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Sökning: WFRF:(Arif Muhammad)

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1.
  • Khan, Inayat Ali, et al. (författare)
  • Stable and Efficient PtRu Electrocatalysts Supported on Zn-BTC MOF Derived Microporous Carbon for Formic Acid Fuel Cells Application
  • 2020
  • Ingår i: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Highly efficient, well-dispersed PtRu alloy nanoparticles supported on high surface area microporous carbon (MPC) electrocatalysts, are prepared and tested for formic acid oxidation reaction (FAOR). The MPC is obtained by controlled carbonization of a zincbenzenetricarboxylate metal-organic framework (Zn-BTC MOF) precursor at 950◦C, and PtRu (30 wt.%) nanoparticles (NPs) are prepared and deposited via a polyol chemical reduction method. The structural and morphological characterization of the synthesized electrocatalysts is carried out using powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), an energy dispersive X-ray (EDX) technique, and gas adsorption analysis (BET). The FAOR performance of the catalysts is investigated through cyclic voltammetry (CV), chronoamperometry (CA), and electrochemical impedance spectroscopy (EIS). A correlation between high electrochemical surface area (ECSA) and high FAOR performance of the catalysts is observed. Among the materials employed, Pt1Ru2/MPC 950 with a high electrochemical surface area (25.3 m2 g −1 ) consequently showed superior activity of the FAOR (Ir = 9.50 mA cm−2 and Jm = 2,403 mA mg−1 Pt ) at room temperature, with improved tolerance and stability toward carbonaceous species. The superior electrochemical performance, and tolerance to CO-poisoning and long-term stability is attributed to the high surface area carbon support (1,455 m2 g −1 ) and high percentage loading of ruthenium (20 wt.%). The addition of Ru promotes the efficiency of electrocatalyst by offering FAOR via a bifunctional mechanism.
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2.
  • Abodayeh, Kamaleldin, et al. (författare)
  • Stochastic Numerical Analysis for Impact of Heavy Alcohol Consumption on Transmission Dynamics of Gonorrhoea Epidemic
  • 2020
  • Ingår i: Computers, Materials and Continua. - : TECH SCIENCE PRESS. - 1546-2218 .- 1546-2226. ; 62:3, s. 1125-1142
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper aims to perform a comparison of deterministic and stochastic models. The stochastic modelling is a more realistic way to study the dynamics of gonorrhoea infection as compared to its corresponding deterministic model. Also, the deterministic solution is itself mean of the stochastic solution of the model. For numerical analysis, first, we developed some explicit stochastic methods, but unfortunately, they do not remain consistent in certain situations. Then we proposed an implicitly driven explicit method for stochastic heavy alcohol epidemic model. The proposed method is independent of the choice of parameters and behaves well in all scenarios. So, some theorems and simulations are presented in support of the article.
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3.
  • Muhammad Marizwan Abdul Manan, Muhammad Marizwan, et al. (författare)
  • Factors Associated with Motorcyclists’ Speed Behaviour on Malaysian Roads.
  • 2017
  • Ingår i: Transportation Research Part F: Traffic Psychology and Behaviour. - : Elsevier BV. - 1369-8478. ; 50, s. 109-127
  • Tidskriftsartikel (refereegranskat)abstract
    • This research uses data from observations of 8277 motorcyclists at various types of roads of the road hierarchy in Malaysia in 2015, to investigate the effects of road characteristics, motorcyclists’ riding behaviour, motorcyclists’ and motorcycles’ characteristics on the occurrence of riding with excessive speed. For data collection and analysis, new software, i.e. MECHROM, was developed. The speed analysis shows that motorcyclists go faster than other vehicles on dual carriageway primary roads with three-lanes and dual carriageway collector roads with four-lanes. In general, 42.2% of the observed motorcycles exceed the speed limit and 28.6% of them go beyond the 85th percentile of the traffic speed. In determining the factors associated with motorcyclists riding with excessive speed, a mixed effect logistic regression model was produced, with three levels statistically significant random effect parameters. The fixed parameters factors are: primary road, roads with no shoulder, motorcycles with engine capacity of more than 150cc, not overloaded motorcycle, bright motorcycle, male rider, wears helmet and shoes, riding in the middle of the lane or shoulder, lane splitting (i.e. passing through in between two vehicles) and weaving between vehicles. The random parameters show that the majority of variation in the outcomes (56.5%) occurs at level 1 (the rider), while 12.2% of variation occurs at level 2 (motorcycle), and 31.2% at level 3 (location). The variations indicate that the motorcyclist’s characteristics and riding behaviour are of importance, while the variable “type of motorcycle” clearly indicates that riding with excessive speed occurs regardless of the type of motorcycle.
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4.
  • Shatanawi, Wasfi, et al. (författare)
  • Essential Features Preserving Dynamics of Stochastic Dengue Model
  • 2021
  • Ingår i: CMES - Computer Modeling in Engineering & Sciences. - : TECH SCIENCE PRESS. - 1526-1492 .- 1526-1506. ; 126:1, s. 201-215
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonlinear stochastic modelling plays an important character in the different fields of sciences such as environmental, material, engineering, chemistry, physics, biomedical engineering, and many more. In the current study, we studied the computational dynamics of the stochastic dengue model with the real material of the model. Positivity, boundedness, and dynamical consistency are essential features of stochastic modelling. Our focus is to design the computational method which preserves essential features of the model. The stochastic non-standard finite difference technique is most efficient as compared to other techniques used in literature. Analysis and comparison were explored in favour of convergence. Also, we address the comparison between the stochastic and deterministic models.
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5.
  • Akhtar, Nadia, et al. (författare)
  • Uncovering Barriers for Industrial Symbiosis : Assessing Prospects for Eco-Industrialization through Small and Medium-Sized Enterprises in Developing Regions
  • 2022
  • Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 14:11, s. 6898-
  • Tidskriftsartikel (refereegranskat)abstract
    • Industrialization is indispensable for socio-economic development but poses far-reaching implications for resources and the environment. Consequently, industrial symbiosis-based collaborations are gaining recognition as a viable strategy to manage resource consumption for mitigating environmental distress. However, these types of synergistic collaborations are more prevalent in developed regions and are linked to larger-sized industries. Admittedly, such collaborative partnerships are less focused in developing regions and small- to medium-size enterprises (SMEs). This calls for discovering the potentials for synergistic partnerships among the small and medium scaled industrial entities in developing economies. Therefore, the study was designed to identify, assess and explore the prospects of symbiotic collaborations among SMEs in Pakistan. Moreover, the inputs are equally relevant for developing and expanding such productive associations in developing regions. Data regarding inputs and outputs was collected from sixty-one (61) SMEs through field survey during the year 2019. It was processed and analyzed to uncover existing and potential synergies among SMEs. The significant findings transpired that the majority of collaborative linkages are bilateral and are driven to maximize economic gains. However, informal networks of recyclers and absence of a stringent regulatory regime are the ground realities in developing/transforming economies. These factors symptomatically interfere with the process of formal/informal exchanges between and among firms. Furthermore, it was observed that the lack of awareness and impulsiveness of SMEs, as well as the inconsistent supply of by-products, act as barriers for such partnerships in developing countries. It calls for proactive engagements and facilitations from the state institutions through policy instruments. The study addresses a broad audience including industrialists, investors, policy makers and researchers engaged in IS studies. Moreover, the inputs will provide impetus for stimulating eco-industrial progress in developing regions such as Pakistan.
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6.
  • Aribowo, Agus, et al. (författare)
  • Finite element method on topology optimization applied to laminate composite of fuselage structure
  • 2023
  • Ingår i: Curved and Layered Structures. - : Walter de Gruyter GmbH. - 2353-7396. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • This research applies a numerical study of topology optimization of laminate composite structures by using a finite element method (FEM). In this methodology, the plies orientation is excluded from the optimization. The geometry-based optimization from frames of a MALE UAV fuselage structure is presented. The minimum strain energy with an optimization constraint of 20% of weight reduction is used in the objective function. Before the primary analysis, benchmark studies of topology optimization without considering orientations from previously published literature are performed. The convergence studies were taken to acquire the appropriate mesh size in the FEM technique, which utilized a four-noded shell element. The finite element analysis and optimization results showed that the structural design of the newly framed composite fuselage MALE UAV meets the structural strength requirements specified in the airworthiness standard STANAG 4671.
