there was a core set of genes that were differentially expressed in the brains of offspring regardless of whether risk was experienced by their father, themselves or both. These results provide strong support for cue integration theory because they show that cues provided by parents and personal experience are comparable at both the phenotypic and molecular level, and draw attention to the importance of nonadditive responses to multiple cues.

Prevalence of hepatitis C virus (HCV) has been seen in more than 15% of Pakistani population. For the treatment of this infection, only two medicines, interferon, and ribavirin were approved in 1998. The concerned physicians evaluate side effects of these two antiviral drugs only during the treatment period. The long-term extra hepatic side effects are being neglected. This retrospective study was conducted with reference to induced infertility in HCV treated 40 male patients from the period 2008-2015. Possible effects of interferon therapy on fertility hormones and seminal parameters were assessed. Level of fertility hormones like serum Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), and testosterone was measured. For seminal parameters, guidelines from World Health Organization (WHO) were followed. Among forty cases of HCV patients who received interferon, only 14 (35%) have children and 26 (65%) could not conceive (p = 0.0372). After HCV treatment, HCV positive patients showed a significant change in the level of FSH, LH (p<0.05). Especially, it decreased testosterone level (p=0.0096). Similarly, HCV treatment significantly decreased sperm count (p=0.001) and motility (p=0.0005).

Retinitis pigmentosa (RP) is the most frequent genetically and clinically heterogeneous inherited retinal degeneration. To date, more than 80 genes have been identified that cause autosomal dominant, autosomal recessive and X linked RP. However, locus and allelic heterogeneity of RP has not been fully captured yet. This heterogeneity and lack of an accurate genotype phenotype correlation makes molecular dissection of the disease more difficult. The present study was designed to characterize the underlying pathogenic variants of RP in Pakistan. For this purpose, a large consanguineous family with RP phenotype showing autosomal recessive mode of inheritance was selected after a complete ophthalmological examination. Next generation sequencing was used for the identification of molecular determinant followed by Sanger-sequencing for confirmation. After sequence analysis a novel homozygous missense mutation, (c.602 C > T) in exon 4 of the RDH5 gene (MIM: 601617) was identified. This mutation resulted in substitution of phenyl alanine for serine at amino acid 201 (p.Ser201Phe) of the RDH5 gene. The same mutation was not detected in the 200 ethnically-matched control samples by Sanger sequencing. The identified mutant allele segregated in homozygous fashion in all the affected individuals of pedigree. Identification of this mutation reveals the allelic heterogeneity of RDH5 in patients with RP phenotype. The findings of this study demonstrate the clinical significance of next generation sequencing to understand the molecular basis of diseases and would help to reveal new proteins and their function in visual cycle will pave the way for early diagnosis, genetic counseling and better therapeutic inventions.

Citrate synthase (CS) is involved in citric acid biosynthesis which is a well-established metabolic pathway. The condensation of acetyl-CoA with oxaloacetate is catalyzed by CS. Citric acid (CA) has a number of applications in pharmaceutical industry. CA in combination with bicarbonates is used as an effervescent in the preparations of tablets and powders. It has also been used as an anticoagulant and acidulant to form mild astringent. In current study, detailed structural and functional analyses of CS protein were carried out using various bioinformatics tools. Structural modeling was also done by building 3D model of CS from Aspergillus niger ANJ-120 using Modeller 9.16 software. The 3D Model was then evaluated using different online approaches. Furthermore, superimposition of query and template structures, Root Mean Squared Deviation and visualization of generated model were done through UCSF Chimera 1.5.3. Even though various roles of CS protein were already known and verified experimentally, here we presented a structural analysis of CS protein. The structural investigation of CS protein will be helpful for protein engineering strategies and understanding the interactions among proteins. Due to large number of applications, the production of citric acid by A. niger and its bioinformatics studies will offer substantial improvement in commercial scale intensification of this useful product.

The original version of this article unfortunately contained typographical errors in the text and figures. This article has been updated to correct these errors as red highlighting in this pages.

