Search results for: beta 2 toxin gene

Authors: Christine Ysabelle G. Roman, Pauline Torres

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Background: Hypertrophic cardiomyopathy is a disease of marked heterogeneity. It is a genetically determined heart disease characterized by significant myocardium hypertrophy that results in diastolic dysfunction, left ventricular outflow tract obstruction, and an increased risk of arrhythmias. The primary treatment in patients with such conditions is negative inotropic drugs, such as beta-blockers, calcium channel antagonists, and disopyramide. However, for those who remain symptomatic and need septal reduction therapy, surgical septal myectomy or alcohol septal ablation are options. Case Summary: A 19 – year old female presented in the authors’ institution with easy fatigability. The consult was done a year prior, and 2D echocardiography was requested which showed concentric left ventricular hypertrophy, asymmetrically hypertrophied interventricular septum (IVS) with the largest diameter of 3.3cm & subaortic dynamic obstruction with a maximum gradient of 47 mmHg. A repeat echo a year later showed asymmetric septal hypertrophy (IVS measuring at 3cm) with the systolic anterior motion of anterior mitral valve leaflet and left ventricular outflow tract obstruction (peak gradient of 50mmHg). The patient then underwent alcohol septal ablation and was discharged stable after four days of admission. Conclusion: Hypertrophic obstructive cardiomyopathy, a cardiovascular genetic disease, results in various patterns of left ventricular hypertrophy and abnormality of mitral valve apparatus. The patient is managed medically initially. However, despite optimal drug therapy and significant left ventricular outflow tract obstruction, significant heart failure symptoms or syncope require invasive treatment.

Keywords: hypertrophic obstructive cardiomyopathy, left ventricular outflow tract obstruction, alcohol septal ablation, alcohol

Procedia PDF Downloads 76

Authors: Shikha Masand, Sudesh Kumar Yadav

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Certain protein kinases have been shown to be crucial for plant cell signaling pathways associated with plant immune responses. Here we identified a horsegram [Macrotyloma uniflorum (Lam.) Verdc.] malectin-like leucine rich receptor-like protein kinase (RLK) gene MuRLK. The functional MuRLK protein preferentially binds to mannose and N-acetyl glucosamine residues. MuRLK exists in the cytoplasm and also localizes to the plasma membrane of plant cells via its N-terminus. Over-expression of MuRLK in Arabidopsis enhances the basal resistance to infection with Pseudomonas syringae pv. tomato, Alternaria brassicicola and Hyaloperonospora arabidopsidis, are associated with elevated ROS bursts, MAPK activation, thus ultimately leading to hypersensitive cell death. Moreover, salicylic acid-dependent and jasmonic acid-dependent defense responses are also enhanced in the MuRLK-overexpressed plants that lead to HR-induced cell death. Together, these results suggest that MuRLK plays a key role in the regulation of plant cell death, early and late defense responses after the recognition of microbial pathogens.

Keywords: horsegram, Pseudomonas syringae pv. tomato, MuRLK, ROS burst, cell death, plant defense

Procedia PDF Downloads 246

Authors: Nendouvhada Livhuwani Portia, Nicole Sibuyi, Kwazikwakhe Gabuza, Adewale Fadaka

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Metabolic dysfunction-associated liver disease (MASLD) is a chronic condition characterized by excessive fat accumulation in the liver, distinct from conditions caused by alcohol, viral hepatitis, or medications. MASLD is often linked with metabolic syndrome, including obesity, diabetes, hyperlipidemia, and hypertriglyceridemia. This disease can progress to metabolic dysfunction-associated steatohepatitis (MASH), marked by liver inflammation and scarring, potentially leading to cirrhosis. However, only 43-44% of patients with steatosis develop MASH, and 7-30% of those with MASH progress to cirrhosis. The exact mechanisms underlying MASLD and its progression remain unclear, and there are currently no specific therapeutic strategies for MASLD/MASH. While anti-obesity and anti-diabetic medications can reduce progression, they do not fully treat or reverse the disease. As an alternative, green-synthesized metal nanoparticles (MNPs) are emerging as potential treatments for liver diseases due to their anti-diabetic, anti-inflammatory, and anti-obesity properties with minimal side effects. MNPs like gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have been shown to improve metabolic processes by lowering blood glucose, body fat, and inflammation. The study aimed to explore the effects of green-synthesized MNPs on gene expression in an in vitro model of MASH using C3A/HepG2 liver cells. The MASH model was created by exposing these cells to free fatty acids (FFAs) followed by lipopolysaccharide (LPS) to induce inflammation. Cell viability was assessed with the Water-Soluble Tetrazolium (WST)-1 assay, and lipid accumulation was measured using the Oil Red O (ORO) assay. Additionally, mitochondrial membrane potential was assessed by the tetramethyl rhodamine, methyl ester (TMRE) assay, and inflammation was measured with an Enzyme-Linked Immunosorbent Assay (ELISA). The study synthesized AuNPs from Carpobrotus edulis fruit (CeF) and avocado seed (AvoSE) and AgNPs from Salvia africana-lutea (SAL) using optimized conditions. The MNPs were characterized by UV-Vis spectrophotometry and Dynamic Light Scattering (DLS). The nanoparticles were tested at various concentrations for their impact on the C3A/HepG2-induced MASH model. Among the MNPs tested, AvoSE-AuNPs showed the most promise. They reduced cell proliferation and intracellular lipid content more effectively than CeFE-AuNPs and SAL-AgNPs. Molecular analysis using real-time polymerase chain reaction revealed that AvoSE-AuNPs could potentially reverse MASH effects by reducing the expression of key pro-inflammatory and metabolic genes, including tumor necrosis factor-alpha (TNF-α), Fas cell surface death receptor (FAS), Peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, and Sterol regulatory element-binding protein (SREBPF)-1. Further research is needed to confirm the molecular mechanisms behind the effects of these MNPs and to identify the specific phytochemicals responsible for their synthesis and bioactivities.