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7.
  • Hameed, Arslan, et al. (författare)
  • ZIF-12/Fe-Cu LDH Composite as a High Performance Electrocatalyst for Water Oxidation
  • 2021
  • Ingår i: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Layered double hydroxides (LDH) are being used as electrocatalysts for oxygen evolution reactions (OERs). However, low current densities limit their practical applications. Herein, we report a facile and economic synthesis of an iron-copper based LDH integrated with a cobalt-based metal-organic framework (ZIF-12) to form LDH-ZIF-12 composite (1) through a co-precipitation method. The as-synthesized composite 1 requires a low overpotential of 337 mV to achieve a catalytic current density of 10 mA cm−2 with a Tafel slope of 89 mV dec−1. Tafel analysis further demonstrates that 1 exhibits a slope of 89 mV dec−1 which is much lower than the slope of 284 mV dec−1 for LDH and 172 mV dec−1 for ZIF-12. The slope value of 1 is also lower than previously reported electrocatalysts, including Ni-Co LDH (113 mV dec−1) and Zn-Co LDH nanosheets (101 mV dec−1), under similar conditions. Controlled potential electrolysis and stability test experiments show the potential application of 1 as a heterogeneous electrocatalyst for water oxidation.
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8.
  • Hussain, Arif, et al. (författare)
  • Methoxy-methylheptane as a cleaner fuel additive : An energy- and cost-efficient enhancement for separation and purification units
  • 2021
  • Ingår i: Energy Science & Engineering. - : John Wiley & Sons. - 2050-0505. ; :9, s. 1632-1646
  • Tidskriftsartikel (refereegranskat)abstract
    • Environmental protection agencies have begun imposing stringent regulations on the existing refineries to control the levels of gasoline additives. In this context, a novel compound, 2-methoxy-2-methylheptane (MMH), had drawn attention as fuel additive for cleaner combustion. The conventional process of MMH production features three distillation columns in a direct sequence. These columns are used to maintain the required product purities and to utilize the unreacted reactants through recycling streams. The distillation system of the existing MMH plant can afford significant energy savings, leading to a reduction in the total annual costs (TAC). The aim of this investigation is to demonstrate that the reported conventional process can be significantly enhanced by modifying the design and operational parameters and by replacing two distillation columns with an intensified dividing wall column (DWC) configuration. The DWC design is further optimized using several algorithms such as the modified coordinate method (MCD), robust particle swarm paradigm (PSP), and firefly (FF) with nonlinear constraints. Compared to conventional process, the optimized DWC resulted in 24% and 11.5% savings in the plant operating and total annual costs, respectively.
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9.
  • Ibrahim, Muhammad Asim, 1980-, et al. (författare)
  • Mitigating the risk of secondary fires at MSW bale storage sites
  • 2024
  • Ingår i: International Journal of Environmental Engineering. - : InderScience Publishers. - 1756-8463 .- 1756-8471. ; 12:3, s. 193-217
  • Tidskriftsartikel (refereegranskat)abstract
    • The article discusses the suitability of several existing empirical models for determining the safe separation distances (SSDs) for waste fuels. Contour plots of SSDs are generated based on isotropic thermal radiation model for safely storing municipal solid waste (MSW) bales under different storage settings and the plots can be employed for routine hazard assessment purposes. Further, experimental design technique was employed, and orthogonal test matrices were generated to conduct the experiments for studying the combustion dynamics of the primary fire under the influence of storage settings of surrounding fuel units. Main and interaction effects of various storage parameters (e.g., height of adjacent fuel sources, clearance between fuel sources and array size) on the response variables (flame height and burn out time) was studied. A list of appropriate measures for minimising the risk of secondary fires at MSW bale storage sites are provided.
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10.
  • Munsif, Fazal, et al. (författare)
  • Dual-purpose wheat technology : a tool for ensuring food security and livestock sustainability in cereal-based cropping pattern
  • 2021
  • Ingår i: Archives of Agronomy and Soil Science. - : Taylor & Francis Group. - 0365-0340 .- 1476-3567. ; 67:13, s. 1889-1900
  • Tidskriftsartikel (refereegranskat)abstract
    • Wheat cultivation under a dual-purpose (DP) system holds great potential to provide additional fodder for livestock with marginal grain reduction. This study explores the potential of wheat as a DP crop for improving both, forage and grain cropping system by finding out optimal sowing dates and cultivars suitable for DP cropping. Field experiments with four cultivars (Saleem-2000, Bathoor-2007, Fakhre Sarhad-99 (FS-99) and Siran-2008), three sowing dates (October 15, October 30 and November 15) and two cutting treatments (cut and no-cut) determines the effects on yield and physiology of wheat. Wheat sown either in mid or end of October resulted in 11 and 8% increase in grain yield while 13 and 9% in biological yield over mid November sowing, respectively. This increase in yield was due to higher grain spike(-1), chlorophyll content, transpiration rate and relative water content. The cultivars Siran-2008 and Saleem-2000 had higher biological and grain yields than other cultivars across cutting and sowing dates treatments. Biological and grain yields were reduced by 4% and 3%, respectively under the DP wheat compared with no-cut treatment, but grains N content was unaffected. Conclusively, DP wheat system (cut treatment) had higher profitability (11.2%) than wheat crop sown only for grain purposes.
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11.
  • Nisa, Zaib Un, et al. (författare)
  • A comparative metabolomic study on desi and kabuli chickpea (Cicer arietinum L.) genotypes under rainfed and irrigated field conditions
  • 2020
  • Ingår i: Scientific Reports. - BERLIN GERMANY : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Chickpea is considered among the most important leguminous crops in the world. However, in recent years drought conditions and/or limited availability of water have significantly reduced the production of chickpea. The current study was aimed to understand the legume stress response at the metabolic level for the determination of chickpea genotypes which can resist yield losses and could be cultivated with limited water availability. Here, we have analyzed two genotypes of chickpea, desi and kabuli under rainfed condition using a GC-MS based untargeted metabolomics approach. Results revealed significant differences in several metabolite features including oxalic acid, threonic acid, inositol, maltose and L-proline between studied groups. Accumulation of plant osmoprotectants such as L-proline, sugars and sugar alcohols was higher in desi genotype than kabuli genotype of chickpea when grown under the rainfed condition. Metabolic pathway analysis suggests that the inositol phosphate metabolism was involved in plant defense mechanisms against the limited water availability.
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12.
  • Rehman, Ahad Abdul, et al. (författare)
  • In vivo assessment of anticoagulant and antiplatelet effects of Syzygium cumini leaves extract in rabbits
  • 2019
  • Ingår i: BMC Complementary and Alternative Medicine. - : Springer Science and Business Media LLC. - 1472-6882. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Syzygium cumini (L.) Skeels. is one of the very popular traditionally used medicinal plants with numerous pharmacological activities including antioxidant, hypoglycemic and anti-inflammatory. However, actions of S. cumini on blood coagulation and other parameters of blood were poorly pharmacologically studied. Therefore, aim of this present investigation is to examine the effects of methanolic extract of S. cumini on blood coagulation and anticoagulation factors in healthy white albino rabbits at different doses. Methods: Blood samples were drawn twice during this study and biochemical assays were performed to determine the effect on different parameters such as coagulation, anticoagulation, hematological, Protein C (PC) and thrombin antithrombin (TAT) complex and platelet aggregation. Results: The results showed significant increase in RBCs, hemoglobin, hematocrit and platelets counts up to 1.4 × 103/cm, 2.2 g/dl, 6%, 248.2 × 103/cm respectively. While, thrombin and bleeding time were also prolonged in dose dependent manner which is highly significant (p ≤ 0.005) as compared to control. Similarly, highly significantly increased (p ≤ 0.005) in levels of protein C, thrombin antithrombin complex at dose of 500 mg/kg were observed. Whereas, levels of platelets aggregation and fibrinogen were decreased at high doses. Conclusion: The obtained findings of hematological and coagulation tests concludes possibly S. cumini possess anticoagulant and antiplatelet effects.