Zika virus belongs to family of viruses 'Flaviviridae' and spreads mostly by daytime-active Aedes mosquitoes. The resulting infection is known as Zika fever. It is usually asymptomatic or often causes mild symptoms, which are very similar to dengue fever. The Aedes aegypti mosquito is also responsible for dengue and chikungunya viruses. Zika virus can spread by crossing the placental barrier from a pregnant mother to a fetus, which can result in microcephaly, severe brain malformations including Guillain-Barre syndrome (GBS), and other birth defects. Until now, there is no specific treatment of Zika fever disease, and Zika virus illness cannot be prevented by medications or vaccines. According to WHO, no vaccine is likely to be available until 2020. The only way of preventing this disease is to prevent the mosquito bites. This article presents the history of Zika virus, its reported cases including microcephaly and GBS, and a comparison of its symptoms with those of dengue and chikungunya diseases, as well as preventive measures. With advances in research and technology, knowledge about the Zika virus has grown, yet some questions remain unanswered regarding Zika virus's genetic diversity, pathophysiology, transmission vectors and reservoirs, potential synergetic of coinfection with other related arboviruses, and treatment. These problems highlight the need for further research to achieve adequate the surveillance, infection management, optimized treatment, and public health mediations in Zika virus outbreaks. This article contributes to our understanding of the disease mechanism, genome structure, diagnosis, transmission, and preventive strategies to combat Zika virus infection.

Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell growth, proliferation, polarity, differentiation, development, and controls transitioning between anabolic and catabolic states of the cell. It collects almost all extracellular and intracellular signals from growth factors, nutrients, and maintains cellular homeostasis, and is involved in several pathological conditions including, neurodegeneration, Type 2 diabetes (T2D), obesity, and cancer. In this review, we summarize current knowledge of upstream signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which state, the role of telomere attrition is explained. We discuss if chronic inhibition of mTORC1 can reverse adverse effects resulting from hyperactivation. In conclusion, we suggest the regulatory roles of telomerase (TERT) and hexokinase II (HKII) on mTORC1 as possible remedies to treat hyperactivation. The former inhibits mTORC1 under nutrientrich while the latter under starved condition. We provide an idea of TOS (TOR signaling) motifs that can be used for regulation of mTORC1. [BMB Reports 2017; 50(12): 601-609].

Hepatitis C Virus (HCV) infection is a worldwide serious health issue which contributes towards most of the hepatic morbidities. So far no prophylaxis is available to prevent this virus; therefore, development of antiviral compounds to fight HCV infection is the need of time. Chemically synthesized peptides that are potent immunogenic antigens are being pursued as candidate vaccines against HCV. The present study was planned to identify peptide inhibitors having potential to block the activity of NS3 protein of HCV that will ultimately arrest HCV multiplication. Docking of NS3 with peptides revealed that the majority of the peptides have strong binding affinity for active sites of NS3. Peptide 1, 2, 3 and 6 were found interactive with NS3 active residues while the active sites of NS3 had hydrophobic contact with the rest of peptides. Thus, these peptides bear therapeutic potential of a candidate drug for the prevention of HCV replication. Post docking analysis revealed important binding abilities of peptides with the active sites of NS3 protein, showing the efficiency of peptides as potential peptide inhibitors against HCV. The study revealed that HCV replication can be inhibited by these peptides. HCV replication inhibition potential of these peptides can contribute in reducing the burden of HCV infection and its associated complications worldwide.

Animals exhibit dramatic immediate behavioral plasticity in response to social interactions, and brief social interactions can shape the future social landscape. However, the molecular mechanisms contributing to behavioral plasticity are unclear. Here, we show that the genome dynamically responds to social interactions with multiple waves of transcription associated with distinct molecular functions in the brain of male threespined sticklebacks, a species famous for its behavioral repertoire and evolution. Some biological functions (e.g., hormone activity) peaked soon after a brief territorial challenge and then declined, while others (e.g., immune response) peaked hours afterwards. We identify transcription factors that are predicted to coordinate waves of transcription associated with different components of behavioral plasticity. Next, using H3K27Ac as a marker of chromatin accessibility, we show that a brief territorial intrusion was sufficient to cause rapid and dramatic changes in the epigenome. Finally, we integrate the time course brain gene expression data with a transcriptional regulatory network, and link gene expression to changes in chromatin accessibility. This study reveals rapid and dramatic epigenomic plasticity in response to a brief, highly consequential social interaction.

