Search results for: genetic polymorphism

Authors: Abejide Dorcas Ropo, Falusi Olamide Ahmed, Daudu Oladipupo Abdulazeez Yusuf, Muhammad Liman Muhammad, Gado Aishatu Adamu

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Bambara groundnut is an indigenous African legume with great potential to tackle the problem of food insecurity in Nigeria. A germplasm collection mission was carried out in collaboration with the Agricultural Developments Project (ADP) Extension officers of Nigeria between October and December 2014. Bambara groundnut seeds were collected from farmers in different States in Nigeria, such as Kaduna, Niger, Kogi, Benue, Plateau, Adamawa, Nasarawa, Jigawa, Enugu, and Federal Capital Territoy (FCT) Abuja. Some seeds were also collected from National Centre for Genetic Resources and Biotechnology (NACGRAB). The seeds were phenotyped using the descriptor list of Vigna subterranea produced by the International Plant Genetic Resource Institute. A total of 45 original seed lots were collected, which comprised of mixed seeds having different seed coat colours (15) and pure seeded accessions having the same seed coat and eye colour (30). After sorting, a total of 83 accessions were derived from the 45 original seed lots collected, and a total of 24 distinct seed morphotypes with varying seed coat colours and eye colours were identified from the collections. They include cream ( cream ash eye, cream plain eye, and cream black eye), cream purplish spots, cream brown spots/stripe, cream black stripe, cream dark brown patches, cream light grey spots, cream black patches, black, red, light red, dark red, brownish red, brown speckled with black, red speckled with black, brown, brown with brown pattern below hilum, brown with black pattern below hilum, cream black, grey brown, grey black and variegated red. The highest number of accessions were collected from NACGRAB (11), followed by Niger State (10), and the lowest from Benue, Jigawa, and Adamawa States (2). Niger State also had the highest number of mixed seeds. The different seed phenotypes observed in the study are important for the field production of true-to-type lines and can be exploited for the genetic improvement of the Bambara groundnut.

Keywords: Bambara groundnut, characterization, collection, germplasm, phenotypic

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Authors: Maria Luisa Nozawa Ribeiro, Maria Teresa Miceli Kerbauy

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This paper aims to present the theories of public participation in order to understand the context of the public GMO (Genetic Modified Organisms) policies in Brazil, highlighting the characteristics of its configuration and the dialog with the experts. As a controversy subject, the commercialization of GMO provoked manifestation of some popular and environmental representative groups questioning the decisions of policy makers and experts on the matter. Many aspects and consequences of the plantation and consumption of this crops emerged and the safety of this technology was questioned. Environmentalists, Civil Right's movement, representatives of rural workers, farmers and organics producers, etc. demonstrated their point of view, also sustained by some experts of medical, genetical, environmental, agronomical sciences, etc. fields. Despite this movement, the precautionary principle (risk management), implemented in 1987, suggested precaution facing new technologies and innovations in the sustainable development society. This principle influenced many legislation and regulation on GMO around the world, including Brazil, which became a reference among the world regulatory GMO systems. The Brazilian legislation ensures the citizens participation on GMO discussion, characteristic that was important to establish the connection between the subject and the participation theory. These deliberation spaces materialized in Brazil through the "Public Audiences", which are managed by the National Biosafety Technical Commission (CTNBio), the department responsible for controlling the research, production and commercialization of GMOs in Brazil.

Keywords: public engagement, public participation, science and technology studies, transgenic politics

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Authors: Sibusiso Trevor Tshabalala, Samuel Lubbe, Vince Vuledzani Ndou

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Dependency on chemicals has had many disadvantages in pest management control strategies. Such genetic rodenticide resistance and secondary exposure risk are what is currently being experienced. Emphasis on integrated pest management suggests that to control future pests, early intervention and economic threshold development are key starting points in crop production. The significance of this research project is to help establish a relationship between Giant African Land Snail (Achatina Fulica) solution extract, its shell chemical properties, and farmer’s perceptions of biological control in eThekwini Municipality Agri-hubs. A mixed design approach to collecting data will be explored using a trial layout in the field and through interviews. The experimental area will be explored using a split-plot design that will be replicated and arranged in a randomised complete block design. The split-plot will have 0, 10, 20 and 30 liters of water to one liter of snail solution extract. Plots were 50 m² each with a spacing of 12 m between each plot and a plant spacing of 0.5 m (inter-row) ‘and 0.5 m (intra-row). Trials will be irrigated using sprinkler irrigation, with objective two being added to the mix every 4-5 days. The expected outcome will be improved soil fertility and micro-organisms population proliferation.

Keywords: giant african land snail, integrated pest management, photosynthesis, genetic rodenticide resistance, control future pests, shell chemical properties

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Authors: Anita Singh, Richa Naula, Manoj Raghav

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Nutrient rich and high-yielding varieties of fenugreek can be developed by using genotypes which are naturally high in nutrients. Gene banks harbour scanty germplasm collection of Trigonella spp. and a very little background information about its genetic diversity. The extent of genetic diversity in a specific breeding population depends upon the genotype included in it. The present investigation aims at the estimation of macronutrient (phosphorus by spectrophotometer and potassium by flame photometer), micronutrients, namely, iron, zinc, manganese, and copper from seeds of fenugreek genotypes using atomic absorption spectrophotometer, protein by Rapid N Cube Analyser and Steroidal Saponins. Twenty-eight genotypes of fenugreek along with two standard checks, namely, Pant Ragini and Pusa Early Bunching were collected from different parts of India, and nutrient contents of each genotype were determined at G. B. P. U. A. & T. Laboratory, Pantnagar. Highest potassium content was observed in PFG-35 (1207 mg/100g). PFG-37 and PFG-20 were richest in phosphorus, iron and manganese content among all the genotypes. The lowest zinc content was found in PFG-26 (1.19 mg/100g), while the maximum zinc content was found in PFG- 28 (4.43 mg/100g). The highest content of copper was found in PFG-26 (1.97 mg/100g). PFG-39 has the highest protein content (29.60 %). Significant differences were observed in the steroidal saponin among the genotypes. Saponin content ranged from 0.38 g/100g to 1.31 g/100g. Steroidal Saponins content was found the maximum in PFG-36 (1.31 g/100g) followed by PFG-17 (1.28 g/100g). Therefore, the genotypes which are rich in nutrient and oil content can be used for plant biofortification, dietary supplements, and herbal products.

