Time-Varying Networks of Inter-Ictal Discharging Reveal Epileptogenic Zone.

PubMed

Zhang, Luyan; Liang, Yi; Li, Fali; Sun, Hongbin; Peng, Wenjing; Du, Peishan; Si, Yajing; Song, Limeng; Yu, Liang; Xu, Peng

2017-01-01

The neuronal synchronous discharging may cause an epileptic seizure. Currently, most of the studies conducted to investigate the mechanism of epilepsy are based on EEGs or functional magnetic resonance imaging (fMRI) recorded during the ictal discharging or the resting-state, and few studies have probed into the dynamic patterns during the inter-ictal discharging that are much easier to record in clinical applications. Here, we propose a time-varying network analysis based on adaptive directed transfer function to uncover the dynamic brain network patterns during the inter-ictal discharging. In addition, an algorithm based on the time-varying outflow of information derived from the network analysis is developed to detect the epileptogenic zone. The analysis performed revealed the time-varying network patterns during different stages of inter-ictal discharging; the epileptogenic zone was activated prior to the discharge onset then worked as the source to propagate the activity to other brain regions. Consistence between the epileptogenic zones detected by our proposed approach and the actual epileptogenic zones proved that time-varying network analysis could not only reveal the underlying neural mechanism of epilepsy, but also function as a useful tool in detecting the epileptogenic zone based on the EEGs in the inter-ictal discharging.

Functional sequencing read annotation for high precision microbiome analysis

PubMed Central

Zhu, Chengsheng; Miller, Maximilian; Marpaka, Srinayani; Vaysberg, Pavel; Rühlemann, Malte C; Wu, Guojun; Heinsen, Femke-Anouska; Tempel, Marie; Zhao, Liping; Lieb, Wolfgang; Franke, Andre; Bromberg, Yana

2018-01-01

Abstract The vast majority of microorganisms on Earth reside in often-inseparable environment-specific communities—microbiomes. Meta-genomic/-transcriptomic sequencing could reveal the otherwise inaccessible functionality of microbiomes. However, existing analytical approaches focus on attributing sequencing reads to known genes/genomes, often failing to make maximal use of available data. We created faser (functional annotation of sequencing reads), an algorithm that is optimized to map reads to molecular functions encoded by the read-correspondent genes. The mi-faser microbiome analysis pipeline, combining faser with our manually curated reference database of protein functions, accurately annotates microbiome molecular functionality. mi-faser’s minutes-per-microbiome processing speed is significantly faster than that of other methods, allowing for large scale comparisons. Microbiome function vectors can be compared between different conditions to highlight environment-specific and/or time-dependent changes in functionality. Here, we identified previously unseen oil degradation-specific functions in BP oil-spill data, as well as functional signatures of individual-specific gut microbiome responses to a dietary intervention in children with Prader–Willi syndrome. Our method also revealed variability in Crohn's Disease patient microbiomes and clearly distinguished them from those of related healthy individuals. Our analysis highlighted the microbiome role in CD pathogenicity, demonstrating enrichment of patient microbiomes in functions that promote inflammation and that help bacteria survive it. PMID:29194524

Bioinformatics functional analysis of let-7a, miR-34a, and miR-199a/b reveals novel insights into immune system pathways and cancer hallmarks for hepatocellular carcinoma.

PubMed

Soliman, Bangly; Salem, Ahmed; Ghazy, Mohamed; Abu-Shahba, Nourhan; El Hefnawi, Mahmoud

2018-05-01

Let-7a, miR-34a, and miR-199 a/b have gained a great attention as master regulators for cellular processes. In particular, these three micro-RNAs act as potential onco-suppressors for hepatocellular carcinoma. Bioinformatics can reveal the functionality of these micro-RNAs through target prediction and functional annotation analysis. In the current study, in silico analysis using innovative servers (miRror Suite, DAVID, miRGator V3.0, GeneTrail) has demonstrated the combinatorial and the individual target genes of these micro-RNAs and further explored their roles in hepatocellular carcinoma progression. There were 87 common target messenger RNAs (p ≤ 0.05) that were predicted to be regulated by the three micro-RNAs using miRror 2.0 target prediction tool. In addition, the functional enrichment analysis of these targets that was performed by DAVID functional annotation and REACTOME tools revealed two major immune-related pathways, eight hepatocellular carcinoma hallmarks-linked pathways, and two pathways that mediate interconnected processes between immune system and hepatocellular carcinoma hallmarks. Moreover, protein-protein interaction network for the predicted common targets was obtained by using STRING database. The individual analysis of target genes and pathways for the three micro-RNAs of interest using miRGator V3.0 and GeneTrail servers revealed some novel predicted target oncogenes such as SOX4, which we validated experimentally, in addition to some regulated pathways of immune system and hepatocarcinogenesis such as insulin signaling pathway and adipocytokine signaling pathway. In general, our results demonstrate that let-7a, miR-34a, and miR-199 a/b have novel interactions in different immune system pathways and major hepatocellular carcinoma hallmarks. Thus, our findings shed more light on the roles of these miRNAs as cancer silencers.

Raman Spectroscopy Reveals New Insights into the Zonal Organization of Native and Tissue-Engineered Articular Cartilage

PubMed Central

2016-01-01

Tissue architecture is intimately linked with its functions, and loss of tissue organization is often associated with pathologies. The intricate depth-dependent extracellular matrix (ECM) arrangement in articular cartilage is critical to its biomechanical functions. In this study, we developed a Raman spectroscopic imaging approach to gain new insight into the depth-dependent arrangement of native and tissue-engineered articular cartilage using bovine tissues and cells. Our results revealed previously unreported tissue complexity into at least six zones above the tidemark based on a principal component analysis and k-means clustering analysis of the distribution and orientation of the main ECM components. Correlation of nanoindentation and Raman spectroscopic data suggested that the biomechanics across the tissue depth are influenced by ECM microstructure rather than composition. Further, Raman spectroscopy together with multivariate analysis revealed changes in the collagen, glycosaminoglycan, and water distributions in tissue-engineered constructs over time. These changes were assessed using simple metrics that promise to instruct efforts toward the regeneration of a broad range of tissues with native zonal complexity and functional performance. PMID:28058277

Molecular Characterization of Mosquitocidal Toxin (Surface Layer Protein, SLP) from Bacillus cereus VCRC B540.

PubMed

Mani, Chinnasamy; Selvakumari, Jeyaperumal; Han, YeonSoo; Jo, YongHun; Thirugnanasambantham, Krishnaraj; Sundarapandian, Somaiah; Poopathi, Subbiah

2018-04-01

A marine Bacillus cereus (VCRC B540) with mosquitocidal effect was recently reported from red snapper fish (Lutjanus sanguineous) gut and surface layer protein (S-layer protein, SLP) was reported to be mosquito larvicidal factor. In this present study, the gene encoding the surface layer protein was amplified from the genomic DNA and functionally characterized. Amplification of SLP-encoding gene revealed 1,518 bp PCR product, and analysis of the sequence revealed the presence of 1482 bp open reading frame with coding capacity for a polypeptide of 493 amino acids. Phylogenetic analysis revealed with homology among closely related Bacillus cereus groups of organisms as well as Bacillus strains. Removal of nucleotides encoding signaling peptide revealed the functional cloning fragment of length 1398 bp. Theoretical molecular weight (51.7 kDa) and isoelectric point (5.99) of the deduced functional SLP protein were predicted using ProtParam. The amplified PCR product was cloned into a plasmid vector (pGEM-T), and the open reading frame free off signaling peptide was subsequently cloned inpET-28a(+) and expressed in Escherichia coli BL21 (DE3). The isopropyl-β-D-thiogalactopyranoside (IPTG)-induced recombinant SLP was confirmed using western blotting, and functional SLP revealed mosquito larvicidal property. Therefore, the major findings revealed that SLP is a factor responsible for mosquitocidal activity, and the molecular characterization of this toxin was extensively studied.

Two novel mutations in the POU1F1 gene generate null alleles through different mechanisms leading to combined pituitary hormone deficiency.

PubMed

Turton, J P; Strom, M; Langham, S; Dattani, M T; Le Tissier, P

2012-03-01

  Mutations in the POU1F1 gene severely affect the development and function of the anterior pituitary gland and lead to combined pituitary hormone deficiency (CPHD).   The clinical and genetic analysis of a patient presenting with CPHD and functional characterization of identified mutations.   We describe a male patient with extreme short stature, learning difficulties, anterior pituitary hypoplasia, secondary hypothyroidism and undetectable prolactin, growth hormone (GH) and insulin-like growth factor 1 (IGF1), with normal random cortisol.   The POU1F1 coding region was amplified by PCR and sequenced; the functional consequence of the mutations was analysed by cell transfection and in vitro assays.   Genetic analysis revealed compound heterozygosity for two novel putative loss of function mutations in POU1F1: a transition at position +3 of intron 1 [IVS1+3nt(A>G)] and a point mutation in exon 6 resulting in a substitution of arginine by tryptophan (R265W). Functional analysis revealed that IVS1+3nt(A>G) results in a reduction in the correctly spliced POU1F1 mRNA, which could be corrected by mutations of the +4, +5 and +6 nucleotides. Analysis of POU1F1(R265W) revealed complete loss of function resulting from severely reduced protein stability.   Combined pituitary hormone deficiency in this patient is caused by loss of POU1F1 function by two novel mechanisms, namely aberrant splicing (IVS1+3nt (A>G) and protein instability (R265W). Identification of the genetic basis of CPHD enabled the cessation of hydrocortisone therapy without the need for further assessment for evolving endocrinopathy. © 2012 Blackwell Publishing Ltd.

Co-expression Network Approach to Studying the Effects of Botulinum Neurotoxin-A.

PubMed

Mukund, Kavitha; Ward, Samuel R; Lieber, Richard L; Subramaniam, Shankar

2017-10-16

Botulinum Neurotoxin A (BoNT-A) is a potent neurotoxin with several clinical applications.The goal of this study was to utilize co-expression network theory to analyze temporal transcriptional data from skeletal muscle after BoNT-A treatment. Expression data for 2000 genes (extracted using a ranking heuristic) served as the basis for this analysis. Using weighted gene co-expression network analysis (WGCNA), we identified 19 co-expressed modules, further hierarchically clustered into 5 groups. Quantifying average expression and co-expression patterns across these groups revealed temporal aspects of muscle's response to BoNT-A. Functional analysis revealed enrichment of group 1 with metabolism; group 5 with contradictory functions of atrophy and cellular recovery; and groups 2 and 3 with extracellular matrix (ECM) and non-fast fiber isoforms. Topological positioning of two highly ranked, significantly expressed genes- Dclk1 and Ostalpha within group 5 suggested possible mechanistic roles in recovery from BoNT-A induced atrophy. Phenotypic correlations of groups with titin and myosin protein content further emphasized the effect of BoNT-A on the sarcomeric contraction machinery in early phase of chemodenervation. In summary, our approach revealed a hierarchical functional response to BoNT-A induced paralysis with early metabolic and later ECM responses and identified putative biomarkers associated with chemodenervation. Additionally, our results provide an unbiased validation of the response documented in our previous workBotulinum Neurotoxin A (BoNT-A) is a potent neurotoxin with several clinical applications.The goal of this study was to utilize co-expression network theory to analyze temporal transcriptional data from skeletal muscle after BoNT-A treatment. Expression data for 2000 genes (extracted using a ranking heuristic) served as the basis for this analysis. Using weighted gene co-expression network analysis (WGCNA), we identified 19 co-expressed modules, further hierarchically clustered into 5 groups. Quantifying average expression and co-expression patterns across these groups revealed temporal aspects of muscle's response to BoNT-A. Functional analysis revealed enrichment of group 1 with metabolism; group 5 with contradictory functions of atrophy and cellular recovery; and groups 2 and 3 with extracellular matrix (ECM) and non-fast fiber isoforms. Topological positioning of two highly ranked, significantly expressed genes- Dclk1 and Ostalpha within group 5 suggested possible mechanistic roles in recovery from BoNT-A induced atrophy. Phenotypic correlations of groups with titin and myosin protein content further emphasized the effect of BoNT-A on the sarcomeric contraction machinery in early phase of chemodenervation. In summary, our approach revealed a hierarchical functional response to BoNT-A induced paralysis with early metabolic and later ECM responses and identified putative biomarkers associated with chemodenervation. Additionally, our results provide an unbiased validation of the response documented in our previous work.

Image Analysis of DNA Fiber and Nucleus in Plants.

PubMed

Ohmido, Nobuko; Wako, Toshiyuki; Kato, Seiji; Fukui, Kiichi

2016-01-01

Advances in cytology have led to the application of a wide range of visualization methods in plant genome studies. Image analysis methods are indispensable tools where morphology, density, and color play important roles in the biological systems. Visualization and image analysis methods are useful techniques in the analyses of the detailed structure and function of extended DNA fibers (EDFs) and interphase nuclei. The EDF is the highest in the spatial resolving power to reveal genome structure and it can be used for physical mapping, especially for closely located genes and tandemly repeated sequences. One the other hand, analyzing nuclear DNA and proteins would reveal nuclear structure and functions. In this chapter, we describe the image analysis protocol for quantitatively analyzing different types of plant genome, EDFs and interphase nuclei.

Exercise training reinstates cortico-cortical sensorimotor functional connectivity following striatal lesioning: Development and application of a subregional-level analytic toolbox for perfusion autoradiographs of the rat brain

NASA Astrophysics Data System (ADS)

Peng, Yu-Hao; Heintz, Ryan; Wang, Zhuo; Guo, Yumei; Myers, Kalisa; Scremin, Oscar; Maarek, Jean-Michel; Holschneider, Daniel

2014-12-01

Current rodent connectome projects are revealing brain structural connectivity with unprecedented resolution and completeness. How subregional structural connectivity relates to subregional functional interactions is an emerging research topic. We describe a method for standardized, mesoscopic-level data sampling from autoradiographic coronal sections of the rat brain, and for correlation-based analysis and intuitive display of cortico-cortical functional connectivity (FC) on a flattened cortical map. A graphic user interface “Cx-2D” allows for the display of significant correlations of individual regions-of-interest, as well as graph theoretical metrics across the cortex. Cx-2D was tested on an autoradiographic data set of cerebral blood flow (CBF) of rats that had undergone bilateral striatal lesions, followed by 4 weeks of aerobic exercise training or no exercise. Effects of lesioning and exercise on cortico-cortical FC were examined during a locomotor challenge in this rat model of Parkinsonism. Subregional FC analysis revealed a rich functional reorganization of the brain in response to lesioning and exercise that was not apparent in a standard analysis focused on CBF of isolated brain regions. Lesioned rats showed diminished degree centrality of lateral primary motor cortex, as well as neighboring somatosensory cortex--changes that were substantially reversed in lesioned rats following exercise training. Seed analysis revealed that exercise increased positive correlations in motor and somatosensory cortex, with little effect in non-sensorimotor regions such as visual, auditory, and piriform cortex. The current analysis revealed that exercise partially reinstated sensorimotor FC lost following dopaminergic deafferentation. Cx-2D allows for standardized data sampling from images of brain slices, as well as analysis and display of cortico-cortical FC in the rat cerebral cortex with potential applications in a variety of autoradiographic and histologic studies.

Comparative genome analysis of the candidate functional starter culture strains Lactobacillus fermentum 222 and Lactobacillus plantarum 80 for controlled cocoa bean fermentation processes.

PubMed

Illeghems, Koen; De Vuyst, Luc; Weckx, Stefan

2015-10-12

Lactobacillus fermentum 222 and Lactobacillus plantarum 80, isolates from a spontaneous Ghanaian cocoa bean fermentation process, proved to be interesting functional starter culture strains for cocoa bean fermentations. Lactobacillus fermentum 222 is a thermotolerant strain, able to dominate the fermentation process, thereby converting citrate and producing mannitol. Lactobacillus plantarum 80 is an acid-tolerant and facultative heterofermentative strain that is competitive during cocoa bean fermentation processes. In this study, whole-genome sequencing and comparative genome analysis was used to investigate the mechanisms of these strains to dominate the cocoa bean fermentation process. Through functional annotation and analysis of the high-coverage contigs obtained through 454 pyrosequencing, plantaricin production was predicted for L. plantarum 80. For L. fermentum 222, genes encoding a complete arginine deiminase pathway were attributed. Further, in-depth functional analysis revealed the capacities of these strains associated with carbohydrate and amino acid metabolism, such as the ability to use alternative external electron acceptors, the presence of an extended pyruvate metabolism, and the occurrence of several amino acid conversion pathways. A comparative genome sequence analysis using publicly available genome sequences of strains of the species L. plantarum and L. fermentum revealed unique features of both strains studied. Indeed, L. fermentum 222 possessed genes encoding additional citrate transporters and enzymes involved in amino acid conversions, whereas L. plantarum 80 is the only member of this species that harboured a gene cluster involved in uptake and consumption of fructose and/or sorbose. In-depth genome sequence analysis of the candidate functional starter culture strains L. fermentum 222 and L. plantarum 80 revealed their metabolic capacities, niche adaptations and functionalities that enable them to dominate the cocoa bean fermentation process. Further, these results offered insights into the cocoa bean fermentation ecosystem as a whole and will facilitate the selection of appropriate starter culture strains for controlled cocoa bean fermentation processes.

Gene Set−Based Integrative Analysis Revealing Two Distinct Functional Regulation Patterns in Four Common Subtypes of Epithelial Ovarian Cancer

PubMed Central

Chang, Chia-Ming; Chuang, Chi-Mu; Wang, Mong-Lien; Yang, Yi-Ping; Chuang, Jen-Hua; Yang, Ming-Jie; Yen, Ming-Shyen; Chiou, Shih-Hwa; Chang, Cheng-Chang

2016-01-01

Clear cell (CCC), endometrioid (EC), mucinous (MC) and high-grade serous carcinoma (SC) are the four most common subtypes of epithelial ovarian carcinoma (EOC). The widely accepted dualistic model of ovarian carcinogenesis divided EOCs into type I and II categories based on the molecular features. However, this hypothesis has not been experimentally demonstrated. We carried out a gene set-based analysis by integrating the microarray gene expression profiles downloaded from the publicly available databases. These quantified biological functions of EOCs were defined by 1454 Gene Ontology (GO) term and 674 Reactome pathway gene sets. The pathogenesis of the four EOC subtypes was investigated by hierarchical clustering and exploratory factor analysis. The patterns of functional regulation among the four subtypes containing 1316 cases could be accurately classified by machine learning. The results revealed that the ERBB and PI3K-related pathways played important roles in the carcinogenesis of CCC, EC and MC; while deregulation of cell cycle was more predominant in SC. The study revealed that two different functional regulation patterns exist among the four EOC subtypes, which were compatible with the type I and II classifications proposed by the dualistic model of ovarian carcinogenesis. PMID:27527159

Electrical stimulation reduces smokers' craving by modulating the coupling between dorsal lateral prefrontal cortex and parahippocampal gyrus.

PubMed

Yang, Li-Zhuang; Shi, Bin; Li, Hai; Zhang, Wei; Liu, Ying; Wang, Hongzhi; Zhou, Yanfei; Wang, Ying; Lv, Wanwan; Ji, Xuebing; Hudak, Justin; Zhou, Yifeng; Fallgatter, Andreas J; Zhang, Xiaochu

2017-08-01

Applying electrical stimulation over the prefrontal cortex can help nicotine dependents reduce cigarette craving. However, the underlying mechanism remains ambiguous. This study investigates this issue with functional magnetic resonance imaging. Thirty-two male chronic smokers received real and sham stimulation over dorsal lateral prefrontal cortex (DLPFC) separated by 1 week. The neuroimaging data of the resting state, the smoking cue-reactivity task and the emotion task after stimulation were collected. The craving across the cue-reactivity task was diminished during real stimulation as compared with sham stimulation. The whole-brain analysis on the cue-reactivity task revealed a significant interaction between the stimulation condition (real vs sham) and the cue type (smoking vs neutral) in the left superior frontal gyrus and the left middle frontal gyrus. The functional connectivity between the left DLPFC and the right parahippocampal gyrus, as revealed by both psychophysical interaction analysis and the resting state functional connectivity, is altered by electrical stimulation. Moreover, the craving change across the real and sham condition is predicted by alteration of functional connectivity revealed by psychophysical interaction analysis. The local and long-distance coupling, altered by the electrical stimulation, might be the underlying neural mechanism of craving regulation. © The Author (2017). Published by Oxford University Press.

GOMA: functional enrichment analysis tool based on GO modules

PubMed Central

Huang, Qiang; Wu, Ling-Yun; Wang, Yong; Zhang, Xiang-Sun

2013-01-01

Analyzing the function of gene sets is a critical step in interpreting the results of high-throughput experiments in systems biology. A variety of enrichment analysis tools have been developed in recent years, but most output a long list of significantly enriched terms that are often redundant, making it difficult to extract the most meaningful functions. In this paper, we present GOMA, a novel enrichment analysis method based on the new concept of enriched functional Gene Ontology (GO) modules. With this method, we systematically revealed functional GO modules, i.e., groups of functionally similar GO terms, via an optimization model and then ranked them by enrichment scores. Our new method simplifies enrichment analysis results by reducing redundancy, thereby preventing inconsistent enrichment results among functionally similar terms and providing more biologically meaningful results. PMID:23237213

Structural, Functional, and Genetic Analysis of Sorangicin Inhibition of Bacterial RNA Polymerase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell,E.; Pavlova, O.; Zenkin, N.

2005-01-01

A combined structural, functional, and genetic approach was used to investigate inhibition of bacterial RNA polymerase (RNAP) by sorangicin (Sor), a macrolide polyether antibiotic. Sor lacks chemical and structural similarity to the ansamycin rifampicin (Rif), an RNAP inhibitor widely used to treat tuberculosis. Nevertheless, structural analysis revealed Sor binds in the same RNAP {beta} subunit pocket as Rif, with almost complete overlap of RNAP binding determinants, and functional analysis revealed that both antibiotics inhibit transcription by directly blocking the path of the elongating transcript at a length of 2-3 nucleotides. Genetic analysis indicates that Rif binding is extremely sensitive tomore » mutations expected to change the shape of the antibiotic binding pocket, while Sor is not. We suggest that conformational flexibility of Sor, in contrast to the rigid conformation of Rif, allows Sor to adapt to changes in the binding pocket. This has important implications for drug design against rapidly mutating targets.« less

Default mode of brain function in monkeys.

PubMed

Mantini, Dante; Gerits, Annelis; Nelissen, Koen; Durand, Jean-Baptiste; Joly, Olivier; Simone, Luciano; Sawamura, Hiromasa; Wardak, Claire; Orban, Guy A; Buckner, Randy L; Vanduffel, Wim

2011-09-07

Human neuroimaging has revealed a specific network of brain regions-the default-mode network (DMN)-that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment.

Default Mode of Brain Function in Monkeys

PubMed Central

Mantini, Dante; Gerits, Annelis; Nelissen, Koen; Durand, Jean-Baptiste; Joly, Olivier; Simone, Luciano; Sawamura, Hiromasa; Wardak, Claire; Orban, Guy A.; Buckner, Randy L.; Vanduffel, Wim

2013-01-01

Human neuroimaging has revealed a specific network of brain regions—the default-mode network (DMN)—that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment. PMID:21900574

Genome wide analysis reveals Zic3 interaction with distal regulatory elements of stage specific developmental genes in zebrafish.

PubMed

Winata, Cecilia L; Kondrychyn, Igor; Kumar, Vibhor; Srinivasan, Kandhadayar G; Orlov, Yuriy; Ravishankar, Ashwini; Prabhakar, Shyam; Stanton, Lawrence W; Korzh, Vladimir; Mathavan, Sinnakaruppan

2013-10-01

Zic3 regulates early embryonic patterning in vertebrates. Loss of Zic3 function is known to disrupt gastrulation, left-right patterning, and neurogenesis. However, molecular events downstream of this transcription factor are poorly characterized. Here we use the zebrafish as a model to study the developmental role of Zic3 in vivo, by applying a combination of two powerful genomics approaches--ChIP-seq and microarray. Besides confirming direct regulation of previously implicated Zic3 targets of the Nodal and canonical Wnt pathways, analysis of gastrula stage embryos uncovered a number of novel candidate target genes, among which were members of the non-canonical Wnt pathway and the neural pre-pattern genes. A similar analysis in zic3-expressing cells obtained by FACS at segmentation stage revealed a dramatic shift in Zic3 binding site locations and identified an entirely distinct set of target genes associated with later developmental functions such as neural development. We demonstrate cis-regulation of several of these target genes by Zic3 using in vivo enhancer assay. Analysis of Zic3 binding sites revealed a distribution biased towards distal intergenic regions, indicative of a long distance regulatory mechanism; some of these binding sites are highly conserved during evolution and act as functional enhancers. This demonstrated that Zic3 regulation of developmental genes is achieved predominantly through long distance regulatory mechanism and revealed that developmental transitions could be accompanied by dramatic changes in regulatory landscape.

Genome wide in silico characterization of Dof gene families of pigeonpea (Cajanus cajan (L) Millsp.).

PubMed

Malviya, N; Gupta, S; Singh, V K; Yadav, M K; Bisht, N C; Sarangi, B K; Yadav, D

2015-02-01

The DNA binding with One Finger (Dof) protein is a plant specific transcription factor involved in the regulation of wide range of processes. The analysis of whole genome sequence of pigeonpea has identified 38 putative Dof genes (CcDof) distributed on 8 chromosomes. A total of 17 out of 38 CcDof genes were found to be intronless. A comprehensive in silico characterization of CcDof gene family including the gene structure, chromosome location, protein motif, phylogeny, gene duplication and functional divergence has been attempted. The phylogenetic analysis resulted in 3 major clusters with closely related members in phylogenetic tree revealed common motif distribution. The in silico cis-regulatory element analysis revealed functional diversity with predominance of light responsive and stress responsive elements indicating the possibility of these CcDof genes to be associated with photoperiodic control and biotic and abiotic stress. The duplication pattern showed that tandem duplication is predominant over segmental duplication events. The comparative phylogenetic analysis of these Dof proteins along with 78 soybean, 36 Arabidopsis and 30 rice Dof proteins revealed 7 major clusters. Several groups of orthologs and paralogs were identified based on phylogenetic tree constructed. Our study provides useful information for functional characterization of CcDof genes.

Olfactory function in chemical workers exposed to acrylate and methacrylate vapors.

PubMed Central

Schwartz, B S; Doty, R L; Monroe, C; Frye, R; Barker, S

1989-01-01

An investigation of the olfactory function of 731 workers at a chemical facility which manufacturers acrylates and methacrylates was undertaken using a standardized quantitative test. In a cross-sectional analysis of the data, no associations of chemical exposure with olfactory test scores were observed. A nested case-control study designed to evaluate the cumulative effects of exposure on olfactory function, however, revealed elevated crude exposure odds ratios (95% confidence interval) of 2.0 (1.1, 3.8) for all workers and 6.0 (1.7, 21.5) for workers who never smoked cigarettes. Logistic regression analysis, adjusting for multiple confounders, revealed exposure odds ratios of 2.8 (1.1, 7.0) and 13.5 (2.1, 87.6) in these same groups, respectively, and a dose-response relationship between olfactory dysfunction and cumulative exposure scores--semi-quantitative indices of lifetime exposure to the acrylates. The data also revealed decreasing exposure odds ratios with increasing duration since last exposure to these chemicals, suggesting that the effects may be reversible. PMID:2784947

Applying meta-pathway analyses through metagenomics to identify the functional properties of the major bacterial communities of a single spontaneous cocoa bean fermentation process sample.

PubMed

Illeghems, Koen; Weckx, Stefan; De Vuyst, Luc

2015-09-01

A high-resolution functional metagenomic analysis of a representative single sample of a Brazilian spontaneous cocoa bean fermentation process was carried out to gain insight into its bacterial community functioning. By reconstruction of microbial meta-pathways based on metagenomic data, the current knowledge about the metabolic capabilities of bacterial members involved in the cocoa bean fermentation ecosystem was extended. Functional meta-pathway analysis revealed the distribution of the metabolic pathways between the bacterial members involved. The metabolic capabilities of the lactic acid bacteria present were most associated with the heterolactic fermentation and citrate assimilation pathways. The role of Enterobacteriaceae in the conversion of substrates was shown through the use of the mixed-acid fermentation and methylglyoxal detoxification pathways. Furthermore, several other potential functional roles for Enterobacteriaceae were indicated, such as pectinolysis and citrate assimilation. Concerning acetic acid bacteria, metabolic pathways were partially reconstructed, in particular those related to responses toward stress, explaining their metabolic activities during cocoa bean fermentation processes. Further, the in-depth metagenomic analysis unveiled functionalities involved in bacterial competitiveness, such as the occurrence of CRISPRs and potential bacteriocin production. Finally, comparative analysis of the metagenomic data with bacterial genomes of cocoa bean fermentation isolates revealed the applicability of the selected strains as functional starter cultures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transcriptome Sequencing Revealed Significant Alteration of Cortical Promoter Usage and Splicing in Schizophrenia

PubMed Central

Wu, Jing Qin; Wang, Xi; Beveridge, Natalie J.; Tooney, Paul A.; Scott, Rodney J.; Carr, Vaughan J.; Cairns, Murray J.

2012-01-01

Background While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression. Methodology/Principal Findings The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22) from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05). Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1) gene. Conclusions This study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia. PMID:22558445

Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality.

PubMed

Jiang, Yue; Xiong, Xuejian; Danska, Jayne; Parkinson, John

2016-01-12

Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. At the same time, our findings show how microbiome complexity and availability of reference genomes can impact comprehensive annotation of metatranscriptomes. Consequently, beyond the application of standardized pipelines, additional caution must be taken when interpreting their output and performing downstream, microbiome-specific, analyses. The pipeline used in these analyses along with a tutorial has been made freely available for download from our project website: http://www.compsysbio.org/microbiome .

Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury.

PubMed

Luo, Dandan; Ge, Weihong; Hu, Xiao; Li, Chen; Lee, Chia-Ming; Zhou, Liqiang; Wu, Zhourui; Yu, Juehua; Lin, Sheng; Yu, Jing; Xu, Wei; Chen, Lei; Zhang, Chong; Jiang, Kun; Zhu, Xingfei; Li, Haotian; Gao, Xinpei; Geng, Yanan; Jing, Bo; Wang, Zhen; Zheng, Changhong; Zhu, Rongrong; Yan, Qiao; Lin, Quan; Ye, Keqiang; Sun, Yi E; Cheng, Liming

2018-06-28

The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

Fragments of Bacterial Endoglycosidase S and Immunoglobulin G Reveal Subdomains of Each That Contribute to Deglycosylation*

PubMed Central

Dixon, Emma V.; Claridge, Jolyon K.; Harvey, David J.; Baruah, Kavitha; Yu, Xiaojie; Vesiljevic, Snezana; Mattick, Susan; Pritchard, Laura K.; Krishna, Benjamin; Scanlan, Christopher N.; Schnell, Jason R.; Higgins, Matthew K.; Zitzmann, Nicole; Crispin, Max

2014-01-01

Endoglycosidase S (EndoS) is a glycoside-hydrolase secreted by the bacterium Streptococcus pyogenes. EndoS preferentially hydrolyzes the N-linked glycans from the Fc region of IgG during infection. This hydrolysis impedes Fc functionality and contributes to the immune evasion strategy of S. pyogenes. Here, we investigate the mechanism of human serum IgG deactivation by EndoS. We expressed fragments of IgG1 and demonstrated that EndoS was catalytically active against all of them including the isolated CH2 domain of the Fc domain. Similarly, we sought to investigate which domains within EndoS could contribute to activity. Bioinformatics analysis of the domain organization of EndoS confirmed the previous predictions of a chitinase domain and leucine-rich repeat but also revealed a putative carbohydrate binding module (CBM) followed by a C-terminal region. Using expressed fragments of EndoS, circular dichroism of the isolated CBM, and a CBM-C-terminal region fusion revealed folded domains dominated by β sheet and α helical structure, respectively. Nuclear magnetic resonance analysis of the CBM with monosaccharides was suggestive of carbohydrate binding functionality. Functional analysis of truncations of EndoS revealed that, whereas the C-terminal of EndoS is dispensable for activity, its deletion impedes the hydrolysis of IgG glycans. PMID:24668806

First Monte Carlo analysis of fragmentation functions from single-inclusive e + e - annihilation

DOE PAGES

Sato, Nobuo; Ethier, J. J.; Melnitchouk, W.; ...

2016-12-02

Here, we perform the first iterative Monte Carlo (IMC) analysis of fragmentation functions constrained by all available data from single-inclusive $e^+ e^-$ annihilation into pions and kaons. The IMC method eliminates potential bias in traditional analyses based on single fits introduced by fixing parameters not well contrained by the data, and provides a statistically rigorous determination of uncertainties. Our analysis reveals specific features of fragmentation functions using the new IMC methodology and those obtained from previous analyses, especially for light quarks and for strange quark fragmentation to kaons.

Cluster analysis differentiates high and low community functioning in schizophrenia: Subgroups differ on working memory but not other neurocognitive domains.

PubMed

Alden, Eva C; Cobia, Derin J; Reilly, James L; Smith, Matthew J

2015-10-01

Schizophrenia is characterized by impairment in multiple aspects of community functioning. Available literature suggests that community functioning may be enhanced through cognitive remediation, however, evidence is limited regarding whether specific neurocognitive domains may be treatment targets. We characterized schizophrenia subjects based on their level of community functioning through cluster analysis in an effort to identify whether specific neurocognitive domains were associated with variation in functioning. Schizophrenia (SCZ, n=60) and control (CON, n=45) subjects completed a functional capacity task, social competence role-play, functional attainment interview, and a neuropsychological battery. Multiple cluster analytic techniques were used on the measures of functioning in the schizophrenia subjects to generate functionally-defined subgroups. MANOVA evaluated between-group differences in neurocognition. The cluster analysis revealed two distinct groups, consisting of 36 SCZ characterized by high levels of community functioning (HF-SCZ) and 24 SCZ with low levels of community functioning (LF-SCZ). There was a main group effect for neurocognitive performance (p<0.001) with CON outperforming both SCZ groups in all neurocognitive domains. Post-hoc tests revealed that HF-SCZ had higher verbal working memory compared to LF-SCZ (p≤0.05, Cohen's d=0.78) but the two groups did not differ in remaining domains. The cluster analysis classified schizophrenia subjects in HF-SCZ and LF-SCZ using a multidimensional assessment of community functioning. Moreover, HF-SCZ demonstrated rather preserved verbal working memory relative to LF-SCZ. The results suggest that verbal working memory may play a critical role in community functioning, and is a potential cognitive treatment target for schizophrenia subjects. Copyright © 2015 Elsevier B.V. All rights reserved.

Mapping Mathematics in Classroom Discourse

ERIC Educational Resources Information Center

Herbel-Eisenmann, Beth A.; Otten, Samuel

2011-01-01

This article offers a particular analytic method from systemic functional linguistics, "thematic analysis," which reveals the mathematical meaning potentials construed in discourse. Addressing concerns that discourse analysis is too often content-free, thematic analysis provides a way to represent semantic structures of mathematical content,…

Validation of Skeletal Muscle cis-Regulatory Module Predictions Reveals Nucleotide Composition Bias in Functional Enhancers

PubMed Central

Kwon, Andrew T.; Chou, Alice Yi; Arenillas, David J.; Wasserman, Wyeth W.

2011-01-01

We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs) using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene expression to differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the assay. The rate of predictive success reveals striking limitations of computational regulatory sequence analysis methods for CRM discovery. Motif-based methods performed no better than predictions based only on sequence conservation. Analysis of the properties of the functional sequences relative to inactive sequences identifies nucleotide sequence composition can be an important characteristic to incorporate in future methods for improved predictive specificity. Muscle-related TFBSs predicted within the functional sequences display greater sequence conservation than non-TFBS flanking regions. Comparison with recent MyoD and histone modification ChIP-Seq data supports the validity of the functional regions. PMID:22144875

Mechanism of the coupling of diazonium to single-walled carbon nanotubes and its consequences.

PubMed

Schmidt, Grégory; Gallon, Salomé; Esnouf, Stéphane; Bourgoin, Jean-Philippe; Chenevier, Pascale

2009-01-01

On the tube: The coupling of diazonium ions onto single-walled carbon nanotubes is shown to proceed through a radical chain reaction by kinetic analysis of the absorption peak drop (see picture). Radical species are also revealed by ESR. Metallic (m) nanotubes play a special catalytic role in the functionalization of semiconducting (sc) nanotubes.Due to its simplicity and versatility, diazonium coupling is the most widely used method for carbon nanotube (CNT) functionalization to increase CNT processability and add new functionalities. Yet, its mechanism is so far mostly unknown. Herein, we use kinetic analysis to shed light on this complex mechanism. A free-radical chain reaction is revealed by absorption spectroscopy and ESR. Metallic CNTs are shown to play an unexpected catalytic role. The step determining the selectivity towards metallic CNTs is identified by a Hammett correlation. A mechanistic model is proposed that predicts reactivity and selectivity as a function of diazonium electrophilicity and metallic-to-semiconducting CNT ratio, thus opening perspectives of controlled high-yield functionalization and purification.

Proteomic analysis reveals diverse proline hydroxylation-mediated oxygen-sensing cellular pathways in cancer cells

PubMed Central

Liu, Bing; Gao, Yankun; Ruan, Hai-Bin; Chen, Yue

2016-01-01

Proline hydroxylation is a critical cellular mechanism regulating oxygen-response pathways in tumor initiation and progression. Yet, its substrate diversity and functions remain largely unknown. Here, we report a system-wide analysis to characterize proline hydroxylation substrates in cancer cells using an immunoaffinity-purification assisted proteomics strategy. We identified 562 sites from 272 proteins in HeLa cells. Bioinformatic analysis revealed that proline hydroxylation substrates are significantly enriched with mRNA processing and stress-response cellular pathways with canonical and diverse flanking sequence motifs. Structural analysis indicates a significant enrichment of proline hydroxylation participating in the secondary structure of substrate proteins. Our study identified and validated Brd4, a key transcription factor, as a novel proline hydroxylation substrate. Functional analysis showed that the inhibition of proline hydroxylation pathway significantly reduced the proline hydroxylation abundance on Brd4 and affected Brd4-mediated transcriptional activity as well as cell proliferation in AML leukemia cells. Taken together, our study identified a broad regulatory role of proline hydroxylation in cellular oxygen-sensing pathways and revealed potentially new targets that dynamically respond to hypoxia microenvironment in tumor cells. PMID:27764789

Network analysis reveals disrupted functional brain circuitry in drug-naive social anxiety disorder.

PubMed

Yang, Xun; Liu, Jin; Meng, Yajing; Xia, Mingrui; Cui, Zaixu; Wu, Xi; Hu, Xinyu; Zhang, Wei; Gong, Gaolang; Gong, Qiyong; Sweeney, John A; He, Yong

2017-12-07

Social anxiety disorder (SAD) is a common and disabling condition characterized by excessive fear and avoidance of public scrutiny. Psychoradiology studies have suggested that the emotional and behavior deficits in SAD are associated with abnormalities in regional brain function and functional connectivity. However, little is known about whether intrinsic functional brain networks in patients with SAD are topologically disrupted. Here, we collected resting-state fMRI data from 33 drug-naive patients with SAD and 32 healthy controls (HC), constructed functional networks with 34 predefined regions based on previous meta-analytic research with task-based fMRI in SAD, and performed network-based statistic and graph-theory analyses. The network-based statistic analysis revealed a single connected abnormal circuitry including the frontolimbic circuit (termed the "fear circuit", including the dorsolateral prefrontal cortex, ventral medial prefrontal cortex and insula) and posterior cingulate/occipital areas supporting perceptual processing. In this single altered network, patients with SAD had higher functional connectivity than HC. At the global level, graph-theory analysis revealed that the patients exhibited a lower normalized characteristic path length than HC, which suggests a disorder-related shift of network topology toward randomized configurations. SAD-related deficits in nodal degree, efficiency and participation coefficient were detected in the parahippocampal gyrus, posterior cingulate cortex, dorsolateral prefrontal cortex, insula and the calcarine sulcus. Aspects of abnormal connectivity were associated with anxiety symptoms. These findings highlight the aberrant topological organization of functional brain network organization in SAD, which provides insights into the neural mechanisms underlying excessive fear and avoidance of social interactions in patients with debilitating social anxiety. Copyright © 2017. Published by Elsevier Inc.

Clinical indicators of paraplegia underplay universal spinal cord neuronal injury from transient aortic occlusion.

PubMed

Bell, Marshall T; Puskas, Ferenc; Bennett, Daine T; Cleveland, Joseph C; Herson, Paco S; Mares, Joshua M; Meng, Xainzhong; Weyant, Michael J; Fullerton, David A; Brett Reece, T

2015-08-27

Paraplegia following complex aortic intervention relies on crude evaluation of lower extremity strength such as whether the patient can lift their legs or flex the ankle. Little attention has been given to the possible long-term neurologic sequelae following these procedures in patients appearing functionally normal. We hypothesize that mice subjected to minimal ischemic time will have functional and histological changes despite the gross appearance of normal function. Male mice underwent 3 min of aortic occlusion (n=14) or sham surgery (n=4) via a median sternotomy. Neurologic function was graded by Basso Motor Score (BMS) preoperatively and at 24h intervals after reperfusion. Mice appearing functionally normal and sham mice were placed on a walking beam and recorded on high-definition, for single-frame motion analysis. After 96 hrs, spinal cords were removed for histological analysis. Following 3 min of ischemia, functional outcomes were split evenly with either mice displaying almost normal function n=7 or near complete paraplegia n=7. Additionally, single-frame motion analysis revealed significant changes in gait. Histologically, there was a significant stepwise reduction of neuronal viability, with even the normal function ischemic group demonstrating significant loss of neurons. Despite the appearance of normal function, temporary ischemia induced marked cyto-architectural changes and neuronal degeneration. Furthermore high-definition gait analysis revealed significant changes in gait and activity following thoracic aortic occlusion. These data suggest that all patients undergoing procedures, even with short ischemic times, may have spinal cord injury that is not evident clinically. Copyright © 2015 Elsevier B.V. All rights reserved.

Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease.

PubMed

Torres, Matthew P; Dewhurst, Henry; Sundararaman, Niveda

2016-11-01

Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable body of potential regulatory elements that impact hundreds of different biological processes important in eukaryotic biology and human health. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease*

PubMed Central

Dewhurst, Henry; Sundararaman, Niveda

2016-01-01

Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable body of potential regulatory elements that impact hundreds of different biological processes important in eukaryotic biology and human health. PMID:27697855

Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke

PubMed Central

Zavaglia, Melissa; Forkert, Nils D.; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C.

2015-01-01

Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’. PMID:26448908

Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke.

PubMed

Zavaglia, Melissa; Forkert, Nils D; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C

2015-01-01

Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a 'map of stroke'.

Soybean kinome: functional classification and gene expression patterns

PubMed Central

Liu, Jinyi; Chen, Nana; Grant, Joshua N.; Cheng, Zong-Ming (Max); Stewart, C. Neal; Hewezi, Tarek

2015-01-01

The protein kinase (PK) gene family is one of the largest and most highly conserved gene families in plants and plays a role in nearly all biological functions. While a large number of genes have been predicted to encode PKs in soybean, a comprehensive functional classification and global analysis of expression patterns of this large gene family is lacking. In this study, we identified the entire soybean PK repertoire or kinome, which comprised 2166 putative PK genes, representing 4.67% of all soybean protein-coding genes. The soybean kinome was classified into 19 groups, 81 families, and 122 subfamilies. The receptor-like kinase (RLK) group was remarkably large, containing 1418 genes. Collinearity analysis indicated that whole-genome segmental duplication events may have played a key role in the expansion of the soybean kinome, whereas tandem duplications might have contributed to the expansion of specific subfamilies. Gene structure, subcellular localization prediction, and gene expression patterns indicated extensive functional divergence of PK subfamilies. Global gene expression analysis of soybean PK subfamilies revealed tissue- and stress-specific expression patterns, implying regulatory functions over a wide range of developmental and physiological processes. In addition, tissue and stress co-expression network analysis uncovered specific subfamilies with narrow or wide interconnected relationships, indicative of their association with particular or broad signalling pathways, respectively. Taken together, our analyses provide a foundation for further functional studies to reveal the biological and molecular functions of PKs in soybean. PMID:25614662

Functional gene profiling through metaRNAseq approach reveals diet-dependent variation in rumen microbiota of buffalo (Bubalus bubalis).

PubMed

Hinsu, Ankit T; Parmar, Nidhi R; Nathani, Neelam M; Pandit, Ramesh J; Patel, Anand B; Patel, Amrutlal K; Joshi, Chaitanya G

2017-04-01

Recent advances in next generation sequencing technology have enabled analysis of complex microbial community from genome to transcriptome level. In the present study, metatranscriptomic approach was applied to elucidate functionally active bacteria and their biological processes in rumen of buffalo (Bubalus bubalis) adapted to different dietary treatments. Buffaloes were adapted to a diet containing 50:50, 75:25 and 100:0 forage to concentrate ratio, each for 6 weeks, before ruminal content sample collection. Metatranscriptomes from rumen fiber adherent and fiber-free active bacteria were sequenced using Ion Torrent PGM platform followed by annotation using MG-RAST server and CAZYmes (Carbohydrate active enzymes) analysis toolkit. In all the samples Bacteroidetes was the most abundant phylum followed by Firmicutes. Functional analysis using KEGG Orthology database revealed Metabolism as the most abundant category at level 1 within which Carbohydrate metabolism was dominating. Diet treatments also exerted significant differences in proportion of enzymes involved in metabolic pathways for VFA production. Carbohydrate Active Enzyme(CAZy) analysis revealed the abundance of genes encoding glycoside hydrolases with the highest representation of GH13 CAZy family in all the samples. The findings provide an overview of the activities occurring in the rumen as well as active bacterial population and the changes occurring through different dietary treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessing Language Dominance with Functional MRI: The Role of Control Tasks and Statistical Analysis

ERIC Educational Resources Information Center

Dodoo-Schittko, Frank; Rosengarth, Katharina; Doenitz, Christian; Greenlee, Mark W.

2012-01-01

There is a discrepancy between the brain regions revealed by functional neuroimaging techniques and those brain regions where a loss of function, either by lesion or by electrocortical stimulation, induces language disorders. To differentiate between essential and non-essential language-related processes, we investigated the effects of linguistic…

Exploring the Phenotype of Phonological Reading Disability as a Function of the Phonological Deficit Severity: Evidence from the Error Analysis Paradigm in Arabic

ERIC Educational Resources Information Center

Taha, Haitham; Ibrahim, Raphiq; Khateb, Asaid

2014-01-01

The dominant error types were investigated as a function of phonological processing (PP) deficit severity in four groups of impaired readers. For this aim, an error analysis paradigm distinguishing between four error types was used. The findings revealed that the different types of impaired readers were characterized by differing predominant error…

Self-harming behavior of a parent with borderline personality disorder assessed using revealed preference and attributional approaches: a case study.

PubMed

Tustin, R Don

2002-08-01

This article discusses a case study involving a parent with Borderline Personality Disorder who exhibited self-harming behaviors. Assessment and intervention were based both on a review of the client's attributions about causes of her own behavior as being either internalizing or externalizing, and on a review of motivation of the behaviors using functional analysis. Antecedent situations for self-harming behaviors were identified to provide a basis for reviewing the client's attributions of reasons for disordered behavior. A new technique of functional analysis was applied using the principle of revealed preference arising from behavioral economics. Revealed preference identified outcomes that were valued by the client, enabling new responses to be identified to attain these reinforcers. Attribution re-training was provided. Significant reductions in self-harming behaviors were achieved during brief therapy and were maintained during follow-up.

Multifractal analysis of information processing in hippocampal neural ensembles during working memory under Δ9-tetrahydrocannabinol administration

PubMed Central

Fetterhoff, Dustin; Opris, Ioan; Simpson, Sean L.; Deadwyler, Sam A.; Hampson, Robert E.; Kraft, Robert A.

