| 1. |
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| 2. |
- Muhammad, Noor, et al.
(author)
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Novel mutations in MPT64 secretory protein of Mycobacterium tuberculosis complex
- 2023
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 20:3
-
Journal article (peer-reviewed)abstract
- Tuberculosis (TB) is a global health problem caused by the Mycobacterium tuberculosis complex (MTBC). These bacteria secrete various proteins involved in the pathogenesis and persistence of MTBC. Among the secretory proteins, MPT64 (Rv1980C) is highly conserved and is also known as a major culture filtrate that is used in rapid diagnosis of MTBC. In the current study, we aimed to find the mutation in this highly conserved protein in isolates from the Pashtun-dominant province of Pakistan. We analyzed 470 M. tuberculosis whole-genome sequences of Khyber Pakhtunkhwa Province. Mutations in the MPT64 gene were screened through TB-Profiler and BioEdit software tools. The DynaMut web server was used to analyze the impact of the mutation on protein dynamics and stability. Among 470 MTB genomes, three non-synonymous mutations were detected in nine isolates, and one synonymous mutation (G208A) was found in four isolates. Mutation G211T (F159L), which was detected at the C-terminal domain of the protein in six isolates, was the most prominent. The second novel mutation, T480C (I70V), was detected in two isolates at the C-terminal side of the protein structure. The third novel mutation, A491C (L66R), was detected in a single isolate at the N-terminal side of the MPT64 protein. The effect of these three mutations was destabilizing on the protein structure. The molecular flexibility of the first two mutations increased, and the last one decreased. MPT64 is a highly conserved secretory protein, harboring only a few mutations. This study provides useful information for better managing the diagnosis of MTB isolates in high TB-burden countries.
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| 3. |
- Ali, Qasim, et al.
(author)
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Drought tolerance potential of Vigna mungo L. lines as deciphered by modulated growth, antioxidant defense, and nutrient acquisition patterns
- 2016
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In: Revista Brasileira de Botânica. - : Springer. - 0100-8404 .- 1806-9959. ; 39:3, s. 801-812
-
Journal article (peer-reviewed)abstract
- Water shortage is one of the major environmental constraints that hamper the crop productivity worldwide. The present study was aimed to examine the drought tolerance potential of seven cultivars/lines of Vigna mungo L. depending upon their germination behavior, seedling growth, antioxidative defense mechanism, and nutrient acquisition. An experiment was conducted in the growth chamber using petri-plates and laid out in a completely randomized design (CRD). Hoagland's nutrient solution supplemented with 12 % PEG-8000 (drought treatment) or without PEG-800 (control) was used. Drought stress significantly altered the germination attributes as well as biomass production of all the studied cultivars/lines. Least adversative effects of drought stress were recorded in lines M-01001-1 and M-6036-21, respectively. The studied cultivars/lines exhibited differential response for various biochemical attributes under drought stress. The maximum increase in MDA and SOD activities and protein content was recorded in line M-603621, while the maximum AsA was recorded in line M-01001-1. Drought stress resulted in a significant reduction of plant N, P, K, Ca, and Mg contents, while the plant iron (Fe) contents remained unaffected. Results revealed that cultivars/lines M-01001-1 and M-6036-21 exhibited enhanced performance in terms of nutrient acquisition when stressed by drought. Based upon seed germination behavior, plant biomass production, biochemical attributes and mineral elements, the cultivars/lines M-01001-1 and M-6036-21 were identified as drought tolerant, while M-97 and Arroj-II were identified as drought sensitive.
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| 4. |
- Arshad, Wajiha, et al.
(author)
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A rare case of retropharyngeal liposarcoma : a rare location of a rare diagnosis
- 2023
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In: Journal of Surgical Case Reports. - : Oxford University Press (OUP). - 2042-8812. ; 2023:3
-
Journal article (peer-reviewed)abstract
- We report a case of retropharyngeal liposarcoma in a 53-year-old female, who had complaints of neck swelling accompanied with dysphagia, orthopnea and dysphonia. Clinical examination revealed huge multinodular swelling in front of neck with bilateral extension, more prominent on left side and moving with deglutition. The diagnosis of retropharyngeal liposarcoma was established following CT scan, MRI and incisional biopsy. Surgical excision of mass along with near total thyroidectomy was performed. Postoperative hospital stay was uneventful. She remained well in follow-up period of 1 year as well. In conclusion, retropharyngeal liposarcoma is a rare tumor. A review of the literature explores the reasons behind the late presentation as well as the difficulties in diagnosis and treatment of this rare tumor.
