Search results for: candidate gene of type-2 diabetes
2398 Isolation and Characterization White Spot Syndrome Protein Envelope Protein 19 from Black Tiger Shrimp (Penaeus monodon)
Authors: Andi Aliah Hidayani, Asmi Citra Malina A. R. Tassakka, Andi Parenrengi
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Vanname Shrimp is one of the high yielding varieties that are more resistant to virus attacks. However, now this shrimp more death due to virus attack such as white spot disease caused by white spot syndrome virus (WSSV). Various efforts have done to prevent the disease, like immunostimulatory, probiotics, and vaccine. White spot syndrome virus (WSSV) envelope protein VP19 gene is important because of its involvement in the system infection of shrimp. This study aimed to isolate and characterize an envelope protein VP19 – encoding gene of WSSV using WSSV infected Vanname Shrimp sample from some areas in South Sulawesi (Pangkep, Barru and Pinrang). The genomic of DNA were isolated from shrimp muscle using DTAB-CTAB method. Isolation of gene encoding envelope protein VP19 WSSV ws successfully performed with the results of the length of DNA fragment was 387 bp. The results of homology analysis using BLASTn homology suggested that these isolates genes from Barru, Pangkep and Pinrang have closest relationship with isolates from Mexican.Keywords: vanname, shrimp, WSSV, viral protein 19
Procedia PDF Downloads 5352397 Profile of Programmed Death Ligand-1 (PD-L1) Expression and PD-L1 Gene Amplification in Indonesian Colorectal Cancer Patients
Authors: Akterono Budiyati, Gita Kusumo, Teguh Putra, Fritzie Rexana, Antonius Kurniawan, Aru Sudoyo, Ahmad Utomo, Andi Utama
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The presence of the programmed death ligand-1 (PD-L1) has been used in multiple clinical trials and approved as biomarker for selecting patients more likely to respond to immune checkpoint inhibitors. However, the expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence. Positive PD-L1 within tumors may result from two mechanisms, induced PD-L1 expression by T-cell presence or genetic mechanism that lead to constitutive PD-L1 expression. Amplification of PD-L1 genes was found as one of genetic mechanism which causes an increase in PD-L1 expression. In case of colorectal cancer (CRC), targeting immune checkpoint inhibitor has been recommended for patients with microsatellite instable (MSI). Although the correlation between PD-L1 expression and MSI status has been widely studied, so far the precise mechanism of PD-L1 gene activation in CRC patients, particularly in MSI population have yet to be clarified. In this present study we have profiled 61 archived formalin fixed paraffin embedded CRC specimens of patients from Medistra Hospital, Jakarta admitted in 2010 - 2016. Immunohistochemistry was performed to measure expression of PD-L1 in tumor cells as well as MSI status using antibodies against PD-L1 and MMR (MLH1, MSH2, PMS2 and MSH6), respectively. PD-L1 expression was measured on tumor cells with cut off of 1% whereas loss of nuclear MMR protein expressions in tumor cells but not in normal or stromal cells indicated presence of MSI. Subset of PD-L1 positive patients was then assessed for copy number variations (CNVs) using single Tube TaqMan Copy Number Assays Gene CD247PD-L1. We also observed KRAS mutation to profile possible genetic mechanism leading to the presence or absence of PD-L1 expression. Analysis of 61 CRC patients revealed 15 patients (24%) expressed PD-L1 on their tumor cell membranes. The prevalence of surface membrane PD-L1 was significantly higher in patients with MSI (87%; 7/8) compared to patients with microsatellite stable (MSS) (15%; 8/53) (P=0.001). Although amplification of PD-L1 gene was not found among PD-L1 positive patients, low-level amplification of PD-L1 gene was commonly observed in MSS patients (75%; 6/8) than in MSI patients (43%; 3/7). Additionally, we found 26% of CRC patients harbored KRAS mutations (16/61), so far the distribution of KRAS status did not correlate with PD-L1 expression. Our data suggest genetic mechanism through amplification of PD-L1 seems not to be the mechanism underlying upregulation of PD-L1 expression in CRC patients. However, further studies are warranted to confirm the results.Keywords: colorectal cancer, gene amplification, microsatellite instable, programmed death ligand-1
Procedia PDF Downloads 2222396 Identification of Significant Genes in Rheumatoid Arthritis, Melanoma Metastasis, Ulcerative Colitis and Crohn’s Disease
Authors: Krishna Pal Singh, Shailendra Kumar Gupta, Olaf Wolkenhauer
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Background: Our study aimed to identify common genes and potential targets across the four diseases, which include rheumatoid arthritis, melanoma metastasis, ulcerative colitis, and Crohn’s disease. We used a network and systems biology approach to identify the hub gene, which can act as a potential target for all four disease conditions. The regulatory network was extracted from the PPI using the MCODE module present in Cytoscape. Our objective was to investigate the significance of hub genes in these diseases using gene ontology and KEGG pathway enrichment analysis. Methods: Our methodology involved collecting disease gene-related information from DisGeNET databases and performing protein-protein interaction (PPI) network and core genes screening. We then conducted gene ontology and KEGG pathway enrichment analysis. Results: We found that IL6 plays a critical role in all disease conditions and in different pathways that can be associated with the development of all four diseases. Conclusions: The theoretical importance of our research is that we employed various systems and structural biology techniques to identify a crucial protein that could serve as a promising target for treating multiple diseases. Our data collection and analysis procedures involved rigorous scrutiny, ensuring high-quality results. Our conclusion is that IL6 plays a significant role in all four diseases, and it can act as a potential target for treating them. Our findings may have important implications for the development of novel therapeutic interventions for these diseases.Keywords: melanoma metastasis, rheumatoid arthritis, inflammatory bowel diseases, integrated bioinformatics analysis
Procedia PDF Downloads 892395 Molecular Characterization of White Spot Syndrome Virus in Some Cultured Penaeid Shrimps of Coastal Regions in Bangladesh
Authors: Md. Baki Billah, Suraiya Parveen, Shuvra Kanti Dey
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Bangladesh is earning a lot of foreign currency by exporting shrimp, but this industry is facing a tremendous problem due to the infection of white spot syndrome virus (WSSV). This study was undermined to develop rapid detection method of WSSV. A total of shrimp samples 240 collected from the 12 shrimp farms of different coastal regions (Satkhira, Khulna, and Bagerhat) were analyzed by conventional PCR using VP28 and VP664 gene-specific primers. In satkhira, Bagerhat and Khulna 39, 41 and 29 samples were found WSSV positive respectively. Real-time PCR using 71-bp amplicon for VP664 gene correlated well with conventional PCR data. The prevalence rates of WSSV among the collected 240 samples were Satkhira 38%, Khulna 47% and Bagerhat 50%. Molecular analysis of the VP28 gene sequences of WSSV revealed that Bangladeshi strains phylogenetically affiliated to the strains belong to India. This work concluded that WSSV infections are widely distributed in the coastal regions cultured shrimp in Bangladesh. Physico-chemical parameters were within the range of fish culture.Keywords: coastal regions of Bangladesh, PCR, shrimp, white spot syndrome virus
