Search results for: gene expression data analysis

Authors: Diego Santibañez Oyarce, Fernanda Bravo Cornejo, Camilo Cerda Sarabia, Belén Díaz Díaz, Esteban Gómez Terán, Hugo Osses Prado, Raúl Caulier-Cisterna, Jorge Vergara-Quezada, Ana Moya-Beltrán

Abstract:

The advent of high-throughput sequencing technologies has revolutionized genomics, generating vast amounts of genetic data that challenge traditional bioinformatics methods. Machine learning addresses these challenges by leveraging computational power to identify patterns and extract information from large datasets. However, biological sequence data, being symbolic and non-numeric, must be converted into numerical formats for machine learning algorithms to process effectively. So far, some encoding methods, such as one-hot encoding or k-mers, have been explored. This work proposes additional approaches for encoding DNA sequences in order to compare them with existing techniques and determine if they can provide improvements or if current methods offer superior results. Data from the 16S rRNA gene, a universal marker, was used to analyze eight bacterial groups that are significant in the pulmonary environment and have clinical implications. The bacterial genes included in this analysis are Prevotella, Abiotrophia, Acidovorax, Streptococcus, Neisseria, Veillonella, Mycobacterium, and Megasphaera. These data were downloaded from the NCBI database in Genbank file format, followed by a syntactic analysis to selectively extract relevant information from each file. For data encoding, a sequence normalization process was carried out as the first step. From approximately 22,000 initial data points, a subset was generated for testing purposes. Specifically, 55 sequences from each bacterial group met the length criteria, resulting in an initial sample of approximately 440 sequences. The sequences were encoded using different methods, including one-hot encoding, k-mers, Fourier transform, and Wavelet transform. Various machine learning algorithms, such as support vector machines, random forests, and neural networks, were trained to evaluate these encoding methods. The performance of these models was assessed using multiple metrics, including the confusion matrix, ROC curve, and F1 Score, providing a comprehensive evaluation of their classification capabilities. The results show that accuracies between encoding methods vary by up to approximately 15%, with the Fourier transform obtaining the best results for the evaluated machine learning algorithms. These findings, supported by the detailed analysis using the confusion matrix, ROC curve, and F1 Score, provide valuable insights into the effectiveness of different encoding methods and machine learning algorithms for genomic data analysis, potentially improving the accuracy and efficiency of bacterial classification and related genomic studies.

Keywords: DNA encoding, machine learning, Fourier transform, Fourier transformation

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Authors: Esmat Noroozi, Elahe Sarfi, Farha Hosseinzadeh Lotfi

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Examining the impacts of data modification is considered as sensitivity analysis. A lot of studies have considered the data modification of inputs and outputs in DEA. The issues which has not heretofore been considered in DEA sensitivity analysis is modification in the number of inputs and (or) outputs and determining the impacts of this modification in the status of efficiency of DMUs. This paper is going to present systems that show the impacts of adding one or multiple inputs or outputs on the status of efficiency of DMUs and furthermore a model is presented for recognizing the minimum number of inputs and (or) outputs from among specified inputs and outputs which can be added whereas an inefficient DMU will become efficient. Finally the presented systems and model have been utilized for a set of real data and the results have been reported.

Keywords: data envelopment analysis, efficiency, sensitivity analysis, input, out put

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Authors: Shirin jalili, Hadi Shirzad, Mahasti Modarresi, Samaneh Nabavi, Somayeh Khanjani

Abstract:

Identifying the source tissue of biological material found at crime scenes can be very informative in a number of cases. Despite their usefulness, current visual, catalytic, enzymatic, and immunologic tests for presumptive and confirmatory tissue identification are applicable only to a subset of samples, might suffer limitations such as low specificity, lack of sensitivity, and are substantially impacted by environmental insults. In addition their results are operator-dependent. Recently the possibility of discriminating body fluids using mRNA expression differences in tissues has been described but lack of long term stability of that Molecule and the need to normalize samples for each individual are limiting factors. The use of DNA should solve these issues because of its long term stability and specificity to each body fluid. Cells in the human body have a unique epigenome, which includes differences in DNA methylation in the promoter of genes. DNA methylation, which occurs at the 5′-position of the cytosine in CpG dinucleotides, has great potential for forensic identification of body fluids, because tissue-specific patterns of DNA methylation have been demonstrated, and DNA is less prone to degradation than proteins or RNA. Previous studies have reported several body fluid-specific DNA methylation markers.The presence or absence of a methyl group on the 5’ carbon of the cytosine pyridine ring in CpG dinucleotide regions called ‘CpG islands’ dictates whether the gene is expressed or silenced in the particular body fluid. Were described methylation patterns at tissue specific differentially methylated regions (tDMRs) to be stable and specific, making them excellent markers for tissue identification. The results demonstrate that methylation-based tissue identification is more than a proof-of-concept. The methodology holds promise as another viable forensic DNA analysis tool for characterization of biological materials.

Keywords: DNA methylation, forensic science, epigenome, tDMRs

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Authors: Sina Mahdavi, Mahdi Asghari Ozma

Abstract:

Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human Varicella-zoster virus (VZV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on VZV retrovirus infection in MS disease progression. For this study, the keywords "Multiple sclerosis", " Human Varicella-zoster virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles were chosen, studied, and analyzed. Analysis of the amino acid sequences of HNRNPA1 with VZV proteins has shown a 62% amino acid sequence similarity between VZV gE and the PrLD/M9 epitope region (TNPO1 binding domain) of mutant HNRNPA1. A heterogeneous nuclear ribonucleoprotein (hnRNP), which is produced by HNRNPA1, is involved in the processing and transfer of mRNA and pre-mRNA. Mutant HNRNPA1 mimics gE of VZV as an antigen that leads to autoantibody production. Mutant HnRNPA1 translocates to the cytoplasm, after aggregation is presented by MHC class I, followed by CD8 + cells. Of these, antibodies and immune cells against the gE epitopes of VZV remain due to the memory immune response, causing neurodegeneration and the development of MS in genetically predisposed individuals. VZV expression during the course of MS is present in genetically predisposed individuals with HNRNPA1 mutation, suggesting a link between VZV and MS, and that this virus may play a role in the development of MS by inducing an inflammatory state. Therefore, measures to modulate VZV expression may be effective in reducing inflammatory processes in demyelinated areas of MS patients in genetically predisposed individuals.

