Single Biological Process Research Articles

Dry environment on the expression of lacrimal gland S100A9, Anxa1, and Clu in rats via proteomics.

To investigate the underlying mechanism of dry environment (autumn dryness) affecting the lacrimal glands in rats. Twenty Sprague-Dawley rats were randomly divided into two groups. The rats were fed in specific pathogen free environment as the control group (n=10), and the rats fed in dry environment as the dryness group (n=10). After 24d, lacrimal glands were collected from the rats. The tissues morphology was observed by hematoxylin-eosin (HE) staining. Tandem mass tags (TMT) quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups, then bioinformatics analysis was performed. Further, the immunohistochemical (IHC) method was used to verify the target proteins. In dryness group, the lacrimal glands lobule atrophied, the glandular cavities enlarged, the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed. The proteomics exhibited that a total of 195 up-regulated and 236 down-regulated differential expressed proteins screened from the lacrimal glands of rats. It was indicated that the biological processes (BP) of differential expressed proteins mainly included cell processes and single BP. The cellular compositions of differential expressed proteins mainly located in cells, organelles. The molecular functions of differential expressed proteins mainly included binding, catalytic activity. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the differential expressed proteins mainly involved lysosome, complement and coagulation cascade, and ribosome pathway. The IHC result verified that the up-regulated expression proteins of Protein S100A9 (S100A9), Annexin A1 (Anxa1), and Clusterin (Clu) in lacrimal glands of rats in dryness group were higher than control group. The up-regulated expression proteins of S100A9, Anxa1, and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment. This study provides clues of dry environments causing eye-related diseases for further studies.

Bringing the underground to the surface: Climate change stressors negatively affect plant growth, with contrasting above and belowground physiological responses.

Terrestrial ecosystems sequester carbon from the atmosphere through a single biological process - photosynthesis - and thus considerable research has centered on how global change factors influence aboveground plant dynamics. This article is protected by copyright. All rights reserved.

Brain transcriptome analysis of a CLN2 mouse model as a function of disease progression

BackgroundNeuronal ceroid lipofuscinoses, (NCLs or Batten disease) are a group of inherited, early onset, fatal neurodegenerative diseases associated with mutations in 13 genes. All forms of the disease are characterized by lysosomal accumulation of fluorescent storage material, as well as profound neurodegeneration, but the relationship of the various genes’ function to a single biological process is not obvious. In this study, we used a well-characterized mouse model of classical late infantile NCL (cLINCL) in which the tripeptidyl peptidase 1 (Tpp1) gene is disrupted by gene targeting, resulting in loss of detectable TPP1 activity and leading to progressive neurological phenotypes including ataxia, increased motor deficiency, and early death.MethodsIn order to identify genes and pathways that may contribute to progression of the neurodegenerative process, we analyzed forebrain/midbrain and cerebellar transcriptional differences at 1, 2, 3 and 4 months of age in control and TPP1-deficient mice by global RNA-sequencing.ResultsProgressive neurodegenerative inflammatory responses involving microglia, astrocytes and endothelial cells were observed, accompanied by activation of leukocyte extravasation signals and upregulation of nitric oxide production and reactive oxygen species. Several astrocytic (i.e., Gfap, C4b, Osmr, Serpina3n) and microglial (i.e., Ctss, Itgb2, Itgax, Lyz2) genes were identified as strong markers for assessing disease progression as they showed increased levels of expression in vivo over time. Furthermore, transient increased expression of choroid plexus genes was observed at 2 months in the lateral and fourth ventricle, highlighting an early role for the choroid plexus and cerebrospinal fluid in the disease pathology. Based on these gene expression changes, we concluded that neuroinflammation starts, for the most part, after 2 months in the Tpp1−/− brain and that activation of microglia and astrocytes occur more rapidly in cerebellum than in the rest of the brain; confirming increased severity of inflammation in this region.ConclusionsThese findings have led to a better understanding of cLINCL pathological onset and progression, which may aid in development of future therapeutic treatments for this disease.

Substrate Protection in Controlled Enzymatic Transformation of Peptides and Proteins.

