Search results for: phenotypes

Authors: Muhammad Fiaz, Muhammad Saqlain, Abid Mahmood, S. M. Saqlan Naqvi, Rizwan Aziz Qazi, Ghazala Kaukab Raja

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Background: Metabolic Syndrome is a clustering of multiple risk factors including central obesity, hypertension, dyslipidemia and hyperglycemia. These risk phenotypes of metabolic syndrome (MetS) prevalent world-wide, Therefore we aimed to identify the frequency of risk phenotypes among metabolic syndrome subjects in local adult Pakistani population. Methods: Screening of subjects visiting out-patient department of medicine, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad was performed to assess the occurrence of risk phenotypes among MetS subjects in Pakistani population. The Metabolic Syndrome was defined based on International Diabetes Federation (IDF) criteria. Anthropometric and biochemical assay results were recorded. Data was analyzed using SPSS software (16.0). Results: Our results showed that dyslipidemia (31.50%) and hyperglycemia (30.50%) was most population specific risk phenotypes of MetS. The results showed the order of association of metabolic risk phenotypes to MetS as follows hyperglycemia>dyslipidemia>obesity >hypertension. Conclusion: The hyperglycemia and dyslipidemia were found be the major risk phenotypes among the MetS subjects and have greater chances of deceloping MetS among Pakistani Population.

Keywords: dyslipidemia, hypertention, metabolic syndrome, obesity

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Authors: Thi Thao Ninh, Yuri Trusov, José Ramón Botella

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Heterotrimeric G proteins, comprised of three subunits, α, β and γ, are involved in signal transduction pathways that mediate a vast number of processes across the eukaryotic kingdom. 23 Gα subunits are present in humans whereas most plant genomes encode for only one canonical Gα. The disparity observed between Arabidopsis, rice, and maize Gα-deficient mutant phenotypes suggest that Gα functions have diversified between eudicots and monocots during evolution. Alternatively, since the only Gα mutations available in dicots have been produced in Arabidopsis, the possibility exists that this species might be an exception to the rule. In order to test this hypothesis, we studied the G protein α subunit (TGA1) in tomato. Four tga1 knockout lines were generated in tomato cultivar Moneymaker using CRISPR/Cas9. The tga1 mutants exhibit a number of auxin-related phenotypes including changes in leaf shape, reduced plant height, fruit size and number of seeds per fruit. In addition, tga1 mutants have increased sensitivity to abscisic acid during seed germination, reduced sensitivity to exogenous auxin during adventitious root formation from cotyledons and excised hypocotyl explants. Our results suggest that Gα mutant phenotypes in tomato are very similar to those observed in monocots, i.e. rice and maize, and cast doubts about the validity of using Arabidopsis as a model system for plant G protein studies.

Keywords: auxin-related phenotypes, CRISPR/Cas9, G protein α subunit, heterotrimeric G proteins, tomato

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Authors: Lina E. Homman, Alexis C. Edwards, Seung Bin Cho, Danielle M. Dick, Kenneth S. Kendler

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Research supports an association between alcohol problems and internalising symptoms, but the understanding of how the two phenotypes relate to each other is poor. It has been hypothesized that the relationship between the phenotypes is causal; however investigations in regards to direction are inconsistent. Clarity of the relationship between the two phenotypes may be provided by investigating the phenotypes developmental inter-relationships longitudinally. The objective of the study was to investigate a) changes in alcohol problems and internalising symptoms in college students across time and b) the direction of effect of growth between alcohol problems and internalising symptoms from late adolescent to emerging adulthood c) possible gender differences. The present study adds to the knowledge of comorbidity of alcohol problems and internalising symptoms by examining a longitudinal sample of college students and by examining the simultaneous development of the symptoms. A sample of college students is of particular interest as symptoms of both phenotypes often have their onset around this age. A longitudinal sample of college students from a large, urban, public university in the United States was used. Data was collected over a time period of 2 years at 3 time points. Latent growth models were applied to examine growth trajectories. Parallel process growth models were used to assess whether initial level and rate of change of one symptom affected the initial level and rate of change of the second symptom. Possible effects of gender and ethnicity were investigated. Alcohol problems significantly increased over time, whereas internalizing symptoms remained relatively stable. The two phenotypes were significantly correlated in each wave, correlations were stronger among males. Initial level of alcohol problems was significantly positively correlated with initial level of internalising symptoms. Rate of change of alcohol problems positively predicted rate of change of internalising symptoms for females but not for males. Rate of change of internalising symptoms did not predict rate of change of alcohol problems for either gender. Participants of Black and Asian ethnicities indicated significantly lower levels of alcohol problems and a lower increase of internalising symptoms across time, compared to White participants. Participants of Black ethnicity also reported significantly lower levels of internalising symptoms compared to White participants. The present findings provide additional support for a positive relationship between alcohol problems and internalising symptoms in youth. Our findings indicated that both internalising symptoms and alcohol problems increased throughout the sample and that the phenotypes were correlated. The findings mainly implied a bi-directional relationship between the phenotypes in terms of significant associations between initial levels as well as rate of change. No direction of causality was indicated in males but significant results were found in females where alcohol problems acted as the main driver for the comorbidity of alcohol problems and internalising symptoms; alcohol may have more detrimental effects in females than in males. Importantly, our study examined a population-based longitudinal sample of college students, revealing that the observed relationships are not limited to individuals with clinically diagnosed mental health or substance use problems.