Keywords: multiple sclerosis, varicella-zoster virus, central nervous system, autoimmunity

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Authors: Michal Pravenec, Miroslava Simakova, Jan Silhavy

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Brown adipose tissue (BAT) plays an important role in lipid and glucose metabolism in rodents and possibly also in humans. Recently, using systems genetics approach in the BAT from BXH/HXB recombinant inbred strains, derived from the SHR (spontaneously hypertensive rat) and BN (Brown Norway) progenitors, we identified Cd36 (fatty acid translocase) as the hub gene of co-expression module associated with BAT relative weight and function. An important aspect of BAT biology is to better understand the mechanisms regulating the uptake and utilization of fatty acids and glucose. Accordingly, BAT function in the SHR that harbors mutant nonfunctional Cd36 variant (hereafter referred to as SHR-Cd36⁻/⁻) was compared with SHR transgenic line expressing wild type Cd36 under control of a universal promoter (hereafter referred to as SHR-Cd36⁺/⁺). BAT was incubated in media containing insulin and 14C-U-glucose alone or 14C-U-glucose together with palmitate. Incorporation of glucose into BAT lipids was significantly higher in SHR-Cd36⁺/⁺ versus SHR-Cd36⁻/⁻ rats when incubation media contained glucose alone (SHR-Cd36⁻/⁻ 591 ± 75 vs. SHR-Cd36⁺/⁺ 1036 ± 135 nmol/gl./2h; P < 0.005). Adding palmitate into incubation media had no effect in SHR-Cd36⁻/⁻ rats but significantly reduced glucose incorporation into BAT lipids in SHR-Cd36⁺/⁺ (SHR-Cd36⁻/⁻ 543 ± 55 vs. SHR-Cd36⁺/⁺ 766 ± 75 nmol/gl./2h; P < 0.05 denotes significant Cd36 x palmitate interaction determined by two-way ANOVA). This Cd36-dependent reduced glucose uptake in SHR-Cd36⁺/⁺ BAT was likely secondary to increased palmitate incorporation and utilization due to the presence of wild type Cd36 fatty acid translocase in transgenic rats. This possibility is supported by increased incorporation of 14C-U-palmitate into BAT lipids in the presence of both palmitate and glucose in incubation media (palmitate alone: SHR-Cd36⁻/⁻ 870 ± 21 vs. SHR-Cd36⁺/⁺ 899 ± 42; glucose+palmitate: SHR-Cd36⁻/⁻ 899 ± 47 vs. SHR-Cd36⁺/⁺ 1460 ± 111 nmol/palm./2h; P < 0.05 denotes significant Cd36 x glucose interaction determined by two-way ANOVA). It is possible that addition of glucose into the incubation media increased palmitate incorporation into BAT lipids in SHR-Cd36⁺/⁺ rats because of glucose availability for glycerol phosphate production and increased triglyceride synthesis. These changes in glucose and palmitate incorporation into BAT lipids were associated with significant differential expression of Irs1, Irs2, Slc2a4 and Foxo1 genes involved in insulin signaling and glucose metabolism only in SHR-Cd36⁺/⁺ rats which suggests Cd36-dependent effects on insulin action. In conclusion, these results provide compelling evidence that Cd36 plays an important role in BAT insulin signaling and energy substrate utilization.

Keywords: brown adipose tissue, Cd36, energy substrate utilization, insulin signaling, spontaneously hypertensive rat

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Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia(CIN)and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, p53, miR-146a, rs2910164, polymorphism

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Authors: Hossein Rassi, Marjan Moradi fard, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human Papillomavirus (HPV) infection is the leading risk factor for Cervical Intraepithelial Neoplasia (CIN) and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33, and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, miR-146a rs2910164 polymorphism, p53 polymorphism, intraepithelial, neoplasia, HPV

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Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

Abstract:

Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

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Authors: Younies Saeed Hassan Mahmoud, Mai Mabrouk, Elsayed Sallam

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Analysing DNA microarray data sets is a great challenge, which faces the bioinformaticians due to the complication of using statistical and machine learning techniques. The challenge will be doubled if the microarray data sets contain missing data, which happens regularly because these techniques cannot deal with missing data. One of the most important data analysis process on the microarray data set is feature selection. This process finds the most important genes that affect certain disease. In this paper, we introduce a technique for imputing the missing data in microarray data sets while performing feature selection.

Keywords: DNA microarray, feature selection, missing data, bioinformatics

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Authors: Thanthrige Thiunuwan Priyathilaka, Don Anushka Sandaruwan Elvitigala, Bong-Soo Lim, Hyung-Bok Jeong, Jehee Lee

Abstract:

Toll like receptors (TLRs) are a phylogeneticaly conserved family of pattern recognition receptors, which participates in the host immune responses against various pathogens and pathogen derived mitogen. TLR21, a non-mammalian type, is almost restricted to the fish species even though those can be identified rarely in avians and amphibians. Herein, this study was carried out to identify and characterize TLR21 from rock bream (Oplegnathus fasciatus) designated as RbTLR21, at transcriptional and genomic level. In this study, the full length cDNA and genomic sequence of RbTLR21 was identified using previously constructed cDNA sequence database and BAC library, respectively. Identified RbTLR21 sequence was characterized using several bioinformatics tools. The quantitative real time PCR (qPCR) experiment was conducted to determine tissue specific expressional distribution of RbTLR21. Further, transcriptional modulation of RbTLR21 upon the stimulation with Streptococcus iniae (S. iniae), rock bream iridovirus (RBIV) and Edwardsiella tarda (E. tarda) was analyzed in spleen tissues. The complete coding sequence of RbTLR21 was 2919 bp in length which can encode a protein consisting of 973 amino acid residues with molecular mass of 112 kDa and theoretical isoelectric point of 8.6. The anticipated protein sequence resembled a typical TLR domain architecture including C-terminal ectodomain with 16 leucine rich repeats, a transmembrane domain, cytoplasmic TIR domain and signal peptide with 23 amino acid residues. Moreover, protein folding pattern prediction of RbTLR21 exhibited well-structured and folded ectodomain, transmembrane domain and cytoplasmc TIR domain. According to the pair wise sequence analysis data, RbTLR21 showed closest homology with orange-spotted grouper (Epinephelus coioides) TLR21with 76.9% amino acid identity. Furthermore, our phylogenetic analysis revealed that RbTLR21 shows a close evolutionary relationship with its ortholog from Danio rerio. Genomic structure of RbTLR21 consisted of single exon similar to its ortholog of zebra fish. Sevaral putative transcription factor binding sites were also identified in 5ʹ flanking region of RbTLR21. The RBTLR 21 was ubiquitously expressed in all the tissues we tested. Relatively, high expression levels were found in spleen, liver and blood tissues. Upon induction with rock bream iridovirus, RbTLR21 expression was upregulated at the early phase of post induction period even though RbTLR21 expression level was fluctuated at the latter phase of post induction period. Post Edwardsiella tarda injection, RbTLR transcripts were upregulated throughout the experiment. Similarly, Streptococcus iniae induction exhibited significant upregulations of RbTLR21 mRNA expression in the spleen tissues. Collectively, our findings suggest that RbTLR21 is indeed a homolog of TLR21 family members and RbTLR21 may be involved in host immune responses against bacterial and DNA viral infections.

Keywords: rock bream, toll like receptor 21 (TLR21), pattern recognition receptor, genomic characterization

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Authors: Dalia. G. Aseel, E. E. Hafez, S. M. Hammad

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Viral RNAs of both potato leaf roll virus (PLRV) and potato virus Y (PVY) were extracted from infected potato leaves collected from different Egyptian regions. Differential Display Polymerase Chain Reaction (DD-PCR) using (Endogluconase, β-1,3-glucanases, Chitinase, Peroxidase and Polyphenol oxidase) primers (forward strand) for was performed. The obtained data revealed different banding patterns depending on the viral type and the region of infection. Regarding PLRV, a 58 up regulated and 19 down regulated genes were detected, while, 31 up regulated and 14 down regulated genes were observed in case of PVY. Based on the nucleotide sequencing, variable phylogenetic relationships were reported for the three sequenced genes coding for: Induced stolen tip protein, Disease resistance RPP-like protein and non-specific lipid-transfer protein. In a complementary approach, using the quantitative Real-time PCR, the expressions of PRs genes understudy were estimated in the infected leaves by PLRV and PVY of three potato cultivars (Spunta, Diamont and Cara). The infection with both viruses inhibited the expressions of the five PRs genes. On the contrary, infected leaves by PLRV or PVY elevated the expression of some defense genes. This interaction also may be enhanced and/or inhibited the expression of some genes responsible for the plant defense mechanisms.

Keywords: PLRV, PVY, PR genes, DD-PCR, qRT-PCR, sequencing

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Authors: W. S. Thulasitha, N. Umasuthan, G. I. Godahewa, Jehee Lee

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In fish, innate immune defense is the first immune response against microbial pathogens which consists of several antimicrobial components. Galectins are one of the carbohydrate binding lectins that have the ability to identify pathogen by recognition of pathogen associated molecular patterns. Galectins play a vital role in the regulation of innate and adaptive immune responses. Rock bream Oplegnathus fasciatus is one of the most important cultured species in Korea and Japan. Considering the losses due to microbial pathogens, present study was carried out to understand the molecular and functional characteristics of a galectin in normal and pathogenic conditions, which could help to establish an understanding about immunological components of rock bream. Complete cDNA of rock bream galectin like protein B (rbGal like B) was identified from the cDNA library, and the in silico analysis was carried out using bioinformatic tools. Genomic structure was derived from the BAC library by sequencing a specific clone and using Spidey. Full length of rbGal like B (contig14775) cDNA containing 517 nucleotides was identified from the cDNA library which comprised of 435 bp in the open reading frame encoding a deduced protein composed of 145 amino acids. The molecular mass of putative protein was predicted as 16.14 kDa with an isoelectric point of 8.55. A characteristic conserved galactose binding domain was located from 12 to 145 amino acids. Genomic structure of rbGal like B consisted of 4 exons and 3 introns. Moreover, pairwise alignment showed that rock bream rbGal like B shares highest similarity (95.9 %) and identity (91 %) with Takifugu rubripes galectin related protein B like and lowest similarity (55.5 %) and identity (32.4 %) with Homo sapiens. Multiple sequence alignment demonstrated that the galectin related protein B was conserved among vertebrates. A phylogenetic analysis revealed that rbGal like B protein clustered together with other fish homologs in fish clade. It showed closer evolutionary link with Takifugu rubripes. Tissue distribution and expression patterns of rbGal like B upon immune challenges were performed using qRT-PCR assays. Among all tested tissues, level of rbGal like B expression was significantly high in gill tissue followed by kidney, intestine, heart and spleen. Upon immune challenges, it showed an up-regulated pattern of expression with Edwardsiella tarda, rock bream irido virus and poly I:C up to 6 h post injection and up to 24 h with LPS. However, In the presence of Streptococcus iniae rbGal like B showed an up and down pattern of expression with the peak at 6 - 12 h. Results from the present study revealed the phylogenetic position and role of rbGal like B in response to microbial infection in rock bream.