2014-01-01

Background Multifractal analysis quantifies the time-scale-invariant properties in data by describing the structure of variability over time. By applying this analysis to hippocampal interspike interval sequences recorded during performance of a working memory task, a measure of long-range temporal correlations and multifractal dynamics can reveal single neuron correlates of information processing. New method Wavelet leaders-based multifractal analysis (WLMA) was applied to hippocampal interspike intervals recorded during a working memory task. WLMA can be used to identify neurons likely to exhibit information processing relevant to operation of brain–computer interfaces and nonlinear neuronal models. Results Neurons involved in memory processing (“Functional Cell Types” or FCTs) showed a greater degree of multifractal firing properties than neurons without task-relevant firing characteristics. In addition, previously unidentified FCTs were revealed because multifractal analysis suggested further functional classification. The cannabinoid-type 1 receptor partial agonist, tetrahydrocannabinol (THC), selectively reduced multifractal dynamics in FCT neurons compared to non-FCT neurons. Comparison with existing methods WLMA is an objective tool for quantifying the memory-correlated complexity represented by FCTs that reveals additional information compared to classification of FCTs using traditional z-scores to identify neuronal correlates of behavioral events. Conclusion z-Score-based FCT classification provides limited information about the dynamical range of neuronal activity characterized by WLMA. Increased complexity, as measured with multifractal analysis, may be a marker of functional involvement in memory processing. The level of multifractal attributes can be used to differentially emphasize neural signals to improve computational models and algorithms underlying brain–computer interfaces. PMID:25086297

Large‐scale analysis reveals populational contributions of cortical spike rate and synchrony to behavioural functions

PubMed Central

Saiki, Akiko; Fujiwara‐Tsukamoto, Yoko; Sakai, Yutaka; Isomura, Yoshikazu

2016-01-01

Key points There have been few systematic population‐wide analyses of relationships between spike synchrony within a period of several milliseconds and behavioural functions.In this study, we obtained a large amount of spike data from > 23,000 neuron pairs by multiple single‐unit recording from deep layer neurons in motor cortical areas in rats performing a forelimb movement task.The temporal changes of spike synchrony in the whole neuron pairs were statistically independent of behavioural changes during the task performance, although some neuron pairs exhibited correlated changes in spike synchrony.Mutual information analyses revealed that spike synchrony made a smaller contribution than spike rate to behavioural functions.The strength of spike synchrony between two neurons was statistically independent of the spike rate‐based preferences of the pair for behavioural functions. Abstract Spike synchrony within a period of several milliseconds in presynaptic neurons enables effective integration of functional information in the postsynaptic neuron. However, few studies have systematically analysed the population‐wide relationships between spike synchrony and behavioural functions. Here we obtained a sufficiently large amount of spike data among regular‐spiking (putatively excitatory) and fast‐spiking (putatively inhibitory) neuron subtypes (> 23,000 pairs) by multiple single‐unit recording from deep layers in motor cortical areas (caudal forelimb area, rostral forelimb area) in rats performing a forelimb movement task. After holding a lever, rats pulled the lever either in response to a cue tone (external‐trigger trials) or spontaneously without any cue (internal‐trigger trials). Many neurons exhibited functional spike activity in association with forelimb movements, and the preference of regular‐spiking neurons in the rostral forelimb area was more biased toward externally triggered movement than that in the caudal forelimb area. We found that a population of neuron pairs with spike synchrony does exist, and that some neuron pairs exhibit a dependence on movement phase during task performance. However, the population‐wide analysis revealed that spike synchrony was statistically independent of the movement phase and the spike rate‐based preferences of the pair for behavioural functions, whereas spike rates were clearly dependent on the movement phase. In fact, mutual information analyses revealed that the contribution of spike synchrony to the behavioural functions was small relative to the contribution of spike rate. Our large‐scale analysis revealed that cortical spike rate, rather than spike synchrony, contributes to population coding for movement. PMID:27488936

Large-scale analysis reveals populational contributions of cortical spike rate and synchrony to behavioural functions.

PubMed

Kimura, Rie; Saiki, Akiko; Fujiwara-Tsukamoto, Yoko; Sakai, Yutaka; Isomura, Yoshikazu

2017-01-01

There have been few systematic population-wide analyses of relationships between spike synchrony within a period of several milliseconds and behavioural functions. In this study, we obtained a large amount of spike data from > 23,000 neuron pairs by multiple single-unit recording from deep layer neurons in motor cortical areas in rats performing a forelimb movement task. The temporal changes of spike synchrony in the whole neuron pairs were statistically independent of behavioural changes during the task performance, although some neuron pairs exhibited correlated changes in spike synchrony. Mutual information analyses revealed that spike synchrony made a smaller contribution than spike rate to behavioural functions. The strength of spike synchrony between two neurons was statistically independent of the spike rate-based preferences of the pair for behavioural functions. Spike synchrony within a period of several milliseconds in presynaptic neurons enables effective integration of functional information in the postsynaptic neuron. However, few studies have systematically analysed the population-wide relationships between spike synchrony and behavioural functions. Here we obtained a sufficiently large amount of spike data among regular-spiking (putatively excitatory) and fast-spiking (putatively inhibitory) neuron subtypes (> 23,000 pairs) by multiple single-unit recording from deep layers in motor cortical areas (caudal forelimb area, rostral forelimb area) in rats performing a forelimb movement task. After holding a lever, rats pulled the lever either in response to a cue tone (external-trigger trials) or spontaneously without any cue (internal-trigger trials). Many neurons exhibited functional spike activity in association with forelimb movements, and the preference of regular-spiking neurons in the rostral forelimb area was more biased toward externally triggered movement than that in the caudal forelimb area. We found that a population of neuron pairs with spike synchrony does exist, and that some neuron pairs exhibit a dependence on movement phase during task performance. However, the population-wide analysis revealed that spike synchrony was statistically independent of the movement phase and the spike rate-based preferences of the pair for behavioural functions, whereas spike rates were clearly dependent on the movement phase. In fact, mutual information analyses revealed that the contribution of spike synchrony to the behavioural functions was small relative to the contribution of spike rate. Our large-scale analysis revealed that cortical spike rate, rather than spike synchrony, contributes to population coding for movement. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

CRISPR/Cas9 and active genetics-based trans-species replacement of the endogenous Drosophila kni-L2 CRM reveals unexpected complexity.

PubMed

Xu, Xiang-Ru Shannon; Gantz, Valentino Matteo; Siomava, Natalia; Bier, Ethan

2017-12-23

The knirps ( kni ) locus encodes transcription factors required for induction of the L2 wing vein in Drosophila . Here, we employ diverse CRISPR/Cas9 genome editing tools to generate a series of targeted lesions within the endogenous cis-regulatory module (CRM) required for kni expression in the L2 vein primordium. Phenotypic analysis of these ' in locus ' mutations based on both expression of Kni protein and adult wing phenotypes, reveals novel unexpected features of L2-CRM function including evidence for a chromosome pairing-dependent process that promotes transcription. We also demonstrate that self-propagating active genetic elements (CopyCat elements) can efficiently delete and replace the L2-CRM with orthologous sequences from other divergent fly species. Wing vein phenotypes resulting from these trans-species enhancer replacements parallel features of the respective donor fly species. This highly sensitive phenotypic readout of enhancer function in a native genomic context reveals novel features of CRM function undetected by traditional reporter gene analysis. © 2017, Xu et al.

CRISPR/Cas9 and active genetics-based trans-species replacement of the endogenous Drosophila kni-L2 CRM reveals unexpected complexity

PubMed Central

Siomava, Natalia

2017-01-01

The knirps (kni) locus encodes transcription factors required for induction of the L2 wing vein in Drosophila. Here, we employ diverse CRISPR/Cas9 genome editing tools to generate a series of targeted lesions within the endogenous cis-regulatory module (CRM) required for kni expression in the L2 vein primordium. Phenotypic analysis of these ‘in locus’ mutations based on both expression of Kni protein and adult wing phenotypes, reveals novel unexpected features of L2-CRM function including evidence for a chromosome pairing-dependent process that promotes transcription. We also demonstrate that self-propagating active genetic elements (CopyCat elements) can efficiently delete and replace the L2-CRM with orthologous sequences from other divergent fly species. Wing vein phenotypes resulting from these trans-species enhancer replacements parallel features of the respective donor fly species. This highly sensitive phenotypic readout of enhancer function in a native genomic context reveals novel features of CRM function undetected by traditional reporter gene analysis. PMID:29274230

Genetic randomization reveals functional relationships among morphologic and tissue-quality traits that contribute to bone strength and fragility

PubMed Central

Hu, Bin; Tommasini, Steven M.; Courtland, Hayden-William; Price, Christopher; Terranova, Carl J.; Nadeau, Joseph H.

2007-01-01

We examined femora from adult AXB/BXA recombinant inbred (RI) mouse strains to identify skeletal traits that are functionally related and to determine how functional interactions among these traits contribute to genetic variability in whole-bone stiffness, strength, and toughness. Randomization of A/J and C57BL/6J genomic regions resulted in each adult male and female RI strain building mechanically functional femora by assembling unique sets of morphologic and tissue-quality traits. A correlation analysis was conducted using the mean trait values for each RI strain. A third of the 66 correlations examined were significant, indicating that many bone traits covaried or were functionally related. Path analysis revealed important functional interactions among bone slenderness, cortical thickness, and tissue mineral density. The path coefficients describing these functional relations were similar for both sexes. The causal relationship among these three traits suggested that cellular processes during growth simultaneously regulate bone slenderness, cortical thickness, and tissue mineral density so that the combination of traits is sufficiently stiff and strong to satisfy daily loading demands. A disadvantage of these functional interactions was that increases in tissue mineral density also deleteriously affected tissue ductility. Consequently, slender bones with high mineral density may be stiff and strong but they are also brittle. Thus, genetically randomized mouse strains revealed a basic biological paradigm that allows for flexibility in building bones that are functional for daily activities but that creates preferred sets of traits under extreme loading conditions. Genetic or environmental perturbations that alter these functional interactions during growth would be expected to lead to loss of function and suboptimal adult bone quality. PMID:17557179

Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia.

PubMed

Damaraju, E; Allen, E A; Belger, A; Ford, J M; McEwen, S; Mathalon, D H; Mueller, B A; Pearlson, G D; Potkin, S G; Preda, A; Turner, J A; Vaidya, J G; van Erp, T G; Calhoun, V D

2014-01-01

Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical-subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences.

Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia

PubMed Central

Damaraju, E.; Allen, E.A.; Belger, A.; Ford, J.M.; McEwen, S.; Mathalon, D.H.; Mueller, B.A.; Pearlson, G.D.; Potkin, S.G.; Preda, A.; Turner, J.A.; Vaidya, J.G.; van Erp, T.G.; Calhoun, V.D.

2014-01-01

Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical–subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences. PMID:25161896

[Noopept in the treatment of mild cognitive impairment in patients with stroke].

PubMed

Amelin, A V; Iliukhina, A Iu; Shmonin, A A

2011-01-01

Noopept is a neuroprotector and nootropics. Literature data revealed the treatment effect of noopept on mild cognitive impairment in patients with discirculatory encephalopathy. The present open prospective study included 60 patients with stroke treated with noopept during 12 months. Cognitive functions were assessed before and after treatment using neuropsychological tests. An analysis of MMSE scores and lateral and categorical associations revealed the significant improvement of cognitive functions after 2 months in patients of the main group compared to the controls. The global assessment of efficacy revealed the mild improvement in the main group while no changes were found in the control group. The results have demonstrated that noopept, used in dose 20 mg daily during 2 months, improves cognitive functions in stroke patients and has a high level of safety.

Development of large-scale functional brain networks in children.

PubMed

Supekar, Kaustubh; Musen, Mark; Menon, Vinod

2009-07-01

The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar "small-world" organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism.

Development of Large-Scale Functional Brain Networks in Children

PubMed Central

Supekar, Kaustubh; Musen, Mark; Menon, Vinod

2009-01-01

The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7–9 y) and 22 young-adults (ages 19–22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar “small-world” organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism. PMID:19621066

Transcriptome mining and in silico structural and functional analysis of ascorbic acid and tartaric acid biosynthesis pathway enzymes in rose-scanted geranium.

PubMed

Narnoliya, Lokesh K; Sangwan, Rajender S; Singh, Sudhir P

2018-06-01

Rose-scented geranium (Pelargonium sp.) is widely known as aromatic and medicinal herb, accumulating specialized metabolites of high economic importance, such as essential oils, ascorbic acid, and tartaric acid. Ascorbic acid and tartaric acid are multifunctional metabolites of human value to be used as vital antioxidants and flavor enhancing agents in food products. No information is available related to the structural and functional properties of the enzymes involved in ascorbic acid and tartaric acid biosynthesis in rose-scented geranium. In the present study, transcriptome mining was done to identify full-length genes, followed by their bioinformatic and molecular modeling investigations and understanding of in silico structural and functional properties of these enzymes. Evolutionary conserved domains were identified in the pathway enzymes. In silico physicochemical characterization of the catalytic enzymes revealed isoelectric point (pI), instability index, aliphatic index, and grand average hydropathy (GRAVY) values of the enzymes. Secondary structural prediction revealed abundant proportion of alpha helix and random coil confirmations in the pathway enzymes. Three-dimensional homology models were developed for these enzymes. The predicted structures showed significant structural similarity with their respective templates in root mean square deviation analysis. Ramachandran plot analysis of the modeled enzymes revealed that more than 84% of the amino acid residues were within the favored regions. Further, functionally important residues were identified corresponding to catalytic sites located in the enzymes. To, our best knowledge, this is the first report which provides a foundation on functional annotation and structural determination of ascorbic acid and tartaric acid pathway enzymes in rose-scanted geranium.

Genome-wide analysis of the Dof transcription factor gene family reveals soybean-specific duplicable and functional characteristics.

PubMed

Guo, Yong; Qiu, Li-Juan

2013-01-01

The Dof domain protein family is a classic plant-specific zinc-finger transcription factor family involved in a variety of biological processes. There is great diversity in the number of Dof genes in different plants. However, there are only very limited reports on the characterization of Dof transcription factors in soybean (Glycine max). In the present study, 78 putative Dof genes were identified from the whole-genome sequence of soybean. The predicted GmDof genes were non-randomly distributed within and across 19 out of 20 chromosomes and 97.4% (38 pairs) were preferentially retained duplicate paralogous genes located in duplicated regions of the genome. Soybean-specific segmental duplications contributed significantly to the expansion of the soybean Dof gene family. These Dof proteins were phylogenetically clustered into nine distinct subgroups among which the gene structure and motif compositions were considerably conserved. Comparative phylogenetic analysis of these Dof proteins revealed four major groups, similar to those reported for Arabidopsis and rice. Most of the GmDofs showed specific expression patterns based on RNA-seq data analyses. The expression patterns of some duplicate genes were partially redundant while others showed functional diversity, suggesting the occurrence of sub-functionalization during subsequent evolution. Comprehensive expression profile analysis also provided insights into the soybean-specific functional divergence among members of the Dof gene family. Cis-regulatory element analysis of these GmDof genes suggested diverse functions associated with different processes. Taken together, our results provide useful information for the functional characterization of soybean Dof genes by combining phylogenetic analysis with global gene-expression profiling.

NbIT - A New Information Theory-Based Analysis of Allosteric Mechanisms Reveals Residues that Underlie Function in the Leucine Transporter LeuT

PubMed Central

LeVine, Michael V.; Weinstein, Harel

2014-01-01

Complex networks of interacting residues and microdomains in the structures of biomolecular systems underlie the reliable propagation of information from an input signal, such as the concentration of a ligand, to sites that generate the appropriate output signal, such as enzymatic activity. This information transduction often carries the signal across relatively large distances at the molecular scale in a form of allostery that is essential for the physiological functions performed by biomolecules. While allosteric behaviors have been documented from experiments and computation, the mechanism of this form of allostery proved difficult to identify at the molecular level. Here, we introduce a novel analysis framework, called N-body Information Theory (NbIT) analysis, which is based on information theory and uses measures of configurational entropy in a biomolecular system to identify microdomains and individual residues that act as (i)-channels for long-distance information sharing between functional sites, and (ii)-coordinators that organize dynamics within functional sites. Application of the new method to molecular dynamics (MD) trajectories of the occluded state of the bacterial leucine transporter LeuT identifies a channel of allosteric coupling between the functionally important intracellular gate and the substrate binding sites known to modulate it. NbIT analysis is shown also to differentiate residues involved primarily in stabilizing the functional sites, from those that contribute to allosteric couplings between sites. NbIT analysis of MD data thus reveals rigorous mechanistic elements of allostery underlying the dynamics of biomolecular systems. PMID:24785005

Transcriptome-wide analysis of WRKY transcription factors in wheat and their leaf rust responsive expression profiling.

PubMed

Satapathy, Lopamudra; Singh, Dharmendra; Ranjan, Prashant; Kumar, Dhananjay; Kumar, Manish; Prabhu, Kumble Vinod; Mukhopadhyay, Kunal

2014-12-01

WRKY, a plant-specific transcription factor family, has important roles in pathogen defense, abiotic cues and phytohormone signaling, yet little is known about their roles and molecular mechanism of function in response to rust diseases in wheat. We identified 100 TaWRKY sequences using wheat Expressed Sequence Tag database of which 22 WRKY sequences were novel. Identified proteins were characterized based on their zinc finger motifs and phylogenetic analysis clustered them into six clades consisting of class IIc and class III WRKY proteins. Functional annotation revealed major functions in metabolic and cellular processes in control plants; whereas response to stimuli, signaling and defense in pathogen inoculated plants, their major molecular function being binding to DNA. Tag-based expression analysis of the identified genes revealed differential expression between mock and Puccinia triticina inoculated wheat near isogenic lines. Gene expression was also performed with six rust-related microarray experiments at Gene Expression Omnibus database. TaWRKY10, 15, 17 and 56 were common in both tag-based and microarray-based differential expression analysis and could be representing rust specific WRKY genes. The obtained results will bestow insight into the functional characterization of WRKY transcription factors responsive to leaf rust pathogenesis that can be used as candidate genes in molecular breeding programs to improve biotic stress tolerance in wheat.

Life in Oligotropic Desert Environments: Contrasting Taxonomic and Functional Diversity of Two Microbial Mats with Metagenomics

NASA Astrophysics Data System (ADS)

Bonilla-Rosso, G.; Peimbert, M.; Olmedo, G.; Alcaraz, L. D.; Eguiarte, L. E.; Souza, V.

2010-04-01

The metagenomic analysis of two microbial mats from the oligotrophic waters in the Cuatrociéngas basin reveals large differences both at taxonomic and functional level. These are explained in terms of environmental stability and nutrient availability.

Effect of functionalization of boron nitride flakes by main group metal clusters on their optoelectronic properties

NASA Astrophysics Data System (ADS)

Chakraborty, Debdutta; Chattaraj, Pratim Kumar

2017-10-01

The possibility of functionalizing boron nitride flakes (BNFs) with some selected main group metal clusters, viz. OLi4, NLi5, CLi6, BLI7 and Al12Be, has been analyzed with the aid of density functional theory (DFT) based computations. Thermochemical as well as energetic considerations suggest that all the metal clusters interact with the BNF moiety in a favorable fashion. As a result of functionalization, the static (first) hyperpolarizability (β ) values of the metal cluster supported BNF moieties increase quite significantly as compared to that in the case of pristine BNF. Time dependent DFT analysis reveals that the metal clusters can lower the transition energies associated with the dominant electronic transitions quite significantly thereby enabling the metal cluster supported BNF moieties to exhibit significant non-linear optical activity. Moreover, the studied systems demonstrate broad band absorption capability spanning the UV-visible as well as infra-red domains. Energy decomposition analysis reveals that the electrostatic interactions principally stabilize the metal cluster supported BNF moieties.

Effect of functionalization of boron nitride flakes by main group metal clusters on their optoelectronic properties.

PubMed

Chakraborty, Debdutta; Chattaraj, Pratim Kumar

2017-10-25

The possibility of functionalizing boron nitride flakes (BNFs) with some selected main group metal clusters, viz. OLi 4 , NLi 5 , CLi 6 , BLI 7 and Al 12 Be, has been analyzed with the aid of density functional theory (DFT) based computations. Thermochemical as well as energetic considerations suggest that all the metal clusters interact with the BNF moiety in a favorable fashion. As a result of functionalization, the static (first) hyperpolarizability ([Formula: see text]) values of the metal cluster supported BNF moieties increase quite significantly as compared to that in the case of pristine BNF. Time dependent DFT analysis reveals that the metal clusters can lower the transition energies associated with the dominant electronic transitions quite significantly thereby enabling the metal cluster supported BNF moieties to exhibit significant non-linear optical activity. Moreover, the studied systems demonstrate broad band absorption capability spanning the UV-visible as well as infra-red domains. Energy decomposition analysis reveals that the electrostatic interactions principally stabilize the metal cluster supported BNF moieties.

The use of regression analysis in determining reference intervals for low hematocrit and thrombocyte count in multiple electrode aggregometry and platelet function analyzer 100 testing of platelet function.

PubMed

Kuiper, Gerhardus J A J M; Houben, Rik; Wetzels, Rick J H; Verhezen, Paul W M; Oerle, Rene van; Ten Cate, Hugo; Henskens, Yvonne M C; Lancé, Marcus D

2017-11-01

Low platelet counts and hematocrit levels hinder whole blood point-of-care testing of platelet function. Thus far, no reference ranges for MEA (multiple electrode aggregometry) and PFA-100 (platelet function analyzer 100) devices exist for low ranges. Through dilution methods of volunteer whole blood, platelet function at low ranges of platelet count and hematocrit levels was assessed on MEA for four agonists and for PFA-100 in two cartridges. Using (multiple) regression analysis, 95% reference intervals were computed for these low ranges. Low platelet counts affected MEA in a positive correlation (all agonists showed r 2 ≥ 0.75) and PFA-100 in an inverse correlation (closure times were prolonged with lower platelet counts). Lowered hematocrit did not affect MEA testing, except for arachidonic acid activation (ASPI), which showed a weak positive correlation (r 2 = 0.14). Closure time on PFA-100 testing was inversely correlated with hematocrit for both cartridges. Regression analysis revealed different 95% reference intervals in comparison with originally established intervals for both MEA and PFA-100 in low platelet or hematocrit conditions. Multiple regression analysis of ASPI and both tests on the PFA-100 for combined low platelet and hematocrit conditions revealed that only PFA-100 testing should be adjusted for both thrombocytopenia and anemia. 95% reference intervals were calculated using multiple regression analysis. However, coefficients of determination of PFA-100 were poor, and some variance remained unexplained. Thus, in this pilot study using (multiple) regression analysis, we could establish reference intervals of platelet function in anemia and thrombocytopenia conditions on PFA-100 and in thrombocytopenia conditions on MEA.

Availability Estimate of a Conceptual ESM System.

DTIC Science & Technology

1979-06-01

affect mission operation.t A functional block level failure modes and effects analysis ( FMEA ) performed on the filter resulted in an assessed failure rate...is based on an FMEA of failures that disable the function (see Appendix A). A further 29 examination of the filter piece-parts reveals that the driver...Digital-to-analog converter DC Direct current DF Direction finding ESM Electronic Support Measures FMEA Failure modes and effects analysis FMPO

High-Throughput Analysis of Promoter Occupancy Reveals New Targets for Arx, a Gene Mutated in Mental Retardation and Interneuronopathies

PubMed Central

Quillé, Marie-Lise; Hirchaud, Edouard; Baron, Daniel; Benech, Caroline; Guihot, Jeanne; Placet, Morgane; Mignen, Olivier; Férec, Claude; Houlgatte, Rémi; Friocourt, Gaëlle

2011-01-01

Genetic investigations of X-linked intellectual disabilities have implicated the ARX (Aristaless-related homeobox) gene in a wide spectrum of disorders extending from phenotypes characterised by severe neuronal migration defects such as lissencephaly, to mild or moderate forms of mental retardation without apparent brain abnormalities but with associated features of dystonia and epilepsy. Analysis of Arx spatio-temporal localisation profile in mouse revealed expression in telencephalic structures, mainly restricted to populations of GABAergic neurons at all stages of development. Furthermore, studies of the effects of ARX loss of function in humans and animal models revealed varying defects, suggesting multiple roles of this gene during brain development. However, to date, little is known about how ARX functions as a transcription factor and the nature of its targets. To better understand its role, we combined chromatin immunoprecipitation and mRNA expression with microarray analysis and identified a total of 1006 gene promoters bound by Arx in transfected neuroblastoma (N2a) cells and in mouse embryonic brain. Approximately 24% of Arx-bound genes were found to show expression changes following Arx overexpression or knock-down. Several of the Arx target genes we identified are known to be important for a variety of functions in brain development and some of them suggest new functions for Arx. Overall, these results identified multiple new candidate targets for Arx and should help to better understand the pathophysiological mechanisms of intellectual disability and epilepsy associated with ARX mutations. PMID:21966449

Evolutionary conservation of the polyproline II conformation surrounding intrinsically disordered phosphorylation sites.

PubMed

Elam, W Austin; Schrank, Travis P; Campagnolo, Andrew J; Hilser, Vincent J

2013-04-01

Intrinsically disordered (ID) proteins function in the absence of a unique stable structure and appear to challenge the classic structure-function paradigm. The extent to which ID proteins take advantage of subtle conformational biases to perform functions, and whether signals for such mechanism can be identified in proteome-wide studies is not well understood. Of particular interest is the polyproline II (PII) conformation, suggested to be highly populated in unfolded proteins. We experimentally determine a complete calorimetric propensity scale for the PII conformation. Projection of the scale into representative eukaryotic proteomes reveals significant PII bias in regions coding for ID proteins. Importantly, enrichment of PII in ID proteins, or protein segments, is also captured by other PII scales, indicating that this enrichment is robustly encoded and universally detectable regardless of the method of PII propensity determination. Gene ontology (GO) terms obtained using our PII scale and other scales demonstrate a consensus for molecular functions performed by high PII proteins across the proteome. Perhaps the most striking result of the GO analysis is conserved enrichment (P < 10(-8) ) of phosphorylation sites in high PII regions found by all PII scales. Subsequent conformational analysis reveals a phosphorylation-dependent modulation of PII, suggestive of a conserved "tunability" within these regions. In summary, the application of an experimentally determined polyproline II (PII) propensity scale to proteome-wide sequence analysis and gene ontology reveals an enrichment of PII bias near disordered phosphorylation sites that is conserved throughout eukaryotes. Copyright © 2013 The Protein Society.

Intrinsic Resting-State Functional Connectivity in the Human Spinal Cord at 3.0 T.

PubMed

San Emeterio Nateras, Oscar; Yu, Fang; Muir, Eric R; Bazan, Carlos; Franklin, Crystal G; Li, Wei; Li, Jinqi; Lancaster, Jack L; Duong, Timothy Q

2016-04-01

To apply resting-state functional magnetic resonance (MR) imaging to map functional connectivity of the human spinal cord. Studies were performed in nine self-declared healthy volunteers with informed consent and institutional review board approval. Resting-state functional MR imaging was performed to map functional connectivity of the human cervical spinal cord from C1 to C4 at 1 × 1 × 3-mm resolution with a 3.0-T clinical MR imaging unit. Independent component analysis (ICA) was performed to derive resting-state functional MR imaging z-score maps rendered on two-dimensional and three-dimensional images. Seed-based analysis was performed for cross validation with ICA networks by using Pearson correlation. Reproducibility analysis of resting-state functional MR imaging maps from four repeated trials in a single participant yielded a mean z score of 6 ± 1 (P < .0001). The centroid coordinates across the four trials deviated by 2 in-plane voxels ± 2 mm (standard deviation) and up to one adjacent image section ± 3 mm. ICA of group resting-state functional MR imaging data revealed prominent functional connectivity patterns within the spinal cord gray matter. There were statistically significant (z score > 3, P < .001) bilateral, unilateral, and intersegmental correlations in the ventral horns, dorsal horns, and central spinal cord gray matter. Three-dimensional surface rendering provided visualization of these components along the length of the spinal cord. Seed-based analysis showed that many ICA components exhibited strong and significant (P < .05) correlations, corroborating the ICA results. Resting-state functional MR imaging connectivity networks are qualitatively consistent with known neuroanatomic and functional structures in the spinal cord. Resting-state functional MR imaging of the human cervical spinal cord with a 3.0-T clinical MR imaging unit and standard MR imaging protocols and hardware reveals prominent functional connectivity patterns within the spinal cord gray matter, consistent with known functional and anatomic layouts of the spinal cord.

Computational gene expression profiling under salt stress reveals patterns of co-expression

PubMed Central

Sanchita; Sharma, Ashok

2016-01-01

Plants respond differently to environmental conditions. Among various abiotic stresses, salt stress is a condition where excess salt in soil causes inhibition of plant growth. To understand the response of plants to the stress conditions, identification of the responsible genes is required. Clustering is a data mining technique used to group the genes with similar expression. The genes of a cluster show similar expression and function. We applied clustering algorithms on gene expression data of Solanum tuberosum showing differential expression in Capsicum annuum under salt stress. The clusters, which were common in multiple algorithms were taken further for analysis. Principal component analysis (PCA) further validated the findings of other cluster algorithms by visualizing their clusters in three-dimensional space. Functional annotation results revealed that most of the genes were involved in stress related responses. Our findings suggest that these algorithms may be helpful in the prediction of the function of co-expressed genes. PMID:26981411

Nasal conchae function as aerodynamic baffles: Experimental computational fluid dynamic analysis in a turkey nose (Aves: Galliformes).

PubMed

Bourke, Jason M; Witmer, Lawrence M

2016-12-01

We tested the aerodynamic function of nasal conchae in birds using CT data from an adult male wild turkey (Meleagris gallopavo) to construct 3D models of its nasal passage. A series of digital "turbinectomies" were performed on these models and computational fluid dynamic analyses were performed to simulate resting inspiration. Models with turbinates removed were compared to the original, unmodified control airway. Results revealed that the four conchae found in turkeys, along with the crista nasalis, alter the flow of inspired air in ways that can be considered baffle-like. However, these baffle-like functions were remarkably limited in their areal extent, indicating that avian conchae are more functionally independent than originally hypothesized. Our analysis revealed that the conchae of birds are efficient baffles that-along with potential heat and moisture transfer-serve to efficiently move air to specific regions of the nasal passage. This alternate function of conchae has implications for their evolution in birds and other amniotes. Copyright © 2016 Elsevier B.V. All rights reserved.

Proteins of unknown function in the Protein Data Bank (PDB): an inventory of true uncharacterized proteins and computational tools for their analysis.

PubMed

Nadzirin, Nurul; Firdaus-Raih, Mohd

2012-10-08

Proteins of uncharacterized functions form a large part of many of the currently available biological databases and this situation exists even in the Protein Data Bank (PDB). Our analysis of recent PDB data revealed that only 42.53% of PDB entries (1084 coordinate files) that were categorized under "unknown function" are true examples of proteins of unknown function at this point in time. The remainder 1465 entries also annotated as such appear to be able to have their annotations re-assessed, based on the availability of direct functional characterization experiments for the protein itself, or for homologous sequences or structures thus enabling computational function inference.

DISCO Interacting Protein 2 regulates axonal bifurcation and guidance of Drosophila mushroom body neurons.

PubMed

Nitta, Yohei; Yamazaki, Daisuke; Sugie, Atsushi; Hiroi, Makoto; Tabata, Tetsuya

2017-01-15

Axonal branching is one of the key processes within the enormous complexity of the nervous system to enable a single neuron to send information to multiple targets. However, the molecular mechanisms that control branch formation are poorly understood. In particular, previous studies have rarely addressed the mechanisms underlying axonal bifurcation, in which axons form new branches via splitting of the growth cone. We demonstrate that DISCO Interacting Protein 2 (DIP2) is required for precise axonal bifurcation in Drosophila mushroom body (MB) neurons by suppressing ectopic bifurcation and regulating the guidance of sister axons. We also found that DIP2 localize to the plasma membrane. Domain function analysis revealed that the AMP-synthetase domains of DIP2 are essential for its function, which may involve exerting a catalytic activity that modifies fatty acids. Genetic analysis and subsequent biochemical analysis suggested that DIP2 is involved in the fatty acid metabolization of acyl-CoA. Taken together, our results reveal a function of DIP2 in the developing nervous system and provide a potential functional relationship between fatty acid metabolism and axon morphogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Between Domain Cognitive Dispersion and Functional Abilities in Older Adults

PubMed Central

Fellows, Robert P.; Schmitter-Edgecombe, Maureen

2016-01-01

Objective Within-person variability in cognitive performance is related to neurological integrity, but the association with functional abilities is less clear. The primary aim of this study was to examine the association between cognitive dispersion, or within-person variability, and everyday multitasking and the way in which these variables may influence performance on a naturalistic assessment of functional abilities. Method Participants were 156 community-dwelling adults, age 50 or older. Cognitive dispersion was calculated by measuring within-person variability in cognitive domains, established through principal components analysis. Path analysis was used to determine the independent contribution of cognitive dispersion to functional ability, mediated by multitasking. Results Results of the path analysis revealed that the number of subtasks interweaved (i.e., multitasked) mediated the association between cognitive dispersion and task sequencing and accuracy. Although increased multitasking was associated with worse task performance in the path model, secondary analyses revealed that for individuals with low cognitive dispersion, increased multitasking was associated with better task performance, whereas for those with higher levels of dispersion multitasking was negatively correlated with task performance. Conclusion These results suggest that cognitive dispersion between domains may be a useful indicator of multitasking and daily living skills among older adults. PMID:26300441

Functional Covariance Networks: Obtaining Resting-State Networks from Intersubject Variability

PubMed Central

Gohel, Suril; Di, Xin; Walter, Martin; Biswal, Bharat B.

2012-01-01

Abstract In this study, we investigate a new approach for examining the separation of the brain into resting-state networks (RSNs) on a group level using resting-state parameters (amplitude of low-frequency fluctuation [ALFF], fractional ALFF [fALFF], the Hurst exponent, and signal standard deviation). Spatial independent component analysis is used to reveal covariance patterns of the relevant resting-state parameters (not the time series) across subjects that are shown to be related to known, standard RSNs. As part of the analysis, nonresting state parameters are also investigated, such as mean of the blood oxygen level-dependent time series and gray matter volume from anatomical scans. We hypothesize that meaningful RSNs will primarily be elucidated by analysis of the resting-state functional connectivity (RSFC) parameters and not by non-RSFC parameters. First, this shows the presence of a common influence underlying individual RSFC networks revealed through low-frequency fluctation (LFF) parameter properties. Second, this suggests that the LFFs and RSFC networks have neurophysiological origins. Several of the components determined from resting-state parameters in this manner correlate strongly with known resting-state functional maps, and we term these “functional covariance networks”. PMID:22765879

Genome-Wide Identification and Structural Analysis of bZIP Transcription Factor Genes in Brassica napus.

PubMed

Zhou, Yan; Xu, Daixiang; Jia, Ledong; Huang, Xiaohu; Ma, Guoqiang; Wang, Shuxian; Zhu, Meichen; Zhang, Aoxiang; Guan, Mingwei; Lu, Kun; Xu, Xinfu; Wang, Rui; Li, Jiana; Qu, Cunmin

2017-10-24

The basic region/leucine zipper motif (bZIP) transcription factor family is one of the largest families of transcriptional regulators in plants. bZIP genes have been systematically characterized in some plants, but not in rapeseed ( Brassica napus ). In this study, we identified 247 BnbZIP genes in the rapeseed genome, which we classified into 10 subfamilies based on phylogenetic analysis of their deduced protein sequences. The BnbZIP genes were grouped into functional clades with Arabidopsis genes with similar putative functions, indicating functional conservation. Genome mapping analysis revealed that the BnbZIPs are distributed unevenly across all 19 chromosomes, and that some of these genes arose through whole-genome duplication and dispersed duplication events. All expression profiles of 247 bZIP genes were extracted from RNA-sequencing data obtained from 17 different B . napus ZS11 tissues with 42 various developmental stages. These genes exhibited different expression patterns in various tissues, revealing that these genes are differentially regulated. Our results provide a valuable foundation for functional dissection of the different BnbZIP homologs in B . napus and its parental lines and for molecular breeding studies of bZIP genes in B . napus .

Genome-Wide Identification and Structural Analysis of bZIP Transcription Factor Genes in Brassica napus

PubMed Central

Zhou, Yan; Xu, Daixiang; Jia, Ledong; Huang, Xiaohu; Ma, Guoqiang; Wang, Shuxian; Zhu, Meichen; Zhang, Aoxiang; Guan, Mingwei; Xu, Xinfu; Wang, Rui; Li, Jiana

2017-01-01

The basic region/leucine zipper motif (bZIP) transcription factor family is one of the largest families of transcriptional regulators in plants. bZIP genes have been systematically characterized in some plants, but not in rapeseed (Brassica napus). In this study, we identified 247 BnbZIP genes in the rapeseed genome, which we classified into 10 subfamilies based on phylogenetic analysis of their deduced protein sequences. The BnbZIP genes were grouped into functional clades with Arabidopsis genes with similar putative functions, indicating functional conservation. Genome mapping analysis revealed that the BnbZIPs are distributed unevenly across all 19 chromosomes, and that some of these genes arose through whole-genome duplication and dispersed duplication events. All expression profiles of 247 bZIP genes were extracted from RNA-sequencing data obtained from 17 different B. napus ZS11 tissues with 42 various developmental stages. These genes exhibited different expression patterns in various tissues, revealing that these genes are differentially regulated. Our results provide a valuable foundation for functional dissection of the different BnbZIP homologs in B. napus and its parental lines and for molecular breeding studies of bZIP genes in B. napus. PMID:29064393

Revealing time bunching effect in single-molecule enzyme conformational dynamics.

PubMed

Lu, H Peter

2011-04-21

In this perspective, we focus our discussion on how the single-molecule spectroscopy and statistical analysis are able to reveal enzyme hidden properties, taking the study of T4 lysozyme as an example. Protein conformational fluctuations and dynamics play a crucial role in biomolecular functions, such as in enzymatic reactions. Single-molecule spectroscopy is a powerful approach to analyze protein conformational dynamics under physiological conditions, providing dynamic perspectives on a molecular-level understanding of protein structure-function mechanisms. Using single-molecule fluorescence spectroscopy, we have probed T4 lysozyme conformational motions under the hydrolysis reaction of a polysaccharide of E. coli B cell walls by monitoring the fluorescence resonant energy transfer (FRET) between a donor-acceptor probe pair tethered to T4 lysozyme domains involving open-close hinge-bending motions. Based on the single-molecule spectroscopic results, molecular dynamics simulation, a random walk model analysis, and a novel 2D statistical correlation analysis, we have revealed a time bunching effect in protein conformational motion dynamics that is critical to enzymatic functions. Bunching effect implies that conformational motion times tend to bunch in a finite and narrow time window. We show that convoluted multiple Poisson rate processes give rise to the bunching effect in the enzymatic reaction dynamics. Evidently, the bunching effect is likely common in protein conformational dynamics involving in conformation-gated protein functions. In this perspective, we will also discuss a new approach of 2D regional correlation analysis capable of analyzing fluctuation dynamics of complex multiple correlated and anti-correlated fluctuations under a non-correlated noise background. Using this new method, we are able to map out any defined segments along the fluctuation trajectories and determine whether they are correlated, anti-correlated, or non-correlated; after which, a cross correlation analysis can be applied for each specific segment to obtain a detailed fluctuation dynamics analysis.

Structural landscape of base pairs containing post-transcriptional modifications in RNA

PubMed Central

Seelam, Preethi P.; Sharma, Purshotam

2017-01-01

Base pairs involving post-transcriptionally modified nucleobases are believed to play important roles in a wide variety of functional RNAs. Here we present our attempts toward understanding the structural and functional role of naturally occurring modified base pairs using a combination of X-ray crystal structure database analysis, sequence analysis, and advanced quantum chemical methods. Our bioinformatics analysis reveals that despite their presence in all major secondary structural elements, modified base pairs are most prevalent in tRNA crystal structures and most commonly involve guanine or uridine modifications. Further, analysis of tRNA sequences reveals additional examples of modified base pairs at structurally conserved tRNA regions and highlights the conservation patterns of these base pairs in three domains of life. Comparison of structures and binding energies of modified base pairs with their unmodified counterparts, using quantum chemical methods, allowed us to classify the base modifications in terms of the nature of their electronic structure effects on base-pairing. Analysis of specific structural contexts of modified base pairs in RNA crystal structures revealed several interesting scenarios, including those at the tRNA:rRNA interface, antibiotic-binding sites on the ribosome, and the three-way junctions within tRNA. These scenarios, when analyzed in the context of available experimental data, allowed us to correlate the occurrence and strength of modified base pairs with their specific functional roles. Overall, our study highlights the structural importance of modified base pairs in RNA and points toward the need for greater appreciation of the role of modified bases and their interactions, in the context of many biological processes involving RNA. PMID:28341704

Time-frequency analysis of human motion during rhythmic exercises.

PubMed

Omkar, S N; Vyas, Khushi; Vikranth, H N

2011-01-01

Biomechanical signals due to human movements during exercise are represented in time-frequency domain using Wigner Distribution Function (WDF). Analysis based on WDF reveals instantaneous spectral and power changes during a rhythmic exercise. Investigations were carried out on 11 healthy subjects who performed 5 cycles of sun salutation, with a body-mounted Inertial Measurement Unit (IMU) as a motion sensor. Variance of Instantaneous Frequency (I.F) and Instantaneous Power (I.P) for performance analysis of the subject is estimated using one-way ANOVA model. Results reveal that joint Time-Frequency analysis of biomechanical signals during motion facilitates a better understanding of grace and consistency during rhythmic exercise.

An empirical analysis of the distribution of overshoots in a stationary Gaussian stochastic process

NASA Technical Reports Server (NTRS)

Carter, M. C.; Madison, M. W.

1973-01-01

The frequency distribution of overshoots in a stationary Gaussian stochastic process is analyzed. The primary processes involved in this analysis are computer simulation and statistical estimation. Computer simulation is used to simulate stationary Gaussian stochastic processes that have selected autocorrelation functions. An analysis of the simulation results reveals a frequency distribution for overshoots with a functional dependence on the mean and variance of the process. Statistical estimation is then used to estimate the mean and variance of a process. It is shown that for an autocorrelation function, the mean and the variance for the number of overshoots, a frequency distribution for overshoots can be estimated.

Early Development of Functional Network Segregation Revealed by Connectomic Analysis of the Preterm Human Brain.

PubMed

Cao, Miao; He, Yong; Dai, Zhengjia; Liao, Xuhong; Jeon, Tina; Ouyang, Minhui; Chalak, Lina; Bi, Yanchao; Rollins, Nancy; Dong, Qi; Huang, Hao

2017-03-01

Human brain functional networks are topologically organized with nontrivial connectivity characteristics such as small-worldness and densely linked hubs to support highly segregated and integrated information processing. However, how they emerge and change at very early developmental phases remains poorly understood. Here, we used resting-state functional MRI and voxel-based graph theory analysis to systematically investigate the topological organization of whole-brain networks in 40 infants aged around 31 to 42 postmenstrual weeks. The functional connectivity strength and heterogeneity increased significantly in primary motor, somatosensory, visual, and auditory regions, but much less in high-order default-mode and executive-control regions. The hub and rich-club structures in primary regions were already present at around 31 postmenstrual weeks and exhibited remarkable expansions with age, accompanied by increased local clustering and shortest path length, indicating a transition from a relatively random to a more organized configuration. Moreover, multivariate pattern analysis using support vector regression revealed that individual brain maturity of preterm babies could be predicted by the network connectivity patterns. Collectively, we highlighted a gradually enhanced functional network segregation manner in the third trimester, which is primarily driven by the rapid increases of functional connectivity of the primary regions, providing crucial insights into the topological development patterns prior to birth. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Null missense ABCR (ABCA4) mutations in a family with stargardt disease and retinitis pigmentosa.

PubMed

Shroyer, N F; Lewis, R A; Yatsenko, A N; Lupski, J R

2001-11-01

To determine the type of ABCR mutations that segregate in a family that manifests both Stargardt disease (STGD) and retinitis pigmentosa (RP), and the functional consequences of the underlying mutations. Direct sequencing of all 50 exons and flanking intronic regions of ABCR was performed for the STGD- and RP-affected relatives. RNA hybridization, Western blot analysis, and azido-adenosine triphosphate (ATP) labeling was used to determine the effect of disease-associated ABCR mutations in an in vitro assay system. Compound heterozygous missense mutations were identified in patients with STGD and RP. STGD-affected individual AR682-03 was compound heterozygous for the mutation 2588G-->C and a complex allele, [W1408R; R1640W]. RP-affected individuals AR682-04 and-05 were compound heterozygous for the complex allele [W1408R; R1640W] and the missense mutation V767D. Functional analysis of the mutation V767D by Western blot and ATP binding revealed a severe reduction in protein expression. In vitro analysis of ABCR protein with the mutations W1408R and R1640W showed a moderate effect of these individual mutations on expression and ATP-binding; the complex allele [W1408R; R1640W] caused a severe reduction in protein expression. These data reveal that missense ABCR mutations may be associated with RP. Functional analysis reveals that the RP-associated missense ABCR mutations are likely to be functionally null. These studies of the complex allele W1408R; R1640W suggest a synergistic effect of the individual mutations. These data are congruent with a model in which RP is associated with homozygous null mutations and with the notion that severity of retinal disease is inversely related to residual ABCR activity.

Effects of Intralaminar Thalamic Stimulation on Language Functions

ERIC Educational Resources Information Center

Bhatnagar, Subhash C.; Mandybur, George T.

2005-01-01

Fifteen neurosurgical subjects, who were undergoing thalamic chronic electrode implants as a treatment for dyskinesia and chronic pain, were evaluated on a series of neurolinguistic functions to determine if the stimulation of the centromedianum nucleus of the thalamus affected language and cognitive processing. Analysis of the data revealed that…

LeuT conformational sampling utilizing accelerated molecular dynamics and principal component analysis.

PubMed

Thomas, James R; Gedeon, Patrick C; Grant, Barry J; Madura, Jeffry D

2012-07-03

Monoamine transporters (MATs) function by coupling ion gradients to the transport of dopamine, norepinephrine, or serotonin. Despite their importance in regulating neurotransmission, the exact conformational mechanism by which MATs function remains elusive. To this end, we have performed seven 250 ns accelerated molecular dynamics simulations of the leucine transporter, a model for neurotransmitter MATs. By varying the presence of binding-pocket leucine substrate and sodium ions, we have sampled plausible conformational states representative of the substrate transport cycle. The resulting trajectories were analyzed using principal component analysis of transmembrane helices 1b and 6a. This analysis revealed seven unique structures: two of the obtained conformations are similar to the currently published crystallographic structures, one conformation is similar to a proposed open inward structure, and four conformations represent novel structures of potential importance to the transport cycle. Further analysis reveals that the presence of binding-pocket sodium ions is necessary to stabilize the locked-occluded and open-inward conformations. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Functional mapping of language networks in the normal brain using a word-association task.

PubMed

Ghosh, Shantanu; Basu, Amrita; Kumaran, Senthil S; Khushu, Subash

2010-08-01

Language functions are known to be affected in diverse neurological conditions, including ischemic stroke, traumatic brain injury, and brain tumors. Because language networks are extensive, interpretation of functional data depends on the task completed during evaluation. The aim was to map the hemodynamic consequences of word association using functional magnetic resonance imaging (fMRI) in normal human subjects. Ten healthy subjects underwent fMRI scanning with a postlexical access semantic association task vs lexical processing task. The fMRI protocol involved a T2*-weighted gradient-echo echo-planar imaging (GE-EPI) sequence (TR 4523 ms, TE 64 ms, flip angle 90°) with alternate baseline and activation blocks. A total of 78 scans were taken (interscan interval = 3 s) with a total imaging time of 587 s. Functional data were processed in Statistical Parametric Mapping software (SPM2) with 8-mm Gaussian kernel by convolving the blood oxygenation level-dependent (BOLD) signal with an hemodynamic response function estimated by general linear method to generate SPM{t} and SPM{F} maps. Single subject analysis of the functional data (FWE-corrected, P≤0.001) revealed extensive activation in the frontal lobes, with overlaps among middle frontal gyrus (MFG), superior, and inferior frontal gyri. BOLD activity was also found in the medial frontal gyrus, middle occipital gyrus (MOG), anterior fusiform gyrus, superior and inferior parietal lobules, and to a smaller extent, the thalamus and right anterior cerebellum. Group analysis (FWE-corrected, P≤0.001) revealed neural recruitment of bilateral lingual gyri, left MFG, bilateral MOG, left superior occipital gyrus, left fusiform gyrus, bilateral thalami, and right cerebellar areas. Group data analysis revealed a cerebellar-occipital-fusiform-thalamic network centered around bilateral lingual gyri for word association, thereby indicating how these areas facilitate language comprehension by activating a semantic association network of words processed postlexical access. This finding is important when assessing the extent of cognitive damage and/or recovery and can be used for presurgical planning after optimization.