Proteins are involved in practically every single biological process. The many enzymes involved in their synthesis, cleavage, and posttranslational modification (PTM) carry out highly specific tasks with no usage of protecting groups. Yet, the chemists’ strategy of protection/deprotection potentially can be highly useful, for example, when a specific biochemical reaction catalyzed by a broad‐specificity enzyme needs to be inhibited, during infection of cells by enveloped viruses, in the invasion and spread of cancer cells, and upon mechanistic investigation of signal‐transduction pathways. Doing so requires highly specific binding of peptide substrates in aqueous solution with biologically competitive affinities. Recent development of peptide‐imprinted cross‐linked micelles allows such protection and affords previously impossible ways of manipulating peptides and proteins in enzymatic transformations.

Analysis of differential genes and metabolic pathway related to functional male sterility in eggplant

Based on observing the cytological characteristics of the flower buds of the functional male sterile line (S13) and the fertile line (F142) in eggplant, it was found that the disintegration period of the annular cell clusters in S13 anther was 2 days later than that of F142, and the cells of stomiun tissue and tapetum in F142 disintegrated on the blooming day, while it did not happen in S13. The comparative transcriptomic analysis showed that there were 1 436 differential expression genes (DEGs) (651 up-regulated and 785 down-regulated) in anthers of F142 and S13 at 8, 5 days before flowering and flowering day. The significance analysis of GO enrichment indicated that there were more unigene clusters involved in single cell biological process, metabolism process and cell process, and more catalytic activity and binding function were involved in molecular functions. Through KEGG annotation we found that the common DEGs were mainly enriched in the biosynthesis of secondary metabolites, metabolic pathway, protein processing in endoplasmic reticulum, biosynthesis of amino acids, carbon metabolism and plant hormone signal transduction. The fifteen genes co-expression modules were identified from 16 465 selected genes by weighted gene co-expression network analysis (WGCNA), three of which (Plum2, Royalblue and Bisque4 modules) were highly related to S13 during flower development. KEGG enrichment showed that the specific modules could be enriched in phenylpropanoid biosynthesis, photosynthesis, porphyrin and chlorophyll metabolism, α-linolenic acid metabolism, polysaccharide biosynthesis and metabolism, fatty acid degradation and the mutual transformation of pentose and glucuronic acid. These genes might play important roles during flower development of S13. It provided a reference for further study on the mechanism of anther dehiscence in eggplant.

Research on the circular RNA bioinformatics in patients with acute myocardial infarction.

ObjectiveThrough the detection of circular RNA (circRNA) using expression profiling chips, we searched for circRNAs related to acute myocardial infarction (AMI) and explored their relationship and possible mechanisms with AMI.MethodThe study subjects included 3 AMI patients and 3 controls, and circRNA expression profiling analysis was performed using a microarray gene chip to identify circRNAs with large differences in expression between groups and to construct a circRNA‐miRNA network.ResultsCompared with the control group, there were 650 differentially expressed circRNAs found in AMI patients (P < .05, fold change > 2), including 535 up‐regulated circRNAs, such as hsa_circ_0050908, hsa_circRNA4010‐22, hsa_circ_0081241, hsa_circ_0010551, hsa_circRNA4010‐20, hsa_circRNA14702, hsa_circ_0115392, has_circRNA1825‐44, has_circRNA8493‐7, and hsa_circ_0025097. Furthermore, there were 115 down‐regulated circRNAs, such as hsa_circ_0066439, hsa_circ_0054211, hsa_circ_0095920, hsa_circ_0122984, hsa_circ_0113067, hsa_circ_0039155, hsa_circRNA4014‐45, hsa_circ_0122979, hsa_circ_0059665, and hsa_circ_0009319. The circRNAs hsa_circ_0066439, hsa_circ_0081241, and hsa_circ_0122984 can regulate multiple signal pathways to participate in the AMI process through hsa‐miR‐1254, hsa‐miR‐328‐5p, and other miRNAs. In addition, the expression of circRNA‐miRNA in peripheral blood is related to the network. Differentially expressed circRNAs are involved in chromatin organization, chromatin‐modifying enzymes, signal transduction, lysine degradation, the mitogen‐activated protein kinase (MAPK) signaling pathway, focal adhesion, and a variety of other pathways, such as myocardial infarction, coronary heart disease, hypertension, and other diseases. The gene ontology analysis results show that molecular function mainly involves binding and molecular structural activity, whereas the biological process mainly involves a single biological process, a cellular component for organization, and a cellular process, and the cellular component mainly involves a protein complex, an extracellular matrix, and a membrane.ConclusioncircRNA and microRNA interact to participate in the development of AMI. circRNA may be involved in the pathogenesis of AMI.