Keywords: galectin like protein B, immune response, Oplegnathus fasciatus, molecular characterization

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Authors: A. Abyar, R. Khavarzadeh

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The most basic and important decision-making tool for industrial and service managers is understanding the market and customer behavior. In this regard, the Apriori algorithm, as one of the well-known machine learning methods, is used to identify customer preferences. On the other hand, with the increasing diversity of goods and services and the speed of changing customer behavior, we are faced with big data. Also, due to the large number of competitors and changing customer behavior, there is an urgent need for continuous analysis of this big data. While the speed of the Apriori algorithm decreases with increasing data volume. In this paper, the big data PCA method is used to reduce the dimension of the data in order to increase the speed of Apriori algorithm. Then, in the simulation section, the results are examined by generating data with different volumes and different diversity. The results show that when using this method, the speed of the a priori algorithm increases significantly.

Keywords: association rules, Apriori algorithm, big data, big data PCA, market basket analysis

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Authors: Dalal Alghawas, Jetty Lee, Kaisa Poutanen, Hani El-Nezami

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Oat β-glucan a water soluble non starch linear polysaccharide has been approved as a cholesterol lowering agent by various food safety administrations and is commonly used to reduce the risk of heart disease. The molecular weight of oat β-glucan can vary depending on the extraction and fractionation methods. It is not clear whether the molecular weight has a significant impact at reducing the acceleration of atherosclerosis. The aim of this study was to investigate three different oat β-glucan fractionations on the development of atherosclerosis in vivo. With special focus on plaque stability and the intestinal barrier function. To test this, ApoE-/- female mice were fed a high fat diet supplemented with oat bran, high molecular weight (HMW) oat β-glucan fractionate and low molecular weight (LMW) oat β-glucan fractionate for 16 weeks. Atherosclerosis risk markers were measured in the plasma, heart and aortic tree. Plaque size was measured in the aortic root and aortic tree. ICAM-1, VCAM-1, E-Selectin, P-Selectin, protein levels were assessed from the aortic tree to determine plaque stability at 16 weeks. The expression of p22phox at the aortic root was evaluated to study the NADPH oxidase complex involved in nitric oxide bioavailability and vascular elasticity. The tight junction proteins E-cadherin and beta-catenin from western blot analyses were analysed as an intestinal barrier function test. Plasma LPS, intestinal D-lactate levels and hepatic FMO gene expression were carried out to confirm whether the compromised intestinal barrier lead to endotoxemia. The oat bran and HMW oat β-glucan diet groups were more effective than the LMW β-glucan diet group at reducing the plaque size and showed marked improvements in plaque stability. The intestinal barrier was compromised for all the experimental groups however the endotoxemia levels were higher in the LMW β-glucan diet group. The oat bran and HMW oat β-glucan diet groups were more effective at attenuating the development of atherosclerosis. Reasons for this could be due to the LMW oat β-glucan diet group’s low viscosity in the gut and the inability to block the reabsorption of cholesterol. Furthermore the low viscosity may allow more bacterial endotoxin translocation through the impaired intestinal barrier. In future food technologists should carefully consider how to incorporate LMW oat β-glucan as a health promoting food.

Keywords: Atherosclerosis, beta glucan, endotoxemia, intestinal barrier function

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Authors: Daria Zabolotnaya, Svetlana Degtyareva, Veronika Kanestri, Danila Konnov

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An adequate choice of the initial antiretroviral treatment determines the treatment efficacy. In the clinical guidelines in Russia non-nucleoside reverse transcriptase inhibitors (NNRTIs) are still considered to be an option for first-line treatment while pretreatment drug resistance (PDR) testing is not routinely performed. We conducted a cohort retrospective study in HIV-positive treatment naïve patients of the H-clinic (Moscow, Russia) who performed PDR testing from July 2017 to November 2021. All the information was obtained from the medical records anonymously. We analyzed the mutations in reverse transcriptase and protease genes. RT-sequences were obtained by AmpliSens HIV-Resist-Seq kit. Drug resistance was defined using the HIVdb Program v. 8.9-1. PDR was estimated using the Stanford algorithm. Descriptive statistics were performed in Excel (Microsoft Office, 2019). A total of 261 HIV-1 infected patients were enrolled in the study including 197 (75.5%) male and 64 (24.5%) female. The mean age was 34.6±8.3 years. The median CD4 count – 521 cells/µl (IQR 367-687 cells/µl). Data on risk factors of HIV-infection were scarce. The total quantity of strains containing mutations in the reverse transcriptase gene was 75 (28.7%). From these 5 (1.9%) mutations were associated with PDR to nucleoside reverse transcriptase inhibitors (NRTIs) and 30 (11.5%) – with PDR to NNRTIs. The number of strains with mutations in protease gene was 43 (16.5%), from these only 3 (1.1%) mutations were associated with resistance to protease inhibitors. For NNRTIs the most prevalent PDR mutations were E138A, V106I. Most of the HIV variants exhibited a single PDR mutation, 2 were found in 3 samples. Most of HIV variants with PDR mutation displayed a single drug class resistance mutation. 2/37 (5.4%) strains had both NRTIs and NNRTIs mutations. There were no strains identified with PDR mutations to all three drug classes. Though earlier data demonstrated a lower level of PDR in HIV treatment naïve population in Russia and our cohort can be not fully representative as it is taken from the private clinic, it reflects the trend of increasing PDR especially to NNRTIs. Therefore, we consider either pretreatment testing or giving the priority to other drugs as first-line treatment necessary.