Keywords: genotypes, macronutrients, micronutrient, protein, seeds

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Authors: Mariam Khaled, Noha Farag, Ghada Mohamed Abdel Salam, Khaled Abu-Aisha, Mohamed El-Azizi

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Gastric and colorectal cancers are among the most frequent causes of cancer-associated mortalities in Africa. They have been considered as a global public health concern, as nearly one million new cases are reported per year. IL-1β is a pro-inflammatory cytokine-produced by activated macrophages and monocytes- and a member of the IL-1 family. The inactive IL-1β precursor is cleaved and activated by caspase-1 enzyme, which itself is activated by the assembly of intracellular structures defined as NLRP3 (Nod Like receptor P3) inflammasomes. Activated IL-1β stimulates the Interleukin-1 receptor type-1 (IL-1R1), which is responsible for the initiation of a signal transduction pathway leading to cell proliferation. It has been proven that the IL-1β gene is a highly polymorphic gene in which single nucleotide polymorphisms (SNPs) may affect its expression. It has been previously reported that SNPs including base transitions between C and T at positions, -511 (C-T; dbSNP: rs16944) and -31 (C-T; dbSNP: rs1143627), from the transcriptional start site, contribute to the pathogenesis of gastric and colorectal cancers by affecting IL-1β levels. Altered production of IL-1β due to such polymorphisms is suspected to stimulate an amplified inflammatory response and promote Epithelial Mesenchymal Transition leading to malignancy. Allele frequency distribution of the IL-1β-31 and -511 SNPs, in different populations, and their correlation to the incidence of gastric and colorectal cancers, has been intriguing to researchers worldwide. The current study aims to investigate allele distributions of the IL-1β SNPs among gastric and colorectal cancers Egyptian patients. In order to achieve to that, 89 Biopsy and surgical specimens from the antrum and corpus mucosa of chronic gastritis subjects and gastric and colorectal carcinoma patients was collected for DNA extraction followed by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). The amplified PCR products of IL-1β-31C > T and IL-1β-511T > C were digested by incubation with the restriction endonuclease enzymes ALu1 and Ava1. Statistical analysis was carried out to determine the allele frequency distribution in the three studied groups. Also, the effect of the IL-1β -31 and -511 SNPs on nuclear factor binding was analyzed using Fluorescence Electrophoretic Mobility Shift Assay (EMSA), preceded by nuclear factor extraction from gastric and colorectal tissue samples and LPS stimulated monocytes. The results of this study showed that a significantly higher percentage of Egyptian gastric cancer patients have a homozygous CC genotype at the IL-1β-31 position and a heterozygous TC genotype at the IL-1β-511 position. Moreover, a significantly higher percentage of the colorectal cancer patients have a homozygous CC genotype at the IL-1β-31 and -511 positions as compared to the control group. In addition, the EMSA results showed that IL-1β-31C/T and IL-1β-511T/C SNPs do not affect nuclear factor binding. Results of this study suggest that the IL-1β-31 C/T and IL-1β-511 T/C may be correlated to the incidence of gastric cancer in Egyptian patients; however, similar findings couldn’t be proven in the colorectal cancer patients group for the IL-1β-511 T/C SNP. This is the first study to investigate IL-1β -31 and -511 SNPs in the Egyptian population.

Keywords: colorectal cancer, Egyptian patients, gastric cancer, interleukin-1β, single nucleotide polymorphisms

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Authors: Mohammed N. Al Kindi, Mazin Al Khabouri, Khalsa Al Lamki, Tommasso Pappuci, Giovani Romeo, Nadia Al Wardy

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Hereditary hearing loss is a heterogeneous group of complex disorders with an overall incidence of one in every five hundred newborns presented as syndromic and non-syndromic forms. Cadherin-related 23 (CDH23) is one of the listed deafness causative genes. CDH23 is found to be expressed in the stereocilia of hair cells and the retina photoreceptor cells. Defective CDH23 has been associated mostly with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic (USH1D) or non-syndromic SNHL (DFNB12). An Omani family diagnosed clinically with severe-profound sensorineural hearing loss was genetically analysed by whole exome sequencing technique. A novel homozygous missense variant, c.A7451C (p.D2484A), in exon 53 of CDH23 was detected. One hundred and thirty control samples were analysed where all were negative for the detected variant. The variant was analysed in silico for pathogenicity verification using several mutation prediction software. The variant proved to be a pathogenic mutation and is reported for the first time in Oman and worldwide. It is concluded that in silico mutation prediction analysis might be used as a useful molecular diagnostics tool benefiting both genetic counseling and mutation verification. The aspartic acid 2484 alanine missense substitution might be the main disease-causing mutation that damages CDH23 function and could be used as a genetic hearing loss marker for this particular Omani family.

Keywords: Cdh23, d2484a, in silico, Oman

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Authors: Nafiseh Noormohammadi, Ahmad Sobhani Najafabadi

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Hypericins (hypericin and pseudohypericin) are natural napthodianthrone derivatives produced by Hypericum perforatum (St. John’s Wort), which have many medicinal properties such as antitumor, antineoplastic, antiviral, and antidepressant activities. Production and accumulation of hypericin in the plant are influenced by both genetic and environmental conditions. Despite the existence of different high-throughput data on the plant, genetic dimensions of hypericin biosynthesis have not yet been completely understood. In this research, 21 high-quality RNA-seq data on different parts of the plant were integrated into metabolic data to reconstruct a coexpression network. Results showed that a cluster of 30 transcripts was correlated with total hypericin. The identified transcripts were divided into three main groups based on their functions, including hypericin biosynthesis genes, transporters, detoxification genes, and transcription factors (TFs). In the biosynthetic group, different isoforms of polyketide synthase (PKSs) and phenolic oxidative coupling proteins (POCPs) were identified. Phylogenetic analysis of protein sequences integrated into gene expression analysis showed that some of the POCPs seem to be very important in the biosynthetic pathway of hypericin. In the TFs group, six TFs were correlated with total hypericin. qPCR analysis of these six TFs confirmed that three of them were highly correlated. The identified genes in this research are a rich resource for further studies on the molecular breeding of H. perforatum in order to obtain varieties with high hypericin production.