Lentinus edodes is a culinary-medicinal mushroom that has an established history of use in Asian therapies. The mushroom offers well-documented beneficial health effects such as antihypercholesterolemic, antitumor, and antibacterial activities. In this study, dried powder of L. edodes fruiting bodies was used to evaluate immunomodulatory, hepatoprotective, and antioxidant effects in hypercholesterolemic rats. Albino rats (n = 24) were divided into 3 groups: the control (CON) group, the hypercholesterolemia-only group (HCG), and the L. edodes group (LEG). Hypercholesterolemia was induced in rats in the HCG and LEG by feeding cholesterol and cholic acid in a chow maintenance diet (CMD) for 24 days. The CON group was fed the CMD throughout the experiment. The HCG continued on the high-cholesterol diet without any L. edodes supplement. The LEG was fed the high-cholesterol diet supplemented with L. edodes for an additional 42 days. Various biological health biomarkers, such as total antioxidant capacity, total oxidant status, arylesterase, paraoxonase activity, and liver enzymes in serum were studied to evaluate antioxidant and hepatoprotective responses. Cell-mediated immunity was evaluated in each group through a delayed type of hypersensitivity reaction. The total oxidant status decreased significantly (P ≤ 0.05) after administration of L. edodes in the diet. The cell-mediated immune response significantly increased (P ≤ 0.05) in the LEG. The significant decrease in liver enzymes supports the hepatoprotective effect of L. edodes. In conclusion, the results show the immunomodulatory, hepatoprotective, and antioxidant activities of L. edodes supplementation in hypercholesterolemic rats.

Amounts of DNA damage and homocysteine (Hcy) in heart patients blood may have strong function in the causation of cardiovascular disease (CVD). The main objective of this work was to know experimentally the role of total oxidants (produced by Reactive Oxygen species (ROS), clinical biochemical indices, their oxidized products and total antioxidant status (TAS) among such patients to find the association of homocysteine, total oxidation status (TOS) and oxidative DNA damage with other clinical parameters in sixty positive CVD patients compared with those of 60 normal subjects. As compared to healthy individuals, CVD patients had significantly higher concentrations of homocysteine (p<0.0001), total oxidants stress (TOS) (p<0.0001), serum total lipids (p<0.04), malondialdehyde (MDA) (p<0.001), high density lipoprotein-cholesterol (HDL-C) (p<0.0001), and low density lipoprotein cholesterol (LDL-C) (p<0.01), than those of healthy individuals. Plasma Hcy content, TOS and amount of DNA were positively and significantly associated with cholesterol, triglycerides, systolic blood pressure, urea, and albumin (p values<0.01). TOS, Hcy and oxidative DNA damage were negatively correlated with HDL-c, TAS and proteins. It is suggested that these parameters have pivotal role in diagnostic process of determining severity in CAD patients. Oxidized products of macromolecules in blood of CVD patients impart major functions in causing CVD disease.

Greenhouse hydroponic experiments were carried out using three different heavy metal accumulation tobacco genotypes to evaluate how different genotypes responded to chromium (Cr) toxicity in the presence of 24-epibrassinolide (EBR; a biologically active brassinosteroid). The results showed that Cr stress caused a marked reduction in plant biomass, chlorophyll content, chlorophyll fluorescence, and photosynthesis parameters but induced malondialdehyde accumulation and ultrastructure damage, with 2010-38 (L) less affected. Foliar application of 24-epibrassinolide (0.1 μM) on Cr-stressed plants greatly alleviated Cr-induced inhibition of growth and photosynthesis, oxidative stress and ultrastructure damage, decreased Cr accumulation in different parts of leaves and roots, with the exception of the upper and lower of leaves of genotype L, and maintained ion homeostasis. Regarding genotypes, L was more tolerant than M and H, as it absorbed less Cr and also performed better in all of the studied parameters. These findings suggest a potential role for 24-epibrassinolide in Cr stress alleviation and the utilization of elite genetic resources in future breeding programs to develop low Cr accumulation genotypes. These results advocate a positive role for 24-epibrassinolide in reducing pollutant residues from health point of view.

