Search results for: biochemical pathway

Authors: Karthik Mittal

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This study performs an unsupervised machine learning analysis to find clusters of related SNPs which highlight biological pathways that are important for the biological mechanisms of breast cancer. Studying genetic variations in isolation is illogical because these genetic variations are known to modulate protein production and function; the downstream effects of these modifications on biological outcomes are highly interconnected. After extracting the SNPs and their effect on different types of breast cancer using the MRBase library, two unsupervised machine learning clustering algorithms were implemented on the genetic variants: a k-means clustering algorithm and a hierarchical clustering algorithm; furthermore, principal component analysis was executed to visually represent the data. These algorithms specifically used the SNP’s beta value on the three different types of breast cancer tested in this project (estrogen-receptor positive breast cancer, estrogen-receptor negative breast cancer, and breast cancer in general) to perform this clustering. Two significant genetic pathways validated the clustering produced by this project: the MAPK signaling pathway and the connection between the BRCA2 gene and the ESR1 gene. This study provides the first proof of concept showing the importance of unsupervised machine learning in interpreting GWAS summary statistics.

Keywords: breast cancer, computational biology, unsupervised machine learning, k-means, PCA

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Authors: Methawee Yuttapongtada

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Intensifier is the linguistic term and device that is generally found in different languages in order to enhance and give additional quantity, quality or emotion to the words of each language. In fact, each language in the world has both of the similar and dissimilar intensifying device. More specially, the wide variety of intensifying device is used for Thai language and one of those is usage of the impolite word or the word that used to mean something negative as intensifier. The data collection in this study was done throughout the spoken language style by collecting from intensifiers regarded as impolite words because these words as employed in the other contexts will be held as the rude, swear words or the words with negative meaning. Then, backward study to the past was done in order to consider the historical change. Explanation of the original meaning and the contexts of words use from the past till the present time were done by use of both textual documents and dictionaries available in different periods. It was found that regarding the semantics and pragmatic aspects, subjectification also is the significant motivation that changed the impolite words to intensifiers. At last, it can explain pathway of the semantic change of these very words undoubtedly. Moreover, it is found that use tendency in the impolite word or the word that used to mean something negative will more be increased and this phenomenon is commonly found in many languages in the world and results of this research may support to the belief that human language in the world is universal and the same still reflected that human has the fundamental thought as the same to each other basically.

Keywords: impolite word, intensifier, Thai, semantic change

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Authors: Sónia Ribeiro, Diana Farinha, Hélia Sales, Rita Pontes, João Nunes

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The demand and commitment to sustainability in the agrifood sector introduce news opportunities for new composite materials. Composite materials are emerging as a vital entity for the sustainable development. Polylactic acid (PLA) has been recognized as a potential polymer with attractive characteristics for agrifood sector applications. PLA that can be beneficial for the development of composites, biocomposites, films, porous gels, and so on. The production of PLA from lignocellulosic biomass residues matrix is a key option towards a sustainable and circular bioeconomy and a non-competitive application with feed and food sector. The Flui and BeirInov projects presents news developments in the production of PLA composites to value the Portuguese forest ecosystem, with high amount of lignocellulosic biomass residues and available. A performance production of lactic acid from lignocellulosic biomass undergoes a process of autohydrolysis, saccharification and fermentation, originating a lactic acid fermentation medium with a 72.27g.L-1 was obtained and a final purification of 72%. The high purification PLA from multi lignocellulosic residues representing one economic expensive process, and a new materials and application for the polymers and a combination with others types of composites matrix characteristic is the drive-up for this green market.

Keywords: polylactic acid, lignocellulosic biomass, agrifood, composite materials

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Authors: Munir Majdalawieh, Adam Marks

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In today’s very competitive higher education industry (HEI), HEIs are faced with the primary concern of developing, deploying, and sustaining high quality academic programs. Today, the HEI has well-established accreditation systems endorsed by a country’s legislation and institutions. The accreditation system is an educational pathway focused on the criteria and processes for evaluating educational programs. Although many aspects of the accreditation process highlight both the past and the present (prove), the “program review” assessment is "forward-looking assessment" (improve) and thus transforms the process into a continuing assessment activity rather than a periodic event. The purpose of this study is to propose a conceptual measurement framework for program review to be used by HEIs to undertake a robust and targeted approach to proactively and continuously review their academic programs to evaluate its practicality and effectiveness as well as to improve the education of the students. The proposed framework consists of two main components: program review principles and the program review measurement matrix.