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13.
  • Saif-Ul-Allah, Muhammad Waqas, et al. (författare)
  • Computationally Inexpensive 1D-CNN for the Prediction of Noisy Data of NOx Emissions From 500 MW Coal-Fired Power Plant
  • 2022
  • Ingår i: Frontiers in Energy Research. - : FRONTIERS MEDIA SA. - 2296-598X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Coal-fired power plants have been used to meet the energy requirements in countries where coal reserves are abundant and are the key source of NOx emissions. Owing to the serious environmental and health concerns associated with NOx emissions, much work has been carried out to reduce NOx emissions. Sophisticated artificial intelligence (AI) techniques have been employed during the past few decades, such as least-squares support vector machine (LSSVM), artificial neural networks (ANN), long short-term memory (LSTM), and gated recurrent unit (GRU), to develop the NOx prediction model. Several studies have investigated deep neural networks (DNN) models for accurate NOx emission prediction. However, there is a need to investigate a DNN-based NOx prediction model that is accurate and computationally inexpensive. Recently, a new AI technique, convolutional neural network (CNN), has been introduced and proven superior for image class prediction accuracy. According to the best of the author's knowledge, not much work has been done on the utilization of CNN on NOx emissions from coal-fired power plants. Therefore, this study investigated the prediction performance and computational time of one-dimensional CNN (1D-CNN) on NOx emissions data from a 500 MW coal-fired power plant. The variations of hyperparameters of LSTM, GRU, and 1D-CNN were investigated, and the performance metrics such as RMSE and computational time were recorded to obtain optimal hyperparameters. The obtained optimal values of hyperparameters of LSTM, GRU, and 1D-CNN were then employed for models' development, and consequently, the models were tested on test data. The 1D-CNN NOx emission model improved the training efficiency in terms of RMSE by 70.6% and 60.1% compared to LSTM and GRU, respectively. Furthermore, the testing efficiency for 1D-CNN improved by 10.2% and 15.7% compared to LSTM and GRU, respectively. Moreover, 1D-CNN (26 s) reduced the training time by 83.8% and 50% compared to LSTM (160 s) and GRU (52 s), respectively. Results reveal that 1D-CNN is more accurate, more stable, and computationally inexpensive compared to LSTM and GRU on NOx emission data from the 500 MW power plant.
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14.
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15.
  • Tanveer, M. K., et al. (författare)
  • Prevalence and chemo-therapeutical investigations of gastrointestinal nematodes in domestic pigeons in Lahore, Pakistan
  • 2011
  • Ingår i: Tropical Biomedicine. - 0127-5720. ; 28:1, s. 102-110
  • Tidskriftsartikel (refereegranskat)abstract
    • The prevalence of gastrointestinal nematodes was studied in 143 (80 male and 63 female) domestic pigeons. Faecal samples were collected to determine the gastrointestinal nematodes of domestic pigeons through qualitative and quantitative faecal examinations. A total of 48 (male 33 and 25 female) naturally infected domestic pigeons were divided into G(1) (albendzdole) and G(2) (fenbendazole) treatment-groups along with one control group (C). The overall prevalence of gastrointestinal nematodes was 40.5% (58/143) in domestic pigeons. Likewise, the prevalence of gastrointestinal nematodes in males and females was found 41.3% (33/58) and 39.7% (25/58) respectively. The overall prevalence of Capillaria obsignata and Ascaridia columbae was found to be 67.2% and 32.8%, respectively. The prevalence of C. obsignata and A. columbae in males was 72.7% (24/33) and 27.8% (9/33) and in females was 60% (15/25) and 40% (10/25), respectively. There was no significant sex related difference seen in the prevalence of C. obsignata (p>0.56) and A. columbae (p>0.40) in domestic pigeons, respectively. The overall efficacy of albendazole and fenbendazole was calculated to be 66% and 71%. A remarkable significant difference (p<0.05) was observed in eggs per gram before and after treatment in both G(1) and G(2) treated-groups. The efficacy of fenbendazole was found to be more significant (p<0.02) than albendazole.
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16.
  • Abdellah, Tebani, et al. (författare)
  • Integration of molecular profiles in a longitudinal wellness profiling cohort.
  • 2020
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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17.
  • Ahmad, Iftikhar, et al. (författare)
  • Drivers and Barriers for Efficient Energy Management Practices in Energy-Intensive Industries: A Case-Study of Iron and Steel Sector
  • 2020
  • Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 12:18
  • Tidskriftsartikel (refereegranskat)abstract
    • The two major reasons behind the worlds energy crisis are losses in energy transmission and less efficient energy use at sinks. The former flaw can be catered by changing the entire energy transmission system which requires investment and planning on a large scale, whereas the later deficiency can be overcome through proper management of energy utilizing systems. Energy-intensive industries have a substantial share in energy consumption and equally high energy saving potentials if they adopt some integrated and improved energy efficiency. This study investigates the energy management systems in the iron and steel sector of Pakistan, and compare it with findings of similar work in Sweden, Bangladesh, and Ghana. A systematic questionnaire was circulated in the iron and steel sector across the country and afterward the collected data was analyzed to find major barriers and drivers for efficient energy management practices. In addition, questions on non-energy benefits and information sources relevant to the energy efficiency were also part of the questionnaire. Cost reduction resulting from lowered energy use was rated as the most important driver for applying energy-efficient operation. On the other hand, the cost of production disruption was considered among high-level barriers to the implementation of improved energy efficiency. An increase in the life-time of equipment was labeled as the top non-energy benefits. Company peers and seminars/conferences were referred as the best information sources related to energy efficiency. The outcome of the study will be helpful to the decision-maker in the industry, as well as the government levels.
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18.
  • Ali, Amjad, et al. (författare)
  • Effect of Manganese Catalysts on the Performance of Anodes in Direct Carbon Fuel Cells
  • 2022
  • Ingår i: ACS Applied Energy Materials. - : AMER CHEMICAL SOC. - 2574-0962. ; 5:6, s. 6878-6885
  • Tidskriftsartikel (refereegranskat)abstract
    • The efficiency of direct carbon fuel cells is higher than that of solid oxide fuel cells. The direct carbon fuel cell transforms chemical energy into electrical energy. In this work, the La0.4Sr0.6MnxTi1-xO3-delta (x = 0.02, 0.04, 0.06, 0.08) anode material has been synthesized by the combustion method to examine the device performance. X-ray analysis confirmed the single-perovskite cubic structure with an average crystalline size of 80 nm. An electrical conductivity of 2.1 S cm-1 and fuel cell performance of 100 mW cm-2 at 600 degrees C are measured with sub-bituminous fuel. Theoretical results describe the minor contribution of manganese (Mn) in the valence band and the major one in the conduction band, and with minimum energy, the Mn electrons may jump in the conduction band. Moreover, density functional theory confirmed that with an increase in the Mn concentration, Mn and Ti energy states appear at the Fermi level, which reveals that the conductivity of the compound has improved, agreeing with the experimental results that the Mn concentration led to the enhancement of the conductivity.
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19.
  • Altay, Özlem, et al. (författare)
  • Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19
  • 2021
  • Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; 8:17
  • Tidskriftsartikel (refereegranskat)abstract
    • COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.
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20.
