Search results for: somatic sequence mutations

Authors: O. I. H. Dimitry, N. A. Mansour, A. L. G. Saad

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Natural sodium montmorillonite (NaMMT), Cloisite Na⁺ and two organophilic montmorillonites (OMMTs), Cloisites 20A and 15A were used. Polycaprolactone (PCL)/MMT composites containing 1, 3, 5, and 10 wt% of Cloisite Na⁺ and PCL/OMMT nanocomposites containing 5 and 10 wt% of Cloisites 20A and 15A were prepared via solution intercalation technique to study the influence of organic modifier loading on particle dispersion of PCL/ NaMMT composites. Thermal stabilities of the obtained composites were characterized by thermal analysis using the thermogravimetric analyzer (TGA) which showed that in the presence of nitrogen flow the incorporation of 5 and 10 wt% of filler brings some decrease in PCL thermal stability in the sequence: Cloisite Na+>Cloisite 15A > Cloisite 20A, while in the presence of air flow these fillers scarcely influenced the thermoxidative stability of PCL by slightly accelerating the process. The interaction between PCL and silicate layers was studied by Fourier transform infrared (FTIR) spectroscopy which confirmed moderate interactions between nanometric silicate layers and PCL segments. The electrical conductivity (σ) which describes the ionic mobility of the systems was studied as a function of temperature and showed that σ of PCL was enhanced on increasing the modifier loading at filler content of 5 wt%, especially at higher temperatures in the sequence: Cloisite Na⁺<Cloisite 20A<Cloisite 15A, and was then decreased to some extent with a further increase to 10 wt%. The activation energy E_σ obtained from the dependency of σ on temperature using Arrhenius equation was found to be lowest for the nanocomposite containing 5 wt% of Cloisite 15A. The dispersed behavior of clay in PCL matrix was evaluated by X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses which revealed partial intercalated structures in PCL/NaMMT composites and semi-intercalated/semi-exfoliated structures in PCL/OMMT nanocomposites containing 5 wt% of Cloisite 20A or Cloisite 15A.

Keywords: electrical conductivity, montmorillonite, nanocomposite, organoclay, polycaprolactone

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Authors: Annet Namusoke, Annet Namayanja, Peter Wasswa, Shakirah Nampijja

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Common bean cultivar G2333 which offers broad resistance for anthracnose has been widely used as a source of resistance in breeding for anthracnose resistance. The cultivar is pyramided with three genes namely CO-4, CO-5 and CO-7 and of these three genes, the CO-4 gene has been found to offer the broadest resistance. The main aim of this work was to identify and validate easily assayable PCR based co-dominant molecular markers for selection of the CO-4 gene in segregating populations derived from crosses of G2333 with RWR 1946 and RWR 2075, two commercial Andean cultivars highly susceptible to anthracnose. Marker sequences for the study were obtained by blasting the sequence of the COK-4 gene in the Phaseolus gene database. Primer sequence pairs that were not provided from the Phaseolus gene database were designed by the use of Primer3 software. PCR conditions were optimized and the PCR products were run on 6% HPAGE gel. Results of the polymorphism test indicated that out of 18 identified markers, only two markers namely BM588 and BM211 behaved co-dominantly. Phenotypic evaluation for reaction to anthracnose disease was done by inoculating 21days old seedlings of three parents, F1 and F2 populations with race 7 of Colletotrichum lindemuthianum in the humid chamber. DNA testing of the BM588 marker onto the F2 segregating population of the crosses RWR 1946 x G 2333 and RWR 2075 x G2333 further revealed that the marker BM588 co-segregated with disease resistance with co-dominance of two alleles of 200bp and 400bp, fitting the expected segregation ratio of 1:2:1. The BM588 marker was significantly associated with disease resistance and gave promising results for marker assisted selection of the CO-4 gene in the breeding lines. Activities to validate the BM211 marker are also underway.

Keywords: codominant, Colletotrichum lindemuthianum, MAS, Phaseolus vulgaris

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Authors: A. T. Adetunji, F. B. Lewu, R. Mundembe

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Plants require nitrogen (N) to support desired production levels. Nitrogen is available to plants in the form of nitrate or ammonium, which are transported into the cell with the aid of various transport proteins. Ammonium transporters (AMTs) play a role in the uptake of ammonium, the form in which nitrogen is preferentially absorbed by plants. Solanum tuberosum AMT1 (StAMT1) was characterized using molecular biology and bioinformatics methods. Nucleotide database sequences were used to design AMT1-specific primers which were used to amplify the AMT1 internal regions. Nucleotide sequencing, alignment and phylogenetic analysis assigned StAMT1 to the AMT1 family. The deduced amino acid sequences showed that StAMT1 is 92%, 83% and 76% similar to Solanum lycopersicum LeAMT1.1, Lotus japonicus LjAMT1.1 and Solanum lycopersicum LeAMT1.2 respectively. StAMT1 fragments were shown to correspond to the 5th - 10th trans-membrane domains. Residue StAMT1 D15 is predicted to be essential for ammonium transport, while mutations of StAMT1 S76A may further enhance ammonium transport.

Keywords: ammonium transporter, bioinformatics, nitrogen, primers, Solanum tuberosum

Procedia PDF Downloads 248

Authors: Hyeon-Kyo Lim, Hyunjung Kim, Kune-Woo Lee

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Decommissioning process of nuclear facilities can be said to consist of a sequence of problem solving activities, partly because there may exist working environments contaminated by radiological exposure, and partly because there may also exist industrial hazards such as fire, explosions, toxic materials, and electrical and physical hazards. As for an individual hazard factor, risk assessment techniques are getting known to industrial workers with advance of safety technology, but the way how to integrate those results is not. Furthermore, there are few workers who experienced decommissioning operations a lot in the past. Therefore, not a few countries in the world have been trying to develop appropriate counter techniques in order to guarantee safety and efficiency of the process. In spite of that, there still exists neither domestic nor international standard since nuclear facilities are too diverse and unique. In the consequence, it is quite inevitable to imagine and assess the whole risk in the situation anticipated one by one. This paper aimed to find out an appropriate technique to integrate individual risk assessment results from the viewpoint of experts. Thus, on one hand the whole risk assessment activity for decommissioning operations was modeled as a sequence of individual risk assessment steps, and on the other, a hierarchical risk structure was developed. Then, risk assessment procedure that can elicit individual hazard factors one by one were introduced with reference to the standard operation procedure (SOP) and hierarchical task analysis (HTA). With an assumption of quantification and normalization of individual risks, a technique to estimate relative weight factors was tried by using the conventional Analytic Hierarchical Process (AHP) and its result was reviewed with reference to judgment of experts. Besides, taking the ambiguity of human judgment into consideration, debates based upon fuzzy inference was added with a mathematical case study.