Keywords: hypericin, St. John’s Wort, data mining, transcription factors, secondary metabolites

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Authors: Faheema Khan

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To investigate the ability of sensitive and tolerant genotype of Glycine max to adapt to a saline environment in a field, we examined the growth performance, water relation and activities of antioxidant enzymes in relation to photosynthetic rate, chlorophyll a fluorescence, photosynthetic pigment concentration, protein and proline in plants exposed to salt stress. Ten soybean genotypes (Pusa-20, Pusa-40, Pusa-37, Pusa-16, Pusa-24, Pusa-22, BRAGG, PK-416, PK-1042, and DS-9712) were selected and grown hydroponically. After 3 days of proper germination, the seedlings were transferred to Hoagland’s solution (Hoagland and Arnon 1950). The growth chamber was maintained at a photosynthetic photon flux density of 430 μmol m−2 s−1, 14 h of light, 10 h of dark and a relative humidity of 60%. The nutrient solution was bubbled with sterile air and changed on alternate days. Ten-day-old seedlings were given seven levels of salt in the form of NaCl viz., T1 = 0 mM NaCl, T2=25 mM NaCl, T3=50 mM NaCl, T4=75 mM NaCl, T5=100 mM NaCl, T6=125 mM NaCl, T7=150 mM NaCl. The investigation showed that genotype Pusa-24, PK-416 and Pusa-20 appeared to be the most salt-sensitive. genotypes as inferred from their significantly reduced length, fresh weight and dry weight in response to the NaCl exposure. Pusa-37 appeared to be the most tolerant genotype since no significant effect of NaCl treatment on growth was found. We observed a greater decline in the photosynthetic variables like photosynthetic rate, chlorophyll fluorescence and chlorophyll content, in salt-sensitive (Pusa-24) genotype than in salt-tolerant Pusa-37 under high salinity. Numerous primers were verified on ten soybean genotypes obtained from Operon technologies among which 30 RAPD primers shown high polymorphism and genetic variation. The Jaccard’s similarity coefficient values for each pairwise comparison between cultivars were calculated and similarity coefficient matrix was constructed. The closer varieties in the cluster behaved similar in their response to salinity tolerance. Intra-clustering within the two clusters precisely grouped the 10 genotypes in sub-cluster as expected from their physiological findings.Salt tolerant genotype Pusa-37, was further analysed by 2-Dimensional gel electrophoresis to analyse the differential expression of proteins at high salt stress. In the Present study, 173 protein spots were identified. Of these, 40 proteins responsive to salinity were either up- or down-regulated in Pusa-37. Proteomic analysis in salt-tolerant genotype (Pusa-37) led to the detection of proteins involved in a variety of biological processes, such as protein synthesis (12 %), redox regulation (19 %), primary and secondary metabolism (25 %), or disease- and defence-related processes (32 %). In conclusion, the soybean plants in our study responded to salt stress by changing their protein expression pattern. The photosynthetic, biochemical and molecular study showed that there is variability in salt tolerance behaviour in soybean genotypes. Pusa-24 is the salt-sensitive and Pusa-37 is the salt-tolerant genotype. Moreover this study gives new insights into the salt-stress response in soybean and demonstrates the power of genomic and proteomic approach in plant biology studies which finally could help us in identifying the possible regulatory switches (gene/s) controlling the salt tolerant genotype of the crop plants and their possible role in defence mechanism.

Keywords: glycine max, salt stress, RAPD, genomic and proteomic variability

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Authors: Ming-Jong Yao, Chin-Sum Shui, Chih-Han Wang

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This paper is developed based on a real-world decision scenario that an industrial gas company that applies the Vendor Managed Inventory model and supplies liquid oxygen with a self-operated heterogeneous vehicle fleet to hospitals in nearby cities. We name it as a Joint Replenishment and Heterogeneous Vehicle Routing Problem with Cyclical Schedule and formulate it as a non-linear mixed-integer linear programming problem which simultaneously determines the length of the planning cycle (PC), the length of the replenishment cycle and the dates of replenishment for each customer and the vehicle routes of each day within PC, such that the average daily operation cost within PC, including inventory holding cost, setup cost, transportation cost, and overtime labor cost, is minimized. A solution method based on genetic algorithm, embedded with an encoding and decoding mechanism and local search operators, is then proposed, and the hash function is adopted to avoid repetitive fitness evaluation for identical solutions. Numerical experiments demonstrate that the proposed solution method can effectively solve the problem under different lengths of PC and number of customers. The method is also shown to be effective in determining whether the company should expand the storage capacity of a customer whose demand increases. Sensitivity analysis of the vehicle fleet composition shows that deploying a mixed fleet can reduce the daily operating cost.

Keywords: cyclic inventory routing problem, joint replenishment, heterogeneous vehicle, genetic algorithm

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

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Acinetobacter baumannii is a notorious bacterial pathogen that is an emerging nightmare in clinical settings and is mainly involved in severe nosocomial infections. However, the data related to carbapenem-resistant A. baumannii (CRAB) from veterinary settings is limited, especially in developing countries like Pakistan. To investigate the genetic diversity and molecular basis of carbapenem resistance in Acinetobacter baumannii isolates from Cattle, a total of 1960 samples were collected from cattle from Punjab, Pakistan. The isolates were analyzed by routine microbiological procedures and confirmed by polymerase chain reaction (PCR). The isolates were further screened for antimicrobial susceptibility and the presence of multiple antimicrobial-resistant determinants by PCR. Multilocus sequence typing (MLST) was performed. The results of the current study revealed that the overall prevalence of A. baumannii in cattle was 3.28% (65/1980). Among cattle 27.7% (18/65) were found CRAB strains. The CRAB isolates harbor class D β- lactamases genes, e-g, blaOXA-23 and blaOXA-51, 94.4% (17/18). CRAB isolates carry class B β- lactamases gene blaIMP, and only one isolate carries the blaNDM-1 gene. The MLST results of CRAB isolates from cattle demonstrated 5 STs and one new ST. The commonly found sequence types in CRAB isolates were ST2 (n=10, 55.5%), followed by ST642 (n=5, 27.8%) and ST600 & ST889 (n=1, 5.55%). The presence of CRAB isolates in cattle indicates an alarming situation in Punjab, Pakistan. Immediate control measures should be taken to stop the transmission of CRAB isolates within cattle, to the environment, and to clinical settings.