Keywords: academic program, program review principles, curriculum development, accreditation, evaluation, assessment, review measurement matrix, program review process, information technologies supporting learning, learning/teaching methodologies and assessment

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Authors: Merzougui Imene, Gherib Asma, Henchiri Cherifa

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This study has allowed to confirm the physico chemical characteristics and fatty acid composition by GC of the oil of Pistacia lentiscus extracted by traditional method and evaluate its effect on some blood lipid parameters. The results showed that the main physico chemical characteristics of Pistacia lentiscus oil are: moisture (0.84 %), a relatively high iodine value (80,44) indicating that this oil has an important degree of unsaturation. The oil is mainly composed of unsaturated fatty acids (MUFA) where oleic acid dominate with 47,01 % of total fatty acids and PUFA's represented by linoleic acid (19,26 %). Concerning the biological survey, oil, at 10% and 20% doses of diet for 15 and 30 days of two periods of treatment, resulted in beneficial effects on the lipid profile of Wistar albinos rats previously fed with animal and vegetable fats. We observed decreases in total cholesterol, triglycerides (TGA), total lipids and LDL-C, and an increase in HDL-C "good cholesterol" probably related to the presence of a large amount of (MUFA) and (PUFA).

Keywords: Pistacia lentiscus, oil, lipid profile, monounsaturated fatty acids, polyunsaturated fatty acids

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Authors: Chloe T. Cohen, Sarah Johnson

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Psychoanalytic literature has traditionally focused on the theoretical explanations of psychological phenomena rather than empirical research to support those ideas. Many clinicians assume a lack of empirical verification of the theories that underpin psychoanalytic treatment disqualifies psychoanalytic psychotherapy as an effective clinical technique. One such theory is Lacan’s ‘Name of the Father’, which extended Freud’s idea of the importance of a successful resolution of the Oedipal problem, situating it even earlier in psychological development. Lacan posited that the Name of the Father construct (establishing psychological structure and preventing psychosis) was best represented in language use, metaphor, and linguistic structure. However, no study to date has empirically examined the Name of the Father construct. The current study attempts to measure Lacan’s ‘Name of the Father’ construct through linguistic structure and metaphor use and to compare it with Freud’s ‘original introject’. We will then investigate whether they relate to adult personality functioning (measured using the Rorschach Inkblot Test). We aim to contribute to the empirical study of psychoanalytic concepts by operationalizing and validating the Name of the Father empirically. We also aim to examine the relationship of the Name of the Father construct to Freud’s concept of the original introject and to adult pathology. We hypothesize that measures of the original introject will mediate the pathway between linguistic indicators of Lacan’s Name of the Father construct and personality functioning.

Keywords: Lacan, Name of the Father, original introject, personality functioning, psychoanalysis

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Authors: Harminder Kaur, Manpreet Kaur, Akanksha Kapila, Reenu

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Schiff base with general formula H₂L was derived from condensation of o-vanillin and 3-nitro-o-phenylenediamine. This Schiff base was used for the synthesis of organotin(IV) complexes with general formula R₂SnL [R=Phenyl or n-octyl] using equimolar quantities. Elemental analysis UV-Vis, FTIR, and multinuclear spectroscopic techniques (¹H, ¹³C, and ¹¹⁹Sn) NMR were carried out for the characterization of the synthesized complexes. These complexes were coloured and soluble in polar solvents. Computational studies have been performed to obtain the details of the geometry and electronic structures of ligand as well as complexes. Geometry of the ligands and complexes have been optimized at the level of Density Functional Theory with B3LYP/6-311G (d,p) and B3LYP/MPW1PW91 respectively followed by vibrational frequency analysis using Gaussian 09. Observed ¹¹⁹Sn NMR chemical shifts of one of the synthesized complexes showed tetrahedral geometry around Tin atom which is also confirmed by DFT. HOMO-LUMO energy distribution was calculated. FTIR, ¹HNMR and ¹³CNMR spectra were also obtained theoretically using DFT. Further IRC calculations were employed to determine the transition state for the reaction and to get the theoretical information about the reaction pathway. Moreover, molecular docking studies can be explored to ensure the anticancer activity of the newly synthesized organotin(IV) complexes.

Keywords: DFT, molecular docking, organotin(IV) complexes, o-vanillin, 3-nitro-o-phenylenediamine

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Authors: Khaled S. Al Salhen

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Aldehyde oxidase is molybdo-flavoenzyme involved in the oxidation of hundreds of endogenous and exogenous and N-heterocyclic compounds and environmental pollutants. Uncharged N-heterocyclic aromatic compounds such phenanthridine are commonly distributed pollutants in soil, air, sediments, surface water and groundwater, and in animal and plant tissues. Phenanthridine as uncharged N-heterocyclic aromatic compound was incubated with partially purified aldehyde oxidase from rainbow trout fish liver. Reversed-phase HLPC method was used to separate the oxidation products from phenanthridine and the metabolite was identified. The 6(5H)-phenanthridinone was identified the major metabolite by partially purified aldehyde oxidase from fish liver. Kinetic constant for the oxidation reactions were determined spectrophotometrically and showed that this substrate has a good affinity (Km = 78 ± 7.6 µM) for hepatic aldehyde oxidase, coupled with a relatively high oxidation rate (0.77± 0.03 nmol/min/mg protein). In addition, the kinetic parameters of hepatic fish aldehyde oxidase towards the phenanthridine substrate indicate that in vitro biotransformation by hepatic fish aldehyde oxidase will be a significant pathway. This study confirms that partially purified aldehyde oxidase from fish liver is indeed the enzyme responsible for the in vitro production 6(5H)-phenanthridinone metabolite as it is a major metabolite by mammalian aldehyde oxidase.