Keywords: decommissioning, risk assessment, analytic hierarchical process (AHP), fuzzy inference

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Authors: Abdoulie K. Ceesay

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Within the sequence of the whole genome, it is known that 99.9% of the human genome is similar, whilst our difference lies in just 0.1%. Among these minor dissimilarities, the most common type of genetic variations that occurs in a population is SNP, which arises due to nucleotide substitution in a protein sequence that leads to protein destabilization, alteration in dynamics, and other physio-chemical properties’ distortions. While causing variations, they are equally responsible for our difference in the way we respond to a treatment or a disease, including various cancer types. There are two types of SNPs; synonymous single nucleotide polymorphism (sSNP) and non-synonymous single nucleotide polymorphism (nsSNP). sSNP occur in the gene coding region without causing a change in the encoded amino acid, while nsSNP is deleterious due to its replacement of a nucleotide residue in the gene sequence that results in a change in the encoded amino acid. Predicting the effects of cancer related nsSNPs on protein stability, function, and dynamics is important due to the significance of phenotype-genotype association of cancer. In this thesis, Data of 5 oncogenes (ONGs) (AKT1, ALK, ERBB2, KRAS, BRAF) and 5 tumor suppressor genes (TSGs) (ESR1, CASP8, TET2, PALB2, PTEN) were retrieved from ClinVar. Five common in silico tools; Polyphen, Provean, Mutation Assessor, Suspect, and FATHMM, were used to predict and categorize nsSNPs as deleterious, benign, or neutral. To understand the impact of each variation on the phenotype, Maestro, PremPS, Cupsat, and mCSM-NA in silico structural prediction tools were used. This study comprises of in-depth analysis of 10 cancer gene variants downloaded from Clinvar. Various analysis of the genes was conducted to derive a meaningful conclusion from the data. Research done indicated that pathogenic variants are more common among ONGs. Our research also shows that pathogenic and destabilizing variants are more common among ONGs than TSGs. Moreover, our data indicated that ALK(409) and BRAF(86) has higher benign count among ONGs; whilst among TSGs, PALB2(1308) and PTEN(318) genes have higher benign counts. Looking at the individual cancer genes predisposition or frequencies of causing cancer according to our research data, KRAS(76%), BRAF(55%), and ERBB2(36%) among ONGs; and PTEN(29%) and ESR1(17%) among TSGs have higher tendencies of causing cancer. Obtained results can shed light to the future research in order to pave new frontiers in cancer therapies.

Keywords: tumor suppressor genes (TSGs), oncogenes (ONGs), non synonymous single nucleotide polymorphism (nsSNP), single nucleotide polymorphism (SNP)

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Authors: Rajkumar Ghosh

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The paper presents a comprehensive study of the structural analysis of the Chaura Thrust in Himachal Pradesh, India. The research focuses on several key aspects, including the activation timing of the Main Central Thrust (MCT) and the South Tibetan Detachment System (STDS), the identification and characterization of mylonitised zones through microscopic examination, and the understanding of box fold characteristics and their implications in the regional geology of the Himachal Himalaya. The primary objective of the study is to provide field documentation of the Chaura Thrust, which was previously considered a blind thrust with limited field evidence. Additionally, the research aims to characterize box folds and their signatures within the broader geological context of the Himachal Himalaya, document the temperature range associated with grain boundary migration (GBM), and explore the overprinting structures related to multiple sets of Higher Himalayan Out-of-Sequence Thrusts (OOSTs). The research methodology employed geological field observations and microscopic studies. Samples were collected along the Jhakri-Chaura transect at regular intervals of approximately 1 km to conduct strain analysis. Microstructural studies at the grain scale along the Jhakri-Wangtu transect were used to document the GBM-associated temperature range. The study reveals that the MCT activated in two parts, as did the STDS, and provides insights into the activation ages of the Main Boundary Thrust (MBT) and the Main Frontal Thrust (MFT). Under microscopic examination, the study identifies two mylonitised zones characterized by S-C fabric, and it documents dynamic and bulging recrystallization, as well as sub-grain formation. Various types of crenulated schistosity are observed in photomicrographs, including a rare occurrence where crenulation cleavage and sigmoid Muscovite are found juxtaposed. The study also notes the presence of S/SE-verging meso- and micro-scale box folds around Chaura, which may indicate structural upliftment. Kink folds near Chaura are visible, while asymmetric shear sense indicators in augen mylonite are predominantly observed under microscopic examination. Moreover, the research highlights the documentation of the Higher Himalayan Out-of-Sequence Thrust (OOST) in Himachal Pradesh, which activated the MCT and occurred within a zone south of the Main Central Thrust Upper (MCTU). The presence of multiple sets of OOSTs suggests a zigzag pattern of strain accumulation in the area. The study emphasizes the significance of understanding the overprinting structures associated with OOSTs. Overall, this study contributes to the understanding of the structural analysis of the Chaura Thrust and its implications in the regional geology of the Himachal Himalaya. The research underscores the importance of microscopic studies in identifying mylonitised zones and various types of crenulated schistosity. Additionally, the study documents the GBM-associated temperature range and provides insights into the activation of the Higher Himalayan Out-of-Sequence Thrust (OOST) in Himachal Pradesh. The findings of the study were obtained through geological field observations, microscopic studies, and strain analysis, offering valuable insights into the activation timing, mylonitization characteristics, and overprinting structures related to the Chaura Thrust and the broader tectonic framework of the region.