Keywords: acinetobacter baumannii, carbapenemases, veterinary, drug resistance

Procedia PDF Downloads 52

Authors: Ha T. T. Ly, Truc B. Truc, Hai N. Truong, Mai P. T. Nguyen, Ngoc D. Ngo, Khanh V. Tran, Hai T. Le

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Beta thalassemia is one of the most common inherited blood disorders, which is characterized by decreased or absent in beta globin expression. Patients with Beta thalassemia whose anemia is not so severe as to necessitate transfusions are said to have thalassemia intermedia. Objective: The goal of this study is prenatal diagnosis for pregnancy woman with Beta thalassemia intermedia and her husband with Beta thalassemia carrier at high risk of Beta thalassemia major in Northern of Vietnam. Material and method: The family has a 6 years-old compound heterozygous thalassemia major for CD71/72(+A) and Hbb:c. -78A>G/nt-28(A>G) male child. The father was heterozygous for CD71/72(+A) mutation which is Beta plus type and the mother was compound heterozygosity of two different variants, namely, Hbb: c. -78A>G/nt-28(A>G) and CD26(A-G) HbE. Prenatal Beta thalassemia mutation detection in fetal DNA was carried out using multiplex Amplification-refractory mutation system ARMS-PCR and confirmed by direct Sanger-sequencing Hbb gene. Prenatal diagnoses were perfomed by amniotic fluid sampling from pregnant woman in the 16-18th week of pregnancy after the genotypes of parents of the probands were identified. Result: When amniotic fluid sample was analyzed for Beta globin gene (Hbb), we found that the genotype is heterozygous for CD71/72(+A) and CD26(A-G) HbE. This genotype is different from the 1st child of this family. Conclusion: Prenatal diagnosis helps the parents to know the genotype and the thalassemia status of the fetus, so they can have early decision on their pregnancy. Genetic diagnosis provided a useful method in diagnosis for familial members in pedigree, genetic counseling and prenatal diagnosis.

Keywords: beta thalassemia intermedia, Hbb gene, pedigree, prenatal diagnosis

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Authors: Boukhalfa Djemouai, Belkadi Souhila, Safsaf Boubakeur

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To increase the profitability of the national herd so that it can meet the needs of the population, Algeria has proceeded to the introduction of new reproductive biotechnologies, including artificial insemination on natural heat, by induction and heat synchronization. This biotechnology uses the male way for the creation and dissemination of genetic progress. The study has focused on 30 goat kids and bucks local breed aged between 03 and 24 months, divided into 03 groups 03-06 months[Grp 1; n=9], 07-10 months [Grp 2; n=13] and 11-24 months [Grp 3; n=8], in order to determine the influence of age on testicular evolution by measurements of testis and scrotum, and the epididymis sperm parameters evaluation. These parameters are influenced by age variations (sperm and spermocytogram). The examined parameters have focused on testicular weight (grams), the scrotal circumference (cm), mass mobility (%), vitality rate (%), sperm concentration (x 109), and percentage of abnormal spermatozoa (%). The ANOVA reveals a significance effect of age on parameters: testis weight, scrotal circumference, sperm concentration, motility varying between high (p < 0.01) to very high significance (p < 0.001), while in viability and abnormalities no significance was observed between all groups. The value of these parameters increased significantly until the age of 02 years, while that of sperm abnormalities has increased in Grp2. The histological study of testicular development shows that the genetic spermatozoa function characterized by cell proliferation, which is more and more intense starting from the age of 05 months and can be considered as an age of puberty in the local breed goat Arbia and increases with animal age.

Keywords: kids and bucks, epididymis sperm, testicular measurements, Arbia breed

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Authors: A. Gopala Krishna, M. Lakshmi Chaitanya, V. Kalyana Manohar

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In the existent analysis, laser micro machining (LMM) of Silicon carbide (SiCp) reinforced Aluminum 7075 Metal Matrix Composite (Al7075/SiCp MMC) was studied. While machining, Because of the intense heat generated, A layer gets formed on the work piece surface which is called recast layer and this layer is detrimental to the surface quality of the component. The recast layer needs to be as small as possible for precise applications. Therefore, The height of recast layer and the depth of groove which are conflicting in nature were considered as the significant manufacturing criteria, Which determines the pursuit of a machining process obtained in LMM of Al7075/10%SiCp composite. The present work formulates the depth of groove and height of recast layer in relation to the machining parameters using the Response Surface Methodology (RSM) and correspondingly, The formulated mathematical models were put to use for optimization. Since the effect of machining parameters on the depth of groove and height of recast layer was contradictory, The problem was explicated as a multi objective optimization problem. Moreover, An evolutionary Non-dominated sorting genetic algorithm (NSGA-II) was employed to optimize the model established by RSM. Subsequently this algorithm was also adapted to achieve the Pareto optimal set of solutions that provide a detailed illustration for making the optimal solutions. Eventually experiments were conducted to affirm the results obtained from RSM and NSGA-II.

Keywords: Laser Micro Machining (LMM), depth of groove, Height of recast layer, Response Surface Methodology (RSM), non-dominated sorting genetic algorithm

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Authors: Dibakar Chakrabarty, Mebada Suiting

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Rapid urbanization coupled with changes in land use pattern results in increasing peak discharge and shortening of catchment time of concentration. The consequence is floods, which often inundate roads and inhabited areas of cities and towns. Management of storm water resulting from rainfall has, therefore, become an important issue for the municipal bodies. Proper management of storm water obviously includes adequate design of storm water drainage networks. The design of storm water network is a costly exercise. Least cost design of storm water networks assumes significance, particularly when the fund available is limited. Optimal design of a storm water system is a difficult task as it involves the design of various components, like, open or closed conduits, storage units, pumps etc. In this paper, a methodology for least cost design of storm water drainage systems is proposed. The methodology proposed in this study consists of coupling a storm water simulator with an optimization method. The simulator used in this study is EPA’s storm water management model (SWMM), which is linked with Genetic Algorithm (GA) optimization method. The model proposed here is a mixed integer nonlinear optimization formulation, which takes care of minimizing the sectional areas of the open conduits of storm water networks, while satisfactorily conveying the runoff resulting from rainfall to the network outlet. Performance evaluations of the developed model show that the proposed method can be used for cost effective design of open conduit based storm water networks.

Keywords: genetic algorithm (GA), optimal design, simulation-optimization, storm water network, SWMM

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Authors: Ruzanna Muradyan

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Medical data mining is a crucial field in contemporary healthcare that offers cutting-edge tactics with enormous potential to transform patient care. This abstract examines how sophisticated data mining techniques could transform the healthcare industry, with a special focus on how they might improve patient outcomes. Healthcare data repositories have dynamically evolved, producing a rich tapestry of different, multi-dimensional information that includes genetic profiles, lifestyle markers, electronic health records, and more. By utilizing data mining techniques inside this vast library, a variety of prospects for precision medicine, predictive analytics, and insight production become visible. Predictive modeling for illness prediction, risk stratification, and therapy efficacy evaluations are important points of focus. Healthcare providers may use this abundance of data to tailor treatment plans, identify high-risk patient populations, and forecast disease trajectories by applying machine learning algorithms and predictive analytics. Better patient outcomes, more efficient use of resources, and early treatments are made possible by this proactive strategy. Furthermore, data mining techniques act as catalysts to reveal complex relationships between apparently unrelated data pieces, providing enhanced insights into the cause of disease, genetic susceptibilities, and environmental factors. Healthcare practitioners can get practical insights that guide disease prevention, customized patient counseling, and focused therapies by analyzing these associations. The abstract explores the problems and ethical issues that come with using data mining techniques in the healthcare industry. In order to properly use these approaches, it is essential to find a balance between data privacy, security issues, and the interpretability of complex models. Finally, this abstract demonstrates the revolutionary power of modern data mining methodologies in transforming the healthcare sector. Healthcare practitioners and researchers can uncover unique insights, enhance clinical decision-making, and ultimately elevate patient care to unprecedented levels of precision and efficacy by employing cutting-edge methodologies.