  • Ambikan, Anoop T., et al. (författare)
  • Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity
  • 2022
  • Ingår i: Cell systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 13:8, s. 665-681
  • Tidskriftsartikel (refereegranskat)abstract
    • The clinical outcome and disease severity in coronavirus disease 2019 (COVID-19) are heterogeneous, and the progression or fatality of the disease cannot be explained by a single factor like age or comorbidities. In this study, we used system-wide network-based system biology analysis using whole blood RNA sequencing, immunophenotyping by flow cytometry, plasma metabolomics, and single-cell-type metabolo-mics of monocytes to identify the potential determinants of COVID-19 severity at personalized and group levels. Digital cell quantification and immunophenotyping of the mononuclear phagocytes indicated a sub-stantial role in coordinating the immune cells that mediate COVID-19 severity. Stratum-specific and person-alized genome-scale metabolic modeling indicated monocarboxylate transporter family genes (e.g., SLC16A6), nucleoside transporter genes (e.g., SLC29A1), and metabolites such as a-ketoglutarate, succi-nate, malate, and butyrate could play a crucial role in COVID-19 severity. Metabolic perturbations targeting the central metabolic pathway (TCA cycle) can be an alternate treatment strategy in severe COVID-19.
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21.
  • Andersson, Linda, 1973, et al. (författare)
  • Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
  • 2021
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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22.
  • Arif, Muhammad, et al. (författare)
  • INetModels 2.0: An interactive visualization and database of multi-omics data
  • 2021
  • Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 49:W1, s. W271-W276
  • Tidskriftsartikel (refereegranskat)abstract
    • It is essential to reveal the associations between various omics data for a comprehensive understanding of the altered biological process in human wellness and disease. To date, very few studies have focused on collecting and exhibiting multi-omics associations in a single database. Here, we present iNetModels, an interactive database and visualization platform of Multi-Omics Biological Networks (MOBNs). This platform describes the associations between the clinical chemistry, anthropometric parameters, plasma proteomics, plasma metabolomics, as well as metagenomics for oral and gut microbiome obtained from the same individuals. Moreover, iNetModels includes tissue- and cancer-specific Gene Co-expression Networks (GCNs) for exploring the connections between the specific genes. This platform allows the user to interactively explore a single feature's association with other omics data and customize its particular context (e.g. male/female specific). The users can also register their data for sharing and visualization of the MOBNs and GCNs. Moreover, iNetModels allows users who do not have a bioinformatics background to facilitate human wellness and disease research. iNetModels can be accessed freely at https://inetmodels.com without any limitation.
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23.
  • Arif, Muhammad, et al. (författare)
  • Integrative transcriptomic analysis of tissue-specific metabolic crosstalk after myocardial infarction
  • 2021
  • Ingår i: Elife. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Myocardial infarction (MI) promotes a range of systemic effects, many of which are unknown. Here, we investigated the alterations associated with MI progression in heart and other metabolically active tissues (liver, skeletal muscle, and adipose) in a mouse model of MI (induced by ligating the left ascending coronary artery) and sham-operated mice. We performed a genomewide transcriptomic analysis on tissue samples obtained 6- and 24 hr post MI or sham operation. By generating tissue-specific biological networks, we observed: (1) dysregulation in multiple biological processes (including immune system, mitochondrial dysfunction, fatty-acid beta-oxidation, and RNA and protein processing) across multiple tissues post MI and (2) tissue-specific dysregulation in biological processes in liver and heart post MI. Finally, we validated our findings in two independent MI cohorts. Overall, our integrative analysis highlighted both common and specific biological responses to MI across a range of metabolically active tissues.
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24.
  • Arif, Muhammad (författare)
  • Systems and Network-based Approaches to Complex Metabolic Diseases
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The future of healthcare is personalized medicine, in which disease treatments are tailored based on the individual characteristics of each patient. To reach that objective, we need to obtain a better understanding of diseases. The main facilitator of personalized medicine is systems and data-driven biology, which makes omics data a top commodity in this era. Coupled with computational and biological expertise, omics data can be a useful asset for obtaining mechanistic insights into the biological conundrum, particularly in disease-related contexts. This thesis describes systems biology approaches and their applications in disease-specific contexts. Systems biology assists us in systematically and comprehensively understanding complex biological systems as a whole interconnected system.The first part of the thesis describes the generation of more than 100 biological networks based on personalized data originated from several different omics, usually referred to as multiomics data, including clinical data and metabolomics, proteomics, and metagenomics data collected from the same individuals. Moreover, we present a web-based multiomics biological network database and visualization platform called iNetModels.In the second part of the thesis, we describe systems biology frameworks and their applications to the study of various biological questions in disease contexts using single- and multiomics data. First, we present our findings on the integrative view of metabolic activities from multiple tissues after myocardial infarction using transcriptomics data from the heart and other metabolically active tissues. Second, we used transcriptomics data to describe the mechanistic effect of lifelong training on skeletal muscle in both men and women and the role of short-term training in reversing damage from metabolic-related diseases. Third, we deciphered the molecular mechanism of nonalcoholic fatty liver disease (NAFLD) based on clinical data, plasma metabolomics, plasma inflammatory proteomics, and oral and gut metagenomics data. Finally, we elucidated the mechanism of action of CMA supplementation, a potential treatment for NAFLD, based on proteomics and metabolomics data.In summary, this thesis presents a novel platform for biological network analysis and proven systems biology frameworks to provide mechanistic and systematic understandings of specific diseases using single- and multiomics data.
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25.
  • Arif, Muhammad, et al. (författare)
  • Unraveling the synergy of interface engineering α-MnO2/Bi2WO6 heterostructures and defective active sites for superdurable photocatalysis: Mechanistic insights into charge separation/transfer
  • 2023
  • Ingår i: Chemical Engineering Journal. - : ELSEVIER SCIENCE SA. - 1385-8947 .- 1873-3212. ; 475
  • Tidskriftsartikel (refereegranskat)abstract
    • The construction of visible-light-driven hybrid heterostructure photocatalysts is of great significance for environmental remediation, although the utilization of strong visible-light response photocatalysts with high efficiency and stability remains a major challenge. Defect engineering is an excellent way to introduce metal cation vacancies in materials, thereby ensuing in highly enhanced catalytic performance. Inspired by this, we effectively constructed a built-in interface alpha-MnO2/Bi2WO6 heterostructure with abundant intimate interfaces and defective Mn3+/Mn4+ active sites for photocatalytic tetracycline hydrochloride (TC-HCl), hexavalent chromium Cr6+ reduction, and Escherichia coli (E. coli) inactivation. The experimental results, such as the active species test and X-ray photoelectron spectroscopy, indicated that the defective sites Mn3+/Mn4+, surface oxygen vacancies, and Bi(3+x)+ boosted the visible light absorption, and highly enhanced the photoinduced charge separation/transfer. Furthermore, experimental and DFT calculations reveal the high charge density at the built-in interface heterostructure and the Z-scheme charge transfer mechanism during the photocatalytic process. The results further reveal that O-2(-) and O-1(2) are the main reactive active species contributing to the photocatalytic reaction. The exceptional TC-HCl decomposition activity of the alpha-MnO2/Bi2WO6 heterostructure (97.56%, 2.31, and 2.04 times higher than bulk), enhanced reaction kinetics (K-app = 0.041 min(-1), 6.4, and 5.2 times higher than bulk), removal rate of 80.3%, Cr6+ reduction to Cr3+ (98.56%, K-app = 0.0599 min(-1)), and almost 100% bacterial inactivation compared to bulk alpha-MnO2 (42.22%) and Bi2WO6 (47.76%), were mainly due to the enhanced charge separation/transfer at the built-in interface and high charge density. This study opens new horizons for constructing Z-scheme MnO-based interface heterostructures with abundant defect sites for exceptional photocatalytic applications.
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26.
