Search results for: candidate genes

Authors: Minhas Alam, Muhammad Hidayat Rasool, Mohsin Khurshid, Bilal Aslam

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The genus Acinetobacter has emerged as a significant concern in hospital-acquired infections, particularly due to the versatility of Acinetobacter baumannii in causing nosocomial infections. The organism's remarkable metabolic adaptability allows it to thrive in various environments, including the environment, animals, and humans. However, the extent of antimicrobial resistance in Acinetobacter species from veterinary settings, especially in developing countries like Pakistan, remains unclear. This study aimed to isolate and characterize Acinetobacter spp. from veterinary settings in Punjab, Pakistan. A total of 2,230 specimens were collected, including 1,960 samples from veterinary settings (nasal and rectal swabs from dairy and beef cattle), 200 from the environment, and 70 from human clinical settings. Isolates were identified using routine microbiological procedures and confirmed by polymerase chain reaction (PCR). Antimicrobial susceptibility was determined by the disc diffusion method, and minimum inhibitory concentration (MIC) was measured by the micro broth dilution method. Molecular techniques, such as PCR and DNA sequencing, were used to screen for antimicrobial-resistant determinants. Genetic diversity was assessed using standard techniques. The results showed that the overall prevalence of A. baumannii in cattle was 6.63% (65/980). However, among cattle, a higher prevalence of A. baumannii was observed in dairy cattle, 7.38% (54/731), followed by beef cattle, 4.41% (11/249). Out of 65 A. baumannii isolates, the carbapenem resistance was found in 18 strains, i.e. 27.7%. The prevalence of A. baumannii in nasopharyngeal swabs was higher, i.e., 87.7% (57/65), as compared to rectal swabs, 12.3% (8/65). Class D β-lactamases genes blaOXA-23 and blaOXA-51 were present in all the CRAB from cattle. Among carbapenem-resistant isolates, 94.4% (17/18) were positive for class B β-lactamases gene blaIMP, whereas the blaNDM-1 gene was detected in only one isolate of A. baumannii. Among 70 clinical isolates of A. baumannii, 58/70 (82.9%) were positive for the blaOXA-23-like gene, and 87.1% (61/70) were CRAB isolates. Among all clinical isolates of A. baumannii, blaOXA-51-like gene was present. Hence, the co-existence of blaOXA-23 and blaOXA-51 was found in 82.85% of clinical isolates. From the environmental settings, a total of 18 A. baumannii isolates were recovered; among these, 38.88% (7/18) strains showed carbapenem resistance. All environmental isolates of A. baumannii harbored class D β-lactamases genes, i.e., blaOXA-51 and blaOXA-23 were detected in 38.9% (7/18) isolates. Hence, the co-existence of blaOXA-23 and blaOXA-51 was found in 38.88% of isolates. From environmental settings, 18 A. baumannii isolates were recovered, with 38.88% showing carbapenem resistance. All environmental isolates harbored blaOXA-51 and blaOXA-23 genes, with co-existence in 38.88% of isolates. MLST results showed ten different sequence types (ST) in clinical isolates, with ST 589 being the most common in carbapenem-resistant isolates. In veterinary isolates, ST2 was most common in CRAB isolates from cattle. Immediate control measures are needed to prevent the transmission of CRAB isolates among animals, the environment, and humans. Further studies are warranted to understand the mechanisms of antibiotic resistance spread and implement effective disease control programs.

Keywords: Acinetobacter baumannii, carbapenemases, drug resistance, MSLT

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Authors: András Farkas, István Molnár, Jan Vrána, Veronika Burešová, Petr Cápal, András Cseh, Márta Molnár-Láng, Jaroslav Doležel

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Species of Aegilops played a central role in the evolution of wheat and are sources of traits related to yield quality and tolerance against biotic and abiotic stresses. These wild genes and alleles are desirable to use in crop improvement programs via introgressive hybridization. However, the success of chromosome mediated gene transfer to wheat are hampered by the pour knowledge on the genome structure of Aegilops relative to wheat and by the low number of cost-effective molecular markers specific for Aegilops chromosomes. The COS markers specific for genes conserved throughout evolution in both sequence and copy number between Triticeae/Aegilops taxa and define orthologous regions, thus enabling the comparison of regions on the chromosomes of related species. The present study compared individual chromosomes of Aegilops umbellulata (UU), Ae. comosa (MM), Ae. speltoides (SS) and Ae. caudata (CC) purified by flourescent labelling with oligonucleotid SSR repeats and biparametric flow cytometry with wheat by identifying orthologous chromosomal regions by COS markers. The linear order of bin-mapped COS markers along the wheat D chromosomes was identified by the use of chromosome-specific sequence data and virtual gene order. Syntenic regions of wheat identifying genome rearrangements differentiating the U, M, S or C genomes from the D genome of wheat were detected. The conserved orthologous set markers assigned to Aegilops chromosomes promise to accelerate gene introgression by facilitating the identification of alien chromatin. The syntenic relationships between the Aegilops species and wheat will facilitate the targeted development of new markers specific for U, M, S and C genomic regions and will contribute to the understanding of molecular processes related to the evolution of Aegilops.

Keywords: Aegilops, cos-markers, flow-sorting, wheat

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Authors: Saranya Ganapathy, Megha N. Parajulee, Michael San Francisco, Hong Zhang

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Insect pests are a serious threat to agricultural productivity. Use of chemical pesticides, the predominant control method thus far, has resulted in environmental damage, pest resurgence, and negative effects on non-target species. Genetically modified (GM) crops offer a promising alternative, and Bacillus thuringiensis endotoxin genes have played a major role in this respect. However, to overcome insect tolerance issues and to broaden the target range, it is critical to identify alternative-insecticidal toxins working through novel mechanisms. Our research group has identified a kinase from Chilo iridescent virus (CIV; Family Iridoviridae) that has insecticidal activity and designated it as ISTK (Iridovirus Serine/Threonine Kinase). A 35 kDa truncated form of ISTK, designated iridoptin, was obtained during expression and purification of ISTK in the yeast system. This yeast-expressed CIV toxin induced 50% mortality in cotton aphids and 100% mortality in green peach aphids (GPA). Optimized viral genes (o-ISTK and o-IRI) were stably transformed into the model plant, Arabidopsis. PCR analysis of genomic DNA confirmed the presence of the gene insert (oISTK/oIRI) in selected transgenic lines. The further screening was performed to identify the PCR positive lines that showed expression of respective toxins at the polypeptide level using Western blot analysis. The stable lines expressing either of these two toxins induced moderate to very high mortality in GPAs and significantly affected GPA development and fecundity. The aphicidal potential of these transgenic Arabidopsis lines will be presented.

