Search results for: altered methionine metabolism

Authors: Morteza Khashehchi, Kamel Hooman

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Thermal effects on the dynamics and stability of the flow past a circular cylinder operating in the mixed convection regime is studied experimentally for Reynolds number (ReD) between 1000 and 4000, and different cylinder wall temperatures (Tw) between 25 and 75°C by means of Particle Image Velocimetry (PIV). The experiments were conducted in a horizontal wind tunnel with the heated cylinder placed horizontally. With such assumptions, the direction of the thermally induced buoyancy force acting on the fluid surrounding the heated cylinder would be perpendicular to the flow direction. In each experiment, to acquire 3000 PIV image pairs, the temperature and Reynolds number of the approach flow were held constant. By adjusting different temperatures in different Reynolds numbers, the corresponding Richardson number (RiD = Gr/Re^2) was varied between 0:0 (unheated) and 10, resulting in a change in the heat transfer process from forced convection to mixed convection. With increasing temperature of the wall cylinder, significant modifications of the wake flow pattern and wake vortex shedding process were clearly revealed. For cylinder at low wall temperature, the size of the wake and the vortex shedding process are found to be quite similar to those of an unheated cylinder. With high wall temperature, however, the high temperature gradient in the wake shear layer creates a type of vorticity with opposite sign to that of the shear layer vorticity. This temperature gradient vorticity weakens the strength of the shear layer vorticity, causing delay in reaching the recreation point. In addition to the wake characteristics, the shedding frequency for the heated cylinder is determined for all aforementioned cases. It is found that, as the cylinder wall is heated, the organization of the vortex shedding is altered and the relative position of the first detached vortices with respect to the second one is changed. This movement of the first detached vortex toward the second one increases the frequency of the shedding process. It is also found that the wake closure length decreases with increasing the Richardson number.

Keywords: heated cylinder, PIV, wake, Reynolds number

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Authors: Alina Goldberg Cavalleri, Sara Franco Ortega, Nawaporn Onkokesung, Richard Dale, Melissa Brazier-Hicks, Robert Edwards

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Non-target site based resistance (NTSR) to herbicides in weeds is a polygenic trait associated with the upregulation of proteins involved in xenobiotic detoxification and translocation we have termed the xenome. Among the xenome proteins, ABC transporters play a key role in enhancing herbicide metabolism by effluxing conjugated xenobiotics from the cytoplasm into the vacuole. The importance of ABC transporters is emphasized by the fact that they often contribute to multidrug resistance in human cells and antibiotic resistance in bacteria. They also play a key role in insecticide resistance in major vectors of human diseases and crop pests. By surveying available databases, transcripts encoding ABCs have been identified as being enhanced in populations exhibiting NTSR in several weed species. Based on a transcriptomics data in black grass (Alopecurus myosuroides, Am), we have identified three proteins from the ABC-C subfamily that are upregulated in NTSR populations. ABC-C transporters are poorly characterized proteins in plants, but in Arabidopsis localize to the vacuolar membrane and have functional roles in transporting glutathionylated (GSH)-xenobiotic conjugates. We found that the up-regulation of AmABCs strongly correlates with the up-regulation of a glutathione transferase termed AmGSTU2, which can conjugate GSH to herbicides. The expression profile of the ABC transcripts was profiled in populations of black grass showing different degree of resistance to herbicides. This, together with a phylogenetic analysis, revealed that AmABCs cluster in different groups which might indicate different substrate and roles in the herbicide resistance phenotype in the different populations

Keywords: black grass, herbicide, resistance, transporters

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Authors: Nitin Pipralia, Amit Kmar Sinha, Gudrun de Boeck

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Atmospheric carbon dioxide (CO2) concentrations have been increasing since the beginning of the industrial revolution due to combustion of fossils fuel and many anthropogenic means. As the number of scenarios assembled by the International Panel on Climate Change (IPCC) predict a rise of pCO2 from today’s 380 μatm to approximately 900 μatm until the year 2100 and a further rise of up to 1900 μatm by the year 2300. A rise in pCO2 results in more dissolution in ocean surface water which lead to cange in water pH, This phenomena of decrease in ocean pH due to increase on pCO2 is ocean acidification is considered a potential threat to the marine ecosystems and expected to affect fish as well as calcerious organisms. The situation may get worste when the stress of salinity adds on, due to migratory movement of fishes, where fish moves to different salinity region for various specific activities likes spawning and other. Therefore, to understand the interactive impact of these whole range of two important environmental abiotic stresses (viz. pCO2 ranging from 380 μatm, 900 μatm and 1900 μatm, along with salinity gradients of 32ppt, 10 ppt and 2.5ppt) on the ecophysiologal performance of fish, we investigated various biological adaptive response in European sea bass (Dicentrarchus labrax), a model estuarine teleost. Overall, we hypothesize that effect of ocean acidification would be exacerbate with shift in ambient salinity. Oxygen consumption, ammonia metabolism, iono-osmoregulation, energy budget, ion-regulatory enzymes, hormones and pH amendments in plasma were assayed as the potential indices of compensatory responses.

Keywords: ocean acidification, sea bass, pH climate change, salinity

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Authors: Szilvia Várallyay, Béla Kovács, Éva Bódi, Farzeneh Garousi, Szilvia Veres

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Arsenic (As) is a naturally occurring substance that can be present in soil, water and air. Vegetables, fruits, and other plants that grow in contaminated soils which are able to accumulate arsenic. Arsenic when presents in plant cells, has various negative physiological effects and when presents in soil will be inorgaic form, namely arsenite (As(III)) and arsenate (As(V)). These two forms of arsenic disrupt plant metabolism by inhibiting its growth and these arsenic species has negative effect on nutrient uptake. A rhizobox experiment was conducted to investigate the effect of arsenite and arsenate on root growth of sunflower seedlings. Sunflower plants were grown in climatic room under irradiance of 300 µmol m-2 s-1, 16-h day and 8-h night photoperiod, day/night temperature of 25/20°C and relative humidity of 65-75%. We applied arsenic in form of arsenite (NaAsO2) and arsenate (KH2AsO4), respectively. The applied arsenic treatments was 0, 10, 30, 90 mg.kg-1. After disinfection, seeds were germinated between moist filter papers. Seedlings with 2-3 cm coleoptils were placed into rhizoboxes. In the rhizoboxes the growing and daily growing rhythm of roots of sunflower can be followed up, moreover possible phytotoxic symptoms of roots resulting from increasing arsenic can be seen. Weights of rhizoboxes were measured daily and also evaporated water added each day. The lengths of roots were measured daily until seedlings roots get at the end of the rhizoboxes. Negative correlation was observed between the higher concentration of arsenic in the soil and the growth of sunflower seedlings roots. The effect of arsenic toxicity was more considerable in 90 mg.kg-1 arsenic treatment than lower concentration. The same arsenite concentration causes slower growth in case of sunflower plant than the same arsenate concentration produced.

