The Epic Battle Between Nature and Technology in Ray Bradbury’s Dystopian Novel, Fahrenheit 451

في رواية برادبري البائسة فهرنهايت 451 ، التي كتبت عام 1953، هناك صراع مؤثر بين الطبيعة والتكنولوجيا. تتحدث القصة عن عالم مستقبلي يمكن للإنسان فيه الوصول إلى مصادر مختلفة للترفيه عبر التكنولوجيا. للأسف، في مسار الحكاية، كان التغاضي عن الطبيعة ومجدها الملهم واستبدالها بالتكنولوجيا في حياة غالبية الشخصيات. يقوم غي مونتاج ، بطل الرواية، برحلة تحرر من السلطة القمعية إلى تحقيق المعرفة المحرمة. الطبيعة في القصة هي الملاذ التي يلجأ إليها روحيًا وجسديًا لتحقيق هدفه. تستكشف هذه الدراسة الصراع بين الطبيعة و التكنولوجيا بعرض أمثلة لسوء استخدام الدولة للتكنولوجيا  وإهمال الطبيعة في مجتمع قمعي. تجادل الدراسة أنه على الرغم من أن التكنولوجيا قد تبدو جذابة في هذا العصر، إلا أن بناء شخصية البطل لن يكون ممكنًا من دون استعادة وظيفة الطبيعة في حياة الإنسان في المستقبل. وتختتم الدراسة بإيجاز يفيد أن الطبيعة تسود في نهاية الصراع.    In Bradbury’s dystopian novel, Fahrenheit 451, written in 1953, there is an influential conflict between nature and technology. The story is about a future world in which people can access different sources of entertainment via technology. Regrettably, during the course of the tale, nature and its inspiring glory is overlooked and substituted by technology in the life of the majority of the characters. Guy Montag, the protagonist of the story, undertakes a voyage of liberation from oppressive authority to the fulfillment of forbidden knowledge. Nature in the book is the haven he resorts to both spiritually and physically to achieve his aim. This study explores the struggle between nature and technology by portraying instances of the state’s ill use of technology and its negligence of nature in an oppressive society. The paper argues that though technology might seem appealing in this age, the construction of the protagonist’s personality would not be possible without the restoration of the function of nature in the future man’s life. The paper concludes with a brief account stating that nature reigns supreme at the end of the conflict

Genome-wide blood DNA methylation alterations at regulatory elements and heterochromatic regions in monozygotic twins discordant for obesity and liver fat

Abstract Background The current epidemic of obesity and associated diseases calls for swift actions to better understand the mechanisms by which genetics and environmental factors affect metabolic health in humans. Monozygotic (MZ) twin pairs showing discordance for obesity suggest that epigenetic influences represent one such mechanism. We studied genome-wide leukocyte DNA methylation variation in 30 clinically healthy young adult MZ twin pairs discordant for body mass index (BMI; average within-pair BMI difference: 5.4 ± 2.0 kg/m2). Results There were no differentially methylated cytosine-guanine (CpG) sites between the co-twins discordant for BMI. However, stratification of the twin pairs based on the level of liver fat accumulation revealed two epigenetically highly different groups. Significant DNA methylation differences (n = 1,236 CpG sites (CpGs)) between the co-twins were only observed if the heavier co-twins had excessive liver fat (n = 13 twin pairs). This unhealthy pattern of obesity was coupled with insulin resistance and low-grade inflammation. The differentially methylated CpGs included 23 genes known to be associated with obesity, liver fat, type 2 diabetes mellitus (T2DM) and metabolic syndrome, and potential novel metabolic genes. Differentially methylated CpG sites were overrepresented at promoters, insulators, and heterochromatic and repressed regions. Based on predictions by overlapping histone marks, repressed and weakly transcribed sites were significantly more often hypomethylated, whereas sites with strong enhancers and active promoters were hypermethylated. Further, significant clustering of differentially methylated genes in vitamin, amino acid, fatty acid, sulfur, and renin-angiotensin metabolism pathways was observed. Conclusions The methylome in leukocytes is altered in obesity associated with metabolic disturbances, and our findings indicate several novel candidate genes and pathways in obesity and obesity-related complications

DNA methylation signatures of aggression and closely related constructs : A meta-analysis of epigenome-wide studies across the lifespan

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 x 10(-7); Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.Peer reviewe

DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10-7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.</p

Differential Methylation Analysis of Monozygotic Twin Pairs Discordant for Body Mass Index