Keywords: Chilo iridescent virus, insecticidal toxin, iridoviruses, plant-incorporated protectants, serine/threonine kinase

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Authors: A. Abbad, W. Benstaali

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Using first-principles calculations based on the density functional theory and generalize gradient approximation, we predict electronic and magnetic properties of CeFeO3 orthorhombic perovskite. The calculated densities of states presented in this study identify the metallic behavior CeFeO3 when we use the GGA scheme, whereas when we use the GGA+U, we see that its exhibits half-metallic character with an integer magnetic moment of 24μB per formula unit at its equilibrium volume which makes this compound promising candidate for applications in spintronics.

Keywords: CeFeO3, magnetic moment, half-metallic, electronic properties

Procedia PDF Downloads 366

Authors: Svetlana Zhikrivetskaya, Nataliya Shirokova, Roman Bikanov, Elizaveta Musatova, Yana Kovaleva, Nataliya Vetrova, Ekaterina Pomerantseva

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Nowadays there is a growing number of couples with conceiving problems due to male or female infertility. Genetic abnormalities are responsible for about 31% of all cases of male infertility. These abnormalities include both chromosomal aberrations or aneuploidies and mutations in certain genes. Chromosomal abnormalities can be easily identified, thus the development of screening panels able to reveal genetic reasons of male infertility on gene level is of current interest. There are approximately 2,000 genes involved in male fertility that is the reason why it is very important to determine the most clinically relevant in certain population and ethnic conditions. An infertility screening panel containing 48 mutations in genes AMHR2, CFTR, DNAI1, HFE, KAL1, TSSK2 and AZF locus which are the most clinically relevant for the European population according to databases NCBI and ClinVar was designed. The aim of this research was to confirm clinic relevance of these mutations in the Russian population. Genotyping was performed in 220 patients with different types of male infertility and in 57 healthy males with normozoospermia. Mutations were identified by end-point PCR with TaqMan probes in microfluidic plates. The frequency of 5 mutations in healthy males and 13 mutations in patients with infertility was revealed and estimated. The frequency of mutation c.187C>G in HFE gene was significantly lower for healthy males (8.8%) compared with patients (17.7%) and the values for the European population according to ExAc database (13.7%) and dbSNP (17.2%). Analysis of c.3454G>C, and c.1545_1546delTA mutations in the CFTR gene revealed increased frequency (0.9 and 0.2%, respectively) in patients with infertility compared with data for the European population (0.04%, respectively (ExAc, European (Non-Finnish) and for the Aggregated Populations (0.002% (ExAc), because there is no data for European population for c.1545_1546delTA mutation. The frequency of del508 mutation (CFTR) in patients (1.59%) were lower comparing with male infertility Europeans (3.34-6.25% depending on nationality) and at the same level with healthy Europeans (1.06%, ExAc, European (Non-Finnish). Analysis of c.845G>A (HFE) mutation resulted in decreased frequency in patients (1.8%) in contrast with the European population data (5.1%, respectively, ExAc, European (Non-Finnish). Moreover, obtained data revealed no statistically significant frequency difference for c.845G>A mutation (HFE) between healthy males in the Russian and the European populations. Allele frequencies of mutations c.350G>A (CFTR), c.193A>T (HFE), c.774C>T, and c.80A>G (gene TSSK2) showed no significantly difference among patients with infertility, healthy males and Europeans. Analysis of AZF locus revealed increased frequency for AZFc microdeletion in patients with male infertility. Thereby, the new data of the allele frequencies in infertility patients in the Russian population was obtained. As well as the frequency differences of mutations associated with male infertility among patients, healthy males in the Russian population and the European one were estimated. The revealed differences showed that for high effectiveness of screening panel detecting genetically caused male infertility it is very important to consider ethnic and population characteristics of patients which will be screened.

Keywords: allele frequency, azoospermia, male infertility, mutation, population

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Authors: John G. Skelly, Peter K. Dearden, Thomas W. R. Harrop, Sarah N. Inwood, Joseph Guhlin

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The Argentine stem weevil (ASW; L. bonariensis) is an economically important pasture pest in New Zealand, which causes about $200 million of damage per annum. Microctonus hyperodae (Mh), a parasite of the ASW in its natural range in South America, was introduced into New Zealand to curb the pasture damage caused by the ASW. Mh is an endoparasitic wasp that lays its eggs in the ASW halting its reproduction. Mh was initially successful at preventing ASW proliferation and reducing pasture damage. The effectiveness of Mh has since declined due to decreased parasitism rates and has resulted in increased pasture damage. Although the mechanism through which ASW has developed resistance to Mh has not been discovered, it has been proposed to be due to the different reproductive modes used by Mh and the ASW in New Zealand. The ASW reproduces sexually, whereas Mh reproduces asexually, which has been hypothesised to have allowed the ASW to ‘out evolve’ Mh. Other species within the Microctonus genus reproduce both sexually and asexually. Strains of Microctonus aethiopoides (Ma), a species closely related to Mh, reproduce either by sexual or asexual reproduction. Comparing the genomes of sexual and asexual Microctonus may allow for the identification of the mechanism of asexual reproduction and other characteristics that may improve Mh as a biocontrol agent. The genomes of Mh and three strains of Ma, two of which reproduce sexually and one reproduces asexually, have been sequenced and annotated. The French (MaFR) and Moroccan (MaMO) reproduce sexually, whereas the Irish strain (MaIR) reproduces asexually. Like Mh, The Ma strains are also used as biocontrol agents, but for different weevil species. The genomes of Mh and MaIR were subsequently upgraded using Hi-C, resulting in a set of high quality, highly contiguous genomes. A subset of the genes involved in mitosis and meiosis, which have been identified though the use of Hidden Markov Models generated from genes involved in these processes in other Hymenoptera, have been catalogued in Mh and the strains of Ma. Meiosis and mitosis genes were broadly conserved in both sexual and asexual Microctonus species. This implies that either the asexual species have retained a subset of the molecular components required for sexual reproduction or that the molecular mechanisms of mitosis and meiosis are different or differently regulated in Microctonus to other insect species in which these mechanisms are more broadly characterised. Bioinformatic analysis of the chemoreceptor compliment in Microctonus has revealed some variation in the number of olfactory receptors, which may be related to host preference. Phylogenetic analysis of olfactory receptors highlights variation, which may be able to explain different host range preferences in the Microctonus. Hi-C clustering implies that Mh has 12 chromosomes, and MaIR has 8. Hence there may be variation in gene regulation between species. Genome alignment of Mh and MaIR implies that there may be large scale genome structural variation. Greater insight into the genetics of these agriculturally important group of parasitic wasps may be beneficial in restoring or maintaining their biocontrol efficacy.