Keywords: Main Central Thrust, Jhakri Thrust, Chaura Thrust, Higher Himalaya, Out-of-Sequence Thrust, Sarahan Thrust

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Authors: Abu Salim Mustafa

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Rv3873 is a relatively large size protein (371 amino acids in length) and its gene is located in the immunodominant genomic region of difference (RD)1 that is present in the genome of Mycobacterium tuberculosis but deleted from the genomes of all the vaccine strains of Bacillus Calmette Guerin (BCG) and most other mycobacteria. However, when tested for cellular immune responses using peripheral blood mononuclear cells from tuberculosis patients and BCG-vaccinated healthy subjects, this protein was found to be a major stimulator of cell mediated immune responses in both groups of subjects. In order to further identify the sequence of immunodominant epitopes and explore their Human Leukocyte Antigen (HLA)-restriction for epitope recognition, 24 peptides (25-mers overlapping with the neighboring peptides by 10 residues) covering the sequence of Rv3873 were synthesized chemically using fluorenylmethyloxycarbonyl chemistry and tested in cell mediated immune responses. The results of these experiments helped in the identification of an immunodominant peptide P9 that was recognized by people expressing varying HLA-DR types. Furthermore, it was also predicted to be a promiscuous binder with multiple epitopes for binding to HLA-DR, HLA-DP and HLA-DQ alleles of HLA-class II molecules that present antigens to T helper cells, and to HLA-class I molecules that present antigens to T cytotoxic cells. In addition, the evaluation of peptide P9 using an immunogenicity predictor server yielded a high score (0.94), which indicated a greater probability of this peptide to elicit a protective cellular immune response. In conclusion, P9, a peptide with multiple epitopes and ability to bind several HLA class I and class II molecules for presentation to cells of the cellular immune response, may be useful as a peptide-based vaccine against tuberculosis.

Keywords: mycobacterium tuberculosis, PPE68, peptides, vaccine

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Authors: V. Karuppaiah, J. C. Padaria, C. Srivastava

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The tobacco caterpillar, Spodoptera litura Fab (Lepidoptera: Noctuidae) is a polyphagous pest various field and horticulture crops in India. Pest had virtually developed resistance to all commonly used insecticides. Enhanced detoxification is the prime mechanism that is dictated by detoxification different enzymes and carboxylesterase is one of the major enzyme responsible development of resistance. In India, insecticide resistance studies on S. litura are mainly deployed on detoxification enzymes activity and investigation at gene level alteration i.e. at nucleotide level is very merger. In the present study, we collected the S. litura larvae from three different cauliflower growing belt viz., IARI, New Delhi (Delhi), Palari, Sonepat (Haryana) and Varanasi (Uttar Pradesh) to study the role of carboxylesterase activity and its gene level variation The CarE activity was measured using UV-VIS spectrophotometer with 3rd instar larvae of S. litura. The elevated activity of CarE was observed in Sonepat strain (28.09 ± 0.09 µmol/min/mg of protein) followed by Delhi (26.72 ± 0.04 µmol/min/mg of protein) and Varanasi strain (10.00 ± 0.44 µmol/min/mg of protein) of S. litura. The genomic DNA was isolated from 3rd instar larvae and CarE gene was amplified using a primer sequence, F:5’tccagagttccttgtcaggcac3’; R:5’ctgcatcaagcatgtctc3. CarE gene, about 500bp was partially amplified, sequenced and submitted to NCBI (Accession No. KF835886, KF835887 and KF835888). The sequence data revealed polymorphism at nucleotide level in all the three strains and gene found to have 88 to 97% similarity with previous available nucleotide sequences of S. litura, S. littoralis and S. exiqua. The polymorphism at the nucleotide level could be a reason for differential activity of carboxylesterase enzymes among the strains. However, investigation at gene expression level would be useful to analyze the overproduction of carboxylesterase enzyme.

Keywords: carboxylesterase, CarE gene, nucleotide polymorphism, insecticide resistance, spodoptera litura

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Authors: Joanna Marie A. Paulino-Morente, Vaneza Valentina L. Penolio, Grace Sabado

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Ovarian cancer is extremely hard to diagnose in its early stages, and those afflicted at the time of diagnosis are typically asymptomatic and in the late stages of the disease, with metastasis to other organs. Ovarian cancers often occur sporadically, with only 5% associated with hereditary mutations. Mutations in the BRCA1 and BRCA2 tumor suppressor genes have been found to be responsible for the majority of hereditary ovarian cancers. One type of ovarian tumor is Malignant Mixed Mullerian Tumor (MMMT), which is a very rare and aggressive type, accounting for only 1% of all ovarian cancers. Reported is a case of a 43-year-old G3P3 (3003), who came into our institution due to a 2-month history of difficulty of breathing. Family history reveals that her eldest and younger sisters both died of ovarian malignancy, with her younger sister having a histopathology report of endometrioid ovarian carcinoma, left ovary stage IIIb. She still has 2 asymptomatic sisters. Physical examination pointed to pleural effusion of right lung, and presence of bilateral ovarian new growth, which had a Sassone score of 13. Admitting Diagnosis was G3P3 (3003), Ovarian New Growth, bilateral, Malignant; Pleural effusion secondary to malignancy. BRCA was requested to establish a hereditary mutation; however, the patient had no funds. Once the patient was stabilized, TAHBSO with surgical staging was performed. Intraoperatively, the pelvic cavity was occupied by firm, irregularly shaped ovaries, with a colorectal metastasis. Microscopic sections from both ovaries and the colorectal metastasis had pleomorphic tumor cells lined by cuboidal to columnar epithelium exhibiting glandular complexity, displaying nuclear atypia and increased nuclear-cytoplasmic ratio, which are infiltrating the stroma, consistent with the features of Malignant Mixed Mullerian Tumor, since MMMT is composed histologically of malignant epithelial and sarcomatous elements. In conclusion, discussed is the clinic-pathological feature of a patient with primary ovarian Malignant Mixed Mullerian Tumor, a rare malignancy comprising only 1% of all ovarian neoplasms. Also, by understanding the hereditary ovarian cancer syndromes and its relation to this patient, it cannot be overemphasized that a comprehensive family history is really fundamental for early diagnosis. The familial association of the disease, given that the patient has two sisters who were diagnosed with an advanced stage of ovarian cancer and succumbed to the disease at a much earlier age than what is reported in the general population, points to a possible hereditary syndrome which occurs in only 5% of ovarian neoplasms. In a low-resource setting, being in a third world country, the following will be recommended for monitoring and/or screening women who are at high risk for developing ovarian cancer, such as the remaining sisters of the patient: 1) Physical examination focusing on the breast, abdomen, and rectal area every 6 months. 2) Transvaginal sonography every 6 months. 3) Mammography annually. 4) CA125 for postmenopausal women. 5) Genetic testing for BRCA1 and BRCA2 will be reserved for those who are financially capable.