Keywords: data mining, healthcare, patient care, predictive analytics, precision medicine, electronic health records, machine learning, predictive modeling, disease prognosis, risk stratification, treatment efficacy, genetic profiles, precision health

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Authors: Saria Almarzook, Monika Reissmann, Gudrun Brockmann

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Due to its history, occurrence in different ecosystems and diverse using, the modern horse (Equus caballus) shows large variability in size, appearance, behavior and habits. At all times, breeders try to create groups (breeds, strains) representing high homology but showing clear differences in comparison to other groups. A great interest of analyzing phenotypic and genetic traits looking for real diversity and genetic uniqueness existents for Arabian horses in Syria. 90 Arabian horses from governmental research center of Arabian horses in Damascus were included. The horses represent three strains (Kahlawi, Saklawi, Hamdani) originated from different geographical zones. They were raised on the same farm, under stable conditions. Twelve phenotypic traits were measured: wither height (WH), croup width (CW), croup height (CH), neck girth (NG), thorax girth (TG), chest girth (ChG), chest depth (ChD), chest width (ChW), back line length (BLL), body length (BL), fore cannon length (FCL) and hind cannon length (HCL). The horses were divided into groups according to age (less than 2 years, 2-4 years, 4-9 years, over 9 years) and to sex (male, female). The statistical analyzes show that age has significant influence of WH while the strain has only a very limited effect. On CW, NG, BLL, FCL and HCL, there is only a significant influence of sex. Age has significant effect on CH and BL. All sources of classes have a significant effect on TG, ChG, ChD and ChW. Strain has a significant effect on the BL. These results provide first information for real biodiversity in and between the strains and can be used to develop the breeding work in the Arabian horse breed.

Keywords: Arabian horse, phenotypic traits, strains, Syria

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Authors: E. A. Asabina, V. I. Pet'kov, P. A. Mayorov, A. V. Markin, N. N. Smirnova, A. M. Kovalskii, A. A. Usenko

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The purpose of this work was to synthesize and investigate phase formation, structure and thermophysical properties of the phosphates M_0.5+xM'_xZr_2–x(PO₄)₃ (M – Cd, Sr, Pb; M' – Mg, Co, Mn). The compounds were synthesized by sol-gel method. The results showed formation of limited solid solutions of NZP/NASICON type. The crystal structures of triple phosphates of the compositions MMg_0.5Zr_1.5(PO₄)₃ were refined by the Rietveld method using XRD data. Heat capacity (8–660 K) of the phosphates Pb_0.5+xMg_xZr_2-x(PO₄)₃ (x = 0, 0.5) was measured, and reversible polymorphic transitions were found at temperatures, close to the room temperature. The results of Rietveld structure refinement showed the polymorphism caused by disordering of lead cations in the cavities of NZP/NASICON structure. Thermal expansion (298−1073 K) of the phosphates MMg_0.5Zr_1.5(PO₄)₃ was studied by XRD method, and the compounds were found to belong to middle and low-expanding materials. Thermal diffusivity (298–573 K) of the ceramic samples of phosphates slightly decreased with temperature increasing. As was demonstrated, the studied phosphates are characterized by the better thermophysical characteristics than widespread fire-resistant materials, such as zirconia and etc.

Keywords: NASICON, NZP, phosphate, structure, synthesis, thermophysical properties

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Authors: Noshaba Dilbar, Aisha Tahir, Amer Jamil

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During the last decade, DNA barcoding proved to be an authentic tool for discovery and identification of plants. In the present study, DNA barcoding of two species, Fagonia arabica and Fagonia indica was done for differentiation by using matK region. matK gene is considered as a universal barcode because of its easy alignment and high discrimination ability. In this study, matK yielded 100% sequencing results. The sequences from both plants were aligned at clustal W and observed that there is no nucleotide variation and polymorphism among both sequences. This was further analysed by BLAST which showed the similar sequences from different plants belonging to same family but didn’t find sequence of both species. Considering this, the resulted sequence was submitted by the name of Fagonia arabica with accession number KM276890. In the end, we analysed the results from BOLD which gave us the final conclusion that both plants are same as their matK sequences are 100% identical. In literature, both Fagonia indica and Fagonia arabica names are used for this plant but there is no clear differentiation has been observed in these plants. Results evaluate that Fagonia indica and Fagonia arabica are the alternative names of same plant.

Keywords: DNA barcoding, Fagonia arabica, Fagonia indica, matK

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Authors: Nadia Belu, Laurenţiu Mihai Ionescu, Agnieszka Misztal

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The automotive industry is one of the most important industries in the world that concerns not only the economy, but also the world culture. In the present financial and economic context, this field faces new challenges posed by the current crisis, companies must maintain product quality, deliver on time and at a competitive price in order to achieve customer satisfaction. Two of the most recommended techniques of quality management by specific standards of the automotive industry, in the product development, are Failure Mode and Effects Analysis (FMEA) and Control Plan. FMEA is a methodology for risk management and quality improvement aimed at identifying potential causes of failure of products and processes, their quantification by risk assessment, ranking of the problems identified according to their importance, to the determination and implementation of corrective actions related. The companies use Control Plans realized using the results from FMEA to evaluate a process or product for strengths and weaknesses and to prevent problems before they occur. The Control Plans represent written descriptions of the systems used to control and minimize product and process variation. In addition Control Plans specify the process monitoring and control methods (for example Special Controls) used to control Special Characteristics. In this paper we propose a computer-aided solution with Genetic Algorithms in order to reduce the drafting of reports: FMEA analysis and Control Plan required in the manufacture of the product launch and improved knowledge development teams for future projects. The solution allows to the design team to introduce data entry required to FMEA. The actual analysis is performed using Genetic Algorithms to find optimum between RPN risk factor and cost of production. A feature of Genetic Algorithms is that they are used as a means of finding solutions for multi criteria optimization problems. In our case, along with three specific FMEA risk factors is considered and reduce production cost. Analysis tool will generate final reports for all FMEA processes. The data obtained in FMEA reports are automatically integrated with other entered parameters in Control Plan. Implementation of the solution is in the form of an application running in an intranet on two servers: one containing analysis and plan generation engine and the other containing the database where the initial parameters and results are stored. The results can then be used as starting solutions in the synthesis of other projects. The solution was applied to welding processes, laser cutting and bending to manufacture chassis for buses. Advantages of the solution are efficient elaboration of documents in the current project by automatically generating reports FMEA and Control Plan using multiple criteria optimization of production and build a solid knowledge base for future projects. The solution which we propose is a cheap alternative to other solutions on the market using Open Source tools in implementation.