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| 5. |
- Al Amli, Ali Sabah, et al.
(author)
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Seismic Behavior of Reinforced Normal Strength Concrete and Reactive powder Concrete Eccentrically Loaded Frames
- 2020
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In: Technology Reports of Kansai University. - Japan : Faculty of Engineering, Kansai University. - 0453-2198. ; 62:3, s. 199-210
-
Journal article (peer-reviewed)abstract
- The purpose of this investigation is to study the effect of repeated load on reinforced concrete beam-column connections. Eight specimens were adopted in this investigation; four specimens were poured with normal strength concrete, and other four specimens were poured with reactive powder concrete. The frames dimensions are constant; 280 mm and 200mm of beam height and width respectively with 1000mm beam length and 200mm square column with 700mm height. The load was applied at mid-span and at a distance 150mm from the mid-span of beam. The reduction in frame capacity reached to 53.3% due to eccentricity. All tested specimens were failed at cycle 5 with different load level; . the decrease in stiffness of cyclically loaded frames of normal strength concrete was higher than that of reactive powder concrete frames. The deflections of cyclically loaded frames higher than that of statically loaded frames. In brief, the frames with eccentrically and cyclically loading give lowest ultimate strength, first crack load and stiffness with highest deflections.
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| 6. |
- Ali, Qasim, 1986, et al.
(author)
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Adaptive damage retention mechanism enables healthier yeast population
- 2019
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In: Journal of Theoretical Biology. - : Elsevier BV. - 0022-5193 .- 1095-8541. ; 473, s. 52-66
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Journal article (peer-reviewed)abstract
- During cytokinesis in budding yeast (Saccharomyces cerevisiae) damaged proteins are distributed asymmetrically between the daughter and the mother cell. Retention of damaged proteins is a crucial mechanism ensuring a healthy daughter cell with full replicative potential and an ageing mother cell. However, the protein quality control (PQC) system is tuned for optimal reproduction success which suggests optimal health and size of the population, rather than long-term survival of the mother cell. Modelling retention of damage as an adaptable mechanism, we propose two damage retention strategies to find an optimal way of decreasing damage retention efficiency to maximize population size and minimize the damage in the individual yeast cell. A pedigree model is used to investigate the impact of small variations in the strategies over the whole population. These impacts are based on the altruistic effects of damage retention mechanism and are measured by a cost function whose minimum value provides the optimal health and size of the population. We showed that fluctuations in the cost function allow yeast cell to continuously vary its strategy, suggesting that optimal reproduction success is a local minimum of the cost function. Our results suggest that a rapid decrease in the efficiency of damage retention, at the time when the mother cell is almost exhausted, produces fewer daughters with high levels of damaged proteins. In addition, retaining more damage during the early divisions increases the number of healthy daughters in the population. (C) 2019 Elsevier Ltd. All rights reserved.
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| 7. |
- Ali, Rouknuddin Qasim
(author)
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Stem cell in-vitro strategies for the induction of sensory neurons for inner ear cell therapy
- 2016
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Doctoral thesis (other academic/artistic)abstract
- The cochlea, a part of the auditory system, is a complex structure consisting of several different types of cells including hair cells and spiral ganglion neurons. In mammals, the regenerative potential of hair cells and spiral ganglion neurons is lost soon after the birth and damage to any of these cells causes sensorineural hearing loss. Cochlear implant is presently the only available treatment for sensorineuronal hearing loss, bypassing the malfunctioning hair cells and directly simulating the spiral ganglion neurons. Cochlear implant functionality depends on the activation of remaining spiral ganglion neurons. A possibility for a stem cell approach replacing auditory neurons in the cochlea has attracted great interest. The aim of this thesis was to identify methods to induce progenitors for sensory neurons from human pluripotent stem cells, with the prospective use in a cell therapy for the inner ear. Paper I focused on differentiation of sensory neural types from precursors at different stages of neural rosette formation derived from human embryonic stem cells (day 4, 7, or 11- rosettes). Neural and sensory neural phenotype differentiation was examined by immunocytochemistry. Cells positive for NESTIN and TUJ1 were present at all tested time points, indicating