Preface Sections in English and Arabic Linguistics Books: A Rhetorico-Cultural Analysis

ERIC Educational Resources Information Center

Al-Zubaidi, Nassier A. G.; Jasim, Tahani Awad

2016-01-01

The present paper is a genre analysis of linguistics books prefaces in English and Arabic. Following Swales' (1990) genre framework, this study is a small scale-based generic analysis of 80 preface texts, equally divided into 40 texts from English and Arabic. The corpus analysis revealed that to perform its communicative function, the genre of the…

A novel analysis strategy for integrating methylation and expression data reveals core pathways for thyroid cancer aetiology

PubMed Central

2015-01-01

Background Recently, a wide range of diseases have been associated with changes in DNA methylation levels, which play a vital role in gene expression regulation. With ongoing developments in technology, attempts to understand disease mechanism have benefited greatly from epigenetics and transcriptomics studies. In this work, we have used expression and methylation data of thyroid carcinoma as a case study and explored how to optimally incorporate expression and methylation information into the disease study when both data are available. Moreover, we have also investigated whether there are important post-translational modifiers which could drive critical insights on thyroid cancer genetics. Results In this study, we have conducted a threshold analysis for varying methylation levels to identify whether setting a methylation level threshold increases the performance of functional enrichment. Moreover, in order to decide on best-performing analysis strategy, we have performed data integration analysis including comparison of 10 different analysis strategies. As a result, combining methylation with expression and using genes with more than 15% methylation change led to optimal detection rate of thyroid-cancer associated pathways in top 20 functional enrichment results. Furthermore, pooling the data from different experiments increased analysis confidence by improving the data range. Consequently, we have identified 207 transcription factors and 245 post-translational modifiers with more than 15% methylation change which may be important in understanding underlying mechanisms of thyroid cancer. Conclusion While only expression or only methylation information would not reveal both primary and secondary mechanisms involved in disease state, combining expression and methylation led to a better detection of thyroid cancer-related genes and pathways that are found in the recent literature. Moreover, focusing on genes that have certain level of methylation change improved the functional enrichment results, revealing the core pathways involved in disease development such as; endocytosis, apoptosis, glutamatergic synapse, MAPK, ErbB, TGF-beta and Toll-like receptor pathways. Overall, in addition to novel analysis framework, our study reveals important thyroid-cancer related mechanisms, secondary molecular alterations and contributes to better knowledge of thyroid cancer aetiology. PMID:26678064

Dynamics of Intersubject Brain Networks during Anxious Anticipation

PubMed Central

Najafi, Mahshid; Kinnison, Joshua; Pessoa, Luiz

2017-01-01

How do large-scale brain networks reorganize during the waxing and waning of anxious anticipation? Here, threat was dynamically modulated during human functional MRI as two circles slowly meandered on the screen; if they touched, an unpleasant shock was delivered. We employed intersubject correlation analysis, which allowed the investigation of network-level functional connectivity across brains, and sought to determine how network connectivity changed during periods of approach (circles moving closer) and periods of retreat (circles moving apart). Analysis of positive connection weights revealed that dynamic threat altered connectivity within and between the salience, executive, and task-negative networks. For example, dynamic functional connectivity increased within the salience network during approach and decreased during retreat. The opposite pattern was found for the functional connectivity between the salience and task-negative networks: decreases during approach and increases during approach. Functional connections between subcortical regions and the salience network also changed dynamically during approach and retreat periods. Subcortical regions exhibiting such changes included the putative periaqueductal gray, putative habenula, and putative bed nucleus of the stria terminalis. Additional analysis of negative functional connections revealed dynamic changes, too. For example, negative weights within the salience network decreased during approach and increased during retreat, opposite what was found for positive weights. Together, our findings unraveled dynamic features of functional connectivity of large-scale networks and subcortical regions across participants while threat levels varied continuously, and demonstrate the potential of characterizing emotional processing at the level of dynamic networks. PMID:29209184

The phosphoproteome of Aspergillus nidulans reveals functional association with cellular processes involved in morphology and secretion.

PubMed

Ramsubramaniam, Nikhil; Harris, Steven D; Marten, Mark R

2014-11-01

We describe the first phosphoproteome of the model filamentous fungus Aspergillus nidulans. Phosphopeptides were enriched using titanium dioxide, separated using a convenient ultra-long reverse phase gradient, and identified using a "high-high" strategy (high mass accuracy on the parent and fragment ions) with higher-energy collisional dissociation. Using this approach 1801 phosphosites, from 1637 unique phosphopeptides, were identified. Functional classification revealed phosphoproteins were overrepresented under GO categories related to fungal morphogenesis: "sites of polar growth," "vesicle mediated transport," and "cytoskeleton organization." In these same GO categories, kinase-substrate analysis of phosphoproteins revealed the majority were target substrates of CDK and CK2 kinase families, indicating these kinase families play a prominent role in fungal morphogenesis. Kinase-substrate analysis also identified 57 substrates for kinases known to regulate secretion of hydrolytic enzymes (e.g. PkaA, SchA, and An-Snf1). Altogether this data will serve as a benchmark that can be used to elucidate regulatory networks functionally associated with fungal morphogenesis and secretion. All MS data have been deposited in the ProteomeXchange with identifier PXD000715 (http://proteomecentral.proteomexchange.org/dataset/PXD000715). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Interaction Properties of the Human Rab GTPase Family – A Comparative Analysis Reveals Determinants of Molecular Binding Selectivity

PubMed Central

Stein, Matthias; Pilli, Manohar; Bernauer, Sabine; Habermann, Bianca H.; Zerial, Marino; Wade, Rebecca C.

2012-01-01

Background Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood. Methodology/Principal Findings Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics. Conclusions/Significance We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity. PMID:22523562

Visual target modulation of functional connectivity networks revealed by self-organizing group ICA.

PubMed

van de Ven, Vincent; Bledowski, Christoph; Prvulovic, David; Goebel, Rainer; Formisano, Elia; Di Salle, Francesco; Linden, David E J; Esposito, Fabrizio

2008-12-01

We applied a data-driven analysis based on self-organizing group independent component analysis (sogICA) to fMRI data from a three-stimulus visual oddball task. SogICA is particularly suited to the investigation of the underlying functional connectivity and does not rely on a predefined model of the experiment, which overcomes some of the limitations of hypothesis-driven analysis. Unlike most previous applications of ICA in functional imaging, our approach allows the analysis of the data at the group level, which is of particular interest in high order cognitive studies. SogICA is based on the hierarchical clustering of spatially similar independent components, derived from single subject decompositions. We identified four main clusters of components, centered on the posterior cingulate, bilateral insula, bilateral prefrontal cortex, and right posterior parietal and prefrontal cortex, consistently across all participants. Post hoc comparison of time courses revealed that insula, prefrontal cortex and right fronto-parietal components showed higher activity for targets than for distractors. Activation for distractors was higher in the posterior cingulate cortex, where deactivation was observed for targets. While our results conform to previous neuroimaging studies, they also complement conventional results by showing functional connectivity networks with unique contributions to the task that were consistent across subjects. SogICA can thus be used to probe functional networks of active cognitive tasks at the group-level and can provide additional insights to generate new hypotheses for further study. Copyright 2007 Wiley-Liss, Inc.

Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.

PubMed

Bock, J; Breuer, S; Poeggel, G; Braun, K

2017-03-01

In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using ( 14 C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.

Single-hole spectral function and spin-charge separation in the t-J model

NASA Astrophysics Data System (ADS)

Mishchenko, A. S.; Prokof'ev, N. V.; Svistunov, B. V.

2001-07-01

Worm algorithm Monte Carlo simulations of the hole Green function with subsequent spectral analysis were performed for 0.1<=J/t<=0.4 on lattices with up to L×L=32×32 sites at a temperature as low as T=J/40, and present, apparently, the hole spectral function in the thermodynamic limit. Spectral analysis reveals a δ-function-sharp quasiparticle peak at the lower edge of the spectrum that is incompatible with the power-law singularity and thus rules out the possibility of spin-charge separation in this parameter range. Spectral continuum features two peaks separated by a gap ~4÷5 t.

Alterations in the coupling functions between cortical and cardio-respiratory oscillations due to anaesthesia with propofol and sevoflurane

NASA Astrophysics Data System (ADS)

Stankovski, Tomislav; Petkoski, Spase; Raeder, Johan; Smith, Andrew F.; McClintock, Peter V. E.; Stefanovska, Aneta

2016-05-01

The precise mechanisms underlying general anaesthesia pose important and still open questions. To address them, we have studied anaesthesia induced by the widely used (intravenous) propofol and (inhalational) sevoflurane anaesthetics, computing cross-frequency coupling functions between neuronal, cardiac and respiratory oscillations in order to determine their mutual interactions. The phase domain coupling function reveals the form of the function defining the mechanism of an interaction, as well as its coupling strength. Using a method based on dynamical Bayesian inference, we have thus identified and analysed the coupling functions for six relationships. By quantitative assessment of the forms and strengths of the couplings, we have revealed how these relationships are altered by anaesthesia, also showing that some of them are differently affected by propofol and sevoflurane. These findings, together with the novel coupling function analysis, offer a new direction in the assessment of general anaesthesia and neurophysiological interactions, in general.

Proteomic analysis of chromoplasts from six crop species reveals insights into chromoplast function and development

USDA-ARS?s Scientific Manuscript database

Chromoplasts are unique plastids that accumulate massive amounts of carotenoids. To gain a general and comparative characterization of chromoplast proteins, we performed proteomic analysis of chromoplasts from six carotenoid-rich crops: watermelon, tomato, carrot, orange cauliflower, red papaya, and...

Trophic hierarchies revealed via amino acid isotopic analysis

USDA-ARS?s Scientific Manuscript database

Despite the potential of isotopic methods to illuminate trophic function, accurate estimates of lifetime feeding tendencies have remained elusive. A relatively new approach—referred to as compound-specific isotopic analysis (CSIA)—has emerged, centering on the measurement of 15N:14N ratios in amino ...

Authentic Discourse and the Survival English Curriculum.

ERIC Educational Resources Information Center

Cathcart, Ruth Larimer

1989-01-01

In-depth analysis of topic distribution, utterance functions, and structural and lexical elements in a doctor-patient interaction revealed significant differences between authentic discourse and English-as-a-Second-Language text discourse, suggesting a need for better collection of more authentic data, for a distributional analysis of…

Identification and functional analysis of the aspergillic acid gene cluster in Aspergillus flavus

USDA-ARS?s Scientific Manuscript database

Aspergillus flavus can colonize important food staples and produces aflatoxins, toxic and carcinogenic secondary metabolites. In silico analysis of the A. flavus genome revealed 56 gene clusters encoding for secondary metabolites. How these many of these metabolites affect fungal development, surviv...

Fungal proteomics: from identification to function.

PubMed

Doyle, Sean

2011-08-01

Some fungi cause disease in humans and plants, while others have demonstrable potential for the control of insect pests. In addition, fungi are also a rich reservoir of therapeutic metabolites and industrially useful enzymes. Detailed analysis of fungal biochemistry is now enabled by multiple technologies including protein mass spectrometry, genome and transcriptome sequencing and advances in bioinformatics. Yet, the assignment of function to fungal proteins, encoded either by in silico annotated, or unannotated genes, remains problematic. The purpose of this review is to describe the strategies used by many researchers to reveal protein function in fungi, and more importantly, to consolidate the nomenclature of 'unknown function protein' as opposed to 'hypothetical protein' - once any protein has been identified by protein mass spectrometry. A combination of approaches including comparative proteomics, pathogen-induced protein expression and immunoproteomics are outlined, which, when used in combination with a variety of other techniques (e.g. functional genomics, microarray analysis, immunochemical and infection model systems), appear to yield comprehensive and definitive information on protein function in fungi. The relative advantages of proteomic, as opposed to transcriptomic-only, analyses are also described. In the future, combined high-throughput, quantitative proteomics, allied to transcriptomic sequencing, are set to reveal much about protein function in fungi. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Social Cognitive Training for Schizophrenia: A Meta-Analytic Investigation of Controlled Research

PubMed Central

Kurtz, Matthew M.; Richardson, Christi L.

2012-01-01

A wealth of evidence has revealed that deficits in social cognitive skills (including facial affect recognition (FAR), social cue perception, Theory of Mind (ToM), and attributional style) are evident in schizophrenia and are linked to a variety of domains of functional outcome. In light of these associations, a growing number of studies have attempted to ameliorate these deficits as a means of improving outcome in the disorder through the use of structured behavioral training. This study used quantitative methods of meta-analysis to assess the efficacy of behavioral training programs designed to improve social cognitive function. A total of 19 studies consisting of 692 clients were aggregated from relevant databases. Outcome measures were organized according to whether they were social cognitive tests proximal to the intervention or whether they represented measures of treatment generalization (symptoms, observer-rated community, and institutional function). With respect to social cognitive measures, weighted effect-size analysis revealed that there were moderate-large effects of social cognitive training procedures on FAR (identification, d = 0.71 and discrimination, d = 1.01) and small-moderate effects of training on ToM (d = 0.46), while effects on social cue perception and attributional style were not significant. For measures of generalization, weighted effect-size analysis revealed that there were moderate-large effect on total symptoms (d = 0.68) and observer-rated community and institutional function (d = 0.78). Effects of social cognitive training programs on positive and negative symptoms of schizophrenia were nonsignificant. Moderating variables and implications for future research and treatment development are discussed. PMID:21525166

[The post-discectomy syndrome: clinical and electroneuromyographic characteristics and methods of treatment].

PubMed

Musaev, A V; Guseĭnova, S G; Musaeva, I R

2008-01-01

The data of the Azerbaijan Neurosurgical Center, including 2618 case-reports of patients operated on for low back discal hernia between 1997 and 2002, have been analyzed. The retrospective analysis of the data reveals that 26,4% of patients need further restorative treatment due to the presence of various neurological disturbances: pain syndromes of different intensity, motor deficits (pareses), sensory disorders and functional disorders of pelvic organs. The retrospective analysis of the data reveals that 26,4% of patients need further restorative treatment due to the presence of various neurological disturbances: pain syndromes of different intensity, motor deficits (pareses), sensory disorders and functional disorders of pelvic organs. Along with these data, the results of our own clinical and neurophysiological study of 110 patients have been summarized as well. Along with these data, the results of our own clinical and neurophysiological study of 110 patients have been summarized as well. A high effectiveness of electrostimulation and naphthalan therapy alone and in combination with massage and medical gymnastics has been revealed. A high effectiveness of electrostimulation and naphthalan therapy alone and in combination with massage and medical gymnastics has been revealed. Electroneuromyographic data revealing the positive dynamics as a result of the treatment of patients with the post-discectomy syndrome are presented. Electroneuromyographic data revealing the positive dynamics as a result of the treatment of patients with the post-discectomy syndrome are presented.

Classical test theory and Rasch analysis validation of the Upper Limb Functional Index in subjects with upper limb musculoskeletal disorders.

PubMed

Bravini, Elisabetta; Franchignoni, Franco; Giordano, Andrea; Sartorio, Francesco; Ferriero, Giorgio; Vercelli, Stefano; Foti, Calogero

2015-01-01

To perform a comprehensive analysis of the psychometric properties and dimensionality of the Upper Limb Functional Index (ULFI) using both classical test theory and Rasch analysis (RA). Prospective, single-group observational design. Freestanding rehabilitation center. Convenience sample of Italian-speaking subjects with upper limb musculoskeletal disorders (N=174). Not applicable. The Italian version of the ULFI. Data were analyzed using parallel analysis, exploratory factor analysis, and RA for evaluating dimensionality, functioning of rating scale categories, item fit, hierarchy of item difficulties, and reliability indices. Parallel analysis revealed 2 factors explaining 32.5% and 10.7% of the response variance. RA confirmed the failure of the unidimensionality assumption, and 6 items out of the 25 misfitted the Rasch model. When the analysis was rerun excluding the misfitting items, the scale showed acceptable fit values, loading meaningfully to a single factor. Item separation reliability and person separation reliability were .98 and .89, respectively. Cronbach alpha was .92. RA revealed weakness of the scale concerning dimensionality and internal construct validity. However, a set of 19 ULFI items defined through the statistical process demonstrated a unidimensional structure, good psychometric properties, and clinical meaningfulness. These findings represent a useful starting point for further analyses of the tool (based on modern psychometric approaches and confirmatory factor analysis) in larger samples, including different patient populations and nationalities. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

A new methodology based on functional principal component analysis to study postural stability post-stroke.

PubMed

Sánchez-Sánchez, M Luz; Belda-Lois, Juan-Manuel; Mena-Del Horno, Silvia; Viosca-Herrero, Enrique; Igual-Camacho, Celedonia; Gisbert-Morant, Beatriz

2018-05-05

A major goal in stroke rehabilitation is the establishment of more effective physical therapy techniques to recover postural stability. Functional Principal Component Analysis provides greater insight into recovery trends. However, when missing values exist, obtaining functional data presents some difficulties. The purpose of this study was to reveal an alternative technique for obtaining the Functional Principal Components without requiring the conversion to functional data beforehand and to investigate this methodology to determine the effect of specific physical therapy techniques in balance recovery trends in elderly subjects with hemiplegia post-stroke. A randomized controlled pilot trial was developed. Thirty inpatients post-stroke were included. Control and target groups were treated with the same conventional physical therapy protocol based on functional criteria, but specific techniques were added to the target group depending on the subjects' functional level. Postural stability during standing was quantified by posturography. The assessments were performed once a month from the moment the participants were able to stand up to six months post-stroke. The target group showed a significant improvement in postural control recovery trend six months after stroke that was not present in the control group. Some of the assessed parameters revealed significant differences between treatment groups (P < 0.05). The proposed methodology allows Functional Principal Component Analysis to be performed when data is scarce. Moreover, it allowed the dynamics of recovery of two different treatment groups to be determined, showing that the techniques added in the target group increased postural stability compared to the base protocol. Copyright © 2018 Elsevier Ltd. All rights reserved.

Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

PubMed

Ferreira, Ari J S; Siam, Rania; Setubal, João C; Moustafa, Ahmed; Sayed, Ahmed; Chambergo, Felipe S; Dawe, Adam S; Ghazy, Mohamed A; Sharaf, Hazem; Ouf, Amged; Alam, Intikhab; Abdel-Haleem, Alyaa M; Lehvaslaiho, Heikki; Ramadan, Eman; Antunes, André; Stingl, Ulrich; Archer, John A C; Jankovic, Boris R; Sogin, Mitchell; Bajic, Vladimir B; El-Dorry, Hamza

2014-01-01

Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

Core Microbial Functional Activities in Ocean Environments Revealed by Global Metagenomic Profiling Analyses

PubMed Central

Ferreira, Ari J. S.; Siam, Rania; Setubal, João C.; Moustafa, Ahmed; Sayed, Ahmed; Chambergo, Felipe S.; Dawe, Adam S.; Ghazy, Mohamed A.; Sharaf, Hazem; Ouf, Amged; Alam, Intikhab; Abdel-Haleem, Alyaa M.; Lehvaslaiho, Heikki; Ramadan, Eman; Antunes, André; Stingl, Ulrich; Archer, John A. C.; Jankovic, Boris R.; Sogin, Mitchell; Bajic, Vladimir B.; El-Dorry, Hamza

2014-01-01

Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light. PMID:24921648

Resting state fMRI reveals a default mode dissociation between retrosplenial and medial prefrontal subnetworks in ASD despite motion scrubbing.

PubMed

Starck, Tuomo; Nikkinen, Juha; Rahko, Jukka; Remes, Jukka; Hurtig, Tuula; Haapsamo, Helena; Jussila, Katja; Kuusikko-Gauffin, Sanna; Mattila, Marja-Leena; Jansson-Verkasalo, Eira; Pauls, David L; Ebeling, Hanna; Moilanen, Irma; Tervonen, Osmo; Kiviniemi, Vesa J

2013-01-01

In resting state functional magnetic resonance imaging (fMRI) studies of autism spectrum disorders (ASDs) decreased frontal-posterior functional connectivity is a persistent finding. However, the picture of the default mode network (DMN) hypoconnectivity remains incomplete. In addition, the functional connectivity analyses have been shown to be susceptible even to subtle motion. DMN hypoconnectivity in ASD has been specifically called for re-evaluation with stringent motion correction, which we aimed to conduct by so-called scrubbing. A rich set of default mode subnetworks can be obtained with high dimensional group independent component analysis (ICA) which can potentially provide more detailed view of the connectivity alterations. We compared the DMN connectivity in high-functioning adolescents with ASDs to typically developing controls using ICA dual-regression with decompositions from typical to high dimensionality. Dual-regression analysis within DMN subnetworks did not reveal alterations but connectivity between anterior and posterior DMN subnetworks was decreased in ASD. The results were very similar with and without motion scrubbing thus indicating the efficacy of the conventional motion correction methods combined with ICA dual-regression. Specific dissociation between DMN subnetworks was revealed on high ICA dimensionality, where networks centered at the medial prefrontal cortex and retrosplenial cortex showed weakened coupling in adolescents with ASDs compared to typically developing control participants. Generally the results speak for disruption in the anterior-posterior DMN interplay on the network level whereas local functional connectivity in DMN seems relatively unaltered.

Representation of the Physiological Factors Contributing to Postflight Changes in Functional Performance Using Motion Analysis Software

NASA Technical Reports Server (NTRS)

Parks, Kelsey

2010-01-01

Astronauts experience changes in multiple physiological systems due to exposure to the microgravity conditions of space flight. To understand how changes in physiological function influence functional performance, a testing procedure has been developed that evaluates both astronaut postflight functional performance and related physiological changes. Astronauts complete seven functional and physiological tests. The objective of this project is to use motion tracking and digitizing software to visually display the postflight decrement in the functional performance of the astronauts. The motion analysis software will be used to digitize astronaut data videos into stick figure videos to represent the astronauts as they perform the Functional Tasks Tests. This project will benefit NASA by allowing NASA scientists to present data of their neurological studies without revealing the identities of the astronauts.

The Functions of Immediate Echolalia in Autistic Children.

ERIC Educational Resources Information Center

Prizant, Barry M.; Duchan, Judith F.

1981-01-01

A multilevel analysis of verbal and nonverbal factors, response latency, and intonation, in four autistic boys (4 to 9 years old) revealed that immediate echolalia is far more than a meaningless behavior. Seven functional categories of echolalia were discovered and are discussed in reference to behavioral and linguistic features of each category.…

Informatic and genomic analysis of melanocyte cDNA libraries as a resource for the study of melanocyte development and function.

PubMed

Baxter, Laura L; Hsu, Benjamin J; Umayam, Lowell; Wolfsberg, Tyra G; Larson, Denise M; Frith, Martin C; Kawai, Jun; Hayashizaki, Yoshihide; Carninci, Piero; Pavan, William J

2007-06-01

As part of the RIKEN mouse encyclopedia project, two cDNA libraries were prepared from melanocyte-derived cell lines, using techniques of full-length clone selection and subtraction/normalization to enrich for rare transcripts. End sequencing showed that these libraries display over 83% complete coding sequence at the 5' end and 96-97% complete coding sequence at the 3' end. Evaluation of the libraries, derived from B16F10Y tumor cells and melan-c cells, revealed that they contain clones for a majority of the genes previously demonstrated to function in melanocyte biology. Analysis of genomic locations for transcripts revealed that the distribution of melanocyte genes is non-random throughout the genome. Three genomic regions identified that showed significant clustering of melanocyte-expressed genes contain one or more genes previously shown to regulate melanocyte development or function. A catalog of genes expressed in these libraries is presented, providing a valuable resource of cDNA clones and sequence information that can be used for identification of new genes important for melanocyte development, function, and disease.

AIRE is a critical spindle-associated protein in embryonic stem cells

PubMed Central

Gu, Bin; Lambert, Jean-Philippe; Cockburn, Katie; Gingras, Anne-Claude; Rossant, Janet

2017-01-01

Embryonic stem (ES) cells go though embryo-like cell cycles regulated by specialized molecular mechanisms. However, it is not known whether there are ES cell-specific mechanisms regulating mitotic fidelity. Here we showed that Autoimmune Regulator (Aire), a transcription coordinator involved in immune tolerance processes, is a critical spindle-associated protein in mouse ES(mES) cells. BioID analysis showed that AIRE associates with spindle-associated proteins in mES cells. Loss of function analysis revealed that Aire was important for centrosome number regulation and spindle pole integrity specifically in mES cells. We also identified the c-terminal LESLL motif as a critical motif for AIRE’s mitotic function. Combined maternal and zygotic knockout further revealed Aire’s critical functions for spindle assembly in preimplantation embryos. These results uncovered a previously unappreciated function for Aire and provide new insights into the biology of stem cell proliferation and potential new angles to understand fertility defects in humans carrying Aire mutations. DOI: http://dx.doi.org/10.7554/eLife.28131.001 PMID:28742026

Structural, functional and pH sensitive release characteristics of water-soluble polysaccharide from the seeds of Albizia lebbeck L.

PubMed

Kumar Varma, Chekuri Ashok; Jayaram Kumar, K

2017-11-01

Plant polysaccharides, generally regarded as safe (GRAS), are gaining importance as excipients in drug delivery. Therefore, the current paper presents the studies on structural, functional and drug release study of water soluble polysaccharide (ALPS) from seeds of Albizia lebbeck L. High swelling, water holding capacity, foam stability and lower moisture content suggests its use as additive in food preparations. The apparent molecular weight of polysaccharide was found to be 1.98×10 2 kDa. Monosaccharide composition analysis indicated that ALPS consists of mannose (4.06%), rhamnose (22.79%), glucose (38.9%), galactose (17.84%) and xylose (16.42%). Micromeritic properties revealed that the polysaccharide possess potential for pharmaceutical applications. From the surface charge analysis, ALPS was found to be non-ionic polysaccharide. Morphological study reveals the polysaccharide with irregular particle shape and rough surface. Fourier transformed infrared spectroscopy (FTIR) study confirms the carbohydrate nature of polysaccharide. From the thermogravimetric analysis (TGA) data, the second mass loss (243-340°C) attributed to polysaccharide degradation. The drug release profile reveals the use of polysaccharide for the preparation of pH sensitive pharmaceutical dosage forms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microbial Communities and Functional Genes Associated with Soil Arsenic Contamination and the Rhizosphere of the Arsenic-Hyperaccumulating Plant Pteris vittata L. ▿ †

PubMed Central

Xiong, Jinbo; Wu, Liyou; Tu, Shuxin; Van Nostrand, Joy D.; He, Zhili; Zhou, Jizhong; Wang, Gejiao

2010-01-01

To understand how microbial communities and functional genes respond to arsenic contamination in the rhizosphere of Pteris vittata, five soil samples with different arsenic contamination levels were collected from the rhizosphere of P. vittata and nonrhizosphere areas and investigated by Biolog, geochemical, and functional gene microarray (GeoChip 3.0) analyses. Biolog analysis revealed that the uncontaminated soil harbored the greatest diversity of sole-carbon utilization abilities and that arsenic contamination decreased the metabolic diversity, while rhizosphere soils had higher metabolic diversities than did the nonrhizosphere soils. GeoChip 3.0 analysis showed low proportions of overlapping genes across the five soil samples (16.52% to 45.75%). The uncontaminated soil had a higher heterogeneity and more unique genes (48.09%) than did the arsenic-contaminated soils. Arsenic resistance, sulfur reduction, phosphorus utilization, and denitrification genes were remarkably distinct between P. vittata rhizosphere and nonrhizosphere soils, which provides evidence for a strong linkage among the level of arsenic contamination, the rhizosphere, and the functional gene distribution. Canonical correspondence analysis (CCA) revealed that arsenic is the main driver in reducing the soil functional gene diversity; however, organic matter and phosphorus also have significant effects on the soil microbial community structure. The results implied that rhizobacteria play an important role during soil arsenic uptake and hyperaccumulation processes of P. vittata. PMID:20833780

Differential involvement of the extracellular 6-O-endosulfatases Sulf1 and Sulf2 in brain development and neuronal and behavioural plasticity

PubMed Central

Kalus, Ina; Salmen, Benedikt; Viebahn, Christoph; von Figura, Kurt; Schmitz, Dietmar; D'Hooge, Rudi; Dierks, Thomas

2009-01-01

The extracellular sulfatases Sulf1 and Sulf2 remove specific 6-O-sulfate groups from heparan sulfate, thereby modulating numerous signalling pathways underlying development and homeostasis. In vitro data have suggested that the two enzymes show functional redundancy. To elucidate their in vivo functions and to further address the question of a putative redundancy, we have generated Sulf1- and Sulf2-deficient mice. Phenotypic analysis of these animals revealed higher embryonic lethality of Sulf2 knockout mice, which can be associated with neuroanatomical malformations during embryogenesis. Sulf1 seems not to be essential for developmental or postnatal viability, as mice deficient in this sulfatase show no overt phenotype. However, neurite outgrowth deficits were observed in hippocampal and cerebellar neurons of both mutant mouse lines, suggesting that not only Sulf2 but also Sulf1 function plays a role in the developing nervous system. Behavioural analysis revealed differential deficits with regard to cage activity and spatial learning for Sulf1- and Sulf2-deficient mouse lines. In addition, Sulf1-specific deficits were shown for synaptic plasticity in the CA1 region of the hippocampus, associated with a reduced spine density. These results reveal that Sulf1 and Sulf2 fulfil non-redundant functions in vivo in the development and maintenance of the murine nervous system. PMID:20394677

Re-orienting discussions of scientific explanation: A functional perspective.

PubMed

Woody, Andrea I

2015-08-01

Philosophy of science offers a rich lineage of analysis concerning the nature of scientific explanation, but the vast majority of this work, aiming to provide an analysis of the relation that binds a given explanans to its corresponding explanandum, presumes the proper analytic focus rests at the level of individual explanations. There are, however, other questions we could ask about explanation in science, such as: What role(s) does explanatory practice play in science? Shifting focus away from explanations, as achievements, toward explaining, as a coordinated activity of communities, the functional perspective aims to reveal how the practice of explanatory discourse functions within scientific communities given their more comprehensive aims and practices. In this paper, I outline the functional perspective, argue that taking the functional perspective can reveal important methodological roles for explanation in science, and consequently, that beginning here provides resources for developing more adequate responses to traditional concerns. In particular, through an examination of the ideal gas law, I emphasize the normative status of explanations within scientific communities and discuss how such status underwrites a compelling rationale for explanatory power as a theoretical virtue. Copyright © 2015 Elsevier Ltd. All rights reserved.

Novel candidate genes of the PARK7 interactome as mediators of apoptosis and acetylation in multiple sclerosis: An in silico analysis.

PubMed

Vavougios, George D; Zarogiannis, Sotirios G; Krogfelt, Karen Angeliki; Gourgoulianis, Konstantinos; Mitsikostas, Dimos Dimitrios; Hadjigeorgiou, Georgios

2018-01-01

currently only 4 studies have explored the potential role of PARK7's dysregulation in MS pathophysiology Currently, no study has evaluated the potential role of the PARK7 interactome in MS. The aim of our study was to assess the differential expression of PARK7 mRNA in peripheral blood mononuclears (PBMCs) donated from MS versus healthy patients using data mining techniques. The PARK7 interactome data from the GDS3920 profile were scrutinized for differentially expressed genes (DEGs); Gene Enrichment Analysis (GEA) was used to detect significantly enriched biological functions. 27 differentially expressed genes in the MS dataset were detected; 12 of these (NDUFA4, UBA2, TDP2, NPM1, NDUFS3, SUMO1, PIAS2, KIAA0101, RBBP4, NONO, RBBP7 AND HSPA4) are reported for the first time in MS. Stepwise Linear Discriminant Function Analysis constructed a predictive model (Wilk's λ = 0.176, χ 2 = 45.204, p = 1.5275e -10 ) with 2 variables (TIDP2, RBBP4) that achieved 96.6% accuracy when discriminating between patients and controls. Gene Enrichment Analysis revealed that induction and regulation of programmed / intrinsic cell death represented the most salient Gene Ontology annotations. Cross-validation on systemic lupus erythematosus and ischemic stroke datasets revealed that these functions are unique to the MS dataset. Based on our results, novel potential target genes are revealed; these differentially expressed genes regulate epigenetic and apoptotic pathways that may further elucidate underlying mechanisms of autorreactivity in MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Structure of an Arrestin2-clathrin Complex Reveals a Novel Clathrin Binding Domain that Modulates Receptor Trafficking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, D.; Kern, R; Puthenveedu, M

2009-01-01

Non-visual arrestins play a pivotal role as adaptor proteins in regulating the signaling and trafficking of multiple classes of receptors. Although arrestin interaction with clathrin, AP-2, and phosphoinositides contributes to receptor trafficking, little is known about the configuration and dynamics of these interactions. Here, we identify a novel interface between arrestin2 and clathrin through x-ray diffraction analysis. The intrinsically disordered clathrin binding box of arrestin2 interacts with a groove between blades 1 and 2 in the clathrin {beta}-propeller domain, whereas an 8-amino acid splice loop found solely in the long isoform of arrestin2 (arrestin2L) interacts with a binding pocket formedmore » by blades 4 and 5 in clathrin. The apposition of the two binding sites in arrestin2L suggests that they are exclusive and may function in higher order macromolecular structures. Biochemical analysis demonstrates direct binding of clathrin to the splice loop in arrestin2L, whereas functional analysis reveals that both binding domains contribute to the receptor-dependent redistribution of arrestin2L to clathrin-coated pits. Mutagenesis studies reveal that the clathrin binding motif in the splice loop is (L/I){sub 2}GXL. Taken together, these data provide a framework for understanding the dynamic interactions between arrestin2 and clathrin and reveal an essential role for this interaction in arrestin-mediated endocytosis.« less

Comparative expression profiling reveals gene functions in female meiosis and gametophyte development in Arabidopsis.

PubMed

Zhao, Lihua; He, Jiangman; Cai, Hanyang; Lin, Haiyan; Li, Yanqiang; Liu, Renyi; Yang, Zhenbiao; Qin, Yuan

2014-11-01

Megasporogenesis is essential for female fertility, and requires the accomplishment of meiosis and the formation of functional megaspores. The inaccessibility and low abundance of female meiocytes make it particularly difficult to elucidate the molecular basis underlying megasporogenesis. We used high-throughput tag-sequencing analysis to identify genes expressed in female meiocytes (FMs) by comparing gene expression profiles from wild-type ovules undergoing megasporogenesis with those from the spl mutant ovules, which lack megasporogenesis. A total of 862 genes were identified as FMs, with levels that are consistently reduced in spl ovules in two biological replicates. Fluorescence-assisted cell sorting followed by RNA-seq analysis of DMC1:GFP-labeled female meiocytes confirmed that 90% of the FMs are indeed detected in the female meiocyte protoplast profiling. We performed reverse genetic analysis of 120 candidate genes and identified four FM genes with a function in female meiosis progression in Arabidopsis. We further revealed that KLU, a putative cytochrome P450 monooxygenase, is involved in chromosome pairing during female meiosis, most likely by affecting the normal expression pattern of DMC1 in ovules during female meiosis. Our studies provide valuable information for functional genomic analyses of plant germline development as well as insights into meiosis. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Analysis of the Mycoplasma bovis lactate dehydrogenase reveals typical enzymatic activity despite the presence of an atypical catalytic site motif.

PubMed

Masukagami, Yumiko; Tivendale, Kelly Anne; Browning, Glenn Francis; Sansom, Fiona Margaret

2018-02-01

The lactate dehydrogenase (LDH) of Mycoplasma genitalium has been predicted to also act as a malate dehydrogenase (MDH), but there has been no experimental validation of this hypothesized dual function for any mollicute. Our analysis of the metabolite profile of Mycoplasma bovis using gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) detected malate, suggesting that there may be MDH activity in M. bovis. To investigate whether the putative l-LDH enzyme of M. bovis has a dual function (MDH and LDH), we performed bioinformatic and functional biochemical analyses. Although the amino acid sequence and predicted structural analysis of M. bovisl-LDH revealed unusual residues within the catalytic site, suggesting that it may have the flexibility to possess a dual function, our biochemical studies using recombinant M. bovis -LDH did not detect any MDH activity. However, we did show that the enzyme has typical LDH activity that could be inhibited by both MDH substrates oxaloacetate (OAA) and malate, suggesting that these substrates may be able to bind to M. bovis LDH. Inhibition of the conversion of pyruvate to lactate by OAA may be one method the mycoplasma cell uses to reduce the potential for accumulation of intracellular lactate.

Differential Adjustment Among Rural Adolescents Exposed to Family Violence

PubMed Central

Sianko, Natallia; Hedge, Jasmine M.; McDonell, James R.

2016-01-01

This study examines differences in psychological adjustment in a sample of rural adolescents who have been exposed to family violence. Self-report questionnaires were administered to 580 adolescents and their primary caregivers. The results revealed that over two thirds of the study participants (68.8%) had been exposed to violence in their families. As hypothesized, cluster analysis identified several profiles among adolescents, distinguished by their psychological and emotional functioning: well adjusted (46.2%), moderately adjusted (44.3%), and struggling (9.5%). Discriminant function analysis confirmed the groupings and revealed that family functioning was among the most influential factors explaining adjustment differences. Multivariate analyses of variance (MANOVAs) further showed that adolescents from each of the three adjustment profiles reported significantly different levels of family social support, parental involvement, and perceived neighborhood safety. Overall, the results confirm heterogeneity of adolescent adaptation in the aftermath of family violence and provide insights into family and neighborhood factors that account for variability in adolescents’ reactions to violence. Implications for future research and practical interventions are discussed. PMID:27106255

Molecular and cellular organization of taste neurons in adult Drosophila pharynx

PubMed Central

Chen, Yu-Chieh (David); Dahanukar, Anupama

2017-01-01

SUMMARY The Drosophila pharyngeal taste organs are poorly characterized despite their location at important sites for monitoring food quality. Functional analysis of pharyngeal neurons has been hindered by the paucity of molecular tools to manipulate them, as well as their relative inaccessibility for neurophysiological investigations. Here, we generate receptor-to-neuron maps of all three pharyngeal taste organs by performing a comprehensive chemoreceptor-GAL4/LexA expression analysis. The organization of pharyngeal neurons reveals similarities and distinctions in receptor repertoires and neuronal groupings compared to external taste neurons. We validate the mapping results by pinpointing a single pharyngeal neuron required for feeding avoidance of L-canavanine. Inducible activation of pharyngeal taste neurons reveals functional differences between external and internal taste neurons and functional subdivision within pharyngeal sweet neurons. Our results provide road maps of pharyngeal taste organs in an insect model system for probing the role of these understudied neurons in controlling feeding behaviors. PMID:29212040

Impact of Plant Functional Types on Coherence Between Precipitation and Soil Moisture: A Wavelet Analysis

NASA Astrophysics Data System (ADS)

Liu, Qi; Hao, Yonghong; Stebler, Elaine; Tanaka, Nobuaki; Zou, Chris B.

2017-12-01

Mapping the spatiotemporal patterns of soil moisture within heterogeneous landscapes is important for resource management and for the understanding of hydrological processes. A critical challenge in this mapping is comparing remotely sensed or in situ observations from areas with different vegetation cover but subject to the same precipitation regime. We address this challenge by wavelet analysis of multiyear observations of soil moisture profiles from adjacent areas with contrasting plant functional types (grassland, woodland, and encroached) and precipitation. The analysis reveals the differing soil moisture patterns and dynamics between plant functional types. The coherence at high-frequency periodicities between precipitation and soil moisture generally decreases with depth but this is much more pronounced under woodland compared to grassland. Wavelet analysis provides new insights on soil moisture dynamics across plant functional types and is useful for assessing differences and similarities in landscapes with heterogeneous vegetation cover.

Analyzing coastal environments by means of functional data analysis

NASA Astrophysics Data System (ADS)

Sierra, Carlos; Flor-Blanco, Germán; Ordoñez, Celestino; Flor, Germán; Gallego, José R.

2017-07-01

Here we used Functional Data Analysis (FDA) to examine particle-size distributions (PSDs) in a beach/shallow marine sedimentary environment in Gijón Bay (NW Spain). The work involved both Functional Principal Components Analysis (FPCA) and Functional Cluster Analysis (FCA). The grainsize of the sand samples was characterized by means of laser dispersion spectroscopy. Within this framework, FPCA was used as a dimension reduction technique to explore and uncover patterns in grain-size frequency curves. This procedure proved useful to describe variability in the structure of the data set. Moreover, an alternative approach, FCA, was applied to identify clusters and to interpret their spatial distribution. Results obtained with this latter technique were compared with those obtained by means of two vector approaches that combine PCA with CA (Cluster Analysis). The first method, the point density function (PDF), was employed after adapting a log-normal distribution to each PSD and resuming each of the density functions by its mean, sorting, skewness and kurtosis. The second applied a centered-log-ratio (clr) to the original data. PCA was then applied to the transformed data, and finally CA to the retained principal component scores. The study revealed functional data analysis, specifically FPCA and FCA, as a suitable alternative with considerable advantages over traditional vector analysis techniques in sedimentary geology studies.

Sliding-window analysis tracks fluctuations in amygdala functional connectivity associated with physiological arousal and vigilance during fear conditioning.

PubMed

Baczkowski, Blazej M; Johnstone, Tom; Walter, Henrik; Erk, Susanne; Veer, Ilya M

2017-06-01

We evaluated whether sliding-window analysis can reveal functionally relevant brain network dynamics during a well-established fear conditioning paradigm. To this end, we tested if fMRI fluctuations in amygdala functional connectivity (FC) can be related to task-induced changes in physiological arousal and vigilance, as reflected in the skin conductance level (SCL). Thirty-two healthy individuals participated in the study. For the sliding-window analysis we used windows that were shifted by one volume at a time. Amygdala FC was calculated for each of these windows. Simultaneously acquired SCL time series were averaged over time frames that corresponded to the sliding-window FC analysis, which were subsequently regressed against the whole-brain seed-based amygdala sliding-window FC using the GLM. Surrogate time series were generated to test whether connectivity dynamics could have occurred by chance. In addition, results were contrasted against static amygdala FC and sliding-window FC of the primary visual cortex, which was chosen as a control seed, while a physio-physiological interaction (PPI) was performed as cross-validation. During periods of increased SCL, the left amygdala became more strongly coupled with the bilateral insula and anterior cingulate cortex, core areas of the salience network. The sliding-window analysis yielded a connectivity pattern that was unlikely to have occurred by chance, was spatially distinct from static amygdala FC and from sliding-window FC of the primary visual cortex, but was highly comparable to that of the PPI analysis. We conclude that sliding-window analysis can reveal functionally relevant fluctuations in connectivity in the context of an externally cued task. Copyright © 2017 Elsevier Inc. All rights reserved.

The Function of Neuroendocrine Cells in Prostate Cancer

DTIC Science & Technology

2013-04-01

integration site. We then performed deep sequencing and aligned reads to the genome. Our analysis revealed that both histological phenotypes are derived from...lentiviral integration site analysis . (B) Laser capture microdissection was performed on individual glands containing both squamous and...lentiviral integration site analysis . LTR: long terminal repeat (viral DNA), PCR: polymerase chain reaction. (D) Venn diagrams depict shared lentiviral

Recent Achievement in Gene Cloning and Functional Genomics in Soybean

PubMed Central

Zhai, Hong; Lü, Shixiang; Wu, Hongyan; Zhang, Yupeng

2013-01-01

Soybean is a model plant for photoperiodism as well as for symbiotic nitrogen fixation. However, a rather low efficiency in soybean transformation hampers functional analysis of genes isolated from soybean. In comparison, rapid development and progress in flowering time and photoperiodic response have been achieved in Arabidopsis and rice. As the soybean genomic information has been released since 2008, gene cloning and functional genomic studies have been revived as indicated by successfully characterizing genes involved in maturity and nematode resistance. Here, we review some major achievements in the cloning of some important genes and some specific features at genetic or genomic levels revealed by the analysis of functional genomics of soybean. PMID:24311973

An empirical analysis of the distribution of the duration of overshoots in a stationary gaussian stochastic process

NASA Technical Reports Server (NTRS)

Parrish, R. S.; Carter, M. C.

1974-01-01

This analysis utilizes computer simulation and statistical estimation. Realizations of stationary gaussian stochastic processes with selected autocorrelation functions are computer simulated. Analysis of the simulated data revealed that the mean and the variance of a process were functionally dependent upon the autocorrelation parameter and crossing level. Using predicted values for the mean and standard deviation, by the method of moments, the distribution parameters was estimated. Thus, given the autocorrelation parameter, crossing level, mean, and standard deviation of a process, the probability of exceeding the crossing level for a particular length of time was calculated.

Structural Analysis of PTM Hotspots (SAPH-ire) – A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families*

PubMed Central

Dewhurst, Henry M.; Choudhury, Shilpa; Torres, Matthew P.

2015-01-01

Predicting the biological function potential of post-translational modifications (PTMs) is becoming increasingly important in light of the exponential increase in available PTM data from high-throughput proteomics. We developed structural analysis of PTM hotspots (SAPH-ire)—a quantitative PTM ranking method that integrates experimental PTM observations, sequence conservation, protein structure, and interaction data to allow rank order comparisons within or between protein families. Here, we applied SAPH-ire to the study of PTMs in diverse G protein families, a conserved and ubiquitous class of proteins essential for maintenance of intracellular structure (tubulins) and signal transduction (large and small Ras-like G proteins). A total of 1728 experimentally verified PTMs from eight unique G protein families were clustered into 451 unique hotspots, 51 of which have a known and cited biological function or response. Using customized software, the hotspots were analyzed in the context of 598 unique protein structures. By comparing distributions of hotspots with known versus unknown function, we show that SAPH-ire analysis is predictive for PTM biological function. Notably, SAPH-ire revealed high-ranking hotspots for which a functional impact has not yet been determined, including phosphorylation hotspots in the N-terminal tails of G protein gamma subunits—conserved protein structures never before reported as regulators of G protein coupled receptor signaling. To validate this prediction we used the yeast model system for G protein coupled receptor signaling, revealing that gamma subunit–N-terminal tail phosphorylation is activated in response to G protein coupled receptor stimulation and regulates protein stability in vivo. These results demonstrate the utility of integrating protein structural and sequence features into PTM prioritization schemes that can improve the analysis and functional power of modification-specific proteomics data. PMID:26070665

Transcriptome-wide identification of salt-responsive members of the WRKY gene family in Gossypium aridum.

PubMed

Fan, Xinqi; Guo, Qi; Xu, Peng; Gong, YuanYong; Shu, Hongmei; Yang, Yang; Ni, Wanchao; Zhang, Xianggui; Shen, Xinlian

2015-01-01

WRKY transcription factors are plant-specific, zinc finger-type transcription factors. The WRKY superfamily is involved in abiotic stress responses in many crops including cotton, a major fiber crop that is widely cultivated and consumed throughout the world. Salinity is an important abiotic stress that results in considerable yield losses. In this study, we identified 109 WRKY genes (GarWRKYs) in a salt-tolerant wild cotton species Gossypium aridum from transcriptome sequencing data to elucidate the roles of these factors in cotton salt tolerance. According to their structural features, the predicted members were divided into three groups (Groups I-III), as previously described for Arabidopsis. Furthermore, 28 salt-responsive GarWRKY genes were identified from digital gene expression data and subjected to real-time quantitative RT-PCR analysis. The expression patterns of most GarWRKY genes revealed by this analysis are in good agreement with those revealed by RNA-Seq analysis. RT-PCR analysis revealed that 27 GarWRKY genes were expressed in roots and one was exclusively expressed in roots. Analysis of gene orthology and motif compositions indicated that WRKY members from Arabidopsis, rice and soybean generally shared the similar motifs within the same subgroup, suggesting they have the similar function. Overexpression-GarWRKY17 and -GarWRKY104 in Arabidopsis revealed that they could positively regulate salt tolerance of transgenic Arabidopsis during different development stages. The comprehensive data generated in this study provide a platform for elucidating the functions of WRKY transcription factors in salt tolerance of G. aridum. In addition, GarWRKYs related to salt tolerance identified in this study will be potential candidates for genetic improvement of cultivated cotton salt stress tolerance.

A Spiking Neural Network Methodology and System for Learning and Comparative Analysis of EEG Data From Healthy Versus Addiction Treated Versus Addiction Not Treated Subjects.

PubMed

Doborjeh, Maryam Gholami; Wang, Grace Y; Kasabov, Nikola K; Kydd, Robert; Russell, Bruce

2016-09-01

This paper introduces a method utilizing spiking neural networks (SNN) for learning, classification, and comparative analysis of brain data. As a case study, the method was applied to electroencephalography (EEG) data collected during a GO/NOGO cognitive task performed by untreated opiate addicts, those undergoing methadone maintenance treatment (MMT) for opiate dependence and a healthy control group. the method is based on an SNN architecture called NeuCube, trained on spatiotemporal EEG data. NeuCube was used to classify EEG data across subject groups and across GO versus NOGO trials, but also facilitated a deeper comparative analysis of the dynamic brain processes. This analysis results in a better understanding of human brain functioning across subject groups when performing a cognitive task. In terms of the EEG data classification, a NeuCube model obtained better results (the maximum obtained accuracy: 90.91%) when compared with traditional statistical and artificial intelligence methods (the maximum obtained accuracy: 50.55%). more importantly, new information about the effects of MMT on cognitive brain functions is revealed through the analysis of the SNN model connectivity and its dynamics. this paper presented a new method for EEG data modeling and revealed new knowledge on brain functions associated with mental activity which is different from the brain activity observed in a resting state of the same subjects.