Keywords: argentine stem weevil, asexual, genomics, Microctonus hyperodae

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Authors: B. Bouadjemi, S. Bentata, W. Benstaali, A. Abbad

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The electronic and magnetic properties of the cubic praseodymium oxides perovskites PrMnO3 were calculated using the density functional theory (DFT) with both generalized gradient approximation (GGA) and GGA+U approaches, where U is on-site Coulomb interaction correction. The results show a half-metallic ferromagnetic ground state for PrMnO3 in GGA+U approached, while semi-metallic ferromagnetic character is observed in GGA. The results obtained, make the cubic PrMnO3 a promising candidate for application in spintronics.

Keywords: first-principles, electronic properties, transition metal, materials science

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Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

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Authors: Sayyed-Javad Ziaolhagh, Mojtaba Hokmabadi

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Introduction: Childhood obesity is a serious medical condition that affects children and adolescents even in the central nervous system. Semaphorins also play a role in the inflammatory process of the nervous system. On the other hand, it has been stated that garlic and stevia extracts following aerobic exercise are effective on immune system inflammation in addition to aerobic activity. Materials and Methods: For 15 weeks, 50 3-week-old male Wistar rats were fed with conventional rodent chow for control and a high-fat diet to induce obesity. Obese rats then were randomly assigned into 7 groups (n=5) based on the Lee index: healthy control (C), obese (OBS), obese + garlic (OBS+GAR), obese + Stevia (OBS+STV), obese + aerobic exercise (OBS+EXE), obese + garlic + aerobic exercise (OBS+GAR+EXE), and obese + stevia + aerobic exercise (OBS+STV+EXE). Training groups completed a progressive aerobic running program (at 8-15 m/min, 5-20 min/day, 5 days/week), and Stevia and garlic extract group (250 mg/kg/day, 5 days/week) were given orally once a day. Real-time PCR was used to determine the levels of Semaphorin 4A, and Plexin D1 gene expressions in the hypothalamus. Fold change analysis with ANOVA was performed for statistical analysis, with a significance threshold of P<0.05. Results: Body weight increased significantly in OBS compared to C (p= 0.013), but was not significantly changed in all treatment rats. Moreover, Semaphorin 4A was significantly increased in obese compared to control group (p= 0.041) and after 8 weeks, stevia extract (p=0.006), aerobic exercise (p=0.012) and garlic extract + aerobic exercise (p=0.008) significantly decreased compared to obese rats. In addition, Plexin D1 genes were also found in the hypothalamus of both obese and control rats but were insignificantly up-regulated when compared with the obese group (p=0.950). Conclusion: High-fat diet caused neuroinflammation by elevation of sema4A in obese rats and stevia, stevia with aerobic and garlic with aerobic could reduce this inflammation in rats. Also, none of them could alter Plexin D1.

Keywords: sema 4A, plexin D1, garlic, stevia

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Authors: Hongping Lu, Kelbinur Tursun, Yaru Li, Yu Zhang, Shunai Liu, Ming Han

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Objective: To investigate whether NS5ATP9 is involved in IL-6 mediated autophagy and the relationship between IL-6 and NS5ATP9 in liver cancer cells. Methods: 1. Detect the mRNA and protein levels of Beclin 1 after HepG2 cells were treated with or without recombinant human IL-6 protein. 2. Measure and compare of the changes of autophagy-related genes with their respective control, after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. 3. HepG2 cells were incubated with 50 ng/ml of IL-6 in the presence or absence of PDTC. The expression of NS5ATP9 was analyzed by Western blot after 48 h. 4. After NS5ATP9-silenced HepG2 cells had been treated with 50 ng/ml recombinant IL-6 protein, we detected the Beclin 1 and LC3B (LC3Ⅱ/Ⅰ) expression. 5. HepG2 cells were transfected with pNS5ATP9, si-NS5ATP9, and their respective control. Total RNA was isolated from cells and analyzed for IL-6. 6. Silence or neutralization of IL-6 in HepG2 cells which has been transfected with NS5ATP9. Beclin 1 and LC3 protein levels were analyzed by Western blot. Result: 1. After HepG2 were treated with recombinant human IL-6 protein, the expression of endogenous Beclin 1 was up-regulated at mRNA and protein level, and the conversion of endogenous LC3-I to LC3-II was also increased. These results indicated that IL-6 could induce autophagy. 2. When HepG2 cells were treated with IL-6 siRNA or monoclonal antibody against human IL-6, the expression of autophagy-related genes were decreased. 3. Exogenous human IL-6 recombinant protein up-regulated NS5ATP9 via NF-κB activation. 4. The expression of Beclin 1 and LC3B was down-regulated after IL-6 treated NS5ATP9-silenced HepG2 cells. 5. NS5ATP9 could reverse regulates IL-6 expression in HepG2 cells. 6. Silence or neutralization of IL-6 attenuates NS5ATP9-induced autophagy slightly. Conclusion: Our results implied that in HCC patients, maybe the higher level of IL-6 in the serum promoted the expression of NS5ATP9 and induced autophagy in cancer cells. And the over-expression of NS5ATP9 which induced by IL-6, in turn, increased IL-6 expression, further, promotes the IL-6/NS5ATP9-mediated autophagy and affects the progression of tumor. Therefore, NS5ATP9 silence might be a potential target for HCC therapy.

Keywords: autophagy, Hepatocellular carcinoma, IL-6, microenvironment, NS5ATP9

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Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

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Authors: M. Borgie, Z. Dagher, F. Ledoux, A. Verdin, F. Cazier, H. Greige, P. Shirali, D. Courcot

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In October 2013, the International Agency for Research on Cancer (IARC) classified outdoor air pollution and fine particulate matter (PM2.5) as carcinogenic to humans. Despite the clearly relationship established by epidemiological studies between PM exposure and the onset of respiratory and cardiovascular diseases, uncertainties remain about the physiopathological mechanisms responsible for these diseases. The aim of this work was to evaluate the toxicological effects of two samples of atmospheric PM2.5 collected at urban and rural sites on human bronchial epithelial cells, BEAS-2B, especially to investigate the metabolic activation of organic compounds, the alteration of epigenetic mechanisms (i.e. microRNAs genes expression), the phosphorylation of H2AX and the telomerase activity. Our results showed a significant increase in CYP1A1, CYP1B1, and AhRR genes expression, miR-21 gene expression, H2AX phosphorylation and telomerase activity in BEAS-2B cells after their exposure to PM2.5, both in a dose and site-dependent manner. These results showed that PM2.5, especially urban PM, are able to induce the expression of metabolizing enzymes which can provide metabolic biotransformation of organic compounds into more toxic and carcinogenic metabolites, and to induce the expression of the oncomiR miR-21 which promotes cell growth and enhances tumor invasion and metastasis in lung cancer. In addition, our results have highlighted the role of PM2.5 in the activation of telomerase, which can maintain the telomeres length and subsequently preventing cell death, and have also demonstrated the ability of PM2.5 to induce DNA breaks and thus to increase the risk of mutations or chromosomal translocations that lead to genomic instability. All these factors may contribute to cell abnormalities, and thus the development of cancer.