Introduction: Alveolar and skeletal chin dimensions with facial height have an impact on diagnosis and treatment planning in orthodontic patients and serves as a reference landmark for facial aesthetics., Aim: To evaluate the alveolar and skeleton chin dimensions among different divergent patterns, to evaluate the lower face height in different divergent growth patterns, to give an estimate to the oral surgeon for any adjunctive procedure., Materials and Methods: The study includes a total sample of 45 non-growing individuals (26 males and 19 females) from the archival records of the Orthodontic Department with age ranging between 18-25 years, classified into different divergent patterns based on the mandibular plane angle. The sample was divided into three groups, of which 15 patients in each group were evaluated: Group-1: Normodivergent, Group-2: Hypodivergent and Group-3: Hyperdivergent patterns respectively. Standardized digital lateral cephalograms and antero-posterior cephalograms of these patients were obtained in Natural Head Position (NHP)., Results: The results of the retrospective cephalometeric study were statistically analyzed by using ANOVA and Tukey's multiple post hoc test which showed that hard tissue chin measurement were greater in hypodivergent group (13.7mm) and the increased lower facial height showed statistically significant difference in high mandibular plane angle group (59.6mm). In antero-posterior cephalograms the transverse width showed statistically significant difference in normodivergent group (32.60mm)., Conclusion: The anterio-posterior width of the symphysis was higher in hypodivergent growth pattern, whereas vertical height of the symphysis was greater in hyperdivergent group. The lower facial height among three groups showed statistically significant difference among hyperdivergent group. In comparison of all the three groups in Anterio-Posterior (AP) cephalograms, statistically significant difference was noted in normodivergent group when compared with the other two groups.

Background/aim: Biochemical, environmental, and genetic factors such as oxidative stress-induced DNA damage and homocysteine (Hcy) accumulation in the blood are involved in the development and progression of ovarian cancer. This study measured some biomarkers closely linked to the progression of ovarian cancer and also found their correlates., Materials and Methods: Thirty patients were diagnosed with ovarian cancer using pelvic examination, transvaginal ultrasound, and cancer antibody (CA-125) measurement. Total oxidative stress (TOS), DNA damage, Hcy, malondialdehyde (MDA), total antioxidant status (TAS), and other biochemical parameters were determined., Results: TOS and DNA damage were positively and significantly correlated between themselves and were involved in causation of tumors as reflected by significantly (P < 0.001) higher CA-125, erythrocyte sedimentation rate (ESR), creatinine, and C-reactive protein (CRP) in both young and old patients. Both were significantly correlated with Hcy, LDL-cholesterol, alanine aminotransferase, aspartate aminotransferase, CRP, MDA, and CA-125. However, they were negatively correlated with TAS. Thus, excessive inflammation and oxidative stress caused an increase in DNA damage and enhanced Hcy content, leading to development of ovarian cancer., Conclusion: This study suggests the use of antioxidants as drugs to reduce oxidative stress, DNA damage, and other causes of cancer development.