Genomic survey, expression profile and co-expression network analysis of OsWD40 family in rice

PubMed Central

2012-01-01

Background WD40 proteins represent a large family in eukaryotes, which have been involved in a broad spectrum of crucial functions. Systematic characterization and co-expression analysis of OsWD40 genes enable us to understand the networks of the WD40 proteins and their biological processes and gene functions in rice. Results In this study, we identify and analyze 200 potential OsWD40 genes in rice, describing their gene structures, genome localizations, and evolutionary relationship of each member. Expression profiles covering the whole life cycle in rice has revealed that transcripts of OsWD40 were accumulated differentially during vegetative and reproductive development and preferentially up or down-regulated in different tissues. Under phytohormone treatments, 25 OsWD40 genes were differentially expressed with treatments of one or more of the phytohormone NAA, KT, or GA3 in rice seedlings. We also used a combined analysis of expression correlation and Gene Ontology annotation to infer the biological role of the OsWD40 genes in rice. The results suggested that OsWD40 genes may perform their diverse functions by complex network, thus were predictive for understanding their biological pathways. The analysis also revealed that OsWD40 genes might interact with each other to take part in metabolic pathways, suggesting a more complex feedback network. Conclusions All of these analyses suggest that the functions of OsWD40 genes are diversified, which provide useful references for selecting candidate genes for further functional studies. PMID:22429805

LncRNA-HIT Functions as an Epigenetic Regulator of Chondrogenesis through Its Recruitment of p100/CBP Complexes.

PubMed

Carlson, Hanqian L; Quinn, Jeffrey J; Yang, Yul W; Thornburg, Chelsea K; Chang, Howard Y; Stadler, H Scott

2015-12-01

Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage.

LncRNA-HIT Functions as an Epigenetic Regulator of Chondrogenesis through Its Recruitment of p100/CBP Complexes

PubMed Central

Carlson, Hanqian L.; Quinn, Jeffrey J.; Yang, Yul W.; Thornburg, Chelsea K.; Chang, Howard Y.; Stadler, H. Scott

2015-01-01

Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage. PMID:26633036

Regulation of the alpha-glucuronidase-encoding gene ( aguA) from Aspergillus niger.

PubMed

de Vries, R P; van de Vondervoort, P J I; Hendriks, L; van de Belt, M; Visser, J

2002-09-01

The alpha-glucuronidase gene aguA from Aspergillus niger was cloned and characterised. Analysis of the promoter region of aguA revealed the presence of four putative binding sites for the major carbon catabolite repressor protein CREA and one putative binding site for the transcriptional activator XLNR. In addition, a sequence motif was detected which differed only in the last nucleotide from the XLNR consensus site. A construct in which part of the aguA coding region was deleted still resulted in production of a stable mRNA upon transformation of A. niger. The putative XLNR binding sites and two of the putative CREA binding sites were mutated individually in this construct and the effects on expression were examined in A. niger transformants. Northern analysis of the transformants revealed that the consensus XLNR site is not actually functional in the aguA promoter, whereas the sequence that diverges from the consensus at a single position is functional. This indicates that XLNR is also able to bind to the sequence GGCTAG, and the XLNR binding site consensus should therefore be changed to GGCTAR. Both CREA sites are functional, indicating that CREA has a strong influence on aguA expression. A detailed expression analysis of aguA in four genetic backgrounds revealed a second regulatory system involved in activation of aguA gene expression. This system responds to the presence of glucuronic and galacturonic acids, and is not dependent on XLNR.

A Factor-Analytic Study of Adaptive Behavior and Intellectual Functioning in Learning Disabled Children.

ERIC Educational Resources Information Center

Yeargan, Dollye R.

The factorial structure of intellectual functioning and adaptive behavior was examined in 160 learning disabled students (6 to 16 years old). Ss were administered the Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Coping Inventory (CI). Factor analysis of WISC-R scores revealed three factors: verbal comprehenson, perceptual…

Global analyses of Ceratocystis cacaofunesta mitochondria: from genome to proteome.

PubMed

Ambrosio, Alinne Batista; do Nascimento, Leandro Costa; Oliveira, Bruno V; Teixeira, Paulo José P L; Tiburcio, Ricardo A; Toledo Thomazella, Daniela P; Leme, Adriana F P; Carazzolle, Marcelo F; Vidal, Ramon O; Mieczkowski, Piotr; Meinhardt, Lyndel W; Pereira, Gonçalo A G; Cabrera, Odalys G

2013-02-11

The ascomycete fungus Ceratocystis cacaofunesta is the causal agent of wilt disease in cacao, which results in significant economic losses in the affected producing areas. Despite the economic importance of the Ceratocystis complex of species, no genomic data are available for any of its members. Given that mitochondria play important roles in fungal virulence and the susceptibility/resistance of fungi to fungicides, we performed the first functional analysis of this organelle in Ceratocystis using integrated "omics" approaches. The C. cacaofunesta mitochondrial genome (mtDNA) consists of a single, 103,147-bp circular molecule, making this the second largest mtDNA among the Sordariomycetes. Bioinformatics analysis revealed the presence of 15 conserved genes and 37 intronic open reading frames in C. cacaofunesta mtDNA. Here, we predicted the mitochondrial proteome (mtProt) of C. cacaofunesta, which is comprised of 1,124 polypeptides - 52 proteins that are mitochondrially encoded and 1,072 that are nuclearly encoded. Transcriptome analysis revealed 33 probable novel genes. Comparisons among the Gene Ontology results of the predicted mtProt of C. cacaofunesta, Neurospora crassa and Saccharomyces cerevisiae revealed no significant differences. Moreover, C. cacaofunesta mitochondria were isolated, and the mtProt was subjected to mass spectrometric analysis. The experimental proteome validated 27% of the predicted mtProt. Our results confirmed the existence of 110 hypothetical proteins and 7 novel proteins of which 83 and 1, respectively, had putative mitochondrial localization. The present study provides the first partial genomic analysis of a species of the Ceratocystis genus and the first predicted mitochondrial protein inventory of a phytopathogenic fungus. In addition to the known mitochondrial role in pathogenicity, our results demonstrated that the global function analysis of this organelle is similar in pathogenic and non-pathogenic fungi, suggesting that its relevance in the lifestyle of these organisms should be based on a small number of specific proteins and/or with respect to differential gene regulation. In this regard, particular interest should be directed towards mitochondrial proteins with unknown function and the novel protein that might be specific to this species. Further functional characterization of these proteins could enhance our understanding of the role of mitochondria in phytopathogenicity.

Global analyses of Ceratocystis cacaofunesta mitochondria: from genome to proteome

PubMed Central

2013-01-01

Background The ascomycete fungus Ceratocystis cacaofunesta is the causal agent of wilt disease in cacao, which results in significant economic losses in the affected producing areas. Despite the economic importance of the Ceratocystis complex of species, no genomic data are available for any of its members. Given that mitochondria play important roles in fungal virulence and the susceptibility/resistance of fungi to fungicides, we performed the first functional analysis of this organelle in Ceratocystis using integrated “omics” approaches. Results The C. cacaofunesta mitochondrial genome (mtDNA) consists of a single, 103,147-bp circular molecule, making this the second largest mtDNA among the Sordariomycetes. Bioinformatics analysis revealed the presence of 15 conserved genes and 37 intronic open reading frames in C. cacaofunesta mtDNA. Here, we predicted the mitochondrial proteome (mtProt) of C. cacaofunesta, which is comprised of 1,124 polypeptides - 52 proteins that are mitochondrially encoded and 1,072 that are nuclearly encoded. Transcriptome analysis revealed 33 probable novel genes. Comparisons among the Gene Ontology results of the predicted mtProt of C. cacaofunesta, Neurospora crassa and Saccharomyces cerevisiae revealed no significant differences. Moreover, C. cacaofunesta mitochondria were isolated, and the mtProt was subjected to mass spectrometric analysis. The experimental proteome validated 27% of the predicted mtProt. Our results confirmed the existence of 110 hypothetical proteins and 7 novel proteins of which 83 and 1, respectively, had putative mitochondrial localization. Conclusions The present study provides the first partial genomic analysis of a species of the Ceratocystis genus and the first predicted mitochondrial protein inventory of a phytopathogenic fungus. In addition to the known mitochondrial role in pathogenicity, our results demonstrated that the global function analysis of this organelle is similar in pathogenic and non-pathogenic fungi, suggesting that its relevance in the lifestyle of these organisms should be based on a small number of specific proteins and/or with respect to differential gene regulation. In this regard, particular interest should be directed towards mitochondrial proteins with unknown function and the novel protein that might be specific to this species. Further functional characterization of these proteins could enhance our understanding of the role of mitochondria in phytopathogenicity. PMID:23394930

A novel loss-of-function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency.

PubMed

Ashkenazi-Hoffnung, Liat; Lebenthal, Yael; Wyatt, Alexander W; Ragge, Nicola K; Dateki, Sumito; Fukami, Maki; Ogata, Tsutomu; Phillip, Moshe; Gat-Yablonski, Galia

2010-06-01

Heterozygous mutations of the gene encoding transcription factor OTX2 were recently shown to be responsible for ocular as well as pituitary abnormalities. Here, we describe a patient with unilateral anophthalmia and short stature. Endocrine evaluation of the hypothalamic-pituitary axis revealed isolated growth hormone deficiency (IGHD) with small anterior pituitary gland, invisible stalk, ectopic posterior lobe, and right anophthalmia on brain magnetic resonance imaging. DNA was analyzed for mutations in the HESX1, SOX2, and OTX2 genes. Molecular analysis yielded a novel heterozygous OTX2 mutation (c.270A>T, p.R90S) within the homeodomain. Functional analysis revealed that the mutation inhibited both the DNA binding and transactivation activities of the protein. This novel loss-of-function mutation is associated with anophthalmia and IGHD in a patient of Sephardic Jewish descent. We recommend that patients with GH deficiency and ocular malformation in whom genetic analysis for classic transcription factor genes (PROP1, POU1F1, HESX1, and LHX4) failed to identify alterations should be checked for the presence of mutations in the OTX2 gene.

Functional network connectivity analysis based on partial correlation in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Zhang, Nan; Guan, Xiaoting; Zhang, Yumei; Li, Jingjing; Chen, Hongyan; Chen, Kewei; Fleisher, Adam; Yao, Li; Wu, Xia

2009-02-01

Functional network connectivity (FNC) measures the temporal dependency among the time courses of functional networks. However, the marginal correlation between two networks used in the classic FNC analysis approach doesn't separate the FNC from the direct/indirect effects of other networks. In this study, we proposed an alternative approach based on partial correlation to evaluate the FNC, since partial correlation based FNC can reveal the direct interaction between a pair of networks, removing dependencies or influences from others. Previous studies have demonstrated less task-specific activation and less rest-state activity in Alzheimer's disease (AD). We applied present approach to contrast FNC differences of resting state network (RSN) between AD and normal controls (NC). The fMRI data under resting condition were collected from 15 AD and 16 NC. FNC was calculated for each pair of six RSNs identified using Group ICA, thus resulting in 15 (2 out of 6) pairs for each subject. Partial correlation based FNC analysis indicated 6 pairs significant differences between groups, while marginal correlation only revealed 2 pairs (involved in the partial correlation results). Additionally, patients showed lower correlation than controls among most of the FNC differences. Our results provide new evidences for the disconnection hypothesis in AD.

A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development.

PubMed

Covassin, L D; Siekmann, A F; Kacergis, M C; Laver, E; Moore, J C; Villefranc, J A; Weinstein, B M; Lawson, N D

2009-05-15

In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying a haploid screening strategy in a transgenic background that allows direct visualization of blood vessels, it was possible to identify several classes of mutant vascular phenotypes. Subsequent characterization of mutant lines revealed that defects in Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison of phenotypes associated with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development. In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1). Together with in vivo structure-function analysis, our results suggest a requirement for Plcg1 catalytic activity downstream of receptor tyrosine kinases. We further find that embryos lacking both maternal and zygotic plcg1 display more severe defects in artery differentiation but are otherwise similar to zygotic mutants. Finally, we demonstrate through mosaic analysis that plcg1 functions autonomously in endothelial cells. Together our genetic analyses suggest that Vegf/Plcg1 signaling acts at multiple time points and in different signaling contexts to mediate distinct aspects of artery development.

A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development

PubMed Central

Covassin, L. D.; Siekmann, A. F.; Kacergis, M. C.; Laver, E.; Moore, J. C.; Villefranc, J. A.; Weinstein, B. M.; Lawson, N. D.

2009-01-01

In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying a haploid screening strategy in a transgenic background that allows direct visualization of blood vessels, it was possible to identify several classes of mutant vascular phenotypes. Subsequent characterization of mutant lines revealed that defects in Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison of phenotypes associated with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development. In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1). Together with in vivo structure-function analysis, our results suggest a requirement for Plcg1 catalytic activity downstream of receptor tyrosine kinases. We further find that embryos lacking both maternal and zygotic plcg1 display more severe defects in artery differentiation but are otherwise similar to zygotic mutants. Finally, we demonstrate through mosaic analysis that plcg1 functions autonomously in endothelial cells. Together our genetic analyses suggest that Vegf/Plcg1 signaling acts at multiple time points and in different signaling contexts to mediate distinct aspects of artery development. PMID:19269286

Characterization of Sweetmeat Waste and Its Suitability for Sorption of As(III) in Aqueous Media.

PubMed

Islam, Md Mirajul; Adak, Asok; Paul, Prabir K

2017-04-01

  Presence of arsenic in effluents from mining, mineral processing, and metal plating industries pose a serious health hazard to human beings. In this research, suitability of cheap sweetmeat waste (SMW), which is sweet industry byproduct, was investigated for the treatment of As(III). The physicochemical properties of the sorbent were characterized. The SEM images revealed highly heterogeneous sorbent surface. XRD analysis showed the presence of different polysaccharides mainly containing hydroxyl functional group. FTIR analysis was also performed to confirm the functional groups present in the sorbent. Batch experiments were conducted for kinetic analysis, effect of initial As(III) concentration, sorbent dose, electrolytes, pH, and temperature in order to understand sorption behavior. Presence of electrolyte, solution pH, and temperature were found to affect the performance of the sorbent. The sorption followed pseudo-second order reaction and Langmuir isotherm model best. The studies revealed SMW to be an efficient media for removal of As(III) from aqueous environment.

Revealing and Quantifying the Impaired Phonological Analysis Underpinning Impaired Comprehension in Wernicke's Aphasia

ERIC Educational Resources Information Center

Robson, Holly; Keidel, James L.; Lambon Ralph, Matthew A.; Sage, Karen

2012-01-01

Wernicke's aphasia is a condition which results in severely disrupted language comprehension following a lesion to the left temporo-parietal region. A phonological analysis deficit has traditionally been held to be at the root of the comprehension impairment in Wernicke's aphasia, a view consistent with current functional neuroimaging which finds…

Argumentation in a Multi Party Asynchronous Computer Mediated Conference: A Generic Analysis

ERIC Educational Resources Information Center

Coffin, Caroline; Painter, Clare; Hewings, Ann

2005-01-01

This paper draws on systemic functional linguistic genre analysis to illuminate the way in which post graduate applied linguistics students structure their argumentation within a multi party asynchronous computer mediated conference. Two conference discussions within the same postgraduate course are compared in order to reveal the way in which…

The Economic Status of Migrant Wives: An Application of Discriminant Analysis.

ERIC Educational Resources Information Center

Rytina, Nancy F.

1981-01-01

Lower work rate of migrant wives after moving is a function of moving for husbands' job opportunities and being in the childrearing stage of life. Discriminant analysis reveals that socioeconomic characteristics are lower for nonworking than migrant wives. Working migrant wives have more education and higher status jobs than nonmigrants.…

Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts.

PubMed

Hose, Alexander J; Depner, Martin; Illi, Sabina; Lau, Susanne; Keil, Thomas; Wahn, Ulrich; Fuchs, Oliver; Pfefferle, Petra Ina; Schmaußer-Hechfellner, Elisabeth; Genuneit, Jon; Lauener, Roger; Karvonen, Anne M; Roduit, Caroline; Dalphin, Jean-Charles; Riedler, Josef; Pekkanen, Juha; von Mutius, Erika; Ege, Markus J

2017-06-01

Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear. We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE). Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort. The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-γ ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk. LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

High Mobility Group N Proteins Modulate the Fidelity of the Cellular Transcriptional Profile in a Tissue- and Variant-specific Manner*

PubMed Central

Kugler, Jamie E.; Horsch, Marion; Huang, Di; Furusawa, Takashi; Rochman, Mark; Garrett, Lillian; Becker, Lore; Bohla, Alexander; Hölter, Sabine M.; Prehn, Cornelia; Rathkolb, Birgit; Racz, Ildikó; Aguilar-Pimentel, Juan Antonio; Adler, Thure; Adamski, Jerzy; Beckers, Johannes; Busch, Dirk H.; Eickelberg, Oliver; Klopstock, Thomas; Ollert, Markus; Stöger, Tobias; Wolf, Eckhard; Wurst, Wolfgang; Yildirim, Ali Önder; Zimmer, Andreas; Gailus-Durner, Valérie; Fuchs, Helmut; Hrabě de Angelis, Martin; Garfinkel, Benny; Orly, Joseph; Ovcharenko, Ivan; Bustin, Michael

2013-01-01

The nuclei of most vertebrate cells contain members of the high mobility group N (HMGN) protein family, which bind specifically to nucleosome core particles and affect chromatin structure and function, including transcription. Here, we study the biological role of this protein family by systematic analysis of phenotypes and tissue transcription profiles in mice lacking functional HMGN variants. Phenotypic analysis of Hmgn1tm1/tm1, Hmgn3tm1/tm1, and Hmgn5tm1/tm1 mice and their wild type littermates with a battery of standardized tests uncovered variant-specific abnormalities. Gene expression analysis of four different tissues in each of the Hmgntm1/tm1 lines reveals very little overlap between genes affected by specific variants in different tissues. Pathway analysis reveals that loss of an HMGN variant subtly affects expression of numerous genes in specific biological processes. We conclude that within the biological framework of an entire organism, HMGNs modulate the fidelity of the cellular transcriptional profile in a tissue- and HMGN variant-specific manner. PMID:23620591

Comparative analysis of taxonomic, functional, and metabolic patterns of microbiomes from 14 full-scale biogas reactors by metagenomic sequencing and radioisotopic analysis.

PubMed

Luo, Gang; Fotidis, Ioannis A; Angelidaki, Irini

2016-01-01

Biogas production is a very complex process due to the high complexity in diversity and interactions of the microorganisms mediating it, and only limited and diffuse knowledge exists about the variation of taxonomic and functional patterns of microbiomes across different biogas reactors, and their relationships with the metabolic patterns. The present study used metagenomic sequencing and radioisotopic analysis to assess the taxonomic, functional, and metabolic patterns of microbiomes from 14 full-scale biogas reactors operated under various conditions treating either sludge or manure. The results from metagenomic analysis showed that the dominant methanogenic pathway revealed by radioisotopic analysis was not always correlated with the taxonomic and functional compositions. It was found by radioisotopic experiments that the aceticlastic methanogenic pathway was dominant, while metagenomics analysis showed higher relative abundance of hydrogenotrophic methanogens. Principal coordinates analysis showed the sludge-based samples were clearly distinct from the manure-based samples for both taxonomic and functional patterns, and canonical correspondence analysis showed that the both temperature and free ammonia were crucial environmental variables shaping the taxonomic and functional patterns. The study further the overall patterns of functional genes were strongly correlated with overall patterns of taxonomic composition across different biogas reactors. The discrepancy between the metabolic patterns determined by metagenomic analysis and metabolic pathways determined by radioisotopic analysis was found. Besides, a clear correlation between taxonomic and functional patterns was demonstrated for biogas reactors, and also the environmental factors that shaping both taxonomic and functional genes patterns were identified.

Combined venomics, antivenomics and venom gland transcriptome analysis of the monocoled cobra (Naja kaouthia) from China.

PubMed

Xu, Ning; Zhao, Hong-Yan; Yin, Yin; Shen, Shan-Shan; Shan, Lin-Lin; Chen, Chuan-Xi; Zhang, Yan-Xia; Gao, Jian-Fang; Ji, Xiang

2017-04-21

We conducted an omics-analysis of the venom of Naja kaouthia from China. Proteomics analysis revealed six protein families [three-finger toxins (3-FTx), phospholipase A 2 (PLA 2 ), nerve growth factor, snake venom metalloproteinase (SVMP), cysteine-rich secretory protein and ohanin], and venom-gland transcriptomics analysis revealed 28 protein families from 79 unigenes. 3-FTx (56.5% in proteome/82.0% in transcriptome) and PLA 2 (26.9%/13.6%) were identified as the most abundant families in venom proteome and venom-gland transcriptome. Furthermore, N. kaouthia venom expressed strong lethality (i.p. LD 50 : 0.79μg/g) and myotoxicity (CK: 5939U/l) in mice, and showed notable activity in PLA 2 but weak activity in SVMP, l-amino acid oxidase or 5' nucleotidase. Antivenomic assessment revealed that several venom components (nearly 17.5% of total venom) from N. kaouthia could not be thoroughly immunocaptured by commercial Naja atra antivenom. ELISA analysis revealed that there was no difference in the cross-reaction between N. kaouthia and N. atra venoms against the N. atra antivenom. The use of commercial N. atra antivenom in treatment of snakebites caused by N. kaouthia is reasonable, but design of novel antivenom with the attention on enhancing the immune response of non-immunocaptured components should be encouraged. The venomics, antivenomics and venom-gland transcriptome of the monocoled cobra (Naja kaouthia) from China have been elucidated. Quantitative and qualitative differences are evident when venom proteomic and venom-gland transcriptomic profiles are compared. Two protein families (3-FTx and PLA 2 ) are found to be the predominated components in N. kaouthia venom, and considered as the major players in functional role of venom. Other protein families with relatively low abundance appear to be minor in the functional significance. Antivenomics and ELISA evaluation reveal that the N. kaouthia venom can be effectively immunorecognized by commercial N. atra antivenom, but still a small number of venom components could not be thoroughly immunocaptured. The findings indicate that exploring the precise composition of snake venom should be executed by an integrated omics-approach, and elucidating the venom composition is helpful in understanding composition-function relationships and will facilitate the clinical application of antivenoms. Copyright © 2017 Elsevier B.V. All rights reserved.

A comprehensive functional analysis of PTEN mutations: implications in tumor- and autism-related syndromes.

PubMed

Rodríguez-Escudero, Isabel; Oliver, María D; Andrés-Pons, Amparo; Molina, María; Cid, Víctor J; Pulido, Rafael

2011-11-01

The PTEN (phosphatase and tensin homolog) phosphatase is unique in mammals in terms of its tumor suppressor activity, exerted by dephosphorylation of the lipid second messenger PIP(3) (phosphatidylinositol 3,4,5-trisphosphate), which activates the phosphoinositide 3-kinase/Akt/mTOR (mammalian target of rapamycin) oncogenic pathway. Loss-of-function mutations in the PTEN gene are frequent in human cancer and in the germline of patients with PTEN hamartoma tumor-related syndromes (PHTSs). In addition, PTEN is mutated in patients with autism spectrum disorders (ASDs), although no functional information on these mutations is available. Here, we report a comprehensive in vivo functional analysis of human PTEN using a heterologous yeast reconstitution system. Ala-scanning mutagenesis at the catalytic loops of PTEN outlined the critical role of residues within the P-catalytic loop for PIP(3) phosphatase activity in vivo. PTEN mutations that mimic the P-catalytic loop of mammalian PTEN-like proteins (TPTE, TPIP, tensins and auxilins) affected PTEN function variably, whereas tumor- or PHTS-associated mutations targeting the PTEN P-loop produced complete loss of function. Conversely, Ala-substitutions, as well as tumor-related mutations at the WPD- and TI-catalytic loops, displayed partial activity in many cases. Interestingly, a tumor-related D92N mutation was partially active, supporting the notion that the PTEN Asp92 residue might not function as the catalytic general acid. The analysis of a panel of ASD-associated hereditary PTEN mutations revealed that most of them did not substantially abrogate PTEN activity in vivo, whereas most of PHTS-associated mutations did. Our findings reveal distinctive functional patterns among PTEN mutations found in tumors and in the germline of PHTS and ASD patients, which could be relevant for therapy.

Functional analysis of the zebrafish ortholog of HMGCS1 reveals independent functions for cholesterol and isoprenoids in craniofacial development

PubMed Central

Hernandez, Jose A.; Gonzalez, Cesar G.

2017-01-01

There are 8 different human syndromes caused by mutations in the cholesterol synthesis pathway. A subset of these disorders such as Smith-Lemli-Opitz disorder, are associated with facial dysmorphia. However, the molecular and cellular mechanisms underlying such facial deficits are not fully understood, primarily because of the diverse functions associated with the cholesterol synthesis pathway. Recent evidence has demonstrated that mutation of the zebrafish ortholog of HMGCR results in orofacial clefts. Here we sought to expand upon these data, by deciphering the cholesterol dependent functions of the cholesterol synthesis pathway from the cholesterol independent functions. Moreover, we utilized loss of function analysis and pharmacological inhibition to determine the extent of sonic hedgehog (Shh) signaling in animals with aberrant cholesterol and/or isoprenoid synthesis. Our analysis confirmed that mutation of hmgcs1, which encodes the first enzyme in the cholesterol synthesis pathway, results in craniofacial abnormalities via defects in cranial neural crest cell differentiation. Furthermore targeted pharmacological inhibition of the cholesterol synthesis pathway revealed a novel function for isoprenoid synthesis during vertebrate craniofacial development. Mutation of hmgcs1 had no effect on Shh signaling at 2 and 3 days post fertilization (dpf), but did result in a decrease in the expression of gli1, a known Shh target gene, at 4 dpf, after morphological deficits in craniofacial development and chondrocyte differentiation were observed in hmgcs1 mutants. These data raise the possibility that deficiencies in cholesterol modulate chondrocyte differentiation by a combination of Shh independent and Shh dependent mechanisms. Moreover, our results describe a novel function for isoprenoids in facial development and collectively suggest that cholesterol regulates craniofacial development through versatile mechanisms. PMID:28686747

Stimulus-related independent component and voxel-wise analysis of human brain activity during free viewing of a feature film.

PubMed

Lahnakoski, Juha M; Salmi, Juha; Jääskeläinen, Iiro P; Lampinen, Jouko; Glerean, Enrico; Tikka, Pia; Sams, Mikko

2012-01-01

Understanding how the brain processes stimuli in a rich natural environment is a fundamental goal of neuroscience. Here, we showed a feature film to 10 healthy volunteers during functional magnetic resonance imaging (fMRI) of hemodynamic brain activity. We then annotated auditory and visual features of the motion picture to inform analysis of the hemodynamic data. The annotations were fitted to both voxel-wise data and brain network time courses extracted by independent component analysis (ICA). Auditory annotations correlated with two independent components (IC) disclosing two functional networks, one responding to variety of auditory stimulation and another responding preferentially to speech but parts of the network also responding to non-verbal communication. Visual feature annotations correlated with four ICs delineating visual areas according to their sensitivity to different visual stimulus features. In comparison, a separate voxel-wise general linear model based analysis disclosed brain areas preferentially responding to sound energy, speech, music, visual contrast edges, body motion and hand motion which largely overlapped the results revealed by ICA. Differences between the results of IC- and voxel-based analyses demonstrate that thorough analysis of voxel time courses is important for understanding the activity of specific sub-areas of the functional networks, while ICA is a valuable tool for revealing novel information about functional connectivity which need not be explained by the predefined model. Our results encourage the use of naturalistic stimuli and tasks in cognitive neuroimaging to study how the brain processes stimuli in rich natural environments.

Stimulus-Related Independent Component and Voxel-Wise Analysis of Human Brain Activity during Free Viewing of a Feature Film

PubMed Central

Lahnakoski, Juha M.; Salmi, Juha; Jääskeläinen, Iiro P.; Lampinen, Jouko; Glerean, Enrico; Tikka, Pia; Sams, Mikko

2012-01-01

Understanding how the brain processes stimuli in a rich natural environment is a fundamental goal of neuroscience. Here, we showed a feature film to 10 healthy volunteers during functional magnetic resonance imaging (fMRI) of hemodynamic brain activity. We then annotated auditory and visual features of the motion picture to inform analysis of the hemodynamic data. The annotations were fitted to both voxel-wise data and brain network time courses extracted by independent component analysis (ICA). Auditory annotations correlated with two independent components (IC) disclosing two functional networks, one responding to variety of auditory stimulation and another responding preferentially to speech but parts of the network also responding to non-verbal communication. Visual feature annotations correlated with four ICs delineating visual areas according to their sensitivity to different visual stimulus features. In comparison, a separate voxel-wise general linear model based analysis disclosed brain areas preferentially responding to sound energy, speech, music, visual contrast edges, body motion and hand motion which largely overlapped the results revealed by ICA. Differences between the results of IC- and voxel-based analyses demonstrate that thorough analysis of voxel time courses is important for understanding the activity of specific sub-areas of the functional networks, while ICA is a valuable tool for revealing novel information about functional connectivity which need not be explained by the predefined model. Our results encourage the use of naturalistic stimuli and tasks in cognitive neuroimaging to study how the brain processes stimuli in rich natural environments. PMID:22496909

Functional Recovery and Life Satisfaction in the First Year After Severe Traumatic Brain Injury: A Prospective Multicenter Study of a Norwegian National Cohort.

PubMed

Anke, Audny; Andelic, Nada; Skandsen, Toril; Knoph, Rein; Ader, Tiina; Manskow, Unn; Sigurdardottir, Solrun; Røe, Cecilie

2015-01-01

(1) To examine the impact of demographic and acute injury-related variables on functional recovery and life satisfaction after severe traumatic brain injury (sTBI) and (2) to test whether postinjury functioning, postconcussive symptoms, emotional state, and functional improvement are related to life satisfaction. Prospective national multicenter study. Level 1 trauma centers in Norway. 163 adults with sTBI. Functional recovery between 3 and 12 months postinjury measured with Glasgow Outcome Scale Extended, Rivermead Postconcussion Symptoms Questionnaire, Hospital Anxiety and Depression Scale, and satisfaction with life situation. 60% of cases experienced functional improvement from 3 to 12 months postinjury. Multivariate logistic regression analysis revealed that discharge to a rehabilitation department from acute care (odds ratio [OR] = 2.14; P < .05) and fewer days with artificial ventilation (OR = 1.04; P < .05) were significantly related to improvement. At 12 months postinjury, 85% were independent in daily activities. Most participants (63%) were satisfied with their life situation. Regression analysis revealed that older age (>65 years), low education, better functional outcome, and the absence of depressive and postconcussion symptoms were significant (P < .05) predictors of life satisfaction. Functional improvement was significantly associated with emotional state but not to life satisfaction. Following sTBI, approximately two-thirds of survivors improve between 3 and 12 months postinjury and are satisfied with their life. Direct discharge from acute care to specialized rehabilitation appears to increase functional recovery.

Extraversion modulates functional connectivity hubs of resting-state brain networks.

PubMed

Pang, Yajing; Cui, Qian; Duan, Xujun; Chen, Heng; Zeng, Ling; Zhang, Zhiqiang; Lu, Guangming; Chen, Huafu

2017-09-01

Personality dimension extraversion describes individual differences in social behaviour and socio-emotional functioning. The intrinsic functional connectivity patterns of the brain are reportedly associated with extraversion. However, whether or not extraversion is associated with functional hubs warrants clarification. Functional hubs are involved in the rapid integration of neural processing, and their dysfunction contributes to the development of neuropsychiatric disorders. In this study, we employed the functional connectivity density (FCD) method for the first time to distinguish the energy-efficient hubs associated with extraversion. The resting-state functional magnetic resonance imaging data of 71 healthy subjects were used in the analysis. Short-range FCD was positively correlated with extraversion in the left cuneus, revealing a link between the local functional activity of this region and extraversion in risk-taking. Long-range FCD was negatively correlated with extraversion in the right superior frontal gyrus and the inferior frontal gyrus. Seed-based resting-state functional connectivity (RSFC) analyses revealed that a decreased long-range FCD in individuals with high extraversion scores showed a low long-range functional connectivity pattern between the medial and dorsolateral prefrontal cortex, middle temporal gyrus, and anterior cingulate cortex. This result suggests that decreased RSFC patterns are responsible for self-esteem, self-evaluation, and inhibitory behaviour system that account for the modulation and shaping of extraversion. Overall, our results emphasize specific brain hubs, and reveal long-range functional connections in relation to extraversion, thereby providing a neurobiological basis of extraversion. © 2015 The British Psychological Society.

Functional Connectivity and Genetic Profile of a “Double-Cortex”-Like Malformation

PubMed Central

Sprugnoli, Giulia; Vatti, Giampaolo; Rossi, Simone; Cerase, Alfonso; Renieri, Alessandra; Mencarelli, Maria A.; Zara, Federico; Rossi, Alessandro; Santarnecchi, Emiliano

2018-01-01

Laminar heterotopia is a rare condition consisting in an extra layer of gray matter under properly migrated cortex; it configures an atypical presentation of periventricular nodular heterotopia (PNH) or a double cortex (DC) syndrome. We conducted an original functional MRI (fMRI) analysis in a drug-resistant epilepsy patient with “double-cortex”-like malformation to reveal her functional connectivity (FC) as well as a wide genetic analysis to identify possible genetic substrates. Heterotopias were segmented into region of interests (ROIs), whose voxel-wise FC was compared to that of (i) its normally migrated counterpart, (ii) its contralateral homologous, and (iii) those of 30 age-matched healthy controls. Extensive genetic analysis was conducted to screen cortical malformations-associated genes. Compared to healthy controls, both laminar heterotopias and the overlying cortex showed significant reduction of FC with the contralateral hemisphere. Two heterozygous variants of uncertain clinical significance were found, involving autosomal recessive disease-causing genes, FAT4 and COL18A1. This first FC analysis of a unique case of “double-cortex”-like malformation revealed a hemispheric connectivity segregation both in the laminar cortex as in the correctly migrated one, with a new pattern of genes’ mutations. Our study suggests the altered FC could have an electrophysiological and functional impact on large-scale brain networks, and the involvement of not yet identified genes in “double-cortex”-like malformation with a possible role of rare variants in recessive genes as pathogenic cofactors. PMID:29946244

Functional and Structural Changes in a Canine Model of Hereditary Primary Angle-Closure Glaucoma

PubMed Central

Kecova, Helga; Harper, Matthew M.; Nilaweera, Wijitha; Kuehn, Markus H.; Kardon, Randy H.

2010-01-01

Purpose. To characterize functional and structural changes in a canine model of hereditary primary angle-closure glaucoma. Methods. Intraocular pressure (IOP) was evaluated with tonometry in a colony of glaucomatous dogs at 8, 15, 18, 20, and 30 months of age. Retinal function was evaluated using electroretinography (scotopic, photopic, and pattern). Examination of anterior segment structures was performed using gonioscopy and high-frequency ultrasonography (HFU). Results. A gradual rise in IOP was observed with an increase in age: 8 months, 14 mm Hg (median value); 15 months, 15.5 mm Hg; 18 months, 17.5 mm Hg; 20 months, 24 mm Hg; 30 months, 36 mm Hg. Provocative testing with mydriatic agents (tropicamide and atropine 1%) caused significant increases in IOP (35% and 50%, respectively). HFU analysis showed complete collapse of iridocorneal angles by 20 months of age. Scotopic and photopic ERG analysis did not reveal significant deficits, but pattern ERG analysis showed significantly reduced amplitudes in glaucomatous dogs (glaucoma, 3.5 ± 0.4 μV; control, 6.2 ± 0.3 μV; P = 0.004; Student's t-test). Histologic analysis revealed collapse of the iridocorneal angle, posterior bowing of the lamina cribrosa, swelling and loss of large retinal ganglion cells, increased glial reactivity, and increased thickening of the lamina cribrosa. Conclusions. Canine hereditary angle-closure glaucoma is characterized by a progressive increase in intraocular pressure, loss of optic nerve function, and retinal ganglion cell loss. PMID:19661222

Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)*

PubMed Central

Yu, Heguo; Diao, Hua; Wang, Chunmei; Lin, Yan; Yu, Fudong; Lu, Hui; Xu, Wei; Li, Zheng; Shi, Huijuan; Zhao, Shimin; Zhou, Yuchuan; Zhang, Yonglian

2015-01-01

Male infertility is a medical condition that has been on the rise globally. Lysine acetylation of human sperm, an essential posttranslational modification involved in the etiology of sperm abnormality, is not fully understood. Therefore, we first generated a qualified pan-anti-acetyllysine monoclonal antibody to characterize the global lysine acetylation of uncapacitated normal human sperm with a proteomics approach. With high enrichment ratios that were up to 31%, 973 lysine-acetylated sites that matched to 456 human sperm proteins, including 671 novel lysine acetylation sites and 205 novel lysine-acetylated proteins, were identified. These proteins exhibited conserved motifs XXXKYXXX, XXXKFXXX, and XXXKHXXX, were annotated to function in multiple metabolic processes, and were localized predominantly in the mitochondrion and cytoplasmic fractions. Between the uncapacitated and capacitated sperm, different acetylation profiles in regard to functional proteins involved in sperm capacitation, sperm-egg recognition, sperm-egg plasma fusion, and fertilization were observed, indicating that acetylation of functional proteins may be required during sperm capacitation. Bioinformatics analysis revealed association of acetylated proteins with diseases and drugs. Novel acetylation of voltage-dependent anion channel proteins was also found. With clinical sperm samples, we observed differed lysine acetyltransferases and lysine deacetylases expression between normal sperm and abnormal sperm of asthenospermia or necrospermia. Furthermore, with sperm samples impaired by epigallocatechin gallate to mimic asthenospermia, we observed that inhibition of sperm motility was partly through the blockade of voltage-dependent anion channel 2 Lys-74 acetylation combined with reduced ATP levels and mitochondrial membrane potential. Taken together, we obtained a qualified pan-anti-acetyllysine monoclonal antibody, analyzed the acetylproteome of uncapacitated human sperm, and revealed associations between functional protein acetylation and sperm functions. PMID:25680958

Rice Phospholipase A Superfamily: Organization, Phylogenetic and Expression Analysis during Abiotic Stresses and Development

PubMed Central

Singh, Amarjeet; Baranwal, Vinay; Shankar, Alka; Kanwar, Poonam; Ranjan, Rajeev; Yadav, Sandeep; Pandey, Amita; Kapoor, Sanjay; Pandey, Girdhar K.

2012-01-01

Background Phospholipase A (PLA) is an important group of enzymes responsible for phospholipid hydrolysis in lipid signaling. PLAs have been implicated in abiotic stress signaling and developmental events in various plants species. Genome-wide analysis of PLA superfamily has been carried out in dicot plant Arabidopsis. A comprehensive genome-wide analysis of PLAs has not been presented yet in crop plant rice. Methodology/Principal Findings A comprehensive bioinformatics analysis identified a total of 31 PLA encoding genes in the rice genome, which are divided into three classes; phospholipase A1 (PLA1), patatin like phospholipases (pPLA) and low molecular weight secretory phospholipase A2 (sPLA2) based on their sequences and phylogeny. A subset of 10 rice PLAs exhibited chromosomal duplication, emphasizing the role of duplication in the expansion of this gene family in rice. Microarray expression profiling revealed a number of PLA members expressing differentially and significantly under abiotic stresses and reproductive development. Comparative expression analysis with Arabidopsis PLAs revealed a high degree of functional conservation between the orthologs in two plant species, which also indicated the vital role of PLAs in stress signaling and plant development across different plant species. Moreover, sub-cellular localization of a few candidates suggests their differential localization and functional role in the lipid signaling. Conclusion/Significance The comprehensive analysis and expression profiling would provide a critical platform for the functional characterization of the candidate PLA genes in crop plants. PMID:22363522

Within-Subject Correlation Analysis to Detect Functional Areas Associated With Response Inhibition.

PubMed

Yamasaki, Tomoko; Ogawa, Akitoshi; Osada, Takahiro; Jimura, Koji; Konishi, Seiki

2018-01-01

Functional areas in fMRI studies are often detected by brain-behavior correlation, calculating across-subject correlation between the behavioral index and the brain activity related to a function of interest. Within-subject correlation analysis is also employed in a single subject level, which utilizes cognitive fluctuations in a shorter time period by correlating the behavioral index with the brain activity across trials. In the present study, the within-subject analysis was applied to the stop-signal task, a standard task to probe response inhibition, where efficiency of response inhibition can be evaluated by the stop-signal reaction time (SSRT). Since the SSRT is estimated, by definition, not in a trial basis but from pooled trials, the correlation across runs was calculated between the SSRT and the brain activity related to response inhibition. The within-subject correlation revealed negative correlations in the anterior cingulate cortex and the cerebellum. Moreover, the dissociation pattern was observed in the within-subject analysis when earlier vs. later parts of the runs were analyzed: negative correlation was dominant in earlier runs, whereas positive correlation was dominant in later runs. Regions of interest analyses revealed that the negative correlation in the anterior cingulate cortex, but not in the cerebellum, was dominant in earlier runs, suggesting multiple mechanisms associated with inhibitory processes that fluctuate on a run-by-run basis. These results indicate that the within-subject analysis compliments the across-subject analysis by highlighting different aspects of cognitive/affective processes related to response inhibition.

On Special Functions in the Context of Clifford Analysis

NASA Astrophysics Data System (ADS)

Malonek, H. R.; Falcão, M. I.

2010-09-01

Considering the foundation of Quaternionic Analysis by R. Fueter and his collaborators in the beginning of the 1930s as starting point of Clifford Analysis, we can look back to 80 years of work in this field. However the interest in multivariate analysis using Clifford algebras only started to grow significantly in the 70s. Since then a great amount of papers on Clifford Analysis referring different classes of Special Functions have appeared. This situation may have been triggered by a more systematic treatment of monogenic functions by their multiple series development derived from Gegenbauer or associated Legendre polynomials (and not only by their integral representation). Also approaches to Special Functions by means of algebraic methods, either Lie algebras or through Lie groups and symmetric spaces gained by that time importance and influenced their treatment in Clifford Analysis. In our talk we will rely on the generalization of the classical approach to Special Functions through differential equations with respect to the hypercomplex derivative, which is a more recently developed tool in Clifford Analysis. In this context special attention will be payed to the role of Special Functions as intermediator between continuous and discrete mathematics. This corresponds to a more recent trend in combinatorics, since it has been revealed that many algebraic structures have hidden combinatorial underpinnings.

Multiple Roles of Integrin-Linked Kinase in Epidermal Development, Maturation and Pigmentation Revealed by Molecular Profiling

PubMed Central

Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E.; Dagnino, Lina

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function. PMID:22574216

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

PubMed

Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

Alternations of functional connectivity in amblyopia patients: a resting-state fMRI study

NASA Astrophysics Data System (ADS)

Wang, Jieqiong; Hu, Ling; Li, Wenjing; Xian, Junfang; Ai, Likun; He, Huiguang

2014-03-01

Amblyopia is a common yet hard-to-cure disease in children and results in poor or blurred vision. Some efforts such as voxel-based analysis, cortical thickness analysis have been tried to reveal the pathogenesis of amblyopia. However, few studies focused on alterations of the functional connectivity (FC) in amblyopia. In this study, we analyzed the abnormalities of amblyopia patients by both the seed-based FC with the left/right primary visual cortex and the network constructed throughout the whole brain. Experiments showed the following results: (1)As for the seed-based FC analysis, FC between superior occipital gyrus and the primary visual cortex was found to significantly decrease in both sides. The abnormalities were also found in lingual gyrus. The results may reflect functional deficits both in dorsal stream and ventral stream. (2)Two increased functional connectivities and 64 decreased functional connectivities were found in the whole brain network analysis. The decreased functional connectivities most concentrate in the temporal cortex. The results suggest that amblyopia may be caused by the deficits in the visual information transmission.

Functional resting-state connectivity of the human motor network: differences between right- and left-handers.

PubMed

Pool, Eva-Maria; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2015-04-01

Handedness is associated with differences in activation levels in various motor tasks performed with the dominant or non-dominant hand. Here we tested whether handedness is reflected in the functional architecture of the motor system even in the absence of an overt motor task. Using resting-state functional magnetic resonance imaging we investigated 18 right- and 18 left-handers. Whole-brain functional connectivity maps of the primary motor cortex (M1), supplementary motor area (SMA), dorsolateral premotor cortex (PMd), pre-SMA, inferior frontal junction and motor putamen were compared between right- and left-handers. We further used a multivariate linear support vector machine (SVM) classifier to reveal the specificity of brain regions for classifying handedness based on individual resting-state maps. Using left M1 as seed region, functional connectivity analysis revealed stronger interhemispheric functional connectivity between left M1 and right PMd in right-handers as compared to left-handers. This connectivity cluster contributed to the individual classification of right- and left-handers with 86.2% accuracy. Consistently, also seeding from right PMd yielded a similar handedness-dependent effect in left M1, albeit with lower classification accuracy (78.1%). Control analyses of the other resting-state networks including the speech and the visual network revealed no significant differences in functional connectivity related to handedness. In conclusion, our data revealed an intrinsically higher functional connectivity in right-handers. These results may help to explain that hand preference is more lateralized in right-handers than in left-handers. Furthermore, enhanced functional connectivity between left M1 and right PMd may serve as an individual marker of handedness. Copyright © 2015 Elsevier Inc. All rights reserved.

Functional resting-state connectivity of the human motor network: Differences between right- and left-handers

PubMed Central

Pool, Eva-Maria; Rehme, Anne K.; Eickhoff, Simon B.; Fink, Gereon R.; Grefkes, Christian

2016-01-01

Handedness is associated with differences in activation levels in various motor tasks performed with the dominant or non-dominant hand. Here we tested whether handedness is reflected in the functional architecture of the motor system even in the absence of an overt motor task. Using resting-state functional magnetic resonance imaging we investigated 18 right- and 18 left-handers. Whole-brain functional connectivity maps of the primary motor cortex (M1), supplementary motor area (SMA), dorsolateral premotor cortex (PMd), pre-SMA, inferior frontal junction and motor putamen were compared between right- and left-handers. We further used a multivariate linear support vector machine (SVM) classifier to reveal the specificity of brain regions for classifying handedness based on individual resting-state maps. Using left M1 as seed region, functional connectivity analysis revealed stronger interhemispheric functional connectivity between left M1 and right PMd in right-handers as compared to left-handers. This connectivity cluster contributed to the individual classification of right- and left-handers with 86.2% accuracy. Consistently, also seeding from right PMd yielded a similar handedness-dependent effect in left M1, albeit with lower classification accuracy (78.1%). Control analyses of the other resting-state networks including the speech and the visual network revealed no significant differences in functional connectivity related to handedness. In conclusion, our data revealed an intrinsically higher functional connectivity in right-handers. These results may help to explain that hand preference is more lateralized in right-handers than in left-handers. Furthermore, enhanced functional connectivity between left M1 and right PMd may serve as an individual marker of handedness. PMID:25613438

An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

PubMed Central

Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

2014-01-01

The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

Metagenomic insights into the microbiota profiles and bioaugmentation mechanism of organics removal in coal gasification wastewater in an anaerobic/anoxic/oxic system by methanol.

PubMed

Xu, Weichao; Zhang, Yuxiu; Cao, Hongbin; Sheng, Yuxing; Li, Haibo; Li, Yuping; Zhao, He; Gui, Xuefei

2018-05-18

Coal gasification wastewater is a typical high phenol-containing, toxic and refractory industrial wastewater. Here, lab-scale anaerobic-anoxic-oxic system was employed to treat real coal gasification wastewater, and methanol was added to oxic tank as the co-substrate to enhance the removal of refractory organic pollutants. The results showed that the average COD removal in oxic effluent increased from 24.9% to 36.0% by adding methanol, the total phenols concentration decreased from 54.4 to 44.9 mg/L. GC-MS analysis revealed that contents of phenolic components and polycyclic aromatic hydrocarbons (PAHs) were decreased compared to the control and their degradation intermediates were observed. Microbial community revealed that methanol increased the abundance of phenolics and PAHs degraders such as Comamonas, Burkholderia and Sphingopyxis. Moreover, functional analysis revealed the relative abundance of functional genes associated with toluene, benzoate and PAHs degradation pathways was higher than that of control based on KEGG database. Copyright © 2018. Published by Elsevier Ltd.