Keywords: BEAS-2B cells, carcinogenesis, epigenetic alterations and genotoxicity, PM2.5

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Authors: D. Leibman, D. Wolf, A. Gal-On

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Viral diseases of tomato crops result in heavy yield losses and may even jeopardize the production of these crops. Classical tomato breeding for disease resistance against Tomato yellow leaf curl virus (TYLCV), leads to partial resistance associated with a number of recessive genes. To author’s best knowledge Pepino mosaic virus (PepMV) genetic resistance is not yet available. The generation of viral resistance by means of genetic engineering was reported and implemented for many crops, including tomato. Transgenic resistance against viruses is based, in most cases, on Post Transcriptional Gene Silencing (PTGS), an endogenous mechanism which destroys the virus genome. In this work, we developed immunity against PepMV and TYLCV in a tomato based on a PTGS mechanism. Tomato plants were transformed with a hairpin-construct-expressed transgene-derived double-strand-RNA (tr-dsRNA). In the case of PepMV, the binary construct harbored three consecutive fragments of the replicase gene from three different PepMV strains (Italian, Spanish and American), to provide resistance against a range of virus strains. In the case of TYLCV, the binary vector included three consecutive fragments of the IR, V2 and C2 viral genes constructed in a hairpin configuration. Selected transgenic lines (T0) showed a high accumulation of transgene siRNA of 21-24 bases, and T1 transgenic lines showed complete immunity to PepMV and TYLCV. Graft inoculation displayed immunity of the transgenic scion against PepMV and TYLCV. The study presents the engineering of resistance in tomato against two serious diseases, which will help in the production of high-quality tomato. However, unfortunately, these resistant plants have not been implemented due to public ignorance and opposition against breeding by genetic engineering.

Keywords: PepMV, PTGS, TYLCV, tr-dsRNA

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Authors: Manar Makhoul, Buthainah Alsalamah, Salam Lawand, Hassan Azzam

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The major storage proteins in endosperm of 33 cultivated and wild barley genotypes (H.vulgare, H. spontaneum, H. bulbosum, H. murinum, H. marinum) were analyzed to demonstrate the variation in the hordein polypeptides encoded by multigene families in grains. The SDS-PAGE revealed 13 and 17 alleles at the Hor1 and the Hor2 loci respectively, with frequencies from 0.83 to 14 and 0.56 to 13.41% respectively, while seven alleles at the Hor3 locus with frequencies from 3.63 to 30.91% were recognized. The phylogenetic analysis indicated to relevance of the polymorphism in hordein patterns as successful tool in identifying the individual genotypes and discriminating the species according to genome type. We also reported in this research complete nucleotide sequence B-hordein genes of seven wild and cultivated barley genotypes. A 152bp upstream sequence of B-hordein promoter contained a TATA box, CATC box, AAAG motif, N-motif and E-motif. In silico analysis of B-Hordein sequences demonstrated that the coding regions were not interrupted by any intron, and included the complete ORF which varied between 882 and 906 bp, and encoded mature proteins with 293-301 residues characterized by high contents of glutamine (29%), and proline (18%). Comparison of the predicted polypeptide sequences with the published ones suggested that all S-rich prolamins genes are descended from common ancestor. The sequence started at N-terminal with a signal peptide, and then followed directly by two domains; a repetitive one based on the repetition of the repeat unit PQQPFPQQ and C-terminal domain. Also, it was found that positions of the eight cysteine residues were highly conserved in all the B-hordein sequences, but Hordeum bulbosum had additional unpaired one. The phylogenetic tree of B-hordein polypeptide separated the genotypes in distinct seven subgroups. In general, the high homology between B-hordeins and LMW glutenin subunits suggests similar bread-making influences for these B-hordeins.

Keywords: hordeum, phylogenetic tree, sequencing, storage protein

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Authors: H. K. Ratre, M. Roy, S. Roy, M. S. Parmar, V. Bhagat

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Mastitis is a common problem of dairy industries. Reduction in milk production and an irreparable damage to the udder associated with the disease are common causes of culling of dairy cows. Milk from infected animals is not suitable for drinking and for making different milk products. So, it has a major economic importance in dairy cattle. The aims of this study were to investigate the bacteriological panorama in milk from udder quarters with subclinical mastitis and to carried out for the molecular characterization of the major isolated organisms, from subclinical mastitis-affected cows in and around Durg and Rajnandgaon district of Chhattisgarh. Isolation and identification of bacteria from the milk samples of subclinical mastitis-affected cows were done by standard and routine culture procedures. A total of 78 isolates were obtained from cows and among the various bacteria isolated, Staphylococcus spp. occupied prime position with occurrence rate of 51.282%. However, other bacteria isolated includeStreptococcus spp. (20.512%), Micrococcus spp. (14.102%), E. coli (8.974%), Klebsiela spp. (2.564%), Salmonella spp. (1.282%) and Proteus spp. (1.282%). Staphylococcus spp. was isolated as the major causative agent of subclinical mastitis in the studied area. Molecular characterization of Staphylococus aureusisolates was done for genetic expression of the virulence genes like ‘nuc’ encoding thermonucleaseexoenzyme, coa and spa by PCR amplification of the respective genes in 25 Staphylococcus isolates. In the present study, 15 isolates (77.27%) out of 20 coagulase positive isolates were found to be genotypically positive for ‘nuc’ where as 20 isolates (52.63%) out of 38 CNS expressed the presence of the same virulence gene. In the present study, three Staphylococcus isolates were found to be genotypically positive for coa gene. The Amplification of the coa gene yielded two different products of 627, 710 bp. The amplification of the gene segment encoding the IgG binding region of protein A (spa) revealed a size of 220 and 253bp in twostaphylococcus isolates. The X-region binding of the spa gene produced an amplicon of 315 bp in one Staphylococcal isolates. Staphylococcus aureus was found to be major isolate (51.28%) responsible for causing subclinical mastitis in cows which also showed expression of virulence genesnuc, coa and spa.