Keywords: arsenic, rhizobox experiment, sunflower, root growth

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Authors: Angelis P. Barlampas

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Purpose of Learning Objective: This case depicts the need for cooperation between the emergency department and the radiologist to achieve the best diagnostic result for the patient. The clinical picture must correlate well with the radiology report and when it does not, this is not necessarily someone’s fault. Careful interpretation and good knowledge of the limitations, advantages and disadvantages of each imaging procedure are essential for the final diagnostic goal. Methods or Background: A patient was brought to the emergency department by their relatives. He was suddenly confused and his mental status was altered. He hadn't any history of mental illness and was otherwise healthy. A computing tomography scan without contrast was done, but it was unremarkable. Because of high clinical suspicion of probable neurologic disease, he was admitted to the hospital. Results or Findings: Another T was done after 48 hours. It showed a hypodense region in both thalamic areas. Taking into account that the first CT was normal, but the initial clinical picture of the patient was alerting of something wrong, the repetitive CT exam is highly suggestive of a probable diagnosis of bilateral thalamic infractions. Differential diagnosis: Primary bilateral thalamic glioma, Wernicke encephalopathy, osmotic myelinolysis, Fabry disease, Wilson disease, Leigh disease, West Nile encephalitis, Greutzfeldt Jacob disease, top of the basilar syndrome, deep venous thrombosis, mild to moderate cerebral hypotension, posterior reversible encephalopathy syndrome, Neurofibromatosis type 1. Conclusion: As is the case of limitations for any imaging procedure, the same applies to CT. The acute ischemic attack can not depict on CT. A period of 24 to 48 hours has to elapse before any abnormality can be seen. So, despite the fact that there are no obvious findings of an ischemic episode, like paresis or imiparesis, one must be careful not to attribute the patient’s clinical signs to other conditions, such as toxic effects, metabolic disorders, psychiatric symptoms, etc. Further investigation with MRI or at least a repeated CT must be done.

Keywords: CNS, CT, thalamus, emergency department

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Authors: Thinakar Mani Balusamy, Venkateswaran A. R., Bharat Narasimhan, Ratnakar Kini S., Kani Sheikh M., Prem Kumar K., Pugazhendi Thangavelu, Arun Murugan, Sibi Thooran Karmegam, Radhakrishnan N., Mohammed Noufal, Amit Soni

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Background and Aims: The liver is integral to lipid metabolism, and a compromise in its function leads to perturbations in these pathways. In this study, we hope to determine the correlation between CLD severity and its effect on lipid parameters. We also look at the etiology-specific effects on lipid levels. Materials and Methods: This is a retrospective cross-sectional analysis of 250 patients with cirrhosis compared to 250 healthy age and sex-matched controls. Severity assessment of CLD using MELD and Child-Pugh scores was performed and etiological details collected. A questionnaire was used to obtain patient demographic details and lastly, a fasting lipid profile (Total, LDL, HDL cholesterol, Triglycerides and VLDL) was obtained. Results: All components of the lipid profile declined linearly with increasing severity of CLD as determined by MELD and Child-Pugh scores. Lipid levels were clearly lower in CLD patients as compared to healthy controls. Interestingly, preliminary analysis indicated that CLD of different etiologies had differential effects on Lipid profiles. This aspect is under further analysis. Conclusion: All components of the lipid profile were definitely lower in CLD patients as compared to controls and demonstrated an inverse correlation with increasing severity. The utilization of this parameter as a prognosticating aid requires further study. Additionally, preliminary analysis indicates that various CLD etiologies appear to have specific effects on the lipid profile – a finding under further analysis.

Keywords: CLD, cholesterol, HDL, LDL, lipid profile, triglycerides, VLDL

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Authors: Rostika Flora, Muhammad Zulkarnain, Syokumawena

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Background: Aerobic physical exercises are recommended to keep body fit and healthy although physical exercises themselves can increase body metabolism and oxygen and can lead into tissue hypoxia. Oxygen pressure can serve as Vascular Endhothelial Growth Factor (VEGF) regulator. Hypoxia increases gene expression of VEGF through ascendant regulation of HIF-1. VEGF is involved in regulating angiogenesis process. Aerobic physical exercises can increase the concentration of VEGF in brain and enables angiogenesis process. We have investigated the influence of aerobic physical exercise to the VGEF concentration of wistar rat’s brain. Methods: This was experimental study using post test only control group design. Independent t-test was used as statistical test. The samples were twenty four wistar rat (Rattus Norvegicus) which were divided into four groups: group P1 (control group), group P2 (treatment group with once-a-week exercise), group P3 (treatment group with three time-a-week exercise), and group P4 (treatment group with seven time-a-week exercise). Group P2, P3, and P4 were treated with treadmil with speed of 20 m/minute for 30 minutes. The concentration of VEGF was determined by ELISA. Results: There was a significant increase of VEGF in treatment group compared with control one (<0.05). The maximum increase was found in group P2 (129.02±64.49) and the minimum increase was in group P4 (96.98±11.20). Conclusion: The frequency of aerobic physical exercises influenced the concentration of Vascular Endhothelial Growth Factor (VEGF) of brain tissue of Rattus Norvegicus.

Keywords: brain tissue, hypoxia, physical exercises, vascular endhothelial growth factor

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Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le, Chi V. Phan

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Wilson’s disease (WD) is an autosomal recessive disorder of the copper metabolism, which is caused by a mutation in the copper-transporting P-type ATPase (ATP7B). The mechanism of this disease is the failure of hepatic excretion of copper to bile, and leads to copper deposits in the liver and other organs. The ATP7B gene is located on the long arm of chromosome 13 (13q14.3). This study aimed to investigate the gene mutation in the Vietnamese patients with WD, and make a presymptomatic diagnosis for their familial members. Forty-three WD patients and their 65 siblings were identified as having ATP7B gene mutations. Genomic DNA was extracted from peripheral blood samples; 21 exons and exon-intron boundaries of the ATP7B gene were analyzed by direct sequencing. We recognized four mutations ([R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G) in the sum of 20 detectable mutations, accounting for 87.2% of the total. Mutation S105* was determined to have a high rate (32.6%) in this study. The hotspot regions of ATP7B were found at exons 2, 16, and 8, and intron 14, in 39.6 %, 11.6 %, 9.3%, and 7 % of patients, respectively. Among nine homozygote/compound heterozygote siblings of the patients with WD, three individuals were determined as asymptomatic by screening mutations of the probands. They would begin treatment after diagnosis. In conclusion, 20 different mutations were detected in 43 WD patients. Of this number, four novel mutations were explored, including [R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G. The mutation S105* is the most prevalent and has been considered as a biomarker that can be used in a rapid detection assay for diagnosis of WD patients. Exons 2, 8, and 16, and intron 14 should be screened initially for WD patients in Vietnam. Based on risk profile for WD, genetic testing for presymptomatic patients is also useful in diagnosis and treatment.