Keywords: aldehyde oxidase, fish, phenanthridine, specificity

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Authors: P. Chihomvu, P. Stegmann, M. Pillay

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Pollution of the Klip River has caused microorganisms inhabiting it to develop protective survival mechanisms. This study isolated and characterized the heavy metal resistant bacteria in the Klip River. Water and sediment samples were collected from six sites along the course of the river. The pH, turbidity, salinity, temperature and dissolved oxygen were measured in-situ. The concentrations of six heavy metals (Cd, Cu, Fe, Ni, Pb, and Zn) of the water samples were determined by atomic absorption spectroscopy. Biochemical and antibiotic profiles of the isolates were assessed using the API 20E® and Kirby Bauer Method. Growth studies were carried out using spectrophotometric methods. The isolates were identified using 16SrDNA sequencing. The uppermost part of the Klip River with the lowest pH had the highest levels of heavy metals. Turbidity, salinity and specific conductivity increased measurably at Site 4 (Henley on Klip Weir). MIC tests showed that 16 isolates exhibited high iron and lead resistance. Antibiotic susceptibility tests revealed that the isolates exhibited multi-tolerances to drugs such as tetracycline, ampicillin, and amoxicillin.

Keywords: Klip River, heavy metals, resistance, 16SrDNA

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Authors: Kazui Sasakii, Seira Mormune-Moriya, Hiroaki Tanahashi, Shigeji Kongaya

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Poly (3.4-ethylenedioxythiophene) doped with poly (4-styrene sulfonate) (PEDOT: PSS) attracted a great deal of attention because of its unique characteristics of flexibility, optical properties, heat resistance and colloidal dispersion in water. It is well known that when high boiling solvents such as ethylene glycol or dimethyl sulfoxide are added as a secondary dopant to the micellar structure, PEDOT microcrystallizes and becomes highly conductive. In previous study bis(4-hydroxyphenyl) sulfone (BPS) was used as a secondary dopant for PEDOT:PSS and the enhancement of the conductivity was revealed. However, ductility is one of the serious issues which limited the application of PEDOT:PSS/BPS. So far, the composition with polymer binders has been conducted, however, polymer binders decrease the conductivity of the materials. In this study, PEDOT: PSS composites with polyester (PEs) were prepared by a simple aqueous process using PEs emulsion. The structural studies revealed that PEDOT:PSS and PEs were homogeneously distributed in the composites. It was found that the properties of PEDOT:PSS were remarkably enhanced by the incorporation of PEs. According to the tensile test, the ductility of PEDOT:PSS was remarkably improved. Interestingly, the conductivity of PEDOT:PSS/PEs composites was higher than that of neat PEDOT:PSS. For example, the conductivity increased by 8% at PEs content of 25 wt%. Since PEDOT:PSS were homogeneously dispersed on the surface of PEs particles, it was assumed that the conductive pathway was constructed by PEs particles in the nanocomposites. Therefore, a significant increase in conductivity was achieved.

Keywords: polymer composites, conductivity, PEDOT:PSS, polyester

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Authors: Christos Bouras, Eirini Stergiou, Charitini Karakostaki, Vasileios Tzanos, Vasileios Kokkinos

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Wind power represents a major pathway to curtailing greenhouse gas emissions and thus reducing the rate of climate change. A wind turbine runs practically emission-free for 20 years, representing one of the most environmentally sustainable sources of energy. Nevertheless, environmental and biodiversity concerns can often slow down or halt the deployment of wind farms due to local public opposition. This opposition is often fueled by poor relationships between wind energy stakeholders and civil society, which in many cases led to conflictual protests and property damage. In this context, addressing these concerns is essential in order to facilitate the proliferation of wind farms in Europe and the phase-out of fossil fuels from the energy mix. The aim of this study is to identify a number of good practices and cases to avoid increasing biodiversity protection at all stages of wind farms’ lifecycle in three participating countries, namely Greece, Latvia, and Poland. The results indicate that although available technological solutions are already being exploited worldwide, in these countries, there is still room for improvement. To address this gap, a set of policy recommendations is proposed to accomplish the wind energy targets in the near future while simultaneously mitigating the pertinent biodiversity risks.