Keywords: alcohol, comorbidity, internalising symptoms, longitudinal modelling

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Authors: Kinnsley Travis, Camerron M. Crowder

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Mapk8ip3 (Mitogen-Activated Protein Kinase 8 Interacting Protein 3) is a gene that codes for the JIP3 protein, which is a part of the JIP scaffolding protein family. This protein is involved in axonal vesicle transport, elongation and regeneration. Variants in the Mapk8ip3 gene are associated with a rare-genetic condition that results in a neurodevelopmental disorder that can cause a range of phenotypes including global developmental delay and intellectual disability. Currently, there are 18 known individuals diagnosed to have sequenced confirmed Mapk8ip3 genetic disorders. This project focuses on examining the impact of a subset of missense patient variants on the Jip3 protein function by overexpressing the mRNA of these variants in a zebrafish knockout model for Jip3. Plasmids containing cDNA with individual missense variants were reverse transcribed, purified, and injected into single-cell zebrafish embryos (Wild Type, Jip3 -/+, and Jip3 -/-). At 6-days post mRNA microinjection, morphological, behavioral, and microscopic phenotypes were examined in zebrafish larvae. Morphologically, we compared the size and shape of the zebrafish during their development over a 5-day period. Total locomotive activity was assessed using the Microtracker assay and patterns of movement over time were examined using the DanioVision assay. Lastly, we used confocal microscopy to examine sensory axons for swelling and shortened length, which are phenotypes observed in the loss-of-function knockout Jip3 zebrafish model. Using these assays during embryonic development, we determined the impact of various missense variants on Jip3 protein function, compared to knockout and wild-type zebrafish embryo models. Variants in the gene Mapk8ip3 cause rare-neurodevelopmental disorders due to an essential role in axonal vesicle transport, elongation and regeneration. A subset of missense variants was examined by overexpressing the mRNA of these variants in a Jip3 knock-out zebrafish. Morphological, behavioral, and microscopic phenotypes were examined in zebrafish larvae. Using these assays, the spectrum of disorders can be phenotypically determined and the impact of variant location can be compared to knockout and wild-type zebrafish embryo models.

Keywords: rare disease, neurodevelopmental disorders, mrna overexpression, zebrafish research

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Authors: Ayse Ozge Demir, Nihat Mert

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In this research, Kilis and Honamli goats are used, which are specific local genetic resources of Turkey. The herds were independent, but they had similar care and nutrition circumstances. From each breed 30 samples were taken, in all 120 samples were collected. Erytrocyte, all blood and serum samples were used for hemoglobine (Hb), glutathione (GSH) and Tf with Cp analysis, respectively. In the analysis of this samples, Hb and Tf bands were determined by electrophoresis. However, Cp and GSH levels were analyzed by the spectrophotometer. Three Hb phenotypes (AA, BB, AB) and Six Tf phenotypes (AA, AB, AC, BB, BC, CC) were determined in this study. In addition, both the observed and the expected values of polymorphic characteristic for 2 characters were presented according to the Hardy-Weinberg Equilibrium (HWE). Cp levels were detected as 0.822 ± 0.055 mg/dl and 1.793 ± 0.109 mg/dl in Kilis and Honamli herds, respectively. GSH levels were detected as, 42,486 ± 1,034 mg/dl and 33.515 ± 0.345 mg/dl in these breeds, respectively,. On the other hand, the high and low GSH levels (GSHH and GSHh) of herds were presented.

Keywords: electrophoresis, gene resource, goat, spectrophotometer

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Authors: Qiao Fan, Xiaobo Guo, Junxian Zhu, Xiaohu Ding, Ching-Yu Cheng, Tien-Yin Wong, Mingguang He, Heping Zhang, Xueqin Wang

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A systematic, simultaneous analysis of multiple phenotypes in genome-wide association studies (GWASs) draws a great attention to integrate the signals from single phenotypes with increased power. However, lacking an interpretable and efficient multivariate GWAS analysis impede the application of such approach. In this study, we propose to decompose the multivariate model into a series of simple univariate models. This transformation illuminates what exactly the individual trait contributes to the significant signals from the multivariate analyses. By employing our approach in the analysis of three myopia-related endophenotypes from the Singapore Malay Eye Study (SIMES), we identify novel candidate loci which were successfully validated in an independent Guangzhou Twin Eye Study (GTES).

Keywords: GWAS multivariate, multiple traits, myopia, association

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Authors: Vivian Correa

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Hypothesis There are typical patterns - phenotypes - of sleep behaviors by age and biological sex groups of parasomnia patients where wearable devices could avoid injuries. Materials and methods We analyzed public video records on sleep-related behaviors likely representing parasomnias, looking for phenotypes in different groups. We searched public internet databases using the keywords “sleepwalking”, “sleep eating,” “sleep sex”, and “aggression in sleep” in six languages. Poor-quality vide-records and those showing apparently faked sleep behaviors were excluded. We classified the videos into estimated sex and age (children, adults, elderly) groups; scored the activity types by a self-made scoring scale; and applied binary logistic regression for analyzing the association between sleep behaviors versus the groups by STATA package providing 95% confidence interval and the probability of statistical significance. Results 224 videos (102 women) were analyzed. The odds of sleepwalking and related dangerous behaviors were lower in the elderly than in adults (P<0.025). Females performed complex risky behaviors during sleepwalking more often than males (P<0.012). Elderly people presented emotional behaviors less frequently than adults (P<0.004), and females showed them twice often as males. Elderly males had 40-fold odds compared to adults and children to perform aggressive movements and 70-fold odds of complex movements in the bed compared to adults. Conclusion Unlike other groups, the high chances of adults being sleepwalkers and elderly males performing intense and violent movements in bed showed us the importance of developing wearable parasomnia devices to prevent injuries.