Functional Annotation of Genes of Predisposition to Schizophrenia and Celiac Disease

In the present study, a functional annotation of genes predisposing to schizophrenia and celiac disease was carried out using Cytoscape version 3.7.1. The identified genes are involved (even jointly) in the regulation of the development and functioning of nerve cells and activation of the immune response. Common genes for both diseases (NOTCH4 and HLA-DQA1) are hereditary factors in the development of schizophrenia and celiac disease. According to the results of functional annotation, genes susceptible to schizophrenia and celiac disease were annotated by terms from Gene Ontology; the number of common groups of functions was 44. The results suggest that molecular mechanisms responsible for the differentiation and proliferation of cells of both the immune system and the nervous system are involved in the comorbid development of schizophrenia and celiac disease. It was found that a significant number (up to 179) of genes could be involved in the implementation of a single biological process. However, in some cases, the same gene could be represented in several related processes.

Tissue-specific Gene Expression Changes Are Associated with Aging in Mice

Aging is a complex process that can be characterized by functional and cognitive decline in an individual. Aging can be assessed based on the functional capacity of vital organs and their intricate interactions with one another. Thus, the nature of aging can be described by focusing on a specific organ and an individual itself. However, to fully understand the complexity of aging, one must investigate not only a single tissue or biological process but also its complex interplay and interdependencies with other biological processes. Here, using RNA-seq, we monitored changes in the transcriptome during aging in four tissues (including brain, blood, skin and liver) in mice at 9 months, 15 months, and 24 months, with a final evaluation at the very old age of 30 months. We identified several genes and processes that were differentially regulated during aging in both tissue-dependent and tissue-independent manners. Most importantly, we found that the electron transport chain (ETC) of mitochondria was similarly affected at the transcriptome level in the four tissues during the aging process. We also identified the liver as the tissue showing the largest variety of differentially expressed genes (DEGs) over time. Lcn2 (Lipocalin-2) was found to be similarly regulated among all tissues, and its effect on longevity and survival was validated using its orthologue in Caenorhabditis elegans. Our study demonstrated that the molecular processes of aging are relatively subtle in their progress, and the aging process of every tissue depends on the tissue’s specialized function and environment. Hence, individual gene or process alone cannot be described as the key of aging in the whole organism.

Diversification history of clown tree frogs in Neotropical rainforests (Anura, Hylidae, Dendropsophus leucophyllatus group)

General consensus emphasizes that no single biological process can explain the patterns of species’ distributions and diversification in the Neotropics. Instead, the interplay of several processes across space and time must be taken into account. Here we investigated the phylogenetic relationships and biogeographic history of tree frogs in the Dendropsophus leucophyllatus species group (Amphibia: Hylidae), which is distributed across Amazonia and the Atlantic rainforests. Using Next Generation Sequencing (NGS) and double digest restriction-site associated DNA (ddRADseq), we inferred phylogenetic relationships, species limits, and temporal and geographic patterns of diversification relative to the history of these biomes. Our results indicate that the D. leucophyllatus species group includes at least 14 independent lineages, which are currently arranged into ten described species. Therefore, a significant portion of species in the group are still unnamed. Different processes were associated to the group diversification history. For instance, the Andes uplift likely caused allopatric speciation for Cis-Andean species, whereas it may also be responsible for changes in the Amazonian landscape triggering parapatric speciation by local adaptation to ecological factors. Meanwhile, Atlantic Forest ancestors unable to cross the dry diagonal biomes after rainforest’s retraction, evolved in isolation into different species. Diversification in the group began in the early Miocene, when connections between Atlantic Forest and the Andes (Pacific Dominion) by way of a south corridor were possible. The historical scenario in Amazonia, characterized by several speciation events and habitat heterogeneity, helped promoting diversification, resulting in the highest species diversity for the group. This marked species diversification did not happen in Atlantic Forest, where speciation is very recent (late Pliocene and Pleistocene), despite its remarkable climatic heterogeneity.