Keywords: biodiversity protection, environmental impact, social acceptance, wind energy

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Authors: Kimuli Ismail, Michael Lubwama, John Baptist Kirabira, Adam Sebbit

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This study develops 4 energy scenarios for Greater Kampala Metropolitan Area (GKMA). GKMA is Uganda’s capital with a population of 4.1million and a GDP growth rate of 5.8 with a nonsustainable energy management system. The study uses TIMES-VEDA to examine the energy impacts of business as usual (BAU), Kabejja, Carbon-Tax, and Lutta scenarios in commercial, industrial, transportation, residential, agricultural, and electricity generation activities. BAU is the baseline scenario with limited CO2 emissions restrictions against which Kabejja with 20% CO2 emissions restriction, a carbon tax of $100/ton imposed in 2050 for Carbon-Tax scenario, and Lutta with 95% CO2 emissions restriction is made. The analysis suggests that if the current policy trends continue as BAU, consumption would increase from 139.6PJ to 497.42PJ and CO2 emissions will increase from 4.6mtns to 7mtns. However, consumption would decrease by 2.3% in Kabejja, 3.4% in Carbon-Tax, and 3.3 % in Lutta compared to BAU. The CO2 emissions would decrease by 8.57% in Kabejja, 55.14% in Carbon-Tax, and 60% in Lutta compared to BAU. Sustainability is achievable when low-carbon electricity is increased by 53.68% in the EMS, and setting up an electrified Kampala metro. The study recommends Lutta as the sustainable pathway to a lowcarbon 2050.

Keywords: Sustainability, Scenario Plannnig, Times-Veda Modelling, Energy Policy Development

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Authors: Zi-Han Li, Lu Fang, Liang Wu, Dong-Yuan Chang, Manyuan Dong, Liang Ji, Qi Zhang, Ming-Hui Zhao, Sydney C. W. Tang, Lemin Zheng, Min Chen

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Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia, which were risk factors for diabetic nephropathy (DN). Recently, we found that ANXA1 could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, we identified uncoupling protein 1 (UCP1), an inner membrane protein of mitochondria, as a key to mitochondrial homeostasis improved by ANXA1. Specifically, ANXA1 attenuated mitochondrial dysfunction via appropriately upregulating UCP1 by stabilizing its transcription factor GATA binding protein 3 (GATA3) by combining it with thioredoxin. Moreover, specific overexpression of UCP1 in the renal cortex rescued renal injuries in diabetic Anxa1-KO mice. UCP1 deletion aggravated renal injuries in HFD/STZ-induced diabetic mice. Mechanistically, UCP1 reduced mitochondrial fission through the aristaless-related homeobox (ARX)/cardiolipin synthase 1 (CRLS1) pathway. Therapeutically, CL316243, a UCP1 agonist, could attenuate established DN in db/db mice. This work established an alternative principle to harness the power of uncouplers for the treatment of DN.

Keywords: diabetic nephropathy, uncoupling protein 1, mitochondrial homeostasis, cardiolipin metabolism

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Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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Authors: Shan-Ying Wu, Sheng-Hui Lan, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu

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In hepatocelluar carcinoma (HCC), dysregulated expression of cyclin D1 and impaired autophagy has been reported separately. However, the relationship between them has not been explored. In this study, we demonstrated that autophagy was inversely correlated with cyclin D1 expression in 147 paired HCC patient specimens. HCC specimen with highly expression of cyclin D1 shows correlation with poor overall survival rate. Furthermore, induction of autophagy by amiodarone (antiarrhythmic drug) in Hep 3B cells, cyclin D1 was recruited into autophagosomes demonstrated by immune-gold labeling of cyclin D1 after extraction of autophagosomes. We further demonstrated that autophagy suppresses Hep 3B cell proliferation, and further analysis revealed that cell cycle was arrested at G1 phase. The interaction between LC3 (maker of autophagy) and cyclin D1 was increased after autophagy induction. In addition, ubiquitinated-cyclin D1 was also increased after autophagy induction, which is selectively degraded by autophagosome through binding with SQSTM1/p62 (an adaptor protein). In vivo study showed that amiodarone induced autophagy suppresses liver tumor formation in xenograft mouse and orthotopic rat model through decreasing cyclin D1 expression and inhibition of cell proliferation. Altogether, we reveal a novel mechanism that ubiquitinated cyclin D1 degraded by autophagic pathway by p62 and amiodarone is a promising drug for targeting cyclin D1 in liver cancer therapy.

Keywords: autophagy, cyclin D1, hepatocellular carcinoma, amiodarone

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Authors: Zi-Han Li, Lu Fang, Liang Wu, Dong-Yuan Chang, Manyuan Dong, Liang Ji, Qi Zhang, Ming-Hui Zhao, Sydney C.W. Tang, Lemin Zheng, Min Chen

Abstract:

Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia, which were risk factors for diabetic nephropathy (DN). Recently, it was found that annexin A1(ANXA1) could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, it was identified that uncoupling protein 1 (UCP1), an inner membrane protein of mitochondria, as a key to mitochondrial homeostasis improved by ANXA1. Specifically, ANXA1 attenuated mitochondrial dysfunction via appropriately upregulating UCP1 by stabilizing its transcription factor GATA binding protein 3 (GATA3) through combining with thioredoxin. Moreover, specific overexpression of UCP1 in renal cortex rescued renal injuries in diabetic Anxa1-KO mice. UCP1 deletion aggravated renal injuries in HFD/STZ-induced diabetic mice. Mechanistically, UCP1 reduced mitochondrial fission through the aristaless-related homeobox (ARX)/cardiolipin synthase 1 (CRLS1) pathway. Therapeutically, CL316243, a UCP1 agonist, could attenuate established DN in db/db mice. This work established a novel principle to harness the power of uncouplers for the treatment of DN.