presence of the earliest stages of neural differentiation. Starting from the 11-days neural rosettes resulted in decreased potential for neural differentiation, compared to starting from the 4-and 7-days protocols which more effectively could be driven into differentiation towards cells with sensory neuron marker phenotype. In paper II an approach using the SB431542 small molecule for blocking of the TGFß/Activin/Nodal signaling pathway was evaluated for effects on sensory neural differentiation, examined by gene expression and immunocytochemistry. Blocking of this pathway significantly facilitated the induction of markers present on sensory neurons; NGN1, NEUROD1 and BRN3A. Consecutive treatment with bFGF further enhanced the expression of these markers, as well as an increase in expression of GATA3. This protocol also enhanced the presence of colonies positive for TUJ1 as well as BRN3A or ISL1. Notably, addition of a third culture step, with exposure to the neurotrophic factors BDNF + NT3 resulted in > 90% presence of colonies with a phenotype compatible with sensory neurons. In paper III, we evaluated the capacity of additional small molecules (Isoxazole-9 and Metformin) to induced sensory neurons, starting from long-term neuroepithelial stem (lt- NES) cells. Here, Isoxazole 9 (ISX9), but not Metformin or SB431542, significantly induced sensory neural genes (GATA3, BRN3A and PERIPHERIN) after a 4-day treatment. Exposure to ISX9 significantly increased the number of BRN3A/TUJ1 positive cells. Further treatment with BDNF7NT3 resulted in increased levels of cells with GATA3 expression and also BRN3A/TUJ1 positive cells in ISX9-exposed populations. In conclusion, this thesis has explored and demonstrated cultural conditions for in vitro induction of sensory neural phenotypes, starting from in vitro cultured human pluripotent stem cells or lt-NES cells. The presented approaches may provide appropriate strategies to develop an effective treatment for sensory neural hearing loss.
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| 8. |
- Anjum, Asad Ur Rehman, et al.
(author)
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Sensitivity Analysis of Mathematical Model to Study the Effect of T Cells Infusion in Treatment of CLL
- 2020
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In: Mathematics. - : MDPI AG. - 2227-7390. ; 8:4
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Journal article (peer-reviewed)abstract
- In this paper, we considered a mathematical model concerned with the treatment of Chronic Lymphocytic Leukemia (CLL) taking into account the effect of superficially infused T cells in this particular type of tumor. The model is described thoroughly by the system of non-linear differential equations explaining the interaction of naive, infected, cancer and immune cell population. The detailed sensitivity analysis with the application is the major part of this paper. The basic objective is to provide insight to how parameters' behavior varies model results by elaborating the results obtained from the application of sensitivity analysis. The sensitivity of the model was evaluated not only theoretically, but also with the help of a numerical approach, producing graphs providing better imminent of results. We argue that the application of the sensitivity analysis method endows an insight into how and which parameters are of primary significance in controlling the spread of leukemia.
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| 9. |
- Arslan, Muhammad, et al.
(author)
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Impact of Varying Load Conditions and Cooling Energy Comparison of a Double-Inlet Pulse Tube Refrigerator
- 2020
-
In: Processes. - : MDPI. - 2227-9717. ; 8:3
-
Journal article (peer-reviewed)abstract
- Modeling and optimization of a double-inlet pulse tube refrigerator (DIPTR) is very difficult due to its geometry and nature. The objective of this paper was to optimize-DIPTR through experiments with the cold heat exchanger (CHX) along the comparison of cooling load with experimental data using different boundary conditions. To predict its performance, a detailed two-dimensional DIPTR model was developed. A double-drop pulse pipe cooler was used for solving continuity, dynamic and power calculations. External conditions for applicable boundaries include sinusoidal pressure from an end of the tube from a user-defined function and constant temperature or limitations of thermal flux within the outer walls of exchanger walls under colder conditions. The results of the system's cooling behavior were reported, along with the connection between the mass flow rates, heat distribution along pulse tube and cold-end pressure, the cooler load's wall temp profile and cooler loads with varied boundary conditions i.e. opening of 20% double-inlet and 40-60% orifice valves, respectively. Different loading conditions of 1 and 5W were applied on the CHX. At 150 K temperature of the cold-end heat exchanger, a maximum load of 3.7 W was achieved. The results also reveal a strong correlation between computational fluid dynamics modeling results and experimental results of the DIPTR.
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| 10. |
- Asif, M., et al.