Procedia PDF Downloads 1282394 Insulin Resistance in Early Postmenopausal Women Can Be Attenuated by Regular Practice of 12 Weeks of Yoga Therapy
Authors: Praveena Sinha
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Context: Diabetes is a global public health burden, particularly affecting postmenopausal women. Insulin resistance (IR) is prevalent in this population, and it is associated with an increased risk of developing type 2 diabetes. Yoga therapy is gaining attention as a complementary intervention for diabetes due to its potential to address stress psychophysiology. This study focuses on the efficacy of a 12-week yoga practice in attenuating insulin resistance in early postmenopausal women. Research Aim: The aim of this research is to investigate the effect of a 3-month long yoga practice on insulin resistance in early postmenopausal women. Methodology: The study conducted a prospective longitudinal design with 67 women within five years of menopause. Participants were divided into two groups based on their willingness to join yoga. The Yoga group (n = 37) received routine gynecological management along with an integrated yoga module, while the Non-Yoga group (n = 30) received only routine management. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR) method before and after the intervention. Statistical analysis was performed using GraphPad Prism Version 5 software, with statistical significance set at P < 0.05. Findings: The results indicate a significant decrease in serum fasting insulin levels and HOMA-IR measurements in the Yoga group, although the decrease did not reach statistical significance. In contrast, the Non-Yoga group showed a significant rise in serum fasting insulin levels and HOMA-IR measurements after 3 months, suggesting a detrimental effect on insulin resistance in these postmenopausal women. Theoretical Importance: This study provides evidence that a 12-week yoga practice can attenuate the increase in insulin resistance in early postmenopausal women. It highlights the potential of yoga as a preventive measure against the early onset of insulin resistance and the development of type 2 diabetes mellitus. Regular yoga practice can be a valuable tool in addressing hormonal imbalances associated with early postmenopause, leading to a decrease in morbidity and mortality related to insulin resistance and type 2 diabetes mellitus in this population. Data Collection and Analysis Procedures: Data collection involved measuring serum fasting insulin levels and calculating HOMA-IR. Statistical analysis was performed using GraphPad Prism Version 5 software, and mean values with standard error of the mean were reported. The significance level was set at P < 0.05. Question Addressed: The study aimed to address whether a 3-month long yoga practice could attenuate insulin resistance in early postmenopausal women. Conclusion: The research findings support the efficacy of a 12-week yoga practice in attenuating insulin resistance in early postmenopausal women. Regular yoga practice has the potential to prevent the early onset of insulin resistance and the development of type 2 diabetes mellitus in this population. By addressing the hormonal imbalances associated with early post menopause, yoga could significantly decrease morbidity and mortality related to insulin resistance and type 2 diabetes mellitus in these subjects.Keywords: post menopause, insulin resistance, HOMA-IR, yoga, type 2 diabetes mellitus
Procedia PDF Downloads 682393 Determination of Parasitic Load in Different Tissues of Murine Toxoplasmosis after Immunization by Excretory-Secretory Antigens using Real Time QPCR
Authors: Ahmad Daryani, Yousef Dadimoghaddam, Mehdi Sharif, Ehsan Ahmadpour, Shahabeddin Sarvi, Baghar Hashemi
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Background: Excretory-secretory antigens (ESAs) of Toxoplasma gondii are one of the candidates for immunization against toxoplasmosis. For evaluation of immunization, we determined the kinetics of the distribution of Toxoplasma and parasite load in different tissues of mice immunized by ESAs. Methods: In this experimental study, 36 mice in case (n= 18) and control (n= 18) groups were immunized with ESAs and PBS, respectively. After 2 weeks, mice were challenged intraperitoneally with Toxoplasma virulent RH strain. Blood and different tissues (brain, spleen, liver, heart, kidney, and muscle) were collected daily after challenge (1, 2, 3 and last day before death). Parasite load was calculated using Real time QPCR targeted at the B1 gene. Results: ESAs as vaccine in different tissues showed various effects. However, infected mice which received the vaccine in comparison with control group, displayed a drastically decreasing in parasite burden, in their blood and tissues (P= 0.000). Conclusion: These results indicated that ESAs with reduction of parasite load in different tissues of host could be evaluable candidate for the development of immunization strategies against toxoplasmosis.Keywords: parasitic load, murine toxoplasmosis, immunization, excretory-secretory antigens, real time QPCR
Procedia PDF Downloads 4452392 Boiling Effect of Momordica charantia with Salt to the Antihiperglicemia Effectiveness of Diabetes Mellitus Rats
Authors: Zulfa D. Putri, Jumayanti Jumayanti, Hatiefah T. I. Melati, Kiki Indriati, Farah U. Mauhibah
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Momordica charantia is a food that is often used for nutrition therapy for patients with Diabetes Mellitus (DM) because of its effect as antihiperglicemia. However, the bitter taste of Momordica charantia may be an obstacle to consume. Some people remove the bitter taste of this by boiling it with salt water. The purpose of this study was to determine the effect of Momordica charantia boiling with salt water in lowering blood glucose levels. This study is a quasi-experimental study with pre-post test with control group design. The research sample consisted of 25 rats Sprague-Dawley were divided into 5 groups: Control group of healthy, control group of DM, control group of DM with the addition of Momordica charantia are boiled by salt for 3 minutes, 6 minutes, and 9 minutes. Blood glucose levels were measured after 4 weeks using a spectrophotometer. These results indicate that there is the effect of bitter taste from Momordica charantia in lowering blood glucose levels in rats significantly. The conclusion of this study is giving a Momordica charantia juice in Sprague-Dawley rats that induced by alloxan has meaningful statistically proven by One Way ANOVA test (p = 0.00) in lowering blood glucose levels of rats.Keywords: antihiperglicemia, diabetes mellitus, momordica charantia, salt
Procedia PDF Downloads 2292391 Genome-Wide Identification and Characterization of MLO Family Genes in Pumpkin (Cucurbita maxima Duch.)