  • Bayraktar, Abdulahad, et al. (författare)
  • Revealing the Molecular Mechanisms of Alzheimer's Disease Based on Network Analysis
  • 2021
  • Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:21
  • Tidskriftsartikel (refereegranskat)abstract
    • The complex pathology of Alzheimer's disease (AD) emphasises the need for comprehensive modelling of the disease, which may lead to the development of efficient treatment strategies. To address this challenge, we analysed transcriptome data of post-mortem human brain samples of healthy elders and individuals with late-onset AD from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) and Mayo Clinic (MayoRNAseq) studies in the AMP-AD consortium. In this context, we conducted several bioinformatics and systems medicine analyses including the construction of AD-specific co-expression networks and genome-scale metabolic modelling of the brain in AD patients to identify key genes, metabolites and pathways involved in the progression of AD. We identified AMIGO1 and GRPRASP2 as examples of commonly altered marker genes in AD patients. Moreover, we found alterations in energy metabolism, represented by reduced oxidative phosphorylation and ATPase activity, as well as the depletion of hexanoyl-CoA, pentanoyl-CoA, (2E)-hexenoyl-CoA and numerous other unsaturated fatty acids in the brain. We also observed that neuroprotective metabolites (e.g., vitamins, retinoids and unsaturated fatty acids) tend to be depleted in the AD brain, while neurotoxic metabolites (e.g., beta-alanine, bilirubin) were more abundant. In summary, we systematically revealed the key genes and pathways related to the progression of AD, gained insight into the crucial mechanisms of AD and identified some possible targets that could be used in the treatment of AD.
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27.
  • Benfeitas, Rui, et al. (författare)
  • Characterization of heterogeneous redox responses in hepatocellular carcinoma patients using network analysis
  • 2019
  • Ingår i: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 40, s. 471-487
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Redox metabolism is often considered a potential target for cancer treatment, but a systematic examination of redox responses in hepatocellular carcinoma (HCC) is missing. Methods: Here, we employed systems biology and biological network analyses to reveal key roles of genes associated with redox metabolism in HCC by integrating multi-omics data. Findings: We found that several redox genes, including 25 novel potential prognostic genes, are significantly co-expressed with liver-specific genes and genes associated with immunity and inflammation. Based on an integrative analysis, we found that HCC tumors display antagonistic behaviors in redox responses. The two HCC groups are associated with altered fatty acid, amino acid, drug and hormone metabolism, differentiation, proliferation, and NADPH-independent vs - dependent antioxidant defenses. Redox behavior varies with known tumor subtypes and progression, affecting patient survival. These antagonistic responses are also displayed at the protein and metabolite level and were validated in several independent cohorts. We finally showed the differential redox behavior using mice transcriptomics in HCC and noncancerous tissues and associated with hypoxic features of the two redox gene groups. Interpretation: Our integrative approaches highlighted mechanistic differences among tumors and allowed the identification of a survival signature and several potential therapeutic targets for the treatment of HCC.
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28.
  • Bidkhori, Gholamreza, et al. (författare)
  • Metabolic Network-Based Identification and Prioritization o f Anticancer Targets Based on Expression Data in Hepatocellular Carcinoma
  • 2018
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:JUL
  • Tidskriftsartikel (refereegranskat)abstract
    • Hepatocellular carcinoma (HCC) is a deadly form of liver cancer with high mortality worldwide. Unfortunately, the large heterogeneity of this disease makes it difficult to develop effective treatment strategies. Cellular network analyses have been employed to study heterogeneity in cancer, and to identify potential therapeutic targets. However, the existing approaches do not consider metabolic growth requirements, i.e., biological network functionality, to rank candidate targets while preventing toxicity to non-cancerous tissues. Here, we developed an algorithm to overcome these issues based on integration of gene expression data, genome-scale metabolic models, network controllability, and dispensability, as well as toxicity analysis. This method thus predicts and ranks potential anticancer non-toxic controlling metabolite and gene targets. Our algorithm encompasses both objective-driven and-independent tasks, and uses network topology to finally rank the predicted therapeutic targets. We employed this algorithm to the analysis of transcriptomic data for 50 HCC patients with both cancerous and non-cancerous samples. We identified several potential targets that would prevent cell growth, including 74 anticancer metabolites, and 3 gene targets (PRKACA, PGS1, and CRLS1). The predicted anticancer metabolites showed good agreement with existing FDA-approved cancer drugs, and the 3 genes were experimentally validated by performing experiments in HepG2 and Hep3B liver cancer cell lines. Our observations indicate that our novel approach successfully identifies therapeutic targets for effective treatment of cancer. This approach may also be applied to any cancer type that has tumor and non-tumor gene or protein expression data.
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29.
  • Chapman, Mark A., et al. (författare)
  • Skeletal Muscle Transcriptomic Comparison between Long-Term Trained and Untrained Men and Women
  • 2020
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 31:12
  • Tidskriftsartikel (refereegranskat)abstract
    • To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9 women) and strength-trained (7 men) humans compared with age-matched untrained controls (7 men, 8 women). Transcriptomic analysis, Gene Ontology, and genome-scale metabolic modeling demonstrate changes in pathways related to the prevention of metabolic diseases, particularly with endurance training. Our data also show prominent sex differences between controls and that these differences are reduced with endurance training. Additionally, we compare our data with studies examining muscle gene expression before and after a months-long training period in individuals with metabolic diseases, This analysis reveals that training shifts gene expression in individuals with impaired metabolism to become more similar to our endurance-trained group. Overall, our data provide an extensive examination of the accumulated transcriptional changes that occur with decades-long training and identify important "exercise-responsive" genes that could attenuate metabolic disease.
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30.
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31.
  • Couch, Fergus J., et al. (författare)
  • Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
  • 2016
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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32.
  • Doran, S., et al. (författare)
  • Multi-omics approaches for revealing the complexity of cardiovascular disease
  • 2021
  • Ingår i: Briefings in bioinformatics. - : Oxford University Press (OUP). - 1467-5463 .- 1477-4054. ; 22:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The development and progression of cardiovascular disease (CVD) can mainly be attributed to the narrowing of blood vessels caused by atherosclerosis and thrombosis, which induces organ damage that will result in end-organ dysfunction characterized by events such as myocardial infarction or stroke. It is also essential to consider other contributory factors to CVD, including cardiac remodelling caused by cardiomyopathies and co-morbidities with other diseases such as chronic kidney disease. Besides, there is a growing amount of evidence linking the gut microbiota to CVD through several metabolic pathways. Hence, it is of utmost importance to decipher the underlying molecular mechanisms associated with these disease states to elucidate the development and progression of CVD. A wide array of systems biology approaches incorporating multi-omics data have emerged as an invaluable tool in establishing alterations in specific cell types and identifying modifications in signalling events that promote disease development. Here, we review recent studies that apply multi-omics approaches to further understand the underlying causes of CVD and provide possible treatment strategies by identifying novel drug targets and biomarkers. We also discuss very recent advances in gut microbiota research with an emphasis on how diet and microbial composition can impact the development of CVD. Finally, we present various biological network analyses and other independent studies that have been employed for providing mechanistic explanation and developing treatment strategies for end-stage CVD, namely myocardial infarction and stroke.
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33.
  • Emanuelsson, Eric B., et al. (författare)
  • MRI characterization of skeletal muscle size and fatty infiltration in long--term trained and untrained individuals
  • 2022
  • Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 54:9, s. 389-389
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigated body composition measures in highly trained and untrained individuals using whole--body magnetic resonance imaging (MRI). Additionally, correlations between these measures and skeletal muscle gene expression were performed. Thirty-six individuals were included: endurance-trained males (ME, n = 8) and females (FE, n = 7), strength-trained males (MS, n = 7), and untrained control males (MC, n = 8) and females (FC, n = 6). MRI scans were performed, and resting M. vastus lateralis (VL) biopsies were subjected to RNA sequencing. Liver fat fraction, visceral adipose tissue volume (VAT), total body fat, and total lean tissue were measured from MRI data. Additionally, cross-sectional area (CSA) and fat signal fraction (FSF) were calculated from Mm. pectoralis, M. erector spinae and M. multifidus combined, Mm. quadriceps, and Mm. triceps surae (TS). Liver fat fraction, VAT, and total body fat relative to body weight were lower in ME and FE compared with corresponding controls. MS had a larger CSA across all four muscle groups and lower FSF in all muscles apart from TS compared with MC. ME had a lower FSF across all muscle groups and a larger CSA in all muscles except TS than MC. FE athletes showed a higher CSA in Mm. pectoralis and Mm. quadriceps and a lower CSA in TS than FC with no CSA differences found in the back muscles investigated. Surprisingly, the only difference in FSF between FE and FC was found in Mm. pectoralis. Lastly, correlations between VL gene expression and VL CSA as well as FSF showed that genes positively correlated with CSA revealed an enrichment of the oxidative phosphorylation and thermogenesis pathways, while the genes positively correlated with FSF showed significant enrichment of the spliceosome pathway. Although limited differences were found with training in females, our study suggests that both regular endurance and resistance training are useful in maintaining muscle mass, reducing adipose tissue deposits, and reducing muscle fat content in males.