Keywords: parasomnia, wearable devices, sleepwalking, RBD

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Authors: Lauren A. Bailey, Amber R. Childs, Nicola C. James, Murray I. Duncan, Alexander Winkler, Warren M. Potts

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For the persistence of fished populations in the Anthropocene, it is critical to predict how fished populations will respond to the coupled threats of exploitation and climate change for adaptive management. The resilience of fished populations will depend on their capacity for physiological plasticity and acclimatization in response to environmental shifts. However, there is evidence for the selection of physiological traits by capture fisheries. Hence, fish populations may have a limited scope for the rapid expansion of their tolerance ranges or physiological adaptation under fishing pressures. To determine the physiological vulnerability of fished populations in the Anthropocene, the metabolic performance was compared between a fished and spatially protected Chrysoblephus laticeps population in response to thermal variability. Individual aerobic scope phenotypes were quantified using intermittent flow respirometry by comparing changes in energy expenditure of each individual at ecologically relevant temperatures, mimicking variability experienced as a result of upwelling and downwelling events. The proportion of high and low-performance individuals were compared between the fished and spatially protected population. The fished population had limited aerobic scope phenotype diversity and fewer high-performance phenotypes, resulting in a significantly lower aerobic scope curve across low (10 °C) and high (24 °C) thermal treatments. The performance of fished populations may be compromised with predicted future increases in cold upwelling events. This requires the conservation of the physiologically fittest individuals in spatially protected areas, which can recruit into nearby fished areas, as a climate resilience tool.

Keywords: climate change, fish physiology, metabolic shifts, over-fishing, respirometry

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Authors: Varsha Gupta, Priya Datta, Gursimran Mohi, Jagdish Chander

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Fluoroquinolones form the mainstay of therapy for the treatment of infections due to Salmonella enterica subsp. enterica. There is a complex interplay between several resistance mechanisms for quinolones and various fluoroquinolones discs, giving varying results, making detection and interpretation of fluoroquinolone resistance difficult. For detection of fluoroquinolone resistance in Salmonella ssp., we compared the use of pefloxacin and nalidixic acid discs as surrogate marker. Using MIC for ciprofloxacin as the gold standard, 43.5% of strains showed MIC as ≥1 μg/ml and were thus resistant to fluoroquinoloes. Based on the performance of nalidixic acid and pefloxacin discs as surrogate marker for ciprofloxacin resistance, both the discs could correctly detect all the resistant phenotypes; however, use of nalidixic acid disc showed false resistance in the majority of the sensitive phenotypes. We have also tested newer antimicrobial agents like cefixime, imipenem, tigecycline and azithromycin against Salmonella spp. Moreover, there was a comeback of susceptibility to older antimicrobials like ampicillin, chloramphenicol, and cotrimoxazole. We can also use cefixime, imipenem, tigecycline and azithromycin in the treatment of multidrug resistant S. typhi due to their high susceptibility.

Keywords: salmonella, pefloxacin, surrogate marker, chloramphenicol

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Authors: Muhammad Fiaz, Muhammad Saqlain, Bernard M. Y. Cheung, S. M. Saqlan Naqvi, Ghazala Kaukab Raja

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Background: Association of C allele of rs662799 SNP of APOA5 gene with metabolic syndrome (MetS) has been reported in different populations around the world. A case control study was conducted to explore the relationship of rs662799 variants (T/C) with the MetS and the associated risk phenotypes in a population of Pakistani origin. Methods: MetS was defined according to the IDF criteria. Blood samples were collected from the Pakistan Institute of Medical Sciences, Islamabad, Pakistan for biochemical profiling and DNA extraction. Genotyping of rs662799 was performed using mass ARRAY, iPEX Gold technology. A total of 712 unrelated case and control subjects were genotyped. Data were analyzed using Plink software and SPSS 16.0. Results: The risk allele C of rs662799 showed highly significant association with MetS (OR=1.5, Ρ=0.002). Among risk phenotypes, dyslipidemia, and obesity showed strong association with SNP (OR=1.49, p=0.03; OR =1.46, p=0.01) respectively in models adjusted for age and gender. Conclusion: The rs662799C allele is a significant risk marker for MetS in the local Pakistani population studied. The effect of the SNP is more on dyslipidemia than the other components of the MetS.

Keywords: metabolic syndrome, APOA5, rs662799, dyslipidemia, obesity

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Authors: Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza S. Baig

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Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1 to M2 phenotypes decides the nature, duration, and severity of an inflammatory response. However, inspite of a substantial understanding of the fate of these phenotypes, the underlying molecular mechanisms are not well understood. We have investigated the role of Neuronal nitric oxide synthase (NOS1) mediated regulation of Activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of jun, Fos, and ATF family proteins. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and jun interaction which induces IL12 & IL23 expression. Pharmacological inhibition of NOS1 inhibits Fos and jun interaction but increases ATF2 and Fos dimerization. Switching of Fos and jun dimer to ATF2 and jun dimerization switches phenotype from IL–12high IL-23high IL-10low to IL–12low IL-23lowIL-10high phenotype, respectively. Together, these findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.

Keywords: inflammation, macrophage, lipopolysaccharide (LPS), proinflammatory cytokines, activator protein 1 (AP-1), neuronal nitric oxide synthase (NOS1)

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Authors: V. V. Lakshmi, Y. V. S. Annapurna

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Urinary tract infection (UTI) is one of the most common infectious diseases seen in the community. Susceptible individuals experience multiple episodes, and progress to acute pyelonephritis or uro-sepsis or develop asymptomatic bacteriuria (ABU). Ability to cause extraintestinal infections depends on several virulence factors required for survival at extraintestinal sites. Presence of virulence phenotypes enhances the pathogenicity of these otherwise commensal organisms and thus augments its ability to cause extraintestinal infections, the most frequent in urinary tract infections(UTI). The present study focuses on detection of the virulence characters exhibited by the uropathogenic organism and most common factors exhibited in the local pathogens. A total of 700 isolates of E.coli and Klebsiella spp were included in the study. These were isolated from patients from local hospitals reported to be suffering with UTI over a period of three years. Isolation and identification was done based on Gram character and IMVIC reactions. Antibiotic sensitivity profile was carried out by disc diffusion method and multi drug resistant strains with MAR index of 0.7 were further selected.. Virulence features examined included their ability to produce exopolysaccharides, protease- gelatinase production, hemolysin production, haemagglutination and hydrophobicity test. Exopolysaccharide production was most predominant virulence feature among the isolates when checked by congo red method. The biofilms production examined by microtitre plates using ELISA reader confirmed that this is the major factor contributing to virulencity of the pathogens followed by hemolysin production

Keywords: Escherichia coli, Klebsiella sp, Uropathogens, Virulence features.