Keywords: HIV, resistance, mutations, treatment

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Authors: A. Watson, G. Telford, D. I. Pritchard

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Objective: We investigated the immunomodulatory ability of licorice (Glycyrrhiza glabra). Such activities could have value for the management of common immunological diseases in dogs, such as environmental allergy. This study investigated the potential of a Licorice root extract (LRE) to influence the relative expression of Th-1, Th-2, and Th-17 cytokines in canine peripheral blood mononuclear cells (PBMC). Methods: A LRE was prepared using an alcoholic-aqueous-based solvent method. The extract was tested in three in vitro assays using canine leukocytes to determine its toxicity and immunoregulatory profile. Extract toxicity was assessed using the human T-lymphocyte cell line, Jurkat E6.1. The impact of the extract on the proliferation of concanavalin-activated canine PBMC was also determined. Finally, the extract was assessed for its ability to influence cytokine release in activated PBMC, measuring culture medium concentrations of interleukin-17, interferon gamma, and interleukin-4. One-way ANOVA followed by Dunnett’s post-test was used for statistics using concanavalin positive control as reference (p ≤ 0.05). Results: There was evidence that the LRE had specific immunomodulatory properties, causing significant inhibition of IL4 expression over a non-toxic/non-cytostatic concentration range (p < 0.001). In the same cell incubations, there was no significant impact on IL17 nor IFNg over the same non-toxic/non-cytostatic concentration range. Conclusion: The study provides in vitro evidence that LRE preferentially reduces the expression of a Th-2-type cytokine, IL4. The dog population, as with humans, is prone to conditions associated with a Th-2 bias of the immune system, such as environmental allergy. Based on these results, licorice merits further evaluation as a useful immune modulator for such allergic diseases.

Keywords: cytokine, Glycyrrhiza glabra, peripheral blood mononuclear cells, T-cell activation

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Authors: Mohamed M. Bumadian, D. James Gilmour

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Three bacterial species were isolated from the River Wye (Derbyshire, England) and identified using 16S rRNA gene sequencing as Serratia proteamaculans, Aeromonas hydrophila and Klebsiella pneumoniae. Respiration rates of the strains were measured in order to determine the metabolic activity under salt stress. The highest respiration rates of all three strains were found at 0.17 M and 0.5 M NaCl and then the respiration rate decreased with increasing concentrations of NaCl. In addition, the effect of increasing concentrations of NaCl on malate dehydrogenase activity was determined using cell-free extracts of the three strains. Malate dehydrogenase activity was stimulated at NaCl concentrations up to 0.5 M, and a small level of activity remained even at 3.5 M NaCl. The pH optimum of the malate dehydrogenase in cell-free extracts of all strains was higher than pH 7.5.

Keywords: fresh water, halotolerant pathogenic bacteria, 16S rRNA gene, cell-free extracts, respiration rates, malate dehydrogenase

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Authors: Salma A. Mahmoud

Abstract:

Epigenetic, or alteration in gene expression influenced by extragenetic factors, has emerged as one of the most promising areas that will address some of the gaps in our current knowledge in understanding patterns of human variation. In the last decade, the research investigating epigenetic mechanisms in many fields has flourished and witnessed significant progress. It paved the way for a new era of integrated research especially between anthropology/archeology and life sciences. Skeletal remains are considered the most significant source of information for studying human variations across history, and by utilizing these valuable remains, we can interpret the past events, cultures and populations. In addition to archeological, historical and anthropological importance, studying bones has great implications in other fields such as medicine and science. Bones also can hold within them the secrets of the future as they can act as predictive tools for health, society characteristics and dietary requirements. Bones in their basic forms are composed of cells (osteocytes) that are affected by both genetic and environmental factors, which can only explain a small part of their variability. The primary objective of this project is to examine the epigenetic landscape/signature within bones of archeological remains as a novel marker that could reveal new ways to conceptualize chronological events, gender differences, social status and ecological variations. We attempted here to address discrepancies in common variants such as methylome as well as novel epigenetic regulators such as chromatin remodelers, which to our best knowledge have not yet been investigated by anthropologists/ paleoepigenetists using plethora of techniques (biological, computational, and statistical). Moreover, extracting epigenetic information from bones will highlight the importance of osseous material as a vector to study human beings in several contexts (social, cultural and environmental), and strengthen their essential role as model systems that can be used to investigate and construct various cultural, political and economic events. We also address all steps required to plan and conduct an epigenetic analysis from bone materials (modern and ancient) as well as discussing the key challenges facing researchers aiming to investigate this field. In conclusion, this project will serve as a primer for bioarcheologists/anthropologists and human biologists interested in incorporating epigenetic data into their research programs. Understanding the roles of epigenetic mechanisms in bone structure and function will be very helpful for a better comprehension of their biology and highlighting their essentiality as interdisciplinary vectors and a key material in archeological research.

Keywords: epigenetics, archeology, bones, chromatin, methylome

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Authors: Maria Luisa Barcena De Arellano, Sofya Pozdniakova, Pavelas Karkacas, Anja Kuhl, Istvan Baczko, Yury Ladilov, Vera Regitz-Zagrosek