Keywords: automotive industry, FMEA, control plan, automotive technology

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Authors: Vaibhav Barve

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Reversible information hiding has drawn a lot of interest as of late. Being reversible, we can restore unique computerized data totally. It is a plan where mystery data is put away in digital media like image, video, audio to maintain a strategic distance from unapproved access and security reason. By and large JPEG bit stream is utilized to store this key data, first JPEG bit stream is encrypted into all around sorted out structure and then this secret information or key data is implanted into this encrypted region by marginally changing the JPEG bit stream. Valuable pixels suitable for information implanting are computed and as indicated by this key subtle elements are implanted. In our proposed framework we are utilizing RC4 algorithm for encrypting JPEG bit stream. Encryption key is acknowledged by framework user which, likewise, will be used at the time of decryption. We are executing enhanced least significant bit supplanting steganography by utilizing genetic algorithm. At first, the quantity of bits that must be installed in a guaranteed coefficient is versatile. By utilizing proper parameters, we can get high capacity while ensuring high security. We are utilizing logistic map for shuffling of bits and utilization GA (Genetic Algorithm) to find right parameters for the logistic map. Information embedding key is utilized at the time of information embedding. By utilizing precise picture encryption and information embedding key, the beneficiary can, without much of a stretch, concentrate the incorporated secure data and totally recoup the first picture and also the original secret information. At the point when the embedding key is truant, the first picture can be recouped pretty nearly with sufficient quality without getting the embedding key of interest.

Keywords: data embedding, decryption, encryption, reversible data hiding, steganography

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Authors: Tatiana Butkova, Nikolai Kibrik, Kristina Malsagova, Alexander Izotov, Alexander Stepanov, Anna Kaysheva

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Relevance. The genetic risk of developing schizophrenia is determined by two factors: single nucleotide polymorphisms and gene copy number variations. The search for serological markers for early diagnosis of schizophrenia is driven by the fact that the first five years of the disease are accompanied by significant biological, psychological, and social changes. It is during this period that pathological processes are most amenable to correction. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) that are hypothesized to potentially influence the onset and development of the endogenous process. Materials and Methods It was analyzed 73 single nucleotide polymorphism variants. The study included 48 patients undergoing inpatient treatment at "Psychiatric Clinical Hospital No. 1" in Moscow, comprising 23 females and 25 males. Inclusion criteria: - Patients aged 18 and above. - Diagnosis according to ICD-10: F20.0, F20.2, F20.8, F21.8, F25.1, F25.2. - Voluntary informed consent from patients. Exclusion criteria included: - The presence of concurrent somatic or neurological pathology, neuroinfections, epilepsy, organic central nervous system damage of any etiology, and regular use of medication. - Substance abuse and alcohol dependence. - Women who were pregnant or breastfeeding. Clinical and psychopathological assessment was complemented by psychometric evaluation using the PANSS scale at the beginning and end of treatment. The duration of observation during therapy was 4-6 weeks. Total DNA extraction was performed using QIAamp DNA. Blood samples were processed on Illumina HiScan and genotyped for 652,297 markers on the Infinium Global Chips Screening Array-24v2.0 using the IMPUTE2 program with parameters Ne=20,000 and k=90. Additional filtration was performed based on INFO>0.5 and genotype probability>0.5. Quality control of the obtained DNA was conducted using agarose gel electrophoresis, with each tested sample having a volume of 100 µL. Results. It was observed that several SNPs exhibited gender dependence. We identified groups of single nucleotide polymorphisms with a membership of 80% or more in either the female or male gender. These SNPs included rs2661319, rs2842030, rs4606, rs11868035, rs518147, rs5993883, and rs6269.Another noteworthy finding was the limited combination of SNPs sufficient to manifest clinical symptoms leading to hospitalization. Among all 48 patients, each of whom was analyzed for deviations in 73 SNPs, it was discovered that the combination of involved SNPs in the manifestation of pronounced clinical symptoms of schizophrenia was 19±3 out of 73 possible. In study, the frequency of occurrence of single nucleotide polymorphisms also varied. The most frequently observed SNPs were rs4849127 (in 90% of cases), rs1150226 (86%), rs1414334 (75%), rs10170310 (73%), rs2857657, and rs4436578 (71%). Conclusion. Thus, the results of this study provide additional evidence that these genes may be associated with the development of schizophrenia spectrum disorders. However, it's impossible cannot rule out the hypothesis that these polymorphisms may be in linkage disequilibrium with other functionally significant polymorphisms that may actually be involved in schizophrenia spectrum disorders. It has been shown that missense SNPs by themselves are likely not causative of the disease but are in strong linkage disequilibrium with non-functional SNPs that may indeed contribute to disease predisposition.

Keywords: gene polymorphisms, genotyping, single nucleotide polymorphisms, schizophrenia.

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Authors: Ja’Afar Umar, Naziru Salisu

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The consumption of powdered or industrialized juices has increased globally due to the fast pace of city life. These foods, with their attractive color, odor, and taste, are easily diluted in water and can lead to obesity, diabetes, hypertension, and cardiovascular problems. In a study, 80 purple varieties of onion bulbs were used to evaluate the cytotoxicity of the Tiara and Bevi mix beverage powder. The viability of the bulbs was tested using the A. cepa toxicity test. The bulbs were divided into five groups, and the root growth was recorded. The mixture was then squashed in a 45% acetic acid solution and examined for chromosomal abnormalities. The chromosomal abnormalities were classified as bridges, c-mitoses, vagrants, fragments, stickiness, bi-nuclei, and multi-polar. The study found that the highest number of dividing cells was in the negative control group, followed by the group treated with BM beverage. The highest number of aberrant cells was in the group treated with TR beverage, followed by BM 5%. Stickiness of cells was observed in both BM and TR 5% beverage concentrations. No lagging chromosome was present in the negative control group. The highest mitotic index was in the negative control group, and bridge fragrance was observed in the groups treated with different beverages. This study highlights the importance of Allium cepa L. in genotoxic substance testing, revealing chromosomal and mitotic abnormalities in root tip cells. The study also reveals that at 5% concentrations, root growth decreases, indicating potential genetic abnormalities in Allium cepa's genetic material.