Abstract 496: The synergistic role of miR-150-5p and miR-661 in regulating epithelial mesenchymal transition in triple negative breast cancer

Abstract MiRNA dysregulation has been linked to cancer initiation and progression, through their control in multiple cancer associated signaling pathways. MiRNA low specificity of target interaction confer them the ability to cooperatively regulate a single biological process. Epithelial mesenchymal transition (EMT) plays pivotal roles in cancer progression and metastasis, through the regulation of transcription factors and proteins, such as E-cadherin, Slug, Snail, Twist and Zeb1. This process is also controlled post-transcriptionally by a complex and regulated network of miRNAs. We have shown that miR-150-5p and miR-661, up-regulated in triple negative breast cancer (TNBC) when compared to normal tissue and other breast cancer subtypes, exert an oncogenic action and modulate cell proliferation, clonogenicity, migration and cytotoxic response in in vitro TNBC models. The main objective of this study was to determine whether the modulation of these phenotypes were due to the regulation of their corresponding gene targets associated with EMT. By conducting an integrated computational and experimental analysis, in which miR-150-5p and miR-661 were suppressed or ectopically expressed in transfected MDA-MB-231 cells, we showed that they present common regulatory roles in cell adhesion and motility signaling networks, including those involved in EMT. Gene expression analysis in a targeted panel of 770 genes with primary functional annotations in EMT, cell adhesion and motility and metastasis, revealed that: i. the suppression of miR-150-5p and miR-661, affected the expression of 160 and 123 genes, respectively; 18% of these genes were commonly affected by both miRNAs, including ACVR1C (ALK-7), CHAD, GIMAP6, SFRCL1, SPARCL1 and TBX1; ii. the ectopic expression of miR-150-5p and miR-661, affected the expression of 283 and 267 genes, respectively; 27% of which commonly affected by both miRNAs, including AKT1, DCL1, MAPK2, MMP1, SFRP1 and TPM2. iii. 26 genes were inversely affected by the suppression and ectopic expression of miR-150-5p and miR-661 (consistent with the general post-transcriptional regulation of miRNA/mRNA targets); 73% of these genes were predicted to be miRs150-5p and 661 direct or indirect targets. In summary, based on the computational and experimental data presented, we provide evidences that strongly suggest that miRNA-150-5p and miR-661 modulate the aggressive tumor phenotype in TNBC cells by regulating common gene targets associated with the EMT process. Further functional studies in TNBC experimental models will allow us to dissect the mechanisms by which they contribute to the TNBC aggressive phenotypes by synergistically regulating EMT. Funding: Partially funded by Georgetown University Center of Excellence in Regulatory Science and Innovation (CERSI U01FD004319), CNPq, Capes-Brazil (scholarship to PMMO, BMS, ASF). Citation Format: Patricia MM Ozawa, Bruna M. Sugita, Aline S. Fonseca, Yara Rodriguez, Yuriy Gusev, Paolo Fadda, Deepak Kumar, Luciane R. Cavalli. The synergistic role of miR-150-5p and miR-661 in regulating epithelial mesenchymal transition in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 496.