Offspring from females that experience stressful conditions during reproduction often exhibit altered phenotypes and many of these effects are thought to arise owing to increased exposure to maternal glucocorticoids. While embryos of placental vertebrates are known to regulate exposure to maternal glucocorticoids via placental steroid metabolism, much less is known about how and whether egg-laying vertebrates can control their steroid environment during embryonic development. We tested the hypothesis that threespine stickleback (Gasterosteus aculeatus) embryos can regulate exposure to maternal steroids via active efflux of maternal steroids from the egg. Embryos rapidly (within 72 h) cleared intact steroids, but blocking ATP-binding cassette (ABC) transporters inhibited cortisol clearance. Remarkably, this efflux of cortisol was sufficient to prevent a transcriptional response of embryos to exogenous cortisol. Taken together, these findings suggest that, much like their placental counterparts, developing fish embryos can actively regulate their exposure to maternal cortisol. These findings highlight the fact that even in egg-laying vertebrates, the realized exposure to maternal steroids is mediated by both maternal and embryonic processes and this has important implications for understanding how maternal stress influences offspring development., (© 2016 The Author(s).)

Within many species, some individuals are consistently more aggressive than others. We examine whether there are differences in brain gene expression between aggressive versus nonaggressive behavioural types of individuals within a natural population of male three-spined sticklebacks ( Gasterosteus aculeatus ). We compared gene expression profiles of aggressive male sticklebacks to nonaggressive males in four regions of the brain (brainstem, cerebellum, diencephalon and telencephalon). Relatively few genes were differentially expressed between behavioural types in telencephalon, cerebellum and diencephalon, but hundreds of genes were differentially expressed in brainstem, a brain area involved in detecting threats. Six genes that were differentially expressed in response to a territorial intrusion in a previous study were also differentially expressed between behavioural types in this study, implying primarily non-shared but some shared molecular mechanisms. Our findings offer new insights into the molecular causes and correlates of behavioural plasticity and individual variation in behaviour.

This project was planned to study the production of cholesterol lowering drug mevastatin by Aspergillus terreus GCBL-03 on pretreated substrate bagasse in solid state fermentation. Bagasse was pretreated by potassium hydroxide to delignify the substrate to readily become available to microorganism. It was noticed that pretreated bagasse exhibited 13.69±0.64 mg/100mL yield of mevastatin and 6.63±0.48 g dry cell mass as compared to nontreated substrate that showed 7.04±0.81 mg/100 mL and 6.04±0.24 g dry cell mass. The fermentation profile like pH (5.5), temperature (30 °C), moisture contents (60%) inoculum size (2 mL), and incubation time (72 h) showed the optimum production (30.63±1.24 mg/100 mL) of mevastatin. Furthermore, fermented drug showed noteworthy antifungal activity against battery of selected fungal strains assessed by disc diffusion and measurement of minimum inhibitory concentration by micro dilution method. It was concluded from the study that fermented mevastatin was effective against fungal strains.

Tobacco easily accumulates certain heavy metals in leaves and thus poses a potential threat to human health. To systematically dissect Cr-responsive microRNAs (miRNAs) and their targets at the global level, 4 small RNA libraries were constructed from the roots of Cr-treated (Cr) and Cr-free (control) for 2 contrasting tobacco genotypes,Yunyan2 (Cr-sensitive) and Guiyan1 (Cr-tolerant). Using high-throughput-sequencing-technology, the authors identified 53 conserved and 29 novel miRNA families. Comparative genomic analysis of 41 conserved Cr-responsive miRNA families revealed that 11 miRNA families showed up-regulation in Guiyan1 but unaltered in Yunyan2, and 17 miRNA families were up-regulated only in Yunyan2 under Cr stress. Only 1 family, miR6149, was down-regulated in Yunyan2 but remained unchanged in Guiyan1. Of the 29 novel miRNA families, 14 expressed differently in the 2 genotypes under Cr stress. Based on a high-throughput degradome sequencing homology search, potential targets were predicted for the 41 conserved and 14 novel Cr-responsive miRNA families. Clusters of Orthologous Groups functional category analysis revealed that some of these predicted target transcripts of miRNAs are responsive to biotic and abiotic stresses. Furthermore, the expression patterns of many Cr-responsive miRNAs were validated by stem-loop real-time transcription polymerase chain reaction. The results of the present study provide valuable information and a framework for understanding the function of miRNAs in Cr tolerance., (© 2015 SETAC.)