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Introduction: Aging is associated with deterioration of the physiological function, leading to systemic inflammation and mitochondrial dysfunction that promote the development of cardiovascular diseases. Sex differences in aging-related cardiovascular diseases have been postulated. However, their precise mechanisms remain unclear. In the current study, we aimed to investigate the sex difference in the age-related alteration in Sirt1-AMPK signaling and its relation to the mitochondrial biogenesis and inflammation. Methods: Male and female human non-disease lateral left ventricular wall tissue (young (17–40 years; n= 7 male and 7 female) and old (50–68 years; n= 9 male and 8 female)) were used. qRT-PCR, western blot and immunohistochemistry assays were performed for expression analyses of Sirt1, AMPK, pAMPK, ac-Ku70, TFAM, PGC-1α, Sirt3, SOD2 and catalase. CD68 was used as a marker for macrophages and the ratio of IL-12:IL10 (pro-inflammatory phenotype (high IL-12/low IL-10) and anti-inflammatory phenotype (low IL-12/high IL-10) was used to examine the inflammatory stage in the heart. Results: Sirt1 expression was significantly higher in young females compared to young males, whereas in aged hearts Sirt1 expression was significantly downregulated in females, but not in males. In line with the Sirt1 downregulation in aged females, acetylation of nuclear Ku70, a direct target of Sirt1, in aged female hearts was significantly elevated. The activity of AMPK was significantly decreased in aged individuals, however no sex differences in the AMPK expression or activity were found in young or old individuals. The expression of mitochondrial proteins TOM40, SOD2 and Sirt3 was significantly higher in young females compared to young males, while in aged female hearts SOD2 and TOM40 were downregulated. In addition, the expression of catalase, a key cytosolic and mitochondrial anti-oxidative enzyme was significantly higher in young females and this female sex benefit was lost in aged hearts. In addition, the number of cardiac macrophages was significantly increased in old female, but not in male hearts. Consistently, the pro-inflammatory shift in old females was further confirmed by differences in the IL12/IL10 ratio in young female cardiac tissue in a favour of the anti-inflammatory mediator IL-10 (ratio 1:4) compared to young males (ratio 1:1). The anti-inflammatory environment in the heart was lost in aged females (ratio 1:1). Conclusion: Aging leads to the significant downregulation of Sirt1 expression and elevated acetylation of Ku70 in female, but not in male hearts. Furthermore, a beneficial upregulation of mitochondrial and anti-oxidative proteins in young females is lost with aging. Moreover, the malfunctions in the expression of Sirt1 and mitochondrial proteins in aged female hearts is accompanied by a significant pro-inflammatory shift. The study provides a molecular basis for the increased incidence of cardiovascular diseases in old women.

Keywords: inflammation, mitochondrial dysfunction, aging, Sirt1-AMPK axis

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Authors: Xiquan Weng, Chaoge Wang, Guoqin Xu, Wentao Lin

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Objective: Cold exposure and exercise serve as two powerful physiological stimuli to launch the conversion of fat-accumulating white adipose tissue (WAT) into energy-dissipating brown adipose tissue (BAT). So far, it remains to be elucidated whether exercise plus cold exposure can produce an addictive effect on promoting WAT browning. Methods: 64 SD rats were subjected to high-fat and high-sugar diets for 9-week and successfully established an obesity model. They were randomly divided into 8 groups: normal control group (NC), normal exercise group (NE), continuous cold control group (CC), continuous cold exercise group (CE), intermittent cold control group (IC) and intermittent cold exercise group (IE). For continuous cold exposure, the rats stayed in a cold environment all day; For intermittent cold exposure, the rats were exposed to cold for only 4h per day. The protocol for treadmill exercises were as follows: 25m/min (speed), 0°C (slope), 30mins each time, an interval for 10 mins between two exercises, twice/two days, lasting for 5 weeks. Sampling were conducted on the 5th weekend. The body length and weight of the rats were measured, and the Lee's index was calculated. The visceral fat rate (VFR), subcutaneous fat rate (SFR), brown fat rate (BrFR) and body fat rate (BoFR) were measured by Micro-CT LCT200, and the expression of UCP1 protein in inguinal fat was examined by Western-blot. SPSS 22.0 was used for statistical analysis of the experimental results, and the ANOVA analysis was performed between groups (P < 0.05 was significant). Results: (1) Compared with the NC group, the weight of obese rats was significantly declined in the NE, CE and IE groups (P < 0.05), the Lee's index of obese rats significantly declined in the CE group (P < 0.05). Compared with the NE group, the weight of obese rats was significantly declined in the CE and IE groups (P < 0.05). (2)Compared with the NC group, the VFR and BoFR of the rats significantly declined in the NE, CE and IE groups (P < 0.05), the SFR of the rats significantly declined in the CE and IE groups (P < 0.05), and the BFR of the rats was significantly higher in the CC and IC groups (P < 0.05), respectively. Compared with the NE group, the VFR and BoFR of the rats significantly declined in the CE group (P < 0.05), the SFR of the rats was significantly higher in the CC and IS groups (P < 0.05), and the BrFR of the rats was significantly higher in the IC group (P < 0.05). (3)Compared with the NC group, the up-regulation of UCP1 protein expression in the inguinal fat of the rats was significant in the NE, CC, CE, IC and IE groups (P < 0.05). Compared with the NE group, the up-regulation of UCP1 protein expression in the inguinal fat of the rats was significant in the CC, CE and IE groups (P < 0.05). Conclusions: Exercise in the continuous and intermittent cold, especially in the former, can effectively decline the weight and body fat rate of obese rats. This is related to the effect of cold and exercise on the browning of white fat in rats.

Keywords: cold, browning of white fat, exercise, obesity

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Authors: Boitumelo Setlhare, Mduduzi P. Mokoena, Ademola O. Olaniran