Keywords: mastitis, bacteria, characterization, expression, gene

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Authors: Okugbe Ebiotubo Ohore, Jingli Zhang, Binessi Edouard Ifon, Mathieu Nsenga Kumwimba, Xiaoying Mu, Dai Kuang, Zhen Wang, Ji-Dong Gu, Guojing Yang

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Antibiotic pollution and the evolution of antibiotic resistance genes (ARGs) are increasingly viewed as major threats to both ecosystem security and human health, and has drawn attention. This study investigated the fate of antibiotics in aqueous and sedimentary substrates and the impact of ecosystem shifts between water and sedimentary phases on resistome profiles. The findings indicated notable variations in the concentration and distribution patterns of antibiotics across various environmental phases. Based on the partition coefficient (Kd), the total antibiotic concentration was significantly greater in the surface water (1405.45 ng/L; 49.5%) compared to the suspended particulate matter (Kd =0.64; 892.59 ng/g; 31.4%) and sediment (Kd=0.4; 542.64 ng/g; 19.1%). However, the relative abundance of ARGs in surface water and sediment was disproportionate to the abundance of antibiotics concentration, and sediments were the predominant ARGs reservoirs. Phylogenetic divergence of the microbial communities between the surface water and the sedimentary ecosystems potentially played important roles in driving the ARGs profiles between the two distinctive ecosystems. ARGs of Clinical importance; including blaGES, MCR-7.1, ermB, tet(34), tet36, tetG-01, and sul2 were significantly increased in the surface water, while blaCTX-M-01, blaTEM, blaOXA10-01, blaVIM, tet(W/N/W), tetM02, and ermX were amplified in the sediments. cfxA was an endemic ARG in surface-water ecosystems while the endemic ARGs of the sedimentary ecosystems included aacC4, aadA9-02, blaCTX-M-04, blaIMP-01, blaIMP-02, bla-L1, penA, erm(36), ermC, ermT-01, msrA-01, pikR2, vgb-01, mexA, oprD, ttgB, and aac. These findings offer a valuable information for the identification of ARGs-specific high-risk reservoirs.

Keywords: antibiotic resistance genes, microbial diversity, suspended particulate matter, sediment, surface water

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Authors: Roxanne J. Kovacs

Abstract:

This paper shows that political corruption in Ghana and Kenya does not, as is assumed by a considerable part of the academic literature, depend on the level of party competition as such, but rather on the kinds of issues that parties compete about. Party competition in Ghana revolves around party performance, which gives political leaders a strong incentive to control corruption. In contrast, party competition in Kenya revolves around ethnic identities, which directly reduces competition based on candidate quality and therefore fosters corruption.

Keywords: corruption, electoral competition, Kenya, Ghana

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Authors: Mane Darbinyan, Lusine Hayrapetyan, Elen Matevosyan

Abstract:

Artificial Intelligence in Education (AIED) has been created to help students get ready for the workforce, and over the past 25 years, it has grown significantly, offering a variety of technologies to support academic, institutional, and administrative services. However, this is still challenging, especially considering the labor market's rapid change. While choosing a career, people face various obstacles because they do not take into consideration their own preferences, which might lead to many other problems like shifting jobs, work stress, occupational infirmity, reduced productivity, and manual error. Besides preferences, people should properly evaluate their technical and non-technical skills, as well as their personalities. Professional counseling has become a difficult undertaking for counselors due to the wide range of career choices brought on by changing technological trends. It is necessary to close this gap by utilizing technology that makes sophisticated predictions about a person's career goals based on their personality. Hence, there is a need to create an automated model that would help in decision-making based on user inputs. Improving career guidance can be achieved by embedding machine learning into the career consulting ecosystem. There are various systems of career guidance that work based on the same logic, such as the classification of applicants, matching applications with appropriate departments or jobs, making predictions, and providing suitable recommendations. Methodologies like KNN, Neural Networks, K-means clustering, D-Tree, and many other advanced algorithms are applied in the fields of data and compute some data, which is helpful to predict the right careers. Besides helping users with their career choice, these systems provide numerous opportunities which are very useful while making this hard decision. They help the candidate to recognize where he/she specifically lacks sufficient skills so that the candidate can improve those skills. They are also capable to offer an e-learning platform, taking into account the user's lack of knowledge. Furthermore, users can be provided with details on a particular job, such as the abilities required to excel in that industry.

Keywords: career guidance system, machine learning, career prediction, predictive decision, data mining, technical and non-technical skills

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Authors: Mane Darbinyan, Lusine Hayrapetyan, Elen Matevosyan

Abstract:

Artificial Intelligence in Education (AIED) has been created to help students get ready for the workforce, and over the past 25 years, it has grown significantly, offering a variety of technologies to support academic, institutional, and administrative services. However, this is still challenging, especially considering the labor market's rapid change. While choosing a career, people face various obstacles because they do not take into consideration their own preferences, which might lead to many other problems like shifting jobs, work stress, occupational infirmity, reduced productivity, and manual error. Besides preferences, people should evaluate properly their technical and non-technical skills, as well as their personalities. Professional counseling has become a difficult undertaking for counselors due to the wide range of career choices brought on by changing technological trends. It is necessary to close this gap by utilizing technology that makes sophisticated predictions about a person's career goals based on their personality. Hence, there is a need to create an automated model that would help in decision-making based on user inputs. Improving career guidance can be achieved by embedding machine learning into the career consulting ecosystem. There are various systems of career guidance that work based on the same logic, such as the classification of applicants, matching applications with appropriate departments or jobs, making predictions, and providing suitable recommendations. Methodologies like KNN, neural networks, K-means clustering, D-Tree, and many other advanced algorithms are applied in the fields of data and compute some data, which is helpful to predict the right careers. Besides helping users with their career choice, these systems provide numerous opportunities which are very useful while making this hard decision. They help the candidate to recognize where he/she specifically lacks sufficient skills so that the candidate can improve those skills. They are also capable of offering an e-learning platform, taking into account the user's lack of knowledge. Furthermore, users can be provided with details on a particular job, such as the abilities required to excel in that industry.