Diabetes mellitus (DM) is a heterogeneous metabolic disorder characterized by chronic hyperglycaemia, higher glycated hemoglobin (HbA1C) as well as protein. Oxidative stress can cause damage to leukocytic DNA and enhancement of homocysteine (Hcy) level in sera of type 2 diabetic patients. Haematological and biochemical parameters are severely affected by oxidative stress, which results in damages to DNA and Hcy in these patients. Eighty DM patients and 80 normal subjects, after having their consent, were selected for the present study. Leukocytes were characterized for DNA damage by comet assay kit while, blood plasma was taken into account for biochemical indices using commercial test kits. Results indicated that DNA damage was strongly linked with erythrocyte sedimentation rate (ESR) (P<0.01), glycated hemoglobin (HbA1C) (P<0.0001), glycated serum protein (P<0.005), cholesterol (P<0.011), triglycerides (P<0.001), albumin (P<0.001), creatinine (P<0.006), urea (P<0.007) and ALT (P<0.02), and negatively associated with packed cell volume (PCV) (P<0.002) and hemoglobin (P<0.001). Homocysteine was strongly linked with ESR, HbA1C, glycated protein (P<0.002), cholesterol (P<0.016), triglycerides (P<0.0001), albumin, creatinine, urea, ALT and AST in diabetic patients. Hyc and DNA damages both were negatively linked with total hemoglobin and PCV. Both of these even in their normal range may have a role in the endothelium damage. Nutritional intervention to lower down Hyc and DNA damages in the Pakistani population may mitigate their effect and guarantee in maintenance of a healthy nation.

Oxidative stress and reactive oxygen species (ROS) have been documented subsist to the pathogenesis of many diseases including diabetes mellitus. The strength of both parameters could be estimated by measuring oxidative stress marker thiobarbituric acid reactive substances (TBARS), its related parameters and the antioxidants glutathione peroxidase and superoxide dismutase (SOD) in plasma of DM patients. Lipid peroxidation was measured as TBARS and presented as malondialdehyde, total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (Tg), the antioxidants (vitamin A (β-carotene), vitamin E, vitamin C, glutathione peroxidase (GPx) and superoxide dismutase) levels. The results showed that these parameters, commonly, were declined appreciably in diabetic individuals as compared to the healthy individuals. In most cases, age and gender were appeared to involve in having greater values of diabetes marker. Further, increased level of lipid peroxidation and random behaviour of antioxidant potential also associated with Diabetes. For that reason these biomarkers might be of great important to diagnosis DNA damages of diabetic patients.

Background/aim: Despite extensive research, normal functionality remains problematic in patients with schizophrenia. Issues such as quality of life, subjective well-being, or psychosocial performance are currently objectives of interest. There are limited data collected prospectively on patients' perception of quality of life as compared between treatment groups, especially in developing countries. The aim of the present study was to analyze the evolution of patients' reported quality of life in patients with schizophrenia or related disorders treated with antipsychotics, in naturalistic settings., Materials and Methods: The study was designed as a 12-month prospective observational study of 131 subjects with schizophrenia or related disorders treated with haloperidol, olanzapine, risperidone, quetiapine, or aripiprazole, recruited from consecutive hospitalized patients in a psychiatry department., Results: The mean scores for patients' reported quality of life and its components and for satisfaction with treatment had a favorable evolution, but increases were of reduced magnitude. The differences among treatment groups were not statistically significant, with few exceptions. A great variability of data was found., Conclusion: Studies with a stratified analysis by factors influencing quality of life perceptions in this category of patients might allow the identification of differences, if any, between antipsychotics in this domain.