PO-401 Detection of mutational patterns associated to HR deficiency from low counts of mutations

Introduction A common source of tumorigenesis in several cancer types such as breast and ovarian is a defect in the homologous recombination (HR) machinery. HR defect can be detected by identifying single nucleotide variants (SNVs), deletions, duplications, and other errors generated by the alternative double-strand break repair machineries. However, current diagnostic tools for HR defect relies on copy number changes with reduced sensitivity and specificity, or on the existence of BRCA mutations. While, recent efforts to detect HR defect using mutational signature require a large number of SNVs, beyond what is typically obtained from panel sequencing which is widely used in clinics. Material and methods We developed a computational software called SigMA to identify signatures of HR defect even from low SNV counts. SigMA carries out a multivariate analysis to isolate the effect of a single biological process in the presence of multiple mutagenic processes. The multivariate analysis includes likelihood estimations, which we suggest as novel and sensitive measures, together with commonly used measures such as cosine similarity, and signature amplitudes. First, we determine the signature composition of SNVs in 720 whole-genome sequenced (WGS) breast cancer samples, with non-negative matrix factorization (NMF). Then, a subset of mutations from each sample is selected based on whether they fall within the coverage of the sequencing technique of interest. We optimise our algorithm using the simulated data and considering NMF results as a baseline measurement, and we validate its performance on panel data of 890 breast tumours. Results and discussions Whereas previous attempts in detection of mutational signatures from panel data were limited to cases with a high mutation burden, SigMA can be applied to a large fraction of samples with panel data. On a panel consisting of 410 genes, we were able to dramatically improve the detection of mutational signature of HR defect, with 0.75 (0.5) sensitivity and 0.1 (0.01) false positive rate. SigMA detected 213 cases with HR defect in 890 breast cancer panels. For exome and whole-genome data, the performance of the tool is further improved. Conclusion We developed a tool which extends the applicability of mutational signatures analysis to low counts of mutations. Application of our SigMA algorithm to detect HR defect and other mutational signatures in panel sequencing data will increase the number of cases that may benefit therapeutic agents that target specific classes of genomic alterations.

Magnetic biochar catalyst derived from biological sludge and ferric sludge using hydrothermal carbonization: Preparation, characterization and its circulation in Fenton process for dyeing wastewater treatment

To solve sludge disposal and management problems during dyeing wastewater treatment, the produced excess biological sludge and ferric sludge were fabricated into a magnetic biochar composite (MBC) under the optimal hydrothermal carbonization (HTC) conditions. With ferric sludge mixing, the generated MBC contained paramagnetic Fe3O4, showed a smaller diameter of approximately 200 nm, a smaller pore size, a larger specific surface area and a higher carbonization degree than BC prepared using a single biological sludge process under the same HTC conditions. Additionally, biochar and Fe3O4 in the MBC were found to be tightly combined through chemical bonding, imparting MBC with its own property of magnetic recycling. The stable high Methylene Blue (MB) degradation performance in a Fenton reaction after recycling designated it as a good catalyst. The MB degradation pathway was proposed based on GC–MS results. When the MBC was used to treat actual dyeing wastewater through a Fenton process, the chemical oxygen demand (COD) and total organic carbon (TOC) removal efficiencies reached 47 ± 3.3% and 49 ± 2.7%, respectively. Therefore, MBC could be recycled as a catalyst in dyeing wastewater treatment. And a methodology is described that minimizes the produced sludge and enables sludge internal recycling in a dyeing wastewater treatment plant.

Degradation of triclosan and its main intermediates during the combined irradiation and biological treatment

ABSTRACTTriclosan is an extensively applied antimicrobial agent which has been frequently detected in the environment. In this paper, the degradation of triclosan and its main intermediates was investigated during the combined irradiation and biological treatment. The results showed that triclosan degradation increased with increase of absorbed dose, the removal efficiency of triclosan was 62%, 77%, 87%, 91% and 94%, respectively at 1, 2, 3, 4 and 5 kGy. The final removal efficiency of triclosan after the combined irradiation and biological process was 81%, 86%, 90%, 92% and 95%, respectively. During the irradiation process, two main intermediates, that is, 4,4′-2′-phenoxyphenol (Intermediate 1) and 4-chloro-2′-phenoxyphenol (Intermediate 2) were detected, in which Intermediate 1 dominated during the irradiation process. In the following biological treatment process, Intermediates 1 and 2 could be further degraded. In single biological treatment process, the final removal efficiency of triclosan was 54%, and Intermediates 1 and 2 were detected. Intermediate 1 could be biodegraded while Intermediate 2 could not. The concentration of Intermediate 2 increased during biological treatment process. In conclusion, irradiation as pre-treatment process can enhance the degradation of triclosan and improve the biodegradability of Intermediate 2. Combined irradiation and biological process can be promising for treating antibiotic-containing wastewater.