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Authors: V. V. Lakshmi, Y. V. S. Annapurna

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Urinary tract infection (UTI) is one of the most common infectious diseases seen in the community. Susceptible individuals experience multiple episodes, and progress to acute pyelonephritis or uro-sepsis or develop asymptomatic bacteriuria (ABU). Ability to cause extraintestinal infections depends on several virulence factors required for survival at extraintestinal sites. Presence of virulence phenotypes enhances the pathogenicity of these otherwise commensal organisms and thus augments its ability to cause extraintestinal infections, the most frequent in urinary tract infections(UTI). The present study focuses on detection of the virulence characters exhibited by the uropathogenic organism and most common factors exhibited in the local pathogens. A total of 700 isolates of E.coli and Klebsiella spp were included in the study.These were isolated from patients from local hospitals reported to be suffering with UTI over a period of three years. Isolation and identification was done based on Gram character and IMVIC reactions. Antibiotic sensitivity profile was carried out by disc diffusion method and multi drug resistant strains with MAR index of 0.7 were further selected. Virulence features examined included their ability to produce exopolysaccharides, protease- gelatinase production, hemolysin production, haemagglutination and hydrophobicity test. Exopolysaccharide production was most predominant virulence feature among the isolates when checked by congo red method. The biofilms production examined by microtitre plates using ELISA reader confirmed that this is the major factor contributing to virulencity of the pathogens followed by hemolysin production.

Keywords: Escherichia coli, Klebsiella spp, Uropathogens, virulence features

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Authors: Ngoc-Hieu Vu

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A study was conducted to estimate the record keeping, genetic selection, educational experience, and farm management effect on monthly milk yield per farm, average milk yield per cow, monthly milk revenue per farm, and monthly milk revenue per cow of dairy farms in the Southern region of Vietnam. The dataset contained 5448 monthly record collected from January 2013 to May 2015. Results showed that longer experience increased (P < 0.001) monthly milk yields and revenues. Better educated farmers produced more monthly milk per farm and monthly milk per cow and revenues (P < 0.001) than lower educated farmers. Farm that kept records on individual animals had higher (P < 0.001) for monthly milk yields and revenues than farms that did not. Farms that used hired people produced the highest (p < 0.05) monthly milk yield per farm, milk yield per cow and revenues, followed by farms that used both hire and family members, and lowest values were for farms that used family members only. Farms that used crosses Holstein in herd were higher performance (p < 0.001) for all traits than farms that used purebred Holstein and other breeds. Farms that used genetic information and phenotypes when selecting sires were higher (p < 0.05) for all traits than farms that used only phenotypes and personal option. Farms that received help from Vet, organization staff, or government officials had higher monthly milk yield and revenues than those that decided by owner. These findings suggest that dairy farmers should be training in systematic, must be considered and continuous support to improve farm milk production and revenues, to increase the likelihood of adoption on a sustainable way.

Keywords: dairy farming, education, milk yield, Southern Vietnam

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Authors: Helen K. Buteme, Rebecca Axelsson-Robertson, Moses L. Joloba, Henry W. Boom, Gunilla Kallenius, Markus Maeurer

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Background: The Ugandan population is heavily affected by infectious diseases and Human leukocyte antigen (HLA) diversity plays a crucial role in the host-pathogen interaction and affects the rates of disease acquisition and outcome. The identification of HLA class 1 alleles and determining which alleles are associated with tuberculosis (TB) outcomes would help in screening individuals in TB endemic areas for susceptibility to TB and to predict resistance or progression to TB which would inevitably lead to better clinical management of TB. Aims: To be able to determine the HLA class 1 phenotype distribution in a Ugandan TB cohort and to establish the relationship between these phenotypes and active and latent TB. Methods: Blood samples were drawn from 32 HIV negative individuals with active TB and 45 HIV negative individuals with latent MTB infection. DNA was extracted from the blood samples and the DNA samples HLA typed by the polymerase chain reaction-sequence specific primer method. The allelic frequencies were determined by direct count. Results: HLA-A*02, A*01, A*74, A*30, B*15, B*58, C*07, C*03 and C*04 were the dominant phenotypes in this Ugandan cohort. There were differences in the distribution of HLA types between the individuals with active TB and the individuals with LTBI with only HLA-A*03 allele showing a statistically significant difference (p=0.0136). However, after FDR computation the corresponding q-value is above the expected proportion of false discoveries (q-value 0.2176). Key findings: We identified a number of HLA class I alleles in a population from Central Uganda which will enable us to carry out a functional characterization of CD8+ T-cell mediated immune responses to MTB. Our results also suggest that there may be a positive association between the HLA-A*03 allele and TB implying that individuals with the HLA-A*03 allele are at a higher risk of developing active TB.