Authors: Khin Thanda Win, Chunying Zhang, Sanghyeob Lee
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Mildew resistance locus o (Mlo), a plant-specific gene family with seven-transmembrane (TM), plays an important role in plant resistance to powdery mildew (PM). PM caused by Podosphaera xanthii is a widespread plant disease and probably represents the major fungal threat for many Cucurbits. The recent Cucurbita maxima genome sequence data provides an opportunity to identify and characterize the MLO gene family in this species. Total twenty genes (designated CmaMLO1 through CmaMLO20) have been identified by using an in silico cloning method with the MLO gene sequences of Cucumis sativus, Cucumis melo, Citrullus lanatus and Cucurbita pepo as probes. These CmaMLOs were evenly distributed on 15 chromosomes of 20 C. maxima chromosomes without any obvious clustering. Multiple sequence alignment showed that the common structural features of MLO gene family, such as TM domains, a calmodulin-binding domain and 30 important amino acid residues for MLO function, were well conserved. Phylogenetic analysis of the CmaMLO genes and other plant species reveals seven different clades (I through VII) and only clade IV is specific to monocots (rice, barley, and wheat). Phylogenetic and structural analyses provided preliminary evidence that five genes belonged to clade V could be the susceptibility genes which may play the importance role in PM resistance. This study is the first comprehensive report on MLO genes in C. maxima to our knowledge. These findings will facilitate the functional analysis of the MLOs related to PM susceptibility and are valuable resources for the development of disease resistance in pumpkin.Keywords: Mildew resistance locus o (Mlo), powdery mildew, phylogenetic relationship, susceptibility genes
Procedia PDF Downloads 1812390 Molecular Detection and Characterization of Shiga Toxogenic Escherichia coli Associated with Dairy Product
Authors: Mohamed Al-Hazmi, Abdullah Al-Arfaj, Moussa Ihab
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Raw, unpasteurized milk can carry dangerous bacteria such as Salmonella, E. coli, and Listeria, which are responsible for causing numerous foodborne illnesses. The objective of this study was molecular characterization of shiga toxogenic E. coli in raw milk collected from different Egyptian governorates by multiplex PCR. During the period of 25th May to 25th October 2012, a total of 320 bulk-tank milk samples were collected from 10 cow farms located in different Egyptian governorates. Bacteriological examination of milk samples revealed the presence of E. coli organisms in 65 samples (20.3%), serotyping of the E. coli isolates revealed, 35 strains (10.94%) O111, 15 strains (4.69%) O157: H7, 10 strains (3.13%) O128 and 5 strains (1.56%) O119. Multiplex PCR for detection of shiga toxin type 2 and intimin genes revealed positive amplification of 255 bp fragment of shiga toxin type 2 gene and 384 bp fragment of intimin gene from all E. coli serovar O157: H7, while from serovar O111 were 25 (71.43%), 20 (57.14%) and from serovar O128 were 6 (60%), 8 (80%), respectively. The results of multiplex PCR assay are useful for identification of STEC possessing the eaeA and stx2 genes.Keywords: raw milk, E. coli, multiplex PCR, Shiga toxin type 2, intimin gene
Procedia PDF Downloads 3062389 Biodegradation of Phenazine-1-Carboxylic Acid by Rhodanobacter sp. PCA2 Proceeds via Decarboxylation and Cleavage of Nitrogen-Containing Ring
Authors: Miaomiao Zhang, Sabrina Beckmann, Haluk Ertan, Rocky Chau, Mike Manefield
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Phenazines are a large class of nitrogen-containing aromatic heterocyclic compounds, which are almost exclusively produced by bacteria from diverse genera including Pseudomonas and Streptomyces. Phenazine-1-carboxylic acid (PCA) as one of 'core' phenazines are converted from chorismic acid before modified to other phenazine derivatives in different cells. Phenazines have attracted enormous interests because of their multiple roles on biocontrol, bacterial interaction, biofilm formation and fitness of their producers. However, in spite of ecological importance, degradation as a part of phenazines’ fate only have extremely limited attention now. Here, to isolate PCA-degrading bacteria, 200 mg L-1 PCA was supplied as sole carbon, nitrogen and energy source in minimal mineral medium. Quantitative PCR and Reverse-transcript PCR were employed to study abundance and activity of functional gene MFORT 16269 in PCA degradation, respectively. Intermediates and products of PCA degradation were identified with LC-MS/MS. After enrichment and isolation, a PCA-degrading strain was selected from soil and was designated as Rhodanobacter sp. PCA2 based on full 16S rRNA sequencing. As determined by HPLC, strain PCA2 consumed 200 mg L-1 (836 µM) PCA at a rate of 17.4 µM h-1, accompanying with significant cells yield from 1.92 × 105 to 3.11 × 106 cells per mL. Strain PCA2 was capable of degrading other phenazines as well, including phenazine (4.27 µM h-1), pyocyanin (2.72 µM h-1), neutral red (1.30 µM h-1) and 1-hydroxyphenazine (0.55 µM h-1). Moreover, during the incubation, transcript copies of MFORT 16269 gene increased significantly from 2.13 × 106 to 8.82 × 107 copies mL-1, which was 2.77 times faster than that of the corresponding gene copy number (2.20 × 106 to 3.32 × 107 copies mL-1), indicating that MFORT 16269 gene was activated and played roles on PCA degradation. As analyzed by LC-MS/MS, decarboxylation from the ring structure was determined as the first step of PCA degradation, followed by cleavage of nitrogen-containing ring by dioxygenase which catalyzed phenazine to nitrosobenzene. Subsequently, phenylhydroxylamine was detected after incubation for two days and was then transferred to aniline and catechol. Additionally, genomic and proteomic analyses were also carried out for strain PCA2. Overall, the findings presented here showed that a newly isolated strain Rhodanobacter sp. PCA2 was capable of degrading phenazines through decarboxylation and cleavage of nitrogen-containing ring, during which MFORT 16269 gene was activated and played important roles.Keywords: decarboxylation, MFORT16269 gene, phenazine-1-carboxylic acid degradation, Rhodanobacter sp. PCA2
Procedia PDF Downloads 2232388 Comparison of Gestational Diabetes Influence on the Ultrastructure of Rectus Abdominis Muscle in Women and Rats
Authors: Giovana Vesentini, Fernanda Piculo, Gabriela Marini, Debora Damasceno, Angelica Barbosa, Selma Martheus, Marilza Rudge