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34.
  • Emanuelsson, Eric B., et al. (författare)
  • Remodeling of the human skeletal muscle proteome found after long-term endurance training but not after strength training
  • 2024
  • Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 27:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Exercise training has tremendous systemic tissue-specific health benefits, but the molecular adaptations to long-term exercise training are not completely understood. We investigated the skeletal muscle proteome of highly endurance-trained, strength-trained, and untrained individuals and performed exercise- and sex-specific analyses. Of the 6,000+ proteins identified, >650 were differentially expressed in endurance-trained individuals compared with controls. Strikingly, 92% of the shared proteins with higher expression in both the male and female endurance groups were known mitochondrial. In contrast to the findings in endurance-trained individuals, minimal differences were found in strength-trained individuals and between females and males. Lastly, a co-expression network and comparative literature analysis revealed key proteins and pathways related to the health benefits of exercise, which were primarily related to differences in mitochondrial proteins. This network is available as an interactive database resource where investigators can correlate clinical data with global gene and protein expression data for hypothesis generation.
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35.
  • Galal, Mohammed Omar, et al. (författare)
  • Percutaneous closure of atrial septal defect with situs solitus and dextrocardia.
  • 2015
  • Ingår i: Asian cardiovascular & thoracic annals. - : SAGE Publications. - 1816-5370 .- 0218-4923. ; 23:2, s. 202-205
  • Tidskriftsartikel (refereegranskat)abstract
    • Percutaneous closure of secundum atrial septal defect associated with situs solitus and dextrocardia has not been reported previously. We describe the technical difficulties encountered during transcatheter closure of a secundum atrial septal defect in a 19-month-old girl with situs solitus and dextrocardia.
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36.
  • Hossain, Mohammad Anwar, et al. (författare)
  • Genetic engineering for heavy metal/metalloid stress tolerance in plants
  • 2023
  • Ingår i: Heavy metal toxicity and tolerance in plants. - : John Wiley & Sons. - 9781119906506 - 9781119906469 ; , s. 573-592
  • Bokkapitel (refereegranskat)abstract
    • Modern agricultural techniques, anthropogenic activities, fast industrialization and urbanization, and the use of fossil fuels are the sources of significant contamination of the environment with various heavy metals (HMs) and metalloids. HM pollution has an impact on agricultural output and quality. What is more, accumulation of HMs in crops poses a threat to the human health. The problem of contamination of the arable lands with HMs and metalloids has to be addressed in various ways. One of the solutions is plant genetic engineering. Developing and cultivating commercial or industrial crop plants that display increased tolerance to HM-induced stress would let to use HM-affected areas for cultivation. Moreover, HM-tolerant hyperaccumulator plants can be used for phytoremediation of contaminated land. This chapter aims to offer a comprehensive review of current advances in genome transformation for improved plant tolerance to HMs/metalloids with special reference to the overexpression of genes encoding metal transporters, sulfur metabolites, metal chelators, and components of antioxidative system and glyoxalase pathways. In addition, we have discussed the potential of using CRISPR/Cas system in developing HM tolerance in plants.
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37.
  • Javed, Rida, et al. (författare)
  • Enhancement mechanism of P dopant on atomically distributed FeN 4 P-C electrocatalyst over a wide pH range
  • 2022
  • Ingår i: Electrochimica Acta. - : Elsevier BV. - 0013-4686. ; 436
  • Tidskriftsartikel (refereegranskat)abstract
    • Heteroatom doping plays an essential role in improving the catalytic performance of electrocatalysts for oxygen reduction reaction (ORR). However, how to regulate heteroatom doping remains a significant challenge. This paper develops an efficient strategy by using a novel versatile chelating ligand to enhance P loading and expose more metal single Fe atom active sites of FeN4P-C catalyst. The electron distribution of active center is considerably changed by P doping, which significantly influences the catalytic ORR performance. The dopant P in the FeN4P-C catalyst induces a small number of d-electrons from t2g-orbitals around the Fermi level, making the interaction between Fe active site and O2 slightly more robust than in the FeN4[sbnd]C catalyst, as studied by DFT calculations. The as-prepared FeN4P-C catalyst exhibits excellent catalytic ORR activity in both acidic (with a half-wave potential of 0.760 V vs. RHE) and basic (with a half-wave potential of 0.885 V vs. RHE) conditions, which are superior to those of the commercial Pt/C (20 wt%) catalyst. Furthermore, this catalyst also demonstrates outstanding stability and good hydrogen peroxide and methanol tolerance. A Zinc-air battery(ZAB) assembled using the cathode catalyst has validated the high performance of this catalyst. This study provides an efficient method for generating well-defined single-atom active sites to improve catalytic performance and paves the way to identify coordinated single metal atom sites for electrocatalysis applications.
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38.
  • Just, Kadri, et al. (författare)
  • Infectivity of Tomato yellow leaf curl virus isolated from imported tomato fruit in Estonia
  • 2017
  • Ingår i: Žemdirbystė. - : LITHUANIAN RESEARCH CENTRE AGRICULTURE & FORESTRY. - 1392-3196 .- 2335-8947. ; 104:1, s. 47-52
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a risk that Tomato yellow leaf curl virus (TYLCV) and its vector, whiteflies of the Bemisia tabaci species complex, will become established in greenhouses in temperate regions of the world, including northern Europe. In this study, TYLCV isolated from imported tomato fruit in Estonia (originating from Spain) was shown to be able to infect plants of tomato and Nicotiana benthamiana using Agrobacterium-mediated inoculation with an infectious clone as well as using biolistic delivery of products from rolling circle amplification (RCA). A 1.8-mer genomic construct of TYLCV was engineered and efficiently agroinfiltrated into plants of tomato and N. benthamiana, and induced symptoms characteristic of natural infection. With Agrobacterium-mediated inoculation, the infection efficiency was 100% for both tomato and N. benthamiana, whereas biolistic inoculation using RCA products resulted in efficiencies of 57% and 36%, respectively. Particle bombardment with monomeric linear genome failed to produce any infection in tomato or N. benthamiana. The genome of TYLCV amplified from tomato fruit was infectious confirming that tomato fruit may serve as a source of virus inoculum. This is the first report of agroinfiltration and particle bombardment assay using TYLCV DNA derived from infected tomato fruit tissue.
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39.
  • Karlsson, Max, et al. (författare)
  • A single-cell type transcriptomics map of human tissues
  • 2021
  • Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:31
  • Tidskriftsartikel (refereegranskat)abstract
    • Advances in molecular profiling have opened up the possibility to map the expression of genes in cells, tissues, and organs in the human body. Here, we combined single-cell transcriptomics analysis with spatial antibody-based protein profiling to create a high-resolution single-cell type map of human tissues. An open access atlas has been launched to allow researchers to explore the expression of human protein-coding genes in 192 individual cell type clusters. An expression specificity classification was performed to determine the number of genes elevated in each cell type, allowing comparisons with bulk transcriptomics data. The analysis highlights distinct expression clusters corresponding to cell types sharing similar functions, both within the same organs and between organs.
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40.