Enhanced biodegradation of triclosan by means of gamma irradiation

Triclosan is an antimicrobial agent which has been frequently detected in the environment. In this paper, the biodegradation of triclosan after radiation-induced advanced oxidation was investigated. The results show that the removal efficiency of triclosan in the combined irradiation and biological treatment process ranged from 88% to 97%, depending on the absorbed dose, while it was only 54% in the single biological treatment process. The removal efficiency of total organic carbon (TOC) was in the range of 53.1%,−59.2% at dose of 1–5 kGy in the combined irradiation and biological treatment process. In comparison, the removal efficiency of TOC in the single biological treatment process was 24.5%, suggesting that irradiation can enhance the mineralization of triclosan. The dechlorination efficiency of triclosan ranged from 48.6% to 78.4% at dose of 1–5 kGy. The intermediates of triclosan degradation were tentatively identified by LC-MS analysis and the possible degradation pathway was proposed. Based on the above results, the combined irradiation and biological treatment process could be an alternative process for treating triclosan-containing wastewater.

A hybrid system comprising an aerobic biological process and electrochemical oxidation for the treatment of black table olive processing wastewaters

In this work table olive processing wastewaters (TOPW) were treated by aerobic biological processes using indigenous microorganisms originating from TOPW, as well as the combination of two successive steps, i.e. aerobic biological treatment followed by electrochemical oxidation over a boron-doped diamond anode.In the single aerobic biological processes, experiments in suspended and attached growth reactors (trickling filters) were carried out using different TOPW feed concentrations of 5500 ± 350, 7500 ± 650 and 15,000 ± 1050 mg dissolved COD L−1. Two different operating modes were used to investigate the optimum performance of the filter, i.e. batch and SBR with recirculation. The latter mode with recirculation of 0.5 L min−1 led to high removal rates of dissolved COD and total phenolic compounds, up to 96.5% and 64.5%, respectively, for the initial COD concentration of 7500 mg dissolved COD L−1.Depending on the type and operating conditions of the bioreactors, residual COD ranged between a few hundred and a few thousand mg L−1, while decolorization could not be achieved even under the most favorable conditions. A biologically treated effluent with residual dissolved COD of 5100 mg L−1 was completely mineralized and decolorized at 187.5 mA cm−2 applied current density; complete removal of COD, color and total phenolic compounds was achieved in 180–240 min, 30–60 min and 30 min of electrochemical oxidation, respectively. Lower treatment times and current densities were needed to polish effluents with lower organic loads.

Hippocampal Pruning as a New Theory of Schizophrenia Etiopathogenesis

Pruning in neurons has been suggested to be strongly involved in Schizophrenia's (SKZ) etiopathogenesis in recent biological, imaging, and genetic studies. We investigated the impact of protein-coding genes known to be involved in pruning, collected by a systematic literature research, in shaping the risk for SKZ in a case-control sample of 9,490 subjects (Psychiatric Genomics Consortium). Moreover, their modifications through evolution (humans, chimpanzees, and rats) and subcellular localization (as indicative of their biological function) were also investigated. We also performed a biological pathways (Gene Ontology) analysis. Genetics analyses found four genes (DLG1, NOS1, THBS4, and FADS1) and 17 pathways strongly involved in pruning and SKZ in previous literature findings to be significantly associated with the sample under analysis. The analysis of the subcellular localization found that secreted genes, and so regulatory ones, are the least conserved through evolution and also the most associated with SKZ. Their cell line and regional brain expression analysis found that their areas of primary expression are neuropil and the hippocampus, respectively. At the best of our knowledge, for the first time, we were able to describe the SKZ neurodevelopmental hypothesis starting from a single biological process. We can also hypothesize how alterations in pruning fine regulation and orchestration, strongly related with the evolutionary newest (and so more sensitive) secreted proteins, may be of particular relevance in the hippocampus. This early alteration may lead to a mis-structuration of neural connectivity, resulting in the different brain alteration that characterizes SKZ patients.