Embryotoxic and pharmacologic potency ranking of six azoles in the rat whole embryo culture by morphological and transcriptomic analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dimopoulou, Myrto, E-mail: myrto.dimopoulou@wur.nl

Differential gene expression analysis in the rat whole embryo culture (WEC) assay provides mechanistic insight into the embryotoxicity of test compounds. In our study, we hypothesized that comparative analysis of the transcriptomes of rat embryos exposed to six azoles (flusilazole, triadimefon, ketoconazole, miconazole, difenoconazole and prothioconazole) could lead to a better mechanism-based understanding of their embryotoxicity and pharmacological action. For evaluating embryotoxicity, we applied the total morphological scoring system (TMS) in embryos exposed for 48 h. The compounds tested showed embryotoxicity in a dose-response fashion. Functional analysis of differential gene expression after 4 h exposure at the ID{sub 10} (effectivemore » dose for 10% decreased TMS), revealed the sterol biosynthesis pathway and embryonic development genes, dominated by genes in the retinoic acid (RA) pathway, albeit in a differential way. Flusilazole, ketoconazole and triadimefon were the most potent compounds affecting the RA pathway, while in terms of regulation of sterol function, difenoconazole and ketoconazole showed the most pronounced effects. Dose-dependent analysis of the effects of flusilazole revealed that the RA pathway related genes were already differentially expressed at low dose levels while the sterol pathway showed strong regulation at higher embryotoxic doses, suggesting that this pathway is less predictive for the observed embryotoxicity. A similar analysis at the 24-hour time point indicated an additional time-dependent difference in the aforementioned pathways regulated by flusilazole. In summary, the rat WEC assay in combination with transcriptomics could add a mechanistic insight into the embryotoxic potency ranking and pharmacological mode of action of the tested compounds. - Highlights: • Embryonic exposure to azoles revealed concentration-dependent malformations. • Transcriptomics could enhance the mechanistic knowledge of embryotoxicants. • Retinoic acid gene set identifies early embryotoxic responses to azoles. • Toxic versus pharmacologic potency determines functional efficacy.« less

Functional characterization and quantitative expression analysis of two GnRH-related peptide receptors in the mosquito, Aedes aegypti.

PubMed

Oryan, Alireza; Wahedi, Azizia; Paluzzi, Jean-Paul V

2018-03-04

To cope with stressful events such as flight, organisms have evolved various regulatory mechanisms, often involving control by endocrine-derived factors. In insects, two stress-related factors include the gonadotropin-releasing hormone-related peptides adipokinetic hormone (AKH) and corazonin (CRZ). AKH is a pleiotropic hormone best known as a substrate liberator of proteins, lipids, and carbohydrates. Although a universal function has not yet been elucidated, CRZ has been shown to have roles in pigmentation, ecdysis or act as a cardiostimulatory factor. While both these neuropeptides and their respective receptors (AKHR and CRZR) have been characterized in several organisms, details on their specific roles within the disease vector, Aedes aegypti, remain largely unexplored. Here, we obtained three A. aegypti AKHR transcript variants and further identified the A. aegypti CRZR receptor. Receptor expression using a heterologous functional assay revealed that these receptors exhibit a highly specific response for their native ligands. Developmental quantitative expression analysis of CRZR revealed enrichment during the pupal and adult stages. In adults, quantitative spatial expression analysis revealed CRZR transcript in a variety of organs including head, thoracic ganglia, primary reproductive organs (ovary and testis), as well as male carcass. This suggest CRZ may play a role in ecdysis, and neuronal expression of CRZR indicates a possible role for CRZ within the nervous system. Quantitative developmental expression analysis of AKHR identified significant transcript enrichment in early adult stages. AKHR transcript was observed in the head, thoracic ganglia, accessory reproductive tissues and the carcass of adult females, while it was detected in the abdominal ganglia and enriched significantly in the carcass of adult males, which supports the known function of AKH in energy metabolism. Collectively, given the enrichment of CRZR and AKHR in the primary and secondary sex organs, respectively, of adult mosquitoes, these neuropeptides may play a role in regulating mosquito reproductive biology. Copyright © 2018 Elsevier Inc. All rights reserved.

Genes encoding calmodulin-binding proteins in the Arabidopsis genome

NASA Technical Reports Server (NTRS)

Reddy, Vaka S.; Ali, Gul S.; Reddy, Anireddy S N.

2002-01-01

Analysis of the recently completed Arabidopsis genome sequence indicates that approximately 31% of the predicted genes could not be assigned to functional categories, as they do not show any sequence similarity with proteins of known function from other organisms. Calmodulin (CaM), a ubiquitous and multifunctional Ca(2+) sensor, interacts with a wide variety of cellular proteins and modulates their activity/function in regulating diverse cellular processes. However, the primary amino acid sequence of the CaM-binding domain in different CaM-binding proteins (CBPs) is not conserved. One way to identify most of the CBPs in the Arabidopsis genome is by protein-protein interaction-based screening of expression libraries with CaM. Here, using a mixture of radiolabeled CaM isoforms from Arabidopsis, we screened several expression libraries prepared from flower meristem, seedlings, or tissues treated with hormones, an elicitor, or a pathogen. Sequence analysis of 77 positive clones that interact with CaM in a Ca(2+)-dependent manner revealed 20 CBPs, including 14 previously unknown CBPs. In addition, by searching the Arabidopsis genome sequence with the newly identified and known plant or animal CBPs, we identified a total of 27 CBPs. Among these, 16 CBPs are represented by families with 2-20 members in each family. Gene expression analysis revealed that CBPs and CBP paralogs are expressed differentially. Our data suggest that Arabidopsis has a large number of CBPs including several plant-specific ones. Although CaM is highly conserved between plants and animals, only a few CBPs are common to both plants and animals. Analysis of Arabidopsis CBPs revealed the presence of a variety of interesting domains. Our analyses identified several hypothetical proteins in the Arabidopsis genome as CaM targets, suggesting their involvement in Ca(2+)-mediated signaling networks.

Macroevolutionary trends of atomic composition and related functional group proportion in eukaryotic and prokaryotic proteins.

PubMed

Zhang, Yu-Juan; Yang, Chun-Lin; Hao, You-Jin; Li, Ying; Chen, Bin; Wen, Jian-Fan

2014-01-25

To fully explore the trends of atomic composition during the macroevolution from prokaryote to eukaryote, five atoms (oxygen, sulfur, nitrogen, carbon, hydrogen) and related functional groups in prokaryotic and eukaryotic proteins were surveyed and compared. Genome-wide analysis showed that eukaryotic proteins have more oxygen, sulfur and nitrogen atoms than prokaryotes do. Clusters of Orthologous Groups (COG) analysis revealed that oxygen, sulfur, carbon and hydrogen frequencies are higher in eukaryotic proteins than in their prokaryotic orthologs. Furthermore, functional group analysis demonstrated that eukaryotic proteins tend to have higher proportions of sulfhydryl, hydroxyl and acylamino, but lower of sulfide and carboxyl. Taken together, an apparent trend of increase was observed for oxygen and sulfur atoms in the macroevolution; the variation of oxygen and sulfur compositions and their related functional groups in macroevolution made eukaryotic proteins carry more useful functional groups. These results will be helpful for better understanding the functional significances of atomic composition evolution. Copyright © 2013 Elsevier B.V. All rights reserved.

Gene cloning, expression and functional characterization of a proliferation-inducing ligand (APRIL) from hedgehog (Erinaceus europaeus).

PubMed

Cui, Xian-Wei; Xiao, Wen; Ji, Chen-Bo; Tian, Ai-Ying; Zhang, Jie; Zhang, Shuang-Quan

2012-05-01

Here we describe the identification of the hedgehog Erinaceus europaeus homologue of a proliferation-inducing ligand (APRIL) of the TNF family (designated heAPRIL). Hedgehog APRIL contains two cysteine residues (Cys(196) and Cys(211)), a furin protease cleavage site and a conserved putative N-glycosylation site (Asn(124)). Real-time quantitative PCR (qPCR) analysis revealed that heAPRIL could be detected in various tissues. MTT assays and flow cytometric analysis revealed that Nus-hesAPRIL and hesAPRIL could promote the survival/proliferation of splenic B cells. Laser scanning confocal microscopy analysis showed GFP-hesAPRIL could successfully bind to the APRIL receptors of lymphocytes.

CCS52A2/FZR1, a cell cycle regulator, is an essential factor for shoot apical meristem maintenance in Arabidopsis thaliana.

PubMed

Liu, Yajie; Ye, Wei; Li, Beibei; Zhou, Xiaojing; Cui, Yuhai; Running, Mark P; Liu, Kede

2012-08-08

Cell division and cell fate decisions regulate organ formation and function in plant growth and development. It is still unclear how specific meristematic regulatory networks operate with the cell cycle machinery to translate stem cell identity and maintenance into cellular behavior. In this study, we address these questions by analysis of a shoot apex defective mutant, namely xcm9. Phenotypic analysis of the xcm9 mutant reveals concomitant premature termination of floral shoots with frequent bifurcation of the shoot apices, stems, and flowers. Microscopic observations show irregular cell organization in shoot apical meristems of xcm9. Positional cloning revealed that xcm9 is a loss of function allele of the CCS52A2/FZR1 gene, which has previously been implicated in root development. Expression analysis demonstrated that CCS52A2 maintains a higher transcriptional expression level in actively dividing tissue. Genetic studies indicated that the CCS52A2 gene functions together with WUSCHEL (WUS) and CLAVATA3 (CLV3) in regulating the development of the shoot meristem, and also contributes to this regulation together with the chromatin remodeling pathway. In addition, fewer xcm9 cells express CYCLIN B1:1, showing that cell cycle progression is disrupted in the mutant. We propose that the CCS52A2 gene is a mediator that functions together with meristematic genes to regulate meristem organization, and cross-functions with chromatin regulators in cell cycle progression during shoot apical meristem development.

Gene expression profiling in equine polysaccharide storage myopathy revealed inflammation, glycogenesis inhibition, hypoxia and mitochondrial dysfunctions.

PubMed

Barrey, Eric; Mucher, Elodie; Jeansoule, Nicolas; Larcher, Thibaut; Guigand, Lydie; Herszberg, Bérénice; Chaffaux, Stéphane; Guérin, Gérard; Mata, Xavier; Benech, Philippe; Canale, Marielle; Alibert, Olivier; Maltere, Péguy; Gidrol, Xavier

2009-08-07

Several cases of myopathies have been observed in the horse Norman Cob breed. Muscle histology examinations revealed that some families suffer from a polysaccharide storage myopathy (PSSM). It is assumed that a gene expression signature related to PSSM should be observed at the transcriptional level because the glycogen storage disease could also be linked to other dysfunctions in gene regulation. Thus, the functional genomic approach could be conducted in order to provide new knowledge about the metabolic disorders related to PSSM. We propose exploring the PSSM muscle fiber metabolic disorders by measuring gene expression in relationship with the histological phenotype. Genotypying analysis of GYS1 mutation revealed 2 homozygous (AA) and 5 heterozygous (GA) PSSM horses. In the PSSM muscles, histological data revealed PAS positive amylase resistant abnormal polysaccharides, inflammation, necrosis, and lipomatosis and active regeneration of fibers. Ultrastructural evaluation revealed a decrease of mitochondrial number and structural disorders. Extensive accumulation of an abnormal polysaccharide displaced and partially replaced mitochondria and myofibrils. The severity of the disease was higher in the two homozygous PSSM horses.Gene expression analysis revealed 129 genes significantly modulated (p < 0.05). The following genes were up-regulated over 2 fold: IL18, CTSS, LUM, CD44, FN1, GST01. The most down-regulated genes were the following: mitochondrial tRNA, SLC2A2, PRKCalpha, VEGFalpha. Data mining analysis showed that protein synthesis, apoptosis, cellular movement, growth and proliferation were the main cellular functions significantly associated with the modulated genes (p < 0.05). Several up-regulated genes, especially IL18, revealed a severe muscular inflammation in PSSM muscles. The up-regulation of glycogen synthase kinase-3 (GSK3beta) under its active form could be responsible for glycogen synthase (GYS1) inhibition and hypoxia-inducible factor (HIF1alpha) destabilization. The main disorders observed in PSSM muscles could be related to mitochondrial dysfunctions, glycogenesis inhibition and the chronic hypoxia of the PSSM muscles.

To 3D or Not to 3D, That Is the Question: Do 3D Surface Analyses Improve the Ecomorphological Power of the Distal Femur in Placental Mammals?

PubMed Central

Gould, Francois D. H.

2014-01-01

Improvements in three-dimensional imaging technologies have renewed interest in the study of functional and ecological morphology. Quantitative approaches to shape analysis are used increasingly to study form-function relationships. These methods are computationally intensive, technically demanding, and time-consuming, which may limit sampling potential. There have been few side-by-side comparisons of the effectiveness of such approaches relative to more traditional analyses using linear measurements and ratios. Morphological variation in the distal femur of mammals has been shown to reflect differences in locomotor modes across clades. Thus I tested whether a geometric morphometric analysis of surface shape was superior to a multivariate analysis of ratios for describing ecomorphological patterns in distal femoral variation. A sample of 164 mammalian specimens from 44 genera was assembled. Each genus was assigned to one of six locomotor categories. The same hypotheses were tested using two methods. Six linear measurements of the distal femur were taken with calipers, from which four ratios were calculated. A 3D model was generated with a laser scanner, and analyzed using three dimensional geometric morphometrics. Locomotor category significantly predicted variation in distal femoral morphology in both analyses. Effect size was larger in the geometric morphometric analysis than in the analysis of ratios. Ordination reveals a similar pattern with arboreal and cursorial taxa as extremes on a continuum of morphologies in both analyses. Discriminant functions calculated from the geometric morphometric analysis were more accurate than those calculated from ratios. Both analysis of ratios and geometric morphometric surface analysis reveal similar, biologically meaningful relationships between distal femoral shape and locomotor mode. The functional signal from the morphology is slightly higher in the geometric morphometric analysis. The practical costs of conducting these sorts of analyses should be weighed against potentially slight increases in power when designing protocols for ecomorphological studies. PMID:24633081

Reveal genes functionally associated with ACADS by a network study.

PubMed

Chen, Yulong; Su, Zhiguang

2015-09-15

Establishing a systematic network is aimed at finding essential human gene-gene/gene-disease pathway by means of network inter-connecting patterns and functional annotation analysis. In the present study, we have analyzed functional gene interactions of short-chain acyl-coenzyme A dehydrogenase gene (ACADS). ACADS plays a vital role in free fatty acid β-oxidation and regulates energy homeostasis. Modules of highly inter-connected genes in disease-specific ACADS network are derived by integrating gene function and protein interaction data. Among the 8 genes in ACADS web retrieved from both STRING and GeneMANIA, ACADS is effectively conjoined with 4 genes including HAHDA, HADHB, ECHS1 and ACAT1. The functional analysis is done via ontological briefing and candidate disease identification. We observed that the highly efficient-interlinked genes connected with ACADS are HAHDA, HADHB, ECHS1 and ACAT1. Interestingly, the ontological aspect of genes in the ACADS network reveals that ACADS, HAHDA and HADHB play equally vital roles in fatty acid metabolism. The gene ACAT1 together with ACADS indulges in ketone metabolism. Our computational gene web analysis also predicts potential candidate disease recognition, thus indicating the involvement of ACADS, HAHDA, HADHB, ECHS1 and ACAT1 not only with lipid metabolism but also with infant death syndrome, skeletal myopathy, acute hepatic encephalopathy, Reye-like syndrome, episodic ketosis, and metabolic acidosis. The current study presents a comprehensible layout of ACADS network, its functional strategies and candidate disease approach associated with ACADS network. Copyright © 2015 Elsevier B.V. All rights reserved.

A Rice PECTATE LYASE-LIKE Gene Is Required for Plant Growth and Leaf Senescence1[OPEN

PubMed Central

Leng, Yujia; Yang, Yaolong; Ren, Deyong; Dai, Liping; Wang, Yuqiong; Chen, Long; Tu, Zhengjun; Gao, Yihong; Zhu, Li; Hu, Jiang; Gao, Zhenyu; Guo, Longbiao; Lin, Yongjun

2017-01-01

To better understand the molecular mechanisms behind plant growth and leaf senescence in monocot plants, we identified a mutant exhibiting dwarfism and an early-senescence leaf phenotype, termed dwarf and early-senescence leaf1 (del1). Histological analysis showed that the abnormal growth was caused by a reduction in cell number. Further investigation revealed that the decline in cell number in del1 was affected by the cell cycle. Physiological analysis, transmission electron microscopy, and TUNEL assays showed that leaf senescence was triggered by the accumulation of reactive oxygen species. The DEL1 gene was cloned using a map-based approach. It was shown to encode a pectate lyase (PEL) precursor that contains a PelC domain. DEL1 contains all the conserved residues of PEL and has strong similarity with plant PelC. DEL1 is expressed in all tissues but predominantly in elongating tissues. Functional analysis revealed that mutation of DEL1 decreased the total PEL enzymatic activity, increased the degree of methylesterified homogalacturonan, and altered the cell wall composition and structure. In addition, transcriptome assay revealed that a set of cell wall function- and senescence-related gene expression was altered in del1 plants. Our research indicates that DEL1 is involved in both the maintenance of normal cell division and the induction of leaf senescence. These findings reveal a new molecular mechanism for plant growth and leaf senescence mediated by PECTATE LYASE-LIKE genes. PMID:28455404

A Rice PECTATE LYASE-LIKE Gene Is Required for Plant Growth and Leaf Senescence.

PubMed

Leng, Yujia; Yang, Yaolong; Ren, Deyong; Huang, Lichao; Dai, Liping; Wang, Yuqiong; Chen, Long; Tu, Zhengjun; Gao, Yihong; Li, Xueyong; Zhu, Li; Hu, Jiang; Zhang, Guangheng; Gao, Zhenyu; Guo, Longbiao; Kong, Zhaosheng; Lin, Yongjun; Qian, Qian; Zeng, Dali

2017-06-01

To better understand the molecular mechanisms behind plant growth and leaf senescence in monocot plants, we identified a mutant exhibiting dwarfism and an early-senescence leaf phenotype, termed dwarf and early-senescence leaf1 ( del1 ). Histological analysis showed that the abnormal growth was caused by a reduction in cell number. Further investigation revealed that the decline in cell number in del1 was affected by the cell cycle. Physiological analysis, transmission electron microscopy, and TUNEL assays showed that leaf senescence was triggered by the accumulation of reactive oxygen species. The DEL1 gene was cloned using a map-based approach. It was shown to encode a pectate lyase (PEL) precursor that contains a PelC domain. DEL1 contains all the conserved residues of PEL and has strong similarity with plant PelC. DEL1 is expressed in all tissues but predominantly in elongating tissues. Functional analysis revealed that mutation of DEL1 decreased the total PEL enzymatic activity, increased the degree of methylesterified homogalacturonan, and altered the cell wall composition and structure. In addition, transcriptome assay revealed that a set of cell wall function- and senescence-related gene expression was altered in del1 plants. Our research indicates that DEL1 is involved in both the maintenance of normal cell division and the induction of leaf senescence. These findings reveal a new molecular mechanism for plant growth and leaf senescence mediated by PECTATE LYASE-LIKE genes. © 2017 American Society of Plant Biologists. All Rights Reserved.

Persulfidation proteome reveals the regulation of protein function by hydrogen sulfide in diverse biological processes in Arabidopsis.

PubMed

Aroca, Angeles; Benito, Juan M; Gotor, Cecilia; Romero, Luis C

2017-10-13

Hydrogen sulfide-mediated signaling pathways regulate many physiological and pathophysiological processes in mammalian and plant systems. The molecular mechanism by which hydrogen sulfide exerts its action involves the post-translational modification of cysteine residues to form a persulfidated thiol motif, a process called protein persulfidation. We have developed a comparative and quantitative proteomic analysis approach for the detection of endogenous persulfidated proteins in wild-type Arabidopsis and L-CYSTEINE DESULFHYDRASE 1 mutant leaves using the tag-switch method. The 2015 identified persulfidated proteins were isolated from plants grown under controlled conditions, and therefore, at least 5% of the entire Arabidopsis proteome may undergo persulfidation under baseline conditions. Bioinformatic analysis revealed that persulfidated cysteines participate in a wide range of biological functions, regulating important processes such as carbon metabolism, plant responses to abiotic and biotic stresses, plant growth and development, and RNA translation. Quantitative analysis in both genetic backgrounds reveals that protein persulfidation is mainly involved in primary metabolic pathways such as the tricarboxylic acid cycle, glycolysis, and the Calvin cycle, suggesting that this protein modification is a new regulatory component in these pathways. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

An analysis of prognostic factors after percutaneous endoscopic gastrostomy placement in Japanese patients with amyotrophic lateral sclerosis.

PubMed

Nagashima, Kazuaki; Furuta, Natsumi; Makioka, Kouki; Fujita, Yukio; Ikeda, Masaki; Ikeda, Yoshio

2017-05-15

A percutaneous endoscopic gastrostomy (PEG) is an useful intervention for feeding of amyotrophic lateral sclerosis (ALS) patients who have lost oral intake function. The aim of this study was to investigate the risk factors for early death and the survival after PEG placement. A total of 102 ALS patients who underwent PEG placement were enrolled in this study. Patients were divided into two groups; the poor prognosis group included patients who died or needed permanent mechanical ventilation within 30days after PEG placement, and the good prognosis group included patients who did not meet the criteria of the poor prognosis group. Clinical characteristics, respiratory function, and nutritional parameters were compared for the two groups to assess the correlations between clinical and laboratory variables and early death after PEG placement. Multivariate analysis between two groups revealed that higher arterial carbon dioxide pressure (PaCO 2 ) and aphagia before PEG placement were significantly associated with the poor prognosis group. Multivariate analysis for survival also revealed that higher PaCO 2 and shorter duration from onset to PEG placement were significantly associated with shorter survival after PEG placement. In conclusion, respiratory and nutritional parameters are revealed to be important prognostic factors for ALS patients who undergo PEG placement. Copyright © 2017 Elsevier B.V. All rights reserved.

Transcriptome profiling of a Saccharomyces cerevisiae mutant with a constitutively activated Ras/cAMP pathway.

PubMed

Jones, D L; Petty, J; Hoyle, D C; Hayes, A; Ragni, E; Popolo, L; Oliver, S G; Stateva, L I

2003-12-16

Often changes in gene expression levels have been considered significant only when above/below some arbitrarily chosen threshold. We investigated the effect of applying a purely statistical approach to microarray analysis and demonstrated that small changes in gene expression have biological significance. Whole genome microarray analysis of a pde2Delta mutant, constructed in the Saccharomyces cerevisiae reference strain FY23, revealed altered expression of approximately 11% of protein encoding genes. The mutant, characterized by constitutive activation of the Ras/cAMP pathway, has increased sensitivity to stress, reduced ability to assimilate nonfermentable carbon sources, and some cell wall integrity defects. Applying the Munich Information Centre for Protein Sequences (MIPS) functional categories revealed increased expression of genes related to ribosome biogenesis and downregulation of genes in the cell rescue, defense, cell death and aging category, suggesting a decreased response to stress conditions. A reduced level of gene expression in the unfolded protein response pathway (UPR) was observed. Cell wall genes whose expression was affected by this mutation were also identified. Several of the cAMP-responsive orphan genes, upon further investigation, revealed cell wall functions; others had previously unidentified phenotypes assigned to them. This investigation provides a statistical global transcriptome analysis of the cellular response to constitutive activation of the Ras/cAMP pathway.

Gene Ontology-Based Analysis of Zebrafish Omics Data Using the Web Tool Comparative Gene Ontology.

PubMed

Ebrahimie, Esmaeil; Fruzangohar, Mario; Moussavi Nik, Seyyed Hani; Newman, Morgan

2017-10-01

Gene Ontology (GO) analysis is a powerful tool in systems biology, which uses a defined nomenclature to annotate genes/proteins within three categories: "Molecular Function," "Biological Process," and "Cellular Component." GO analysis can assist in revealing functional mechanisms underlying observed patterns in transcriptomic, genomic, and proteomic data. The already extensive and increasing use of zebrafish for modeling genetic and other diseases highlights the need to develop a GO analytical tool for this organism. The web tool Comparative GO was originally developed for GO analysis of bacterial data in 2013 ( www.comparativego.com ). We have now upgraded and elaborated this web tool for analysis of zebrafish genetic data using GOs and annotations from the Gene Ontology Consortium.

Racial and Socioeconomic Gaps in Executive Function Skills in Early Elementary School: Nationally Representative Evidence From the ECLS-K:2011

ERIC Educational Resources Information Center

Little, Michael

2017-01-01

This brief leverages the first ever nationally representative data set with a direct assessment of elementary school-aged children's executive function skills to examine racial and socioeconomic gaps in performance. The analysis reveals large gaps in measures of working memory and cognitive flexibility, the two components of executive function…

Vocal function after transoral videolaryngoscopic surgery (TOVS) for hypopharyngeal and supraglottic cancer.

PubMed

Tanaka, Shingo; Tomifuji, Masayuki; Araki, Koji; Uno, Kosuke; Tanaka, Yuya; Mizokami, Daisuke; Suzuki, Hiroshi; Miyagawa, Yoshihiro; Taniai, Shinichi; Shiotani, Akihiro

2017-04-01

The resection of the medial and lateral pyriform sinus was associated with post-operative voice impairment after TOVS. Scar contracture around the cricoarytenoid joint lead to arytenoid fixation toward lateral position, and this wound healing process caused insufficient glottis closure. Although oncological and functional outcomes of TOVS was satisfactory, surgeons should mention the risk of post-operative voice impairment in pre-operative counseling. Transoral surgery is a minimally invasive treatment option for hypopharyngeal and supraglottic cancer. Post-operative vocal function was satisfactory in most cases, but in some cases vocal cord was fixed and occasionally voice impairment persists. Vocal function of 55 patients who underwent transoral videolaryngoscopic surgery (TOVS) for hypopharyngeal and supraglottic cancers was evaluated by the GRBAS perceptive scale, aerodynamic tests and acoustic analyses, and the Voice Handicap Index questionnaire. The risk factors for voice impairment were identified. Voice impairment (G score ≧2) was found in 16 cases (29.1%). Univariate analysis revealed that the resection of medial and lateral pyriform sinus (p = .0018) and neck dissection (p = .0421) were associated with post-operative voice impairment. Multivariate analysis revealed that the resection of medial and lateral pyriform sinus (p = .0021) was associated with post-operative voice impairment.

Enzyme-mediated assimilation of DNA-functionalized single-walled carbon nanotubes.

PubMed

Arnett, Clint M; Marsh, Charles P; Welch, Charles R; Strano, Michael S; Han, Jae-Hee; Gray, Jeffry H; Carlson, Thomas A

2010-01-19

When pyrimidine-functionalized carbon nanotubes were incubated with single-stranded DNA ligase, formations of macroscopic aggregates were observed. Wet-cell transmission electron microscopy imaging revealed that the nanotubes were radially bound to form a 3D latticelike structure. These structures were not observed in control reactions lacking ligase or adenosine triphosphate. Raman spectroscopy analysis revealed no spectra indicative of carbon nanotubes in ligase-unamended controls; however, spectra were observed in radial breathing mode and in the G and G' bands in reactions containing ligase. Furthermore, the addition of deoxyribonuclease to the ligated reactions dispersed the aggregates, and a reduction in Raman spectral intensity was observed.

Repression of enhancer II activity by a negative regulatory element in the hepatitis B virus genome.

PubMed Central

Lo, W Y; Ting, L P

1994-01-01

Enhancer II of human hepatitis B virus has dual functions in vivo. Located at nucleotides (nt) 1646 to 1741, it can stimulate the surface and X promoters from a downstream position. Moreover, the same sequence can also function as upstream regulatory element that activates the core promoter in a position- and orientation-dependent manner. In this study, we report the identification and characterization of a negative regulatory element (NRE) upstream of enhancer II (nt 1613 to 1636) which can repress both the enhancer and upstream stimulatory function of the enhancer II sequence in differentiated liver cells. This NRE has marginal inhibitory effect by itself but a strong repressive function in the presence of a functional enhancer II. Mutational analysis reveals that sequence from nt 1616 to 1621 is required for repression of enhancer activity by the NRE. Gel shift analysis reveals that this negative regulatory region can be recognized by a specific protein factor(s) present at the 0.4 M NaCl fraction of HepG2 nuclear extracts. The discovery of the NRE indicates that HBV gene transcription is controlled by combined effects of both positive and negative regulation. It also provides a unique system with which to study the mechanism of negative regulation of gene expression. Images PMID:8107237

Lysine acetylome profiling uncovers novel histone deacetylase substrate proteins in Arabidopsis.

PubMed

Hartl, Markus; Füßl, Magdalena; Boersema, Paul J; Jost, Jan-Oliver; Kramer, Katharina; Bakirbas, Ahmet; Sindlinger, Julia; Plöchinger, Magdalena; Leister, Dario; Uhrig, Glen; Moorhead, Greg Bg; Cox, Jürgen; Salvucci, Michael E; Schwarzer, Dirk; Mann, Matthias; Finkemeier, Iris

2017-10-23

Histone deacetylases have central functions in regulating stress defenses and development in plants. However, the knowledge about the deacetylase functions is largely limited to histones, although these enzymes were found in diverse subcellular compartments. In this study, we determined the proteome-wide signatures of the RPD3/HDA1 class of histone deacetylases in Arabidopsis Relative quantification of the changes in the lysine acetylation levels was determined on a proteome-wide scale after treatment of Arabidopsis leaves with deacetylase inhibitors apicidin and trichostatin A. We identified 91 new acetylated candidate proteins other than histones, which are potential substrates of the RPD3/HDA1-like histone deacetylases in Arabidopsis , of which at least 30 of these proteins function in nucleic acid binding. Furthermore, our analysis revealed that histone deacetylase 14 (HDA14) is the first organellar-localized RPD3/HDA1 class protein found to reside in the chloroplasts and that the majority of its protein targets have functions in photosynthesis. Finally, the analysis of HDA14 loss-of-function mutants revealed that the activation state of RuBisCO is controlled by lysine acetylation of RuBisCO activase under low-light conditions. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Chronic kidney disease: Pathological and functional evaluation with intravoxel incoherent motion diffusion-weighted imaging.

PubMed

Mao, Wei; Zhou, Jianjun; Zeng, Mengsu; Ding, Yuqin; Qu, Lijie; Chen, Caizhong; Ding, Xiaoqiang; Wang, Yaqiong; Fu, Caixia

2018-05-01

Because chronic kidney disease (CKD) is a worldwide problem, accurate pathological and functional evaluation is required for planning treatment and follow-up. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can assess both capillary perfusion and tissue diffusion and may be helpful in evaluating renal function and pathology. To evaluate functional and pathological alterations in CKD by applying IVIM-DWI. Prospective study. In all, 72 CKD patients who required renal biopsy and 20 healthy volunteers. 1.5T. All subjects underwent IVIM-DWI of the kidneys, and image analysis was performed by two radiologists. The mean values of true diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f) were acquired from renal parenchyma. Correlation between IVIM-DWI parameters and estimated glomerular filtration rate (eGFR), as well as pathological damage, were assessed. One-way analysis of variance (ANOVA), paired sample t-test and Spearman correlation analysis. The paired sample t-test revealed that IVIM-DWI parameters were significantly lower in medulla than cortex for both patients and controls (P < 0.01). Regardless of whether eGFR was reduced, ANOVA revealed that f values of renal parenchyma were significantly lower in patients than controls (P < 0.05). Spearman correlation analysis revealed that there were positive correlations between eGFR and D (cortex, r = 0.466, P < 0.001; medulla, r = 0.491, P < 0.001), and between eGFR and f (cortex, r = 0.713, P < 0.001; medulla, r = 0.512, P < 0.001). Negative correlations were found between f and glomerular injury (cortex, r = -0.773, P < 0.001; medulla, r = -0.629, P < 0.001), and between f and tubulointerstitial lesion (cortex, r = -0.728, P < 0.001; medulla, r = -0.547, P < 0.001). IVIM-DWI might be feasible for noninvasive evaluation of renal function and pathology of CKD, especially in detection of renal insufficiency at an early stage. 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1251-1259. © 2017 International Society for Magnetic Resonance in Medicine.

Optical properties of boron-group (V) hexagonal nanowires: DFT investigation

NASA Astrophysics Data System (ADS)

Santhibhushan, B.; Soni, Mahesh; Srivastava, Anurag

2017-07-01

The paper presents structural, electronic and optical properties of boron-group V hexagonal nanowires (h-NW) within the framework of density functional theory. The h-NW of boron-group V compounds with an analogous diameter of 12 Å have been designed in (1 1 1) plane. Stability analysis performed through formation energies reveal that, the stability of these structures decreases with increasing atomic number of the group V element. The band nature predicts that these nanowires are good electrical conductors. Optical behaviour of the nanowires has been analysed through absorption coefficient, reflectivity, refractive index, optical conductivity and electron energy loss spectrum (EELS), that are computed from the frequency-dependent complex dielectric function. The analysis reveals high reactivity of BP and BAs h-NWs to the incident light especially in the IR and visible ranges, and the optical transparency of BN h-NW in the visible and UV ranges.

Structural analysis and biomedical applications of dextran produced by a new isolate Pediococcus pentosaceus screened from biodiversity hot spot Assam.

PubMed

Patel, Seema; Kasoju, Naresh; Bora, Utpal; Goyal, Arun

2010-09-01

Dextran produced by a natural isolate of Pediococcus pentosaceus, screened from Assam, in the Northeastern region of India, was estimated, purified, structure characterised and functionality analysed. The dextran concentration in the cell free supernatant of the isolate P. pentosaceus was 10.2mg/ml. FT-IR analysis revealed the hydroxyl and carboxyl functional groups present in the dextran. (1)H NMR and (13)C NMR spectral data revealed that the dextran has a linear backbone of alpha-(1-->6) linked D-glucose residues. The decrease in viscosity of dextran solution with the increase in shear rate, threw light on its typical non-Newtonian pseudoplastic behaviour. The cytotoxicity tests on human cervical cancer (HeLa) cell line was studied which showed the dextran is non-toxic and biocompatible, rendering it safe for drug delivery, tissue engineering and various other biomedical applications. (c) 2010 Elsevier Ltd. All rights reserved.

Neurocognitive Functioning in Patients with 22q11.2 Deletion Syndrome: A Meta-Analytic Review.

PubMed

Moberg, Paul J; Richman, Mara J; Roalf, David R; Morse, Chelsea L; Graefe, Anna C; Brennan, Laura; Vickers, Kayci; Tsering, Wangchen; Kamath, Vidyulata; Turetsky, Bruce I; Gur, Ruben C; Gur, Raquel E

2018-06-19

The 22q11.2 deletion syndrome (22q11.2DS) is a known risk factor for development of schizophrenia and is characterized by a complex neuropsychological profile. To date, a quantitative meta-analysis examining cognitive functioning in 22q11.2DS has not been conducted. A systematic review of cross-sectional studies comparing neuropsychological performance of individuals with 22q11.2DS with age-matched healthy typically developing and sibling comparison subjects was carried out. Potential moderators were analyzed. Analyses included 43 articles (282 effects) that met inclusion criteria. Very large and heterogeneous effects were seen for global cognition (d = - 1.21) and in specific neuropsychological domains (intellectual functioning, achievement, and executive function; d range = - 0.51 to - 2.43). Moderator analysis revealed a significant role for type of healthy comparison group used (typically developing or siblings), demographics (age, sex) and clinical factors (externalizing behavior). Results revealed significant differences between pediatric and adult samples, with isolated analysis within the pediatric sample yielding large effects in several neuropsychological domains (intellectual functioning, achievement, visual memory; d range = - 0.56 to - 2.50). Large cognitive deficits in intellectual functioning and specific neuropsychological variables in individuals with 22q11.2DS represent a robust finding, but these deficits are influenced by several factors, including type of comparison group utilized, age, sex, and clinical status. These findings highlight the clinical relevance of characterizing cognitive functioning in 22q11.2DS and the importance of considering demographic and clinical moderators in future analyses.

The point-spread function of fiber-coupled area detectors

PubMed Central

Holton, James M.; Nielsen, Chris; Frankel, Kenneth A.

2012-01-01

The point-spread function (PSF) of a fiber-optic taper-coupled CCD area detector was measured over five decades of intensity using a 20 µm X-ray beam and ∼2000-fold averaging. The ‘tails’ of the PSF clearly revealed that it is neither Gaussian nor Lorentzian, but instead resembles the solid angle subtended by a pixel at a point source of light held a small distance (∼27 µm) above the pixel plane. This converges to an inverse cube law far from the beam impact point. Further analysis revealed that the tails are dominated by the fiber-optic taper, with negligible contribution from the phosphor, suggesting that the PSF of all fiber-coupled CCD-type detectors is best described as a Moffat function. PMID:23093762

Do tasks make a difference? Accounting for heterogeneity of performance of children with reading difficulties on tasks of executive function: findings from a meta-analysis.

PubMed

Booth, Josephine N; Boyle, James M E; Kelly, Steve W

2010-03-01

Research studies have implicated executive functions in reading difficulties (RD). But while some studies have found children with RD to be impaired on tasks of executive function other studies report unimpaired performance. A meta-analysis was carried out to determine whether these discrepant findings can be accounted for by differences in the tasks of executive function that are utilized. A total of 48 studies comparing the performance on tasks of executive function of children with RD with their typically developing peers were included in the meta-analysis, yielding 180 effect sizes. An overall effect size of 0.57 (SE .03) was obtained, indicating that children with RD have impairments on tasks of executive function. However, effect sizes varied considerably suggesting that the impairment is not uniform. Moderator analysis revealed that task modality and IQ-achievement discrepancy definitions of RD influenced the magnitude of effect; however, the age and gender of participants and the nature of the RD did not have an influence. While the children's RD were associated with executive function impairments, variation in effect size is a product of the assessment task employed, underlying task demands, and definitional criteria.

[PSYCHO PHYSIOLOGICAL MARKERS OF ACCELERATED AGING AMONG THOSE WORKING WITH OCCUPATIONAL HAZARDS].

PubMed

Bashkireva, A S; Kachan, Ye Yu; Kulapina, M E

2015-01-01

We assessed the significance of psycho physiological markers of accelerated aging of the function of attention using comparative analysis of two occupational groups in order to reveal how the working process affects mental work capacity. We revealed peculiarities of systemic structure of functions which determine mental work capacity depending on the age and length of service in lorry drivers. It was proved that decrease in the mnestic functions of lorry-drivers takes place 10-15 years earlier compared to the control group. Psycho physiological indices, reflecting the functioning of attention, decreased not only with aging but also with longer driving experience. Our results show that it is necessary to conduct further studies of psycho physiological markers of age-related decrease in short-term memory depending on the activities at work in order to prevent accelerated aging and achieve professional longevity.

Revealing the Strong Functional Association of adipor2 and cdh13 with adipoq: A Gene Network Study.

PubMed

Bag, Susmita; Anbarasu, Anand

2015-04-01

In the present study, we have analyzed functional gene interactions of adiponectin gene (adipoq). The key role of adipoq is in regulating energy homeostasis and it functions as a novel signaling molecule for adipose tissue. Modules of highly inter-connected genes in disease-specific adipoq network are derived by integrating gene function and protein interaction data. Among twenty genes in adipoq web, adipoq is effectively conjoined with two genes: Adiponectin receptor 2 (adipor2) and cadherin 13 (cdh13). The functional analysis is done via ontological briefing and candidate disease identification. We observed that the highly efficient-interlinked genes connected with adipoq are adipor2 and cdh13. Interestingly, the ontological aspect of adipor2 and cdh13 in the adipoq network reveal the fact that adipoq and adipor2 are involved mostly in glucose and lipid metabolic processes. The gene cdh13 indulge in cell adhesion process with adipoq and adipor2. Our computational gene web analysis also predicts potential candidate disease recognition, thus indicating the involvement of adipoq, adipor2, and cdh13 with not only with obesity but also with breast cancer, leukemia, renal cancer, lung cancer, and cervical cancer. The current study provides researchers a comprehensible layout of adipoq network, its functional strategies and candidate disease approach associated with adipoq network.

DELINEATING SUBTYPES OF SELF-INJURIOUS BEHAVIOR MAINTAINED BY AUTOMATIC REINFORCEMENT

PubMed Central

Hagopian, Louis P.; Rooker, Griffin W.; Zarcone, Jennifer R.

2016-01-01

Self-injurious behavior (SIB) is maintained by automatic reinforcement in roughly 25% of cases. Automatically reinforced SIB typically has been considered a single functional category, and is less understood than socially reinforced SIB. Subtyping automatically reinforced SIB into functional categories has the potential to guide the development of more targeted interventions and increase our understanding of its biological underpinnings. The current study involved an analysis of 39 individuals with automatically reinforced SIB and a comparison group of 13 individuals with socially reinforced SIB. Automatically reinforced SIB was categorized into 3 subtypes based on patterns of responding in the functional analysis and the presence of self-restraint. These response features were selected as the basis for subtyping on the premise that they could reflect functional properties of SIB unique to each subtype. Analysis of treatment data revealed important differences across subtypes and provides preliminary support to warrant additional research on this proposed subtyping model. PMID:26223959

Horizontal gene transfer in silkworm, Bombyx mori.

PubMed

Zhu, Bo; Lou, Miao-Miao; Xie, Guan-Lin; Zhang, Guo-Qing; Zhou, Xue-Ping; Li, Bin; Jin, Gu-Lei

2011-05-19

The domesticated silkworm, Bombyx mori, is the model insect for the order Lepidoptera, has economically important values, and has gained some representative behavioral characteristics compared to its wild ancestor. The genome of B. mori has been fully sequenced while function analysis of BmChi-h and BmSuc1 genes revealed that horizontal gene transfer (HGT) maybe bestow a clear selective advantage to B. mori. However, the role of HGT in the evolutionary history of B. mori is largely unexplored. In this study, we compare the whole genome of B. mori with those of 382 prokaryotic and eukaryotic species to investigate the potential HGTs. Ten candidate HGT events were defined in B. mori by comprehensive sequence analysis using Maximum Likelihood and Bayesian method combining with EST checking. Phylogenetic analysis of the candidate HGT genes suggested that one HGT was plant-to- B. mori transfer while nine were bacteria-to- B. mori transfer. Furthermore, functional analysis based on expression, coexpression and related literature searching revealed that several HGT candidate genes have added important characters, such as resistance to pathogen, to B. mori. Results from this study clearly demonstrated that HGTs play an important role in the evolution of B. mori although the number of HGT events in B. mori is in general smaller than those of microbes and other insects. In particular, interdomain HGTs in B. mori may give rise to functional, persistent, and possibly evolutionarily significant new genes.

Analysis/forecast experiments with a flow-dependent correlation function using FGGE data

NASA Technical Reports Server (NTRS)

Baker, W. E.; Bloom, S. C.; Carus, H.; Nestler, M. S.

1986-01-01

The use of a flow-dependent correlation function to improve the accuracy of an optimum interpolation (OI) scheme is examined. The development of the correlation function for the OI analysis scheme used for numerical weather prediction is described. The scheme uses a multivariate surface analysis over the oceans to model the pressure-wind error cross-correlation and it has the ability to use an error correlation function that is flow- and geographically-dependent. A series of four-day data assimilation experiments, conducted from January 5-9, 1979, were used to investigate the effect of the different features of the OI scheme (error correlation) on forecast skill for the barotropic lows and highs. The skill of the OI was compared with that of a successive correlation method (SCM) of analysis. It is observed that the largest difference in the correlation statistics occurred in barotropic and baroclinic lows and highs. The comparison reveals that the OI forecasts were more accurate than the SCM forecasts.

The heptanucleotide motif GAGACGC is a key component of a cis-acting promoter element that is critical for SnSAG1 expression in Sarcocystis neurona.

PubMed

Gaji, Rajshekhar Y; Howe, Daniel K

2009-07-01

The apicomplexan parasite Sarcocystis neurona undergoes a complex process of intracellular development, during which many genes are temporally regulated. The described study was undertaken to begin identifying the basic promoter elements that control gene expression in S. neurona. Sequence analysis of the 5'-flanking region of five S. neurona genes revealed a conserved heptanucleotide motif GAGACGC that is similar to the WGAGACG motif described upstream of multiple genes in Toxoplasma gondii. The promoter region for the major surface antigen gene SnSAG1, which contains three heptanucleotide motifs within 135 bases of the transcription start site, was dissected by functional analysis using a dual luciferase reporter assay. These analyses revealed that a minimal promoter fragment containing all three motifs was sufficient to drive reporter molecule expression, with the presence and orientation of the 5'-most heptanucleotide motif being absolutely critical for promoter function. Further studies should help to identify additional sequence elements important for promoter function and for controlling gene expression during intracellular development by this apicomplexan pathogen.

The Thiamine-Pyrophosphate-Motif

NASA Technical Reports Server (NTRS)

Ciszak, Ewa; Dominiak, Paulina

2004-01-01

Thiamin pyrophosphate (TPP), a derivative of vitamin B1, is a cofactor for enzymes performing catalysis in pathways of energy production including the well known decarboxylation of a-keto acid dehydrogenases followed by transketolation. TPP-dependent enzymes constitute a structurally and functionally diverse group exhibiting multimeric subunit organization, multiple domains and two chemically equivalent catalytic centers. Annotation of functional TPP-dependcnt enzymes, therefore, has not been trivial due to low sequence similarity related to this complex organization. Our approach to analysis of structures of known TPP-dependent enzymes reveals for the first time features common to this group, which we have termed the TPP-motif. The TPP-motif consists of specific spatial arrangements of structural elements and their specific contacts to provide for a flip-flop, or alternate site, enzymatic mechanism of action. Analysis of structural elements entrained in the flip-flop action displayed by TPP-dependent enzymes reveals a novel definition of the common amino acid sequences. These sequences allow for annotation of TPP-dependent enzymes, thus advancing functional proteomics. Further details of three-dimensional structures of TPP-dependent enzymes will be discussed.

Differential Adjustment Among Rural Adolescents Exposed to Family Violence.

PubMed

Sianko, Natallia; Hedge, Jasmine M; McDonell, James R

2016-04-22

This study examines differences in psychological adjustment in a sample of rural adolescents who have been exposed to family violence. Self-report questionnaires were administered to 580 adolescents and their primary caregivers. The results revealed that over two thirds of the study participants (68.8%) had been exposed to violence in their families. As hypothesized, cluster analysis identified several profiles among adolescents, distinguished by their psychological and emotional functioning: well adjusted (46.2%), moderately adjusted (44.3%), and struggling (9.5%). Discriminant function analysis confirmed the groupings and revealed that family functioning was among the most influential factors explaining adjustment differences. Multivariate analyses of variance (MANOVAs) further showed that adolescents from each of the three adjustment profiles reported significantly different levels of family social support, parental involvement, and perceived neighborhood safety. Overall, the results confirm heterogeneity of adolescent adaptation in the aftermath of family violence and provide insights into family and neighborhood factors that account for variability in adolescents' reactions to violence. Implications for future research and practical interventions are discussed. © The Author(s) 2016.

Metagenomic analysis of microbial consortia enriched from compost: new insights into the role of Actinobacteria in lignocellulose decomposition.

PubMed

Wang, Cheng; Dong, Da; Wang, Haoshu; Müller, Karin; Qin, Yong; Wang, Hailong; Wu, Weixiang

2016-01-01

Compost habitats sustain a vast ensemble of microbes specializing in the degradation of lignocellulosic plant materials and are thus important both for their roles in the global carbon cycle and as potential sources of biochemical catalysts for advanced biofuels production. Studies have revealed substantial diversity in compost microbiomes, yet how this diversity relates to functions and even to the genes encoding lignocellulolytic enzymes remains obscure. Here, we used a metagenomic analysis of the rice straw-adapted (RSA) microbial consortia enriched from compost ecosystems to decipher the systematic and functional contexts within such a distinctive microbiome. Analyses of the 16S pyrotag library and 5 Gbp of metagenomic sequence showed that the phylum Actinobacteria was the predominant group among the Bacteria in the RSA consortia, followed by Proteobacteria, Firmicutes, Chloroflexi, and Bacteroidetes. The CAZymes profile revealed that CAZyme genes in the RSA consortia were also widely distributed within these bacterial phyla. Strikingly, about 46.1 % of CAZyme genes were from actinomycetal communities, which harbored a substantially expanded catalog of the cellobiohydrolase, β-glucosidase, acetyl xylan esterase, arabinofuranosidase, pectin lyase, and ligninase genes. Among these communities, a variety of previously unrecognized species was found, which reveals a greater ecological functional diversity of thermophilic Actinobacteria than previously assumed. These data underline the pivotal role of thermophilic Actinobacteria in lignocellulose biodegradation processes in the compost habitat. Besides revealing a new benchmark for microbial enzymatic deconstruction of lignocelluloses, the results suggest that actinomycetes found in compost ecosystems are potential candidates for mining efficient lignocellulosic enzymes in the biofuel industry.