Keywords: gold nanoparticles, green nanotechnology, metal nanoparticles, obesity

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Authors: Darshan Panda, Lambodar Behera, M. J. Baig, Sudhanshu Sekhar

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Low light intensity is a significant limitation for grain yield and quality in rice. However, yield is not significantly reduced in low-light tolerant rice varieties. The work, therefore, planned for comparative transcriptome profiling under low light stress to decipher the genes involved and molecular mechanism of low light tolerance in rice. At the active tillering stage, 50% low light exposure for one day, three days, and five days were given to Swarnaprabha (low light tolerant) and IR8 (low light sensitive) rice varieties. Illumina (HiSeq) platform was used for transcriptome sequencing. A total of 6,652 and 12,042 genes were differentially expressed due to low light intensity in Swarnaprabha and IR8, respectively, as compared to control. CAB, LRP, SBPase, MT15, TF PCL1, and Photosystem I & II complex related gene expressions were mostly increased in Swarnaprabha upon the longer duration of low light exposure, which was not found in IR8 as compared to control. Their expressions were validated by qRT-PCR. The overall study suggested that the maintenance of grain yield in the tolerant variety under low light might be the result of accelerated expression of the genes, which enable the plant to keep the photosynthetic processes moving at the same pace even under low light.

Keywords: rice, low light, photosynthesis, yield

Procedia PDF Downloads 191

Authors: Michael Josef Schwerer

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Background: Analyzing any aircraft accident is mandatory based on the regulations of the International Civil Aviation Organization and the respective country’s criminal prosecution authorities. Legal medicine investigations are unavoidable when fatalities involve the flight crew or when doubts arise concerning the pilot’s aeromedical health status before the event. As a result of frequently tremendous blunt and sharp force trauma along with the impact of the aircraft to the ground, consecutive blast or fire exposition of the occupants or putrefaction of the dead bodies in cases of delayed recovery, relevant findings can be masked or destroyed and therefor being inaccessible in standard pathology practice comprising just forensic autopsy and histopathology. Such cases are of considerable risk of remaining unsolved without legal consequences for those responsible. Further, no lessons can be drawn from these scenarios to improve flight safety and prevent future mishaps. Aims and Methods: To learn from previously unsolved aircraft accidents, re-evaluations of the investigation files and modern molecular pathology studies were performed. Genetic testing involved predominantly PCR-based analysis of gene regulation, studying DNA promotor methylations, RNA transcription and posttranscriptional regulation. In addition, the presence or absence of infective agents, particularly DNA- and RNA-viruses, was studied. Technical adjustments of molecular genetic procedures when working with archived sample material were necessary. Standards for the proper interpretation of the respective findings had to be settled. Results and Discussion: Additional molecular genetic testing significantly contributes to the quality of forensic pathology assessment in aviation mishaps. Previously undetected cardiotropic viruses potentially explain e.g., a pilot’s sudden incapacitation resulting from cardiac failure or myocardial arrhythmia. In contrast, negative results for infective agents participate in ruling out concerns about an accident pilot’s fitness to fly and the aeromedical examiner’s precedent decision to issue him or her an aeromedical certificate. Care must be taken in the interpretation of genetic testing for pre-existing diseases such as hypertrophic cardiomyopathy or ischemic heart disease. Molecular markers such as mRNAs or miRNAs, which can establish these diagnoses in clinical patients, might be misleading in-flight crew members because of adaptive changes in their tissues resulting from repeated mild hypoxia during flight, for instance. Military pilots especially demonstrate significant physiological adjustments to their somatic burdens in flight, such as cardiocirculatory stress and air combat maneuvers. Their non-pathogenic alterations in gene regulation and expression will likely be misinterpreted for genuine disease by inexperienced investigators. Conclusions: The growing influence of molecular pathology on legal medicine practice has found its way into aircraft accident investigation. As appropriate quality standards for laboratory work and data interpretation are provided, forensic genetic testing supports the medico-legal analysis of aviation mishaps and potentially reduces the number of unsolved events in the future.