Keywords: BRCA, hereditary breast-ovarian cancer syndrome, malignant mixed mullerian tumor, ovarian cancer

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Authors: M. Mikušová

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The main aim of this paper is to present a clear and comprehensive picture of the process of a crisis in the organization which will help to better understand its possible developments. For a description of the sequence of individual steps and an indication of their causation and possible variants of the developments, a detailed flow diagram with verbal comment is applied. For simplicity, the process of the crisis is observed in four basic phases called: symptoms of the crisis, diagnosis, action and prevention. The model highlights the complexity of the phenomenon of the crisis and that the various phases of the crisis are interweaving.

Keywords: crisis, management, model, organization

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Authors: Barry Majeed, Eka Febriana, Seto Julianto

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Kepulauan Seribu National Parks is a marine preservation region in Indonesia. It is located in 5°23' - 5°40' LS, 106°25' - 106°37' BT North of Jakarta City. Covered with area 107,489 ha, Kepulauan Seribu has a lot of tourism spots such as cluster islands, fringing reef and many more. Kepulauan Seribu is also nominated as Strategic Tourism Region In Indonesia (KSPN). So, these islands have a lot of potential sides more than preservation function as a national park, hence the development of sustainable geotourism. The aim of this study is for enhancing the development of eco-geotourism in Kepulauan Seribu. This study concern for three main aspect of eco-geotourism such as tourism, form and process. Study for the tourism aspect includes attractions, accommodations, tours, activities, interpretation, and planning & management in Kepulauan Seribu. Study for the form aspect focused on the carbonate platform situated between two islands. Primarily in carbonate reef such as head coral, branchy coral, platy coral that created the carbonate sequence in Kepulauan Seribu. Study for the process aspect primarily discussed the process of forming of carbonate from carbonate factory later becomes Kepulauan Seribu. Study for the regional geology of Kepulauan Seribu has been conducted and suggested that Kepulauan Seribu lithologies are mainly quarternary limestone. In this study, primary data was taken from an observation of quarternary carbonate platform between two islands from Hati Island, Macan Island, Bulat Island, Ubi Island and Kelapa Island. From this observation, the best routes for tourist have been made from Island to Island. Qualitative methods such as depth interview to the local people in purposive sampling also have been made. Finally, this study also giving education about geological site – carbonate sequence - in Kepulauan Seribu for the local wisdom so that this study can support the development of sustainable eco-geotourism in Kepulauan Seribu.

Keywords: carbonate factory, carbonate platform, geotourism, Kepulauan Seribu

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Authors: Worawanna Panyakotkaew, Falan Srisuriyachai

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Cyclic steam injection (CSI) is a thermal recovery technique performed by injecting periodically heated steam into heavy oil reservoir. Oil viscosity is substantially reduced by means of heat transferred from steam. Together with gas pressurization, oil recovery is greatly improved. Nevertheless, prediction of effectiveness of the process is difficult when reservoir contains degree of heterogeneity. Therefore, study of heterogeneity together with interest reservoir properties must be evaluated prior to field implementation. In this study, thermal reservoir simulation program is utilized. Reservoir model is firstly constructed as multi-layered with coarsening upward sequence. The highest permeability is located on top layer with descending of permeability values in lower layers. Steam is injected from two wells located diagonally in quarter five-spot pattern. Heavy oil is produced by adjusting operating parameters including soaking period and steam quality. After selecting the best conditions for both parameters yielding the highest oil recovery, effects of degree of heterogeneity (represented by Lorenz coefficient), vertical permeability and permeability sequence are evaluated. Surprisingly, simulation results show that reservoir heterogeneity yields benefits on CSI technique. Increasing of reservoir heterogeneity impoverishes permeability distribution. High permeability contrast results in steam intruding in upper layers. Once temperature is cool down during back flow period, condense water percolates downward, resulting in high oil saturation on top layers. Gas saturation appears on top after while, causing better propagation of steam in the following cycle due to high compressibility of gas. Large steam chamber therefore covers most of the area in upper zone. Oil recovery reaches approximately 60% which is of about 20% higher than case of heterogeneous reservoir. Vertical permeability exhibits benefits on CSI. Expansion of steam chamber occurs within shorter time from upper to lower zone. For fining upward permeability sequence where permeability values are reversed from the previous case, steam does not override to top layers due to low permeability. Propagation of steam chamber occurs in middle of reservoir where permeability is high enough. Rate of oil recovery is slower compared to coarsening upward case due to lower permeability at the location where propagation of steam chamber occurs. Even CSI technique produces oil quite slowly in early cycles, once steam chamber is formed deep in the reservoir, heat is delivered to formation quickly in latter cycles. Since reservoir heterogeneity is unavoidable, a thorough understanding of its effect must be considered. This study shows that CSI technique might be one of the compatible solutions for highly heterogeneous reservoir. This competitive technique also shows benefit in terms of heat consumption as steam is injected periodically.

Keywords: cyclic steam injection, heterogeneity, reservoir simulation, thermal recovery

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Authors: Boxiang Zhuang

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This study analyzes the clinical manifestations, hearing rehabilitation methods and outcomes of a complex case of neurofibromatosis type II (NF2). Methods: The clinical manifestations, medical history, clinical data, surgical methods and postoperative hearing rehabilitation outcomes of an NF2 patient were analyzed to determine the hearing reconstruction method and postoperative effect for a special type of NF2 acoustic neuroma. Results: The patient had bilateral acoustic neuromas with profound sensorineural hearing loss in both ears. Peripheral blood genetic testing did not reveal pathogenic gene mutations, suggesting mosaicism. The patient had an intracochlear schwannoma in the right ear and severely impaired vision in both eyes. Cochlear implantation with tumor retention was performed in the right ear. After 2 months of family-based auditory and speech rehabilitation, the Categories of Auditory Performance (CAP) score improved from 0 to 5. Conclusion: NF2 has complex clinical manifestations and poor prognosis. For NF2 patients with intracochlear tumors, cochlear implantation with tumor retention can be used to reconstruct hearing.