Keywords: HLA, phenotype, tuberculosis, Uganda

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Authors: Irshad Ali Khan, Jian-Ping Lu, Xiao-Hong Liu, Fu-Cheng Lin

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This study reports the functional analysis of a gene MoNUC1 in M. oryzae, which is homologous to the Saccharomyces cerevisiae NUC1 encoding a mitochondrial nuclease protein. The MoNUC1 having a gene locus MGG_05324 is 1002-bp in length and encodes an identical protein of 333 amino acids. We disrupted the gene through gene disruption strategy and isolated two mutants confirmed by southern blotting. The deleted mutants were then used for phenotypic studies and their phenotypes were compared to those of the Guy-11 strain. The mutants were first grown on CM medium to find the effect of MoNUC1 gene disruption on colony growth and the mutants were found to show normal culture colony growth similar to that of the Guy-11 strain. Conidial germination and appressorial formation were also similar in both the mutants and Guy-11 strains showing that this gene plays no significant role in these phenotypes. For pathogenicity, the mutants and Guy-11 mycelium blocks were inoculated on blast susceptible barley seedlings and it was found that both the strains exhibited full pathogenicity showing coalesced and necrotic blast lesions suggesting that this gene is not involved in pathogenicity. Mating of the mutants with 2539 strain formed numerous perithecia showing that MoNUC1 is not essential for sexual reproduction in M. oryzae. However, the mutants were found to form reduced conidia (1.06±8.03B and 1.08±9.80B) than those of the Guy-11 strain (1.46±10.61A) and we conclude that this protein is not required for the blast fungus to cause pathogenicity but plays significant role in conidiation. Proteins of signal transduction pathways that could be disrupted/ intervened genetically or chemically could lead to antifungal products of important fungal cereal diseases and reduce rice yield losses. Tipping the balance toward understanding the whole of pathogenesis, rather than simply conidiation will take some time, but clearly presents the most exciting challenge of all.

Keywords: appressorium formation, conidiation, NUC1, Magnaporthe oryzae, pathogenicity

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Authors: Gary J. Pickering, Sarah Lucas, Catherine E. Klodnicki, Nicole J. Gaudette

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Two taste pheno types that are of interest in the study of habitual diet-related risk factors and disease are 6-n-propylthiouracil (PROP) responsiveness and thermal tasting. Individuals differ considerable in how intensely they experience the bitterness of PROP, which is partially explained by three major single nucleotide polymorphisms associated with the TAS2R38 gene. Importantly, this variable responsiveness is a useful proxy for general taste responsiveness, and links to diet-related disease risk, including body mass index, in some studies. Thermal tasting - a newly discovered taste phenotype independent of PROP responsiveness - refers to the capacity of many individuals to perceive phantom tastes in response to lingual thermal stimulation, and is linked with TRPM5 channels. Thermal tasters (TTs) also experience oral sensations more intensely than thermal non-tasters (TnTs), and this was shown to associate with differences in self-reported food preferences in a previous survey from our lab. Here we report on two related studies, where we sought to determine whether PROP responsiveness and thermal tasting would associate with perceptual differences in the oral sensations elicited by sampled energy-dense foods, and whether in turn this would influence liking. We hypothesized that hyper-tasters (thermal tasters and individuals who experience PROP intensely) would (a) rate sweet and high-fat foods more intensely than hypo-tasters, and (b) would differ from hypo-tasters in liking scores. (Liking has been proposed recently as a more accurate measure of actual food consumption). In Study 1, a range of energy-dense foods and beverages, including table cream and chocolate, was assessed by 25 TTs and 19 TnTs. Ratings of oral sensation intensity and overall liking were obtained using gVAS and gDOL scales, respectively. TTs and TnTs did not differ significantly in intensity ratings for most stimuli (ANOVA). In a 2nd study, 44 female participants sampled 22 foods and beverages, assessing them for intensity of oral sensations (gVAS) and overall liking (9-point hedonic scale). TTs (n=23) rated their overall liking of creaminess and milk products lower than did TnTs (n=21), and liked milk chocolate less. PROP responsiveness was negatively correlated with liking of food and beverages belonging to the sweet or sensory food grouping. No other differences in intensity or liking scores between hyper- and hypo-tasters were found. Taken overall, our results are somewhat unexpected, lending only modest support to the hypothesis that these taste phenotypes associate with energy-dense food liking and consumption through differences in the oral sensations they elicit. Reasons for this lack of concordance with expectations and some prior literature are discussed, and suggestions for future research are advanced.

Keywords: taste phenotypes, sensory evaluation, PROP, thermal tasting, diet-related health risk

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Authors: Shivani Sharma, Prashant Saxena, Inamul Hasan Madar

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Since the time of Darwin, it has been considered that genetic change is the direct indicator of variation in phenotype. But a few studies in system biology in the past years have proposed that epigenetic developmental processes also affect the phenotype thus shifting the focus from a linear genotype-phenotype map to a non-linear G-P map. In this paper, we attempt at explaining the evolution of colour vision in mammals by taking LWS/ Long-wave sensitive gene under consideration.

Keywords: evolution, phenotypes, epigenetics, LWS gene, G-P map

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Authors: Rosa Tsegaye Aga, Xuan Jiang, Pavel Vazquez Faci, Siqing Liu, Simon Rayner, Endalkachew Alemu, Markos Abebe

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Tuberculosis (TB) is a major cause of disease globally. In most cases, TB is treatable and curable, but only with the proper treatment. There is a time when drug-resistant TB occurs when bacteria become resistant to the drugs that are used to treat TB. Current strategies to identify drug-resistant TB bacteria are laboratory-based, and it takes a longer time to identify the drug-resistant bacteria and treat the patient accordingly. But machine learning (ML) and data science approaches can offer new approaches to the problem. In this study, we propose to develop an ML-based model to predict the antibiotic resistance phenotypes of TB isolates in minutes and give the right treatment to the patient immediately. The study has been using the whole genome sequence (WGS) of TB isolates as training data that have been extracted from the NCBI repository and contain different countries’ samples to build the ML models. The reason that different countries’ samples have been included is to generalize the large group of TB isolates from different regions in the world. This supports the model to train different behaviors of the TB bacteria and makes the model robust. The model training has been considering three pieces of information that have been extracted from the WGS data to train the model. These are all variants that have been found within the candidate genes (F1), predetermined resistance-associated variants (F2), and only resistance-associated gene information for the particular drug. Two major datasets have been constructed using these three information. F1 and F2 information have been considered as two independent datasets, and the third information is used as a class to label the two datasets. Five machine learning algorithms have been considered to train the model. These are Support Vector Machine (SVM), Random forest (RF), Logistic regression (LR), Gradient Boosting, and Ada boost algorithms. The models have been trained on the datasets F1, F2, and F1F2 that is the F1 and the F2 dataset merged. Additionally, an ensemble approach has been used to train the model. The ensemble approach has been considered to run F1 and F2 datasets on gradient boosting algorithm and use the output as one dataset that is called F1F2 ensemble dataset and train a model using this dataset on the five algorithms. As the experiment shows, the ensemble approach model that has been trained on the Gradient Boosting algorithm outperformed the rest of the models. In conclusion, this study suggests the ensemble approach, that is, the RF + Gradient boosting model, to predict the antibiotic resistance phenotypes of TB isolates by outperforming the rest of the models.