Keywords: aviation medicine, aircraft accident investigation, forensic pathology, molecular pathology

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Authors: Deepa Gandhi, Pravin K. Naoghare, Amit Bafana, Krishnamurthi Kannan, Saravanadevi Sivanesana

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Oxidative stress is known to depreciate normal functioning of osteoblast cells. Present study reports oxidative/inflammatory signatures in fluoride exposed human osteosarcoma (HOS) cells and its possible association with the genes involved in bone developmental pathway. Microarray analysis was performed to understand the possible molecular mechanisms of stress-mediated bone lose in HOS cells. Cells were chronically exposed with sub-lethal concentration of fluoride. Global gene expression is profiling revealed 34 up regulated and 2598 down-regulated genes, which were associated with several biological processes including bone development, osteoblast differentiation, stress response, inflammatory response, apoptosis, regulation of cell proliferation. Microarray data were further validated through qRT-PCR and western blot analyses using key representative genes. Based on these findings, it can be proposed that chronic exposure of fluoride may impair bone development via oxidative and inflammatory stress. The present finding also provides important biological clues, which will be helpful for the development of therapeutic targets against diseases related bone.

Keywords: bone, HOS cells, microarray, stress

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Authors: Raeed Alanazi

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Introduction: Nursing students have a crucial role to play in the inhibition of infectious diseases and, therefore, must be trained in infection control and prevention modules prior to entering clinical settings. Simulations have been found to have a positive impact on infection control skills and the use of standard precautions. Aim: The purpose of this study was to use the four sources of self-efficacy in explaining the level of clinical self-efficacy and adherence to infection control practices in Saudi nursing students during simulation practice. Method: A cross-sectional design with convenience sampling was used. This study was conducted in all Saudi nursing schools, with a total number of 197 students participated in this study. Three scales were used simulation self- efficacy Scale (SSES), the four sources of self-efficacy scale (SSES), and Compliance with Standard Precautions Scale (CSPS). Multiple linear regression was used to test the use of the four sources of self-efficacy (SSES) in explaining level of clinical self-efficacy and adherence to infection control in nursing students. Results: The vicarious experience subscale (p =.044) was statistically significant. The regression model indicated that for every one unit increase in vicarious experience (observation and reflection in simulation), the participants’ adherence to infection control increased by .13 units (β =.22, t = 2.03, p =.044). In addition, the regression model indicated that for every one unit increase in education level, the participants’ adherence to infection control increased by 1.82 units (beta=.34= 3.64, p <.001). Also, the mastery experience subscale (p <.001) and vicarious experience subscale (p = .020) were shared significant associations with clinical self-efficacy. Conclusion: The findings of this research support the idea that simulation-based learning can be a valuable teaching-learning method to help nursing students develop clinical competence, which is essential in providing quality and safe nursing care.

Keywords: simulation-based learning, clinical self-efficacy, infection control, nursing students

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Authors: Ghazal Mortazavi, S. M. J. Mortazavi

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Electricians, power line engineers and power station workers, welders, aluminum reduction workers, MRI operators and railway workers are occupationally exposed to different levels of electromagnetic fields. Mercury is among the most toxic metals. Dental amalgam fillings cause significant exposure to elemental mercury vapour in the general population. Today, substantial evidence indicates that mercury even at low doses may lead to toxicity. Increased release of mercury from dental amalgam fillings after exposure to MRI or microwave radiation emitted by mobile phones has been previously shown by our team. Moreover, our recent studies on the effects of stronger magnetic fields entirely confirmed our previous findings. From the other point of view, we have also shown that papers which reported no increased release of mercury after MRI, may have some methodological flaws. Over the past several years, our lab has focused on the health effects of exposure of laboratory animals and humans to different sources of electromagnetic fields such as mobile phones and their base stations, mobile phone jammers, laptop computers, radars, dentistry cavitrons, and MRI. As a strong association between exposure to electromagnetic fields and mercury level has been found in our studies, our findings lead us to this conclusion that occupational exposure to electromagnetic fields in workers with dental amalgam fillings can lead to elevated levels of mercury. Studies which reported that exposure to mercury can be a risk factor of Alzheimer’s disease (AD) due to the accumulation of amyloid beta protein (Aβ) in the brain and those reported that long-term occupational exposure to high levels of electromagnetic fields can increase the risk of Alzheimer's disease and dementia in male workers support our concept and confirm the significant role of the occupational exposure to electromagnetic fields in increasing the mercury level in workers with amalgam fillings.

Keywords: occupational exposure, electromagnetic fields, workers, mercury release, dental amalgam, restorative dentistry

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Authors: Safa Abusara Mohammed Ali, Mohammed Khair Abdallah, Gurdon A. Brockmann, M. Reissmann

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The aim of the study was the characterization of DGAT1 variants in Sudanese dairy cattle breeds. In this study, we examined 94 Kenana and 91 Butana dairy cattle from two regions of Sudan. We genotyped the DGAT1 sequence variant AJ318490.1:g.10433/10434 AA>GC that leads to the Lysine – Alanine substitution at position 232 (K232A) in the protein and the VNTR polymorphism in the promoter region. Genotyping was performed by allele specific PCR and PCR fragment lengths determination, respectively. In both breeds, the DGAT1 Lysine variant (232K) that is associated with high fat and protein content as well as high fat yield in other breeds is the high frequent allele. The frequencies of the 232K allele were 96.3% and 84.6% in Kenana and Butana breeds, respectively. At the DGAT1 promoter VNTR locus, four alleles containing four to seven repeats of the 18 bp motif were found in both breeds. The highest frequent allele was the VNTR allele 3 containing five repeats with 60.4 % and 57.5 % in Kenana and Butana breeds, respectively. In conclusion, the two examined Sudanese dairy cattle breeds do not differ in allele frequencies at the DGAT1 locus.