  • Karlsson, Max, et al. (författare)
  • Genome-wide annotation of protein-coding genes in pig
  • 2022
  • Ingår i: BMC Biology. - : Springer Nature. - 1741-7007. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is a need for functional genome-wide annotation of the protein-coding genes to get a deeper understanding of mammalian biology. Here, a new annotation strategy is introduced based on dimensionality reduction and density-based clustering of whole-body co-expression patterns. This strategy has been used to explore the gene expression landscape in pig, and we present a whole-body map of all protein-coding genes in all major pig tissues and organs. Results: An open-access pig expression map (www.rnaatlas.org ) is presented based on the expression of 350 samples across 98 well-defined pig tissues divided into 44 tissue groups. A new UMAP-based classification scheme is introduced, in which all protein-coding genes are stratified into tissue expression clusters based on body-wide expression profiles. The distribution and tissue specificity of all 22,342 protein-coding pig genes are presented. Conclusions: Here, we present a new genome-wide annotation strategy based on dimensionality reduction and density-based clustering. A genome-wide resource of the transcriptome map across all major tissues and organs in pig is presented, and the data is available as an open-access resource (www.rnaatlas.org), including a comparison to the expression of human orthologs.
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41.
  • Khan, Inayat, et al. (författare)
  • Zinc-Coordination Polymer-Derived Porous Carbon-Supported Stable PtM Electrocatalysts for Methanol Oxidation Reaction
  • 2021
  • Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 6:10, s. 6780-6790
  • Tidskriftsartikel (refereegranskat)abstract
    • Porous carbon (PC) is obtained by carbonizing a zinc-coordination polymer (MOF-5) at 950 °C and PtM (M = Fe, Co, Ni, Cu, Zn) nanoparticles (NPs), which are deposited on PC using the polyol method. Structural and morphological characterizations of the synthesized materials are carried out by powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), and high-resolution transmission electron microscopy (HRTEM), and the porosity was determined using a N2 adsorption/desorption technique. The results revealed that PtM NPs are alloyed in the fcc phase and are well dispersed on the surface of PC. The electrochemical results show that PtM/PC 950 catalysts have higher methanol oxidation reaction (MOR) performances than commercial Pt/C (20%) catalysts. After 3000 s of chronoamperometry (CA) test, the MOR performances decreased in the order of Pt1Cu1/PC 950 > Pt1Ni1/PC 950 > Pt1Fe1/PC 950 > Pt1Zn1/PC 950 > Pt1Co1/PC 950. The high MOR activities of the synthesized catalysts are attributed to the effect of M on methanol dissociative chemisorption and improved tolerance of Pt against CO poisoning. The high specific surface area and porosity of the carbon support have an additional effect in boosting the MOR activities. Screening of the first row transition metals (d5+n, n = 1, 2, 3, 4, 5) alloyed with Pt binary catalysts for MOR shows that Pt with d8 (Ni) and d9 (Cu) transition metals, in equivalent atomic ratios, are good anode catalysts for alcohol fuel cells. 
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42.
  • Klevstig, Martina, et al. (författare)
  • Cardiac expression of the microsomal triglyceride transport protein protects the heart function during ischemia
  • 2019
  • Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 0022-2828 .- 1095-8584. ; 137, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: The microsomal triglyceride transport protein (MTTP) is critical for assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins and is most abundant in the liver and intestine. Surprisingly, MTTP is also expressed in the heart. Here we tested the functional relevance of cardiac MTTP expression. Materials and methods: We combined clinical studies, advanced expression analysis of human heart biopsies and analyses in genetically modified mice lacking cardiac expression of the MTTP-A isoform of MTTP. Results: Our results indicate that lower cardiac MTTP expression in humans is associated with structural and perfusion abnormalities in patients with ischemic heart disease. MTTP-A deficiency in mice heart does not affect total MTTP expression, activity or lipid concentration in the heart. Despite this, MTTP-A deficient mice displayed impaired cardiac function after a myocardial infarction. Expression analysis of MTTP indicates that MTTP expression is linked to cardiac function and responses in the heart. Conclusions: Our results indicate that MTTP may play an important role for the heart function in conjunction to ischemic events.
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43.
  • Lam, Simon, et al. (författare)
  • Machine Learning Analysis Reveals Biomarkers for the Detection of Neurological Diseases
  • 2022
  • Ingår i: Frontiers in Molecular Neuroscience. - : Frontiers Media SA. - 1662-5099. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • It is critical to identify biomarkers for neurological diseases (NLDs) to accelerate drug discovery for effective treatment of patients of diseases that currently lack such treatments. In this work, we retrieved genotyping and clinical data from 1,223 UK Biobank participants to identify genetic and clinical biomarkers for NLDs, including Alzheimer's disease (AD), Parkinson's disease (PD), motor neuron disease (MND), and myasthenia gravis (MG). Using a machine learning modeling approach with Monte Carlo randomization, we identified a panel of informative diagnostic biomarkers for predicting AD, PD, MND, and MG, including classical liver disease markers such as alanine aminotransferase, alkaline phosphatase, and bilirubin. A multinomial model trained on accessible clinical markers could correctly predict an NLD diagnosis with an accuracy of 88.3%. We also explored genetic biomarkers. In a genome-wide association study of AD, PD, MND, and MG patients, we identified single nucleotide polymorphisms (SNPs) implicated in several craniofacial disorders such as apnoea and branchiootic syndrome. We found evidence for shared genetic risk loci among NLDs, including SNPs in cancer-related genes and SNPs known to be associated with non-brain cancers such as Wilms tumor, leukemia, and colon cancer. This indicates overlapping genetic characterizations among NLDs which challenges current clinical definitions of the neurological disorders. Taken together, this work demonstrates the value of data-driven approaches to identify novel biomarkers in the absence of any known or promising biomarkers.
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44.
  • Lam, Simon, et al. (författare)
  • Systems Analysis Reveals Ageing-Related Perturbations in Retinoids and Sex Hormones in Alzheimer's and Parkinson's Diseases
  • 2021
  • Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 9:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurodegenerative diseases, including Alzheimer's (AD) and Parkinson's diseases (PD), are complex heterogeneous diseases with highly variable patient responses to treatment. Due to the growing evidence for ageing-related clinical and pathological commonalities between AD and PD, these diseases have recently been studied in tandem. In this study, we analysed transcriptomic data from AD and PD patients, and stratified these patients into three subclasses with distinct gene expression and metabolic profiles. Through integrating transcriptomic data with a genome-scale metabolic model and validating our findings by network exploration and co-analysis using a zebrafish ageing model, we identified retinoids as a key ageing-related feature in all subclasses of AD and PD. We also demonstrated that the dysregulation of androgen metabolism by three different independent mechanisms is a source of heterogeneity in AD and PD. Taken together, our work highlights the need for stratification of AD/PD patients and development of personalised and precision medicine approaches based on the detailed characterisation of these subclasses.
  •  
45.