Keywords: machine learning, MTB, WGS, drug resistant TB

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Authors: Mustafa Malki, Ewan R. Pearson

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Tools utilized by health care practitioners to flag potential adverse drug reactions secondary to drug-drug interactions ignore individual genetic variation, which has the potential to markedly alter the severity of these interactions. To our best knowledge, there have been limited published studies on the impact of genetic variation on drug-drug interactions. Therefore, our aim in this project is the discovery of previously unrecognized, clinically important drug-drug-gene interactions (DDGIs) within the list of most commonly used drug combinations in the UK. The UKBB database was utilized to identify the top most frequently prescribed drug combinations in the UK with at least one route of interaction (over than 200 combinations were identified). We have recognised 37 common and unique interacting genes considering all of our drug combinations. Out of around 600 potential genetic variants found in these 37 genes, 100 variants have met the selection criteria (common variant with minor allele frequency ≥ 5%, independence, and has passed HWE test). The association between these variants and the use of each of our top drug combinations has been tested with a case-control analysis under the log-additive model. As the data is cross-sectional, drug intolerance has been identified from the genotype distribution as presented by the lower percentage of patients carrying the risky allele and on the drug combination compared to those free of these risk factors and vice versa with drug tolerance. In GoDARTs database, the same list of common drug combinations identified by the UKBB was utilized here with the same list of candidate genetic variants but with the addition of 14 new SNPs so that we have a total of 114 variants which have met the selection criteria in GoDARTs. From the list of the top 200 drug combinations, we have selected 28 combinations where the two drugs in each combination are known to be used chronically. For each of our 28 combinations, three drug response phenotypes have been identified (drug stop/switch, dose decrease, or dose increase of any of the two drugs during their interaction). The association between each of the three phenotypes belonging to each of our 28 drug combinations has been tested against our 114 candidate genetic variants. The results show replication of four findings between both databases : (1) Omeprazole +Amitriptyline +rs2246709 (A > G) variant in CYP3A4 gene (p-values and ORs with the UKBB and GoDARTs respectively = 0.048,0.037,0.92,and 0.52 (dose increase phenotype)) (2) Simvastatin + Ranitidine + rs9332197 (T > C) variant in CYP2C9 gene (0.024,0.032,0.81, and 5.75 (drug stop/switch phenotype)) (3) Atorvastatin + Doxazosin + rs9282564 (T > C) variant in ABCB1 gene (0.0015,0.0095,1.58,and 3.14 (drug stop/switch phenotype)) (4) Simvastatin + Nifedipine + rs2257401 (C > G) variant in CYP3A7 gene (0.025,0.019,0.77,and 0.30 (drug stop/switch phenotype)). In addition, some other non-replicated, but interesting, significant findings were detected. Our work also provides a great source of information for researchers interested in DD, DG, or DDG interactions studies as it has highlighted the top common drug combinations in the UK with recognizing 114 significant genetic variants related to drugs' pharmacokinetic.

Keywords: adverse drug reactions, common drug combinations, drug-drug-gene interactions, pharmacogenomics

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Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

Abstract:

Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

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Authors: Mhaned Oubounyt, Jan Baumbach

Abstract:

Differences in co-expression networks between two or multiple cells (sub)types across conditions is a pressing problem in single-cell RNA sequencing (scRNA-seq). A key challenge is to define those co-variations that differ between or among cell types and/or conditions and phenotypes to examine small regulatory networks that can explain mechanistic differences. To this end, we developed SCANet, an all-in-one Python package that uses state-of-the-art algorithms to facilitate the workflow of a combined single-cell GCN (Gene Correlation Network) and GRN (Gene Regulatory Networks) pipeline, including inference of gene co-expression modules from scRNA-seq, followed by trait and cell type associations, hub gene detection, co-regulatory networks, and drug-gene interactions. In an example case, we illustrate how SCANet can be applied to identify regulatory drivers behind a cytokine storm associated with mortality in patients with acute respiratory illness. SCANet is available as a free, open-source, and user-friendly Python package that can be easily integrated into systems biology pipelines.

Keywords: single-cell, co-expression networks, drug-gene interactions, co-regulatory networks

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Authors: T. Büyüksırıt, H. Kuleaşan

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Natural antimicrobials are used to preserve foods that can be found in plants, animals, and microorganisms. Antimicrobial substances are natural or artificial agents that produced by microorganisms or obtained semi/total chemical synthesis are used at low concentrations to inhibit the growth of other microorganisms. Food borne pathogens and spoilage microorganisms are inactivated by the use of antagonistic microorganisms and their metabolites. Yeasts can produce toxic proteins or glycoproteins (toxins) that cause inhibition of sensitive bacteria and yeast species. Antimicrobial substance producing phenotypes belonging different yeast genus were isolated from different sources. Toxins secreted by many yeast strains inhibiting the growth of other yeast strains. These strains show antimicrobial activity, inhibiting the growth of mold and bacteria. The effect of antimicrobial agents produced by yeasts can be extremely fast, and therefore may be used in various treatment procedures. Rapid inhibition of microorganisms is possibly caused by microbial cell membrane lipopolysaccharide binding and in activation (neutralization) effect. Antimicrobial agents inhibit the target cells via different mechanisms of action.