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Problem statement: Skeletal muscle is highly adaptable, muscle fiber composition and size can respond to a variety of stimuli, such physiologic, as pregnancy, and metabolic abnormalities, as Diabetes mellitus. This study aimed to analyze the effects of pregnancy-associated diabetes on the rectus abdominis muscle (RA), and to compare this changes in rats and women. Methods: Female Wistar rats were maintained under controlled conditions and distributed in Pregnant (P) and Long-term mild pregnant diabetic (LTMd) (n=3 r/group). Diabetes in rats was induced by streptozotocin (100mg/Kg, sc) on the first day of life, for a hyperglycemic state between 120-300 mg/dL in adult life. Female rats were mated overnight, at day 21 of pregnancy were anesthetized, and killed for the harvesting of maternal RA. Pregnant women who attended the Diabetes Prenatal Care Clinic of Botucatu Medical School were distributed in Pregnant non-diabetic (Pnd) and Gestational Diabetic (GDM) (n=3 w/group). The diagnosis of GDM was established according to ADA’s criteria (2016). The harvesting of RA was during the cesarean section. Transversal cross-sections of the RA of both women and rats were analyzed by transmission electron microscopy. All procedures were approved by the Ethics Committee on Animal Experiments of the Botucatu Medical School (Protocol Number 1003/2013) and by the Botucatu Medical School Ethical Committee for Human Research in Medical Sciences (CAAE: 41570815.0.0000.5411). Results: The photomicrographs of the RA of rats revealed disorganized Z lines, thinning sarcomeres, and a usual quantity of intermyofibrillar mitochondria in the P group. The LTMd group showed swollen sarcoplasmic reticulum, dilated T tubes and areas with sarcomere disruption. The ultrastructural analysis of Pnd non-diabetic women in the RA showed well-organized myofibrils forming intact sarcomeres, organized Z lines and a normal distribution of intermyofibrillar mitochondria. The GDM group revealed increase in intermyofibrillar mitochondria, areas with sarcomere disruption and increased lipid droplets. Conclusion: Pregnancy and diabetes induce adaptations in the ultrastructure of the rectus abdominis muscle for both women and rats, changing the architectural design of these tissues. However, in rats these changes are more severe maybe because, besides the high blood glucose levels, the quadrupedal animal may suffer an excessive mechanical tension during pregnancy by gravity. Probably, these findings may suggest that these alterations are a risk factor that contributes to the development of muscle dysfunction in women with GDM and may motivate treatment strategies in these patients.Keywords: gestational diabetes, muscle dysfunction, pregnancy, rectus abdominis
Procedia PDF Downloads 2922387 Functional Slow Release of Encapsulated Ibuprofen in Cross-linked Gellan Gum Hydrogel for Tissue Engineering Application
Authors: Nor Jannah Mohd Sebri, Khairul Anuar Mat Amin
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Dication cross-linked gellan gum hydrogel loaded with Ibuprofen with excellent mechanical properties had been synthesized as potential candidate for non-toxic biocompatible polymer material in tissue engineering. The gellan gum hydrogel with 5% Ibuprofen had produced a slow release profile with total drug release time of 25 hours as a resulting low swelling value recorded at 22+0.5%. Its compressive strength, 200.13+21 kPa was highest of all other hydrogel ratio of 0.5% and 1.0% Ibuprofen incorporation. Young’s Modulus of the hydrogel with 5% Ibuprofen was recorded at 1.8+0.01 MPa, indicating good gel strength in which it is capable of withstanding a fair amount of subjected force during topical wound dressing application. Excellent mechanical properties, together with slow release profile, make the ibuprofen-loaded hydrogel a prospect candidate as biocompatible extracellular matrices in wound management.Keywords: gellan gum, ibuprofen, slow drug release, hydrogel
Procedia PDF Downloads 4002386 Influence of Genetic Counseling in Family Dynamics in Patients with Deafness in Merida, Yucatán, Mexico
Authors: Damaris Estrella Castillo, Zacil ha Vilchis Zapata, Leydi Peraza Gómez
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Hearing loss is an etiologically heterogeneous condition, where almost 60% is genetic in origin, 20% is due to environmental factors, and 20% have unknown causes. However, it is now known that the gene, GJB2, which encodes the connexin 26 protein, accounts for a large percentage of non-syndromic genetic hearing loss, and variants in this gene have been identified to be a common cause of hereditary hearing loss in many populations. The literature reports that the etiology in deafness helps improve family functioning but low-income countries this is difficult. Therefore, it is difficult to contribute the right of families to know about the genetic risk in future pregnancies as well as determining the certainty of being a carrier or affected. In order to assess the impact of genetic counseling and the functionality, 100 families with at least one child with profound hearing loss, were evaluated by specialists in audiology, clinical genetics and psychology. Targeted mutation analysis for one of the two known large deletions of upstream of GJB2/GJB6 gene (35delG; and including GJB2 regulatory sequences and GJB6) were performed in patients with diagnosis of non-syndromic hearing loss. Genetic counseling was given to all parents and primary caregivers, and APGAR family test was applied before and after the counseling. We analyzed a total of 300 members (children, parents) to determine the presence of the GJB2 gene mutation. Twelve patients (carriers and affected) were positive for the mutation, from 5 different families. The subsequent family APGAR testing and genetic counseling, showed that 14% perceived their families as functional, 62 % and 24 % moderately functional dysfunctional. This shows the importance of genetic counseling in the perception of family function that can directly impact the quality of life of these families.Keywords: family dynamics, deafness, APGAR, counseling
Procedia PDF Downloads 6432385 Associations between Physical Activity and Risk Factors for Type II Diabetes in Prediabetic Adults
Authors: Rukia Yosuf
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Diabetes is a national healthcare crisis related to both macrovascular and microvascular complications. We hypothesized that higher levels of physical activity are associated with lower total and visceral fat mass, lower systolic blood pressure, and increased insulin sensitivity. Participant inclusion criteria: 21-50 years old, BMI ≥ 30 kg/m2, hemoglobin A1C 5.7-6.4, fasting glucose 100-125 mg/dL, and HOMA IR ≥ 2.5. Exclusion criteria: history of diabetes, hypertension, HIV, renal disease, hearing loss, alcoholic intake over four drinks daily, use of organic nitrates or PDE5 inhibitors, and decreased cardiac function. Total physical activity was measured using accelerometers, body composition using DXA, and insulin resistance via fsIVGTT. Clinical and biochemical cardiometabolic risk factors, blood pressure and heart rate were obtained using a calibrated sphygmomanometer. Anthropometric measures, fasting glucose, insulin, lipid profile, C-reactive protein, and BMP were analyzed using standard procedures. Within our study, we found correlations between levels of physical activity in a heterogeneous group of prediabetic adults. Patients with more physical activity had a higher degree of insulin sensitivity, lower blood pressure, total visceral adipose tissue, and overall lower total mass. Total physical activity levels showed small, but significant correlations with systolic blood pressure, visceral fat, lean mass and insulin sensitivity. After normalizing for the race, age, and gender using multiple regression, these associations were no longer significant considering our small sample size. More research into prediabetes will decrease the population of diabetics overall. In the future, we could increase sample size and conduct cross sectional and longitudinal studies in various populations with prediabetes.Keywords: diabetes, kidney disease, nephrology, prediabetes