Keywords: ATP7B gene, mutation detection, presymptomatic diagnosis, Vietnamese Wilson’s disease

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Authors: Omkar Gaonkar, Indumathi Nambi, Suresh G. Kumar

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The functional and morphological aspects of soil structure determine the soil quality. The dispersion of colloidal soil particles, especially the clay fraction and rupture of soil aggregates, both of which play an important role in soil structure development, lead to degradation of soil quality. The main objective of this work was to determine the effect of the behaviour of soil colloids on the agricultural soil structure and quality. The effect of commercial humic acid and soil natural organic matter on the electrical and structural properties of the soil colloids was also studied. Agricultural soil, belonging to the sandy loam texture class from northern part of India was considered in this study. In order to understand the changes in the soil quality in the presence and absence of humic acids, the soil fabric and structure was analyzed by X-ray diffraction (XRD), Fourier Transform Infrared (FTIR) Spectroscopy and Scanning Electron Microscopy (SEM). Electrical properties of natural soil colloids in aqueous suspensions were assessed by zeta potential measurements at varying pH values with and without the presence of humic acids. The influence of natural organic matter was analyzed by oxidizing the natural soil organic matter with hydrogen peroxide. The zeta potential of the soil colloids was found to be negative in the pH range studied. The results indicated that hydrogen peroxide treatment leads to deflocculation of colloidal soil particles. In addition, the humic acids undergoes effective adsorption onto the soil surface imparting more negative zeta potential to the colloidal soil particles. The soil hydrophilicity decreased in the presence of humic acids which was confirmed by surface free energy determination. Thus, it can be concluded that the presence of humic acids altered the soil fabric and structure, thereby affecting the soil quality. This study assumes significance in understanding soil aggregation and the interactions at soil solid-liquid interface.

Keywords: humic acids, natural organic matter, zeta potential, soil quality

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Authors: Maha Alhussain, Moira A Taylor, Ian A. Macdonald

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Background: It is well established that dietary composition has effects on metabolism and therefore impacts on health; however other aspects of diet, such as meal pattern, could also be important in both obesity management and promoting health. The present study investigated the effect of irregular meal frequency on anthropometric measurements and energy expenditure (EE) in healthy women. Design: 11 healthy weight women (18–40 years) were studied in a randomized crossover trial with two phases of 2 weeks each. In Phase 1, participants consumed either a regular meal pattern (6 meals/day) or an irregular meal pattern (varying from 3 to 9 meals/day). In Phase 2, participants followed the alternative meal pattern to that followed in Phase 1, after a 2-weeks washout period. In the two phases, identical foods were provided to a participant in amounts designed to keep body weight constant. Participants came to the laboratory after an overnight fast at the start and end of each phase. EE was measured in fasting state by indirect calorimetry. Postprandial EE was measured during the 3 h period after consumption of a milkshake, test drink. Results: There were no significant changes in body weight and anthropometric measurements after both meal pattern interventions. There was also no significant difference in mean daily energy intake between the regular and irregular meal pattern (2043 ±31 and 2099 ±33 respectively). EE in the fasting state showed no significant differences cross the experiment visits. There was a significant difference in Postprandial EE (measured for 3 h) by visit (P=0.04). Postprandial EE after the regular meal pattern was significantly higher than at baseline (P=0.002) or than after the irregular meal pattern (P= 0.04). Conclusion: Eating regularly for 14-day period significantly increases Postprandial EE which may contribute to weight loss and obesity management.

Keywords: energy expenditure, energy intake, meal pattern, weight loss

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Authors: Abhishek Soti, Aditya Sharma, Akhilendra Bhushan Gupta

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Fouled reverse osmosis membranes are primarily characterized by Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectrometer (EDS) for a detailed investigation of foulants; however, this has severe limitations on several accounts. Apart from inaccuracy in spectral properties and inevitable interferences and interactions between sample and instrument, misidentification of elements due to overlapping peaks is a significant drawback of EDS. This paper discusses this limitation by analyzing fouled polyamide RO membranes derived from community RO plants of Rajasthan treating brackish water via a combination of results obtained from EDS and Raman spectroscopy and cross corroborating with ICP-MS analysis of water samples prepared by dissolving the deposited salts. The anomalous behavior of different morphic forms of CaCO₃ in aqueous suspensions tends to introduce false reporting of the presence of certain heavy metals and rare earth metals in the scales of the fouled RO membranes used for treating brackish groundwater when analyzed using the commonly adopted techniques like SEM-EDS or Raman spectrometry. Peaks of CaCO₃ reflected in EDS spectra of the membrane were found to be misinterpreted as Scandium due to the automatic assignment of elements by the software. Similarly, the morphic forms merged with the dominant peak of CaCO₃ might be reflected as a single peak of Molybdenum in the Raman spectrum. A subsequent ICP-MS analysis of the deposited salts showed that both Sc and Mo were below detectable levels. It is always essential to cross-confirm the results through a destructive analysis method to avoid such interferences. It is further recommended to study different morphic forms of CaCO₃ scales, as they exhibit anomalous properties like reverse solubility with temperature and hence altered precipitation tendencies, for an accurate description of the composition of scales, which is vital for the smooth functioning of RO systems.

Keywords: reverse osmosis, foulant analysis, groundwater, EDS, artifacts

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Authors: Abdul Soofi, Katherine Wolf, Egon Ranghini, Gregory Dressler

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Obesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions. In mice, the TGF-β superfamily is implicated in the regulation of white and brown adipose tissues differentiation. The Kielin/Chordin-like Protein (KCP) is a secreted regulator of the TGF-β superfamily pathways that can inhibit both TGF-β and Activin signals while enhancing the Bone Morphogenetic protein (BMP) signaling. However, the effects of KCP on metabolism and obesity have not been studied in animal models. Thus, we examined the effects of KCP loss or gain of function in mice that were maintained on either a regular or a high fat diet. Loss of KCP sensitized mice to obesity and associated complications such as hepatic steatosis and glucose intolerance. In contrast, transgenic mice that expressed KCP in the kidney, liver and adipose tissues were resistant to developing high fat diet induced obesity and had significantly reduced white adipose tissue. KCP over-expression was able to shift the pattern of Smad signaling in vivo, to increase the levels of P-Smad1 and decrease P-Smad3, resulting in resistance to high fat diet induced hepatic steatosis and glucose intolerance. In aging mice, loss of KCP promoted liver pathology even when mice were fed a normal diet. The data demonstrate that shifting the TGF-β superfamily signaling with a secreted inhibitor or enhancer can alter the physiology of adipose tissue to reduce obesity and can inhibit the initiation and progression of hepatic steatosis to significantly reduce the effects of high fat diet induced metabolic disease.