Keywords: antimicrobial agents, yeast, toxic protein, glycoprotein

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Authors: Mingxi Zhou, Jiří Kubásek, Iva Mozgová

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In Arabidopsis thaliana, histone 3 lysine 27 tri-methylation catalysed byPRC2 is playing essential functions in the regulation of plant development, growth, and reproduction[1-2]. Despite numerous studies related to the role of PRC2 in developmental control, how PRC2 works in the operational control in plants is unknown. In the present, the evidence that PRC2 probably participates in the regulation of retrograde singalling pathway in Arabidopsisis found. Firstly, we observed that the rosette size and biomass in PRC2-depletion mutants (clf-29 and swn-3) is significantly higher than WTunder medium light condition (ML: 125 µmol m⁻² s⁻²), while under medium high light condition (MHL: 300 µmol m⁻² s-2), the increase was reverse. Under ML condition, the photosynthesis related parameters determined by fluorCam did not show significant differences between WT and mutants, while the pigments concentration increased in the leaf of PRC2-depletion mutants, especially in swn. The dynamic of light-responsive genes and circadian clock genes expression by RT-qPCRwithin 24 hours in the mutants were comparable to WT. However, we observed upregulation of photosynthesis-associated nuclear genes in the PRC2-depletion mutants under chloroplast damaging condition (treated by lincomycin), corresponding to the so-called genome uncoupled (gun) phenotype. Here, we will present our results describing these phenotypes and our suggestion and outlook for studying the involvement of PRC2 in chloroplast-to-nucleus retrograde signalling.

Keywords: PRC2, retrograde signalling, light acclimation, photosyntheis

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Authors: Young-Ji Kim, Jin-Hyeong Park, Hong-Seok Kim, Jung-Whan Chon, Kwang-Yeop Kim, Dong-Hyeon Kim, Il-Byeong Kang, Da-Na Jeong, Jin-Hyeok Yim, Ho-Seok Jang, Kwang-Young Song, Kun-Ho Seo

Abstract:

Stenotrophomonas maltophilia is one of the emerging opportunistic pathogens, and also known to have extensive drug resistance intrinsically including carbepenems which is last resort for most serious infections. One possible way for S. maltophilia to infect human is via wastewater treatment plant (WWTP). In the period between October 2016 and February 2017, effluent samples of WWTP from 3 different pig farms were collected once a month and screened for isolation of S. maltophilia. Total 16 strains of S. maltophilia were isolated and, the antibiotic susceptibility phenotypes were determined by Vitek 2 system for 16 antibiotics, ampicillin (AMP), amoxicillin/clavulanic acid (AMC), piperacillin/tazobactam (TZP), cefazolin (CZ), cefoxitin (FOX), cefotaxime (CTX), ceftazidime (CAZ), cefepime (FEP), aztreonam (AZT), ertapenem (ETP), imipenem (IMP), amikacin (AK), gentamicin (GN), ciprofloxacin (CIP), tigecycline (TGC) and trimethoprim/sulfamethoxazole (SXT). All isolates showed high resistance to AMP (100%), CZ (100%), FOX (100%), CTX (100%), CAZ (100%), FEP (94%), AZT (100%), ETP (100%), IMP (100%), AK (100%), GN (100%) whereas were susceptible to CIP (0%), TGC (0%), SXT (6%). All strains harbored at least one of the antibiotic resistance determinant such as spgM, rmlA, and rpfF. Some isolates had similar MLST (multilocus sequence typing) types with clinical isolates, suggesting WWTP could have potential role in the transmission of S. maltophilia to aquatic environment and, possibly, to humans.

Keywords: Stenotrophomonas maltophilia, Carbapenem resistance, waste water treatment plant, pig farm

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Authors: Neena Kanojia, R. K. Kanojia

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Background: Osteoarthritis OA of the knee is one of the leading causes of disability characterized by degeneration of hyaline cartilage combined with reparative processes. Its strong association with metabolic syndrome is postulated to be due to both mechanical and biochemical factors. Our study aims to study differential effect of metabolic risk factors on cartilage degeneration and regeneration at biomarker level. Design: After screening 281 patients presenting with knee pain, 41 patients who met the selection criteria were included and were divided into metabolic MetS OA and non-metabolic Non-MetS OA phenotypes using National Cholesterol Education Programme-Adult Treatment Panel-III NCEP ATP III criteria for metabolic syndrome. Serum Cartilage Oligomeric Matrix Protein COMP and Procollagen type IIA N terminal Propeptide PIIANP levels were used as tools to assess cartilage degeneration and regeneration, respectively. Results: 22 among 41 patients 53.66% had metabolic syndrome. Covariates like age, gender, Kellgren Lawrence KL grades were comparable in both groups. MetS OA group showed significant increase in serum COMP levels (p 0.03 with no significant effect on serum PIIANP levels (p 0.46. Hypertriglyceridemia showed independent association with both cartilage anabolism (p 0.03 and catabolism (p 0.03. Conclusion: Metabolic syndrome, though has no effect on cartilage regeneration tends to shift cartilage homeostasis towards degeneration with hypertriglyceridemia showing significant independent effect on cartilage metabolism.