Certain complex phenotypes appear repeatedly across diverse species due to processes of evolutionary conservation and convergence. In some contexts like developmental body patterning, there is increased appreciation that common molecular mechanisms underlie common phenotypes; these molecular mechanisms include highly conserved genes and networks that may be modified by lineage-specific mutations. However, the existence of deeply conserved mechanisms for social behaviors has not yet been demonstrated. We used a comparative genomics approach to determine whether shared neuromolecular mechanisms could underlie behavioral response to territory intrusion across species spanning a broad phylogenetic range: house mouse (Mus musculus), stickleback fish (Gasterosteus aculeatus), and honey bee (Apis mellifera). Territory intrusion modulated similar brain functional processes in each species, including those associated with hormone-mediated signal transduction and neurodevelopment. Changes in chromosome organization and energy metabolism appear to be core, conserved processes involved in the response to territory intrusion. We also found that several homologous transcription factors that are typically associated with neural development were modulated across all three species, suggesting that shared neuronal effects may involve transcriptional cascades of evolutionarily conserved genes. Furthermore, immunohistochemical analyses of a subset of these transcription factors in mouse again implicated modulation of energy metabolism in the behavioral response. These results provide support for conserved genetic "toolkits" that are used in independent evolutions of the response to social challenge in diverse taxa.

The present study was conducted to determine the effect of three different levels of sorbic acid (0.1 %, 0.2 % and 0.3 %) on the shelf life and storage quality of Kaladhi. Kaladhi was prepared from pasteurized buffalo milk standardized to 6 % fat and 9 % SNF with coagulation at 40 °C using 5 % lactic acid as a coagulant. Kaladhi prepared without sorbic acid served as control and was compared with the products treated with different levels of sorbic acid for a storage period of 35 days at ambient temperature. The results showed a significant (P < 0.05) effect of sorbic acid on most of the physicochemical parameters i.e. titratable acidity, free fatty acid content (% oleic acid) and thiobarbituric acid value which showed a decreasing trend with increasing concentration of sorbic acid. However, a non-significant (P > 0.05) effect of sorbic acid was observed on pH and proximate parameters of the product. Kaladhi treated with 0.3 % sorbic acid retained most desirable physicochemical and sensory properties throughout the storage period hence, was considered the best.

Diabetes mellitus is a life threatening disease and scientists are doing their best to find a cost effective and permanent treatment of this malady. The recent trend is to control the disease by target base inhibiting of enzymes or proteins. Secreted frizzled-related protein 4 (SFRP4) is found to cause five times more risk of diabetes when expressed above average levels. This study was therefore designed to analyze the SFRP4 and to find its potential inhibitors. SFRP4 was analyzed by bio-informatics tools of sequence tool and structure tool. A total of three potential inhibitors of SFRP4 were found, namely cyclothiazide, clopamide and perindopril. These inhibitors showed significant interactions with SFRP4 as compared to other inhibitors as well as control (acetohexamide). The findings suggest the possible treatment of diabetes mellitus type 2 by inhibiting the SFRP4 using the inhibitors cyclothiazide, clopamide and perindopril.

Background: In recent years, the desire to adopt a healthy diet has drawn attention to legume seeds and food products derived from them. Mash bean is an important legume crop used in Pakistan however a systematic mapping of the chemical composition of mash bean seeds is lacking. Therefore seeds of four mash bean (Vigna mungo (L.) Hepper, family Leguminoseae) cultivars (NARC-Mash-1, NARC-Mash-2, NARC-Mash-3, NARC-Mash-97) commonly consumed in Pakistan have been analyzed for their chemical composition, antioxidant potential and biological activities like inhibition of formation of advanced glycation end products (AGE) activity and tyrosinase inhibition activity., Results: The investigated cultivars varied in terms of biochemical composition to various extents. Mineral composition indicated potassium and zinc in highest and lowest amounts respectively, in all cultivars. The amino acid profile in protein of these cultivars suggested cysteine is present in lowest quantity in all cultivars while fatty acid distribution pattern indicated unsaturated fatty acids as major fatty acids in all cultivars. All cultivars were found to be rich source of tocopherols and sterols. Fourier transform infrared spectroscopy (FTIR) fingerprints of seed flour and extracts indicated major functional groups such as polysaccharides, lipids, amides, amines and amino acids. Results indicated that all investigated cultivars possessed appreciable antioxidant potential., Conclusions: All cultivars are rich source of protein and possess sufficient content of dietary fiber, a balanced amino acid profile, low saturated fatty acids and antioxidant capacity that rationalizes many traditional uses of seeds of this crop besides its nutritional importance. The collected data will be useful for academic and corporate researchers, nutritionists and clinical dieticians as well as consumers. If proper attention is paid, it may become an important export commodity and may fetch considerable foreign exchange for Pakistan.