Keywords: diabetic nephropathy, uncoupling protein 1, mitochondrial homeostasis, cardiolipin metabolism

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Authors: Pui Shan Wong, Kosuke Tashiro, Satoru Kuhara, Sachiyo Aburatani

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Functional genomics and gene regulation inference has readily expanded our knowledge and understanding of gene interactions with regards to expression regulation. With the advancement of transcriptome sequencing in time-series comes the ability to study the sequential changes of the transcriptome. This method presented here works to augment existing regulation networks accumulated in literature with transcriptome data gathered from time-series experiments to construct a sequential representation of transcription factor activity. This method is applied on a time-series RNA-Seq data set from Escherichia coli as it transitions from growth to stationary phase over five hours. Investigations are conducted on the various metabolic activities in gene regulation processes by taking advantage of the correlation between regulatory gene pairs to examine their activity on a dynamic network. Especially, the changes in metabolic activity during phase transition are analyzed with focus on the pagP gene as well as other associated transcription factors. The visualization of the sequential transcriptional activity is used to describe the change in metabolic pathway activity originating from the pagP transcription factor, phoP. The results show a shift from amino acid and nucleic acid metabolism, to energy metabolism during the transition to stationary phase in E. coli.

Keywords: Escherichia coli, gene regulation, network, time-series

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Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Y. S. Mohamed, L. A. Ahmed, H. A. Salem, A. M. Agha

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Liver Fibrosis is one of the most serious conditions that affect the Egyptian society. In the present study, the effect of nicorandil was investigated in experimentally-induced liver fibrosis by bile duct ligation in rats. Nicorandil (3mg/kg/day) was given orally 24 h after bile duct ligation for 14 days till the end of the experiment. Nicorandil group showed a significant improvement in liver function tests (ALT and ALP) as well as a significant decrease in oxidative stress biomarkers (TBARS and GSH), area of fibrosis and activity of hepatic stellate cells as indicated by decreased expression of alpha smooth muscle actin.Moreover, nicorandil treatment decreased HSCs proliferation due to its inhibitory effects on protein kinase C(PKC) and Platelet derived growth factor (PDGF) . Oral administration of either glibenclamide (10 mg/kg/day)(a KATP channel blocker) or L-NAME (30 mg/kg/day) (an inhibitor of nitric oxide synthase) blocked the protective effects of nicorandil. However, nicorandil and L-NAME treated group showed more or less results similar to that of untreated bile duct ligated group. In conclusion, nicorandil was effective against the development of bile duct ligated-induced liver fibrosis in rats where activation of the NO pathway plays an important role in the protective effect nicorandil.

Keywords: hepatic stellate cells, nicorandil, nitric oxide donor, liver fibrosis

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Authors: A. Duncan, A. Blake, A. O'Gara, J. Fitzgerald

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Introduction: Acute traumatic rib fractures have significant morbidity and mortality and are a commonly seen injury in trauma patients. Rib fracture pain can often be acute and can prove challenging to manage. We performed an audit on patients with acute traumatic rib fractures with the aim of composing a referral and treatment pathway for such patients. Methods: From January 2021 to January 2022, the pain medicine service encouraged early referral of all traumatic rib fractures to the pain service for a multi-modal management approach. A retrospective audit of analgesic management was performed on a select cohort of 24 patients, with a mean age of 67, of which 19 had unilateral rib fractures. Results: 17 of 24 patients (71%) underwent local, regional block as part of a multi-modal analgesia regime. Only one regional complication was observed, seen with hypotension occurring in one patient with a thoracic epidural. The group who did not undergo regional block had a length of stay (LOS) 17 days longer than those who did (27 vs. 10) and higher rates of pneumonia (29% vs. 18%). Conclusion: Early referral to pain specialists is an important component of the effective management of acute traumatic rib fractures. From our audit, it is evident that regional blocks can be effectively used in these cases as part of a multi-modal analgesia regime and may confer benefits in terms of respiratory complications and length of stay.

Keywords: rib fractures, regional blocks, thoracic epidural, erector spina block

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Authors: Orapan Paecharoenchai, Tanasait Ngawhirunpat, Theerasak Rojanarata, Auayporn Apirakaramwong, Praneet Opanasopit

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Cationic niosomes formulated with Span20, cholesterol and novel synthesized spermine-cationic lipids (2-hydrocarbon tail and 4- hydrocarbon tail) in a molar ratio of 2.5:2.5:1 can mediate high gene transfection in vitro. However, the uptake mechanisms of these systems are not well clarified. In the present study, effect of endocytic inhibitors on the transfection efficiency of niosomes/DNA complexes was determined on a human cervical carcinoma cell line (HeLa cells) using the inhibitors of macropinocytosis (wortmannin), clathrin- and caveolae-mediated endocytosis (methyl-β-cyclodextrin), clathrin-mediated endocytosis (chlorpromazine), caveolae-mediated endocytosis (genistein and filipin), cytosolic transfer (ammonium chloride) and microtubules polymerization (nocodazole). The transfection of niosomes with 2-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride and filipin, respectively, whereas, the transfection of niosomes with 4-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride, methyl-β-cyclodextrin and filipin, respectively. It can be concluded that these niosomes/DNA complexes were internalized predominantly by endocytosis via clathrin and caveolae-independent pathway.