Keywords: metabolic, syndrome, cartilage, degernation

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Authors: H. Sakamoto, J. Tochimoto, S. Kurosawa, M. Suzuki, S. Oguri

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Salt stress adversely affects plant growth at various stages of development including seed germination, seedling establishment, vegetative growth and finally reproduction. Because of their immobile nature, plants have evolved mechanisms to sense and respond to salt stress. Seed dormancy is an adaptive trait that enables seed germination to coincide with favorable environmental conditions. We identified a novel locus of Arabidopsis, designated SHG1 (salt hypersensitive germination 1), whose disruption leads to reduced germination rate under moderate salt stress conditions. SHG1 encodes a transmembrane protein with an ankyrin repeat motif that has been implicated in diverse cellular processes such as signal transduction. The SGH1-disrupted Arabidopsis mutant died at the cotyledon stage when sown on salt-containing medium, although wild type plants could form true leaves under the same conditions. On the other hand, this mutant showed similar phenotypes to wild type plants when sown on medium without salt and transferred to salt-containing medium at the vegetative stage. These results suggested that SHG1 played indispensable role in the seed germination and seedling establishment under moderate salt stress conditions. SHG1 may be involved in the release of seed dormancy.

Keywords: germination, ankyrin repeat, arabidopsis, salt tolerance

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Authors: Ligia Florio, João Mauricio Castaldelli-Maia

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Background: Food addiction (FA) emerged in the 1990s as a possible contributor to the increasing prevalence of obesity and overweight, in conjunction with changing food environments and mental health conditions. However, FA is not yet listed as one of the disorders in the DSM-5 and/or the ICD-11. Although there are controversies and debates in the literature about the classification and construct of FA, the most common approach to access it is the use of a research tool - the Yale Food Addiction Scale (YFAS) - which approximates the concept of FA to the concept diagnosis of dependence on psychoactive substances. There is a need to explore the dimensional phenotypes accessed by YFAS in different population groups for a better understanding and scientific support of FA diagnoses. Methods: The primary objective of this project was to investigate the construct validity of the FA concept by mYFAS 2.0 in individuals who underwent bariatric surgery (n = 100) at the Hospital Estadual Mário Covas since 2011. Statistical analyzes were conducted using the STATA software. In this sense, structural or factor validity was the type of construct validity investigated using exploratory factor analysis (EFA) and item response theory (IRT) techniques. Results: EFA showed that the one-dimensional model was the most parsimonious. The IRT showed that all criteria contributed to the latent structure, presenting discrimination values greater than 0.5, with most presenting values greater than 2. Conclusion: This study reinforces a FA dimension in patients who underwent bariatric surgery. Within this dimension, we identified the most severe and discriminating criteria for the diagnosis of FA.

Keywords: obesity, food addiction, bariatric surgery, regain

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Authors: Mukund Ramchandra Mogarekar, Pankaj Kumar, Shraddha Vilas More

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Background: Myocardial infarction (MI) is defined as myocardial cell death due to prolonged ischemia as a consequence of atherosclerosis. TC, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), Apo B, and lipoprotein(a) was found as atherogenic factors while high-density lipoprotein cholesterol (HDL-C) was anti-atherogenic. Methods and Results: The study group consists of 40, MI subjects and 40 healthy individuals in control group. PON 1 Arylesterase activity (ARE) was measured by using phenylacetate. Phenotyping was done by double substrate method, serum AOPP by using chloramine T and Apo B by Turbidimetric immunoassay. PON 1 ARE activities were significantly lower (p< 0.05) and AOPPs & Apo B were higher in MI subjects (p> 0.05). Trimodal distribution of QQ, QR, and RR phenotypes of study population showed no significant difference among cases and controls (p> 0.05). Univariate binary logistic regression analysis showed independent association of TC, HDL, LDL, AOPP, Apo B, and PON 1 ARE activity with MI and multiple forward binary logistic regression showed PON 1 ARE activity and serum Apo B as an independent predictor of MI. Conclusions: Decrease in PON 1 ARE activity in MI subjects than in controls suggests increased oxidative stress in MI which is reflected by significantly increased AOPP and Apo B. PON1 polymorphism of QQ, QR and RR showed no significant difference in protection against MI. Univariate and multiple binary logistic regression showed PON1 ARE activity and serum Apo B as an independent predictor of MI.

Keywords: advanced oxidation protein product, apolipoprotein B, PON 1 arylesterase activity, myocardial infarction

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Authors: Nunthawan Nowwarote, Waleerat Sukarawan, Prasit Pavasant, Thanaphum Osathanon

Abstract:

Interleukin 6 (IL-6) is a multifunctional cytokine, regulating various biological responses in several tissues. A Recent study shows that IL-6 plays a role in stemness maintenance in stem cells isolated from human exfoliated deciduous teeth (SHEDs). However, the role of IL-6 on cell differentiation in SHEDs remains unknown. The present study investigated the effect of IL-6 on SHEDs differentiation. Cells were isolated from dental pulp tissues of human deciduous teeth. Flow cytometry was used to determined mesenchymal stem cell marker expression, and the multipotential differentiation (osteogenic, adipogenic and neurogenic lineage ) was also determined. The mRNA was determined using real-time quantitative polymerase chain reaction, and the phenotypes were confirmed by chemical and immunofluorescence staining. Results demonstrated that SHEDs expressed CD44, CD73, CD90, CD105 but not CD45. Further, the up-regulation of osteogenic, adipogenic and neurogenic marker genes was observed upon maintaining cells in osteogenic, adipogenic and neurogenic induction medium, respectively. The addition of IL-6 induced osteogenic by up-regulated osteogenic marker gene also increased in vitro mineralization. Under neurogenic medium supplement with IL-6, up-regulated neurogenic marker. Whereas, an addition of IL-6 attenuated adipogenic differentiation by SHEDs. In conclusion, this evidence implies that IL-6 may participate in cells differentiation ability of SHEDs.

Keywords: SHEDs, IL-6, cell differentiations, dental pulp

Procedia PDF Downloads 139