Procedia PDF Downloads 1872384 PARP1 Links Transcription of a Subset of RBL2-Dependent Genes with Cell Cycle Progression
Authors: Ewelina Wisnik, Zsolt Regdon, Kinga Chmielewska, Laszlo Virag, Agnieszka Robaszkiewicz
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Apart from protecting genome, PARP1 has been documented to regulate many intracellular processes inter alia gene transcription by physically interacting with chromatin bound proteins and by their ADP-ribosylation. Our recent findings indicate that expression of PARP1 decreases during the differentiation of human CD34+ hematopoietic stem cells to monocytes as a consequence of differentiation-associated cell growth arrest and formation of E2F4-RBL2-HDAC1-SWI/SNF repressive complex at the promoter of this gene. Since the RBL2 complexes repress genes in a E2F-dependent manner and are widespread in the genome in G0 arrested cells, we asked (a) if RBL2 directly contributes to defining monocyte phenotype and function by targeting gene promoters and (b) if RBL2 controls gene transcription indirectly by repressing PARP1. For identification of genes controlled by RBL2 and/or PARP1,we used primer libraries for surface receptors and TLR signaling mediators, genes were silenced by siRNA or shRNA, analysis of gene promoter occupation by selected proteins was carried out by ChIP-qPCR, while statistical analysis in GraphPad Prism 5 and STATISTICA, ChIP-Seq data were analysed in Galaxy 2.5.0.0. On the list of 28 genes regulated by RBL2, we identified only four solely repressed by RBL2-E2F4-HDAC1-BRM complex. Surprisingly, 24 out of 28 emerged genes controlled by RBL2 were co-regulated by PARP1 in six different manners. In one mode of RBL2/PARP1 co-operation, represented by MAP2K6 and MAPK3, PARP1 was found to associate with gene promoters upon RBL2 silencing, which was previously shown to restore PARP1 expression in monocytes. PARP1 effect on gene transcription was observed only in the presence of active EP300, which acetylated gene promoters and activated transcription. Further analysis revealed that PARP1 binding to MA2K6 and MAPK3 promoters enabled recruitment of EP300 in monocytes, while in proliferating cancer cell lines, which actively transcribe PARP1, this protein maintained EP300 at the promoters of MA2K6 and MAPK3. Genome-wide analysis revealed a similar distribution of PARP1 and EP300 around transcription start sites and the co-occupancy of some gene promoters by PARP1 and EP300 in cancer cells. Here, we described a new RBL2/PARP1/EP300 axis which controls gene transcription regardless of the cell type. In this model cell, cycle-dependent transcription of PARP1 regulates expression of some genes repressed by RBL2 upon cell cycle limitation. Thus, RBL2 may indirectly regulate transcription of some genes by controlling the expression of EP300-recruiting PARP1. Acknowledgement: This work was financed by Polish National Science Centre grants nr DEC-2013/11/D/NZ2/00033 and DEC-2015/19/N/NZ2/01735. L.V. is funded by the National Research, Development and Innovation Office grants GINOP-2.3.2-15-2016-00020 TUMORDNS, GINOP-2.3.2-15-2016-00048-STAYALIVE and OTKA K112336. AR is supported by Polish Ministry of Science and Higher Education 776/STYP/11/2016.Keywords: retinoblastoma transcriptional co-repressor like 2 (RBL2), poly(ADP-ribose) polymerase 1 (PARP1), E1A binding protein p300 (EP300), monocytes
Procedia PDF Downloads 2092383 Correlation of Depression and Anxiety with Glycemic Control in Children with Type I Diabetes Mellitus
Authors: Sujata Sethi, Pawan Kumar, Sameer Aggarwal
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Depression and anxiety are of significant concern in youth with type 1 diabetes mellitus (T1DM) and these are correlated with glycemic control in multiple ways. The extent of depression and anxiety in children with T1DM remains poorly studied in India. The index study aimed to find the prevalence of depression and anxiety and their correlation with HbA1c (glycated hemoglobin) levels in children with T1DM. Material and methods: This study was a cross-sectional study carried out on a purposive sample of 45 children with T1DM. Depressive symptoms were assessed using Children’s Depression Rating Scale-Revised (CDRS-R) and anxiety symptoms were assessed using Spence Children’s Anxiety Scale (SCAS). Glycated hemoglobin (HbA1c) levels of all the participants were recorded. Results: 43 out of 45 children were analyzed as HbA1c status for two was not known. 48.8% were females. Mean age was 12.95+2.04. The average duration of diabetes was 3.63+1.82. Mean CDRS-R score was 41.6+12.25 and mean SCAS score was 33.07+12.29. Mean recording of HbA1c level was 7.90+1.51. 27 (62.8%) out of 43 participants had abnormal scores on CDRS-R and 24 (55.8%) out of 43 had abnormal scores on SCAS. The correlation coefficient between HbA1c levels and the CDRS-R score came out to be 0.57 and between HbA1c and SCAS, it was 0.53. Both correlations were significant with the p-value of < 0.02. Conclusion: Children with T1DM have high co-morbidity of depression and anxiety which is significantly correlated with the HbA1c levels. Thus, it becomes important to screen the patients for depression and anxiety for better outcomes.Keywords: anxiety, depression, HbA1c, T1DM
Procedia PDF Downloads 2262382 Characterization of a Novel Hemin-Binding Protein, HmuX, in Porphyromonas gingivalis W50
Authors: Kah Yan How, Peh Fern Ong, Keang Peng Song
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Porphyromonas gingivalis is a black-pigmented, anaerobic Gram-negative bacterium that is important in the progression of chronic and severe periodontitis. This organism has an essential requirement for iron, which is usually obtained from hemin, using specific membrane receptors, proteases, and lipoproteins. In this study, we report the characterization of a novel 24 kDa hemin-binding protein, HmuX, in P. gingivalis W50. The hmuX gene is 651 bp long which encodes for a 217 amino acid protein. HmuX was found to be identical at the C-terminus to the previously reported HmuY protein, differing by an additional 74 amino acids at the N-terminus. Recombinant HmuX demonstrated hemin-binding ability by LDS- PAGE and TMBZ staining. Sequence analysis of HmuX revealed a putative lipoprotein attachment site, suggesting its possible role as a lipoprotein. HmuX was also localized to the outer cell surface by transmission electron microscopy. Northern analysis showed hmuX to be transcribed as a single gene and that hmuX mRNA was tightly regulated by the availability of extra-cellular hemin. P. gingivalis isogenic mutant deficient in hmuX gene exhibited significant growth retardation under hemin-limited conditions. Taken together, these results suggest that HmuX is a hemin-binding lipoprotein, important in hemin utilization for the growth of P. gingivalis.Keywords: Porphyromonas gingivalis, periodontal diseases, HmuX, protein characterization
Procedia PDF Downloads 2222381 Role of Endonuclease G in Exogenous DNA Stability in HeLa Cells
Authors: Vanja Misic, Mohamed El-Mogy, Yousef Haj-Ahmad