Keywords: career guidance system, machine learning, career prediction, predictive decision, data mining, technical and non-technical skills

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Authors: Nehal F. Hassib, Rasha M. ElHossini, Inas M. sayed, Maha R. Abouzeid, Nermeen A. Bayoumi, Aida M. Mosaad, Lamia K. Gadallah, Moataz Bellah A. T. Abdelbari, Heba A El-Sayed, Hasnaa Elbendary, Ghada Abdel-Salam, Maha Zaki, Mostafa I. Mostafa, Mohamed S. Abdel-Hamid

Abstract:

Enamel, the outermost layer of the tooth crown, is the hardest dental tissue and serves as a protective barrier. Amelogenesis, the process of enamel formation, is regulated by multiple genes to ensure normal, defect-free enamel. Defective enamel manifests as hypoplasia or as amelogenesis imperfecta (AI), which may occur in isolation or as part of a syndrome. This study presents 29 patients from 18 unrelated families (16 females and 13 males) who exhibited distinctive enamel abnormalities. We conducted thorough clinical examinations and requested laboratory and radiological investigations. Blood samples were collected for molecular analysis, utilizing a targeted panel for known AI variants and whole exome sequencing for unknown variants. Eleven variants linked to enamel anomalies were identified: four genes associated with isolated AI (WDR72, ACP4, SLC24A4, and FAM83H) and seven associated with syndromic forms, including enamel renal syndrome (FAM20A), tricho-dento-osseous syndrome (DLX3), Jalili syndrome (CNNM4), and others linked to neurological and mitochondrial disorders, skeletal dysplasia, and peroxisome disorders. Abnormal oral and dental phenotypes in individuals may indicate serious inherited disorders. Enamel defects have significant implications for aesthetics, function, and patients' psychological well-being. Dental examination, alongside clinical and molecular investigations, is crucial for the accurate diagnosis and prediction of inherited conditions.

Keywords: amelogenesis imperfecta, enamel defect, Enamel renal syndrome, DLX3, Jalili syndrome, WDR72, FAM83H, whole exome sequencing

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Authors: Tarek Duzan, Walid Esayed

Abstract:

Fluid flow in porous media is attributed fundamentally to parameters that are controlled by depositional and post-depositional environments. After deposition, digenetic events can act negatively on the reservoir and reduce the effective porosity, thereby making the rock less permeable. Therefore, exploiting hydrocarbons from such resources requires partially altering the rock properties to improve the long-term production rate and enhance the recovery efficiency. In this study, we try to address, firstly, the phenomena of permeability reduction in tight sandstone reservoirs and illustrate the implemented procedures to investigate the problem roots; finally, benchmark the candidate solutions at the field scale and recommend the mitigation strategy for the field development plan. During the study, two investigations have been considered: subsurface analysis using ( PLT ) and Laboratory tests for four candidate wells of the interested reservoir. Based on the above investigations, it was obvious that the Production logging tool (PLT) has shown areas of contribution in the reservoir, which is considered very limited, considering the total reservoir thickness. Also, Alcohol treatment was the first choice to go with for the AA9 well. The well productivity has been relatively restored but not to its initial productivity. Furthermore, Alcohol treatment in the lab was effective and restored permeability in some plugs by 98%, but operationally, the challenge would be the ability to distribute enough alcohol in a wellbore to attain the sweep Efficiency obtained within a laboratory core plug. However, the Second solution, which is based on fracking wells, has shown excellent results, especially for those wells that suffered a high drop in oil production. It is suggested to frac and pack the wells that are already damaged in the Waha field to mitigate the damage and restore productivity back as much as possible. In addition, Critical fluid velocity and its effect on fine sand migration in the reservoir have to be well studied on core samples, and therefore, suitable pressure drawdown will be applied in the reservoir to limit fine sand migration.

Keywords: alcohol treatment, post-depositional environments, permeability, tight sandstone

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Authors: Syed Beenish Rufai, Sarman Singh

Abstract:

Background: Performance of Genotype MTBDRsl (Hain Life science GmbH Germany) for detection of mutations associated with second-line drug resistance is well known. However, less evidence regarding the association of mutations and genetic background of strains is known which, in the future, is essential for clinical management of anti-tuberculosis drugs in those settings where the probability of particular genotype is predominant. Material and Methods: During this retrospective study, a total of 259 MDR-TB isolates obtained from pulmonary TB patients were tested for second-line drug susceptibility testing (DST) using Genotype MTBDRsl VER 1.0 and compared with BACTEC MGIT-960 as a reference standard. All isolates were further characterized using spoligotyping. The spoligo patterns obtained were compared and analyzed using SITVIT_WEB. Results: Of total 259 MDR-TB isolates which were screened for second-line DST by Genotype MTBDRsl, mutations were found to be associated with gyrA, rrs and emb genes in 82 (31.6%), 2 (0.8%) and 90 (34.7%) isolates respectively. 16 (6.1%) isolates detected mutations associated with both FQ as well as to AG/CP drugs (XDR-TB). No mutations were detected in 159 (61.4%) isolates for corresponding gyrA and rrs genes. Genotype MTBDRsl showed a concordance of 96.4% for detection of sensitive isolates in comparison with second-line DST by BACTEC MGIT-960 and 94.1%, 93.5%, 60.5% and 50% for detection of XDR-TB, FQ, EMB, and AMK/CAP respectively. D94G was the most prevalent mutation found among (38 (46.4%)) OFXR isolates (37 FQ mono-resistant and 1 XDR-TB) followed by A90V (23 (28.1%)) (17 FQ mono-resistant and 6 XDR-TB). Among AG/CP resistant isolates A1401G was the most frequent mutation observed among (11 (61.1%)) isolates (2 AG/CP mono-resistant isolates and 9 XDR-TB isolates) followed by WT+A1401G (6 (33.3%)) and G1484T (1 (5.5%)) respectively. On spoligotyping analysis, Beijing strain (46%) was found to be the most predominant strain among pre-XDR and XDR TB isolates followed by CAS (30%), X (6%), Unique (5%), EAI and T each of 4%, Manu (3%) and Ural (2%) respectively. Beijing strain was found to be strongly associated with D94G (47.3%) and A90V mutations by (47.3%) and 34.8% followed by CAS strain by (31.6%) and 30.4% respectively. However, among AG/CP resistant isolates, only Beijing strain was found to be strongly associated with A1401G and WT+A1401G mutations by 54.5% and 50% respectively. Conclusion: Beijing strain was found to be strongly associated with the most prevalent mutations among pre-XDR and XDR TB isolates. Acknowledgments: Study was supported with Grant by All India Institute of Medical Sciences, New Delhi reference No. P-2012/12452.