Keywords: dairy cattle, DGAT1, Kenana, Butana.

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Authors: Meryem Abi-Ayad, Biagio Arcidiacono, Eusebio Chiefari, Daniela Foti, Mohamed Benyoucef, Antonio Brunetti

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Lipoprotein Lipase (LPL) is a key enzyme for lipid metabolism; its genetic polymorphism can be a candidate for modulating lipids parameters in metabolic syndrome. The objective of the present study was to determine whether lipoproteins lipase polymorphisMetS (LPL-HindIII) could be associated with moderate hypertriglyceridemia (secondary to metabolism syndrome). The polymorphism Hind III (rs320) was assessed by PCR-RFLP in 51 MetS patients and 17 healthy controls from the hospital in Tlemcen. The logistic regression analyses showed no significant association with Hind III genotype and hypertriglyceridemia (TG ≥ 1,5g/l or TG lower treatment) (P=0,455), metabolic syndrome (P=0,455), hypertension (P=0,802) and type 2 diabetes (P=0,144). In terms of plasma biomarkers, although not statistically significant, there was a difference in TG levels (P > 0,05), which was lowest among carriers of the homogenous mutant allele (H-). In this study, there was no association between the rare allele (H-) and disease protection, and between the frequent allele (H+) and disease prevalence (hypertriglyceridemia, metabolic syndrome, hypertension, type 2 diabetes).

Keywords: moderate secondary hypertriglyceridemia, metabolic syndrome, lipids, polymorphism lipoprotein lipase, HindIII(rs320)

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Authors: Mohamed Wahba

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Objective: To build a comparative arm for product (X) in specific gene mutated advanced gastrointestinal cancer using real world evidence to fulfill HTA requirements in drug evaluation. Methods: Data for product (X) were collected from phase II clinical trial while real world data for (Y) and (Z) were collected from US database. Real-world (RW) cohorts were matched to clinical trial base line characteristics using weighting by odds method. Outcomes included progression-free survival (PFS) and overall survival (OS) rates. Study location and participants: Internationally (product X, n=80) and from USA (Product Y and Z, n=73) Results: Two comparisons were made: trial cohort 1 (X) versus real-world cohort 1 (Z), trial cohort 2 (X) versus real-world cohort 2 (Y). For first line, the median OS was 9.7 months (95% CI 8.6- 11.5) and the median PFS was 5.2 months (95% CI 4.7- not reached) for real-world cohort 1. For second line, the median OS was 10.6 months (95% CI 4.7- 27.3) for real-world cohort 2 and the median PFS was 5.0 months (95% CI 2.1- 29.3). For OS analysis, results were statistically significant but not for PFS analysis. Conclusion: This study provided the clinical comparative outcomes needed for HTA evaluation.

Keywords: real world evidence, pharmacoeconomics, HTA agencies, oncology

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Authors: Fabio Fabris, Alex A. Freitas

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Hierarchical classification is a special type of classification task where the class labels are organised into a hierarchy, with more generic class labels being ancestors of more specific ones. Meta-learning for classification-algorithm recommendation consists of recommending to the user a classification algorithm, from a pool of candidate algorithms, for a dataset, based on the past performance of the candidate algorithms in other datasets. Meta-learning is normally used in conventional, non-hierarchical classification. By contrast, this paper proposes a meta-learning approach for more challenging task of hierarchical classification, and evaluates it in a large number of bioinformatics datasets. Hierarchical classification is especially relevant for bioinformatics problems, as protein and gene functions tend to be organised into a hierarchy of class labels. This work proposes meta-learning approach for recommending the best hierarchical classification algorithm to a hierarchical classification dataset. This work’s contributions are: 1) proposing an algorithm for splitting hierarchical datasets into new datasets to increase the number of meta-instances, 2) proposing meta-features for hierarchical classification, and 3) interpreting decision-tree meta-models for hierarchical classification algorithm recommendation.

Keywords: algorithm recommendation, meta-learning, bioinformatics, hierarchical classification

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Authors: Houria Hamitouche, Abdellah Khelifa

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Quaternary ammonium salts (QACs) are the most common cationic surfactants of natural or synthetic origin usually. They possess one or more hydrophobic hydrocarbon chains and hydrophilic cationic group. In fact, the hydrophobic groups are derived from three main sources: petrochemicals, vegetable oils, and animal fats. These QACs have attracted the attention of chemists for a long time, due to their general simple synthesis and their broad application in several fields. They are important as ingredients of cosmetic products and are also used as corrosion inhibitors, in emulsion polymerization and textile processing. Within biological applications, QACs show a good antimicrobial activity and can be used as medicines, gene delivery agents or in DNA extraction methods. The 2004 worldwide annual consumption of QACs was reported as 500,000 tons. The petroleum product is considered a true reservoir of a variety of chemical species, which can be used in the synthesis of quaternary ammonium salts. The purpose of the present contribution is to synthesize the quaternary ammonium salts by Menschutkin reaction, via chloromethylation/quaternization sequences, from Algerian petroleum products namely: reformate, light naphtha and kerosene and characterize.