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Endonuclease G (EndoG) is a well conserved mitochondrio-nuclear nuclease with dual lethal and vital roles in the cell. The aim of our study was to examine whether EndoG exerts its nuclease activity on exogenous DNA substrates such as plasmid DNA (pDNA), considering their importance in gene therapy applications. The effects of EndoG knockdown on pDNA stability and levels of encoded reporter gene expression were evaluated in the cervical carcinoma HeLa cells. Transfection of pDNA vectors encoding short-hairpin RNAs (shRNAs) reduced levels of EndoG mRNA and nuclease activity in HeLa cells. In physiological circumstances, EndoG knockdown did not have an effect on the stability of pDNA or the levels of encoded transgene expression as measured over a four day time-course. However, when endogenous expression of EndoG was induced by an extrinsic stimulus, targeting of EndoG by shRNA improved the perceived stability and transgene expression of pDNA vectors. Therefore, EndoG is not a mediator of exogenous DNA clearance, but in non-physiological circumstances it may non-specifically cleave intracellular DNA regardless of its origin. These findings make it unlikely that targeting of EndoG is a viable strategy for improving the duration and level of transgene expression from non-viral DNA vectors in gene therapy efforts.Keywords: EndoG, silencing, exogenous DNA stability, HeLa cells
Procedia PDF Downloads 4622380 C-eXpress: A Web-Based Analysis Platform for Comparative Functional Genomics and Proteomics in Human Cancer Cell Line, NCI-60 as an Example
Authors: Chi-Ching Lee, Po-Jung Huang, Kuo-Yang Huang, Petrus Tang
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Background: Recent advances in high-throughput research technologies such as new-generation sequencing and multi-dimensional liquid chromatography makes it possible to dissect the complete transcriptome and proteome in a single run for the first time. However, it is almost impossible for many laboratories to handle and analysis these “BIG” data without the support from a bioinformatics team. We aimed to provide a web-based analysis platform for users with only limited knowledge on bio-computing to study the functional genomics and proteomics. Method: We use NCI-60 as an example dataset to demonstrate the power of the web-based analysis platform and data delivering system: C-eXpress takes a simple text file that contain the standard NCBI gene or protein ID and expression levels (rpkm or fold) as input file to generate a distribution map of gene/protein expression levels in a heatmap diagram organized by color gradients. The diagram is hyper-linked to a dynamic html table that allows the users to filter the datasets based on various gene features. A dynamic summary chart is generated automatically after each filtering process. Results: We implemented an integrated database that contain pre-defined annotations such as gene/protein properties (ID, name, length, MW, pI); pathways based on KEGG and GO biological process; subcellular localization based on GO cellular component; functional classification based on GO molecular function, kinase, peptidase and transporter. Multiple ways of sorting of column and rows is also provided for comparative analysis and visualization of multiple samples.Keywords: cancer, visualization, database, functional annotation
Procedia PDF Downloads 6182379 Assessing Brain Targeting Efficiency of Ionisable Lipid Nanoparticles Encapsulating Cas9 mRNA/gGFP Following Different Routes of Administration in Mice
Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal
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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.Keywords: CRISPR, nanoparticles, brain diseases, administration routes
Procedia PDF Downloads 1012378 Evolutionary Genomic Analysis of Adaptation Genomics
Authors: Agostinho Antunes
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The completion of the human genome sequencing in 2003 opened a new perspective into the importance of whole genome sequencing projects, and currently multiple species are having their genomes completed sequenced, from simple organisms, such as bacteria, to more complex taxa, such as mammals. This voluminous sequencing data generated across multiple organisms provides also the framework to better understand the genetic makeup of such species and related ones, allowing to explore the genetic changes underlining the evolution of diverse phenotypic traits. Here, recent results from our group retrieved from comparative evolutionary genomic analyses of varied species will be considered to exemplify how gene novelty and gene enhancement by positive selection might have been determinant in the success of adaptive radiations into diverse habitats and lifestyles.Keywords: adaptation, animals, evolution, genomics
Procedia PDF Downloads 4292377 Effect of Scaling and Root Planing on Improvement of Glycemic Control in Periodontitis Patients with Type-2 Diabetes Mellitus
Authors: Shivalal Sharma, Sanjib K. Sharma, Madhab Lamsal
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Background: The aim of this study was to evaluate the clinical and laboratory changes three months after full-mouth scaling and root planing (SRP) in periodontitis patients with type 2 diabetes mellitus (DM). Methods: Forty-seven type 2 DM subjects with moderate to severe periodontitis were randomly divided into two groups. Treatment group (TG), 25 subjects, received full-mouth scaling and root planning; control group (CG), 22 subjects, received no treatment. At baseline and at the end of three months, glycated hemoglobin (HbA1c) values, fasting glucose, and clinical parameters like plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded in all the patients. Following SRP, the patients were enrolled in a monthly interval maintenance program for 3 months. Results: A statistically significant effect could be demonstrated for PI, GI, PPD, and CAL for the treatment group. HbA1c levels in the treatment group decreased significantly whereas the control group showed a slight but insignificant increase for these parameters. Conclusions: The results of this study showed that non-surgical periodontal treatment (SRP) is associated with improved glycemic control in type 2 DM patients and could be undertaken along with the standard measures for the diabetic patient care.Keywords: periodontitis, type 2 diabetes mellitus, non-surgical periodontal therapy, SRP
Procedia PDF Downloads 3002376 Al₂O₃ Nano-Particles Impact on Pseudomonas Putida Gene Expression: Implications for Environmental Risk
Authors: Nina Doskocz, Katarzyna Affek, Magdalena Matczuk, Monika Załęska-Radziwiłł