Keywords: cellular internalization, cationic niosomes, gene carriers, spermine-cationic lipids

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Authors: Saroj Poudel, Joshua Mancini, Douglas Pike, Jennifer Timm, Alexei Tyryshkin, Vikas Nanda, Paul Falkowski

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On the early Earth, protein-metal complexes likely harvested energy from a reduced environment. These complexes would have been precursors to the metabolic enzymes of ancient organisms. Hydrogenase is an essential enzyme in most anaerobic organisms for the reduction and oxidation of hydrogen in the environment and is likely one of the earliest evolved enzymes. To attempt to reinvent a precursor to modern hydrogenase, we computationally designed a short thirteen amino acid peptide that binds the often-required catalytic transition metal Nickel in hydrogenase. This simple complex can achieve hundreds of hydrogen evolution cycles using light energy in a broad range of temperature and pH. Biophysical and structural investigations strongly indicate the peptide forms a di-nickel active site analogous to Acetyl-CoA synthase, an ancient protein central to carbon reduction in the Wood-Ljungdahl pathway and capable of hydrogen evolution. This work demonstrates that prior to the complex evolution of multidomain enzymes, early peptide-metal complexes could have catalyzed energy transfer from the environment on the early Earth and enabled the evolution of modern metabolism

Keywords: hydrogenase, prebiotic enzyme, metalloenzyme, computational design

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Authors: Mabruka S. Elashheb, Adullah Ali Bakush

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Schizophrenia is referred to as a disorder, not a disease, because there has not been any clear, reliable, and specific etiological factor. Even if schizophrenia is not a very frequent disease, it is among the most burdensome and costly illnesses worldwide. Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. We performed a comparison of a newer, atypical antipsychotic drug, Risperidone, and an older, conventional neuroleptic drug, Haloperidol, in terms of the effect on the usual kidney and liver functions and negative and positive symptoms in patients with schizophrenia and schizoaffective disorder after three and five weeks of their treatments. It is apparent from the comparative data of Haloperidol and Risperidone treatments in schizophrenic patients that Resperidone had superior improvement of negative and positive symptoms of patients, no harmful effect on liver and kidney functions and greater efficacy and faster recovery from schizophrenic symptoms in patients. On the basis of our findings of the present study, we concluded that treatment with Risperidone is superior to Haloperidol in reducing the risk of relapse among outpatients with schizophrenic disorders.

Keywords: schizophrenia, Haloperidol, Risperidone, positive and negative symptom

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Authors: Anusha Bhardwaj, Shekhar Shinde

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Nitric oxide (NO•) has been documented in research papers as one of the most versatile player in the therapeutics. It is identified as a biological multifunctional messenger molecule which is synthesized by the action of nitric oxide synthase (NOS) enzyme from L-arginine. The protective and the toxic effect in conjunction form the complete picture of the biological function of nitric oxide in humans. The dual nature is because of various factors such as concentration of NO, the isoform of NOS involved, type of cells in which it is synthesized, reaction partners like proteins, reactive oxygen intermediates, prosthetic groups, thiols etc., availability of the substrate L-arginine, intracellular environment in which NO is produced and generation of guanosine 3, 5’- cyclic monophosphate (cGMP). Activation of NOS through infection or trauma leads to one or more systemic effects including enhanced immune activity against invading pathogens, vaso/bronchodilatation in the cardiovascular and respiratory systems and altered neurotransmission which can be protective or toxic. Hence, NO affects the balance between healthy signaling and neurodegeneration in the brain. In lungs, it has beneficial effects on the function of airways as a bronchodilator and acts as the neurotransmitter of bronchodilator nerves. Whereas, on the other hand, NO may have deleterious effects by amplifying the asthmatic inflammatory response and also act as a vasodilator in the airways by increasing plasma exudation. But NOS Inhibitors and NO donors hamper the signalling pathway and hence a therapeutic application of NO is compromised.

Keywords: nitric oxide, multifunctional, dual nature, therapeutic applications

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Authors: Abdelgawad, Salah El-Tahawy

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This paper aimed to establish econometrical equation models for the Nile delta region in Egypt, which will represent a basement for future predictions of Lumpy skin disease outbreaks and its pathway in relation to climate change. Data of lumpy skin disease (LSD) outbreaks were collected from the cattle farms located in the provinces representing the Nile delta region during 1 January, 2015 to December, 2015. The obtained results indicated that there was a significant association between the degree of the LSD outbreaks and the investigated climate factors (temperature, wind speed, and humidity) and the outbreaks peaked during the months of June, July, and August and gradually decreased to the lowest rate in January, February, and December. The model obtained depicted that the increment of these climate factors were associated with evidently increment on LSD outbreaks on the Nile Delta of Egypt. The model validation process was done by the root mean square error (RMSE) and means bias (MB) which compared the number of LSD outbreaks expected with the number of observed outbreaks and estimated the confidence level of the model. The value of RMSE was 1.38% and MB was 99.50% confirming that this established model described the current association between the LSD outbreaks and the change on climate factors and also can be used as a base for predicting the of LSD outbreaks depending on the climatic change on the future.