Keywords: quaternary ammonium salts, reformate, light naphtha, kerosene

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Authors: Frank Boris Feutmba Keutchou, Saurelle Fabienne Bieghan Same, Verelle Elsa Fogang Pokam, Charles Ursula Metapi Meikeu, Angel Marilyne Messop Nzomo, Ousman Tamgue

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Infectious diseases are one of the most important causes of morbidity and mortality worldwide. These diseases are caused by micro-pathogenic organisms, such as bacteria, viruses, parasites, and fungi. Heritable changes in gene expression that do not involve changes to the underlying DNA sequence are referred to as epigenetics. Emerging evidence suggests that epigenetic mechanisms are important in the emergence and progression of infectious diseases. Pathogens can manipulate host epigenetic machinery to promote their own replication and evade immune responses. The Human Genome Project has provided new opportunities for developing better tools for the diagnosis and identification of target genes. Several epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA expression, have been shown to influence infectious disease outcomes. Understanding the epigenetic mechanisms underlying infectious diseases may result in the progression of new therapeutic approaches focusing on host-pathogen interactions. The goal of this study is to show how different infectious agents interact with host cells after infection.

Keywords: epigenetic, infectious disease, micro-pathogenic organism, phenotype

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Authors: Monty Vacura

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Hamilton’s Rule is a universal law of biology expressed in protists, plants and animals. When applied to human populations, this model explains: 1) Origin of religion in society as a biopsychological need naturally selected to increase population size; 2) Instincts of racism expressed through intergroup competition; 3) Simultaneous selection for human cooperation and conflict, love and hate; 4) Places Dawkins’s selfish gene as the r, relationship variable; 5) Flipping the equation variable themes (close relationship to distant relationship, and benefit to threat) the new equation can now be used to identify the offensive and defensive sides of conflict; 6) Connection between sporting events and instinctive social messaging for stimulating offensive and defensive responses; 6) Pathway to reduce human sacrifice through manipulation of variables. This paper discusses the deep psychological influences of Hamilton’s Rule. Suggestions are provided to reduce human deaths via our instinctive sacrificial behavior, by consciously monitoring Hamilton’s Rule variables highlighted throughout our media outlets.

Keywords: psychology, Hamilton’s rule, evolution, human instincts

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Authors: Vongsathorn Ngampuak, Yutachai Chookaew, Wipawee Dejtisakdi

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Dunaliella salina has great potential as a system for generating commercially valuable products, including beta-carotene, pharmaceuticals, and biofuels. Our goal is to improve this potential by enhancing growth rate and other properties of D. salina under optimal growth conditions. We used ethyl methane sulfonate (EMS) to generate random mutants in D. salina KU11, a strain classified in Thailand. In a preliminary experiment, we first treated D. salina cells with 0%, 0.8%, 1.0%, 1.2%, 1.44% and 1.66% EMS to generate a killing curve. After that, we randomly picked 30 candidates from approximately 300 isolated survivor colonies from the 1.44% EMS treatment (which permitted 30% survival) as an initial test of the mutant screen. Among the 30 survivor lines, we found that 2 strains (mutant #17 and #24) had significantly improved growth rates and cell number accumulation at stationary phase approximately up to 1.8 and 1.45 fold, respectively, 2 strains (mutant #6 and #23) had significantly decreased growth rates and cell number accumulation at stationary phase approximately down to 1.4 and 1.35 fold, respectively, while 26 of 30 lines had similar growth rates compared with the wild type control. We also analyzed cell size for each strain and found there was no significant difference comparing all mutants with the wild type. In addition, mutant #24 had shown an increase of biomass accumulation approximately 1.65 fold compared with the wild type strain on day 5 that was entering early stationary phase. From these preliminary results, it could be feasible to identify D. salina mutants with significant improved growth rate, cell accumulation and biomass production compared to the wild type for the further study; this makes it possible to improve this microorganism as a platform for biotechnology application.

Keywords: Dunaliella salina, ethyl methyl sulfonate, growth rate, biomass

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Authors: Hany M. Fayed, Rehab F. Abdel-Rahman, Alyaa F. Hessin, Hanan A. Ogaly, Gihan F. Asaad, Abeer A. A. Salama, Sahar Abdelrahman, Mahmoud S. Arbid, Marwan Abd Elbaset Mohamed

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Liver fibrosis is a serious global health problem that occurs as a result of a variety of chronic liver disorders. Apigenin, a flavonoid found in many plants, has several pharmacological properties. The aim of this study was to evaluate the antifibrotic efficacy of apigenin (APG) against experimentally induced hepatic fibrosis in rats via using thioacetamide (TAA) and to explore the possible underlying mechanisms. TAA (100 mg/kg, i.p.) was given three times each week for two weeks to induce liver fibrosis. After TAA injections, APG was given orally (5 and 10 mg/kg) daily for two weeks. Biochemical, molecular, histological and immunohistochemical analyses were performed on blood and liver tissue samples. The functioning of the liver, oxidative stress, inflammation, and liver fibrosis indicators were all evaluated. The findings showed that TAA markedly increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as the levels of malondialdehyde (MDA), focal adhesion kinase (FAK), hypoxia-inducible factor-1 (HIF-1), nuclear factor-κB (NF-κB), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) with a reduction in albumin, total protein, A/G ratio, GSH content and interleukin-10 (IL-10). Moreover, TAA elevated the content of collagen I, α -smooth muscle actin (α-SMA), and hydroxyproline in the liver. The treatment with APG in a dose-dependent manner has obviously prevented these alterations and amended the harmful effects induced by TAA. The histopathological and immunohistochemical observations supported this biochemical evidence. The higher dose of APG produced the most significant antifibrotic effect. As a result of these data, APG appears to be a promising antifibrotic drug and could be used as a new herbal medication or dietary supplement in the future for the treatment of liver fibrosis. This effect might be related to the inhibition of the HIF-1/FAK signaling pathway.