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Wastewater treatment is a critical environmental issue, especially in the face of increasing urbanization and industrialization. One of the emerging issues related to wastewater is the presence of nanoparticles (NPs) - tiny particles with dimensions measured in nanometers. These nanoparticles are widely used in various industries, including medicine, electronics, and consumer products. With technological advances, NPs are increasingly finding their way into water and wastewater systems, posing new environmental challenges that require urgent research and regulation. Therefore, research on the impact of nanoparticles on wastewater treatment processes is critical to protect environmental health and ensure sustainable development in the face of advancing nanotechnology. Traditional ecotoxicological tests are often inadequate for routine analysis as they do not provide insight into the mechanisms of toxicity of these compounds. The development of (geno)toxicity biomarkers for nanoparticles will greatly aid in the rapid assessment and prediction of the effects of current and emerging nanomaterials on various organisms. However, despite growing interest in gene expression responses to nanoparticle-induced stress, the toxic mechanisms of action and defense responses against nanoparticle toxicity remain poorly understood. The aim of our research was to investigate the expression of several molecular biomarkers related to essential cellular functions - such as oxidative stress, xenobiotic detoxification, and mitochondrial electron transport - in Pseudomonas putida in response to Al₂O₃ nanoparticles found in wastewater, both before and after biological treatment, as well as in their native form. Real-time PCR (qPCR) was used to assess gene expression changes after 1 hour and 16 hours of exposure to Al₂O₃ NPs and wastewater containing these nanoparticles, both before and after biological treatment. In addition, gene expression measurements were performed on P. putida in the presence of bulk Al₂O₃ (pristine and in wastewater). The results showed increased expression of ahpC, katE and ctaD genes, indicating oxidative stress, increased detoxification capacity and impaired mitochondrial function. Both untreated and treated wastewater containing nanoparticles caused significant changes in gene expression, demonstrating the persistent bioactivity and potential toxicity of these nanoparticles. Nanoparticles exhibited greater reactivity and bioavailability compared to their bulk counterparts.Keywords: nanoparticles, wastewater, gene expression, qPCR
Procedia PDF Downloads 172375 Screening of Potential Sources of Tannin and Its Therapeutic Application
Authors: Mamta Kumari, Shashi Jain
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Tannins are a unique category of plant phytochemicals especially in terms of their vast potential health-benefiting properties. Researchers have described the capacity of tannins to enhance glucose uptake and inhibit adipogenesis, thus being potential drugs for the treatment of non-insulin dependent diabetes mellitus. Thus, the present research was conducted to find out tannin content of food products. The percentage of tannin in various analyzed sources ranged from 0.0 to 108.53%; highest in kathaa and lowest in ker and mango bark. The percentage of tannins present in the plants, however, varies. Numerous studies have confirmed that the naturally occurring polyphenols are key factor for the beneficial effects of the herbal medicines. Isolation and identification of active constituents from plants, preparation of standardized dose & dosage regimen can play a significant role in improving the hypoglycaemic action.Keywords: tannins, diabetes, polyphenols, antioxidant, hypoglycemia
Procedia PDF Downloads 3922374 Association of Non Synonymous SNP in DC-SIGN Receptor Gene with Tuberculosis (Tb)
Authors: Saima Suleman, Kalsoom Sughra, Naeem Mahmood Ashraf
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Mycobacterium tuberculosis is a communicable chronic illness. This disease is being highly focused by researchers as it is present approximately in one third of world population either in active or latent form. The genetic makeup of a person plays an important part in producing immunity against disease. And one important factor association is single nucleotide polymorphism of relevant gene. In this study, we have studied association between single nucleotide polymorphism of CD-209 gene (encode DC-SIGN receptor) and patients of tuberculosis. Dry lab (in silico) and wet lab (RFLP) analysis have been carried out. GWAS catalogue and GEO database have been searched to find out previous association data. No association study has been found related to CD-209 nsSNPs but role of CD-209 in pulmonary tuberculosis have been addressed in GEO database.Therefore, CD-209 has been selected for this study. Different databases like ENSEMBLE and 1000 Genome Project has been used to retrieve SNP data in form of VCF file which is further submitted to different software to sort SNPs into benign and deleterious. Selected SNPs are further annotated by using 3-D modeling techniques using I-TASSER online software. Furthermore, selected nsSNPs were checked in Gujrat and Faisalabad population through RFLP analysis. In this study population two SNPs are found to be associated with tuberculosis while one nsSNP is not found to be associated with the disease.Keywords: association, CD209, DC-SIGN, tuberculosis
Procedia PDF Downloads 3092373 Identification of Anaplasma Species in Sheep of Khouzestan Province by PCR
Authors: Masoud Soltanialvar, Ali Bagherpour
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The aim of this study was to determinate the variety of Anaplasma species among sheep of khouzestan province, Iran. From April 2013 to June 2013, a total of 200 blood samples were collected via the jugular vein from healthy sheep (100), randomly. The extracted DNA from blood cells were amplified by Anaplasma-all primers, which amplify an approximately 1468bp DNA fragment from region of 16S rRNA gene from various members of the genus Anaplasma. For raising the test sensivity, the PCR products were amplified with the primers, which were designed from the region flanked by the first primers. The amplified nested PCR product had an expected PCR product with 345 nucleotides in length. In 100 sheep blood samples, 7 samples were Anaplasma spp. positive by first PCR and nested PCR. The results showed that 2 of total 100 blood samples (2%) were A.phagocytophilum positive by specific nested PCR based on 16S rRNA gene. The extracted DNA from positive Anaplasma spp. samples were amplified by Anaplasma ovis specific primers, which amplify an approximately 866bp DNA fragment from region of msp4 gene. 5 out of 100 sheep blood samples (5%) were positive for Anaplasma ovis. This study is the first molecular detection of A. ovis and A.phagocytophilum from sheep in Iran.Keywords: Iran, anaplasma species, sheep, A. ovis, A. phagocytophilum, PCR
Procedia PDF Downloads 5232372 A Comparison of Antibiotic Resistant Enterobacteriaceae: Diabetic versus Non-Diabetic Infections
Authors: Zainab Dashti, Leila Vali