(author)
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A dataset about anthropometric measurements of the Pakistani children and adolescents using a cross-sectional multi-ethnic anthropometric survey
- 2021
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In: Data in Brief. - : Elsevier. - 2352-3409. ; 34
-
Journal article (peer-reviewed)abstract
- Evaluation of nutritional status is necessary during childhood and the juvenile years when the level of hydration and the adipose tissues experience significant changes. Anthropometric measurements and their derived indices are valid proxies to predict body fat, obesity (general or central) and their associated cardiovascular risks. The dataset under consideration also provides the socio-demographic related information and anthropometric measurement values related to height, weight, body mass index (BMI), waist circumference (WC), hip circumference (HpC), waist-to-hip ratio (WHpR), waist-to-height ratio (WHtR), mid-upper arm circumference (MUAC), neck circumference (NC), and wrist circumference (WrC). Standard procedure was adopted for quantifying the body measurements. The data were consisting of 10,782 children and adolescents aged 2–19 years, belonging four major cities of Pakistan viz. Multan, Lahore, Rawalpindi and Islamabad. This dataset is beneficial to develop anthropometric growth charts which will provide the essential knowledge of growth and nutritional disorders (e.g., stunted, overweight and obesity) of Pakistani children and adolescents. The dataset can also be used by researchers to calculate body surface area (BSA), body frame size (BFS), body shape index (BSI), and tri-ponderal mass index (TMI) of children and adolescents that are also some other reliable indicators of obesity and insulin resistance as well as cardiometabolic risk in children and adults.
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| 11. |
- Asif, M., et al.
(author)
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Developing Neck Circumference Growth Reference Charts for Pakistani Children and Adolescents Using the Lambda-Mu-Sigma (LMS) and Quantile Regression Method
- 2021
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In: Public Health Nutrition. - : Cambridge University Press. - 1368-9800 .- 1475-2727. ; 24:17, s. 5641-5649
-
Journal article (peer-reviewed)abstract
- Objective: Neck circumference (NC) is currently used as an embryonic marker of obesity and its associated risks. But its use in clinical evaluations and other epidemiological purposes requires sex and age-specific standardized cut-offs which are still scarce for the Pakistani pediatric population. We therefore developed sex and age-specific growth reference charts for NC for Pakistani children and adolescents aged 2-18 years.Design: Cross-sectional multi-ethnic anthropometric survey (MEAS) study.Setting: Multan, Lahore, Rawalpindi and Islamabad.Participants: The dataset of 10,668 healthy Pakistani children and adolescents aged 2 to 18 years collected in MEAS were used. Information related to age, sex and NC were taken as study variables. The lambda-mu-sigma (LMS) and quantile regression (QR) methods were applied to develop growth reference charts for NC.Results: The 5th, 10th, 25th, 50th, 75th, 90th and 95th smoothed percentile values of NC were presented. The centile values showed that neck size increased with age in both boys and girls. During 8 and 14 years of age, girls were found to have larger NC than boys. A comparison of NC median (50th) percentile values with references from Iranian and Turkish populations reveals substantially lower NC percentiles in Pakistani children and adolescents compared to their peers in the reference population.Conclusion: The comparative results suggest that the uses of NC references of developed countries are inadequate for Pakistani children. A small variability between empirical centiles and centiles obtained by QR procedure recommends that growth charts should be constructed by QR as an alternative method.
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| 12. |
- Asif, Muhammad, et al.
(author)
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Diagnostic Performance and Appropriate Cut-Offs of Different Anthropometric Indicators for Detecting Children with Overweight and Obesity
- 2021
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In: BioMed Research International. - : Hindawi Publishing Corporation. - 2314-6133 .- 2314-6141.