Keywords: apigenin, FAK, HIF-1, liver fibrosis, rat, thioacetamide

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Authors: Mahdi Rahaie

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MicroRNAs are a novel class of small RNAs which regulate gene expression by translational repression or degradation of messenger RNAs. To produce sensitive, simple and cost-effective assays for microRNAs, detection is in urgent demand due to important role of these biomolecules in progression of human disease such as Alzheimer’s, Multiple sclerosis, and some other neurodegenerative diseases. Herein, we report several novel, sensitive and specific microRNA nanobiosensors which were designed based on colorimetric and fluorescence detection of nanoparticles and hybridization chain reaction amplification as an enzyme-free amplification. These new strategies eliminate the need for enzymatic reactions, chemical changes, separation processes and sophisticated equipment whereas less limit of detection with most specify are acceptable. The important features of these methods are high sensitivity and specificity to differentiate between perfectly matched, mismatched and non-complementary target microRNAs and also decent response in the real sample analysis with blood plasma. These nanobiosensors can clinically be used not only for the early detection of neuro diseases but also for every sickness related to miRNAs by direct detection of the plasma microRNAs in real clinical samples, without a need for sample preparation, RNA extraction and/or amplification.

Keywords: hybridization chain reaction, microRNA, nanobiosensor, neurodegenerative diseases

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Authors: Ahmad Shahin, Fadi Chakik, Walid Moudani

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Our study is about elaborating a potential solution for a search engine that involves semantic technology to retrieve information and display it significantly. Semantic search engines are not used widely over the web as the majorities are still in Beta stage or under construction. Many problems face the current applications in semantic search, the major problem is to analyze and calculate the meaning of query in order to retrieve relevant information. Another problem is the ontology based index and its updates. Ranking results according to concept meaning and its relation with query is another challenge. In this paper, we are offering a light meta-engine (QESM) which uses Google search, and therefore Google’s index, with some adaptations to its returned results by adding multi-query expansion. The mission was to find a reliable ranking algorithm that involves semantics and uses concepts and meanings to rank results. At the beginning, the engine finds synonyms of each query term entered by the user based on a lexical database. Then, query expansion is applied to generate different semantically analogous sentences. These are generated randomly by combining the found synonyms and the original query terms. Our model suggests the use of semantic similarity measures between two sentences. Practically, we used this method to calculate semantic similarity between each query and the description of each page’s content generated by Google. The generated sentences are sent to Google engine one by one, and ranked again all together with the adapted ranking method (QESM). Finally, our system will place Google pages with higher similarities on the top of the results. We have conducted experimentations with 6 different queries. We have observed that most ranked results with QESM were altered with Google’s original generated pages. With our experimented queries, QESM generates frequently better accuracy than Google. In some worst cases, it behaves like Google.

Keywords: semantic search engine, Google indexing, query expansion, similarity measures

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Authors: Anna Amato

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Every child needs communication. If spoken language is not or not fully available due to congenital or acquired limitations, those affected need appropriate ways. These can be found in many possibilities of Augmentative and Alternative Communications (AAC). In the communication promotion of severely impaired children, who can use their own body communication forms only to a limited extent for the differentiated understanding, computers with eye control play an essential role. It takes some time to understand the individual forms of communication of the child. Children who depend on the AAC need competent support to learn to communicate in a motivated way in their everyday life. The aim of the present parents' survey (n = 4), which was evaluated descriptively, is to demonstrate the development of communicative abilities as well as the motivation to use complex communication aids with eye control by patients with atypical Rett Syndrome. An increase in communication skills, well-being, self-reliance, and self-esteem, an improvement in social participation, as well as a reduction in anger and screaming events, were noted. The complex visual communication tools were available daily for 3 out of 4 patients with atypical Rett Syndrome. It raises research questions regarding speech understanding and the ability to drive eye control technology in a larger group of atypical Rett Syndrome patients.

Keywords: augmentative and alternative communications, AAC, atypical Rett-syndrome, children, development

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Authors: Nourhan G. Sahly, Ahmed Moustafa, Mohamed S. Zaghloul, Tamer Z. Salem

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The gut microbiome plays important roles in the human body that includes but not limited to digestion, immunity, homeostasis and response to some drugs such as chemotherapy and immunotherapy. Its role has also been linked to radiotherapy and associated gastrointestinal injuries, where the microbial dysbiosis could be the driving force for dose determination or the complete suspension of the treatment protocol. Linking the gut microbiota alterations to different cancer treatment protocols is not easy especially in humans. However, enormous effort was exerted to understand this complex relationship. In the current study, we described the gut microbiota dysbiosis in pediatric sarcoma patients, in the pelvic region, with regards to radiotherapy and antibiotics. Fecal samples were collected as a source of microbial DNA for which the gene encoding for V3-V5 regions of 16S rRNA was sequenced. Two of the three patients understudy had experienced an increase in alpha diversity post exposure to 50.4 Gy. Although phylum Firmicutes overall relative abundance has generally decreased, six of its taxa increased in all patients. Our results may indicate the possibility of radiosensitivity or enrichment of the antibiotic resistance of the elevated taxa. Further studies are needed to describe the extent of radiosensitivity with regards to antibiotic resistance.