Keywords: tuberculosis, line probe assay, XDR TB, drug susceptibility

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Authors: I. M. L. Nadeesha Jayaweera, Adao Alex Trindade

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In choosing a candidate model in likelihood-based modeling via an information criterion, the practitioner is often faced with the difficult task of deciding just how far up the ranked list to look. Motivated by this pragmatic necessity, we construct an uncertainty band for a generalized (model selection) information criterion (GIC), defined as a criterion for which the limit in probability is identical to that of the normalized log-likelihood. This includes common special cases such as AIC & BIC. The method starts from the asymptotic normality of the GIC for the joint distribution of the candidate models in an independent and identically distributed (IID) data framework and proceeds by deriving the (asymptotically) exact distribution of the minimum. The calculation of an upper quantile for its distribution then involves the computation of multivariate Gaussian integrals, which is amenable to efficient implementation via the R package "mvtnorm". The performance of the methodology is tested on simulated data by checking the coverage probability of nominal upper quantiles and compared to the bootstrap. Both methods give coverages close to nominal for large samples, but the bootstrap is two orders of magnitude slower. The methodology is subsequently extended to two other commonly used model structures: regression and time series. In the regression case, we derive the corresponding asymptotically exact distribution of the minimum GIC invoking Lindeberg-Feller type conditions for triangular arrays and are thus able to similarly calculate upper quantiles for its distribution via multivariate Gaussian integration. The bootstrap once again provides a default competing procedure, and we find that similar comparison performance metrics hold as for the IID case. The time series case is complicated by far more intricate asymptotic regime for the joint distribution of the model GIC statistics. Under a Gaussian likelihood, the default in most packages, one needs to derive the limiting distribution of a normalized quadratic form for a realization from a stationary series. Under conditions on the process satisfied by ARMA models, a multivariate normal limit is once again achieved. The bootstrap can, however, be employed for its computation, whence we are once again in the multivariate Gaussian integration paradigm for upper quantile evaluation. Comparisons of this bootstrap-aided semi-exact method with the full-blown bootstrap once again reveal a similar performance but faster computation speeds. One of the most difficult problems in contemporary statistical methodological research is to be able to account for the extra variability introduced by model selection uncertainty, the so-called post-model selection inference (PMSI). We explore ways in which the GIC uncertainty band can be inverted to make inferences on the parameters. This is being attempted in the IID case by pivoting the CDF of the asymptotically exact distribution of the minimum GIC. For inference one parameter at a time and a small number of candidate models, this works well, whence the attained PMSI confidence intervals are wider than the MLE-based Wald, as expected.

Keywords: model selection inference, generalized information criteria, post model selection, Asymptotic Theory

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Authors: Reihane Mehrparvar

Abstract:

Human age could exceed further by altering gene expression through food intaking, although as a consequence of recent century eating patterns, human life-span getting shorter by emerging irregulating in autophagy mechanism, insulin, leptin, gut microbiota which are important etiological factors of type-2 diabetes, obesity, infertility, cancer, metabolic and autoimmune diseases. However, restricted calorie intake and vigorous exercise might be beneficial for losing weight and metabolic regulation in a short period but could not be implementable in the long term as a way of life. Therefore, the lack of a dietary program that is compatible with the genes of the body is essential. Sweet and high-glycemic-index (HGI) foods were associated with type-2 diabetes and cancer morbidity. The neuropsychological perspective characterizes the inclination of sweet and HGI-food consumption as addictive behavior; hence this process engages preference of gut microbiota, neural node, and dopaminergic functions. Moreover, meal composition is not the only factor that affects body hemostasis. In this narrative review, it is believed to attempt to investigate how the body responded to different food intakes and represent an accurate model based on current evidence. Eating frequently and ingesting unassimilable protein and carbohydrates may not be compatible with human genes and could cause impairments in the self-renovation mechanism. This trajectory indicates our body is more adapted to starvation and eating animal meat and marrow. Here has been recommended a model that takes into account three important factors: frequent eating, meal composition, and circadian rhythm, which may offer a promising intervention for obesity, inflammation, cardiovascular, autoimmune disorder, type-2 diabetes, insulin resistance, infertility, and cancer through intensifying autophagy-mechanism and eliminate medical costs.

Keywords: metabolic disease, anti-aging, type-2 diabetes, autophagy

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Authors: Yong-Kian Lim, Khan Cheung, Xin Dang, Steven Roberts, Xiaotong Wang, Vengatesen Thiyagarajan

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Unprecedented rate of increased CO₂ level in the ocean and the subsequent changes in carbonate system including decreased pH, known as ocean acidification (OA), is predicted to disrupt not only the calcification process but also several other physiological and developmental processes in a variety of marine organisms, including edible oysters. Nonetheless, not all species are vulnerable to those OA threats, e.g., some species may be able to cope with OA stress using environmentally induced modifications on gene and protein expressions. For example, external environmental stressors, including OA, can influence the addition and removal of methyl groups through epigenetic modification (e.g., DNA methylation) process to turn gene expression “on or off” as part of a rapid adaptive mechanism to cope with OA. In this study, the above hypothesis was tested through testing the effect of OA, using decreased pH 7.4 as a proxy, on the DNA methylation pattern of an endemic and a commercially important estuary oyster species, Crassostrea hongkongensis, at the time of larval habitat selection and metamorphosis. Larval growth rate did not differ between control pH 8.1 and treatment pH 7.4. The metamorphosis rate of the pediveliger larvae was higher at pH 7.4 than those in control pH 8.1; however, over one-third of the larvae raised at pH 7.4 failed to attach to an optimal substrate as defined by biofilm presence. During larval development, a total of 130 genes were differentially methylated across the two treatments. The differential methylation in the larval genes may have partially accounted for the higher metamorphosis success rate under decreased pH 7.4 but with poor substratum selection ability. Differentially methylated loci were concentrated in the exon regions and appear to be associated with cytoskeletal and signal transduction, oxidative stress, metabolic processes, and larval metamorphosis, which implies the high potential of C. hongkongensis larvae to acclimate and adapt through non-genetic ways to OA threats within a single generation.

Keywords: adaptive plasticity, DNA methylation, larval metamorphosis, ocean acidification

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Authors: Sandra Smieszek, Jonathan Haines

Abstract:

Introduction: Numerous research efforts have focused on searching for ‘longevity genes’. However, attempting to decipher the genetic component of the longevous phenotype have resulted in limited success and the mechanisms governing longevity remain to be explained. We conducted a genome-wide homozygosity analysis (GWHA) of the founder population of the Amish community in central Ohio. While genome-wide association studies using unrelated individuals have revealed many interesting longevity associated variants, these variants are typically of small effect and cannot explain the observed patterns of heritability for this complex trait. The Amish provide a large cohort of extended kinships allowing for in depth analysis via family-based approach excellent population due to its. Heritability of longevity increases with age with significant genetic contribution being seen in individuals living beyond 60 years of age. In our present analysis we show that the heritability of longevity is estimated to be increasing with age particularly on the paternal side. Methods: The present analysis integrated both phenotypic and genotypic data and led to the discovery of a series of variants, distinct for stratified populations across ages and distinct for paternal and maternal cohorts. Specifically 5437 subjects were analyzed and a subset of 893 successfully genotyped individuals was used to assess CHIP heritability. We have conducted the homozygosity analysis to examine if homozygosity is associated with increased risk of living beyond 90. We analyzed AMISH cohort genotyped for 614,957 SNPs. Results: We delineated 10 significant regions of homozygosity (ROH) specific for the age group of interest (>90). Of particular interest was ROH on chromosome 13, P < 0.0001. The lead SNPs rs7318486 and rs9645914 point to COL4A2 and our lead SNP. COL25A1 encodes one of the six subunits of type IV collagen, the C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities. The second region of interest points to IRS2. Furthermore we built a classifier using the obtained SNPs from the significant ROH region with 0.945 AUC giving ability to discriminate between those living beyond to 90 years of age and beyond. Conclusion: In conclusion our results suggest that a history of longevity does indeed contribute to increasing the odds of individual longevity. Preliminary results are consistent with conjecture that heritability of longevity is substantial when we start looking at oldest fifth and smaller percentiles of survival specifically in males. We will validate all the candidate variants in independent cohorts of centenarians, to test whether they are robustly associated with human longevity. The identified regions of interest via ROH analysis could be of profound importance for the understanding of genetic underpinnings of longevity.

Keywords: regions of homozygosity, longevity, SNP, Amish

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Authors: Swathi Sampath, V. Kalaichelvi

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The assessment of the risk posed by a borrower to a lender is one of the common problems that financial institutions have to deal with. Consumers vying for a mortgage are generally compared to each other by the use of a number called the Credit Score, which is generated by applying a mathematical algorithm to information in the applicant’s credit report. The higher the credit score, the lower the risk posed by the candidate, and the better he is to be taken on by the lender. The objective of the present work is to use fuzzy logic and linguistic rules to create a model that generates Credit Scores.

Keywords: credit scoring, fuzzy logic, mortgage, risk assessment

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Authors: Pei Chi Fang, Wei Chen Lin

Abstract:

Trichomonas tenax is a microaerophilic oral protozoan found in patients with poor oral hygiene. It participates in the inflammatory process of periodontal disease and can potentially be aspirated into the lungs, giving rise to pulmonary trichomoniasis. However, the precise roles of T. tenax in the pulmonary system remain largely unexplored and warrant comprehensive epidemiological investigation. To assess the prevalence of T. tenax infection, we collected bronchoalveolar lavage fluid (BALF) samples from hospitalized patients with lung diseases. A specific nested PCR approach was employed to determine prevalence rates, yielding 21 positive cases out of 61 samples from Ditmanson Medical Foundation Chia-Yi Christian Hospital, and 11 positive cases out of 55 samples from National Cheng Kung University Hospital. Furthermore, there is a critical need for comprehensive data regarding the presence of T. tenax in environmental surface watersheds. In this context, we present findings from investigations in the Yanshuei and Donggang river basins in southern Taiwan, which are crucial sources for public drinking water in the region. In order to elucidate potential implications on pulmonary virus infections, we conducted an analysis of gene expression level changes in H292 cell line after exposure to T. tenax. Our findings revealed significant regulation of multiple virus-related genes, including IFI44L and IFITM3. Ongoing research endeavors are focused on identifying the key components within T. tenax responsible for these observed effects. Crucially, this study lays the groundwork for a preliminary understanding of T. tenax prevalence in patients with pulmonary diseases. It also seeks to establish a meaningful correlation between lung infections and oral hygiene practices, with the ultimate aim of informing distinct treatment and prevention strategies.

Keywords: parasitology, genes, virus, human health, infection, lung

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Authors: Sheraz Gul

Abstract:

The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.

Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics

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Authors: Anuj Tyagi, Balwinder Singh, Naveen Kumar B. T., Niraj K. Singh

Abstract:

Characterization of diverse microbial communities in specific environment plays a crucial role in the better understanding of their functional relationship with the ecosystem. It is now well established that gut microbiome of fish is not the simple replication of microbiota of surrounding local habitat, and extensive species, dietary, physiological and metabolic variations in fishes may have a significant impact on its composition. Moreover, overuse of antibiotics in human, veterinary and aquaculture medicine has led to rapid emergence and propagation of antibiotic resistance genes (ARGs) in the aquatic environment. Microbial communities harboring specific ARGs not only get a preferential edge during selective antibiotic exposure but also possess the significant risk of ARGs transfer to other non-resistance bacteria within the confined environments. This phenomenon may lead to the emergence of habitat-specific microbial resistomes and subsequent emergence of virulent antibiotic-resistant pathogens with severe fish and consumer health consequences. In this study, gut microbiota of freshwater carp (Labeo rohita) was investigated by shotgun metagenomics to understand its taxonomic composition and functional capabilities. Metagenomic DNA, extracted from the fish gut, was subjected to sequencing on Illumina NextSeq to generate paired-end (PE) 2 x 150 bp sequencing reads. After the QC of raw sequencing data by Trimmomatic, taxonomic analysis by Kraken2 taxonomic sequence classification system revealed the presence of 36 phyla, 326 families and 985 genera in the fish gut microbiome. At phylum level, Proteobacteria accounted for more than three-fourths of total bacterial populations followed by Actinobacteria (14%) and Cyanobacteria (3%). Commonly used probiotic bacteria (Bacillus, Lactobacillus, Streptococcus, and Lactococcus) were found to be very less prevalent in fish gut. After sequencing data assembly by MEGAHIT v1.1.2 assembler and PROKKA automated analysis pipeline, pathway analysis revealed the presence of 1,608 Metacyc pathways in the fish gut microbiome. Biosynthesis pathways were found to be the most dominant (51%) followed by degradation (39%), energy-metabolism (4%) and fermentation (2%). Almost one-third (33%) of biosynthesis pathways were involved in the synthesis of secondary metabolites. Metabolic pathways for the biosynthesis of 35 antibiotic types were also present, and these accounted for 5% of overall metabolic pathways in the fish gut microbiome. Fifty-one different types of antibiotic resistance genes (ARGs) belonging to 15 antimicrobial resistance (AMR) gene families and conferring resistance against 24 antibiotic types were detected in fish gut. More than 90% ARGs in fish gut microbiome were against beta-lactams (penicillins, cephalosporins, penems, and monobactams). Resistance against tetracycline, macrolides, fluoroquinolones, and phenicols ranged from 0.7% to 1.3%. Some of the ARGs for multi-drug resistance were also found to be located on sequences of plasmid origin. The presence of pathogenic bacteria and ARGs on plasmid sequences suggested the potential risk due to horizontal gene transfer in the confined gut environment.

Keywords: antibiotic resistance, fish gut, metabolic pathways, microbial diversity

Procedia PDF Downloads 140