-
Journal article (peer-reviewed)abstract
- In the clinical settings, different anthropometric indicators like neck circumference (NC), waist circumference (WC), midupper arm circumference (MUAC), waist-to-height ratio (WHtR), and arm-to-height ratio (AHtR) have been suggested for evaluating overweight and obesity in children. The comparative ability of these indicators in Pakistan is yet unknown. This study is aimed at examining the validity of different anthropometric indicators of overweight and obesity simultaneously and at determining their superlative cut-off values that would correctly detect overweight and obesity in children. For this purpose, the dataset of anthropometric measurements height, weight, WC, MUAC, and NC of 5,964 Pakistani children, aged 5-12 years collected in a cross-sectional multiethnic anthropometric survey (MEAS), was used. Receiver operating characteristic (ROC) curve analysis was performed to assess the validity of different anthropometric indicators. The most sensitive and specific cut-off points, positive and negative predictive values of each indicator were also calculated. The results of the ROC curve indicated that all the studied indicators had a good performance but the indicators AHtR and WHtR had the highest value of the area under the curve (AUC) for the screening of children with overweight and obesity (AUC > 0.80). In the overall sample, AHtR, WHtR, MUAC, WC, and NC cut-off points indicative of overweight, in both boys and girls, were 0.14, 0.46, 18.41 cm, 62.86 cm, and 26.36 cm and 0.14, 0.47, 18.16 cm, 64.39 cm, and 26.54 cm, respectively; the corresponding values for obesity were 0.14, 0.47, 18.67 cm, 62.10 cm, and 26.36 cm and 0.14, 0.48, 20.19 cm, 64.39 cm, and 25.27 cm. We concluded that the sex-specific cut-off points for AHtR, WHtR, MUAC, WC, and NC can be used to diagnose overweight and obesity in Pakistani children.
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| 13. |
- Chaudhry, Qasim Ali
(author)
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Computational Modeling of Reaction and Diffusion Processes in Mammalian Cell
- 2012
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Doctoral thesis (other academic/artistic)abstract
- PAHs are the reactive toxic chemical compounds which are present as environmental pollutants. These reactive compounds not only diffuse through the membranes of the cell but also partition into the membranes. They react with the DNA of the cell giving rise to toxicity and may cause cancer. To understand the cellular behavior of these foreign compounds, a mathematical model including the reaction-diffusion system and partitioning phenomenon has been developed. In order to reduce the complex structure of the cytoplasm due to the presence of many thin membranes, and to make the model less computationally expensive and numerically treatable, homogenization techniques have been used. The resulting complex system of PDEs generated from the model is implemented in Comsol Multiphysics. The numerical results obtained from the model show a nice agreement with the in vitro cell experimental results. Then the model was reduced to a system of ODEs, a compartment model (CM). The quantitative analysis of the results of the CM shows that it cannot fully capture the features of metabolic system considered in general. Thus the PDE model affords a more realistic representation. In order to see the influence of cell geometry in drug diffusion, the non-spherical axi-symmetric cell geometry is considered, where we showed that the cellular geometry plays an important role in diffusion through the membranes. For further reduction of complexity of the model, another simplified model was developed. In the simplified model, we used PDEs for the extracellular domain, cytoplasm and nucleus, whereas the plasma and nuclear membranes were taken away, and replaced by the membrane flux, using Fick's Law. We further extended the framework of our previously developed model by benchmarking against the results from four different cell lines. Global optimization techniques are used for the parameters describing the diffusion and reaction to fit the measured data. Numerical results were in good agreement with the in vitro results. For the further development of the model, the process of surface bound reactions were added, thus developing a new cell model. The effective equations were derived using iterative homogenization for this model. The numerical results of some of the species were qualitatively verified against the in vitro results found in literature.
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| 14. |
- Chaudhry, Qasim Ali, et al.
(author)
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Influence of Biological Cell Geometry on Reaction and Diffusion Simulation
- 2012
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Reports (other academic/artistic)abstract
- Mathematical modeling of reaction-diffusion system in a biological cellis an important and difficult task, especially when the chemical compoundsare lipophilic. The difficulty level increases, when we take into account theheterogeneity of the cell, and the variation of cellular architecture. Mathematicalmodeling of reaction-diffusion systems in spherical cell geometryhas earlier been performed by us. In the present paper, we have workedwith non-spherical cell geometry, because the cellular geometry can play animportant role for drug diffusion in the cell. Homogenization techniques,which were earlier applied in the case of a spherical cell model, have beenused for the numerical treatment of the model. This technique considerablyreduces the complexity of the model. To further reduce the complexity ofthe model, a simplified model was also developed. The key idea of this simplifiedmodel has been advocated in Virtual Cell, where PDEs are used forthe extracellular domain, cytoplasm and nucleus, whereas the plasma andnuclear membranes have been taken away, and replaced by membrane flux,using Fick’s Law of diffusion. The numerical results of the non-sphericalcell model have been compared with the results of the spherical cell model,where the numerical results of spherical cell model have already been validatedagainst in vitro cell experimental results. From the numerical results,we conclude that the plasma and nuclear membranes can be protective reservoirsof significance. The numerical results of the simplified model werecompared against the numerical results of our detailed model, revealing theimportance of detailed modeling of membranes in our model.
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| 15. |
- Chaudhry, Qasim Ali, et al.