Keywords: NF2, intracochlear schwannoma, hearing reconstruction, cochlear implantation

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Authors: Kai-Yao Huang, Tzong-Yi Lee, Pin-Hao Ho, Tzu-Hao Chang, Cheng-Wei Chang

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Background: Human cytomegalovirus (HCMV) infects much people around the world, and there were many researches mention that many diseases were caused by HCMV. To understand the mechanism of HCMV lead to diseases during infection. We observe a microRNA (miRNA) – miRNA interaction between HCMV and host during infection. We found HCMV miRNA sequence component complementary with host miRNA precursors, and we also found that the host miRNA abundances were decrease in HCMV infection. Hence, we focus on the host miRNA which may target by the other HCMV miRNA to find theirs target mRNAs expression and analysis these mRNAs affect what kind of signaling pathway. Interestingly, we found the affected mRNA play an important role in some diseases related pathways, and these diseases had been annotated by HCMV infection. Results: From our analysis procedure, we found 464 human miRNAs might be targeted by 26 HCMV miRNAs and there were 291 human miRNAs shows the concordant decrease trend during HCMV infection. For case study, we found hcmv-miR-US22-5p may regulate hsa-mir-877 and we analysis the KEGG pathway which built by hsa-mir-877 validate target mRNA. Additionally, through survey KEGG Disease database found that these mRNA co-regulate some disease related pathway for instance cancer, nerve disease. However, there were studies annotated that HCMV infection casuse cancer and Alzheimer. Conclusions: This work supply a different scenario of miRNA target interactions(MTIs). In previous study assume miRNA only target to other mRNA. Here we wonder there is possibility that miRNAs might regulate non-mRNA targets, like other miRNAs. In this study, we not only consider the sequence similarity with HCMV miRNAs and human miRNA precursors but also the expression trend of these miRNAs. Then we analysis the human miRNAs validate target mRNAs and its associated KEGG pathway. Finally, we survey related works to validate our investigation.

Keywords: human cytomegalovirus, HCMV, microRNA, miRNA

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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: William Ramirez-Benavides

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The mite Varroa destructor Anderson & Trueman (Mesostigmata: Varroidae), is an exclusive hematophagous parasite of the Apis honey bees (Apidae: Hymenoptera). The early phoretic female mites have multiple small inactivated oocytes. Consequently, for the initial growth and vitellogenesis of the oocytes, the mother mite must feed on the hemolymph of the host, as a unique food source, by taking intermittently variable number of blood meals: 1. During the phoretic phase, to initiate vitellogenesis of the terminal oocyte, 2. From a freshly capped bee cell with a bee larva, up to the apolysis stage, to complete vitellogenesis and embryogenesis of the terminal oocyte, and 3. From all pupal stages, up to the imago stage, to induce oogenesis and vitellogenesis of the would-be nonembryonic female eggs. Additionally, oogenesis and vitellogenesis expressions in Varroa destructor and other Varroidae varies according to environmental conditions, e.g., chemical attractions produced by the adult bee and larvae, race of bees, sex of the larva, developmental period of the bee larva, food quality and quantity, and superparasitism (several cofoundressess). Also, the feeding stimuli obtained from the host hemolymph, indirectly regulate the reproductive physiology of the mite, by inducing different vitellogenin expressions, the production of a male egg first in the sequence followed by vitellogenesis of the would-be female eggs during the pupal stages. Furthermore, the different uptakes of hemolymph from the host, also indirectly induce the production of the male egg first in the sequence, local mate competition (LMC) and variable adaptive female sex ratios in the broods, especially when superparasitism occurs. Consequently, reproduction in Varroa destructor, and probably in other Varroidae, depends exclusively on feeding in the hemolymph of the bee host, even during the phoretic phase, the prepupal stages and during the pupal stages; and that, the feeding factors are common syndromes in other Varroidae.

Keywords: oogenesis, sex determination, varroa destructor, vitellogenesis

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Authors: Zeliha Erdogan, Hatice Torcu Koc

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The fish, Sarpa salpa (L.), is one of the main macroherbivores in the Mediterranean. A total of 600 Salema individuals were collected from around Gökçeada, Sea of Northern Aegean, between January 2014 and January 2015 in order to evaluate some information on the biology of the Salema population. For this aim, measurements of the Salema were obtained using a caliper. The age readings were made from otoliths. The population was composed of 6 age classes (I-VI). The total lengths and total weights of sampled fish were determined to be ranged from 12.5 to 33.1 cm and 33.57 to 559.33 g, respectively. Length-weight relationship for all individuals was calculated as W=0.0085*L3.1723, R2=0.9524. Growth parameters were determined as L∞= 35.55cm, k=0.31, t0= -9.2, '=2.60. As the sexual ratio was 1.08:1 (M: F), the Salema population consisted of 51.66% male and 47.5% female individuals. The highest average condition factors were observed for females in May (1.68) and for males in May (1.67). According to gonad somatic index values, the spawning period was determined twice a year in spring (April) and autumn (October). The highest average hepatosomatix index value was observed for all individuals in May and December. It was estimated that total (Z) mortality, natural (M) mortality, and fishing (F) mortality rates were Z=0.44 year-1, M=0.064 year-1 and F=0.38 year-1, respectively. As the exploitation rate was estimated as E=0.86, it can be shown that the Salema stock was highly influenced by overfishing.

Keywords: biology, sarpa salpa, Gökceada, meadows

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Authors: Hassan S. Naeini

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Nowadays a lot of people are working in several sorts of industrial sectors in which there are some risk factors which threaten human being especially in developing countries. One of the main problems which effect on workers’ health refers to Ergonomics. Ergonomics as multidisciplinary science concerns workers’ health and safety in terms of somatic and mental concepts. Surely ergonomics interventions and improvement make a better condition for workers and change the quality of working life to better condition. In this study, one of the factories in Iran which is producing some kinds of small and medium size of refrigerators was chosen as the sample. The preliminary ergonomics observation of the mentioned factory showed that there are some risk factors in terms of ergonomics aspects, so an ergonomic intervention was defined, then some ergonomic assessment methods such as NMQ,OWAS, and Environmental Ergonomic Assessment were used. Also Anthropometric measurement was done. This study shows that there are some workstations and plants which suffer some degrees of ergonomic problems. Considering with the gathered data, illumination, noise control and workstation design in metal workstation are known as the priority actions. Some parts of the mentioned interventions are ongoing actions. it seems that the mentioned intervention and workstations design make a better condition for workers, because ergonomics make a safer and more sustainable environments for human being.