Keywords: cytotoxicity, Allium cepa, Beverages, Chromosome

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Authors: Hamid Ghasemzadeh-Nava, Behrang Ekrami

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Persian fallow deer (Dama dama mesopotamica) is belonging to the family Cervidae and is only found in a few protected areas in the northwest, north, and southwest of Iran. The aims of this study were the analysis of inbreeding and morphometric parameters of semen in male Persian fallow deer to investigate the cause of reduced fertility of this endangered species in Dasht-e-Naz National Refuge, Sari, Iran. The Persian fallow deer semen was collected from four adult bucks randomly during the breeding and non-breeding season from five dehorned and horned deer's by using a ram electroejaculator. The post-mating season collected ejaculates contained abnormal spermatozoa, debris and secretion of accessory glands in horned bucks and accessory glands secretion free of any spermatozoa in dehorned or early velvet budding bucks. Many dag defect abnormalities observed in all samples may be the cause of high rate of polymorphism because of small primary herd size of Persian fallow deer in this area, so needs be evaluated genetically.

Keywords: electroejaculator, Persian fallow deer, reproductive characteristics, spermatozoa

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Authors: Mohammad Asadpour, Gholamreza Razmi, Gholamreza Mohammadi, Abolghasem Naghibi

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Cryptosporidium Spp., protozoan parasites of the phylum Apicomplexa, have a wide spectrum of hosts including humans, domestic animals and wild mammals, birds, reptiles, amphibians and fish. Dairy cattle have been identified in numerous reports as a major source of environmental contamination with this pathogen. In this study, a Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP) analysis of the Small-Subunit (SSU) rRNA gene was used to detect and identify Cryptosporidium Spp. in 300 fecal specimens from 1 to 30 days pre-wean calves in 10 farms in Mashhad, Iran. Eighty five (28.3%) and forty five (15%) of the specimens were positive for Cryptosporidium by microscopic and PCR examination respectively. Restriction digestion of the PCR products by VSPI and Ssp1 restriction enzymes and analysis of sequence data revealed the presence of C. parvum, bovine genotype in all isolates. Our findings suggest that cattle can be a source of Cryptosporidial infections for humans and animals in Mashhad area. This is the first published description of Cryptosporidium sub genotyping in Mashhad.

Keywords: cryptosporidium, genotype, dairy calves, 18S rRNA, Mashhad

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Authors: Seungchul Lee, Minjeong Kim, Iman Janghorban Esfahani, Jeong Tai Kim, ChangKyoo Yoo

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It is hard to maintain the effluent quality of the wastewater treatment plants (WWTPs) under with fixed types of operational control because of continuously changed influent flow rate and pollutant load. The aims of this study is development of multi-loop multi-objective control (ML-MOC) strategy in plant-wide scope targeting four objectives: 1) maximization of nutrient removal efficiency, 2) minimization of operational cost, 3) maximization of CH4 production in anaerobic digestion (AD) for CH4 reuse as a heat source and energy source, and 4) minimization of N2O gas emission to cope with global warming. First, benchmark simulation mode is modified to describe N2O dynamic in biological process, namely benchmark simulation model for greenhouse gases (BSM2G). Then, three types of single-loop proportional-integral (PI) controllers for DO controller, NO3 controller, and CH4 controller are implemented. Their optimal set-points of the controllers are found by using multi-objective genetic algorithm (MOGA). Finally, multi loop-MOC in BSM2G is implemented and evaluated in BSM2G. Compared with the reference case, the ML-MOC with the optimal set-points showed best control performances than references with improved performances of 34%, 5% and 79% of effluent quality, CH4 productivity, and N2O emission respectively, with the decrease of 65% in operational cost.

Keywords: Benchmark simulation model for greenhouse gas, multi-loop multi-objective controller, multi-objective genetic algorithm, wastewater treatment plant

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Authors: Micheale Yifter Weldemichael, Hailay Mehari Gebremedhn, Teklehaimanot Hailesslasie Teklu

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Recent developments in targeted genome editing accelerated genetic research and opened new potentials to improve crops for better yields and quality. Given the significance of cereal crops as a primary source of food for the global population, the utilization of contemporary genome editing techniques like CRISPR/Cas9 is timely and crucial. CRISPR/Cas technology has enabled targeted genomic modifications, revolutionizing genetic research and exploration. Application of gene editing through CRISPR/Cas9 in enhancing sorghum is particularly vital given the current ecological, environmental, and agricultural challenges exacerbated by climate change. As sorghum is one of the main staple foods of our region and is known to be a resilient crop with a high potential to overcome the above challenges, the application of genome editing technology will enhance the investigation of gene functionality. CRISPR/Cas9 enables the improvement of desirable sorghum traits, including nutritional value, yield, resistance to pests and diseases, and tolerance to various abiotic stresses. Furthermore, CRISPR/Cas9 has the potential to perform intricate editing and reshape the existing elite sorghum varieties, and introduce new genetic variations. However, current research primarily focuses on improving the efficacy of the CRISPR/Cas9 system in successfully editing endogenous sorghum genes, making it a feasible and successful undertaking in sorghum improvement. Recent advancements and developments in CRISPR/Cas9 techniques have further empowered researchers to modify additional genes in sorghum with greater efficiency. Successful application and advancement of CRISPR techniques in sorghum will aid not only in gene discovery and the creation of novel traits that regulate gene expression and functional genomics but also in facilitating site-specific integration events. The purpose of this review is, therefore, to elucidate the current advances in sorghum genome editing and highlight its potential in addressing food security issues. It also assesses the efficiency of CRISPR-mediated improvement and its long-term effects on crop improvement and host resistance against parasites, including tissue-specific activity and the ability to induce resistance. This review ends by emphasizing the challenges and opportunities of CRISPR technology in combating parasitic plants and proposing directions for future research to safeguard global agricultural productivity.