Keywords: combined radiotherapy and chemotherapy, gut microbiome, pediatric cancer, radiosensitivity

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Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

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Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

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Authors: Ranjeeta Kumari, Makesh M, Gayatri Tripathi, K V Rajendran, Megha Bedekar

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A comparative study on DNA immunization with recombinant glyceraldehyde-3-phosphate dehydrogenase (GAPDH) construct of Edwardsiella tarda (pGPD group) and a bicistronic construct expressing GAPDH plus IFN-γ of Labeo rohita as adjuvant (pGPD+IFN group) was undertaken in Labeo rohita along with the control animals. Successful co-expression of two genes that is GAPDH and IFN-γ was confirmed in SSN-1 cells line by RT-qPCR and western blot. The protective immune response of host to DNA vaccine construct was determined by RPS and specific antibody production. Fishes immunized with plasmids via intramuscular injection (I/M) exhibited a considerable relative percentage survivability of 66.66% in pGPD+IFN immunized group and 53.34% in pGPD immunized group after challenge with E. tarda. Antibody response was also significantly high in pGPD+IFN group at all time points under study. This was analysed by competitive ELISA, using anti GAPDH monoclonal antibodies. The experiment revealed that the GAPDH gene of E. tarda is one of the ideal candidates for generating protective immune response in L. rohita. Further addition of Interferon gamma to DNA vaccine construct can enhance the immune response in host.

Keywords: DNA vaccine, Edwardsiella tarda, Labeo rohita, zoonosis, immune response

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Authors: J. Wicks

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Aim: To develop a simple methodology to allow collected heart rate (HR) data from inexpensive wearable devices to be expressed in a suitable format (METs) to quantitate occupational (and recreational) activity. Introduction: Assessment of occupational activity is commonly done by utilizing questionnaires in combination with prescribed MET levels of a vast range of previously measured activities. However for any individual the intensity of performing a specific activity can vary significantly. Ideally objective measurement of individual activity is preferred. Though there are a wide range of HR recording devices there is a distinct lack methodology to allow processing of collected data to quantitate energy expenditure (EE). The HR index equation expresses METs in relation to relative HR i.e. the ratio of activity HR to resting HR. The use of this equation provides a simple utility for objective measurement of EE. Methods: During a typical occupational work period of approximately 8 hours HR data was recorded using a Polar RS 400 wrist monitor. Recorded data was downloaded to a Windows PC and non HR data was stripped from the ASCII file using ‘Notepad’. The HR data was exported to a spread sheet program and sorted by HR range into a histogram format. Three HRs were determined, namely a resting HR (the HR delimiting the lowest 30 minutes of recorded data), a mean HR and a peak HR (the HR delimiting the highest 30 minutes of recorded data). HR indices were calculated (mean index equals mean HR/rest HR and peak index equals peak HR/rest HR) with mean and peak indices being converted to METs using the HR index equation. Conclusion: Inexpensive HR recording devices can be utilized to make reasonable estimates of occupational (or recreational) EE suitable for large scale demographic screening by utilizing the HR index equation. The intrinsic value of the HR index equation is that it is independent of factors that influence absolute HR, namely fitness, smoking and beta-blockade.

Keywords: energy expenditure, heart rate histograms, heart rate index, occupational activity

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Authors: Gimhani Madhushika Hewayalage, Thilini Ariyadasa, Sanja Gunawardena

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In Sri Lanka, the largest contribution for the industrial export earnings is governed by textile and apparel industry. However, this industry generates huge quantities of effluent consists of unfixed dyes which enhance the effluent colour and toxicity thereby leading towards environmental pollution. Therefore, the effluent should properly be treated prior to the release into the environment. The biological technique has now captured much attention as an environmental-friendly and cost-competitive effluent decolourization method due to the drawbacks of physical and chemical treatment techniques. The present study has focused on identifying dye decolourizing potential of several bacterial isolates obtained from the effluent of the local textile industry. Yellow EXF, Red EXF, Blue EXF, Nova Black WNN and Nylosan-Rhodamine-EB dyes have been selected for the study to represent different chromophore groups such as Azo and Xanthene. The rates of decolorization of each dye have been investigated by employing distinct bacterial isolates. Bacterial isolate which exhibited effective dye decolorizing potential was identified as Proteus mirabilis using 16S rRNA gene sequencing analysis. The high decolorizing rates of identified bacterial strain indicate its potential applicability in the treatment of dye-containing wastewaters.