  • Laudette, Marion, et al. (författare)
  • Cardiomyocyte-specific PCSK9 deficiency compromises mitochondrial bioenergetics and heart function
  • 2023
  • Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:7, s. 1537-1552
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Pro-protein convertase subtilisin-kexin type 9 (PCSK9), which is expressed mainly in the liver and at low levels in the heart, regulates cholesterol levels by directing low-density lipoprotein receptors to degradation. Studies to determine the role of PCSK9 in the heart are complicated by the close link between cardiac function and systemic lipid metabolism. Here, we sought to elucidate the function of PCSK9 specifically in the heart by generating and analysing mice with cardiomyocyte-specific Pcsk9 deficiency (CMPcsk9−/− mice) and by silencing Pcsk9 acutely in a cell culture model of adult cardiomyocyte-like cells. Methods and results Mice with cardiomyocyte-specific deletion of Pcsk9 had reduced contractile capacity, impaired cardiac function, and left ventricular dilatation at 28 weeks of age and died prematurely. Transcriptomic analyses revealed alterations of signalling pathways linked to cardiomyopathy and energy metabolism in hearts from CM-Pcsk9−/− mice vs. wild-type littermates. In agreement, levels of genes and proteins involved in mitochondrial metabolism were reduced in CM-Pcsk9−/− hearts. By using a Seahorse flux analyser, we showed that mitochondrial but not glycolytic function was impaired in cardiomyocytes from CM-Pcsk9−/− mice. We further showed that assembly and activity of electron transport chain (ETC) complexes were altered in isolated mitochondria from CM-Pcsk9−/− mice. Circulating lipid levels were unchanged in CM-Pcsk9−/− mice, but the lipid composition of mitochondrial membranes was altered. In addition, cardiomyocytes from CM-Pcsk9−/− mice had an increased number of mitochondria–endoplasmic reticulum contacts and alterations in the morphology of cristae, the physical location of the ETC complexes. We also showed that acute Pcsk9 silencing in adult cardiomyocyte-like cells reduced the activity of ETC complexes and impaired mitochondrial metabolism. Conclusion PCSK9, despite its low expression in cardiomyocytes, contributes to cardiac metabolic function, and PCSK9 deficiency in cardiomyocytes is linked to cardiomyopathy, impaired heart function, and compromised energy production.
  •  
46.
  • Lee, Sunjae, et al. (författare)
  • TCSBN: a database of tissue and cancer specific biological networks
  • 2018
  • Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 46:D1
  • Tidskriftsartikel (refereegranskat)abstract
    • Biological networks provide new opportunities for understanding the cellular biology in both health and disease states. We generated tissue specific integrated networks (INs) for liver, muscle and adipose tissues by integratingmetabolic, regulatory and protein-protein interaction networks. We also generated human co-expression networks (CNs) for 46 normal tissues and 17 cancers to explore the functional relationships between genes as well as their relationships with biological functions, and investigate the overlap between functional and physical interactions provided by CNs and INs, respectively. These networks can be employed in the analysis of omics data, provide detailed insight into disease mechanisms by identifying the key biological components and eventually can be used in the development of efficient treatment strategies. Moreover, comparative analysis of the networks may allow for the identification of tissue-specific targets that can be used in the development of drugs with the minimum toxic effect to other human tissues. These context-specific INs and CNs are presented in an interactive website http://inetmodels.com without any limitation.
  •  
47.
  • Li, Xiangyu, et al. (författare)
  • Classification of clear cell renal cell carcinoma based on PKM alternative splicing
  • 2020
  • Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 6:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Clear cell renal cell carcinoma (ccRCC) accounts for 70-80% of kidney cancer diagnoses and displays high molecular and histologic heterogeneity. Hence, it is necessary to reveal the underlying molecular mechanisms involved in progression of ccRCC to better stratify the patients and design effective treatment strategies. Here, we analyzed the survival outcome of ccRCC patients as a consequence of the differential expression of four transcript isoforms of the pyruvate kinase muscle type (PKM). We first extracted a classification biomarker consisting of eight gene pairs whose within-sample relative expression orderings (REOs) could be used to robustly classify the patients into two groups with distinct molecular characteristics and survival outcomes. Next, we validated our findings in a validation cohort and an independent Japanese ccRCC cohort. We finally performed drug repositioning analysis based on transcriptomic expression profiles of drug-perturbed cancer cell lines and proposed that paracetamol, nizatidine, dimethadione and conessine can be repurposed to treat the patients in one of the subtype of ccRCC whereas chenodeoxycholic acid, fenoterol and hexylcaine can be repurposed to treat the patients in the other subtype.
  •  
48.
  • Li, Xiangyu, et al. (författare)
  • Discovery of Functional Alternatively Spliced PKM Transcripts in Human Cancers
  • 2021
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:2, s. 1-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Simple Summary Pyruvate kinase muscle type (PKM) is a key enzyme in glycolysis and is a mediator of the Warburg effect in tumors. The association of PKM with survival of cancer patients is controversial. In this study, we investigated the associations of the alternatively spliced transcripts of PKM with cancer patients' survival outcomes and explained the conflicts in previous studies. We discovered three poorly studied alternatively spliced PKM transcripts that exhibited opposite prognostic indications in different human cancers based on integrative systems analysis. We also detected their protein products and explored their potential biological functions based on in-vitro experiments. Our analysis demonstrated that alternatively spliced transcripts of not only PKM but also other genes should be considered in cancer studies, since it may enable the discovery and targeting of the right protein product for development of the efficient treatment strategies. Pyruvate kinase muscle type (PKM) is a key enzyme in glycolysis and plays an important oncological role in cancer. However, the association of PKM expression and the survival outcome of patients with different cancers is controversial. We employed systems biology methods to reveal prognostic value and potential biological functions of PKM transcripts in different human cancers. Protein products of transcripts were shown and detected by western blot and mass spectrometry analysis. We focused on different transcripts of PKM and investigated the associations between their mRNA expression and the clinical survival of the patients in 25 different cancers. We find that the transcripts encoding PKM2 and three previously unstudied transcripts, namely ENST00000389093, ENST00000568883, and ENST00000561609, exhibited opposite prognostic indications in different cancers. Moreover, we validated the prognostic effect of these transcripts in an independent kidney cancer cohort. Finally, we revealed that ENST00000389093 and ENST00000568883 possess pyruvate kinase enzymatic activity and may have functional roles in metabolism, cell invasion, and hypoxia response in cancer cells. Our study provided a potential explanation to the controversial prognostic indication of PKM, and could invoke future studies focusing on revealing the biological and oncological roles of these alternative spliced variants of PKM.
  •  
49.
  • Li, Xiangyu, et al. (författare)
  • Stratification of patients with clear cell renal cell carcinoma to facilitate drug repositioning
  • 2021
  • Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 24:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Clear cell renal cell carcinoma (ccRCC) is the most common histological type of kidney cancer and has high heterogeneity. Stratification of ccRCC is important since distinct subtypes differ in prognosis and treatment. Here, we applied a systems biology approach to stratify ccRCC into three molecular subtypes with different mRNA expression patterns and prognosis of patients. Further, we developed a set of biomarkers that could robustly classify the patients into each of the three subtypes and predict the prognosis of patients. Then, we reconstructed subtype-specific metabolic models and performed essential gene analysis to identify the potential drug targets. We identified four drug targets, including SOAT1, CRLS1, and ACACB, essential in all the three subtypes and GPD2, exclusively essential to subtype 1. Finally, we repositioned mitotane, an FDA-approved SOAT1 inhibitor, to treat ccRCC and showed that it decreased tumor cell viability and inhibited tumor cell growth based on in vitro experiments.
  •  
50.
  • Liu, Zhengtao, et al. (författare)
  • Pyruvate kinase L/R is a regulator of lipid metabolism and mitochondrial function
  • 2019
  • Ingår i: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 52, s. 263-272
  • Tidskriftsartikel (refereegranskat)abstract
    • The pathogenesis of non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) has been associated with altered expression of liver-specific genes including pyruvate kinase liver and red blood cell (PKLR), patatin-like phospholipase domain containing 3 (PNPLA3) and proprotein convertase subtilisin/kexin type 9 (PCSK9). Here, we inhibited and overexpressed the expression of these three genes in HepG2 cells, generated RNA-seq data before and after perturbation and revealed the altered global biological functions with the modulation of these genes using integrated network (IN) analysis. We found that modulation of these genes effects the total triglycerides levels within the cells and viability of the cells. Next, we generated IN for HepG2 cells, identified reporter transcription factors based on IN and found that the modulation of these genes affects key metabolic pathways associated with lipid metabolism (steroid biosynthesis, PPAR signalling pathway, fatty acid synthesis and oxidation) and cancer development (DNA replication, cell cycle and p53 signalling) involved in the progression of NAFLD and HCC. Finally, we observed that inhibition of PKLR lead to decreased glucose uptake and decreased mitochondrial activity in HepG2 cells. Hence, our systems level analysis indicated that PKLR can be targeted for development efficient treatment strategy for NAFLD and HCC.
  •  
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