(author)
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Mathematical Modeling of Reaction and Diffusion Systems in a Cell Including Surface Reactions on the Cytoplasmic Membranes
- 2012
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Reports (other academic/artistic)abstract
- Benzo[a]pyrene (BP) is a toxic polycyclic aromatic hydrocarbon (PAH) whichis found in our environment. These BPs are metabolized to benzo[a]pyrene diol(BPD) by enzymes bound to the cytoplasmic membranes e.g. members of thecytochrome P450 protein family and epoxide hydrolyses. BPDs are further metabolizedto two stereochemical variants of Benzo[a]pyrene diol expoxide (BPDE) bythe cytochrome P450 family of proteins. These are the two steps of metabolismcategorized as Phase I. In Phase II, BPDEs are further metabolized by soluble enzymesin the cytoplasm e.g. members of the glutathione transferase protein familyto GSH conjugates. BPDE can also diffuse into the cellular nucleus and reactwith DNA forming mutagenic DNA adducts. The formation of GSH conjugatesand DNA adducts, was earlier studied by us by developing a mathematical modeldescribing the intracellular reaction and diffusion of lipophilic PAHs taking intoaccount the partitioning phenomenon (Dreij K et al. PLoS One 6(8), 2011). In thispaper part of Phase I metabolism i.e formation of BPDE metabolites, will be addedto the model, thus enhancing the previous model. These cytochrome P450 reactionstake place on the intracellular membranes, and are modeled as a membranesurface reaction within the cytoplasm using the standard process of adsorption anddesorption. The effective equations are derived using iterative homogenization forthe numerical treatment of the cytoplasm including surface effects. The numericalresults of some of the species have been qualitatively verified against in vitroresults found in the literature.
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| 16. |
- Chaudhry, Qasim Ali, 1982-
(author)
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Numerical Approximation of Reaction and Diffusion Systems in Complex Cell Geometry
- 2010
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Licentiate thesis (other academic/artistic)abstract
- The mathematical modelling of the reaction and diffusion mechanism of lipophilic toxic compounds in the mammalian cell is a challenging task because of its considerable complexity and variation in the architecture of the cell. The heterogeneity of the cell regarding the enzyme distribution participating in the bio-transformation, makes the modelling even more difficult. In order to reduce the complexity of the model, and to make it less computationally expensive and numerically treatable, Homogenization techniques have been used. The resulting complex system of Partial Differential Equations (PDEs), generated from the model in 2-dimensional axi-symmetric setting is implemented in Comsol Multiphysics. The numerical results obtained from the model show a nice agreement with the in vitro cell experimental results. The model can be extended to more complex reaction systems and also to 3-dimensional space. For the reduction of complexity and computational cost, we have implemented a model of mixed PDEs and Ordinary Differential Equations (ODEs). We call this model as Non-Standard Compartment Model. Then the model is further reduced to a system of ODEs only, which is a Standard Compartment Model. The numerical results of the PDE Model have been qualitatively verified by using the Compartment Modeling approach. The quantitative analysis of the results of the Compartment Model shows that it cannot fully capture the features of metabolic system considered in general. Hence we need a more sophisticated model using PDEs for our homogenized cell model.
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| 17. |
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| 18. |
- Chaudhry, Qasim Ali, 1982-, et al.
(author)
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On the numerical approximation of drug diffusion in complex cell geometry
- 2009
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In: Proceedings of the 6th International Conference on Frontiers of Information Technology, FIT '09. - Abbottabad : ACM. - 9781605586427
-
Conference paper (other academic/artistic)abstract
- The mathematical modeling of a mammalian cell is a very tedious work due to its very complex geometry. Especially, taking into account the spatial distribution and the inclusion of lipophilic toxic compounds greatly increases its complexity. The nonhomogeneity and the different cellular architecture of the cell certainly affect the diffusion of these compounds. The complexity of the whole system can be reduced by a homogenization technique. To see the effect of these compounds on different cell architectures, we have implemented a mathematical model. The work has been done in 2-dimensional space. The simulation results have been qualitatively verified using compartmental modeling approach. This work can be extended with a more complex reaction-diffusion system and to 3-dimensional space as well. Copyright 2009 ACM.
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| 19. |
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| 20. |
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| 21. |
- Dreij, Kristian, et al.