Keywords: CRISPR/Cas9, genome editing, quality, sorghum, stress, yield

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Authors: Surekha Rathod

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Sickle cell disease is a vascular disorder characterized by chronic, ongoing organ damage that is punctuated by episodes of acutely painful vascular complications.1 It is the most common genetic blood disorder in the United States, with about 2000 infants being identified through routine blood screenings annually, and an estimated 104,000-138,000 affected individuals living in the United States. Approximately 0.3%-1.3% of African American are affected by Sickle Cell Diseases (SCD).3 The aim of this paper is to present oral health status of patients with SCD. A total of 200 subjects of both sexes in the age group 18- 40 years were included in this study. The subjects were examined and the following indices were recorded • Oral hygiene index – Simplified (OHI-S). • Probing depths (PD). • Clinical Attachment Levels (CAL). • Gingival Index - Loe and Sillness. • Turesky Gillmore Glickman Modification of the Quigley Hein Plaque Index. (1970) • DMFT index. • Sickle Cell Disease Severity Index. A total of 1478 patients were screened of which 200 subjects were found to be diagnosed with SCD by electrophoresis. The study thus, included 200 subjects (111 females & 89 males) diagnosed with Sickle Cell Disease in the age group of 18-40 years. The probing pocket depths (PPD) were measured in millimeters. 36% had PPD in the range of 2-4mm, 48% had PPD in the range of 4-6mm while 16% had PPD of more than 6mm. Similar results were obtained for the Clinical Attachment Levels (CAL). 29.5 % subjects had CAL 2-4mm, 44.5% had 4-6mm & 26% had CAL 6mm & above. We can thus conclude that although oral health is not a priority for patients with SCD, it is supported by increased plaque accumulation. Because of the chronic anemic state of the patients with SCD, they should be encouraged to pay strict attention to oral hygiene instructions and practice.

Keywords: chronic, genetic, oral, sickle cell disease, vascular

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Authors: Anyaphat Srithanasuwan, Noppason Pangprasit, Montira Intanon, Phongsakorn Chuammitri, Witaya Suriyasathaporn, Ynte H. Schukken

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Streptococcus uberis is one of the most common mastitis-causing pathogens, with a wide range of intramammary infection (IMI) durations and pathogenicity. This study aimed to compare shared or unique virulence factor gene clusters distinguishing persistent and transient strains of S. uberis. A total of 139 S. uberis strains were isolated from three small-holder dairy herds with a high prevalence of S. uberis mastitis. The duration of IMI was used to categorize bacteria into two groups: transient and persistent strains with an IMI duration of less than 1 month and longer than 2 months, respectively. Six representative S. uberis strains, three from each group (transience and persistence) were selected for analysis. All transient strains exhibited multi-locus sequence types (MLST), indicating a highly diverse population of transient S. uberis. In contrast, MLST of persistent strains was available in an online database (pubMLST). Identification of virulence genes was performed using whole-genome sequencing (WGS) data. Differences in genomic size and number of virulent genes were found. For example, the BCA gene or alpha-c protein and the gene associated with capsule formation (hasAB), found in persistent strains, are important for attachment and invasion, as well as the evasion of the antimicrobial mechanisms and survival persistence, respectively. These findings suggest a genetic-level difference between the two strain types. Consequently, a comprehensive study of 139 S. uberis isolates will be conducted to perform an in-depth genetic assessment through WGS analysis on an Illumina platform.

Keywords: Streptococcus Uberis, mastitis, whole genome sequence, intramammary infection, persistent S. Uberis, transient s. Uberis

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Authors: Sreeja Shaw, Prosenjit Samanta, Asish Kumar Mukhopadhyay

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Cholera is still a global public health burden and is caused by Vibrio cholerae O1 and O139 serogroups. Evidence from recent outbreaks in Haiti and Yemen suggested that circulating V. cholerae O1 El Tor variant strains are continuously changing to cause more ruinous outbreaks worldwide, and most of them have emerged from the Indian subcontinents. Therefore, we studied the changing virulence characteristics along with the antibiotic resistance profile of V. cholerae O1strains isolated from seasonal outbreaks in three cholera endemic regions during 2018, Gujarat and Maharashtra in Western India (87 strains), and to compare those features with the isolates of West Bengal in Eastern India (48 strains) collected during the same period. All the strains from Western India were of Ogawa serotype, polymyxin B-sensitive, hemolytic, and contained a large fragment deletion in VSP-II genomic region similar with Yemen outbreak strains and carried more virulent Haitian genetic alleles of major virulence associated genes ctxB, tcpA, and rtxA. Conversely, 14.6% (7/48) of the strains from Eastern India were belong to the Inaba serotype, polymyxin B-resistant, non-hemolytic, harbored intact VSP-II region, classical ctxB, Haitian tcpA, and El Tor rtxA alleles. Interestingly, resistance to tetracycline and chloramphenicol was seen in isolates from both regions, which are not very common among V. cholerae O1 isolates in India. Therefore, this study indicated West Bengal as a diverse region where two different types of El Tor variant hypervirulent strains are co-existed, probably competing for their better environmental survival, which may result in severe irrepressible disease outcome in the future.

Keywords: cholera, vibrio cholerae, polymyxin B, Non-hemolytic, ctxB, tcpA, rtxA, VSP-II

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Authors: Larisa Gheber

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Mitosis is an essential process by which duplicated genetic information is transmitted from mother to daughter cells. Incorrect chromosome segregation during mitosis can lead to genetic diseases, chromosome instability and cancer. This process is mediated by a dynamic microtubule-based intracellular structure, the mitotic spindle. One of the major factors that govern the mitotic spindle dynamics are the kinesin-5 biological nano motors that were believed to move unidirectionally on the microtubule filaments, using ATP hydrolysis, thus performing essential functions in mitotic spindle dynamics. Surprisingly, several reports from our and other laboratories have demonstrated that some kinesin-5 motors are bi-directional: they move in minus-end direction on the microtubules as single-molecules and can switch directionality under a number of conditions. These findings broke a twenty-five-years old dogma regarding kinesin directionality (1, 2). The mechanism of this bi-directional motility and its physiological significance remain unclear. To address this unresolved problem, we apply an interdisciplinary approach combining live cell imaging, biophysical single molecule, and structural experiments to examine the activity of these motors and their mutated variants in vivo and in vitro. Our data shows that factors such as protein phosphorylation (3, 4), motor clustering on the microtubules (5, 6) and structural elements (7, 8) regulate the bi-directional motility of kinesin motors. We also show, using Cryo-EM, that bi-directional kinesin motors obtain non-canonical microtubule binding, which is essential to their special motile properties and intracellular functions. We will discuss the implication of these findings to mechanism bi-directional motility and physiological roles in mitosis.

Keywords: mitosis, cancer, kinesin, microtubules, biochemistry, biophysics

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