Obesity is associated with life styles involving overconsumption of high-energy food and having low amount of physical activity but the heritability of obesity has also been shown to be high. Results from genome wide association studies (GWAS), however, could explain only 5% of this heritability. This evidence points towards epigenetics acting as a mediator that allows the environment to affect the phenotype without changing the genotype, and epigenetics as a factor that may explain the missing heritability. DNA methylation, which plays an important role in cell differentiation and which has already been associated with diseases such as cancer and diabetes, is the most studied epigenetic factor. DNA methylation is the addition of a methyl group to a cytosine occurring next to a guanine connected by the phosphate backbone, the positions known as CpG sites. This thesis is based on the study of DNA methylation in obesity, using monozygotic twins discordant for obesity where obesity discordance is defined as having a difference in body mass index (BMI) greater than 3m2/kg. MZ twin pairs share the same genome and are matched for age, sex, cohort effects, intrauterine environment and the environment in which they grow up after birth. This helps to cancel out many confounding factors that may affect the results otherwise. The samples for this analysis was obtained from 22 obesity-discordant pairs and 8 obesity-concordant pairs. DNA from whole-blood was bisulfite-converted and hybridized to the Infinium HumanMethylation450 BeadChip. The data was then preprocessed and analyzed for within-pair differences in twins discordant for BMI, and this showed no CpG sites as differentially methylated within pairs. The analysis was then repeated on twins discordant for both BMI and liver-fat and this showed 180 CpG sites as significantly differentially methylated within pairs. However, it was not possible to use these results for pathway analysis using the methods used in gene expression analysis, as too few of these CpG sites mapped to genes on pathways. Gene-set analysis (GSA) was then applied to the methylation data to identify interesting pathways, using predefined groups of CpG sites (probe-sets), each group representing a pathway in the KEGG database. The significant pathways were further analyzed to identify the CpG sites that were most discordant within twin pairs. The results from GSA and the initial paired analysis provided an interesting list of genes and pathways most of which had previously been associated with obesity. However, the analyses can be improved by using a normalization method that is more specific to the Infinium 450K array and also by increasing the sample size. This is listed as future work, together with the analysis of DNA from adipose tissue. The pipeline developed from this analysis will be used in the future analyses, but with modifications wherever necessary

Computational Design of a Chimeric Vaccine against Plesiomonas shigelloides Using Pan-Genome and Reverse Vaccinology

The swift emergence of antibiotic resistance (AR) in bacterial pathogens to make themselves adaptable to changing environments has become an alarming health issue. To prevent AR infection, many ways can be accomplished such as by decreasing the misuse of antibiotics in human and animal medicine. Among these AR bacterial species, Plesiomonas shigelloides is one of the etiological agents of intestinal infection in humans. It is a gram-negative rod-shaped bacterium that is highly resistant to several classes of antibiotics, and no licensed vaccine against the aforementioned pathogen is available. Hence, substantial efforts are required to screen protective antigens from the pathogen whole genome that can be subjected easily to experimental evaluations. Here, we employed a reverse vaccinology (RV) approach to design a multi-antigenic epitopes based vaccine against P. shigelloides. The complete genomes of P. shigelloides were retrieved from the National Center for Biotechnological Information (NCBI) that on average consist of 5226 proteins. The complete proteomes were subjected to different subtractive proteomics filters, and in the results of that analysis, out of total proteins, 2399 were revealed as non-redundant and 2827 as redundant proteins. The non-redundant proteins were further checked for subcellular localization analysis, in which three were localized in the extracellular matrix, eight were outer membrane, and 13 were found in the periplasmic membrane. All surface localized proteins were found to be virulent. Out of a total of 24 virulent proteins, three proteins (flagellar hook protein (FlgE), hypothetical protein, and TonB-dependent hemoglobin/transferrin/lactoferrin family receptor protein) were considered as potential vaccine targets and subjected to epitopes prediction. The predicted epitopes were further examined for antigenicity, toxicity, and solubility. A total of 10 epitopes were selected (GFKESRAEF, VQVPTEAGQ, KINENGVVV, ENKALSQET, QGYASANDE, RLNPTDSRW, TLDYRLNPT, RVTKKQSDK, GEREGKNRP, RDKKTNQPL). The selected epitopes were linked with each other via specific GPGPG linkers in order to design a multi-epitopes vaccine construct, and linked with cholera toxin B subunit adjuvant to make the designed vaccine construct more efficient in terms of antigenicity. The 3D structure of the vaccine construct was modeled ab initio as no appropriate template was available. Furthermore, molecular docking was carried out to check the interaction affinity of the designed vaccine with major histocompatibility complex (MHC-)I (PDB ID: 1L1Y), MHC-II (1KG0), and toll-like receptor 4 ((TLR-4) (PDB: 4G8A). Molecular dynamic simulation was applied to evaluate the dynamic behavior of vaccine-receptor complexes. Lastly, the binding free energies of the vaccine with receptors were estimated by using MMPB/GBSA methods. All of the aforementioned analyses concluded that the designed vaccine molecule as a good candidate to be used in experimental studies to disclose its immune protective efficacy in animal models

Hormone Replacement Therapy Associated White Blood Cell DNA Methylation and Gene Expression are Associated With Within-Pair Differences of Body Adiposity and Bone Mass

The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body composition, including muscle and bone measures of monozygotic (MZ) female twin pairs discordant for HRT. We identified 7,855 nominally significant differentially methylated regions (DMRs) associated with 4,044 genes. Of the genes with DMRs, five (ACBA1, CCL5, FASLG, PPP2R2B, and UHRF1) were also differentially expressed. All have been previously associated with HRT or estrogenic regulation, but not with HRT-associated DNA methylation. All five genes were associated with bone mineral content (BMC), and ABCA1, FASLG, and UHRF1 were also associated with body adiposity. Our study is the first to show that HRT associates with genome-wide DNA methylation alterations in WBCs. Moreover, we show that five differentially expressed genes with DMRs associate with clinical measures, including body fat percentage, lean body mass, bone mass, and blood lipids. Our results indicate that at least part of the known beneficial HRT effects on body composition and bone mass may be regulated by DNA methylation associated alterations in gene expression in circulating WBCs.peerReviewe