(author)
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A Method for Efficient Calculation of Diffusion and Reactions of Lipophilic Compounds in Complex Cell Geometry
- 2011
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:8, s. e23128-
-
Journal article (peer-reviewed)abstract
- A general description of effects of toxic compounds in mammalian cells is facing several problems. Firstly, most toxic compounds are hydrophobic and partition phenomena strongly influence their behaviour. Secondly, cells display considerable heterogeneity regarding the presence, activity and distribution of enzymes participating in the metabolism of foreign compounds i.e. bioactivation/biotransformation. Thirdly, cellular architecture varies greatly. Taken together, complexity at several levels has to be addressed to arrive at efficient in silico modelling based on physicochemical properties, metabolic preferences and cell characteristics. In order to understand the cellular behaviour of toxic foreign compounds we have developed a mathematical model that addresses these issues. In order to make the system numerically treatable, methods motivated by homogenization techniques have been applied. These tools reduce the complexity of mathematical models of cell dynamics considerably thus allowing to solve efficiently the partial differential equations in the model numerically on a personal computer. Compared to a compartment model with well-stirred compartments, our model affords a more realistic representation. Numerical results concerning metabolism and chemical solvolysis of a polycyclic aromatic hydrocarbon carcinogen show good agreement with results from measurements in V79 cell culture. The model can easily be extended and refined to include more reactants, and/or more complex reaction chains, enzyme distribution etc, and is therefore suitable for modelling cellular metabolism involving membrane partitioning also at higher levels of complexity.
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| 22. |
- Dreij, Kristian, et al.
(author)
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In silico Modeling of Intracellular Diffusion and Reaction of Benzo[a]pyrene Diol Epoxide
- 2012
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Reports (other academic/artistic)abstract
- Several studies has suggested that glutathione conjugation of polycyclicaromatic hydrocarbons (PAHs) catalyzed by glutathione transferases (GSTs)are important factors in protecting cells against toxicity and DNA damagederived from these compounds. To further characterize the intracellular dynamicsof PAH DEs and the role of GSTs in protection against DNA damage,we recently developed a PDE model using techniques for mathematicalhomogenization (Dreij K et al. PLoS One 6(8), 2011). In this study, wewanted to further develop our model by benchmarking against results fromfour V79 cell lines; control cells and cells overexpressing human GSTs A1-1, M1-1 and P1-1. We used an approach of global optimization of the parametersdescribing the diffusion and reaction of the ultimate carcinogenic PAHmetabolite benzo[a]pyrene diol epoxide to fit measured values from the fourV79 cell lines. Numerical results concerning the formation of glutathioneconjugates and hydrolysis were in good agreement with results from measurementsin V79 cell culture. Cellular results showed significant protectionby GST expression against formation of DNA adducts with more than 10-fold reduced levels compared to control cells. Results from the model usingglobally optimized parameters showed that the model cannot predict theprotective effects of GSTs. Extending the model to also include effects fromprotein interactions and GST localization showed the same discrepancy. Insummary, the results show that we have an incomplete understanding of theintracellular dynamics of the interaction between BPDE and GST that warrantsfurther investigation and development of the model.
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| 23. |
- Enattah, Nabil Sabri, et al.
(author)
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Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture
- 2008
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 82:1, s. 57-72
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Journal article (peer-reviewed)abstract
- The T-13910 variant located in the enhancer element of the lactase (LCT) gene correlates perfectly with lactase persistence (LP) in Eurasian populations whereas the variant is almost nonexistent among Sub-Saharan African populations, showing high prevalence of LP. Here, we report identification of two new mutations among Saudis, also known for the high prevalence of LP. We confirmed the absence of the European T-13910 and established two new mutations found as a compound allete: T/G(-13915) within the -13910 enhancer region and a synonymous SNP in the exon 17 of the MCM6 gene T/C-3712, -3712 bp from the LCT gene. The compound allele is driven to a high prevalence among Middle East population(s). Our functional analyses in vitro showed that both SNPs of the compound allele, located 10 kb apart, are required for the enhancer effect, most probably mediated through the binding of the hepatic nuclear factor 1 alpha (HNF1 alpha). High selection coefficient (s) similar to 0.04 for LP phenotype was found for both T-13910 and the compound allele. The European T-13910 and the earlier identified East African G(-13907) LP allele share the same ancestral background and most likely the same history, probably related to the same cattle domestication event. In contrast, the compound Arab allele shows a different, highly divergent ancestral haplotype, suggesting that these two major global LP alleles have arisen independently, the latter perhaps in response to camel milk consumption. These results support the convergent evolution of the LP in diverse populations, most probably reflecting different histories of adaptation to milk culture.