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Agricultural and industrial activities have led to increasing production of xenobiotics such as 2,4-dichlorophenol (2,4-DCP), a derivative of 2,4-dichlorophenoxyacetic acid (2,4-D), which is a widely used herbicide. Bioremediation offers an efficient, cost-effective and environmentally friendly method for degradation of the compound through the activities of the various microbial enzymes involved in the catabolic pathway. The aim of this study was to isolate and characterize bacterial isolate indigenous to contaminated sites in Durban, South Africa for 2,4-DCP degradation. One bacterium capable of utilizing 2,4-DCP as sole carbon source was isolated using culture enrichment technique and identified as Pseudomonas chlororaphis strain UFB2 via PCR amplification and analysis of 16S rRNA gene sequence. This isolate was able to degrade up to 75.11% of 2,4-DCP in batch cultures within 10 days, with the degradation rate constant of 0.14 mg/l/d. Phylogenetic analysis revealed the relatedness of this bacterial isolate to other Pseudomonas sp. previously characterized for chlorophenol degradation. PCR amplification of the catabolic genes involved in 2,4-DCP degradation revealed the presence of the correct amplicons for phenol hydroxylase (600 bp), catechol 1,2-dioxygenase (214 bp), muconate isomerase (851 bp), cis-dienelactone hydrolase (577 bp), and trans-dienelactone hydrolase (491 bp) genes. Enzyme assays revealed activity as high as 21840 mU/mg, 15630 mU/mg, 2340 mU/mg and 1490 mU/mg obtained for phenol hydroxylase, catechol 1,2-dioxygenase, cis-dienelactone hydroxylase and trans-dienelactone hydroxylase, respectively. The absence of catechol 2,3-dioxygenase gene and the corresponding enzyme in this isolate suggests that the organism followed ortho-pathway for 2,4-DCP degradation. Furthermore, the absence of malaycetate reductase genes showed that the bacterium may not be able to completely mineralize 2,4-DCP. Further studies are required to optimize 2,4-DCP degradation by this isolate as well as to elucidate the mechanism of 2,4-DCP degradation.

Keywords: biodegradation, catechol 1, 2-dioxygenase, 2, 4-dichlorophenol, phenol hydroxylase, Pseudomonas chlororaphis

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Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand

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Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia (CIN) and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, HPV18, p53 codon 72 polymorphism, miR-146a rs2910164 polymorphism

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Authors: Ekaterina Zubkova, Irina Beloglazova, Iurii Stafeev, Konsyantin Dergilev, Yelena Parfyonova, Mikhail Menshikov

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Mesenchymal stromal cells from adipose tissue (MSC) currently are widely used in regenerative medicine to restore the function of damaged tissues, but that is significantly hampered by their heterogeneity. One of the modern approaches to overcoming this obstacle is the polarization of cell subpopulations into a specific phenotype under the influence of cytokines and other factors that activate receptors and signal transmission to cells. We polarized MSC with factors affecting the inflammatory signaling and functional properties of cells, followed by verification of their expression profile and ability to affect the polarization of macrophages. RT-PCR evaluation showed that cells treated with LPS, interleukin-17, tumor necrosis factor α (TNF α), primarily express pro-inflammatory factors and cytokines, and after treatment with polyninosin polycytidic acid and interleukin-4 (IL4) anti-inflammatory factors and some proinflammatory factors. MSC polarized with pro-inflammatory cytokines showed a more robust pro-angiogenic effect in fibrin gel bead 3D angiogenesis assay. Further, we evaluated the possibility of paracrine effects of MSCs on the polarization of intact macrophages. Polarization efficiency was assesed by expression of M1/M2 phenotype markers CD80 and CD206. We showed that conditioned media from MSC preincubated in the presence of IL-4 cause an increase in CD206 expression similar to that observed in M2 macrophages. Conditioned media from MSC polarized in the presence of LPS or TNF-α increased the expression of CD80 antigen in macrophages, similar to that observed in M1 macrophages. In other cases, a pronounced paracrine effect of MSC on the polarization of macrophages was not detected. Thus, our study showed that the polarization of MSC along the pro-inflammatory or anti-inflammatory pathway allows us to obtain cell subpopulations that have a multidirectional modulating effect on the polarization of macrophages. (RFBR grants 20-015-00405 and 18-015-00398.)

Keywords: angiogenesis, cytokines, mesenchymal, polarization, inflammation

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Authors: Shishen Xie, Yingda L. Xie

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Tuberculosis (TB) is a potentially serious infectious disease that remains a health concern. The Interferon Gamma Release Assay (IGRA) is a blood test to find out if an individual is tuberculous positive or negative. This study applies statistical analysis to the clinical data of interferon-gamma levels of seventy-three subjects who diagnosed pulmonary TB in an anti-tuberculous treatment. Data analysis is performed to determine if there is a significant decline in interferon-gamma levels for the subjects during a period of six months, and to infer if the anti-tuberculous treatment is effective.

Keywords: data analysis, interferon gamma release assay, statistical methods, tuberculosis infection

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Authors: Mariam Khaled, Noha Farag, Ghada Mohamed Abdel Salam, Khaled Abu-Aisha, Mohamed El-Azizi

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Gastric and colorectal cancers are among the most frequent causes of cancer-associated mortalities in Africa. They have been considered as a global public health concern, as nearly one million new cases are reported per year. IL-1β is a pro-inflammatory cytokine-produced by activated macrophages and monocytes- and a member of the IL-1 family. The inactive IL-1β precursor is cleaved and activated by caspase-1 enzyme, which itself is activated by the assembly of intracellular structures defined as NLRP3 (Nod Like receptor P3) inflammasomes. Activated IL-1β stimulates the Interleukin-1 receptor type-1 (IL-1R1), which is responsible for the initiation of a signal transduction pathway leading to cell proliferation. It has been proven that the IL-1β gene is a highly polymorphic gene in which single nucleotide polymorphisms (SNPs) may affect its expression. It has been previously reported that SNPs including base transitions between C and T at positions, -511 (C-T; dbSNP: rs16944) and -31 (C-T; dbSNP: rs1143627), from the transcriptional start site, contribute to the pathogenesis of gastric and colorectal cancers by affecting IL-1β levels. Altered production of IL-1β due to such polymorphisms is suspected to stimulate an amplified inflammatory response and promote Epithelial Mesenchymal Transition leading to malignancy. Allele frequency distribution of the IL-1β-31 and -511 SNPs, in different populations, and their correlation to the incidence of gastric and colorectal cancers, has been intriguing to researchers worldwide. The current study aims to investigate allele distributions of the IL-1β SNPs among gastric and colorectal cancers Egyptian patients. In order to achieve to that, 89 Biopsy and surgical specimens from the antrum and corpus mucosa of chronic gastritis subjects and gastric and colorectal carcinoma patients was collected for DNA extraction followed by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). The amplified PCR products of IL-1β-31C > T and IL-1β-511T > C were digested by incubation with the restriction endonuclease enzymes ALu1 and Ava1. Statistical analysis was carried out to determine the allele frequency distribution in the three studied groups. Also, the effect of the IL-1β -31 and -511 SNPs on nuclear factor binding was analyzed using Fluorescence Electrophoretic Mobility Shift Assay (EMSA), preceded by nuclear factor extraction from gastric and colorectal tissue samples and LPS stimulated monocytes. The results of this study showed that a significantly higher percentage of Egyptian gastric cancer patients have a homozygous CC genotype at the IL-1β-31 position and a heterozygous TC genotype at the IL-1β-511 position. Moreover, a significantly higher percentage of the colorectal cancer patients have a homozygous CC genotype at the IL-1β-31 and -511 positions as compared to the control group. In addition, the EMSA results showed that IL-1β-31C/T and IL-1β-511T/C SNPs do not affect nuclear factor binding. Results of this study suggest that the IL-1β-31 C/T and IL-1β-511 T/C may be correlated to the incidence of gastric cancer in Egyptian patients; however, similar findings couldn’t be proven in the colorectal cancer patients group for the IL-1β-511 T/C SNP. This is the first study to investigate IL-1β -31 and -511 SNPs in the Egyptian population.