Keywords: anthropometry, ergonomics, health, NMQ, OWAS

Procedia PDF Downloads 755

Authors: Shivam Yadav, Neelam Atri

Abstract:

Cyanobacteria are photoautotrophic prokaryotes able to grow in diverse ecological habitats, originated 2.5 - 3.5 billion years ago and brought oxygenic photosynthesis. Since then superoxide dismutases (SODs) acquired great significance due to their ability to catalyze detoxification of byproducts of oxygenic photosynthesis, i.e. superoxide radicals. Sequence information from several cyanobacterial genomes offers a unique opportunity to conduct a comprehensive comparative analysis of the superoxide dismutases family. In the present study, we extracted information regarding SODs from species of sequenced cyanobacteria and investigated their diversity, conservation, domain structure, and evolution. 144 putative SOD homologues were identified. SODs are present in all cyanobacterial species reflecting their significant role in survival. However, their distribution varies, fewer in unicellular marine strains whereas abundant in filamentous nitrogen-fixing cyanobacteria. Motifs and invariant amino acids typical in eukaryotic SODs were conserved well in these proteins. These SODs were classified into three major families according to their domain structures. Interestingly, they lack additional domains as found in proteins of other family. Phylogenetic relationships correspond well with phylogenies based on 16S rRNA and clustering occurs on the basis of structural characteristics such as domain organization. Similar conserved motifs and amino acids indicate that cyanobacterial SODs make use of a similar catalytic mechanism as eukaryotic SODs. Gene gain-and-loss is insignificant during SOD evolution as evidenced by absence of additional domain. This study has not only examined an overall background of sequence-structure-function interactions for the SOD gene family but also revealed variation among SOD distribution based on ecophysiological and morphological characters.

Keywords: comparative genomics, cyanobacteria, phylogeny, superoxide dismutases

Procedia PDF Downloads 133

Authors: Masoud Alipanah, Sekineh Akbari, Gholamreza Dashab

Abstract:

Myostatin genes or factor 8 affecting on growth and making differentiation works (GDF8) as a moderator in the development of skeletal muscle inhibitor. If mutations occurs in the coding region of myostatin, alter its inhibitory role and the muscle growth is increased. In this study, blood samples were collected randomly from 60 Kurdish sheep in northern Khorasan and DNA extraction was performed using a modified salt. A fragment 337 bp from exon 3 myostatin gene and-specific primers by using a polymerase chain reaction (PCR) were amplified. In order to detect different forms of an allele at this locus HaeΙΙΙ restriction enzymes and PCR-RFLP analysis were used. Band patterns clarification was performed using agarose gel electrophoresis. The frequency of genotypes mm, Mm, and MM, were respectively detected, 0, 0.15 and 0.85. The allele frequency for alleles m and M, were respectively, 0.07 and 0.93. The statistical analyses indicated that m allele was significantly associated with body weight. The results of this study suggest that the Myostatin gene possibly is a candidate gene that affects growth traits in Kurdish sheep.

Keywords: GDF8 gene, Kurdi Sheep of Northern Khorasan, polymorphism, weight traits

Procedia PDF Downloads 340

Authors: Amir Shahab Shahabi, Mohsen Hasirian

Abstract:

Modern societies, marked by expansive Internet connectivity and the rise of e-commerce, are now integrated with digital platforms at an unprecedented level. The efficiency, speed, and accessibility of e-commerce have garnered a substantial consumer base. Against this backdrop, electronic banking has undergone rapid proliferation within the realm of online activities. However, this growth has inadvertently given rise to an environment conducive to illicit activities, notably electronic payment fraud, posing a formidable challenge to the domain of electronic banking. A pivotal role in upholding the integrity of electronic commerce and business transactions is played by electronic fraud detection, particularly in the context of credit cards which underscores the imperative of comprehensive research in this field. To this end, our study introduces an Attentional Bi-Stream Sequence Learner (AttBiSeL) framework that leverages attention mechanisms and recurrent networks. By incorporating bidirectional recurrent layers, specifically bidirectional Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU) layers, the proposed model adeptly extracts past and future transaction sequences while accounting for the temporal flow of information in both directions. Moreover, the integration of an attention mechanism accentuates specific transactions to varying degrees, as manifested in the output of the recurrent networks. The effectiveness of the proposed approach in automatic credit card fraud classification is evaluated on the European Cardholders' Fraud Dataset. Empirical results validate that the hybrid architectural paradigm presented in this study yields enhanced accuracy compared to previous studies.

Keywords: credit card fraud, deep learning, attention mechanism, recurrent neural networks

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Authors: Mohammed Hakim Jafferali, Balaje Vijayaraghavan, Ricardo A. Figueroa, Ellinor Crafoord, Veronica J. Larsson, Einar Hallberg, Santhosh Gudise

Abstract:

The nuclear envelope which surrounds the chromatin of eukaryotic cells contains more than a hundred transmembrane proteins. Mutations in some genes encoding nuclear envelope proteins give rise to human diseases including neurological disorders. The function of many nuclear envelope proteins is not well established. This is partly because nuclear envelope proteins and their interactions are difficult to study due to the inherent resistance to extraction of nuclear envelope proteins. We have developed a novel method called MCLIP, to identify interacting partners of nuclear envelope proteins in live cells. Using MCLIP, we found three new binding partners of the inner nuclear membrane protein Samp1: the intermediate filament protein Lamin B1, the LINC complex protein Sun1 and the G-protein Ran. Furthermore, using in vitro studies, we show that Samp1 binds both Emerin and Ran directly. We have also studied the interaction between Samp1 and Ran in detail. The results show that the Samp1 binds stronger to RanGTP than RanGDP. Samp1 is the first transmembrane protein known to bind Ran and it is tempting to speculate that Samp1 may provide local binding sites for RanGTP at membranes.