A genomic random interval model for statistical analysis of genomic lesion data.

Tumors exhibit numerous genomic lesions such as copy number variations, structural variations and sequence variations. It is difficult to determine whether a specific constellation of lesions observed across a cohort of multiple tumors provides statistically significant evidence that the lesions target a set of genes that may be located across different chromosomes but yet are all involved in a single specific biological process or function. We introduce the genomic random interval (GRIN) statistical model and analysis method that evaluates the statistical significance of the abundance of genomic lesions that overlap a specific locus or a pre-defined set of biologically related loci. The GRIN model retains certain biologically important properties of genomic lesions that are ignored by other methods. In a simulation study and two example analyses of leukemia genomic lesion data, GRIN more effectively identified important loci as significant than did three methods based on a permutation-of-markers model. GRIN also identified biologically relevant pathways with a significant abundance of lesions in both examples. An R package will be freely available at CRAN and www.stjuderesearch.org/site/depts/biostats/software.

MiRNA Mediated Regulation of Rice (Oryza sativa) Genome

miRNAs play important roles in plant post-transcriptional gene regulation by targeting mRNAs through cleavage or repressing translation. Here, we have reconstructed genome scale level miRNA-miRNA co-targeting network of rice plant and identified several significant modules (high-density sub-graphs). Some of the modules are involved in multiple biological processes, while some are involved in a single biological process. The distribution of the out-going connectivities of co-target network can be approximated best by a power-law equation. We have also observed a wide variation in inter chromosomal regulation. The genes of chromosome 3 are highly targeted by the miRNAs synthesized from other chromosomes. The results presented here might provide a platform for testing the hypothetical role of co-targeting associations in rice post-transcriptional control.

Comparison of Two Diverse Measurement Methods by Graphical Agreement

Biological processes are complex, and several methods are often used to measure them. However, different methods could determine diverse parts of a single biological process. To date, there are no widely accepted and convenient methods for comparison between the results, so we consider graphical analysis with the ability to demonstrate the pattern of distribution of findings from one method across another. It appears that a two-series area plot is the most appropriate. After using normal values and a coding reference and examining the variables, unnecessary information is diminished and the graphics become more obvious. Three possibilities may be found: agreement or disagreement between variables or disagreement from normal values. Therefore, the graph may also be used to determine the corresponding normal values between variables. The association between variables may be tested using kappa coefficients, although graphical analysis remains more informative. Therefore, graphical analysis could compare two completely different variables that measure the same biological process or determine the range of normal values.

Cytokine Antibody Arrays in Biomarker Discovery and Validation

Many normal physiological and disease-related pathophysiological processes are regulated by the interactions of complex signaling networks of pro- and anti-inflammatory markers, growth factors, soluble receptors and extracellular matrix proteins, as well as other cell–cell signaling proteins, which we define collectively as cytokines. Because multiple cell–cell signaling factors may be involved in a single biological process, detection of expression of multiple cytokines is essential to unraveling the mechanisms and effects of many disease processes. Cytokine antibody arrays have been developed to meet this growing demand for multiplexed protein detection. In particular, discovery and validation of diseaserelated protein biomarkers require high-throughput detection of many proteins simultaneously. This review will address the complexity of cytokine biology, discuss current and future antibody array technologies and explore their applications in cytokine biomarker discovery and validation for variety of human diseases. Specific examples of these applications will be presented, including the search for cytokine biomarkers related to neurological and neurodegenerative diseases (such as autism and Alzheimerâ € ™ s), immunological disorders (including asthma), and various cancers. Keywords: Antibody arrays, biomarker, cytokine, protein arrays, physiological, Alzheimer's, immunological disorders, Asthma, Cancer, enzymelinked immunosorbent assay (ELISA), systemic lupus erythematosus, Crohn's disease, multiple sclerosis