The Effects of Vitamin E on Liver and Kidney Damage Induced by Dianabol in Small Laboratory Mice

BACKGROUND AND OBJECTIVE: Anabolic steroids, especially dianabol, are used by athletes as a performance-enhancing drugs that damage the liver and cause structural changes. The aim of this study was to evaluate the effects of vitamin E on liver and kidney toxicity caused by dianabol. METHODS: In this experimental study, 72 adult male mice were randomly divided into 8 groups of 9. Four groups of mice received 100 IU / kg vitamin E orally for 42 days through gavage. Three groups of the above groups received 5, 10 and 20 mg / kg oral dianabol four hours after receiving vitamin E, respectively. The control group and the groups receiving only 5, 10 and 20 mg / kg oral dianabol were also considered. 24 hours after the final treatment, serum samples were collected for biochemical evaluations and tissue samples were collected for histological, histomorphometric and histochemical evaluations. FINDINGS: The results showed that dianabol significantly increased the level of AST (158.52±9.76), ALT (113.70±11.02), and ALP (141.30±5.94), and significantly decreased albumin (1.04±0.47) compared to the control group (72.61±7.54, 41.47±7.03, 112.80±4.30, 3.14±0.25, respectively) (p<0.05). Administration of vitamin E significantly increased the level of AST (110.56±9.86), ALT (80.19±4.02) and ALP (120.52±4.94) and improved albumin (2.1±0.28) (p<0.05). CONCLUSION: The results of the study showed that vitamin E can reduce the oxidative damage caused by dianabol in the liver and kidney of the mouse

A short survey on fault diagnosis in wireless sensor networks

Fault diagnosis is one of the most important and demand- able issues of the network. It makes the networks reliable and robust to operate in the normal way to handle almost all types of faults or failures. Additionally, it helps sensor nodes to work smoothly and efficiently till the end of their lifetime. This short survey paper not only presents a clear picture of the recent proposed techniques, but also draws comparisons and contrasts among them to diagnose the potential faults. In addition, it proposes some potential future-work directions which would lead to open new research directions in the field of fault diagnosis

Human Embryonic Stem Cells and Embryonal Carcinoma Cells Have Overlapping and Distinct Metabolic Signatures

While human embryonic stem cells (hESCs) and human embryonal carcinoma cells (hECCs) have been studied extensively at the levels of the genome, transcriptome, proteome and epigenome our knowledge of their corresponding metabolomes is limited. Here, we present the metabolic signatures of hESCs and hESCs obtained by untargeted gas chromatography coupled to mass spectrometry (GC-MS). Whilst some metabolites are common to both cell types, representing the self-renewal and house-keeping signatures, others were either higher (e.g., octadecenoic acid, glycerol-3-phosphate, 4-hydroxyproline) or lower (e.g., glutamic acid, mannitol, malic acid, GABA) in hESCs (H9) compared to hECCs (NTERA2), these represent cell type specific signatures. Further, our combined results of GC-MS and microarray based gene expression profiling of undifferentiated and OCT4-depleted hESCs are consistent with the Warburg effect which is increased glycolysis in embryonic cells and tumor cells in the presence of O2 while oxidative phosphorylation (OXPHOS) is impaired or even shut down. RNAi-based OCT4 knock down mediated differentiation resulted in the activation of the poised OXPHOS machinery by expressing missing key proteins such as NDUFC1, UQCRB and COX, increase in TCA cycle activity and decreased lactate metabolism. These results shed light on the metabolite layer of pluripotent stem cells and could potentially establish novel metabolic markers of self renewal and pluripotency

A Novel and Critical Role for Oct4 as a Regulator of the Maternal-Embryonic Transition

Compared to the emerging embryonic stem cell (ESC) gene network, little is known about the dynamic gene network that directs reprogramming in the early embryo. We hypothesized that Oct4, an ESC pluripotency regulator that is also highly expressed at the 1- to 2-cell stages in embryos, may be a critical regulator of the earliest gene network in the embryo.Using antisense morpholino oligonucleotide (MO)-mediated gene knockdown, we show that Oct4 is required for development prior to the blastocyst stage. Specifically, Oct4 has a novel and critical role in regulating genes that encode transcriptional and post-transcriptional regulators as early as the 2-cell stage. Our data suggest that the key function of Oct4 may be to switch the developmental program from one that is predominantly regulated by post-transcriptional control to one that depends on the transcriptional network. Further, we propose to rank candidate genes quantitatively based on the inter-embryo variation in their differential expression in response to Oct4 knockdown. Of over 30 genes analyzed according to this proposed paradigm, Rest and Mta2, both of which have established pluripotency functions in ESCs, were found to be the most tightly regulated by Oct4 at the 2-cell stage.We show that the Oct4-regulated gene set at the 1- to 2-cell stages of early embryo development is large and distinct from its established network in ESCs. Further, our experimental approach can be applied to dissect the gene regulatory network of Oct4 and other pluripotency regulators to deconstruct the dynamic developmental program in the early embryo

Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation

Stemming Cancer: Functional Genomics of Cancer Stem Cells in Solid Tumors

Cancer stem cells (CSCs) were discovered about 15 years ago in hematopoietic cancers. Subsequently, cancer stem cells were discovered in various solid tumors. Based on parallels with normal stem cells, a developmental process of cancer stem cells follows paths of organized, hierarchical structure of cells with different degrees of maturity. While some investigators have reported particular markers as identification of cancer stem cells, these markers require further research. In this review, we focus on the functional genomics of cancer stem cells. Functional genomics provides useful information on the signaling pathways which are consecutively activated or inactivated amongst those cells. This information is of particular importance for cancer research and clinical treatment in many respects. (1) Understanding of self-renewal mechanisms crucial to tumor growth. (2) Allow the identification of new, more specific marker for CSCs, and (3) pathways that are suitable as future targets for anti-cancer drugs. This is of particular importance, because today’s chemotherapy targets the proliferating cancer cells sparing the relatively slow dividing cancer stem cells. The first step on this long road therefore is to analyze genome-wide expression-profiles within the same type of cancer and then between different types of cancer, encircling those target genes and pathways, which are specific to these cells