Keywords: MCLIP, nuclear envelope, ran, Samp1

Procedia PDF Downloads 352

Authors: Danny Barash

Abstract:

Riboswitches are RNA genetic control elements that were originally discovered in bacteria and provide a unique mechanism of gene regulation. They work without the participation of proteins and are believed to represent ancient regulatory systems in the evolutionary timescale. One of the biggest challenges in riboswitch research is that many are found in prokaryotes but only a small percentage of known riboswitches have been found in certain eukaryotic organisms. The few examples of eukaryotic riboswitches were identified using sequence-based bioinformatics search methods that include some slight structural considerations. These pattern-matching methods were the first ones to be applied for the purpose of riboswitch detection and they can also be programmed very efficiently using a data structure called affix arrays, making them suitable for genome-wide searches of riboswitch patterns. However, they are limited by their ability to detect harder to find riboswitches that deviate from the known patterns. Several methods have been developed since then to tackle this problem. The most commonly used by practitioners is Infernal that relies on Hidden Markov Models (HMMs) and Covariance Models (CMs). Profile Hidden Markov Models were also carried out in the pHMM Riboswitch Scanner web application, independently from Infernal. Other computational approaches that have been developed include RMDetect by the use of 3D structural modules and RNAbor that utilizes Boltzmann probability of structural neighbors. We have tried to incorporate more sophisticated secondary structure considerations based on RNA folding prediction using several strategies. The first idea was to utilize window-based methods in conjunction with folding predictions by energy minimization. The moving window approach is heavily geared towards secondary structure consideration relative to sequence that is treated as a constraint. However, the method cannot be used genome-wide due to its high cost because each folding prediction by energy minimization in the moving window is computationally expensive, enabling to scan only at the vicinity of genes of interest. The second idea was to remedy the inefficiency of the previous approach by constructing a pipeline that consists of inverse RNA folding considering RNA secondary structure, followed by a BLAST search that is sequence-based and highly efficient. This approach, which relies on inverse RNA folding in general and our own in-house fragment-based inverse RNA folding program called RNAfbinv in particular, shows capability to find attractive candidates that are missed by Infernal and other standard methods being used for riboswitch detection. We demonstrate attractive candidates found by both the moving-window approach and the inverse RNA folding approach performed together with BLAST. We conclude that structure-based methods like the two strategies outlined above hold considerable promise in detecting riboswitches and other conserved RNAs of functional importance in a variety of organisms.

Keywords: riboswitches, RNA folding prediction, RNA structure, structure-based methods

Procedia PDF Downloads 234

Authors: Daniel Botero, Oscar Rubiano, Pedro P. Barragan, Jaime Baron, Leonardo Rodriguez Perdomo, Jaime Rodriguez

Abstract:

In the last decade interval training (IT) has gained importance when is compare with strength training (ST). However, there are few studies analyzing the impact of these training over the autonomic nervous system (ANS). This work has aimed to compare the activity of the autonomic nervous system, when is expose to an IT or ST indoor cycling mode. After approval by the ethics committee, a cross-over clinical trial with 22 healthy participants (age 21 ± 3 years) was implemented. The selection of participants for the groups with sequence force-interval (F-I) and interval-force (I-F) was made randomly with assignation of 11 participants for each group. The temporal series of heart rate was obtained before and after each training using the POLAR TEAM® heart monitor. The evaluation of the ANS was performed with spectral analysis of the heart rate variability (HRV) using the fast Fourier transform (Kubios software). A training of 8 weeks in each sequence (4 weeks with each training) with an intermediate period of two weeks of washout was implemented for each group. The power parameter of the HRV in the low frequency band (LF = 0.04-0.15Hz related to the sympathetic nervous system), high frequency (HF = 0.15-0.4Hz, related to the parasympathetic) and LF/HF (with reference to a modulation of parasympathetic over the sympathetic), were calculated. Afterward, the difference between the parameters before and after was realized. Then, to evaluate statistical differences between each training was implemented the method of Wellek (Wellek and Blettner, 2012, Medicine, 109 (15), 276-81). To determine the difference of effect over parasympathetic when FT and IT are used, the T test is implemented obtaining a T value of 0.73 with p-value ≤ 0.1. For the sympathetic was obtained a T of 0.33 with p ≤ 0.1 and for LF/HF the T was 1.44 with a p ≥ 0.1. Then, the carry over effect was evaluated and was not present. Significant changes over autonomic activity with strength or interval training were not observed. However, a modulation of the parasympathetic over the sympathetic can be observed. Probably, these findings should be explained because the sample is little and/or the time of training was insufficient to generate changes.

Keywords: autonomic nervous, force training, indoor cycling, interval training

Procedia PDF Downloads 225

Authors: Diego Santibañez Oyarce, Fernanda Bravo Cornejo, Camilo Cerda Sarabia, Belén Díaz Díaz, Esteban Gómez Terán, Hugo Osses Prado, Raúl Caulier-Cisterna, Jorge Vergara-Quezada, Ana Moya-Beltrán

Abstract:

The advent of high-throughput sequencing technologies has revolutionized genomics, generating vast amounts of genetic data that challenge traditional bioinformatics methods. Machine learning addresses these challenges by leveraging computational power to identify patterns and extract information from large datasets. However, biological sequence data, being symbolic and non-numeric, must be converted into numerical formats for machine learning algorithms to process effectively. So far, some encoding methods, such as one-hot encoding or k-mers, have been explored. This work proposes additional approaches for encoding DNA sequences in order to compare them with existing techniques and determine if they can provide improvements or if current methods offer superior results. Data from the 16S rRNA gene, a universal marker, was used to analyze eight bacterial groups that are significant in the pulmonary environment and have clinical implications. The bacterial genes included in this analysis are Prevotella, Abiotrophia, Acidovorax, Streptococcus, Neisseria, Veillonella, Mycobacterium, and Megasphaera. These data were downloaded from the NCBI database in Genbank file format, followed by a syntactic analysis to selectively extract relevant information from each file. For data encoding, a sequence normalization process was carried out as the first step. From approximately 22,000 initial data points, a subset was generated for testing purposes. Specifically, 55 sequences from each bacterial group met the length criteria, resulting in an initial sample of approximately 440 sequences. The sequences were encoded using different methods, including one-hot encoding, k-mers, Fourier transform, and Wavelet transform. Various machine learning algorithms, such as support vector machines, random forests, and neural networks, were trained to evaluate these encoding methods. The performance of these models was assessed using multiple metrics, including the confusion matrix, ROC curve, and F1 Score, providing a comprehensive evaluation of their classification capabilities. The results show that accuracies between encoding methods vary by up to approximately 15%, with the Fourier transform obtaining the best results for the evaluated machine learning algorithms. These findings, supported by the detailed analysis using the confusion matrix, ROC curve, and F1 Score, provide valuable insights into the effectiveness of different encoding methods and machine learning algorithms for genomic data analysis, potentially improving the accuracy and efficiency of bacterial classification and related genomic studies.