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| 24. |
- Javed, M. Tariq, et al.
(author)
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Cadmium spiked soil modulates root organic acids exudation and ionic contents of two differentially Cd tolerant maize (Zea mays L.) cultivars
- 2017
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In: Ecotoxicology and Environmental Safety. - : Elsevier BV. - 0147-6513 .- 1090-2414. ; 141, s. 216-225
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Journal article (peer-reviewed)abstract
- Our earlier work described that the roots of two maize cultivars, grown hydroponically, differentially responded to cadmium (Cd) stress by initiating changes in medium pH depending on their Cd tolerance. The current study investigated the root exudation, elemental contents and antioxidant behavior of the same maize cultivars (cv. 3062 (Cd-tolerant) and cv. 31P41 (Cd-sensitive)] under Cd stress. Plants were maintained in a rhizobox-like system carrying soil spiked with Cd concentrations of 0, 10, 20, 30, 40 and 50 mu mol/kg soil. The root and shoot Cd contents increased, while Mg, Ca and Fe contents mainly decreased at higher Cd levels, and preferentially in the sensitive cultivar. Interestingly, the K contents increased in roots of cv. 3062 at low Cd treatments. The Cd stress caused acidosis of the maize root exudates predominantly in cv. 3062. The concentration of various organic acids was significantly increased in the root exudates of cv. 3062 with applied Cd levels. This effect was diminished in cv. 31P41 at higher Cd levels. Cd exposure increased the relative membrane permeability, anthocyanin (only in cv. 3062), proline contents and the activities of peroxidases (POD) and superoxide dismutase (SOD). The only exception was the catalase activity, which was diminished in both cultivars. Root Cd contents were positively correlated with the secretion of acetic acid, oxalic acid, glutamic acid, citric acid, and succinic acid. The antioxidants like POD and SOD exhibited a positive correlation with the organic acids under Cd stress. It is likly that a high exudation of dicarboxylic organic acids improves nutrient uptake and activities of antioxidants, which enables the tolerant cultivar to acclimatize in Cd polluted environment.
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| 25. |
- Qasim, Ali, et al.
(author)
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Effect of Hydrogen Bonding Energy and Freezing Point Depression of Quaternary Ammonium Salts on the Thermodynamic Gas Hydrate Inhibition
- 2023
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In: Journal of Chemical and Engineering Data. - : American Chemical Society (ACS). - 0021-9568 .- 1520-5134. ; 68:8, s. 1856-1864
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Journal article (peer-reviewed)abstract
- Theeffects of the hydrogen bonding energy interactionand freezingpoint depression on five quaternary ammonium salts (QAS) of gas hydratesystems are discussed in this study. Tetramethylammonium bromide,tetraethylammonium bromide, tetramethylammonium acetate, tetraethylammoniumacetate tetrahydrate, and tetramethylammonium iodide were among theQAS studied. Methane (CH4) and carbon dioxide (CO2), frequently encountered in flow assurance pipelines, are includedin the considered hydrate system. The experimental temperature rangeis 274-285 K, with 3.40-8.30 and 2.0-4.0 as thecorresponding pipeline pressures for CH4 and CO2. For different mass concentrations (1, 5, and 10 wt.%), the thermodynamicinfluence, i.e., average suppression temperature (& UDelta; T ), of the studied system was reported, and itsrelationship with the hydrogen bonding energy (E (HB)) interaction and freezing point temperature (T (f)) of QAS was investigated. The structural impact of QAS(in the form of alkyl chain variation) and anions on thermodynamichydrate inhibition (THI) behavior via hydrogen bonding energy interactionsand freezing point is also covered in the research. According to thefindings, the increase in the alkyl chain length of QAS reduced thedecrease in E (HB) bonding ability. On theother hand, the presence of an anion had a significant impact on QAS.The E (HB) and QAS freezing T (f) are concentration-dependent phenomena; higher QAS concentrationin the system resulted in lower T (f) temperaturesand higher E (HB) energies, which influencedhydrate mitigation positively. The work is novel as it establishesthe relationship between E (HB) and averagesuppression temperature and also between depression in freezing pointwith average suppression temperature. Since QAS are considered amongpotential THI inhibitors, further development is required for a generalizedcorrelation based on the E (HB) interactionand T (f).
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