Keywords: adipose tissue, KCP, obesity, TGF-β, BMP, hepatic steatosis, metabolic syndrome

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Authors: Al Ameen H., Rakesh P.

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To improve the combustion efficiency of fuels and to reduce the emissions of pollutants as well as to improve heat transfer characteristics of fuels, both non-metallic and metallic nanoparticles can be added into it. By varying the concentration and size of nano particles added into the fuels, behaviour of droplet combustion and hence heat generated can be altered. In case of solid or liquid fuels, surface area of the fuel in contact with oxidizer(gaseous) is small because of higher density compared to gases. If the surface area of fuel exposed to the oxidizer is very small, then the combustion will not occur, because the combustion rate is proportional to the surface area of fuel droplet. To avoid such instance there is a way to increase the exposed surface area. To increase the specific surface area available for reaction, the particle size can be reduced. If the additives are solid then by reducing the particles size the specific surface area of liquid fuel can be increased. For the liquid fuels the exposed surface area available for combustion can be increased by suspending nanoparticles. Addition of non-metallic and metallic nanoparticles in fuels improves its combustion efficiency by enhancing the thermo-physical properties. The burn rate constants and temperatures of Kerosene-Oxygen combustion for fuel droplet sizes of 50μm, 75μm, 100μm and 125μm under varying concentrations of 25%, 50%, 75% and 100% are studied numerically and its characteristic velocities are determined. Later the burn rate constants of fuel with concentrations of 0.5%, 1.0% and 2.0% by weight of aluminium nanoparticles are added. The spray combustion characteristics of such nano-fuel has improved the combustion temperature by the addition of aluminium nanoparticles. Thus, aluminium nanoparticles have improved burn rate and characteristic velocity of Kerosene-Oxygen combustion. An increase of 40% in characteristic velocity is observed.

Keywords: burn rate, characteristic velocity, combustion, thermo-physical properties

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Authors: Soudeh Tabashi, Mohammadreza Moshari, Parisa Sezari

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Introduction: Postoperative analgesia in Orthotopic Liver Transplantation (OLT) surgery is challenging for anesthesiologists. Although OLT is one of the most extensive abdominal operations, it seems that patients don’t suffer from severe post operative pain. On the other hands drug metabolism is unpredictable due to unknown graft function. The aim of this study was to compare intraoperative infusion of remifentanil versus fentanyl in postoperative opioid demand in patients with OLT and evaluating the complications in two groups. Method: In this double-blind clinical trial 34 patients who had OLT were included. They divided randomly in two groups of Remifentanil (R) and Fentanyl (F). Patients in group R and F received infusion of Remifentanil 0.3-1 µg/Kg/min and Fentanyl 0.3-1 µg/Kg/min during maintenance of anesthesia. Post operative pain were measured in 6, 12, 18, 24 hours and second and third days after surgery with Numeric Rate Scale (NRS). Patients had received intravenous acetaminophen as rescue therapy with NRS of 3 or more. In addition to demographic information, post operative opioid consumption were recorded as the primary outcome. Intraoperative blood transfusion, intraoperative inotropic drugs consumption, weaning time and intensive care unit stay were also evaluated. Results: Total dose of acetaminophen consumption in first 3 days after surgery did not have significant difference between two groups (Pvalue=0.716). intraoperative inotrope consumption, blood transfusion and post operative weaning time and ICU stay were also similar in both groups. Conclusion: This study demonstrates that intraoperative infusion of remifentanil in OLT have the same effect on post operative pain management as fentanyl. Despite the complications of operation were not increased by remifentanil.

Keywords: liver transplantation, postoperative pain, remifentanil, fentanyl

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Authors: Vincent Murray

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The chromatin structure at the transcription start sites (TSSs) of genes is very important in the control of gene expression. In order for gene expression to occur, the chromatin structure at the TSS has to be altered so that the transcriptional machinery can be assembled and RNA transcripts can be produced. In particular, the nucleosome structure and positioning around the TSS has to be changed. Bleomycin is utilized as an anti-tumor agent to treat Hodgkin's lymphoma, squamous cell carcinoma, and testicular cancer. Bleomycin produces DNA damage in human cells and DNA strand breaks, especially double-strand breaks, are thought to be responsible for the cancer chemotherapeutic activity of bleomycin. Bleomycin is a large glycopeptide with molecular weight of approximately 1500 Daltons and hence its DNA strand cleavage activity can be utilized as a probe of chromatin structure. In this project, Illumina next-generation DNA sequencing technology was used to determine the position of DNA double-strand breaks at the TSSs of genes in intact cells. In this genome-wide study, it was found that bleomycin cleavage preferentially occurred at the TSSs of actively transcribed human genes in comparison with non-transcribed genes. There was a correlation between the level of enhanced bleomycin cleavage at TSSs and the degree of transcriptional activity. In addition, bleomycin was able to determine the position of nucleosomes at the TSSs of human genes. Bleomycin analogues were also utilized as probes of chromatin structure at the TSSs of human genes. In a similar manner to bleomycin, the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin preferentially cleaved at the TSSs of human genes. Interestingly this degree of enhanced TSS cleavage inversely correlated with the cytotoxicity (IC50 values) of BLM analogues. This indicated that the degree of cleavage by bleomycin analogues at the TSSs of human genes was very important in the cytotoxicity of bleomycin and analogues. It also provided a deeper insight into the mechanism of action of this cancer chemotherapeutic agent since actively transcribed genes were preferentially targeted.