Functional diversity of Csk, Chk, and Src SH2 domains due to a single residue variation.

PubMed

Ayrapetov, Marina K; Nam, Nguyen Hai; Ye, Guofeng; Kumar, Anil; Parang, Keykavous; Sun, Gongqin

2005-07-08

The C-terminal Src kinase (Csk) family of protein tyrosine kinases contains two members: Csk and Csk homologous kinase (Chk). Both phosphorylate and inactivate Src family kinases. Recent reports suggest that the Src homology (SH) 2 domains of Csk and Chk may bind to different phosphoproteins, which provides a basis for different cellular functions for Csk and Chk. To verify and characterize such a functional divergence, we compared the binding properties of the Csk, Chk, and Src SH2 domains and investigated the structural basis for the functional divergence. First, the study demonstrated striking functional differences between the Csk and Chk SH2 domains and revealed functional similarities between the Chk and Src SH2 domains. Second, structural analysis and mutagenic studies revealed that the functional differences among the three SH2 domains were largely controlled by one residue, Glu127 in Csk, Ile167 in Chk, and Lys200 in Src. Mutating these residues in the Csk or Chk SH2 domain to the Src counterpart resulted in dramatic gain of function similar to Src SH2 domain, whereas mutating Lys200 in Src SH2 domain to Glu (the Csk counterpart) resulted in loss of Src SH2 function. Third, a single point mutation of E127K rendered Csk responsive to activation by a Src SH2 domain ligand. Finally, the optimal phosphopeptide sequence for the Chk SH2 domain was determined. These results provide a compelling explanation for the functional differences between two homologous protein tyrosine kinases and reveal a new structure-function relationship for the SH2 domains.

Genetics Home Reference: hereditary neuralgic amyotrophy

MedlinePlus

... tissues. This change in the functioning of septin proteins seems to particularly affect the brachial plexus, but the reason for this ... SH, Andermann E, Bird TD, Chance PF. SEPT9 gene sequencing analysis reveals recurrent mutations in hereditary neuralgic amyotrophy. ...

Sleep and Nutritional Deprivation and Performance of House Officers.

ERIC Educational Resources Information Center

Hawkins, Michael R.; And Others

1985-01-01

A study to compare cognitive functioning in acutely and chronically sleep-deprived house officers is described. A multivariate analysis of variance revealed significant deficits in primary mental tasks involving basic rote memory, language, and numeric skills. (Author/MLW)

Resting State Network Topology of the Ferret Brain

PubMed Central

Zhou, Zhe Charles; Salzwedel, Andrew P.; Radtke-Schuller, Susanne; Li, Yuhui; Sellers, Kristin K.; Gilmore, John H.; Shih, Yen-Yu Ian; Fröhlich, Flavio; Gao, Wei

2016-01-01

Resting state functional magnetic resonance imaging (rsfMRI) has emerged as a versatile tool for non-invasive measurement of functional connectivity patterns in the brain. RsfMRI brain dynamics in rodents, non-human primates, and humans share similar properties; however, little is known about the resting state functional connectivity patterns in the ferret, an animal model with high potential for developmental and cognitive translational study. To address this knowledge-gap, we performed rsfMRI on anesthetized ferrets using a 9.4 tesla MRI scanner, and subsequently performed group-level independent component analysis (gICA) to identify functionally connected brain networks. Group-level ICA analysis revealed distributed sensory, motor, and higher-order networks in the ferret brain. Subsequent connectivity analysis showed interconnected higher-order networks that constituted a putative default mode network (DMN), a network that exhibits altered connectivity in neuropsychiatric disorders. Finally, we assessed ferret brain topological efficiency using graph theory analysis and found that the ferret brain exhibits small-world properties. Overall, these results provide additional evidence for pan-species resting-state networks, further supporting ferret-based studies of sensory and cognitive function. PMID:27596024

The Information Content of Discrete Functions and Their Application in Genetic Data Analysis.

PubMed

Sakhanenko, Nikita A; Kunert-Graf, James; Galas, David J

2017-12-01

The complex of central problems in data analysis consists of three components: (1) detecting the dependence of variables using quantitative measures, (2) defining the significance of these dependence measures, and (3) inferring the functional relationships among dependent variables. We have argued previously that an information theory approach allows separation of the detection problem from the inference of functional form problem. We approach here the third component of inferring functional forms based on information encoded in the functions. We present here a direct method for classifying the functional forms of discrete functions of three variables represented in data sets. Discrete variables are frequently encountered in data analysis, both as the result of inherently categorical variables and from the binning of continuous numerical variables into discrete alphabets of values. The fundamental question of how much information is contained in a given function is answered for these discrete functions, and their surprisingly complex relationships are illustrated. The all-important effect of noise on the inference of function classes is found to be highly heterogeneous and reveals some unexpected patterns. We apply this classification approach to an important area of biological data analysis-that of inference of genetic interactions. Genetic analysis provides a rich source of real and complex biological data analysis problems, and our general methods provide an analytical basis and tools for characterizing genetic problems and for analyzing genetic data. We illustrate the functional description and the classes of a number of common genetic interaction modes and also show how different modes vary widely in their sensitivity to noise.

Metagenomic analysis reveals a green sulfur bacterium as a potential coral symbiont.

PubMed

Cai, Lin; Zhou, Guowei; Tian, Ren-Mao; Tong, Haoya; Zhang, Weipeng; Sun, Jin; Ding, Wei; Wong, Yue Him; Xie, James Y; Qiu, Jian-Wen; Liu, Sheng; Huang, Hui; Qian, Pei-Yuan

2017-08-24

Coral reefs are ecologically significant habitats. Coral-algal symbiosis confers ecological success on coral reefs and coral-microbial symbiosis is also vital to coral reefs. However, current understanding of coral-microbial symbiosis on a genomic scale is largely unknown. Here we report a potential microbial symbiont in corals revealed by metagenomics-based genomic study. Microbial cells in coral were enriched for metagenomic analysis and a high-quality draft genome of "Candidatus Prosthecochloris korallensis" was recovered by metagenome assembly and genome binning. Phylogenetic analysis shows "Ca. P. korallensis" belongs to the Prosthecochloris clade and is clustered with two Prosthecochloris clones derived from Caribbean corals. Genomic analysis reveals "Ca. P. korallensis" has potentially important ecological functions including anoxygenic photosynthesis, carbon fixation via the reductive tricarboxylic acid (rTCA) cycle, nitrogen fixation, and sulfur oxidization. Core metabolic pathway analysis suggests "Ca. P. korallensis" is a green sulfur bacterium capable of photoautotrophy or mixotrophy. Potential host-microbial interaction reveals a symbiotic relationship: "Ca. P. korallensis" might provide organic and nitrogenous nutrients to its host and detoxify sulfide for the host; the host might provide "Ca. P. korallensis" with an anaerobic environment for survival, carbon dioxide and acetate for growth, and hydrogen sulfide as an electron donor for photosynthesis.

Concordance Between Patient and Family Reports of Family Functioning in Bipolar I Disorder and Major Depressive Disorder

PubMed Central

Weinstock, Lauren M.; Wenze, Susan J.; Munroe, Mary K.; Miller, Ivan W.

2013-01-01

Despite the extensive literature on family functioning and mood disorders, less is known about concordance between patient- and family-reported family functioning. To address this question, adults with bipolar I disorder (BD; n = 92), major depressive disorder (MDD; n = 121), and their family members (ns = 135 and 201, respectively) were recruited from hospital sources. All patients and their family members completed the Family Assessment Device (Epstein et al., 1983). Intraclass correlation coefficients revealed that, in contrast to the moderate degree of concordance in the MDD sample, degree of concordance between patient- and family-reported family functioning was significantly weaker in BD. Subsequent analysis revealed that this discordance was driven by the reports of the child and young adolescent family members of the patients with BD. Results highlight the importance of collateral reports in the assessment of family functioning, especially among families of patients with BD, in research and treatment. PMID:23588224

Consistency between the luminosity function of resolved millisecond pulsars and the galactic center excess

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ploeg, Harrison; Gordon, Chris; Crocker, Roland

Fermi Large Area Telescope data reveal an excess of GeV gamma rays from the direction of the Galactic Center and bulge. Several explanations have been proposed for this excess including an unresolved population of millisecond pulsars (MSPs) and self-annihilating dark matter. It has been claimed that a key discriminant for or against the MSP explanation can be extracted from the properties of the luminosity function describing this source population. Specifically, is the luminosity function of the putative MSPs in the Galactic Center consistent with that characterizing the resolved MSPs in the Galactic disk? To investigate this we have used amore » Bayesian Markov Chain Monte Carlo to evaluate the posterior distribution of the parameters of the MSP luminosity function describing both resolved MSPs and the Galactic Center excess. At variance with some other claims, our analysis reveals that, within current uncertainties, both data sets can be well fit with the same luminosity function.« less

Concordance between patient and family reports of family functioning in bipolar I disorder and major depressive disorder.

PubMed

Weinstock, Lauren M; Wenze, Susan J; Munroe, Mary K; Miller, Ivan W

2013-05-01

Despite the extensive literature on family functioning and mood disorders, less is known about concordance between patient- and family-reported family functioning. To address this question, adults with bipolar I disorder (BD; n = 92) or major depressive disorder (MDD; n = 121) and their family members (n = 135 and 201, respectively) were recruited from hospital sources. All patients and their family members completed the Family Assessment Device (Epstein, Baldwin, Bishop. J Marital Fam Ther. 9:171-180, 1983). Intraclass correlation coefficients revealed that, in contrast to the moderate degree of concordance in the MDD sample, degree of concordance between patient- and family-reported family functioning was significantly weaker in BD. Subsequent analysis revealed that this discordance was driven by the reports of the child and young adolescent family members of the patients with BD. Results highlight the importance of collateral reports in the assessment of family functioning, especially among families of patients with BD, in research and treatment.

Exploring the Yeast Acetylome Using Functional Genomics

PubMed Central

Duffy, Supipi Kaluarachchi; Friesen, Helena; Baryshnikova, Anastasia; Lambert, Jean-Philippe; Chong, Yolanda T.; Figeys, Daniel; Andrews, Brenda

2014-01-01

SUMMARY Lysine acetylation is a dynamic posttranslational modification with a well-defined role in regulating histones. The impact of acetylation on other cellular functions remains relatively uncharacterized. We explored the budding yeast acetylome with a functional genomics approach, assessing the effects of gene overexpression in the absence of lysine deacetylases (KDACs). We generated a network of 463 synthetic dosage lethal (SDL) interactions involving class I and II KDACs, revealing many cellular pathways regulated by different KDACs. A biochemical survey of genes interacting with the KDAC RPD3 identified 72 proteins acetylated in vivo. In-depth analysis of one of these proteins, Swi4, revealed a role for acetylation in G1-specific gene expression. Acetylation of Swi4 regulates interaction with its partner Swi6, both components of the SBF transcription factor. This study expands our view of the yeast acetylome, demonstrates the utility of functional genomic screens for exploring enzymatic pathways, and provides functional information that can be mined for future studies. PMID:22579291

Functional wiring of the yeast kinome revealed by global analysis of genetic network motifs

PubMed Central

Sharifpoor, Sara; van Dyk, Dewald; Costanzo, Michael; Baryshnikova, Anastasia; Friesen, Helena; Douglas, Alison C.; Youn, Ji-Young; VanderSluis, Benjamin; Myers, Chad L.; Papp, Balázs; Boone, Charles; Andrews, Brenda J.

2012-01-01

A combinatorial genetic perturbation strategy was applied to interrogate the yeast kinome on a genome-wide scale. We assessed the global effects of gene overexpression or gene deletion to map an integrated genetic interaction network of synthetic dosage lethal (SDL) and loss-of-function genetic interactions (GIs) for 92 kinases, producing a meta-network of 8700 GIs enriched for pathways known to be regulated by cognate kinases. Kinases most sensitive to dosage perturbations had constitutive cell cycle or cell polarity functions under standard growth conditions. Condition-specific screens confirmed that the spectrum of kinase dosage interactions can be expanded substantially in activating conditions. An integrated network composed of systematic SDL, negative and positive loss-of-function GIs, and literature-curated kinase–substrate interactions revealed kinase-dependent regulatory motifs predictive of novel gene-specific phenotypes. Our study provides a valuable resource to unravel novel functional relationships and pathways regulated by kinases and outlines a general strategy for deciphering mutant phenotypes from large-scale GI networks. PMID:22282571

Quantitative Proteomics Reveals the Regulatory Networks of Circular RNA CDR1as in Hepatocellular Carcinoma Cells.

PubMed

Yang, Xue; Xiong, Qian; Wu, Ying; Li, Siting; Ge, Feng

2017-10-06

Circular RNAs (circRNAs), a class of widespread endogenous RNAs, play crucial roles in diverse biological processes and are potential biomarkers in diverse human diseases and cancers. Cerebellar-degeneration-related protein 1 antisense RNA (CDR1as), an oncogenic circRNA, is involved in human tumorigenesis and is dysregulated in hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying CDR1as functions in HCC remain unclear. Here we explored the functions of CDR1as and searched for CDR1as-regulated proteins in HCC cells. A quantitative proteomics strategy was employed to globally identify CDR1as-regulated proteins in HCC cells. In total, we identified 330 differentially expressed proteins (DEPs) upon enhanced CDR1as expression in HepG2 cells, indicating that they could be proteins regulated by CDR1as. Bioinformatic analysis revealed that many DEPs were involved in cell proliferation and the cell cycle. Further functional studies of epidermal growth factor receptor (EGFR) found that CDR1as exerts its effects on cell proliferation at least in part through the regulation of EGFR expression. We further confirmed that CDR1as could inhibit the expression of microRNA-7 (miR-7). EGFR is a validated target of miR-7; therefore, CDR1as may exert its function by regulating EGFR expression via targeting miR-7 in HCC cells. Taken together, we revealed novel functions and underlying mechanisms of CDR1as in HCC cells. This study serves as the first proteome-wide analysis of a circRNA-regulated protein in cells and provides a reliable and highly efficient method for globally identifying circRNA-regulated proteins.

Trends in genome dynamics among major orders of insects revealed through variations in protein families.

PubMed

Rappoport, Nadav; Linial, Michal

2015-08-07

Insects belong to a class that accounts for the majority of animals on earth. With over one million identified species, insects display a huge diversity and occupy extreme environments. At present, there are dozens of fully sequenced insect genomes that cover a range of habitats, social behavior and morphologies. In view of such diverse collection of genomes, revealing evolutionary trends and charting functional relationships of proteins remain challenging. We analyzed the relatedness of 17 complete proteomes representative of proteomes from insects including louse, bee, beetle, ants, flies and mosquitoes, as well as an out-group from the crustaceans. The analyzed proteomes mostly represented the orders of Hymenoptera and Diptera. The 287,405 protein sequences from the 18 proteomes were automatically clustered into 20,933 families, including 799 singletons. A comprehensive analysis based on statistical considerations identified the families that were significantly expanded or reduced in any of the studied organisms. Among all the tested species, ants are characterized by an exceptionally high rate of family gain and loss. By assigning annotations to hundreds of species-specific families, the functional diversity among species and between the major clades (Diptera and Hymenoptera) is revealed. We found that many species-specific families are associated with receptor signaling, stress-related functions and proteases. The highest variability among insects associates with the function of transposition and nucleic acids processes (collectively coined TNAP). Specifically, the wasp and ants have an order of magnitude more TNAP families and proteins relative to species that belong to Diptera (mosquitoes and flies). An unsupervised clustering methodology combined with a comparative functional analysis unveiled proteomic signatures in the major clades of winged insects. We propose that the expansion of TNAP families in Hymenoptera potentially contributes to the accelerated genome dynamics that characterize the wasp and ants.

A density difference based analysis of orbital-dependent exchange-correlation functionals

NASA Astrophysics Data System (ADS)

Grabowski, Ireneusz; Teale, Andrew M.; Fabiano, Eduardo; Śmiga, Szymon; Buksztel, Adam; Della Sala, Fabio

2014-03-01

We present a density difference based analysis for a range of orbital-dependent Kohn-Sham functionals. Results for atoms, some members of the neon isoelectronic series and small molecules are reported and compared with ab initio wave function calculations. Particular attention is paid to the quality of approximations to the exchange-only optimised effective potential (OEP) approach: we consider both the localised Hartree-Fock as well as the Krieger-Li-Iafrate methods. Analysis of density differences at the exchange-only level reveals the impact of the approximations on the resulting electronic densities. These differences are further quantified in terms of the ground state energies, frontier orbital energy differences and highest occupied orbital energies obtained. At the correlated level, an OEP approach based on a perturbative second-order correlation energy expression is shown to deliver results comparable with those from traditional wave function approaches, making it suitable for use as a benchmark against which to compare standard density functional approximations.

Transcriptional profiling reveals the expression of novel genes in response to various stimuli in the human dermatophyte Trichophyton rubrum

PubMed Central

2010-01-01

Background Cutaneous mycoses are common human infections among healthy and immunocompromised hosts, and the anthropophilic fungus Trichophyton rubrum is the most prevalent microorganism isolated from such clinical cases worldwide. The aim of this study was to determine the transcriptional profile of T. rubrum exposed to various stimuli in order to obtain insights into the responses of this pathogen to different environmental challenges. Therefore, we generated an expressed sequence tag (EST) collection by constructing one cDNA library and nine suppression subtractive hybridization libraries. Results The 1388 unigenes identified in this study were functionally classified based on the Munich Information Center for Protein Sequences (MIPS) categories. The identified proteins were involved in transcriptional regulation, cellular defense and stress, protein degradation, signaling, transport, and secretion, among other functions. Analysis of these unigenes revealed 575 T. rubrum sequences that had not been previously deposited in public databases. Conclusion In this study, we identified novel T. rubrum genes that will be useful for ORF prediction in genome sequencing and facilitating functional genome analysis. Annotation of these expressed genes revealed metabolic adaptations of T. rubrum to carbon sources, ambient pH shifts, and various antifungal drugs used in medical practice. Furthermore, challenging T. rubrum with cytotoxic drugs and ambient pH shifts extended our understanding of the molecular events possibly involved in the infectious process and resistance to antifungal drugs. PMID:20144196

Efficacy of pirfenidone and disease severity of idiopathic pulmonary fibrosis: Extended analysis of phase III trial in Japan.

PubMed

Taguchi, Yoshio; Ebina, Masahito; Hashimoto, Seishu; Ogura, Takashi; Azuma, Arata; Taniguchi, Hiroyuki; Kondoh, Yasuhiro; Suga, Moritaka; Takahashi, Hiroki; Nakata, Koichiro; Sugiyama, Yukihiko; Kudoh, Shoji; Nukiwa, Toshihiro

2015-11-01

A phase III clinical trial of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) in Japan has revealed that pirfenidone attenuated the decline in vital capacity (VC) and improved progression-free survival (PFS). We conducted an extended analysis of the pirfenidone trial to investigate its efficacy with respect to IPF severity in the trial population. Patients in the phase III trial were stratified by baseline pulmonary functions including %VC predicted, %diffusion capacity for carbon monoxide predicted, and oxygen saturation by pulse oximetry on exertion and were categorized into mild, moderate, and severe groups of functional impairment. The efficacy of pirfenidone for VC and PFS over 52 weeks was compared among the three sub-populations. Of 264 patients, 102 (39%), 90 (34%), and 72 patients (27%) were classified as having mild, moderate, and severe grades of functional impairment, respectively. This classification was associated with arterial oxygen partial pressure at rest and degree of dyspnea at baseline. While pirfenidone attenuated VC decline at all grades of severity, covariance analysis revealed pirfenidone to have better efficacy in the sub-population with mild-grade IPF. Mixed model repeated measures analysis confirmed that pirfenidone markedly attenuated VC decline in patients with mild-grade IPF compared to its effects in patients with moderate or severe IPF. Pirfenidone also improved PFS markedly in patients with mild-grade IPF. This extended analysis suggested that pirfenidone exerted better therapeutic effects in patients with milder IPF. Further analysis with a larger population is needed to confirm these results. Copyright © 2015. Published by Elsevier B.V.

Three 3D metal coordination polymers based on triazol-functionalized rigid ligand: Synthesis, topological structure and properties

NASA Astrophysics Data System (ADS)

Meng, Lingkun; Liu, Kang; Liang, Chen; Guo, Xiaolei; Han, Xu; Ren, Siyuan; Ma, Dingxuan; Li, Guanghua; Shi, Zhan; Feng, Shouhua

2018-02-01

By using a triazol-functionalized tricarboxylate, three novel metal coordination polymers, namely, [Zn2L(OH)]·0.5H2O (1), [Co2L(OH)(H2O)]·5.5H2O (2), [Cu2(HL)] (3) L = ［5-(3-(4-carboxyphenyl)-5-methyl-4H-1,2,4-triazol-4-yl)isophthalate］ were synthesized under hydrothermal reactions. All the compounds were characterized by element analysis, IR spectroscopy, thermogravimetric analysis, power X-ray diffrcation and single-crystal X-ray diffrcation. Structural analysis reveals that compounds 1 and 2 have 3D networks with flu topologies where rigid trizaol-functionalized ligands as 4-connected nodes and Zn4(COO)6 or Co4(COO)6 clusters serves as 8-connected secondary building units. Compound 3 has 3D network with pcu topology where Cu4(COO)4 clusters serve as 6-connected secondary building units. Gas adsorption studies reveal that desolvated compoud 1 exhibits high H2 absorption capacity at 77 K and highly selective separation abilities of CO2 and C3H8 over CH4 at room temperature. The results suggest that 1 has potential application in gas storage and separation. In addition, the magnetic properties of compound 2 were also investigated.

Functional Connectivity Parcellation of the Human Thalamus by Independent Component Analysis.

PubMed

Zhang, Sheng; Li, Chiang-Shan R

2017-11-01

As a key structure to relay and integrate information, the thalamus supports multiple cognitive and affective functions through the connectivity between its subnuclei and cortical and subcortical regions. Although extant studies have largely described thalamic regional functions in anatomical terms, evidence accumulates to suggest a more complex picture of subareal activities and connectivities of the thalamus. In this study, we aimed to parcellate the thalamus and examine whole-brain connectivity of its functional clusters. With resting state functional magnetic resonance imaging data from 96 adults, we used independent component analysis (ICA) to parcellate the thalamus into 10 components. On the basis of the independence assumption, ICA helps to identify how subclusters overlap spatially. Whole brain functional connectivity of each subdivision was computed for independent component's time course (ICtc), which is a unique time series to represent an IC. For comparison, we computed seed-region-based functional connectivity using the averaged time course across all voxels within a thalamic subdivision. The results showed that, at p < 10 -6 , corrected, 49% of voxels on average overlapped among subdivisions. Compared with seed-region analysis, ICtc analysis revealed patterns of connectivity that were more distinguished between thalamic clusters. ICtc analysis demonstrated thalamic connectivity to the primary motor cortex, which has eluded the analysis as well as previous studies based on averaged time series, and clarified thalamic connectivity to the hippocampus, caudate nucleus, and precuneus. The new findings elucidate functional organization of the thalamus and suggest that ICA clustering in combination with ICtc rather than seed-region analysis better distinguishes whole-brain connectivities among functional clusters of a brain region.

Novel Single-Cell Analysis Platform Based on a Solid-State Zinc-Coadsorbed Carbon Quantum Dots Electrochemiluminescence Probe for the Evaluation of CD44 Expression on Breast Cancer Cells.

PubMed

Qiu, Youyi; Zhou, Bin; Yang, Xiaojuan; Long, Dongping; Hao, Yan; Yang, Peihui

2017-05-24

A novel single-cell analysis platform was fabricated using solid-state zinc-coadsorbed carbon quantum dot (ZnCQDs) nanocomposites as an electrochemiluminescence (ECL) probe for the detection of breast cancer cells and evaluation of the CD44 expression level. Solid-state ZnCQDs nanocomposite probes were constructed through the attachment of ZnCQDs to gold nanoparticles and then the loading of magnetic beads to amplify the ECL signal, exhibiting a remarkable 120-fold enhancement of the ECL intensity. Hyaluronic acid (HA)-functionalized solid-state probes were used to label a single breast cancer cell by the specific recognition of HA with CD44 on the cell surface, revealing more stable, sensitive, and effective tagging in comparison with the water-soluble CQDs. This strategy exhibited a good analytical performance for the analysis of MDA-MB-231 and MCF-7 single cells with linear range from 1 to 18 and from 1 to 12 cells, respectively. Furthermore, this single-cell analysis platform was used for evaluation of the CD44 expression level of these two cell lines, in which the MDA-MB-231 cells revealed a 2.8-5.2-fold higher CD44 expression level. A total of 20 single cells were analyzed individually, and the distributions of the ECL intensity revealed larger variations, indicating the high cellular heterogeneity of the CD44 expression level on the same cell line. The as-proposed single-cell analysis platform might provide a novel protocol to effectively study the individual cellular function and cellular heterogeneity.

Canonical correlation analysis of synchronous neural interactions and cognitive deficits in Alzheimer's dementia

NASA Astrophysics Data System (ADS)

Karageorgiou, Elissaios; Lewis, Scott M.; Riley McCarten, J.; Leuthold, Arthur C.; Hemmy, Laura S.; McPherson, Susan E.; Rottunda, Susan J.; Rubins, David M.; Georgopoulos, Apostolos P.

2012-10-01

In previous work (Georgopoulos et al 2007 J. Neural Eng. 4 349-55) we reported on the use of magnetoencephalographic (MEG) synchronous neural interactions (SNI) as a functional biomarker in Alzheimer's dementia (AD) diagnosis. Here we report on the application of canonical correlation analysis to investigate the relations between SNI and cognitive neuropsychological (NP) domains in AD patients. First, we performed individual correlations between each SNI and each NP, which provided an initial link between SNI and specific cognitive tests. Next, we performed factor analysis on each set, followed by a canonical correlation analysis between the derived SNI and NP factors. This last analysis optimally associated the entire MEG signal with cognitive function. The results revealed that SNI as a whole were mostly associated with memory and language, and, slightly less, executive function, processing speed and visuospatial abilities, thus differentiating functions subserved by the frontoparietal and the temporal cortices. These findings provide a direct interpretation of the information carried by the SNI and set the basis for identifying specific neural disease phenotypes according to cognitive deficits.

Differential Effects of the Catechol-O-Methyltransferase Val158Met Genotype on the Cognitive Function of Schizophrenia Patients and Healthy Japanese Individuals

PubMed Central

Tsuchimine, Shoko; Yasui-Furukori, Norio; Kaneda, Ayako; Kaneko, Sunao

2013-01-01

Background The functional polymorphism Val158Met in the catechol-O-methyltransferase (COMT) gene has been associated with differences in prefrontal cognitive functions in patients with schizophrenia and healthy individuals. Several studies have indicated that the Met allele is associated with better performance on measures of cognitive function. We investigated whether the COMT Val158Met genotype was associated with cognitive function in 149 healthy controls and 118 patients with schizophrenia. Methods Cognitive function, including verbal memory, working memory, motor speed, attention, executive function and verbal fluency, was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS-J). We employed a one-way analysis of variance (ANOVA) and a multiple regression analysis to determine the associations between the COMT Val158Met genotype and the BACS-J measurements. Results The one-way ANOVA revealed a significant difference in the scores on the Tower of London, a measure of executive function, between the different Val158Met genotypes in the healthy controls (p = 0.023), and a post-hoc analysis showed significant differences between the scores on the Tower of London in the val/val genotype group (18.6 ± 2.4) compared to the other two groups (17.6 ± 2.7 for val/met and 17.1 ± 3.2 for met/met; p = 0.027 and p = 0.024, respectively). Multiple regression analyses revealed that executive function was significantly correlated with the Val158Met genotype (p = 0.003). However, no evidence was found for an effect of the COMT on any cognitive domains of the BACS-J in the patients with schizophrenia. Conclusion These data support the hypothesis that the COMT Val158Met genotype maintains an optimal level of dopamine activity. Further studies should be performed that include a larger sample size and include patients on and off medication, as these patients would help to confirm our findings. PMID:24282499

Genetic analysis of teat number in pigs reveals some developmental pathways independent of vertebra number and several loci which only affect a specific side

USDA-ARS?s Scientific Manuscript database

Background: Number of functional teats is an important trait in commercial swine production. As litter size increases, the number of teats must also increase to supply nutrition to all piglets. Therefore, a genome-wide association analysis was conducted to identify genomic regions that affect this ...

Gene expression analysis reveals schizophrenia-associated dysregulation of immune pathways in peripheral blood mononuclear cells.

PubMed

Gardiner, Erin J; Cairns, Murray J; Liu, Bing; Beveridge, Natalie J; Carr, Vaughan; Kelly, Brian; Scott, Rodney J; Tooney, Paul A

2013-04-01

Peripheral blood mononuclear cells (PBMCs) represent an accessible tissue source for gene expression profiling in schizophrenia that could provide insight into the molecular basis of the disorder. This study used the Illumina HT_12 microarray platform and quantitative real time PCR (QPCR) to perform mRNA expression profiling on 114 patients with schizophrenia or schizoaffective disorder and 80 non-psychiatric controls from the Australian Schizophrenia Research Bank (ASRB). Differential expression analysis revealed altered expression of 164 genes (59 up-regulated and 105 down-regulated) in the PBMCs from patients with schizophrenia compared to controls. Bioinformatic analysis indicated significant enrichment of differentially expressed genes known to be involved or associated with immune function and regulating the immune response. The differential expression of 6 genes, EIF2C2 (Ago 2), MEF2D, EVL, PI3, S100A12 and DEFA4 was confirmed by QPCR. Genome-wide expression analysis of PBMCs from individuals with schizophrenia was characterized by the alteration of genes with immune system function, supporting the hypothesis that the disorder has a significant immunological component in its etiology. Copyright © 2012 Elsevier Ltd. All rights reserved.

Srs2 overexpression reveals a helicase-independent role at replication forks that requires diverse cell functions

PubMed Central

León Ortiz, Ana María; Reid, Robert J. D.; Dittmar, John C.; Rothstein, Rodney; Nicolas, Alain

2011-01-01

Srs2 is a 3’ to 5’ DNA helicase that regulates many aspects of DNA metabolism in Saccharomyces cerevisiae. It is best known for its ability to counteract homologous recombination by dismantling Rad51 filaments, but is also involved in checkpoint activation, adaptation and recovery, and in resolution of late recombination intermediates. To further address its biological roles and uncover new genetic interactions, we examined the consequences of overexpressing SRS2 as well as two helicase-dead mutants, srs2-K41A and srs2-K41R, in the collection of 4827 yeast haploid deletion mutants. We identified 274 genes affecting a large variety of cellular functions that are required for cell growth when SRS2 or its mutants are overexpressed. Further analysis of these interactions reveals that Srs2 acts independently of its helicase function at replication forks likely through its recruitment by the sumoylated PCNA replication clamp. This helicase-independent function is responsible for the negative interactions with DNA metabolism genes and for the toxicity of SRS2 overexpression in many of the diverse cellular pathways revealed in our screens. PMID:21459050

Global gene expression analysis reveals pathway differences between teratogenic and non-teratogenic exposure concentrations of bisphenol A and 17β-estradiol in embryonic zebrafish

PubMed Central

Saili, Katerine S.; Tilton, Susan C.; Waters, Katrina M.; Tanguay, Robert L.

2013-01-01

Transient developmental exposure to 0.1 μM bisphenol A (BPA) results in larval zebrafish hyperactivity and learning impairments in the adult, while exposure to 80 μM BPA results in teratogenic responses, including craniofacial abnormalities and edema. The mode of action underlying these effects is unclear. We used global gene expression analysis to identify candidate genes and signaling pathways that mediate BPA’s developmental toxicity in zebrafish. Exposure concentrations were selected and anchored to the positive control, 17β-estradiol (E2), based on previously determined behavioral or teratogenic phenotypes. Functional analysis of differentially expressed genes revealed distinct expression profiles at 24 hours post fertilization for 0.1 versus 80 μM BPA and 0.1 versus 15 μM E2 exposure, identification of prothrombin activation as a top canonical pathway impacted by both 0.1 μM BPA and 0.1 μM E2 exposure, and suppressed expression of several genes involved in nervous system development and function following 0.1 μM BPAexposure. PMID:23557687

A multivariate analysis of age-related differences in functional networks supporting conflict resolution.

PubMed

Salami, Alireza; Rieckmann, Anna; Fischer, Håkan; Bäckman, Lars

2014-02-01

Functional neuroimaging studies demonstrate age-related differences in recruitment of a large-scale attentional network during interference resolution, especially within dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). These alterations in functional responses have been frequently observed despite equivalent task performance, suggesting age-related reallocation of neural resources, although direct evidence for a facilitating effect in aging is sparse. We used the multi-source interference task and multivariate partial-least-squares to investigate age-related differences in the neuronal signature of conflict resolution, and their behavioral implications in younger and older adults. There were interference-related increases in activity, involving fronto-parietal and basal ganglia networks that generalized across age. In addition an age-by-task interaction was observed within a distributed network, including DLPFC and ACC, with greater activity during interference in the old. Next, we combined brain-behavior and functional connectivity analyses to investigate whether compensatory brain changes were present in older adults, using DLPFC and ACC as regions of interest (i.e. seed regions). This analysis revealed two networks differentially related to performance across age groups. A structural analysis revealed age-related gray-matter losses in regions facilitating performance in the young, suggesting that functional reorganization may partly reflect structural alterations in aging. Collectively, these findings suggest that age-related structural changes contribute to reductions in the efficient recruitment of a youth-like interference network, which cascades into instantiation of a different network facilitating conflict resolution in elderly people. © 2013. Published by Elsevier Inc. All rights reserved.

Insulin growth factor-I promotes functional recovery after a focal lesion in the dentate gyrus.

PubMed

Liquitaya-Montiel, Adhemar; Aguilar-Arredondo, Andrea; Arias, Clorinda; Zepeda, Angélica

2012-11-01

The adult brain is plastic and able to reorganize structurally and functionally after damage. Growth factors are key molecules underlying the recovery process and among trophic molecules, Insulin-Like Growth Factor-I (IGF-I) is of particular interest given that it modulates neuronal and glial responses in the hippocampus including neurogenesis, which has been proposed as a mechanism of neurorepair. In this study we analyzed the effect of intracerebroventricular chronic infusion of IGF-I on functional recovery and morphological restoration after the induction of an excitotoxic lesion in the dentate gyrus (DG) of young-adult rats. Our results show that the lesion impairs contextual fear memory which is a DG dependent task, but not cued fear memory or performance in the open field motor task, which are independent of the DG integrity. Chronic administration of IGF-I, but not vehicle, promotes functional recovery to control levels in injured subjects. Analysis in NeuN immunoprocessed tissue revealed that the lesion volume was not different between groups and that the DG was not evidently restructured in the IGF-I treated group. Glial fibrillary acidic protein (GFAP) analysis revealed an increased astrocytic response in the injured region in both groups and Doublecortin (DCX) analysis showed a similar increase in number of newly born neurons in both groups. However, a remarkable increase in young neurons dendritic arborization was observed in the IGF-I treated group. These results provide evidence for IGF-I as a molecule mediating functional and cellular plasticity during a reorganization process after damage to a neurogenic niche.

Structure-function analysis of Sua5 protein reveals novel functional motifs required for the biosynthesis of the universal t6A tRNA modification.

PubMed

Pichard-Kostuch, Adeline; Zhang, Wenhua; Liger, Dominique; Daugeron, Marie-Claire; Letoquart, Juliette; Li de la Sierra-Gallay, Ines; Forterre, Patrick; Collinet, Bruno; van Tilbeurgh, Herman; Basta, Tamara

2018-04-12

N6-threonyl-carbamoyl adenosine (t6A) is a universal tRNA modification found at position 37, next to the anticodon, in almost all tRNAs decoding ANN codons (where N = A, U, G or C). t6A stabilizes the codon-anticodon interaction and hence promotes translation fidelity. The first step of the biosynthesis of t6A, the production of threonyl-carbamoyl adenylate (TC-AMP), is catalyzed by the Sua5/TsaC family of enzymes. While TsaC is a single domain protein, Sua5 enzymes are composed of the TsaC-like domain, a linker and an extra domain called SUA5 of unknown function. In the present study, we report structure-function analysis of Pyrococcus abyssi Sua5 (Pa-Sua5). Crystallographic data revealed binding sites for bicarbonate substrate and pyrophosphate product. The linker of Pa-Sua5 forms a loop structure that folds into the active site gorge and closes it. Using structure-guided mutational analysis we established that the conserved sequence motifs in the linker and the domain-domain interface are essential for the function of Pa-Sua5. We propose that the linker participates actively in the biosynthesis of TC-AMP by binding to ATP/PPi and by stabilizing the N-carboxy-L-threonine intermediate. Hence, TsaC orthologs which lack such a linker and SUA5 domain use different mechanism for TC-AMP synthesis. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Characterization of Rubia cordifolia L. root extract and its evaluation of cardioprotective effect in Wistar rat model

PubMed Central

Chandrashekar, BS; Prabhakara, S; Mohan, T; Shabeer, D; Bhandare, Basavaraj; Nalini, M; Sharmila, PS; Meghana, DL; Reddy, Basanth Kumar; Hanumantha Rao, HM; Sahajananda, H; Anbazhagan, K

2018-01-01

OBJECTIVES: Rubia cordifolia L. (RC) is a well-known and highly valuable medicinal plant in the Ayurvedic system. The present study involves evaluating antioxidant and cardioprotective property of RC root extract. MATERIALS AND METHODS: The characterization of RC root extract was carried out using standard phytochemical and biochemical analysis. The functional groups were analyzed by Fourier transform infrared (FTIR) spectroscopy and phytotherapeutic compounds were identified using high-resolution mass spectrometry (HR-MS). Cardioprotective activity of RC root extract was investigated against cyclophosphamide (CP; 100 mg/kg, i.p)-induced cardiotoxicity in male albino Wistar rats. RC (100, 200, and 400 mg/kg, p.o) or silymarin (100 mg/kg, p.o) was administered immediately after CP on the 1st day and the next consecutive 10 days. Biochemical and histopathological analysis was performed to observe the cardioprotective effects of RC root extract. RESULTS: Phytochemical analysis revealed the presence of secondary metabolites that include alkaloids, flavonoids, saponins, and anthraquinones in RC root extract. FTIR analysis revealed the presence of several functional groups. Based on HR-MS analysis, eight major phytotherapeutic compounds were identified in methanol root extract of RC. Biochemical analysis in CP-induced rat model administered with RC extract revealed significantly enhanced levels of antioxidant markers such as superoxide dismutase, catalase, and glutathione S-transferase. Histopathological study showed that the rat model treated with the root extract had reduced the cardiac injury. CONCLUSION: Our results have shown that the RC extract contains various antioxidant compounds with cardioprotective effect. Treatment with RC root extract could significantly protect CP-induced rats from cardiac tissue injury by restoring the antioxidant markers. PMID:29861523

Allosteric effects in bacteriophage HK97 procapsids revealed directly from covariance analysis of cryo EM data.

PubMed

Xu, Nan; Veesler, David; Doerschuk, Peter C; Johnson, John E

2018-05-01

The information content of cryo EM data sets exceeds that of the electron scattering potential (cryo EM) density initially derived for structure determination. Previously we demonstrated the power of data variance analysis for characterizing regions of cryo EM density that displayed functionally important variance anomalies associated with maturation cleavage events in Nudaurelia Omega Capensis Virus and the presence or absence of a maturation protease in bacteriophage HK97 procapsids. Here we extend the analysis in two ways. First, instead of imposing icosahedral symmetry on every particle in the data set during the variance analysis, we only assume that the data set as a whole has icosahedral symmetry. This change removes artifacts of high variance along icosahedral symmetry axes, but retains all of the features previously reported in the HK97 data set. Second we present a covariance analysis that reveals correlations in structural dynamics (variance) between the interior of the HK97 procapsid with the protease and regions of the exterior (not seen in the absence of the protease). The latter analysis corresponds well with hydrogen deuterium exchange studies previously published that reveal the same correlation. Copyright © 2018 Elsevier Inc. All rights reserved.

Evidence for an anterior-posterior differentiation in the human hippocampal formation revealed by meta-analytic parcellation of fMRI coordinate maps: focus on the subiculum.

PubMed

Chase, Henry W; Clos, Mareike; Dibble, Sofia; Fox, Peter; Grace, Anthony A; Phillips, Mary L; Eickhoff, Simon B

2015-06-01

Previous studies, predominantly in experimental animals, have suggested the presence of a differentiation of function across the hippocampal formation. In rodents, ventral regions are thought to be involved in emotional behavior while dorsal regions mediate cognitive or spatial processes. Using a combination of modeling the co-occurrence of significant activations across thousands of neuroimaging experiments and subsequent data-driven clustering of these data we were able to provide evidence of distinct subregions within a region corresponding to the human subiculum, a critical hub within the hippocampal formation. This connectivity-based model consists of a bilateral anterior region, as well as separate posterior and intermediate regions on each hemisphere. Functional connectivity assessed both by meta-analytic and resting fMRI approaches revealed that more anterior regions were more strongly connected to the default mode network, and more posterior regions were more strongly connected to 'task positive' regions. In addition, our analysis revealed that the anterior subregion was functionally connected to the ventral striatum, midbrain and amygdala, a circuit that is central to models of stress and motivated behavior. Analysis of a behavioral taxonomy provided evidence for a role for each subregion in mnemonic processing, as well as implication of the anterior subregion in emotional and visual processing and the right posterior subregion in reward processing. These findings lend support to models which posit anterior-posterior differentiation of function within the human hippocampal formation and complement other early steps toward a comparative (cross-species) model of the region. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantitative Proteomics Analysis Reveals Novel Insights into Mechanisms of Action of Long Noncoding RNA Hox Transcript Antisense Intergenic RNA (HOTAIR) in HeLa Cells*

PubMed Central

Zheng, Peng; Xiong, Qian; Wu, Ying; Chen, Ying; Chen, Zhuo; Fleming, Joy; Gao, Ding; Bi, Lijun; Ge, Feng

2015-01-01

Long noncoding RNAs (lncRNAs), which have emerged in recent years as a new and crucial layer of gene regulators, regulate various biological processes such as carcinogenesis and metastasis. HOTAIR (Hox transcript antisense intergenic RNA), a lncRNA overexpressed in most human cancers, has been shown to be an oncogenic lncRNA. Here, we explored the role of HOTAIR in HeLa cells and searched for proteins regulated by HOTAIR. To understand the mechanism of action of HOTAIR from a systems perspective, we employed a quantitative proteomic strategy to systematically identify potential targets of HOTAIR. The expression of 170 proteins was significantly dys-regulated after inhibition of HOTAIR, implying that they could be potential targets of HOTAIR. Analysis of this data at the systems level revealed major changes in proteins involved in diverse cellular components, including the cytoskeleton and the respiratory chain. Further functional studies on vimentin (VIM), a key protein involved in the cytoskeleton, revealed that HOTAIR exerts its effects on migration and invasion of HeLa cells, at least in part, through the regulation of VIM expression. Inhibition of HOTAIR leads to mitochondrial dysfunction and ultrastructural alterations, suggesting a novel role of HOTAIR in maintaining mitochondrial function in cancer cells. Our results provide novel insights into the mechanisms underlying the function of HOTAIR in cancer cells. We expect that the methods used in this study will become an integral part of functional studies of lncRNAs. PMID:25762744

Recent Advances in Clinical Glycoproteomics of Immunoglobulins (Igs).

PubMed

Plomp, Rosina; Bondt, Albert; de Haan, Noortje; Rombouts, Yoann; Wuhrer, Manfred

2016-07-01

Antibody glycosylation analysis has seen methodological progress resulting in new findings with regard to antibody glycan structure and function in recent years. For example, antigen-specific IgG glycosylation analysis is now applicable for clinical samples because of the increased sensitivity of measurements, and this has led to new insights in the relationship between IgG glycosylation and various diseases. Furthermore, many new methods have been developed for the purification and analysis of IgG Fc glycopeptides, notably multiple reaction monitoring for high-throughput quantitative glycosylation analysis. In addition, new protocols for IgG Fab glycosylation analysis were established revealing autoimmune disease-associated changes. Functional analysis has shown that glycosylation of IgA and IgE is involved in transport across the intestinal epithelium and receptor binding, respectively. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Environmental drivers of heterogeneity in the trophic-functional structure of protozoan communities during an annual cycle in a coastal ecosystem.

PubMed

Xu, Guangjian; Yang, Eun Jin; Xu, Henglong

2017-08-15

Trophic-functional groupings are an important biological trait to summarize community structure in functional space. The heterogeneity of the tropic-functional pattern of protozoan communities and its environmental drivers were studied in coastal waters of the Yellow Sea during a 1-year cycle. Samples were collected using the glass slide method at four stations within a water pollution gradient. A second-stage matrix-based analysis was used to summarize spatial variation in the annual pattern of the functional structure. A clustering analysis revealed significant variability in the trophic-functional pattern among the four stations during the 1-year cycle. The heterogeneity in the trophic-functional pattern of the communities was significantly related to changes in environmental variables, particularly ammonium-nitrogen and nitrates, alone or in combination with dissolved oxygen. These results suggest that the heterogeneity in annual patterns of protozoan trophic-functional structure may reflect water quality status in coastal ecosystems. Copyright © 2017. Published by Elsevier Ltd.

Depressive symptoms in schizophrenia and dopamine and serotonin gene polymorphisms.

PubMed

Peitl, Vjekoslav; Štefanović, Mario; Karlović, Dalibor

2017-07-03

Although depressive symptoms seem to be frequent in schizophrenia they have received significantly less attention than other symptom domains. As impaired serotonergic and dopaminergic neurotransmission is implicated in the pathogenesis of depression and schizophrenia this study sought to investigate the putative association between several functional gene polymorphisms (SERT 5-HTTLPR, MAO-A VNTR, COMT Val158Met and DAT VNTR) and schizophrenia. Other objectives of this study were to closely examine schizophrenia symptom domains by performing factor analysis of the two most used instruments in this setting (Positive and negative syndrome scale - PANSS and Calgary depression rating scale - CDSS) and to examine the influence of investigated gene polymorphisms on the schizophrenia symptom domains, focusing on depressive scores. A total of 591 participants were included in the study (300 schizophrenic patients and 291 healthy volunteers). 192 (64%) of schizophrenic patients had significant depressive symptoms. Genotype distribution revealed no significant differences regarding all investigated polymorphisms except the separate gender analysis for MAO-A gene polymorphism which revealed significantly more allele 3 carriers in schizophrenic males. Factor analysis of the PANSS scale revealed the existence of five separate factors (symptom domains), while the CDSS scale revealed two distinct factors. Several investigated gene polymorphisms (mostly SERT and MAO-A, but also COMT) significantly influenced two factors from the PANSS (aggressive/impulsive and negative symptoms) and one from the CDSS scale (suicidality), respectively. Depressive symptoms in schizophrenic patients may be influenced by functional gene polymorphisms, especially those implicated in serotonergic neurotransmission. Copyright © 2017 Elsevier Inc. All rights reserved.

The Critical Role of Arabidopsis Electron-Transfer Flavoprotein:Ubiquinone Oxidoreductase during Dark-Induced StarvationW⃞

PubMed Central

Ishizaki, Kimitsune; Larson, Tony R.; Schauer, Nicolas; Fernie, Alisdair R.; Graham, Ian A.; Leaver, Christopher J.

2005-01-01

In mammals, electron-transfer flavoprotein:ubiquinone oxidoreductase (ETFQO) and electron-transfer flavoprotein (ETF) are functionally associated, and ETF accepts electrons from at least nine mitochondrial matrix flavoprotein dehydrogenases and transfers them to ubiquinone in the inner mitochondrial membrane. In addition, the mammalian ETF/ETFQO system plays a key role in β-oxidation of fatty acids and catabolism of amino acids and choline. By contrast, nothing is known of the function of ETF and ETFQO in plants. Sequence analysis of the unique Arabidopsis thaliana homologue of ETFQO revealed high similarity to the mammalian ETFQO protein. Moreover, green fluorescent protein cellular localization experiments suggested a mitochondrial location for this protein. RNA gel blot analysis revealed that Arabidopsis ETFQO transcripts accumulated in long-term dark-treated leaves. Analysis of three independent insertional mutants of Arabidopsis ETFQO revealed a dramatic reduction in their ability to withstand extended darkness, resulting in senescence and death within 10 d after transfer, whereas wild-type plants remained viable for at least 15 d. Metabolite profiling of dark-treated leaves of the wild type and mutants revealed a dramatic decline in sugar levels. In contrast with the wild type, the mutants demonstrated a significant accumulation of several amino acids, an intermediate of Leu catabolism, and, strikingly, high-level accumulation of phytanoyl-CoA. These data demonstrate the involvement of a mitochondrial protein, ETFQO, in the catabolism of Leu and potentially of other amino acids in higher plants and also imply a novel role for this protein in the chlorophyll degradation pathway activated during dark-induced senescence and sugar starvation. PMID:16055629

[NUCLEAR STRUCTURE IN THE SECRETORY CELLS OF MAMMARY GLANDS IN LACTATING AND NON-LACTATING RATS].