Keywords: LSD, climate factors, Nile delta, modeling

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Authors: Vijay H. Ingole, Efthimia Lioliou

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Indirubin, a key bioactive component of traditional Chinese medicine, has gained increasing recognition for its potential in modern biomedical applications, particularly in pharmacology and therapeutics. The present work aimed to harness the potential by engineering an Escherichia coli strain capable of high-yield indirubin production. Through meticulous genetic engineering, we optimized the metabolic pathways in E. coli to enhance indirubin synthesis. Further, to explored the optimization of culture media and indirubin yield via batch and fed-batch fermentation techniques. By fine-tuning upstream process (USP) parameters, including nutrient composition, pH, temperature, and aeration, we established conditions that maximized both cell growth and indirubin production. Additionally, significant efforts were dedicated to refining downstream process (DSP) conditions for the extraction, purification, and quantification of indirubin. Utilizing advanced biochemical methods and analytical techniques such as UHPLC, we ensured the production of high purity indirubin. This approach not only improved the economic viability of indirubin bioproduction but also aligned with the principles of green production and sustainability.

Keywords: indirubin, bacterial strain, fermentation, HPLC

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Authors: Thaminda Liyanage, Chamila Shamika Kurukulasuriya

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Introduction: Morbid obesity has been successfully treated with bariatric surgery for over 60 years. Although operative procedures have improved and associated complications have reduced substantially, surgery still carries the risk of post-operative malabsorption, malnutrition and a range of gastrointestinal disorders. Overweight by itself can impair libido in both sexes and cause erectile dysfunction in males by inducing a state of hypogonadotropic hypogonadism, proportional to the degree of obesity. Impact of weight reduction on libido and sexual activity remains controversial, however it is broadly accepted that weight loss improves sexual drive. Zinc deficiency, subsequent to malabsorption, may lead to impaired testosterone synthesis in men while excessive and/or rapid weight loss in females may result in reversible amenorrhoea leading to sub-fertility. Methods: We describe a 37 year old male, 6 years post Roux-en-Y gastric bypass surgery, who presented with erectile dysfunction, loss of libido, worsening fatigue and generalized weakness for 4 months. He also complained of constipation and frequent muscle cramps but denied having headache, vomiting or visual disturbances. Patient had lost 38 kg of body weight post gastric bypass surgery over four years {135kg (BMI 42.6 kg/m2) to 97 kg (BMI 30.6 kg/m2)} and the weight had been stable for past two years. He had no recognised co-morbidities at the time of the surgery and noted marked improvement in general wellbeing, physical fitness and psychological confident post surgery, up until four months before presentation. Clinical examination revealed dry pale skin with normal body hair distribution, no thyroid nodules or goitre, normal size testicles and normal neurological examination with no visual field defects or diplopia. He had low serum testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH), T3, T4, thyroid stimulating hormone (TSH), insulin like growth factor 1 (IGF-1) and 24-hour urine cortisol levels. Serum cortisol demonstrated an appropriate rise to ACTH stimulation test but growth hormone (GH) failed increase on insulin tolerance test. Other biochemical and haematological studies were normal, except for low zinc and folate with minimally raised liver enzymes. MRI scan of the head confirmed a solid pituitary mass with no mass effect on optic chiasm. Results: In this patient clinical, biochemical and radiological findings were consistent with anterior pituitary dysfunction. However, there were no features of raised intracranial pressure or neurological compromise. He was commenced on appropriate home replacement therapy and referred for neurosurgical evaluation. Patient reported marked improvement in his symptoms, specially libido and erectile dysfunction, on subsequent follow up visits. Conclusion: Sexual dysfunction coupled with non specific constitutional symptoms has multiple aetiologies. Clinical symptoms out of proportion to nutritional deficiencies post bariatric surgery should be thoroughly investigated. Close long term follow up is crucial for overall success.