Keywords: anti-cancer activity, chromatin structure, cytotoxicity, gene expression, next-generation DNA sequencing

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Authors: Marcel Duh, Jadranka Stricevic, David Halozan, Dusan Celan

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Back pain is not only the result of structural or biomechanical abnormalities of the spine but is also associated with cognitive and behavioral aspects of pain and thus represents biopsychosocial problem. Stressors are not only interpersonal conflicts, negative life events, and dangerous situations but also noise. Effects of noise on human beings are psychological (excitement, stress), sensory, and physiological. The harmful effects of noise can be seen in the 40-65 dB range and are manifested as fatigue, irritability, poor sleep and psychological discomfort of the worker. Within 65-90 dB range, body metabolism increases, oxygen consumption is higher, tachycardia and hypertension appear, and the tone of skeletal muscles increases. The purpose of the study was to determine whether the stress caused by noise at the work place increases the incidence of back pain. Measurements of noise levels were carried out in three different wards of social care institution. The measurement on each ward was repeated 3 times (total of 9 measurements) for 8 hours during the morning shift. The device was set up in the room where clients spent most of the day. The staff on the ward replied to the questionnaire consisting of closed type questions about basic demographic information and information about back pain. We find that noise levels as measured in our study had no statistically significant effect on the incidence of back pain (p = 0.90). We also find that health care workers who perceive their work as stressful, have more back pain than those who perceive their job as unstressful, but correlation is statistically insignificant (p = 0.682). With our study, we have proven findings of other authors, that noise level below 65 dB does not have a significant influence on the incidence of back pain.

Keywords: health care workers, musculoskeletal disorder, noise, sick leave

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Authors: Angela Maria Sarmiento

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Since the end of the 19th century, the Bora people struggled to survive two stages of colonial domination, which resulted in situations of forced contact with the Western world. Their inclusion in global designs altered the configuration of their local spaces and social practices; thus the Bora language was affected and prone to transformation. This descriptive, interpretive study, within the indigenous and minoritized groups’ research field, aimed at analysing the linguistic attitudes as well as the contextual situation of the Bora language in Providencia, an ancestral territory and a speech community contained in the midst of the Colombian Amazon rainforest. Through the inquiry of their sociolinguistic practices, this study also considered the effects of the course of events derived from the rubber exploitation in the late 19th century, and the arrival of the Capuchin’s mission in the early 20th century. The methodology used in this study had an ethnographic approach, which allowed the researcher to study the social phenomena from the perspective of the participants. Fieldwork, diary, field notes, and semi-structured interviews were conducted and then triangulated with participant observations. The findings of this study suggest that there is a transition from current individual bilingualism towards Spanish monolingualism; this is enhanced by the absence of a functional distribution of the three varieties (Bora, Huitoto, and Spanish). Also, the positive attitudes towards the Spanish language are based on its functionality while positive attitudes towards the Bora language mostly refer to pride and identity. Negative attitudes are only directed towards the Bora language. In the search for the roots of these negative attitudes, appeared the traumatic experiences of the rubber exploitation and the indigenous experiences at the capuchin’s boarding school. Finally, the situation of the Bora language can be configured as a social fact strongly connected to previous years of colonial dominations and to the current and continuous incursion of new global-colonial designs.

Keywords: Bora language, language contact, linguistic attitudes, speech communities

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Authors: M. Ntšolo, D. Kalumba, N. Lefu, G. Letlatsa

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Rock mass damage due to shear tectonic activity has been investigated largely in geoscience where fluid transport is of major interest. However, little has been studied on the effect of shear zones on rock mass behavior and its impact on stability of rock slopes. At Letšeng Diamonds open pit mine in Lesotho, the shear zone composed of sheared kimberlite material, calcite and altered basalt is forming part of the haul ramp into the main pit cut 3. The alarming rate at which the shear zone is deteriorating has triggered concerns about both local and global stability of pit the walls. This study presents the numerical modelling of the open pit slope affected by shear zone at Letšeng Diamond Mine (LDM). Analysis of the slope involved development of the slope model by using a two-dimensional finite element code RS2. Interfaces between shear zone and host rock were represented by special joint elements incorporated in the finite element code. The analysis of structural geological mapping data provided a good platform to understand the joint network. Major joints including shear zone were incorporated into the model for simulation. This approach proved successful by demonstrating that continuum modelling can be used to evaluate evolution of stresses, strain, plastic yielding and failure mechanisms that are consistent with field observations. Structural control due to geological shear zone structure proved to be important in its location, size and orientation. Furthermore, the model analyzed slope deformation and sliding possibility along shear zone interfaces. This type of approach can predict shear zone deformation and failure mechanism, hence mitigation strategies can be deployed for safety of human lives and property within mine pits.

Keywords: numerical modeling, open pit mine, shear zone, slope stability

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Authors: Morenike Abimbola Adeleye, Anthony Temidayo Bolarinwa

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The genesis of talc bodies around Wonu, Ibadan-Apomu area, southwestern Nigeria, has been speculative due to inadequate compositional data on the talc and the mafic-ultramafic protoliths. Petrography, morphology, using scanning electron microscope, mineral chemistry, X-ray diffraction, and major, trace and rare-earth element compositions of the talc and the mafic-ultramafic in the area were undertaken with a view to determine the genesis of the talc bodies. Fine-grained amphibolite and lherzolite are the major mafic-ultramafic rocks in the study area. The amphibolite is fine-grained, composed of amphiboles, pyroxenes plagioclase, K-feldspar, ilmenite, magnetite, and garnet. The lherzolite and talc are composed of olivines, pyroxenes, amphiboles, and plagioclase. Alteration minerals include serpentine, amesite, talc, Cr-bearing clinochlore, and ferritchromite. Cr-spinel, pyrite, and magnetite are the accessory minerals present. Alteration of olivines, pyroxenes, and amphiboles to talc and chlinochlore; and spinel to ferritchchromite by hydrothermal (H₂O-CO₂-Cl-HF) fluids, provided by the granitic intrusions in the area, showed retrograde metasomatism of amphibolites to greenschist facies at 500-550ºC. This led to the formation of talc, amesite, anthophyllite, actinolite, and tremolite. The Al₂O₃-Fe₂O₃+TiO₂-MgO discrimination diagram suggests tholeiitic protolith for the amphibolite and komatitic protolith for the lherzolite. The lherzolite has flat rare-earth element patterns typical of komatiites and dunites. The Al₂O₃/TiO₂ ratios, Ce/Nb vs. Th/Nb, Cr-TiO₂, TiO₂ vs. Al₂O₃, and Nd vs. Nb discrimination diagrams indicated that the talcs are from two-parent sources: altered metacarbonates and tholeiitic basalts (amphibolites) to komatitic basalts (lherzolites).