Advanced Computational Biology Methods Identify Molecular Switches for Malignancy in an EGF Mouse Model of Liver Cancer

The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification

Combinatorial Binding in Human and Mouse Embryonic Stem Cells Identifies Conserved Enhancers Active in Early Embryonic Development

Transcription factors are proteins that regulate gene expression by binding to cis-regulatory sequences such as promoters and enhancers. In embryonic stem (ES) cells, binding of the transcription factors OCT4, SOX2 and NANOG is essential to maintain the capacity of the cells to differentiate into any cell type of the developing embryo. It is known that transcription factors interact to regulate gene expression. In this study we show that combinatorial binding is strongly associated with co-localization of the transcriptional co-activator Mediator, H3K27ac and increased expression of nearby genes in embryonic stem cells. We observe that the same loci bound by Oct4, Nanog and Sox2 in ES cells frequently drive expression in early embryonic development. Comparison of mouse and human ES cells shows that less than 5% of individual binding events for OCT4, SOX2 and NANOG are shared between species. In contrast, about 15% of combinatorial binding events and even between 53% and 63% of combinatorial binding events at enhancers active in early development are conserved. Our analysis suggests that the combination of OCT4, SOX2 and NANOG binding is critical for transcription in ES cells and likely plays an important role for embryogenesis by binding at conserved early developmental enhancers. Our data suggests that the fast evolutionary rewiring of regulatory networks mainly affects individual binding events, whereas “gene regulatory hotspots” which are bound by multiple factors and active in multiple tissues throughout early development are under stronger evolutionary constraints

Note on analysis of quartz grain dimensions in foliated greywackes

Quarzkorn-Abmessungen aus Grauwacken wurden auf ein internes Referenzsystem (reference aspect ratio, RAR) bezogen und mit Hilfe der linearen Regressionsanalyse der reduzierten Hauptachse (reduced major axis, RMA) ausgewertet. Das verwendete statistische Verfahren unterscheidet im Gegensatz zur Methode der kleinsten Quadrate nicht zwischen abhängigen und unabhängigen Variablen. Die Anwendung der RMX-Methode in Verbindung mit den RAR-Meßwerten kann sehr hilfreich für Vergleiche innerhalb geschieferter Grauwacken sein, bei denen unterschiedliche Prozesse in Korngrößenbereich wirksam waren wie etwa Drucklösung und Festkörper-Rotation. Die RAR/RMA-Analyse erfaßt Kornregelungen und ist daher auch einsetzbar für die Klassifikation von Schieferungen. Darüber hinaus wird die Anwendung der RAR/RMA-Analyse für die Bestimmung der Deformation diskutiert. Robin strain-Werte werden mit arithmetischen und harmonischen Mittelwerten der RAR-Analyse verglichen. Es zeigt sich, daß das arithmetische Mittel des RAR ein vernünftiges Maß für die longitudinale Deformation darstellt. Quartz grain dimensions, measured parallel to an internal reference system (reference aspect ratio, RAR), were analyzed using the »reduced major axis« (RMA) linear regression analysis. In contrast to least-squares analysis, this statistical technique does not distinguish between dependent and independent variables. Application of the RMA analysis in conjunction with RAR values can be most useful for comparisons between foliated greywackes in which different grain scale processes, such as pressure solution and rigid-body rotation, were active. The RAR/RMA analysis reflects grain alignment and is therefore also useful for cleavage classification. In addition to the above, the application of RAR/RMA analysis for the determination of strain is discussed. Robin strains are compared with the arithmetic and harmonic means from RAR's and it is concluded that the arithmetic mean RAR produces a reasonable estimate of longitudinal strain in these rocks. Les dimensions des grains de quartz, mesurés parallèlement à un système de référence interne (»reference aspect ratio«: RAR) ont été traitées par la méthode de la régression linéaire (»reduced major axis«: RMA). Contrairement à la méthode des moindres carrés, cette technique statistique ne fait pas de distinction entre les variables dépendantes et indépendantes. L'application de ce type de méthode s'avère très utile à la comparaison de grauwackes schisteuses dans lesquelles les dimensions des grains peuvent être la conséquence de processus différents, tels que la dissolution (pressure solution) et la rotation. L'analyse RAR/RMA traduit l'alignement des grains et peut, de ce fait, être utilisée aussi à l'appréciation du type de schistosité. D'autre part, l'auteur discute l'application de l'analyse RAR/RMA à la détermination de la déformation finie. Si on compare les déformations »Robin« aux moyennes arithmétique et harmonique des RAR, on peut conclure que les moyennes RAR arithmétiques fournissent une estimation raisonnable de la déformation longitudinale. Помимо интернациона льной системы RAR, разме ры зерен кварца анализи ровали с помощью регр ессивного анализа «Изменение о сновных осей» — RMA. В отличие от анализа ме тодом наименьшего кв адратов, при названном статис тическом методе разл ичия между зависимыми и не зависимыми переменн ыми не учитываются. Компл ексное применение RAR иPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47848/1/531_2005_Article_BF01821068.pd