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Background: The Middle East, in particular Kuwait, contains one of the highest rates of patients with Diabetes in the world. Generally, infections resistant to antibiotics among the diabetic population has been shown to be on the rise. This is the first study in Kuwait to compare the antibiotic resistance profiles and genotypic differences between the resistant isolates of Enterobacteriaceae obtained from diabetic and non-diabetic patients. Material/Methods: In total, 65 isolates were collected from diabetic patients consisting of 34 E. coli, 15 K. pneumoniae and 16 other Enterobacteriaceae species (including Salmonella spp. Serratia spp and Proteus spp.). In our control group, a total of 49 isolates consisting of 37 E. coli, 7 K. pneumoniae and 5 other species (including Salmonella spp. Serratia spp and Proteus spp.) were included. Isolates were identified at the species level and antibiotic resistance profiles, including Colistin, were determined using initially the Vitek system followed by double dilution MIC and E-test assays. Multi drug resistance (MDR) was defined as isolates resistant to a minimum of three antibiotics from three different classes. PCR was performed to detect ESBL genes (blaCTX-M, blaTEM & blaSHV), flouroquinolone resistance genes (qnrA, qnrB, qnrS & aac(6’)-lb-cr) and carbapenem resistance genes (blaOXA, blaVIM, blaGIM, blaKPC, blaIMP, & blaNDM) in both groups. Pulse field gel electrophoresis (PFGE) was performed to compare clonal relatedness of both E. coli and K.pneumonaie isolates. Results: Colistin resistance was determined in three isolates with MICs of 32-128 mg/L. A significant difference in resistance to ampicillin (Diabetes 93.8% vs control 72.5%, P value <0.002), augmentin (80% vs 52.5%, p value < 0.003), cefuroxime (69.2% vs 45%, p value < 0.0014), ceftazadime (73.8% vs 42.5%, p value <0.001) and ciprofloxacin (67.6% vs 40%, p value < 0.005) were determined. Also, a significant difference in MDR rates between the two groups (Diabetes 76.9%, control 57.5%, p value <0.036 were found. All antibiotic resistance genes showed a higher prevalence among the diabetic group, except for blaCTX-M, which was higher among the control group. PFGE showed a high rate of diversity between each group of isolates. Conclusions: Our results suggested an alarming rate of antibiotic resistance, in particular Colistin resistance (1.8%) among K. pneumoniea isolated from diabetic patients in Kuwait. MDR among Enterobacteriaceae infections also seems to be a worrying issue among the diabetics of Kuwait. More efforts are required to limit the issue of antibiotic resistance in Kuwait, especially among patients with diabetes mellitus.Keywords: antibiotic resistance, diabetes, enterobacreriacae, multi antibiotic resistance
Procedia PDF Downloads 3652371 Measures of Phylogenetic Support for Phylogenomic and the Whole Genomes of Two Lungfish Restate Lungfish and Origin of Land Vertebrates
Authors: Yunfeng Shan, Xiaoliang Wang, Youjun Zhou
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Whole-genome data from two lungfish species, along with other species, present a valuable opportunity to reassess the longstanding debate regarding the evolutionary relationships among tetrapods, lungfishes, and coelacanths. However, the use of bootstrap support has become outdated for large-scale phylogenomic data. Without robust phylogenetic support, the phylogenetic trees become meaningless. Therefore, it is necessary to re-evaluate the phylogenies of tetrapods, lungfishes, and coelacanths using novel measures of phylogenetic support specifically designed for phylogenomic data, as the previous phylogenies were based on 100% bootstrap support. Our findings consistently provide strong evidence favoring lungfish as the closest living relative of tetrapods. This conclusion is based on high gene support confidence with confidence intervals exceeding 95%, high internode certainty, and high gene concordance factor. The evidence stems from two datasets containing recently deciphered whole genomes of two lungfish species, as well as five previous datasets derived from lungfish transcriptomes. These results yield fresh insights into the three hypotheses regarding the phylogenies of tetrapods, lungfishes, and coelacanths. Importantly, these hypotheses are not mere conjectures but are substantiated by a significant number of genes. Analyzing real biological data further demonstrates that the inclusion of additional taxa diminishes the number of orthologues and leads to more diverse tree topologies. Consequently, gene trees and species trees may not be identical even when whole-genome sequencing data is utilized. However, it is worth noting that many gene trees can accurately reflect the species tree if an appropriate number of taxa, typically ranging from six to ten, are sampled. Therefore, it is crucial to carefully select the number of taxa and an appropriate outgroup while excluding fast-evolving taxa as outgroups to mitigate the adverse effects of long-branch attraction (LBA) and achieve an accurate reconstruction of the species tree. This is particularly important as more whole-genome sequencing data becomes available.Keywords: gene support confidence (GSC), origin of land vertebrates, coelacanth, two whole genomes of lungfishes, confidence intervals
Procedia PDF Downloads 872370 Genome-Wide Significant SNPs Proximal to Nicotinic Receptor Genes Impact Cognition in Schizophrenia
Authors: Mohammad Ahangari
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Schizophrenia is a psychiatric disorder with symptoms that include cognitive deficits and nicotine has been suggested to have an effect on cognition. In recent years, the advents of Genome-Wide Association Studies(GWAS) has evolved our understanding about the genetic causes of complex disorders such as schizophrenia and studying the role of genome-wide significant genes could potentially lead to the development of new therapeutic agents for treatment of cognitive deficits in schizophrenia. The current study identified six Single Nucleotide Polymorphisms (SNP) from schizophrenia and smoking GWAS that are located on or in close proximity to the nicotinic receptor gene cluster (CHRN) and studied their association with cognition in an Irish sample of 1297 cases and controls using linear regression analysis. Further on, the interaction between CHRN gene cluster and Dopamine receptor D2 gene (DRD2) during working memory was investigated. The effect of these polymorphisms on nicotinic and dopaminergic neurotransmission, which is disrupted in schizophrenia, have been characterized in terms of their effects on memory, attention, social cognition and IQ as measured by a neuropsychological test battery and significant effects in two polymorphisms were found across global IQ domain of the test battery.Keywords: cognition, dopamine, GWAS, nicotine, schizophrenia, SNPs
Procedia PDF Downloads 3462369 Synthesis of a Model Predictive Controller for Artificial Pancreas
Authors: Mohamed El Hachimi, Abdelhakim Ballouk, Ilyas Khelafa, Abdelaziz Mouhou
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Introduction: Type 1 diabetes occurs when beta cells are destroyed by the body's own immune system. Treatment of type 1 diabetes mellitus could be greatly improved by applying a closed-loop control strategy to insulin delivery, also known as an Artificial Pancreas (AP). Method: In this paper, we present a new formulation of the cost function for a Model Predictive Control (MPC) utilizing a technic which accelerates the speed of control of the AP and tackles the nonlinearity of the control problem via asymmetric objective functions. Finding: The finding of this work consists in a new Model Predictive Control algorithm that leads to good performances like decreasing the time of hyperglycaemia and avoiding hypoglycaemia. Conclusion: These performances are validated under in silico trials.Keywords: artificial pancreas, control algorithm, biomedical control, MPC, objective function, nonlinearity
Procedia PDF Downloads 307