Keywords: amphibolites, lherzolites, talc, komatiite

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Authors: Abazar Ghorbani, W. M. Wishwajith W. Kandegama, Seyed Mehdi Razavi, Moxian Chen

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The roles of hydrogen sulfide (H₂S) and melatonin (MT) as gasotransmitters in plants are widely recognised. Nevertheless, the precise nature of their involvement in defensive reactions remains uncertain. This study investigates the impact of the ML-H2S interaction on tomato plants exposed to vanadium (V) toxicity, focusing on synthesising secondary metabolites and V metal sequestration. The treatments applied in this study included a control (T1), V stress (T2), MT+V (T3), MT+H2S+V (T4), MT+hypotaurine (HT)+V (T5), and MT+H2S+HT+V (T6). These treatments were administered: MT (150 µM) as a foliar spray pre-treatment (3X), HT treatment (0.1 mM, an H2S scavenger) as root immersion for 12 hours as pre-treatments, and H2S (NaHS, 0.2 mM) and V (40 mg/L) treatments added to the Hoagland solution for 2 weeks. Results demonstrate that ML and H2S+ML treatments alleviate V toxicity by promoting the transcription of key genes (ANS, F3H, CHS, DFR, PAL, and CHI) involved in phenolic and anthocyanin biosynthesis. Moreover, they decreased V uptake and accumulation and enhanced the transcription of genes involved in glutathione and phytochelatin synthesis (GSH1, PCS, and ABC1), leading to V sequestration in roots and protection against V-induced damage. Additionally, ML and H2S+ML treatments optimize chlorophyll metabolism, and increase internal H2S levels, thereby promoting tomato growth under V stress. The combined treatment of ML+H2S shows superior effects compared to ML alone, suggesting synergistic/interactive effects between these two substances. Furthermore, inhibition of the beneficial impact of ML+H2S and ML treatments by HT, an H2S scavenger, underscores the significant involvement of H₂S in the signaling pathway activated by ML during V toxicity. Overall, these findings suggest that ML requires the presence of endogenous H₂S to mitigate V-induced adverse effects on tomato seedlings.

Keywords: vanadium toxicity, secondary metabolites, vanadium sequestration, h2s-melatonin crosstalk

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Authors: M. D. Asemoloye, S. G. Jonathan, A. Rafiq, O. J. Olawuyi, D. O. Adejoye

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Calmodulin is one of the intracellular calcium proteins that regulates large spectrum of enzymes and cellular functions including metabolism of cyclic nucleotides and glycogen. The potentials of calmodulin gene in fungi necessitates their genetic response and their strong cassette of enzyme secretions for pesticide degradation. Therefore, this study was carried out to investigate the ‘Transcriptomic’ response of calmodulin encoding genes in Talaromyces fungi in response to 2, 2-dichlorovinyl dimethyl phosphate (DDVP or Dichlorvos) an organophosphate pesticide and γ-Hexachlorocyclohexane (Lindane) an organochlorine pesticide. Fungi strains isolated from rhizosphere from grasses rhizosphere in pesticide polluted sites were subjected to percentage incidence test. Two most frequent fungi were further characterized using ITS gene amplification (ITS1 and ITS4 combinations), they were thereafter subjected to In-vitro DDVP and lindane tolerance tests at different concentrations. They were also screened for presence and expression of calmodulin gene (caM) using RT-PCR technique. The two Talaromyces strains had the highest incidence of 50-72% in pesticide polluted site, they were both identified as Talaromyces astroroseus asemoG and Talaromyces purpurogenum asemoN submitted in NCBI gene-bank with accession numbers KY488464 and KY488468 respectively. T. astroroseus KY488464 tolerated DDVP (1.23±0.023 cm) and lindane (1.11±0.018 cm) at 25 % concentration while T. purpurogenum KY488468 tolerated DDVP (1.33±0.061 cm) and lindane (1.54±0.077 cm) at this concentration. Calmodulin gene was detected in both strains, but RT-PCR expression of caM gene revealed at 900-1000 bp showed an under-expression of caM in T. astrorosues KY488464 but overexpressed in T. purpurogenum KY488464. Thus, the calmodulin gene response of these fungal strains to both pesticides could be considered in monitoring the potentials of fungal strains to pesticide tolerance and bioremediation of pesticide in polluted soil.

Keywords: Calmodulin gene, pesticide, RT-PCR, talaromyces, tolerance

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Authors: A. O Amosu, A. M Hammed, G. W. Maneveldt, D. V. Robertson-Andersson

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In aquaculture, feed utilization is an important factor affecting growth of the target species, and thus the success of the aquaculture operation. Growth of C. gariepinus fingerlings (weight 1.60 ± 0.05 g; length 4.50 ± 0.07cm) was monitored in a closed door hatchery for a period of 21 days in an experiment consisting of 4 treatments stocked at 20 fish/10 litre tanks, fed in triplicate twice daily (08:30, 17:30) at 4% body weight with weight changes recorded every 3 days. Treatments were: 1) FeedX; 2) 35% crude protein diet + non enriched Ulva spp (11.18% crude protein) (CD + NEU); 3) 35% crude protein diet + enriched Ulva spp (11.98% crude protein)(CD +EU) and 4) control diet of 35% crude protein (CD). The production of Ulva spp. biomass was cultivated for a period of 3 months. The result shows that the fish fed macroalgal enriched diet had good growth, though no significant difference (p > 0.05) was recorded amongst the weight gain, %weight gain, specific growth rates and nitrogen metabolism of diets CD + NEU, CD + EU and CD. Significant differences (p < 0.05), were, however, found in the food conversion ratio (FCR) and gross food conversion ratio (gFCR) among the fingerlings across all the different experimental diets. The best FCRs were recorded for control diet (0.79 ± 2.39) and the Ulva enriched (1.75 ± 1.34) diets. The results suggest that the fingerlings were able to utilize Ulva supplemented with control diet better than the FeedX. We have shown that Ulva supplemented diets are good substitutes for formulated and commercial feeds, with potential to be successful fish feed in aquaculture systems.

Keywords: aquaculture, clarias gariepinus, growth, macroalgae, nutrient, ulva

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Authors: Rashmi Tomar, A. Srinivasan, Nayan K. Mohanty, Arun K. Jain

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Phthalates have been used as additives in industrial products since the 1930s, and are universally considered to be ubiquitous environmental contaminants. The general population is exposed to phthalates through consumer products, as well as diet and medical treatments. Animal studies showing the existence of an association between some phthalates and testicular toxicity have generated public and scientific concern about the potential adverse effects of environmental changes on male reproductive health. Unprecedented declines in fertility rates and semen quality have been reported during the last half of the 20th century in developed countries and increasing interest exists on the potential relationship between exposure to environmental contaminants, including phthalates, and human male reproductive health Studies. Phthalates may be associated with altered endocrine function and adverse effects on male reproductive development and function, but human studies are limited. The aim of the present study was detection of phthalate compounds, estimation of their metabolites in infertile & fertile male. Blood and urine samples were collected from 150 infertile patients & 75 fertile volunteers recruited through Department of Urology, Safdarjung Hospital, New Delhi. Blood have been collected in separate glass tubes from the antecubital vein of the patients, serum have been separate and estimate the phthalate level in serum samples by Gas Chromatography / Mass Spectrometry using NIOSH / OSHA detailed protocol. Urine of Infertile & Fertile Subjects was collected & extracted using solid phase extraction method, analysis by HPLC. In conclusion, to the best of our knowledge the present study based on human is first to show the presence of phthalate in human serum samples and their metabolites in urine samples. Significant differences were observed between several phthalates in infertile and fertile healthy individuals.