Seven indigenously isolated fungal strains (Aspergillus niger, Aspergillus flavus, Aspergillus terreus, Penicillium citrinum, Penicillium notatum, Pleurotus ostreatus and Trichoderma viradae) were tested for their potential to produce cholesterol lowering drug lovastatin by using different agro-industrial wastes (Corn cobs, corn stover, banana stalk, wheat straw, wheat bran, bagasse) in submerged as well as solid state fermentation. Aspergillus terreus showed maximum production of 18.74 mg/100 mL by wheat bran in solid state fermentation. The fermentation parameters (pH, temperature, Inoculum size, moisture contents and fermentation time) were also optimized for optimum production of lovastatin. It was found that Aspergillus terreus could produce 27.14 mg/100 mL lovastatin under optimum condition of pH (6), temperature (30°C), Inoculum size (2 mL), moisture contents (60%) and fermentation time (120 hrs) in solid state fermentation. The optimized lovastatin was extracted from fermented broth and orally administered to rats. The hypocholesterolemic effect of fermented lovastatin was evaluated on serum ALT, AST, HDL-C, LDL-C, TG and TC level of rats. It was concluded from the study, fermented lovastatin effectively lower the cholesterol level of rats.

This article is aimed to discuss the modification of guar gum through microwave irradiation by varying the time of irradiation. The characterization of the modified products was carried out using FTIR spectroscopic analysis. The FT-IR spectrum of the pure guar gum (GG) sample showed a broad peak at 3298 cm(-1) while the modified GG sample displayed a peak at 1541 cm(-1) which was absent in the crude sample. The X-ray diffraction (XRD) analysis confirmed the increase in crystallinity due to grafting of the sample with polyacrylamide (GG-g-PAM). Scanning electron microscope (SEM) images revealed that granular form of guar gum was changed into fibrillar structure after grafting. Thermo-gravimetric analysis of the modified samples was also carried out and discussed. The role of guar gum as a matrix for controlled release of drug triamcinolone was evaluated. The GG-acrylamide grafted samples presented a correlation between drug release and time of microwave exposure. The results revealed that such modified product has potential applications in colonic drug delivery system., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Six cultivars of safflower which were (PI-387820, PI-251978, PI-170274, PI-387821, PI-386174 and Thori-78) grown in net house of NIAB under salinity (10 ds m⁻¹) and drought (60% field capacity) conditions and compared to their oxidative damage and antioxidative responses. Plant samples (leaves) were collected for the determination of malonidialdehyde (MDA), antioxidative enzymes (catalase, ascorbate peroxidase, glutathione reductase, and peroxidase), proline, and photosynthetic pigments. Salinity and drought decreased the chlorophyll a and b contents but a decrease in chlorophyll a and b was less in safflower variety (THORI-78) which could be a useful marker for selecting a stress tolerant variety. Both stresses considerable increases the accumulation of proline in PI-251978, PI-170274, PI-387821, PI-386174 and THORI-78 varieties of safflower whereas the proline accumulation did not appear to be an essential part of the protection mechanism against salinity and drought in variety PI-387820. Enzyme activity measurements revealed that THORI-78 can tolerate salinity and drought stress well by increasing the activity of catalase and APX enzymes whereas variety PI- 386174 showed increased activity of glutathione reductase enzyme under salinity and drought and appear to be very crucial antioxidative defenses during intense stress conditions. The results indicate that the photosynthetic pigments, proline and activities of the enzymes are important mechanism for the stress tolerance in safflower plant and can be considered as genetic improvement for the plant in salinity and drought soil conditions.