Keywords: DNA encoding, machine learning, Fourier transform, Fourier transformation

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Authors: Maryam Beiranvand, Sajad Yaghoubi

Abstract:

Background: Some microbes can colonize plants’ inner tissues without causing obvious damage and can even produce useful bioactive substances. In the present study, the diversity of the endophytic bacteria associated with medicinal plants from Iran was investigated by culturing techniques, molecular gene identification, as well as measuring them for antibacterial activity. Results: In the spring season from 2013 to 2014, 35 herb pharmacology samples were collected, sterilized, meshed, and then cultured on selective media culture. A total of 199 endophytic bacteria were successfully isolated from 35 tissue cultures of medical plants, and sixty-seven out of 199 bacterial isolates were subjected to identification by the 16S rRNA gene sequence analysis method. Based on the sequence similarity gene and phylogenetic analyses, these isolates were grouped into five classes, fourteen orders, seventeen families, twenty-one genera, and forty strains. The most abundant group of endophytic bacteria was actinobacterial, consisting of thirty-two (47%) out of 67 bacterial isolates. Ten (22.3%) out of 67 bacterial isolates remained unidentified and classified at the genus level. The signature of the 16S rRNA gene formed a distinct line in a phylogenetic tree showing that they might be new species of bacteria. One (5.2%) out of 67 bacterial isolates was still not well categorized. Forty-two out of 67 strains were candidates for antimicrobial activity tests. Nineteen (45%) out of 42 strains showed antimicrobial activity multidrug resistance (MDR); thirteen (68%) out of 19 strains were allocated to classes actinobacteria. Four (21%) out of 19 strains belonged to the Bacillaceae family, one (5.2%) out of 19 strains was the Paenibacillaceae family, and one (5.2%) out of 19 strains belonged to the Pseudomonadaceae family. The other twenty-three strains did not show inhibitory activities. Conclusions: Our research showed a high-level phylogenetic diversity and the intoxicating antibiotic activity of endophytic bacteria in the herb pharmacology of Iran.

Keywords: Antibacterial activity, endophytic bacteria, multidrug-resistant bacteria, whole genom sequencing

Procedia PDF Downloads 86

Authors: Yuxi Liu, Boris Belousov, Mehrzad Esmaeili Charkhab, Oliver Tessmann

Abstract:

This paper presents a computational solution for designing reconfigurable interlocking structures that are fully assembled with SL Blocks. Formed by S-shaped and L-shaped tetracubes, SL Block is a specific type of interlocking puzzle. Analogous to molecular self-assembly, the aggregation of SL blocks will build a reversible hierarchical and discrete system where a single module can be numerously replicated to compose semi-interlocking components that further align, wrap, and braid around each other to form complex high-order aggregations. These aggregations can be disassembled and reassembled, responding dynamically to design inputs and changes with a unique capacity for reconfiguration. To use these aggregations as architectural structures, we developed computational tools that automate the configuration of SL blocks based on architectural design objectives. There are three critical phases in our work. First, we revisit the hierarchy of the SL block system and devise a top-down-type design strategy. From this, we propose two key questions: 1) How to translate 3D polyominoes into SL block assembly? 2) How to decompose the desired voxelized shapes into a set of 3D polyominoes with interlocking joints? These two questions can be considered the Hamiltonian path problem and the 3D polyomino tiling problem. Then, we derive our solution to each of them based on two methods. The first method is to construct the optimal closed path from an undirected graph built from the voxelized shape and translate the node sequence of the resulting path into the assembly sequence of SL blocks. The second approach describes interlocking relationships of 3D polyominoes as a joint connection graph. Lastly, we formulate the desired shapes and leverage our methods to achieve their reconfiguration within different levels. We show that our computational strategy will facilitate the efficient design of hierarchical interlocking structures with a self-replicating geometric module.

Keywords: computational design, SL-blocks, 3D polyomino puzzle, combinatorial problem

Procedia PDF Downloads 129

Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

Abstract:

Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

Procedia PDF Downloads 114

Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

Abstract:

ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

Procedia PDF Downloads 110

Authors: Maryam Beiranvand, Sajad Yaghoubi

Abstract:

Background: Some microbes can colonize plants’ inner tissues without causing obvious damage and can even produce useful bioactive substances. In the present study, the diversity of the endophytic bacteria associated with medicinal plants from Iran was investigated by culturing techniques, molecular gene identification, as well as measuring them for antibacterial activity. Results: In the spring season from 2013 to 2014, 35 herb pharmacology samples were collected, sterilized, meshed, and then cultured on selective media culture. A total of 199 endophytic bacteria were successfully isolated from 35 tissue cultures of medical plants, and sixty-seven out of 199 bacterial isolates were subjected to identification by the 16S rRNA gene sequence analysis method. Based on the sequence similarity gene and phylogenetic analyses, these isolates were grouped into five classes, fourteen orders, seventeen families, twenty-one genera, and forty strains. The most abundant group of endophytic bacteria was actinobacterial, consisting of thirty-two (47%) out of 67 bacterial isolates. Ten (22.3%) out of 67 bacterial isolates remained unidentified and classified at the genus level. The signature of the 16S rRNA gene formed a distinct line in a phylogenetic tree showing that they might be new species of bacteria. One (5.2%) out of 67 bacterial isolates was still not well categorized. Forty-two out of 67 strains were candidates for antimicrobial activity tests. Nineteen (45%) out of 42 strains showed antimicrobial activity multidrug-resistance (MDR); thirteen (68%) out of 19 strains were allocated to classes actinobacteria. Four (21%) out of 19 strains belonged to the Bacillaceae family, one (5.2%) out of 19 strains was the Paenibacillaceae family, and one (5.2%) out of 19 strains belonged to the Pseudomonadaceae family. The other twenty-three strains did not show inhibitory activities. Conclusions: Our research showed a high-level phylogenetic diversity and the intoxicating antibiotic activity of endophytic bacteria in the herb pharmacology of Iran.

Keywords: medical plant, endophytic bacteria, antimicrobial activity, whole genome sequencing analysis

Procedia PDF Downloads 124