Keywords: Gas Chromatography, HPLC, male infertility, phthalates, serum, toxicity, urine

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Authors: Mudrika Singhal

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The research paper is basically about how the genetically modified organisms evolved and their significance in today’s world. It also highlights about the various pros and cons of the genetically modified organisms and the progress of India in this field. A genetically modified organism is the one whose genetic material has been altered using genetic engineering techniques. They have a wide range of uses such as transgenic plants, genetically modified mammals such as mouse and also in insects and aquatic life. Their use is rooted back to the time around 12,000 B.C. when humans domesticated plants and animals. At that humans used genetically modified organisms produced by the procedure of selective breeding and not by genetic engineering techniques. Selective breeding is the procedure in which selective traits are bred in plants and animals and then are domesticated. Domestication of wild plants into a suitable cultigen is a well known example of this technique. GMOs have uses in varied fields ranging from biological and medical research, production of pharmaceutical drugs to agricultural fields. The first organisms to be genetically modified were the microbes because of their simpler genetics. At present the genetically modified protein insulin is used to treat diabetes. In the case of plants transgenic plants, genetically modified crops and cisgenic plants are the examples of genetic modification. In the case of mammals, transgenic animals such as mice, rats etc. serve various purposes such as researching human diseases, improvement in animal health etc. Now coming upon the pros and cons related to the genetically modified organisms, pros include crops with higher yield, less growth time and more predictable in comparison to traditional breeding. Cons include that they are dangerous to mammals such as rats, these products contain protein which would trigger allergic reactions. In India presently, group of GMOs include GM microorganisms, transgenic crops and animals. There are varied applications in the field of healthcare and agriculture. In the nutshell, the research paper is about the progress in the field of genetic modification, taking along the effects in today’s world.

Keywords: applications, mammals, transgenic, engineering and technology

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Authors: Rona Hanani Simamora, Bahagia Loebis, M. Surya Husada

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Background: The exact cause of schizophrenia is not known, although several etiology theories have been proposed for the disease, including immune dysfunction or autoimmune mechanisms. Cytokines including Tnf-α has an important role in the pathophysiology of schizophrenia and the effects of pharmacological treatment with antipsychotics. Nicotine is widespread effects on the brain, immune system and cytokine levels. Smoking among schizophrenic patients could play a role in the altered cytokine profiles of schizophrenia such as Tnf-α. Aims: To determine differences of serum Tnf-α levels between schizophrenic patients with smoking in male and healthy control. Methods: This study was a comparative analytic study, divided into two groups: 1) group of male schizophrenic patients with smoking (n1=30) with inclusion criteria were patients who have been diagnosed schizophrenic based PPDGJ-III, 20-60 years old, male, smoking, chronic schizophrenic patients in the stable phase and willing to participate this study. Exclusion criteria were having other mental disorders and comorbidity with other medical illnesses. 2) healthy control group (n2=30) with inclusion criteria were 20-60 years old, male, smoking, willing to participate this study. Exclusion criteria were having mental disorder, a family history of psychiatric disorders, the other medical illnesses, a history of alcohol and other substances abuse (except caffeine and nicotine). Serum Tnf-α were analyzed using the Quantikine HS Human Tnf –α Immunoassay. Results: Serum Tnf-α level measure in patient schizophrenia male with smoking and compared with the healthy control subjects. Tnf-α levels were significantly higher in patients schizophrenic male with smoking (25,79±27,96) to healthy control subjects (2,74±2,19), by using the Mann Whitney U test showed a statistically significant difference was observed for serum Tnf-α level (p < 0,001). Conclusions: Schizophrenia is a highly heterogeneous disorder, and this study shows an increase Tnf-α as pro-inflammation cytokines in schizophrenics. These results suggest an immune abnormalities may be involved in the etiology and pathophysiology of schizophrenia.

Keywords: male, schizophrenic, smoking, Tnf Alpha

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Authors: Yiyuan Tao

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Under the impact of global warming together with the intensification of human activities, the hydrological regimes may be altered, and the traditional stationary assumption was no longer satisfied. However, most of the current design standards of water infrastructures were still based on the hypothesis of stationarity, which may inevitably result in severe biases. Many critical impacts of climate on ecosystems, society, and the economy are controlled by extreme events rather than mean values. Therefore, it is of great significance to identify the non-stationarity of precipitation extremes and model the precipitation extremes in a nonstationary framework. The Wei River Basin (WRB), located in a continental monsoon climate zone in China, is selected as a case study in this study. Six extreme precipitation indices were employed to investigate the changing patterns and stationarity of precipitation extremes in the WRB. To identify if precipitation extremes are stationary, the Mann-Kendall trend test and the Pettitt test, which is used to examine the occurrence of abrupt changes are adopted in this study. Extreme precipitation indices series are fitted with non-stationary distributions that selected from six widely used distribution functions: Gumbel, lognormal, Weibull, gamma, generalized gamma and exponential distributions by means of the time-varying moments model generalized additive models for location, scale and shape (GAMLSS), where the distribution parameters are defined as a function of time. The results indicate that: (1) the trends were not significant for the whole WRB, but significant positive/negative trends were still observed in some stations, abrupt changes for consecutive wet days (CWD) mainly occurred in 1985, and the assumption of stationarity is invalid for some stations; (2) for these nonstationary extreme precipitation indices series with significant positive/negative trends, the GAMLSS models are able to capture well the temporal variations of the indices, and perform better than the stationary model. Finally, the differences between the quantiles of nonstationary and stationary models are analyzed, which highlight the importance of nonstationary modeling of precipitation extremes in the WRB.