PubMed

Tyutina, K V; Skopichev, V G; Bogolyubov, D S; Bogolyubova, I O

2016-01-01

The features of structural and functional organization of the main nuclear compartments and distribution of their key molecular components (chromatin-remodeling protein ATRX, RNA polymerase I and II, and the splicing factor SC35) has been studied in the nuclei of mammary gland cells at different functional states. No significant differences between the nuclei of the cells in the lactating and non-lactating mammary glands have been revealed at the ultrastructural level. At the same time, photometric analysis has revealed higher intensity of nucleoplasmic immunofluorescent staining of mammary glands in the lactating animals when antibodies against the proteins ATRX and SC35 were used. Apparently, this observation reflects the changes of the structural and functional status of chromatin as well as the redistribution of splicing factors between the sites of their deposition and transcription.

Variation analysis of transcriptome changes reveals cochlear genes and their associated functions in cochlear susceptibility to acoustic overstimulation.

PubMed

Yang, Shuzhi; Cai, Qunfeng; Bard, Jonathan; Jamison, Jennifer; Wang, Jianmin; Yang, Weiping; Hu, Bo Hua

2015-12-01

Individual variation in the susceptibility of the auditory system to acoustic overstimulation has been well-documented at both the functional and structural levels. However, the molecular mechanism responsible for this variation is unclear. The current investigation was designed to examine the variation patterns of cochlear gene expression using RNA-seq data and to identify the genes with expression variation that increased following acoustic trauma. This study revealed that the constitutive expressions of cochlear genes displayed diverse levels of gene-specific variation. These variation patterns were altered by acoustic trauma; approximately one-third of the examined genes displayed marked increases in their expression variation. Bioinformatics analyses revealed that the genes that exhibited increased variation were functionally related to cell death, biomolecule metabolism, and membrane function. In contrast, the stable genes were primarily related to basic cellular processes, including protein and macromolecular syntheses and transport. There was no functional overlap between the stable and variable genes. Importantly, we demonstrated that glutamate metabolism is related to the variation in the functional response of the cochlea to acoustic overstimulation. Taken together, the results indicate that our analyses of the individual variations in transcriptome changes of cochlear genes provide important information for the identification of genes that potentially contribute to the generation of individual variation in cochlear responses to acoustic overstimulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Dependency Network Analysis (DEPNA) Reveals Context Related Influence of Brain Network Nodes

PubMed Central

Jacob, Yael; Winetraub, Yonatan; Raz, Gal; Ben-Simon, Eti; Okon-Singer, Hadas; Rosenberg-Katz, Keren; Hendler, Talma; Ben-Jacob, Eshel

2016-01-01

Communication between and within brain regions is essential for information processing within functional networks. The current methods to determine the influence of one region on another are either based on temporal resolution, or require a predefined model for the connectivity direction. However these requirements are not always achieved, especially in fMRI studies, which have poor temporal resolution. We thus propose a new graph theory approach that focuses on the correlation influence between selected brain regions, entitled Dependency Network Analysis (DEPNA). Partial correlations are used to quantify the level of influence of each node during task performance. As a proof of concept, we conducted the DEPNA on simulated datasets and on two empirical motor and working memory fMRI tasks. The simulations revealed that the DEPNA correctly captures the network’s hierarchy of influence. Applying DEPNA to the functional tasks reveals the dynamics between specific nodes as would be expected from prior knowledge. To conclude, we demonstrate that DEPNA can capture the most influencing nodes in the network, as they emerge during specific cognitive processes. This ability opens a new horizon for example in delineating critical nodes for specific clinical interventions. PMID:27271458

Functional organization of a single nif cluster in the mesophilic archaeon Methanosarcina mazei strain Gö1

PubMed Central

Ehlers, Claudia; Veit, Katharina; Gottschalk, Gerhard; Schmitz, Ruth A.

2002-01-01

The mesophilic methanogenic archaeon Methanosarcina mazei strain Gö1 is able to utilize molecular nitrogen (N2) as its sole nitrogen source. We have identified and characterized a single nitrogen fixation (nif) gene cluster in M. mazei Gö1 with an approximate length of 9 kbp. Sequence analysis revealed seven genes with sequence similarities to nifH, nifI1, nifI2, nifD, nifK, nifE and nifN, similar to other diazotrophic methanogens and certain bacteria such as Clostridium acetobutylicum, with the two glnB-like genes (nifI1 and nifI2) located between nifH and nifD. Phylogenetic analysis of deduced amino acid sequences for the nitrogenase structural genes of M. mazei Gö1 showed that they are most closely related to Methanosarcina barkeri nif2 genes, and also closely resemble those for the corresponding nif products of the gram-positive bacterium C. acetobutylicum. Northern blot analysis and reverse transcription PCR analysis demonstrated that the M. mazei nif genes constitute an operon transcribed only under nitrogen starvation as a single 8 kb transcript. Sequence analysis revealed a palindromic sequence at the transcriptional start site in front of the M. mazei nifH gene, which may have a function in transcriptional regulation of the nif operon. PMID:15803652

Identification of three duplicated Spin genes in medaka (Oryzias latipes).

PubMed

Wang, Xiao-Lei; Mei, Jie; Sun, Min; Hong, Yun-Han; Gui, Jian-Fang

2005-05-09

Gene and genomic duplications are very important and frequent events in fish evolution, and the divergence of duplicated genes in sequences and functions is a focus of research on gene evolution. Here, we report the identification and characterization of three duplicated Spindlin (Spin) genes from medaka (Oryzias latipes): OlSpinA, OlSpinB, and OlSpinC. Molecular cloning, genomic DNA Blast analysis and phylogenetic relationship analysis demonstrated that the three duplicated OlSpin genes should belong to gene duplication. Furthermore, Western blot analysis revealed significant expression differences of the three OlSpins among different tissues and during embryogenesis in medaka, and suggested that sequence and functional divergence might have occurred in evolution among them.

Analysis of sequence repeats of proteins in the PDB.

PubMed

Mary Rajathei, David; Selvaraj, Samuel

2013-12-01

Internal repeats in protein sequences play a significant role in the evolution of protein structure and function. Applications of different bioinformatics tools help in the identification and characterization of these repeats. In the present study, we analyzed sequence repeats in a non-redundant set of proteins available in the Protein Data Bank (PDB). We used RADAR for detecting internal repeats in a protein, PDBeFOLD for assessing structural similarity, PDBsum for finding functional involvement and Pfam for domain assignment of the repeats in a protein. Through the analysis of sequence repeats, we found that identity of the sequence repeats falls in the range of 20-40% and, the superimposed structures of the most of the sequence repeats maintain similar overall folding. Analysis sequence repeats at the functional level reveals that most of the sequence repeats are involved in the function of the protein through functionally involved residues in the repeat regions. We also found that sequence repeats in single and two domain proteins often contained conserved sequence motifs for the function of the domain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Analysis of full-length sequences of two Citrus yellow mosaic badnavirus isolates infecting Citrus jambhiri (Rough Lemon) and Citrus sinensis L. Osbeck (Sweet Orange) from a nursery in India.

PubMed

Anthony Johnson, A M; Borah, B K; Sai Gopal, D V R; Dasgupta, I

2012-12-01

Citrus yellow mosaic badna virus (CMBV), a member of the Family Caulimoviridae, Genus Badnavirus is the causative agent of mosaic disease among Citrus species in southern India. Despite its reported prevalence in several citrus species, complete information on clear functional genomics or functional information of full-length genomes from all the CMBV isolates infecting citrus species are not available in publicly accessible databases. CMBV isolates from Rough Lemon and Sweet Orange collected from a nursery were cloned and sequenced. The analysis revealed high sequence homology of the two CMBV isolates with previously reported CMBV sequences implying that they represent new variants. Based on computational analysis of the predicted secondary structures, the possible functions of some CMBV proteins have been analyzed.

Structural Analysis of PTM Hotspots (SAPH-ire)--A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families.

PubMed

Dewhurst, Henry M; Choudhury, Shilpa; Torres, Matthew P

2015-08-01

Predicting the biological function potential of post-translational modifications (PTMs) is becoming increasingly important in light of the exponential increase in available PTM data from high-throughput proteomics. We developed structural analysis of PTM hotspots (SAPH-ire)--a quantitative PTM ranking method that integrates experimental PTM observations, sequence conservation, protein structure, and interaction data to allow rank order comparisons within or between protein families. Here, we applied SAPH-ire to the study of PTMs in diverse G protein families, a conserved and ubiquitous class of proteins essential for maintenance of intracellular structure (tubulins) and signal transduction (large and small Ras-like G proteins). A total of 1728 experimentally verified PTMs from eight unique G protein families were clustered into 451 unique hotspots, 51 of which have a known and cited biological function or response. Using customized software, the hotspots were analyzed in the context of 598 unique protein structures. By comparing distributions of hotspots with known versus unknown function, we show that SAPH-ire analysis is predictive for PTM biological function. Notably, SAPH-ire revealed high-ranking hotspots for which a functional impact has not yet been determined, including phosphorylation hotspots in the N-terminal tails of G protein gamma subunits--conserved protein structures never before reported as regulators of G protein coupled receptor signaling. To validate this prediction we used the yeast model system for G protein coupled receptor signaling, revealing that gamma subunit-N-terminal tail phosphorylation is activated in response to G protein coupled receptor stimulation and regulates protein stability in vivo. These results demonstrate the utility of integrating protein structural and sequence features into PTM prioritization schemes that can improve the analysis and functional power of modification-specific proteomics data. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Discovery and functional characterisation of a luqin-type neuropeptide signalling system in a deuterostome.

PubMed

Yañez-Guerra, Luis Alfonso; Delroisse, Jérôme; Barreiro-Iglesias, Antón; Slade, Susan E; Scrivens, James H; Elphick, Maurice R

2018-05-08

Neuropeptides are diverse and evolutionarily ancient regulators of physiological/behavioural processes in animals. Here we have investigated the evolution and comparative physiology of luqin-type neuropeptide signalling, which has been characterised previously in protostomian invertebrates. Phylogenetic analysis indicates that luqin-type receptors and tachykinin-type receptors are paralogous and probably originated in a common ancestor of the Bilateria. In the deuterostomian lineage, luqin-type signalling has been lost in chordates but interestingly it has been retained in ambulacrarians. Therefore, here we characterised luqin-type signalling for the first time in an ambulacrarian - the starfish Asterias rubens (phylum Echinodermata). A luqin-like neuropeptide with a C-terminal RWamide motif (ArLQ; EEKTRFPKFMRW-NH 2 ) was identified as the ligand for two luqin-type receptors in A. rubens, ArLQR1 and ArLQR2. Furthermore, analysis of the expression of the ArLQ precursor using mRNA in situ hybridisation revealed expression in the nervous system, digestive system and locomotory organs (tube feet) and in vitro pharmacology revealed that ArLQ causes dose-dependent relaxation of tube feet. Accordingly, previous studies have revealed that luqin-type signalling regulates feeding and locomotor activity in protostomes. In conclusion, our phylogenetic analysis combined with characterisation of luqin-type signalling in a deuterostome has provided new insights into neuropeptide evolution and function in the animal kingdom.

Hydrophobic Coatings on Cotton Obtained by in Situ Plasma Polymerization of a Fluorinated Monomer in Ethanol Solutions.

PubMed

Molina, Ricardo; Teixidó, Josep Maria; Kan, Chi-Wai; Jovančić, Petar

2017-02-15

Plasma polymerization using hydrophobic monomers in the gas phase is a well-known technology to generate hydrophobic coatings. However, synthesis of functional hydrophobic coatings using plasma technology in liquids has not yet been accomplished. This work is consequently focused on polymerization of a liquid fluorinated monomer on cotton fabric initiated by atmospheric plasma in a dielectric barrier discharge configuration. Functional hydrophobic coatings on cotton were successfully achieved using in situ atmospheric plasma-initiated polymerization of fluorinated monomer dissolved in ethanol. Gravimetric measurements reveal that the amount of polymer deposited on cotton substrates can be modulated with the concentration of monomer in ethanol solution, and cross-linking reactions occur during plasma polymerization of a fluorinated monomer even without the presence of a cross-linking agent. FTIR and XPS analysis were used to study the chemical composition of hydrophobic coatings and to get insights into the physicochemical processes involved in plasma treatment. SEM analysis reveals that at high monomer concentration, coatings possess a three-dimensional pattern with a characteristic interconnected porous network structure. EDX analysis reveals that plasma polymerization of fluorinated monomers takes place preferentially at the surface of cotton fabric and negligible polymerization takes place inside the cotton fabric. Wetting time measurements confirm the hydrophobicity of cotton coatings obtained although equilibrium moisture content was slightly decreased. Additionally, the abrasion behavior and resistance to washing of plasma-coated cotton has been evaluated.

Abnormal rsFC and GMV changes in parahippocampal and DLPFC for high Déjà vu experienced subjects.

PubMed

Qiu, Jiang; Xia, Yunman; He, Li; Chen, Qunlin; Sang, Na; Liu, Wei; Li, Hong

2018-03-01

How déjà vu works has long been a mystery, partially because of its characteristics of unpredictable occurrences and quick disappearances, which make it difficult to be explored. Previous studies have described the anatomical structures underlying déjà vu in healthy subjects; however, the functional mechanism of déjà vu remains unclear. Therefore, this study investigated the brain structural and functional components underlying déjà vu by combining voxel-based morphometry analysis (VBM) with resting-state functional connectivity (rsFC). The VBM analysis revealed that the anterior parahippocampal gyrus (PHG) had significantly less grey matter volume (GMV) in high déjà vu group than low group, confirming previous studies. Further functional connectivity analysis revealed that the frequency of déjà vu experiences was negatively correlated with the strength of the rsFC between anterior dorsal lateral prefrontal cortex (DLPFC) and anterior PHG but positively correlated with the strength of the rsFC between posterior DLPFC and posterior PHG. Moreover, the frequency of déjà vu experiences was negatively correlated with the strength of the rsFC between the anterior and posterior regions of the PHG. These findings indicated that familiarity without recollection (PHG) and superior context monitoring (DLPFC) are critical for real-life déjà vu experiences. Copyright © 2018 Elsevier B.V. All rights reserved.

Large-scale Granger causality analysis on resting-state functional MRI

NASA Astrophysics Data System (ADS)

D'Souza, Adora M.; Abidin, Anas Zainul; Leistritz, Lutz; Wismüller, Axel

2016-03-01

We demonstrate an approach to measure the information flow between each pair of time series in resting-state functional MRI (fMRI) data of the human brain and subsequently recover its underlying network structure. By integrating dimensionality reduction into predictive time series modeling, large-scale Granger Causality (lsGC) analysis method can reveal directed information flow suggestive of causal influence at an individual voxel level, unlike other multivariate approaches. This method quantifies the influence each voxel time series has on every other voxel time series in a multivariate sense and hence contains information about the underlying dynamics of the whole system, which can be used to reveal functionally connected networks within the brain. To identify such networks, we perform non-metric network clustering, such as accomplished by the Louvain method. We demonstrate the effectiveness of our approach to recover the motor and visual cortex from resting state human brain fMRI data and compare it with the network recovered from a visuomotor stimulation experiment, where the similarity is measured by the Dice Coefficient (DC). The best DC obtained was 0.59 implying a strong agreement between the two networks. In addition, we thoroughly study the effect of dimensionality reduction in lsGC analysis on network recovery. We conclude that our approach is capable of detecting causal influence between time series in a multivariate sense, which can be used to segment functionally connected networks in the resting-state fMRI.

Differential Dynamic Engagement within 24 SH3 Domain: Peptide Complexes Revealed by Co-Linear Chemical Shift Perturbation Analysis

PubMed Central

Stollar, Elliott J.; Lin, Hong; Davidson, Alan R.; Forman-Kay, Julie D.

2012-01-01

There is increasing evidence for the functional importance of multiple dynamically populated states within single proteins. However, peptide binding by protein-protein interaction domains, such as the SH3 domain, has generally been considered to involve the full engagement of peptide to the binding surface with minimal dynamics and simple methods to determine dynamics at the binding surface for multiple related complexes have not been described. We have used NMR spectroscopy combined with isothermal titration calorimetry to comprehensively examine the extent of engagement to the yeast Abp1p SH3 domain for 24 different peptides. Over one quarter of the domain residues display co-linear chemical shift perturbation (CCSP) behavior, in which the position of a given chemical shift in a complex is co-linear with the same chemical shift in the other complexes, providing evidence that each complex exists as a unique dynamic rapidly inter-converting ensemble. The extent the specificity determining sub-surface of AbpSH3 is engaged as judged by CCSP analysis correlates with structural and thermodynamic measurements as well as with functional data, revealing the basis for significant structural and functional diversity amongst the related complexes. Thus, CCSP analysis can distinguish peptide complexes that may appear identical in terms of general structure and percent peptide occupancy but have significant local binding differences across the interface, affecting their ability to transmit conformational change across the domain and resulting in functional differences. PMID:23251481

Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity

PubMed Central

Anastassiadis, Theonie; Deacon, Sean W.; Devarajan, Karthik; Ma, Haiching; Peterson, Jeffrey R.

2011-01-01

Small-molecule protein kinase inhibitors are central tools for elucidating cellular signaling pathways and are promising therapeutic agents. Due to evolutionary conservation of the ATP-binding site, most kinase inhibitors that target this site promiscuously inhibit multiple kinases. Interpretation of experiments utilizing these compounds is confounded by a lack of data on the comprehensive kinase selectivity of most inhibitors. Here we profiled the activity of 178 commercially available kinase inhibitors against a panel of 300 recombinant protein kinases using a functional assay. Quantitative analysis revealed complex and often unexpected kinase-inhibitor interactions, with a wide spectrum of promiscuity. Many off-target interactions occur with seemingly unrelated kinases, revealing how large-scale profiling can be used to identify multi-targeted inhibitors of specific, diverse kinases. The results have significant implications for drug development and provide a resource for selecting compounds to elucidate kinase function and for interpreting the results of experiments that use them. PMID:22037377

Genome-wide STAT3 binding analysis after histone deacetylase inhibition reveals novel target genes in dendritic cells

PubMed Central

Sun, Yaping; Iyer, Matthew; McEachin, Richard; Zhao, Meng; Wu, Yi-Mi; Cao, Xuhong; Oravecz-Wilson, Katherine; Zajac, Cynthia; Mathewson, Nathan; Wu, Shin-Rong Julia; Rossi, Corinne; Toubai, Tomomi; Qin, Zhaohui S.; Chinnaiya, Arul M.; Reddy, Pavan

2016-01-01

STAT3 is a master transcriptional regulator that plays an important role in the induction of both immune activation and immune tolerance in dendritic cells (DCs). The transcriptional targets of STAT3 in promoting DC activation are becoming increasingly understood; however, the mechanisms underpinning its role in causing DC suppression remain largely unknown. To determine the functional gene targets of STAT3, we compared the genome-wide binding of STAT3 using ChIP-seq coupled with gene expression microarrays to determine STAT3-dependent gene regulation in DCs after histone deacetylase (HDAC) inhibition. HDAC inhibition boosted the ability of STAT3 to bind to distinct DNA targets and regulate gene expression. Among the top 500 STAT3 binding sites, the frequency of canonical motifs was significantly higher than that of non-canonical motifs. Functional analysis revealed that after treatment with an HDAC inhibitor, the upregulated STAT3 target genes were those that were primarily the negative regulators of pro-inflammatory cytokines and those in the IL-10 signaling pathway. The downregulated STAT3-dependent targets were those involved in immune effector processes and antigen processing/presentation. The expression and functional relevance of these genes were validated. Specifically, functional studies confirmed that the upregulation of IL-10Ra by STAT3 contributed to the suppressive function of DCs following HDAC inhibition. PMID:27866206

Characterization and functional analyses of a novel chicken CD8a variant X1 (CD8a1)

USDA-ARS?s Scientific Manuscript database

We provide the first description of cloning, as well as structural and functional analysis of a novel variant in the chicken CD8alpha family, termed the CD8-alpha X1 (CD8alpha1) gene. Multiple alignment of CD8alpha1 with known CD8alpha and beta sequences of other species revealed relatively low con...

Stress and Coping: A Comparison of Self-Report Measures of Functioning in Families of Young Children with Cerebral Palsy or No Medical Diagnosis

ERIC Educational Resources Information Center

Britner, Preston A.; Morog, Maria C.; Pianta, Robert C.; Marvin, Robert S.

2003-01-01

We analyzed data from 87 mothers of children ages 15 to 44 months with cerebral palsy (CP) or no diagnosis, who completed the Dyadic Adjustment Scale, Parenting Stress Index, Support Functions Scale, and Inventory of Social Support. Principal components analysis of the 15 subscales from the 5 measures revealed few cross-measure loadings. Mothers…

Profiling of proteins secreted in the bovine oviduct reveals diverse functions of this luminal microenvironment.

PubMed

Pillai, Viju Vijayan; Weber, Darren M; Phinney, Brett S; Selvaraj, Vimal

2017-01-01

The oviductal microenvironment is a site for key events that involve gamete maturation, fertilization and early embryo development. Secretions into the oviductal lumen by either the lining epithelium or by transudation of plasma constituents are known to contain elements conducive for reproductive success. Although previous studies have identified some of these factors involved in reproduction, knowledge of secreted proteins in the oviductal fluid remains rudimentary with limited definition of function even in extensively studied species like cattle. In this study, we used a shotgun proteomics approach followed by bioinformatics sequence prediction to identify secreted proteins present in the bovine oviductal fluid (ex vivo) and secretions from the bovine oviductal epithelial cells (in vitro). From a total of 2087 proteins identified, 266 proteins could be classified as secreted, 109 (41%) of which were common for both in vivo and in vitro conditions. Pathway analysis indicated different classes of proteins that included growth factors, metabolic regulators, immune modulators, enzymes, and extracellular matrix components. Functional analysis revealed mechanisms in the oviductal lumen linked to immune homeostasis, gamete maturation, fertilization and early embryo development. These results point to several novel components that work together with known elements mediating functional homeostasis, and highlight the diversity of machinery associated with oviductal physiology and early events in cattle fertility.

Insight, symptoms and executive functions in schizophrenia.

PubMed

Simon, Andor E; Berger, Gregor E; Giacomini, Véronique; Ferrero, François; Mohr, Sylvia

2006-09-01

We investigated the relationship of insight with executive functions and symptoms in a group of stabilised inpatients with schizophrenia. Executive functions using an extensive battery constituted of several tests as well as psychopathology were assessed in 38 inpatients with a DSM-IV diagnosis of schizophrenia. Insight was assessed with the Scale to assess Unawareness of Mental Disorder (SUMD). A principal component analysis of the insight dimensions revealed a three-factor model which accounted for 98% of the variance. Of particular interest is the finding that a composite factor that accounted for 74% of the variance covered insight dimensions that represent a higher degree of insight (awareness of mental disorder, its social consequences, and attribution of symptoms). Only an association between letter fluency and this composite factor was found, which was weakly mediated by depressive symptoms. A stepwise multiple regression analysis revealed a relationship between antipsychotic dose and awareness of medication effect. No association of illness duration and insight was found. The findings of partial association between dimensions of insight and measures of executive function supports the growing evidence that insight is a multidimensional phenomenon. Accordingly, they emphasise that in the framework of therapeutic interventions, enhancement of higher levels of insight needs to take into account that patients suffering from schizophrenia have differential impairment in insight dimensions.

PRODUCTION ENGINEERING AND MARKETING ANALYSIS OF THE ROTATING DISK EVAPORATOR

EPA Science Inventory

Recent EPA-funded research into the onsite, mechanical evaporation of wastewater from single family homes revealed that a rotating disk evaporator (RDE) could function in a nondischarging mode. Such a device has potential use where site limitations preclude conventional methods o...

Grey Matter Alterations Co-Localize with Functional Abnormalities in Developmental Dyslexia: An ALE Meta-Analysis

PubMed Central

Linkersdörfer, Janosch; Lonnemann, Jan; Lindberg, Sven; Hasselhorn, Marcus; Fiebach, Christian J.

2012-01-01

The neural correlates of developmental dyslexia have been investigated intensively over the last two decades and reliable evidence for a dysfunction of left-hemispheric reading systems in dyslexic readers has been found in functional neuroimaging studies. In addition, structural imaging studies using voxel-based morphometry (VBM) demonstrated grey matter reductions in dyslexics in several brain regions. To objectively assess the consistency of these findings, we performed activation likelihood estimation (ALE) meta-analysis on nine published VBM studies reporting 62 foci of grey matter reduction in dyslexic readers. We found six significant clusters of convergence in bilateral temporo-parietal and left occipito-temporal cortical regions and in the cerebellum bilaterally. To identify possible overlaps between structural and functional deviations in dyslexic readers, we conducted additional ALE meta-analyses of imaging studies reporting functional underactivations (125 foci from 24 studies) or overactivations (95 foci from 11 studies ) in dyslexics. Subsequent conjunction analyses revealed overlaps between the results of the VBM meta-analysis and the meta-analysis of functional underactivations in the fusiform and supramarginal gyri of the left hemisphere. An overlap between VBM results and the meta-analysis of functional overactivations was found in the left cerebellum. The results of our study provide evidence for consistent grey matter variations bilaterally in the dyslexic brain and substantial overlap of these structural variations with functional abnormalities in left hemispheric regions. PMID:22916214

Extracting neuronal functional network dynamics via adaptive Granger causality analysis.

PubMed

Sheikhattar, Alireza; Miran, Sina; Liu, Ji; Fritz, Jonathan B; Shamma, Shihab A; Kanold, Patrick O; Babadi, Behtash

2018-04-24

Quantifying the functional relations between the nodes in a network based on local observations is a key challenge in studying complex systems. Most existing time series analysis techniques for this purpose provide static estimates of the network properties, pertain to stationary Gaussian data, or do not take into account the ubiquitous sparsity in the underlying functional networks. When applied to spike recordings from neuronal ensembles undergoing rapid task-dependent dynamics, they thus hinder a precise statistical characterization of the dynamic neuronal functional networks underlying adaptive behavior. We develop a dynamic estimation and inference paradigm for extracting functional neuronal network dynamics in the sense of Granger, by integrating techniques from adaptive filtering, compressed sensing, point process theory, and high-dimensional statistics. We demonstrate the utility of our proposed paradigm through theoretical analysis, algorithm development, and application to synthetic and real data. Application of our techniques to two-photon Ca 2+ imaging experiments from the mouse auditory cortex reveals unique features of the functional neuronal network structures underlying spontaneous activity at unprecedented spatiotemporal resolution. Our analysis of simultaneous recordings from the ferret auditory and prefrontal cortical areas suggests evidence for the role of rapid top-down and bottom-up functional dynamics across these areas involved in robust attentive behavior.

Native KCC2 interactome reveals PACSIN1 as a critical regulator of synaptic inhibition.

PubMed

Mahadevan, Vivek; Khademullah, C Sahara; Dargaei, Zahra; Chevrier, Jonah; Uvarov, Pavel; Kwan, Julian; Bagshaw, Richard D; Pawson, Tony; Emili, Andrew; De Koninck, Yves; Anggono, Victor; Airaksinen, Matti; Woodin, Melanie A

2017-10-13

KCC2 is a neuron-specific K + -Cl - cotransporter essential for establishing the Cl - gradient required for hyperpolarizing inhibition in the central nervous system (CNS). KCC2 is highly localized to excitatory synapses where it regulates spine morphogenesis and AMPA receptor confinement. Aberrant KCC2 function contributes to human neurological disorders including epilepsy and neuropathic pain. Using functional proteomics, we identified the KCC2-interactome in the mouse brain to determine KCC2-protein interactions that regulate KCC2 function. Our analysis revealed that KCC2 interacts with diverse proteins, and its most predominant interactors play important roles in postsynaptic receptor recycling. The most abundant KCC2 interactor is a neuronal endocytic regulatory protein termed PACSIN1 (SYNDAPIN1). We verified the PACSIN1-KCC2 interaction biochemically and demonstrated that shRNA knockdown of PACSIN1 in hippocampal neurons increases KCC2 expression and hyperpolarizes the reversal potential for Cl - . Overall, our global native-KCC2 interactome and subsequent characterization revealed PACSIN1 as a novel and potent negative regulator of KCC2.

Native KCC2 interactome reveals PACSIN1 as a critical regulator of synaptic inhibition

PubMed Central

Mahadevan, Vivek; Chevrier, Jonah; Uvarov, Pavel; Kwan, Julian; Bagshaw, Richard D; Pawson, Tony; Emili, Andrew; De Koninck, Yves; Anggono, Victor; Airaksinen, Matti

2017-01-01

KCC2 is a neuron-specific K+-Cl– cotransporter essential for establishing the Cl- gradient required for hyperpolarizing inhibition in the central nervous system (CNS). KCC2 is highly localized to excitatory synapses where it regulates spine morphogenesis and AMPA receptor confinement. Aberrant KCC2 function contributes to human neurological disorders including epilepsy and neuropathic pain. Using functional proteomics, we identified the KCC2-interactome in the mouse brain to determine KCC2-protein interactions that regulate KCC2 function. Our analysis revealed that KCC2 interacts with diverse proteins, and its most predominant interactors play important roles in postsynaptic receptor recycling. The most abundant KCC2 interactor is a neuronal endocytic regulatory protein termed PACSIN1 (SYNDAPIN1). We verified the PACSIN1-KCC2 interaction biochemically and demonstrated that shRNA knockdown of PACSIN1 in hippocampal neurons increases KCC2 expression and hyperpolarizes the reversal potential for Cl-. Overall, our global native-KCC2 interactome and subsequent characterization revealed PACSIN1 as a novel and potent negative regulator of KCC2. PMID:29028184

The neural correlates of obsessive-compulsive disorder: a multimodal perspective.

PubMed

Moreira, P S; Marques, P; Soriano-Mas, C; Magalhães, R; Sousa, N; Soares, J M; Morgado, P

2017-08-29

Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric conditions. An extensive body of the literature has described some of the neurobiological mechanisms underlying the core manifestations of the disorder. Nevertheless, most reports have focused on individual modalities of structural/functional brain alterations, mainly through targeted approaches, thus possibly precluding the power of unbiased exploratory approaches. Eighty subjects (40 OCD and 40 healthy controls) participated in a multimodal magnetic resonance imaging (MRI) investigation, integrating structural and functional data. Voxel-based morphometry analysis was conducted to compare between-group volumetric differences. The whole-brain functional connectome, derived from resting-state functional connectivity (FC), was analyzed with the network-based statistic methodology. Results from structural and functional analysis were integrated in mediation models. OCD patients revealed volumetric reductions in the right superior temporal sulcus. Patients had significantly decreased FC in two distinct subnetworks: the first, involving the orbitofrontal cortex, temporal poles and the subgenual anterior cingulate cortex; the second, comprising the lingual and postcentral gyri. On the opposite, a network formed by connections between thalamic and occipital regions had significantly increased FC in patients. Integrative models revealed direct and indirect associations between volumetric alterations and FC networks. This study suggests that OCD patients display alterations in brain structure and FC, involving complex networks of brain regions. Furthermore, we provided evidence for direct and indirect associations between structural and functional alterations representing complex patterns of interactions between separate brain regions, which may be of upmost relevance for explaining the pathophysiology of the disorder.

Expression and functional characterization of Smyd1a in myofibril organization of skeletal muscles.

PubMed

Gao, Jie; Li, Junling; Li, Bao-Jun; Yagil, Ezra; Zhang, Jianshe; Du, Shao Jun

2014-01-01

Smyd1, the founding member of the Smyd family including Smyd-1, 2, 3, 4 and 5, is a SET and MYND domain containing protein that plays a key role in myofibril assembly in skeletal and cardiac muscles. Bioinformatic analysis revealed that zebrafish genome contains two highly related smyd1 genes, smyd1a and smyd1b. Although Smyd1b function is well characterized in skeletal and cardiac muscles, the function of Smyd1a is, however, unknown. To investigate the function of Smyd1a in muscle development, we isolated smyd1a from zebrafish, and characterized its expression and function during muscle development via gene knockdown and transgenic expression approaches. The results showed that smyd1a was strongly expressed in skeletal muscles of zebrafish embryos. Functional analysis revealed that knockdown of smyd1a alone had no significant effect on myofibril assembly in zebrafish skeletal muscles. However, knockdown of smyd1a and smyd1b together resulted in a complete disruption of myofibril organization in skeletal muscles, a phenotype stronger than knockdown of smyd1a or smyd1b alone. Moreover, ectopic expression of zebrafish smyd1a or mouse Smyd1 transgene could rescue the myofibril defects from the smyd1b knockdown in zebrafish embryos. Collectively, these data indicate that Smyd1a and Smyd1b share similar biological activity in myofibril assembly in zebrafish embryos. However, Smyd1b appears to play a major role in this process.

Identification and characterisation of midbrain nuclei using optimised functional magnetic resonance imaging

PubMed Central

Limbrick-Oldfield, Eve H.; Brooks, Jonathan C.W.; Wise, Richard J.S.; Padormo, Francesco; Hajnal, Jo V.; Beckmann, Christian F.; Ungless, Mark A.

2012-01-01

Localising activity in the human midbrain with conventional functional MRI (fMRI) is challenging because the midbrain nuclei are small and located in an area that is prone to physiological artefacts. Here we present a replicable and automated method to improve the detection and localisation of midbrain fMRI signals. We designed a visual fMRI task that was predicted would activate the superior colliculi (SC) bilaterally. A limited number of coronal slices were scanned, orientated along the long axis of the brainstem, whilst simultaneously recording cardiac and respiratory traces. A novel anatomical registration pathway was used to optimise the localisation of the small midbrain nuclei in stereotactic space. Two additional structural scans were used to improve registration between functional and structural T1-weighted images: an echo-planar image (EPI) that matched the functional data but had whole-brain coverage, and a whole-brain T2-weighted image. This pathway was compared to conventional registration pathways, and was shown to significantly improve midbrain registration. To reduce the physiological artefacts in the functional data, we estimated and removed structured noise using a modified version of a previously described physiological noise model (PNM). Whereas a conventional analysis revealed only unilateral SC activity, the PNM analysis revealed the predicted bilateral activity. We demonstrate that these methods improve the measurement of a biologically plausible fMRI signal. Moreover they could be used to investigate the function of other midbrain nuclei. PMID:21867762

Comparative evolutionary genomics of Corynebacterium with special reference to codon and amino acid usage diversities.

PubMed

Pal, Shilpee; Sarkar, Indrani; Roy, Ayan; Mohapatra, Pradeep K Das; Mondal, Keshab C; Sen, Arnab

2018-02-01

The present study has been aimed to the comparative analysis of high GC composition containing Corynebacterium genomes and their evolutionary study by exploring codon and amino acid usage patterns. Phylogenetic study by MLSA approach, indel analysis and BLAST matrix differentiated Corynebacterium species in pathogenic and non-pathogenic clusters. Correspondence analysis on synonymous codon usage reveals that, gene length, optimal codon frequencies and tRNA abundance affect the gene expression of Corynebacterium. Most of the optimal codons as well as translationally optimal codons are C ending i.e. RNY (R-purine, N-any nucleotide base, and Y-pyrimidine) and reveal translational selection pressure on codon bias of Corynebacterium. Amino acid usage is affected by hydrophobicity, aromaticity, protein energy cost, etc. Highly expressed genes followed the cost minimization hypothesis and are less diverged at their synonymous positions of codons. Functional analysis of core genes shows significant difference in pathogenic and non-pathogenic Corynebacterium. The study reveals close relationship between non-pathogenic and opportunistic pathogenic Corynebaterium as well as between molecular evolution and survival niches of the organism.

The Information Content of Discrete Functions and Their Application in Genetic Data Analysis

DOE PAGES

Sakhanenko, Nikita A.; Kunert-Graf, James; Galas, David J.

2017-10-13

The complex of central problems in data analysis consists of three components: (1) detecting the dependence of variables using quantitative measures, (2) defining the significance of these dependence measures, and (3) inferring the functional relationships among dependent variables. We have argued previously that an information theory approach allows separation of the detection problem from the inference of functional form problem. We approach here the third component of inferring functional forms based on information encoded in the functions. Here, we present here a direct method for classifying the functional forms of discrete functions of three variables represented in data sets. Discretemore » variables are frequently encountered in data analysis, both as the result of inherently categorical variables and from the binning of continuous numerical variables into discrete alphabets of values. The fundamental question of how much information is contained in a given function is answered for these discrete functions, and their surprisingly complex relationships are illustrated. The all-important effect of noise on the inference of function classes is found to be highly heterogeneous and reveals some unexpected patterns. We apply this classification approach to an important area of biological data analysis—that of inference of genetic interactions. Genetic analysis provides a rich source of real and complex biological data analysis problems, and our general methods provide an analytical basis and tools for characterizing genetic problems and for analyzing genetic data. Finally, we illustrate the functional description and the classes of a number of common genetic interaction modes and also show how different modes vary widely in their sensitivity to noise.« less

The Information Content of Discrete Functions and Their Application in Genetic Data Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakhanenko, Nikita A.; Kunert-Graf, James; Galas, David J.

The complex of central problems in data analysis consists of three components: (1) detecting the dependence of variables using quantitative measures, (2) defining the significance of these dependence measures, and (3) inferring the functional relationships among dependent variables. We have argued previously that an information theory approach allows separation of the detection problem from the inference of functional form problem. We approach here the third component of inferring functional forms based on information encoded in the functions. Here, we present here a direct method for classifying the functional forms of discrete functions of three variables represented in data sets. Discretemore » variables are frequently encountered in data analysis, both as the result of inherently categorical variables and from the binning of continuous numerical variables into discrete alphabets of values. The fundamental question of how much information is contained in a given function is answered for these discrete functions, and their surprisingly complex relationships are illustrated. The all-important effect of noise on the inference of function classes is found to be highly heterogeneous and reveals some unexpected patterns. We apply this classification approach to an important area of biological data analysis—that of inference of genetic interactions. Genetic analysis provides a rich source of real and complex biological data analysis problems, and our general methods provide an analytical basis and tools for characterizing genetic problems and for analyzing genetic data. Finally, we illustrate the functional description and the classes of a number of common genetic interaction modes and also show how different modes vary widely in their sensitivity to noise.« less

EEG Cortical Connectivity Analysis of Working Memory Reveals Topological Reorganization in Theta and Alpha Bands

PubMed Central

Dai, Zhongxiang; de Souza, Joshua; Lim, Julian; Ho, Paul M.; Chen, Yu; Li, Junhua; Thakor, Nitish; Bezerianos, Anastasios; Sun, Yu

2017-01-01

Numerous studies have revealed various working memory (WM)-related brain activities that originate from various cortical regions and oscillate at different frequencies. However, multi-frequency band analysis of the brain network in WM in the cortical space remains largely unexplored. In this study, we employed a graph theoretical framework to characterize the topological properties of the brain functional network in the theta and alpha frequency bands during WM tasks. Twenty-eight subjects performed visual n-back tasks at two difficulty levels, i.e., 0-back (control task) and 2-back (WM task). After preprocessing, Electroencephalogram (EEG) signals were projected into the source space and 80 cortical brain regions were selected for further analysis. Subsequently, the theta- and alpha-band networks were constructed by calculating the Pearson correlation coefficients between the power series (obtained by concatenating the power values of all epochs in each session) of all pairs of brain regions. Graph theoretical approaches were then employed to estimate the topological properties of the brain networks at different WM tasks. We found higher functional integration in the theta band and lower functional segregation in the alpha band in the WM task compared with the control task. Moreover, compared to the 0-back task, altered regional centrality was revealed in the 2-back task in various brain regions that mainly resided in the frontal, temporal and occipital lobes, with distinct presentations in the theta and alpha bands. In addition, significant negative correlations were found between the reaction time with the average path length of the theta-band network and the local clustering of the alpha-band network, which demonstrates the potential for using the brain network metrics as biomarkers for predicting the task performance during WM tasks. PMID:28553215

Neural correlates of social exclusion across ages: A coordinate-based meta-analysis of functional MRI studies.

PubMed

Vijayakumar, Nandita; Cheng, Theresa W; Pfeifer, Jennifer H

2017-06-01

Given the recent surge in functional neuroimaging studies on social exclusion, the current study employed activation likelihood estimation (ALE) based meta-analyses to identify brain regions that have consistently been implicated across different experimental paradigms used to investigate exclusion. We also examined the neural correlates underlying Cyberball, the most commonly used paradigm to study exclusion, as well as differences in exclusion-related activation between developing (7-18 years of age, from pre-adolescence up to late adolescence) and emerging adult (broadly defined as undergraduates, including late adolescence and young adulthood) samples. Results revealed involvement of the bilateral medial prefrontal and posterior cingulate cortices, right precuneus and left ventrolateral prefrontal cortex across the different paradigms used to examine social exclusion; similar activation patterns were identified when restricting the analysis to Cyberball studies. Investigations into age-related effects revealed that ventrolateral prefrontal activations identified in the full sample were driven by (i.e. present in) developmental samples, while medial prefrontal activations were driven by emerging adult samples. In addition, the right ventral striatum was implicated in exclusion, but only in developmental samples. Subtraction analysis revealed significantly greater activation likelihood in striatal and ventrolateral prefrontal clusters in the developmental samples as compared to emerging adults, though the opposite contrast failed to identify any significant regions. Findings integrate the knowledge accrued from functional neuroimaging studies on social exclusion to date, highlighting involvement of lateral prefrontal regions implicated in regulation and midline structures involved in social cognitive and self-evaluative processes across experimental paradigms and ages, as well as limbic structures in developing samples specifically. Copyright © 2017 Elsevier Inc. All rights reserved.

EEG Cortical Connectivity Analysis of Working Memory Reveals Topological Reorganization in Theta and Alpha Bands.

PubMed

Dai, Zhongxiang; de Souza, Joshua; Lim, Julian; Ho, Paul M; Chen, Yu; Li, Junhua; Thakor, Nitish; Bezerianos, Anastasios; Sun, Yu

2017-01-01

Numerous studies have revealed various working memory (WM)-related brain activities that originate from various cortical regions and oscillate at different frequencies. However, multi-frequency band analysis of the brain network in WM in the cortical space remains largely unexplored. In this study, we employed a graph theoretical framework to characterize the topological properties of the brain functional network in the theta and alpha frequency bands during WM tasks. Twenty-eight subjects performed visual n -back tasks at two difficulty levels, i.e., 0-back (control task) and 2-back (WM task). After preprocessing, Electroencephalogram (EEG) signals were projected into the source space and 80 cortical brain regions were selected for further analysis. Subsequently, the theta- and alpha-band networks were constructed by calculating the Pearson correlation coefficients between the power series (obtained by concatenating the power values of all epochs in each session) of all pairs of brain regions. Graph theoretical approaches were then employed to estimate the topological properties of the brain networks at different WM tasks. We found higher functional integration in the theta band and lower functional segregation in the alpha band in the WM task compared with the control task. Moreover, compared to the 0-back task, altered regional centrality was revealed in the 2-back task in various brain regions that mainly resided in the frontal, temporal and occipital lobes, with distinct presentations in the theta and alpha bands. In addition, significant negative correlations were found between the reaction time with the average path length of the theta-band network and the local clustering of the alpha-band network, which demonstrates the potential for using the brain network metrics as biomarkers for predicting the task performance during WM tasks.

ERBB4 Mutations that Disrupt the Neuregulin-ErbB4 Pathway Cause Amyotrophic Lateral Sclerosis Type 19

PubMed Central

Takahashi, Yuji; Fukuda, Yoko; Yoshimura, Jun; Toyoda, Atsushi; Kurppa, Kari; Moritoyo, Hiroyoko; Belzil, Veronique V.; Dion, Patrick A.; Higasa, Koichiro; Doi, Koichiro; Ishiura, Hiroyuki; Mitsui, Jun; Date, Hidetoshi; Ahsan, Budrul; Matsukawa, Takashi; Ichikawa, Yaeko; Moritoyo, Takashi; Ikoma, Mayumi; Hashimoto, Tsukasa; Kimura, Fumiharu; Murayama, Shigeo; Onodera, Osamu; Nishizawa, Masatoyo; Yoshida, Mari; Atsuta, Naoki; Sobue, Gen; Fifita, Jennifer A.; Williams, Kelly L.; Blair, Ian P.; Nicholson, Garth A.; Gonzalez-Perez, Paloma; Brown, Robert H.; Nomoto, Masahiro; Elenius, Klaus; Rouleau, Guy A.; Fujiyama, Asao; Morishita, Shinichi; Goto, Jun; Tsuji, Shoji

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3–5 years from onset. Familial ALS (FALS) comprises 5%–10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis. We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded. A whole- genome sequencing and parametric linkage analysis under the assumption of an autosomal-dominant mode of inheritance with incomplete penetrance revealed the mutation c.2780G>A (p. Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation in a Canadian individual with familial ALS and a de novo mutation, c.3823C>T (p. Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve amino acids highly conserved among species, are predicted as probably damaging, and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a receptor tyrosine kinase. Functional analysis revealed that these mutations led to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation. Clinical presentations of the individuals with mutations were characterized by the involvement of both upper and lower motor neurons, a lack of obvious cognitive dysfunction, and relatively slow progression. This study indicates that disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS and potentially paves the way for the development of innovative therapeutic strategies such using NRGs or their agonists to upregulate ErbB4 functions. PMID:24119685

Molecular modeling and docking studies of human 5-hydroxytryptamine 2A (5-HT2A) receptor for the identification of hotspots for ligand binding.

PubMed

Kanagarajadurai, Karuppiah; Malini, Manoharan; Bhattacharya, Aditi; Panicker, Mitradas M; Sowdhamini, Ramanathan

2009-12-01

The serotonergic system has been implicated in emotional and cognitive function. In particular, 5-HT(2A) (5-hydroxytrytamine receptor 2A) is attributed to a number of disorders like schizophrenia, depression, eating disorders and anxiety. 5-HT(2A), being a GPCR (G-protein coupled receptor), is important in the pharmaceutical industry as a proven target for these disorders. Despite their extensive clinical importance, the structural studies of this protein is lacking due to difficulties in determining its crystal structure. We have performed sequence analysis and molecular modeling of 5-HT(2A) that has revealed a set of conserved residues and motifs considered to play an important role in maintaining structural integrity and function of the receptor. The analysis also revealed a set of residues specific to the receptor which distinguishes them from other members of the subclass and their orthologs. Further, starting from the model structure of human 5-HT(2A) receptor, docking studies were attempted to envisage how it might interact with eight of its ligands (such as serotonin, dopamine, DOI, LSD, haloperidol, ketanserin, risperidone and clozapine). The binding studies of dopamine to 5-HT(2A) receptor can bring up better understanding in the etiology of a number of neurological disorders involving both these two receptors. Our sequence analysis and study of interactions of this receptor with other ligands reveal additional residue hotspots such as Asn 363 and Tyr 370. The function of these residues can be further analyzed by rational design of site-directed mutagenesis. Two distinct binding sites are identified which could play important roles in ligand binding and signaling.

Photoelectron spectra and biological activity of cinnamic acid derivatives revisited

NASA Astrophysics Data System (ADS)

Novak, Igor; Klasinc, Leo; McGlynn, Sean P.

2018-01-01

The electronic structures of several derivatives of cinnamic acid have been studied by UV photoelectron spectroscopy (UPS) and Green's function quantum chemical calculations. The spectra reveal the presence of dimers in the gas phase for p-coumaric and ferulic acids. The electronic structure analysis has been related to the biological properties of these compounds through the analysis of some structure-activity relationships (SAR).

Neuroimaging with functional near infrared spectroscopy: From formation to interpretation

NASA Astrophysics Data System (ADS)

Herrera-Vega, Javier; Treviño-Palacios, Carlos G.; Orihuela-Espina, Felipe

2017-09-01

Functional Near Infrared Spectroscopy (fNIRS) is gaining momentum as a functional neuroimaging modality to investigate the cerebral hemodynamics subsequent to neural metabolism. As other neuroimaging modalities, it is neuroscience's tool to understand brain systems functions at behaviour and cognitive levels. To extract useful knowledge from functional neuroimages it is critical to understand the series of transformations applied during the process of the information retrieval and how they bound the interpretation. This process starts with the irradiation of the head tissues with infrared light to obtain the raw neuroimage and proceeds with computational and statistical analysis revealing hidden associations between pixels intensities and neural activity encoded to end up with the explanation of some particular aspect regarding brain function.To comprehend the overall process involved in fNIRS there is extensive literature addressing each individual step separately. This paper overviews the complete transformation sequence through image formation, reconstruction and analysis to provide an insight of the final functional interpretation.