Keywords: azo, bacterial, biological, decolourization, xanthene

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Authors: John Onolame Unuofin, Uchechukuw U. Nwodo, Anthony I. Okoh

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Laccase is constantly gaining status as important biocatalyst in biotechnology. The illimitable potential of its industrial applications and the corresponding aggressive need for phenomenal volumes of extracellularly secreted laccases have called for its interminable production from sources which are able to meet this demand within a relatively short period of time, preferably bacteria. In response to this call, this study was designed to source for laccase-producing bacteria from different environmental matrices. Three sampling environments were chosen such as wastewater treatment plants, University of Fort Hare vicinity and the Hogback woodland, all within the Eastern Cape, South Africa. Samples such as effluents, sediments, leaf litters, degrading wood and rock scrapings were selectively enriched with some model aromatic compounds and were further screened qualitatively and quantitatively on five phenolic substrates ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), Guaiacol, 1-Naphthol, Potassium Ferric Cyanide and Syringaldazine). Basis for selection was their ability to elicit a colour change on at least three of the above mentioned agar based assay substrates. The choice isolates were further identified based on 16S rRNA molecular identification techniques. 33 isolates were screened out of the 40 representative distinct colonies during the qualitative plate screens, while quantitative screens selected out 11 bacterial isolates. They were, based on molecular identification, desginated as members of the genera Pseudomonas, Stenotrophomonas and Citrobacter of the gammaproteobacteria and Bordetalla and Achromobacter of the betaproteobacteria respectively. We therefore conclude based on our outcomes that we may have isolated efficient laccase-producing bacteria, which might be of beneficial significance in catalysis and biotechnology.

Keywords: beta proteobacteria, catalysis, gammaproteobacteria, laccase

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Authors: Guyue Zhu, Liangping Hong

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Chinese overall urban design faces a large number of problems such as the neglect of urban characteristics, generalization of content, and difficulty in implementation. Focusing on these issues, this paper proposes the main points of shaping urban characteristics in overall urban design: focuses on core problems in city function and scale, landscape pattern, historical culture, social resources and modern city style and digs the urban characteristic genes. Then, we put forward “core problem location and characteristic gene enhancement” as a kind of overall urban design technical method. Firstly, based on the main problems in urban space as a whole, for the operability goal, the method extracts the key genes and integrates into the multi-dimension system in a targeted manner. Secondly, hierarchical management and guidance system is established which may be in line with administrative management. Finally, by converting the results, action plan is drawn up that can be dynamically implemented. Based on the above idea and method, a practical exploration has been performed in the case of Xiangyang central city.

Keywords: city characteristics, overall urban design, planning implementation, Xiangyang central city

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Authors: Isobel Hambleton, Mark Carrington

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Trypanosoma brucei, the causal agent of a range of diseases in humans and livestock, evades the mammalian immune system through a population survival strategy based on the expression of a series of antigenically distinct variant surface glycoproteins (VSGs). RNAi mediated knockdown of the active VSG gene triggers a precytokinesis cell cycle arrest. To determine whether this phenotype is the result of reduced VSG transcript or depleted VSG protein, we used morpholino antisense oligonucleotides to block translation of VSG mRNA. The same precytokinesis cell cycle arrest was observed, suggesting that VSG protein abundance is monitored closely throughout the cell cycle. An inducible expression system has been developed to test various GPI-anchored proteins for their ability to rescue this cell cycle arrest. This system has been used to demonstrate that wild-type VSG expressed from a T7 promoter rescues this phenotype. This indicates that VSG expression from one of the specialised bloodstream expression sites (BES) is not essential for cell division. The same approach has been used to define the minimum essential features of a VSG necessary for function.

Keywords: bloodstream expression site, morpholino, precytokinesis cell cycle arrest, variant surface glycoprotein

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Authors: Khaled M. Khleifat

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An extracellular methanol and ethanol tolerant lipase producing bacterial strain K5b4 was isolated from soil samples contaminated with hydrocarbon residues. It was identified by using morphological and biochemical characteristics and 16srRNA technique as Acinetobacter species. The immobilized lipase from Acinetobacter sp. K5b4 retained more than 98% of its residual activity after incubation with pure methanol and ethanol for 24 hours. The highest hydrolytic activity of the immobilized enzyme was obtained in the presence of 75% (v/v) methanol in the assay solution. In contrary, the enzyme was able to maintain its original activity up to only 25% (v/v) ethanol whereas at elevated concentrations of 50 and 75% (v/v) the enzyme activity was reduced to 10 and 40%, respectively. Maximum lipase activity of 31.5 mU/mL was achieved after 48 hr cultivation when the optimized medium (pH 7.0) that composed of 1.0% (w/v) olive oil, 0.2% (w/v) glycerol, 0.15% (w/v) yeast extract, and 0.05% (w/v) NaCl was inoculated with 0.4% (v/v) seed culture and incubated at 30°C and 150 rpm agitation speed. However, the presence of CaCl2 in the growth media did not show any inhibitory or stimulatory effect on the enzyme production as it compared to the control experiment. Meanwhile, the other mineral salts MgCl2, MnCl2, KCl and CoCl2 were negatively affected the production of lipase enzyme. The inhibition of lipase production from Acinetobacter sp. K5b4 in presence of glucose suggesting that lipase gene expression is prone to catabolic repression.

Keywords: K5B4, methanol and ethanol, acinetobacter, morphological

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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