Keywords: colorectal cancer, Egyptian patients, gastric cancer, interleukin-1β, single nucleotide polymorphisms

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Authors: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan

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Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

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Authors: Changfeng Fu

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Sustainable urban development has been widely accepted a common sense in the modern urban planning and design. However, the measurement and assessment of urban sustainability, especially the quantitative assessment have been always an issue obsessing planning and design professionals. This paper will present an on-going research on the principles and technologies to develop a quantitative urban sustainability assessment principles and techniques which aim to integrate indicators, geospatial and geo-reference data, and assessment techniques together into a mechanism. It is based on the principles and techniques of geospatial analysis with GIS and statistical analysis methods. The decision-making technologies and methods such as AHP and SMART are also adopted to address overall assessment conclusions. The possible interfaces and presentation of data and quantitative assessment results are also described. This research is based on the knowledge, situations and data sources of UK, but it is potentially adaptable to other countries or regions. The implementation potentials of the mechanism are also discussed.

Keywords: urban sustainability assessment, quantitative analysis, sustainability indicator, geospatial data, big data

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Authors: Aslı Şalcıoğlu, Grigorous Krey, Raşit Bilgin

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In this study, the effect of the Turkish Straits System (TSS), comprising a biogeographical boundary that forms the connection between the Mediterranean and the Black Sea, on the evolutionary history, phylogeography and intraspecific gene flow of the whiting (Merlangius merlangus) a demersal fish species, was investigated. For these purposes, the mitochondrial DNA (CO1, cyt-b) genes were used. In addition, genetic comparisons samples from other regions (Greece, France, Atlantic) obtained from GenBank and Barcode of Life Database were made to better understand the phylogeographic history of the species at a larger geographic scale. Within this study, high level of genetic differentiation was observed along the Turkish coastal waters based on cyt-b gene, suggesting that TSS is a barrier to dispersal. Two different sub-species were also observed based on mitochondrial DNA, one found in Turkish coastal waters and Greece (M.m euxinus) and other (M.m. merlangus) in Atlantic, France.

Keywords: genetic, phylogeography, TSS, whiting

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Human Herpesvirus 6 (HHV-6), and MS is one potential cause that is not well understood. In this study, we aim to summarize the available data on HHV-6 infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", " Human Herpesvirus 6 ", and "central nervous system" in the databases PubMed and Google Scholar between 2017 and 2022 were searched, and 12 articles were chosen, studied, and analyzed. Results: HHV 6 tends towards TCD 4+ lymphocytes and enters the CNS due to the weakening of the blood-brain barrier due to inflammatory damage. Following the observation that the HHV-6 U24 protein has a seven amino acid sequence with myelin basic protein, which is one of the main components of the myelin sheath, it could cause a molecular mimicry mechanism followed by cross-reactivity. Reactivation of HHV-6 in the CNS can cause the release of proinflammatory cytokines, including TNF-α, leading to immune-mediated demyelination in patients with MS. Conclusion: There is a high expression of endogenous retroviruses during the course of MS, which indicates the relationship between HHV-6 and MS, and that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of HHV-6 may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human herpesvirus 6, central nervous system, autoimmunity

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Authors: David Percy

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Landslides are a geologic phenomenon that affects a large number of inhabited places and are constantly being monitored and studied for the prediction of future occurrences. Reconstructability analysis (RA) is a methodology for extracting informative models from large volumes of data that work exclusively with discrete data. While RA has been used in medical applications and social science extensively, we are introducing it to the spatial sciences through applications like landslide prediction. Since RA works exclusively with discrete data, such as soil classification or bedrock type, working with continuous data, such as porosity, requires that these data are binned for inclusion in the model. RA constructs models of the data which pick out the most informative elements, independent variables (IVs), from each layer that predict the dependent variable (DV), landslide occurrence. Each layer included in the model retains its classification data as a primary encoding of the data. Unlike other machine learning algorithms that force the data into one-hot encoding type of schemes, RA works directly with the data as it is encoded, with the exception of continuous data, which must be binned. The usual physical and derived layers are included in the model, and testing our results against other published methodologies, such as neural networks, yields accuracy that is similar but with the advantage of a completely transparent model. The results of an RA session with a data set are a report on every combination of variables and their probability of landslide events occurring. In this way, every combination of informative state combinations can be examined.

Keywords: reconstructability analysis, machine learning, landslides, raster analysis

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