Keywords: obesity, bariatric surgery, erectile dysfunction, loss of libido

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Authors: Azza A. Ali, Toqa M. Elnahhas, Abeer I. Abd El-Fattah, Mona M. Kamal, Karema Abu-Elfotuh

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Background: Environmental pollution with the different aluminium (Al) containing compounds especially those in industrial waste water exposes people to higher than normal levels of Al that represents an environmental risk factor. Cosmetics, Al ware, and containers are also sources of Al besides some foods and food additives. In addition to its known neurotoxicity, Al affects other body structures like skeletal system, blood cells, liver and kidney. Accumulation of Al in kidney and liver induces nephrotoxicity and hepatotoxicity. Coenzyme Q10 (CoQ10) is a pseudo-vitamin substance primarily present in the mitochondria. It is a powerful antioxidant and acts as radical scavenger. Wheat grass is a natural product that contains carbohydrates, proteins, vitamins, minerals, enzymes and has antioxidant, anti-inflammatory, anticancer and cardiovascular protection activities. Cocoa is an excellent source of iron, potent antioxidants and can protect against many diseases. Vinpocetine is an antioxidant and anti inflammatory while zinc is an essential trace element involved in cell division and its deficiency is observed in many types of liver disease. Objective: To evaluate and compare the potency of different drugs (CoQ10, wheatgrass, cocoa, vinpocetine and zinc) against nephro- and hepato-toxicity induced by Al in rats. Methods: Rats were divided to seven groups and received daily for three weeks either saline for control group or AlCl3 (70 mg/kg, IP) for Al-toxicity model groups. Five groups of Al-toxicity model (treated groups) were orally received together with Al each of the following; CoQ10 (200mg/kg), wheat grass (100mg/kg), cocoa powder (24mg/kg), vinpocetine (20mg/kg) or zinc (32mg/kg). Biochemical changes in the serum level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) as well as total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea were measured. Liver and kidney specimens from all groups were also collected for the assessment of hepatic and nephrotic level of inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3, oxidative parameters (MDA, SOD, TAC, NO) and DNA fragmentation. Histopathological changes in liver and kidney were also evaluated. Results: Three weeks of AlCl3 (70 mg/kg, IP) exposure induced nephro- and hepato-toxicity in rats. Treatment by the all used drugs showed protection against hazards of AlCl3. The protective effects were indicated by the significant decrease in ALT, AST, ALP, LDH as well as total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels which were increased by Al. Liver and kidney of the treated groups showed decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation which were increased by Al, together with significant increase in total proteins, SOD and TAC which were decreased by Al. The protection against both nephro- and hepato-toxicity was more pronounced especially with CoQ10 and wheat grass than the other used drugs. Histopathological examinations confirmed the biochemical results of toxicity and of protection. Conclusion: Protection from nephrotoxicity, hepatotoxicity and the consequent degenerations induced by Al can be achieved by using different drugs as CoQ10, wheatgrass, cocoa, vinpocetine and zinc, but CoQ10 as well as wheat grass possesses the most superior protection.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, coenzyme Q10, wheatgrass, cocoa, vinpocetine, zinc

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Authors: Samad Alipour, Khadije Mosavi Onlaghi

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Urmia Salt Lake (USL) is a hypersaline lake in the northwest of Iran. It contains halite as main dissolved and precipitated mineral and the major mineral mixed with lake bed sediments. Other detrital minerals such as calcite, aragonite, dolomite, quartz, feldspars, augite are forming lake sediments. This study examined the impact of weathering of this sediments collected from 1.5 meters depth and augite placers. The study indicated that weathering of tephritic and adakite rocks of the Islamic Island at the immediate boundary of the lake play a main control of lake bed sediments and has produced a large volume of augite placer along the lake bank. Weathering increases from south to toward north with increasing distance from Islamic Island. Geochemistry of lake sediments demonstrated the enrichment of MgO, CaO, Sr with an elevated anomaly of Eu, possibly due to surface absorbance of Mn and Fe associated Sr elevation originating from adakite volcanic rocks in the vicinity of the lake basin. The study shows the local geology is the major factor in origin of lake sediments than chemical and biochemical produced mineral during diagenetic processes.

Keywords: Urmia Lake, weathering, mineralogy, augite, Iran

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Authors: Anurag Kumar Pandey, Tapan Kumar Nath, Santanu Dhara

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Polluted water by industrial effluents or dyes has become a major global concern, particularly in developing countries. Such environmental contaminants constitute a serious threat to biodiversity, ecosystems, and human health worldwide; thus, their treatment is critical. The usage of nanoparticles has been discovered to be a potential water treatment method with high efficiency, cheap manufacturing costs, and green synthesis. Carbon dots have attracted the interest of researchers due to their unique properties, such as high water solubility, ease of production, great electron-donating ability, and low toxicity. In this context, we synthesized iodine-doped clove buds-derived carbon dots (I-CCDs) for the Fenton-like degradation of environmental contaminants in water (such as methylene blue (MB) and rhodamine-B (Rh-B) dye). The formation of I-CCDs has been confirmed using various spectroscopy techniques. I-CCDs have demonstrated remarkable optical, cytocompatibility, and antibacterial capabilities. The C-dots that were synthesized were found to be an effective catalyst for the reduction of MB and Rh-B utilizing NaBH4 as a reducing agent. UV-visible spectroscopy was used to construct a detailed pathway for dye reduction step by step. As-prepared I-CCDs have the potential to be a promising solution for wastewater purification and treatment systems.

Keywords: iodine-doped carbon dots, wastewater treatment and purification, environmental friendly, antibacterial

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