Keywords: extreme precipitation, GAMLSSS, non-stationary, Wei River Basin

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Authors: Varsha Shinde, Belle Damodara Shenoy

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Tarballs are crude oil remnants found in oceans after long term weathering process and are a global concern since several decades as potential marine pollutant. Being complicated in structure microbial remediation of tarballs in natural environment is a slow process. They are rich in high molecular weight alkanes and poly aromatic hydrocarbons which are resistant to microbial attack and other environmental factors, therefore remain in environment for long time. However, it has been found that many bacteria and fungi inhabit on tarballs for nutrients and shelter. Many of them are supposed to be oil degraders, while others are supposed to be getting benefited by byproducts formed during hydrocarbon metabolism. Thus tarballs are forming special interesting ecological niche of microbes. This work aimed to study diversity of bacteria and fungi from tarballs and to see their potential application in crude oil degradation. The samples of tarballs were collected from Betul beach of south Goa (India). Different methods were used to isolate culturable fraction of bacteria and fungi from it. Those were sequenced for 16S rRNA gene and ITS for molecular level identification. The 16S rRNA gene sequence analysis revealed the presence of 13 bacterial genera/clades (Alcanivorax, Brevibacterium, Bacillus, Cellulomonas, Enterobacter, Klebsiella, Marinobacter, Nitratireductor, Pantoea, Pseudomonas, Pseudoxanthomonas, Tistrella and Vibrio), while the ITS sequence analysis placed the fungi in 8 diverse genera/ clades (Aspergillus, Byssochlamys, Monascus, Paecilomyces, Penicillium, Scytalidium/ Xylogone, Talaromyces and Trichoderma). All bacterial isolates were screened for oil degradation capacity. Potential strains were subjected to crude oil degradation experiment for quantification. Results were analyzed by GC-MS-MS.

Keywords: bacteria, biodegradation, crude oil, diversity, fungi, tarballs

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Authors: Liang-Jen Wang, Sung-Chou Li, Yuan-Ming Yeh, Sheng-Yu Lee, Ho-Chang Kuo, Chia-Yu Yang

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Background: Dysbiosis in the gut microbial community might be involved in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). The fungal component of the gut microbiome, namely the mycobiota, is a hyperdiverse group of multicellular eukaryotes that can influence host intestinal permeability. This study therefore aimed to investigate the impact of fungal mycobiome dysbiosis and intestinal permeability on ADHD. Methods: Faecal samples were collected from 35 children with ADHD and from 35 healthy controls. Total DNA was extracted from the faecal samples, and the internal transcribed spacer (ITS) regions were sequenced using high-throughput next-generation sequencing (NGS). The fungal taxonomic classification was analysed using bioinformatics tools, and the differentially expressed fungal species between the ADHD and healthy control groups were identified. An in vitro permeability assay (Caco-2 cell layer) was used to evaluate the biological effects of fungal dysbiosis on intestinal epithelial barrier function. Results: The β-diversity (the species diversity between two communities), but not α-diversity (the species diversity within a community), reflected the differences in fungal community composition between ADHD and control groups. At the phylum level, the ADHD group displayed a significantly higher abundance of Ascomycota and significantly lower abundance of Basidiomycota than the healthy control group. At the genus level, the abundance of Candida (especially Candida albicans) was significantly increased in ADHD patients compared to the healthy controls. In addition, the in vitro cell assay revealed that C. albicans secretions significantly enhanced the permeability of Caco-2 cells. Conclusions: The current study is the first to explore altered gut mycobiome dysbiosis using the NGS platform in ADHD. The findings from this study indicated that dysbiosis of the fungal mycobiome and intestinal permeability might be associated with susceptibility to ADHD.

Keywords: ADHD, fungus, gut–brain axis, biomarker, child psychiatry

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Authors: Magdalena Rusady Goey, Gordon Strathdee, Neil Perkins

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Background: Acute lymphoblastic leukaemia (ALL) is the most frequent type of childhood malignancy, accounting for 25% of all cases. TWIST2, a basic helix-loop-helix transcription factor, has been implicated in ALL development. Prior studies found that TWIST2 undergoes epigenetic silencing in more than 50% cases of ALL through promoter hypermethylation and suggested that re-expression of TWIST2 may inhibit cell growth/survival of leukaemia cell lines. TWIST2 has also been implicated as a regulator of NF-kappaB activity, which is constitutively active in leukaemia. Here, we use a lentiviral transductions system to confirm the importance of TWIST2 in controlling leukaemia cell growth and to investigate whether this is achieved through altered regulation of NF-kappaB activity. Method: Re-expression of TWIST2 in leukaemia cell lines was achieved using lentiviral-based transduction. The lentiviral vector also expresses enhanced green fluorescent protein (eGFP), allowing transduced cells to be tracked using flow cytometry. Analysis of apoptosis and cell proliferation were done using annexinV and VPD450 staining, respectively. Result and Discussion: TWIST2-expressing cells were rapidly depleted from a mixed population in ALL cell lines (NALM6 and Reh), indicating that TWIST2 inhibited cell growth/survival of ALL cells. In contrast, myeloid cell lines (HL60 and K562) were comparatively insensitive to TWIST2 re-expression. Analysis of apoptosis and cell proliferation found no significant induction of apoptosis, but did find a rapid induction of proliferation arrest in TWIST2-expressing Reh and NALM6 cells. Initial experiment with NF-kappaB inhibitor demonstrated that inhibition of NF-kappaB has similar impact on cell proliferation in the ALL cell lines, suggesting that TWITST2 may induce cell proliferation arrest through inhibition of NF-kappaB. Conclusion: The results of this study suggest that epigenetic inactivation of TWIST2 in primary ALL leads to increased proliferation, potentially by altering the regulation of NF-kappaB.

Keywords: leukaemia, acute lymphoblastic leukaemia, NF-kappaB, TWIST2, lentivirus

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Authors: Ali Bayram, Remzi Yiğiter

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Objective: Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. Herein, we conducted a study to investigate the unc-51 like autophagy activating kinase-1 (ULK1) mRNA expression levels in human peripheral blood mononuclear cells from patients with Alzheimer's disease. Method: To determine whether ULK1 gene expression are altered in AD patients, we measured their gene expression in human peripheral blood cell in 50 patients with AD and 50 age and gender matched healthy controls by quantitative real-time PCR technique. Results: We found that both ULK1 gene expression in peripheral blood cell were significantly decreased in patients with AD as compared with controls (p <0.05). Lower levels of ULK1 gene expression were significantly associated with the increased risk for AD. Conclusions: Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2, and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. Alzheimer is the most common neurodegenerative disease. Our results provide useful information that the ULK1 gene expression is decreased in the neurodegeneration and AD patients with, indicating their possible systemic involvement in AD.

Keywords: Alzheimer’s sisease, ULK1, mRNA expression, RT-PCR

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