Dynamic Functional Connectivity States Between the Dorsal and Ventral Sensorimotor Networks Revealed by Dynamic Conditional Correlation Analysis of Resting-State Functional Magnetic Resonance Imaging.

PubMed

Syed, Maleeha F; Lindquist, Martin A; Pillai, Jay J; Agarwal, Shruti; Gujar, Sachin K; Choe, Ann S; Caffo, Brian; Sair, Haris I

2017-12-01

Functional connectivity in resting-state functional magnetic resonance imaging (rs-fMRI) has received substantial attention since the initial findings of Biswal et al. Traditional network correlation metrics assume that the functional connectivity in the brain remains stationary over time. However, recent studies have shown that robust temporal fluctuations of functional connectivity among as well as within functional networks exist, challenging this assumption. In this study, these dynamic correlation differences were investigated between the dorsal and ventral sensorimotor networks by applying the dynamic conditional correlation model to rs-fMRI data of 20 healthy subjects. k-Means clustering was used to determine an optimal number of discrete connectivity states (k = 10) of the sensorimotor system across all subjects. Our analysis confirms the existence of differences in dynamic correlation between the dorsal and ventral networks, with highest connectivity found within the ventral motor network.

Horizontal gene transfer in silkworm, Bombyx mori

PubMed Central

2011-01-01

Background The domesticated silkworm, Bombyx mori, is the model insect for the order Lepidoptera, has economically important values, and has gained some representative behavioral characteristics compared to its wild ancestor. The genome of B. mori has been fully sequenced while function analysis of BmChi-h and BmSuc1 genes revealed that horizontal gene transfer (HGT) maybe bestow a clear selective advantage to B. mori. However, the role of HGT in the evolutionary history of B. mori is largely unexplored. In this study, we compare the whole genome of B. mori with those of 382 prokaryotic and eukaryotic species to investigate the potential HGTs. Results Ten candidate HGT events were defined in B. mori by comprehensive sequence analysis using Maximum Likelihood and Bayesian method combining with EST checking. Phylogenetic analysis of the candidate HGT genes suggested that one HGT was plant-to- B. mori transfer while nine were bacteria-to- B. mori transfer. Furthermore, functional analysis based on expression, coexpression and related literature searching revealed that several HGT candidate genes have added important characters, such as resistance to pathogen, to B. mori. Conclusions Results from this study clearly demonstrated that HGTs play an important role in the evolution of B. mori although the number of HGT events in B. mori is in general smaller than those of microbes and other insects. In particular, interdomain HGTs in B. mori may give rise to functional, persistent, and possibly evolutionarily significant new genes. PMID:21595916

Bioinformatic analysis of the neprilysin (M13) family of peptidases reveals complex evolutionary and functional relationships.

PubMed

Bland, Nicholas D; Pinney, John W; Thomas, Josie E; Turner, Anthony J; Isaac, R Elwyn

2008-01-23

The neprilysin (M13) family of endopeptidases are zinc-metalloenzymes, the majority of which are type II integral membrane proteins. The best characterised of this family is neprilysin, which has important roles in inactivating signalling peptides involved in modulating neuronal activity, blood pressure and the immune system. Other family members include the endothelin converting enzymes (ECE-1 and ECE-2), which are responsible for the final step in the synthesis of potent vasoconstrictor endothelins. The ECEs, as well as neprilysin, are considered valuable therapeutic targets for treating cardiovascular disease. Other members of the M13 family have not been functionally characterised, but are also likely to have biological roles regulating peptide signalling. The recent sequencing of animal genomes has greatly increased the number of M13 family members in protein databases, information which can be used to reveal evolutionary relationships and to gain insight into conserved biological roles. The phylogenetic analysis successfully resolved vertebrate M13 peptidases into seven classes, one of which appears to be specific to mammals, and insect genes into five functional classes and a series of expansions, which may include inactive peptidases. Nematode genes primarily resolved into groups containing no other taxa, bar the two nematode genes associated with Drosophila DmeNEP1 and DmeNEP4. This analysis reconstructed only one relationship between chordate and invertebrate clusters, that of the ECE sub-group and the DmeNEP3 related genes. Analysis of amino acid utilisation in the active site of M13 peptidases reveals a basis for their biochemical properties. A relatively invariant S1' subsite gives the majority of M13 peptidases their strong preference for hydrophobic residues in P1' position. The greater variation in the S2' subsite may be instrumental in determining the specificity of M13 peptidases for their substrates and thus allows M13 peptidases to fulfil a broad range of physiological roles. The M13 family of peptidases have diversified extensively in all species examined, indicating wide ranging roles in numerous physiological processes. It is predicted that differences in the S2' subsite are fundamental to determining the substrate specificities that facilitate this functional diversity.

Proteomics profiling of interactome dynamics by colocalisation analysis (COLA).

PubMed

Mardakheh, Faraz K; Sailem, Heba Z; Kümper, Sandra; Tape, Christopher J; McCully, Ryan R; Paul, Angela; Anjomani-Virmouni, Sara; Jørgensen, Claus; Poulogiannis, George; Marshall, Christopher J; Bakal, Chris

2016-12-20

Localisation and protein function are intimately linked in eukaryotes, as proteins are localised to specific compartments where they come into proximity of other functionally relevant proteins. Significant co-localisation of two proteins can therefore be indicative of their functional association. We here present COLA, a proteomics based strategy coupled with a bioinformatics framework to detect protein-protein co-localisations on a global scale. COLA reveals functional interactions by matching proteins with significant similarity in their subcellular localisation signatures. The rapid nature of COLA allows mapping of interactome dynamics across different conditions or treatments with high precision.

A Prototype System for Retrieval of Gene Functional Information

PubMed Central

Folk, Lillian C.; Patrick, Timothy B.; Pattison, James S.; Wolfinger, Russell D.; Mitchell, Joyce A.

2003-01-01

Microarrays allow researchers to gather data about the expression patterns of thousands of genes simultaneously. Statistical analysis can reveal which genes show statistically significant results. Making biological sense of those results requires the retrieval of functional information about the genes thus identified, typically a manual gene-by-gene retrieval of information from various on-line databases. For experiments generating thousands of genes of interest, retrieval of functional information can become a significant bottleneck. To address this issue, we are currently developing a prototype system to automate the process of retrieval of functional information from multiple on-line sources. PMID:14728346

Diamond surface functionalization with biomimicry - Amine surface tether and thiol moiety for electrochemical sensors

NASA Astrophysics Data System (ADS)

Sund, James B.; Causey, Corey P.; Wolter, Scott D.; Parker, Charles B.; Stoner, Brian R.; Toone, Eric J.; Glass, Jeffrey T.

2014-05-01

The surface of conducting diamond was functionalized with a terminal thiol group that is capable of binding and detecting nitrogen-oxygen species. The functionalization process employed multiple steps starting with doped diamond films grown by plasma enhanced chemical vapor deposition followed by hydrogen termination and photochemical attachment of a chemically protected amine alkene. The surface tether was deprotected to reveal the amine functionality, which enabled the tether to be extended with surface chemistry to add a terminal thiol moiety for electrochemical sensing applications. Each step of the process was validated using X-ray photoelectron spectroscopy analysis.

Identification and expression profiling analysis of TCP family genes involved in growth and development in maize.

PubMed

Chai, Wenbo; Jiang, Pengfei; Huang, Guoyu; Jiang, Haiyang; Li, Xiaoyu

2017-10-01

The TCP family is a group of plant-specific transcription factors. TCP genes encode proteins harboring bHLH structure, which is implicated in DNA binding and protein-protein interactions and known as the TCP domain. TCP genes play important roles in plant development and have been evolutionarily and functionally elaborated in various plants, however, no overall phylogenetic analysis or expression profiling of TCP genes in Zea mays has been reported. In the present study, a systematic analysis of molecular evolution and functional prediction of TCP family genes in maize ( Z . mays L.) has been conducted. We performed a genome-wide survey of TCP genes in maize, revealing the gene structure, chromosomal location and phylogenetic relationship of family members. Microsynteny between grass species and tissue-specific expression profiles were also investigated. In total, 29 TCP genes were identified in the maize genome, unevenly distributed on the 10 maize chromosomes. Additionally, ZmTCP genes were categorized into nine classes based on phylogeny and purifying selection may largely be responsible for maintaining the functions of maize TCP genes. What's more, microsynteny analysis suggested that TCP genes have been conserved during evolution. Finally, expression analysis revealed that most TCP genes are expressed in the stem and ear, which suggests that ZmTCP genes influence stem and ear growth. This result is consistent with the previous finding that maize TCP genes represses the growth of axillary organs and enables the formation of female inflorescences. Altogether, this study presents a thorough overview of TCP family in maize and provides a new perspective on the evolution of this gene family. The results also indicate that TCP family genes may be involved in development stage in plant growing conditions. Additionally, our results will be useful for further functional analysis of the TCP gene family in maize.

Motivational and neurocognitive deficits are central to the prediction of longitudinal functional outcome in schizophrenia.

PubMed

Fervaha, G; Foussias, G; Agid, O; Remington, G

2014-10-01

Functional impairment is characteristic of most individuals with schizophrenia; however, the key variables that undermine community functioning are not well understood. This study evaluated the association between selected clinical variables and one-year longitudinal functional outcomes in patients with schizophrenia. The sample included 754 patients with schizophrenia who completed both baseline and one-year follow-up visits in the CATIE study. Patients were evaluated with a comprehensive battery of assessments capturing symptom severity and cognitive performance among other variables. The primary outcome variable was functional status one-year postbaseline measured using the Heinrichs-Carpenter Quality of Life Scale. Factor analysis of negative symptom items revealed two factors reflecting diminished expression and amotivation. Multivariate regression modeling revealed several significant independent predictors of longitudinal functioning scores. The strongest predictors were baseline amotivation and neurocognition. Both amotivation and neurocognition also had independent predictive value for each of the domains of functioning assessed (e.g., vocational). Both motivational and neurocognitive deficits independently contribute to longitudinal functional outcomes assessed 1 year later among patients with schizophrenia. Both of these domains of psychopathology impede functional recovery; hence, it follows that treatments ameliorating each of these symptoms should promote community functioning among individuals with schizophrenia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Higher-order Brain Areas Associated with Real-time Functional MRI Neurofeedback Training of the Somato-motor Cortex.

PubMed

Auer, Tibor; Dewiputri, Wan Ilma; Frahm, Jens; Schweizer, Renate

2018-05-15

Neurofeedback (NFB) allows subjects to learn self-regulation of neuronal brain activation based on information about the ongoing activation. The implementation of real-time functional magnetic resonance imaging (rt-fMRI) for NFB training now facilitates the investigation into underlying processes. Our study involved 16 control and 16 training right-handed subjects, the latter performing an extensive rt-fMRI NFB training using motor imagery. A previous analysis focused on the targeted primary somato-motor cortex (SMC). The present study extends the analysis to the supplementary motor area (SMA), the next higher brain area within the hierarchy of the motor system. We also examined transfer-related functional connectivity using a whole-volume psycho-physiological interaction (PPI) analysis to reveal brain areas associated with learning. The ROI analysis of the pre- and post-training fMRI data for motor imagery without NFB (transfer) resulted in a significant training-specific increase in the SMA. It could also be shown that the contralateral SMA exhibited a larger increase than the ipsilateral SMA in the training and the transfer runs, and that the right-hand training elicited a larger increase in the transfer runs than the left-hand training. The PPI analysis revealed a training-specific increase in transfer-related functional connectivity between the left SMA and frontal areas as well as the anterior midcingulate cortex (aMCC) for right- and left-hand trainings. Moreover, the transfer success was related with training-specific increase in functional connectivity between the left SMA and the target area SMC. Our study demonstrates that NFB training increases functional connectivity with non-targeted brain areas. These are associated with the training strategy (i.e., SMA) as well as with learning the NFB skill (i.e., aMCC and frontal areas). This detailed description of both the system to be trained and the areas involved in learning can provide valuable information for further optimization of NFB trainings. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders.

PubMed

Sato, Wataru; Toichi, Motomi; Uono, Shota; Kochiyama, Takanori

2012-08-13

Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD.We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex-MTG-IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.

Use of a Drosophila Genome-Wide Conserved Sequence Database to Identify Functionally Related cis-Regulatory Enhancers

PubMed Central

Brody, Thomas; Yavatkar, Amarendra S; Kuzin, Alexander; Kundu, Mukta; Tyson, Leonard J; Ross, Jermaine; Lin, Tzu-Yang; Lee, Chi-Hon; Awasaki, Takeshi; Lee, Tzumin; Odenwald, Ward F

2012-01-01

Background: Phylogenetic footprinting has revealed that cis-regulatory enhancers consist of conserved DNA sequence clusters (CSCs). Currently, there is no systematic approach for enhancer discovery and analysis that takes full-advantage of the sequence information within enhancer CSCs. Results: We have generated a Drosophila genome-wide database of conserved DNA consisting of >100,000 CSCs derived from EvoPrints spanning over 90% of the genome. cis-Decoder database search and alignment algorithms enable the discovery of functionally related enhancers. The program first identifies conserved repeat elements within an input enhancer and then searches the database for CSCs that score highly against the input CSC. Scoring is based on shared repeats as well as uniquely shared matches, and includes measures of the balance of shared elements, a diagnostic that has proven to be useful in predicting cis-regulatory function. To demonstrate the utility of these tools, a temporally-restricted CNS neuroblast enhancer was used to identify other functionally related enhancers and analyze their structural organization. Conclusions: cis-Decoder reveals that co-regulating enhancers consist of combinations of overlapping shared sequence elements, providing insights into the mode of integration of multiple regulating transcription factors. The database and accompanying algorithms should prove useful in the discovery and analysis of enhancers involved in any developmental process. Developmental Dynamics 241:169–189, 2012. © 2011 Wiley Periodicals, Inc. Key findings A genome-wide catalog of Drosophila conserved DNA sequence clusters. cis-Decoder discovers functionally related enhancers. Functionally related enhancers share balanced sequence element copy numbers. Many enhancers function during multiple phases of development. PMID:22174086

Can You Ride a Bicycle? The Ability to Ride a Bicycle Prevents Reduced Social Function in Older Adults With Mobility Limitation

PubMed Central

Sakurai, Ryota; Kawai, Hisashi; Yoshida, Hideyo; Fukaya, Taro; Suzuki, Hiroyuki; Kim, Hunkyung; Hirano, Hirohiko; Ihara, Kazushige; Obuchi, Shuichi; Fujiwara, Yoshinori

2016-01-01

Background The health benefits of bicycling in older adults with mobility limitation (ML) are unclear. We investigated ML and functional capacity of older cyclists by evaluating their instrumental activities of daily living (IADL), intellectual activity, and social function. Methods On the basis of interviews, 614 community-dwelling older adults (after excluding 63 participants who never cycled) were classified as cyclists with ML, cyclists without ML, non-cyclists with ML (who ceased bicycling due to physical difficulties), or non-cyclists without ML (who ceased bicycling for other reasons). A cyclist was defined as a person who cycled at least a few times per month, and ML was defined as difficulty walking 1 km or climbing stairs without using a handrail. Functional capacity and physical ability were evaluated by standardized tests. Results Regular cycling was documented in 399 participants, and 74 of them (18.5%) had ML; among non-cyclists, 49 had ML, and 166 did not. Logistic regression analysis for evaluating the relationship between bicycling and functional capacity revealed that non-cyclists with ML were more likely to have reduced IADL and social function compared to cyclists with ML. However, logistic regression analysis also revealed that the risk of bicycle-related falls was significantly associated with ML among older cyclists. Conclusions The ability and opportunity to bicycle may prevent reduced IADL and social function in older adults with ML, although older adults with ML have a higher risk of falls during bicycling. It is important to develop a safe environment for bicycling for older adults. PMID:26902165

Impact of cognitive function on oral perception in independently living older people.

PubMed

Fukutake, Motoyoshi; Ogawa, Taiji; Ikebe, Kazunori; Mihara, Yusuke; Inomata, Chisato; Takeshita, Hajime; Matsuda, Kenichi; Hatta, Kodai; Gondo, Yasuyuki; Masui, Yukie; Inagaki, Hiroki; Arai, Yasumichi; Kamide, Kei; Ishizaki, Tatsuro; Maeda, Yoshinobu

2018-04-10

Oral tactile perception is important for better mastication, appetite, and enjoyment of food. However, previous investigations have not utilized comprehensible variables thought to have negative effect on oral perception, including aging, denture wearing, and cognitive function. The aim of this study was to elucidate the impact of cognitive function on oral perception in independently living older individuals. The study sample was comprised of 987 participants (466 males, 521 females; age 69-71 years). Oral examinations, assessments of cognitive function in preclinical level by Montreal Cognitive Assessment (MoCA)-J, and determination of oral stereognostic ability as an indicator of oral perception were performed. Related variables were selected by univariate analyses; then, multivariate logistic regression model analysis was conducted. Univariate analyses revealed that number of teeth, removable dentures usage, and cognitive function respectively had a significant relationship with stereognostic score. Next, the subjects were classified into good and poor perception groups (lowest 17.4%) according to oral stereognostic ability. Logistic regression analysis revealed that lower cognitive function was significantly associated with poor oral perception (OR = 0.934, p = 0.017) after controlling for other variables. Cognitive decline even in preclinical stage was associated with reduced oral perception after controlling for gender, tooth number and denture use in independent living older people. This study suggested that preclinical level of change in cognitive function affected oral perception. Dental practitioners and caregivers may need to pay attention to reduced oral perception among older people even if they do not have trouble in daily life.

The role of the right temporoparietal junction in attention and social interaction as revealed by ALE meta-analysis

PubMed Central

Rottschy, C.; Oberwelland, E.; Bzdok, D.; Fox, P. T.; Eickhoff, S. B.; Fink, G. R.; Konrad, K.

2016-01-01

The right temporoparietal junction (rTPJ) is frequently associated with different capacities that to shift attention to unexpected stimuli (reorienting of attention) and to understand others’ (false) mental state [theory of mind (ToM), typically represented by false belief tasks]. Competing hypotheses either suggest the rTPJ representing a unitary region involved in separate cognitive functions or consisting of subregions subserving distinct processes. We conducted activation likelihood estimation (ALE) meta-analyses to test these hypotheses. A conjunction analysis across ALE meta-analyses delineating regions consistently recruited by reorienting of attention and false belief studies revealed the anterior rTPJ, suggesting an overarching role of this specific region. Moreover, the anatomical difference analysis unravelled the posterior rTPJ as higher converging in false belief compared with reorienting of attention tasks. This supports the concept of an exclusive role of the posterior rTPJ in the social domain. These results were complemented by meta-analytic connectivity mapping (MACM) and resting-state functional connectivity (RSFC) analysis to investigate whole-brain connectivity patterns in task-constrained and task-free brain states. This allowed for detailing the functional separation of the anterior and posterior rTPJ. The combination of MACM and RSFC mapping showed that the posterior rTPJ has connectivity patterns with typical ToM regions, whereas the anterior part of rTPJ co-activates with the attentional network. Taken together, our data suggest that rTPJ contains two functionally fractionated subregions: while posterior rTPJ seems exclusively involved in the social domain, anterior rTPJ is involved in both, attention and ToM, conceivably indicating an attentional shifting role of this region. PMID:24915964

Chordee and Penile Shortening Rather Than Voiding Function Are Associated With Patient Dissatisfaction After Urethroplasty.

PubMed

Maciejewski, Conrad C; Haines, Trevor; Rourke, Keith F

2017-05-01

To identify factors that predict patient satisfaction after urethroplasty by prospectively examining patient-reported quality of life scores using 3 validated instruments. A 3-part prospective survey consisting of the International Prostate Symptom Score (IPSS), the International Index of Erectile Function (IIEF) score, and a urethroplasty quality of life survey was completed by patients who underwent urethroplasty preoperatively and at 6 months postoperatively. The quality of life score included questions on genitourinary pain, urinary tract infection (UTI), postvoid dribbling, chordee, shortening, overall satisfaction, and overall health. Data were analyzed using descriptive statistics, paired t test, univariate and multivariate logistic regression analyses, and Wilcoxon signed-rank analysis. Patients were enrolled in the study from February 2011 to December 2014, and a total of 94 patients who underwent a total of 102 urethroplasties completed the study. Patients reported statistically significant improvements in IPSS (P < .001). Ordinal linear regression analysis revealed no association between age, IPSS, or IIEF score and patient satisfaction. Wilcoxon signed-rank analysis revealed significant improvements in pain scores (P = .02), UTI (P < .001), perceived overall health (P = .01), and satisfaction (P < .001). Univariate logistic regression identified a length >4 cm and the absence of UTI, pain, shortening, and chordee as predictors of patient satisfaction. Multivariate analysis of quality of life domain scores identified absence of shortening and absence of chordee as independent predictors of patient satisfaction following urethroplasty (P < .01). Patient voiding function and quality of life improve significantly following urethroplasty, but improvement in voiding function is not associated with patient satisfaction. Chordee status and perceived penile shortening impact patient satisfaction, and should be included in patient-reported outcome measures. Copyright © 2017 Elsevier Inc. All rights reserved.

SPECT and PET analysis of subthalamic stimulation in Parkinson's disease: analysis using a manual segmentation.

PubMed

Haegelen, Claire; García-Lorenzo, Daniel; Le Jeune, Florence; Péron, Julie; Gibaud, Bernard; Riffaud, Laurent; Brassier, Gilles; Barillot, Christian; Vérin, Marc; Morandi, Xavier

2010-03-01

The subthalamic nucleus (STN) has become an effective target of deep-brain stimulation (DBS) in severely disabled patients with advanced Parkinson's disease (PD). Clinical studies have reported DBS-induced adverse effects on cognitive functions, mood, emotion and behavior. STN DBS seems to interfere with the limbic functions of the basal ganglia, but the limbic effects of STN DBS are controversial. We measured prospectively resting regional cerebral metabolism (rCMb) with 18-fluorodeoxyglucose and PET, and resting regional cerebral blood flow (rCBF) with HMPAO and SPECT in six patients with Parkinson's disease. We compared PET and SPECT 1 month before and 3 months after STN DBS. On cerebral MRI, 13 regions of interest (ROI) were manually delineated slice by slice in frontal and limbic lobes. We obtained mean rCBF and rCMb values for each ROI and the whole brain. We normalized rCBF and rCMB values to ones for the whole brain volume, which we compared before and following STN DBS. No significant difference emerged in the SPECT analysis. PET analysis revealed a significant decrease in rCMb following STN DBS in the superior frontal gyri and left and right dorsolateral prefrontal cortex (p < 0.05). A non-significant decrease in rCMb in the left anterior cingulate gyrus appeared following STN DBS (p = 0.075). Our prospective SPECT and PET study revealed significantly decreased glucose metabolism of the two superior frontal gyri without any attendant perfusion changes following STN DBS. These results suggest that STN DBS may change medial prefrontal function and therefore the integration of limbic information, either by disrupting emotional processes within the STN, or by hampering the normal function of a limbic circuit.

Microbiome Analysis of Stool Samples from African Americans with Colon Polyps

PubMed Central

Brim, Hassan; Yooseph, Shibu; Zoetendal, Erwin G.; Lee, Edward; Torralbo, Manolito; Laiyemo, Adeyinka O.; Shokrani, Babak; Nelson, Karen; Ashktorab, Hassan

2013-01-01

Background Colonic polyps are common tumors occurring in ~50% of Western populations with ~10% risk of malignant progression. Dietary agents have been considered the primary environmental exposure to promote colorectal cancer (CRC) development. However, the colonic mucosa is permanently in contact with the microbiota and its metabolic products including toxins that also have the potential to trigger oncogenic transformation. Aim To analyze fecal DNA for microbiota composition and functional potential in African Americans with pre-neoplastic lesions. Materials & Methods We analyzed the bacterial composition of stool samples from 6 healthy individuals and 6 patients with colon polyps using 16S ribosomal RNA-based phylogenetic microarray; the Human intestinal Tract Chip (HITChip) and 16S rRNA gene barcoded 454 pyrosequencing. The functional potential was determined by sequence-based metagenomics using 454 pyrosequencing. Results Fecal microbiota profiling of samples from the healthy and polyp patients using both a phylogenetic microarraying (HITChip) and barcoded 454 pyrosequencing generated similar results. A distinction between both sets of samples was only obtained when the analysis was performed at the sub-genus level. Most of the species leading to the dissociation were from the Bacteroides group. The metagenomic analysis did not reveal major differences in bacterial gene prevalence/abundances between the two groups even when the analysis and comparisons were restricted to available Bacteroides genomes. Conclusion This study reveals that at the pre-neoplastic stages, there is a trend showing microbiota changes between healthy and colon polyp patients at the sub-genus level. These differences were not reflected at the genome/functions levels. Bacteria and associated functions within the Bacteroides group need to be further analyzed and dissected to pinpoint potential actors in the early colon oncogenic transformation in a large sample size. PMID:24376500

Comprehensive Genomic Analysis and Expression Profiling of the NOX Gene Families under Abiotic Stresses and Hormones in Plants.

PubMed

Chang, Yan-Li; Li, Wen-Yan; Miao, Hai; Yang, Shuai-Qi; Li, Ri; Wang, Xiang; Li, Wen-Qiang; Chen, Kun-Ming

2016-02-23

Plasma membrane NADPH oxidases (NOXs) are key producers of reactive oxygen species under both normal and stress conditions in plants and they form functional subfamilies. Studies of these subfamilies indicated that they show considerable evolutionary selection. We performed a comparative genomic analysis that identified 50 ferric reduction oxidases (FRO) and 77 NOX gene homologs from 20 species representing the eight major plant lineages within the supergroup Plantae: glaucophytes, rhodophytes, chlorophytes, bryophytes, lycophytes, gymnosperms, monocots, and eudicots. Phylogenetic and structural analysis classified these FRO and NOX genes into four well-conserved groups represented as NOX, FRO I, FRO II, and FRO III. Further analysis of NOXs of phylogenetic and exon/intron structures showed that single intron loss and gain had occurred, yielding the diversified gene structures during the evolution of NOXs family genes and which were classified into four conserved subfamilies which are represented as Sub.I, Sub.II, Sub.III, and Sub.IV. Additionally, both available global microarray data analysis and quantitative real-time PCR experiments revealed that the NOX genes in Arabidopsis and rice (Oryza sativa) have different expression patterns in different developmental stages, various abiotic stresses and hormone treatments. Finally, coexpression network analysis of NOX genes in Arabidopsis and rice revealed that NOXs have significantly correlated expression profiles with genes which are involved in plants metabolic and resistance progresses. All these results suggest that NOX family underscores the functional diversity and divergence in plants. This finding will facilitate further studies of the NOX family and provide valuable information for functional validation of this family in plants. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Regional autonomy changes in resting-state functional MRI in patients with HIV associated neurocognitive disorder

NASA Astrophysics Data System (ADS)

DSouza, Adora M.; Abidin, Anas Z.; Chockanathan, Udaysankar; Wismüller, Axel

2018-03-01

In this study, we investigate whether there are discernable changes in influence that brain regions have on themselves once patients show symptoms of HIV Associated Neurocognitive Disorder (HAND) using functional MRI (fMRI). Simple functional connectivity measures, such as correlation cannot reveal such information. To this end, we use mutual connectivity analysis (MCA) with Local Models (LM), which reveals a measure of influence in terms of predictability. Once such measures of interaction are obtained, we train two classifiers to characterize difference in patterns of regional self-influence between healthy subjects and subjects presenting with HAND symptoms. The two classifiers we use are Support Vector Machines (SVM) and Localized Generalized Matrix Learning Vector Quantization (LGMLVQ). Performing machine learning on fMRI connectivity measures is popularly known as multi-voxel pattern analysis (MVPA). By performing such an analysis, we are interested in studying the impact HIV infection has on an individual's brain. The high area under receiver operating curve (AUC) and accuracy values for 100 different train/test separations using MCA-LM self-influence measures (SVM: mean AUC=0.86, LGMLVQ: mean AUC=0.88, SVM and LGMLVQ: mean accuracy=0.78) compared with standard MVPA analysis using cross-correlation between fMRI time-series (SVM: mean AUC=0.58, LGMLVQ: mean AUC=0.57), demonstrates that self-influence features can be more discriminative than measures of interaction between time-series pairs. Furthermore, our results suggest that incorporating measures of self-influence in MVPA analysis used commonly in fMRI analysis has the potential to provide a performance boost and indicate important changes in dynamics of regions in the brain as a consequence of HIV infection.

Sequence analysis of serum albumins reveals the molecular evolution of ligand recognition properties.

PubMed

Fanali, Gabriella; Ascenzi, Paolo; Bernardi, Giorgio; Fasano, Mauro

2012-01-01

Serum albumin (SA) is a circulating protein providing a depot and carrier for many endogenous and exogenous compounds. At least seven major binding sites have been identified by structural and functional investigations mainly in human SA. SA is conserved in vertebrates, with at least 49 entries in protein sequence databases. The multiple sequence analysis of this set of entries leads to the definition of a cladistic tree for the molecular evolution of SA orthologs in vertebrates, thus showing the clustering of the considered species, with lamprey SAs (Lethenteron japonicum and Petromyzon marinus) in a separate outgroup. Sequence analysis aimed at searching conserved domains revealed that most SA sequences are made up by three repeated domains (about 600 residues), as extensively characterized for human SA. On the contrary, lamprey SAs are giant proteins (about 1400 residues) comprising seven repeated domains. The phylogenetic analysis of the SA family reveals a stringent correlation with the taxonomic classification of the species available in sequence databases. A focused inspection of the sequences of ligand binding sites in SA revealed that in all sites most residues involved in ligand binding are conserved, although the versatility towards different ligands could be peculiar of higher organisms. Moreover, the analysis of molecular links between the different sites suggests that allosteric modulation mechanisms could be restricted to higher vertebrates.

Determination of equilibrium structures of bromothymol blue revealed by using quantum chemistry with an aid of multivariate analysis of electronic absorption spectra

NASA Astrophysics Data System (ADS)

Shimada, Toru; Hasegawa, Takeshi

2017-10-01

The pH dependent chemical structures of bromothymol blue (BTB), which have long been under controversy, are determined by employing a combined technique of multivariate analysis of electronic absorption spectra and quantum chemistry. Principle component analysis (PCA) of the pH dependent spectra apparently reveals that only two chemical species are adequate to fully account for the color changes, with which the spectral decomposition is readily performed by using augmented alternative least-squares (ALS) regression analysis. The quantity variation by the ALS analysis also reveals the practical acid dissociation constant, pKa‧. The determination of pKa‧ is performed for various ionic strengths, which reveals the thermodynamic acid constant (pKa = 7.5) and the number of charge on each chemical species; the yellow form is negatively charged species of - 1 and the blue form that of - 2. On this chemical information, the quantum chemical calculation is carried out to find that BTB molecules take the pure quinoid form in an acid solution and the quinoid-phenolate form in an alkaline solution. The time-dependent density functional theory (TD-DFT) calculations for the theoretically determined chemical structures account for the peak shift of the electronic spectra. In this manner, the structures of all the chemical species appeared in equilibrium have finally been confirmed.

Determination of equilibrium structures of bromothymol blue revealed by using quantum chemistry with an aid of multivariate analysis of electronic absorption spectra.

PubMed

Shimada, Toru; Hasegawa, Takeshi

2017-10-05

The pH dependent chemical structures of bromothymol blue (BTB), which have long been under controversy, are determined by employing a combined technique of multivariate analysis of electronic absorption spectra and quantum chemistry. Principle component analysis (PCA) of the pH dependent spectra apparently reveals that only two chemical species are adequate to fully account for the color changes, with which the spectral decomposition is readily performed by using augmented alternative least-squares (ALS) regression analysis. The quantity variation by the ALS analysis also reveals the practical acid dissociation constant, pK a '. The determination of pK a ' is performed for various ionic strengths, which reveals the thermodynamic acid constant (pK a =7.5) and the number of charge on each chemical species; the yellow form is negatively charged species of -1 and the blue form that of -2. On this chemical information, the quantum chemical calculation is carried out to find that BTB molecules take the pure quinoid form in an acid solution and the quinoid-phenolate form in an alkaline solution. The time-dependent density functional theory (TD-DFT) calculations for the theoretically determined chemical structures account for the peak shift of the electronic spectra. In this manner, the structures of all the chemical species appeared in equilibrium have finally been confirmed. Copyright © 2017 Elsevier B.V. All rights reserved.

Political Implications of Heavy Television Viewing.

ERIC Educational Resources Information Center

Jackson-Beeck, Marilyn

This paper empirically evaluates the proposition that political conformism, specifically structural, passive, psychological, and defensive conformism, is a function of exposure to mass media. Secondary analysis of data from the National Opinion Research Center's 1975 General Social Survey revealed a significant relationship between TV viewing and…

Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland.

PubMed

Lilja, Anna M; Rodilla, Veronica; Huyghe, Mathilde; Hannezo, Edouard; Landragin, Camille; Renaud, Olivier; Leroy, Olivier; Rulands, Steffen; Simons, Benjamin D; Fre, Silvia

2018-06-01

Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer.

Functional and structural characterization of a β-glucosidase involved in saponin metabolism from intestinal bacteria.

PubMed

Yan, Shan; Wei, Peng-Cheng; Chen, Qiao; Chen, Xin; Wang, Shi-Cheng; Li, Jia-Ru; Gao, Chuan

2018-02-19

Saponins are natural glycosides widely used in medicine and the food industry. Although saponin metabolism in human is dependent on intestinal microbes, few involving bacteria enzymes have been identified. We cloned BlBG3, a GH3 β-glucosidase from Bifidobacterium longum, from human stool. We found that BlBG3 catalyzes the hydrolysis of glycoside furostanol and ginsenoside Rb1 at higher efficiency than other microbial β-glucosidases. Structural analysis of BlBG3 in complex with d-glucose revealed its three unique loops, which form a deep pocket and participate in substrate binding. To understand how substrate is bound to the pocket, molecular docking was performed and the binding interactions of protobioside with BlBG3 were revealed. Mutational study suggested that R484 and H642 are critical for enzymatic activity. Our study presents the first structural and functional analysis of a saponin-processing enzyme from human microbiota. Copyright © 2018 Elsevier Inc. All rights reserved.

RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways

PubMed Central

Jiang, Lulu; Hindmarch, Charles C. T.; Rogers, Mark; Campbell, Colin; Waterfall, Christy; Coghill, Jane; Mathieson, Peter W.; Welsh, Gavin I.

2016-01-01

Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or ‘podocytes’, the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes. PMID:27774996

Assignment of simian rotavirus SA11 temperature-sensitive mutant groups B and E to genome segments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gombold, J.L.; Estes, M.K.; Ramig, R.F.

1985-05-01

Recombinant (reassortant) viruses were selected from crosses between temperature-sensitive (ts) mutants of simian rotavirus SA11 and wild-type human rotavirus Wa. The double-stranded genome RNAs of the reassortants were examined by electrophoresis in Tris-glycine-buffered polyacrylamide gels and by dot hybridization with a cloned DNA probe for genome segment 2. Analysis of replacements of genome segments in the reassortants allowed construction of a map correlating genome segments providing functions interchangeable between SA11 and Wa. The reassortants revealed a functional correspondence in order of increasing electrophoretic mobility of genome segments. Analysis of the parental origin of genome segments in ts+ SA11/Wa reassortants derivedmore » from the crosses SA11 tsB(339) X Wa and SA11 tsE(1400) X Wa revealed that the group B lesion of tsB(339) was located on genome segment 3 and the group E lesion of tsE(1400) was on segment 8.« less

A PDGF/VEGF homologue provides new insights into the nucleus grafting operation and immune response in the pearl oyster Pinctada fucata.

PubMed

Huang, Xian-De; Zhang, Hua; He, Mao-Xian

2017-12-30

The platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF, PVF) family of proteins have been implicated in a wide range of biological functions in vertebrates, including cell proliferation, cell differentiation, cell migration, neural development and especially angiogenesis/vasculogenesis. In this study, a PVF gene, belonging to the PDGF/VEGF family, was cloned and characterized from Pinctada fucata. It contained an ORF of 1110bp encoding a putative protein of 369 amino acids. The deduced amino acid sequence presented the typical structural features of PDGF family members and the N-terminal signal peptide for secretion. Comparative phylogenetic analysis revealed that PfPVF shows relatively high identity with other invertebrate PVF homologues. Furthermore, gene expression analysis revealed that PfPVF is involved in not only the nucleus grafting operation and but also the response to immune stimulation. The study may help to increase understanding of the functions of molluscan PVF. Copyright © 2017 Elsevier B.V. All rights reserved.

Application of the ex-Gaussian function to the effect of the word blindness suggestion on Stroop task performance suggests no word blindness

PubMed Central

Parris, Benjamin A.; Dienes, Zoltan; Hodgson, Timothy L.

2013-01-01

The aim of the present paper was to apply the ex-Gaussian function to data reported by Parris et al. (2012) given its utility in studies involving the Stroop task. Parris et al. showed an effect of the word blindness suggestion when Response-Stimulus Interval (RSI) was 500 ms but not when it was 3500 ms. Analysis revealed that: (1) The effect of the suggestion on interference is observed in μ, supporting converging evidence indicating the suggestion operates over response competition mechanisms; and, (2) Contrary to Parris et al. an effect of the suggestion was observed in μ when RSI was 3500 ms. The reanalysis of the data from Parris et al. (2012) supports the utility of ex-Gaussian analysis in revealing effects that might otherwise be thought of as absent. We suggest that word reading itself is not suppressed by the suggestion but instead that response conflict is dealt with more effectively. PMID:24065947

Contributions of familiarity and recollection rejection to recognition: Evidence from the time course of false recognition for semantic and conjunction lures

PubMed Central

Matzen, Laura E.; Taylor, Eric G.; Benjamin, Aaron S.

2010-01-01

It has been suggested that both familiarity and recollection contribute to the recognition decision process. In this paper, we leverage the form of false alarm rate functions—in which false-alarm rates describe an inverted U-shaped function as the time between study and test increases—to assess how these processes support retention of semantic and surface form information from previously studied words. We directly compare the maxima of these functions for lures that are semantically related and lures that are related by surface form to previously studied material. This analysis reveals a more rapid loss of access to surface form than to semantic information. To separate the contributions of item familiarity and reminding-induced recollection rejection to this effect, we use a simple multinomial process model; this analysis reveals that this loss of access reflects both a more rapid loss of familiarity and lower rates of recollection for surface form information. PMID:21240745

Application of the ex-Gaussian function to the effect of the word blindness suggestion on Stroop task performance suggests no word blindness.

PubMed

Parris, Benjamin A; Dienes, Zoltan; Hodgson, Timothy L

2013-01-01

The aim of the present paper was to apply the ex-Gaussian function to data reported by Parris et al. (2012) given its utility in studies involving the Stroop task. Parris et al. showed an effect of the word blindness suggestion when Response-Stimulus Interval (RSI) was 500 ms but not when it was 3500 ms. Analysis revealed that: (1) The effect of the suggestion on interference is observed in μ, supporting converging evidence indicating the suggestion operates over response competition mechanisms; and, (2) Contrary to Parris et al. an effect of the suggestion was observed in μ when RSI was 3500 ms. The reanalysis of the data from Parris et al. (2012) supports the utility of ex-Gaussian analysis in revealing effects that might otherwise be thought of as absent. We suggest that word reading itself is not suppressed by the suggestion but instead that response conflict is dealt with more effectively.

Benchmarking the Performance of Exchange-Correlation Functionals for Predicting Two-Photon Absorption Strengths.

PubMed

Beerepoot, Maarten T P; Alam, Md Mehboob; Bednarska, Joanna; Bartkowiak, Wojciech; Ruud, Kenneth; Zaleśny, Robert

2018-06-15

The present work investigates the performance of exchange-correlation functionals in the prediction of two-photon absorption (2PA) strengths. For this purpose, we considered six common functionals used for studying 2PA processes and tested these on six organoboron chelates. The set consisted of two semilocal (PBE and BLYP), two hybrid (B3LYP and PBE0), and two range-separated (LC-BLYP and CAM-B3LYP) functionals. The RI-CC2 method was chosen as a reference level and was found to give results consistent with the experimental data that are available for three of the molecules considered. Of the six exchange-correlation functionals studied, only the range-separated functionals predict an ordering of the 2PA strengths that is consistent with experimental and RI-CC2 results. Even though the range-separated functionals predict correct relative trends, the absolute values for the 2PA strengths are underestimated by a factor of 2-6 for the molecules considered. An in-depth analysis, on the basis of the derived generalized few-state model expression for the 2PA strength for a coupled-cluster wave function, reveals that the problem with these functionals can be linked to underestimated excited-state dipole moments and, to a lesser extent, overestimated excitation energies. The semilocal and hybrid functionals exhibit less predictable errors and a variation in the 2PA strengths in disagreement with the reference results. The semilocal and hybrid functionals show smaller average errors than the range-separated functionals, but our analysis reveals that this is due to fortuitous error cancellation between excitation energies and the transition dipole moments. Our results constitute a warning against using currently available exchange-correlation functionals in the prediction of 2PA strengths and highlight the need for functionals that correctly describe the electron density of excited electronic states.

Structural variations in prefrontal cortex mediate the relationship between early childhood stress and spatial working memory

PubMed Central

Hanson, Jamie L.; Chung, Moo K.; Avants, Brian B.; Rudolph, Karen D.; Shirtcliff, Elizabeth A.; Gee, James C.; Davidson, Richard J.; Pollak, Seth D.

2012-01-01

A large corpus of research indicates exposure to stress impairs cognitive abilities, specifically executive functioning dependent on the prefrontal cortex (PFC). We collected structural MRI scans (n=61), well-validated assessments of executive functioning, and detailed interviews assessing stress exposure in humans, to examine whether cumulative life stress affected brain morphometry and one type of executive functioning, spatial working memory, during adolescence—a critical time of brain development and reorganization. Analysis of variations in brain structure revealed that cumulative life stress and spatial working memory were related to smaller volumes in the PFC, specifically prefrontal gray and white matter between the anterior cingulate and the frontal poles. Mediation analyses revealed that individual differences in prefrontal volumes accounted for the association between cumulative life stress and spatial working memory. These results suggest that structural changes in the PFC may serve as a mediating mechanism through which greater cumulative life stress engenders decrements in cognitive functioning. PMID:22674267

Mirror neurons and imitation: a computationally guided review.

PubMed

Oztop, Erhan; Kawato, Mitsuo; Arbib, Michael

2006-04-01

Neurophysiology reveals the properties of individual mirror neurons in the macaque while brain imaging reveals the presence of 'mirror systems' (not individual neurons) in the human. Current conceptual models attribute high level functions such as action understanding, imitation, and language to mirror neurons. However, only the first of these three functions is well-developed in monkeys. We thus distinguish current opinions (conceptual models) on mirror neuron function from more detailed computational models. We assess the strengths and weaknesses of current computational models in addressing the data and speculations on mirror neurons (macaque) and mirror systems (human). In particular, our mirror neuron system (MNS), mental state inference (MSI) and modular selection and identification for control (MOSAIC) models are analyzed in more detail. Conceptual models often overlook the computational requirements for posited functions, while too many computational models adopt the erroneous hypothesis that mirror neurons are interchangeable with imitation ability. Our meta-analysis underlines the gap between conceptual and computational models and points out the research effort required from both sides to reduce this gap.

From Whole-Brain Data to Functional Circuit Models: The Zebrafish Optomotor Response.

PubMed

Naumann, Eva A; Fitzgerald, James E; Dunn, Timothy W; Rihel, Jason; Sompolinsky, Haim; Engert, Florian

2016-11-03

Detailed descriptions of brain-scale sensorimotor circuits underlying vertebrate behavior remain elusive. Recent advances in zebrafish neuroscience offer new opportunities to dissect such circuits via whole-brain imaging, behavioral analysis, functional perturbations, and network modeling. Here, we harness these tools to generate a brain-scale circuit model of the optomotor response, an orienting behavior evoked by visual motion. We show that such motion is processed by diverse neural response types distributed across multiple brain regions. To transform sensory input into action, these regions sequentially integrate eye- and direction-specific sensory streams, refine representations via interhemispheric inhibition, and demix locomotor instructions to independently drive turning and forward swimming. While experiments revealed many neural response types throughout the brain, modeling identified the dimensions of functional connectivity most critical for the behavior. We thus reveal how distributed neurons collaborate to generate behavior and illustrate a paradigm for distilling functional circuit models from whole-brain data. Copyright © 2016 Elsevier Inc. All rights reserved.

Structure and function of complex brain networks

PubMed Central

Sporns, Olaf

2013-01-01

An increasing number of theoretical and empirical studies approach the function of the human brain from a network perspective. The analysis of brain networks is made feasible by the development of new imaging acquisition methods as well as new tools from graph theory and dynamical systems. This review surveys some of these methodological advances and summarizes recent findings on the architecture of structural and functional brain networks. Studies of the structural connectome reveal several modules or network communities that are interlinked by hub regions mediating communication processes between modules. Recent network analyses have shown that network hubs form a densely linked collective called a “rich club,” centrally positioned for attracting and dispersing signal traffic. In parallel, recordings of resting and task-evoked neural activity have revealed distinct resting-state networks that contribute to functions in distinct cognitive domains. Network methods are increasingly applied in a clinical context, and their promise for elucidating neural substrates of brain and mental disorders is discussed. PMID:24174898

C-RAF function at the genome-wide transcriptome level: A systematic view.

PubMed

Huang, Ying; Zhang, Xin-Yu; An, Su; Yang, Yang; Liu, Ying; Hao, Qian; Guo, Xiao-Xi; Xu, Tian-Rui

2018-05-20

C-RAF was the first member of the RAF kinase family to be discovered. Since its discovery, C-RAF has been found to regulate many fundamental cell processes, such as cell proliferation, cell death, and metabolism. However, the majority of these functions are achieved through interactions with different proteins; the genes regulated by C-RAF in its active or inactive state remain unclear. In the work, we used RNA-seq analysis to study the global transcriptomes of C-RAF bearing or C-RAF knockout cells in quiescent or EGF activated states. We identified 3353 genes that are promoted or suppressed by C-RAF. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these genes are involved in drug addiction, cardiomyopathy, autoimmunity, and regulation of cell metabolism. Our results provide a panoramic view of C-RAF function, including known and novel functions, and have revealed potential targets for elucidating the role of C-RAF. Copyright © 2018 Elsevier B.V. All rights reserved.

Merging metagenomics and geochemistry reveals environmental controls on biological diversity and evolution.

PubMed

Alsop, Eric B; Boyd, Eric S; Raymond, Jason

2014-05-28

The metabolic strategies employed by microbes inhabiting natural systems are, in large part, dictated by the physical and geochemical properties of the environment. This study sheds light onto the complex relationship between biology and environmental geochemistry using forty-three metagenomes collected from geochemically diverse and globally distributed natural systems. It is widely hypothesized that many uncommonly measured geochemical parameters affect community dynamics and this study leverages the development and application of multidimensional biogeochemical metrics to study correlations between geochemistry and microbial ecology. Analysis techniques such as a Markov cluster-based measure of the evolutionary distance between whole communities and a principal component analysis (PCA) of the geochemical gradients between environments allows for the determination of correlations between microbial community dynamics and environmental geochemistry and provides insight into which geochemical parameters most strongly influence microbial biodiversity. By progressively building from samples taken along well defined geochemical gradients to samples widely dispersed in geochemical space this study reveals strong links between the extent of taxonomic and functional diversification of resident communities and environmental geochemistry and reveals temperature and pH as the primary factors that have shaped the evolution of these communities. Moreover, the inclusion of extensive geochemical data into analyses reveals new links between geochemical parameters (e.g. oxygen and trace element availability) and the distribution and taxonomic diversification of communities at the functional level. Further, an overall geochemical gradient (from multivariate analyses) between natural systems provides one of the most complete predictions of microbial taxonomic and functional composition. Clustering based on the frequency in which orthologous proteins occur among metagenomes facilitated accurate prediction of the ordering of community functional composition along geochemical gradients, despite a lack of geochemical input. The consistency in the results obtained from the application of Markov clustering and multivariate methods to distinct natural systems underscore their utility in predicting the functional potential of microbial communities within a natural system based on system geochemistry alone, allowing geochemical measurements to be used to predict purely biological metrics such as microbial community composition and metabolism.

Circularly-symmetric complex normal ratio distribution for scalar transmissibility functions. Part III: Application to statistical modal analysis

NASA Astrophysics Data System (ADS)

Yan, Wang-Ji; Ren, Wei-Xin

2018-01-01

This study applies the theoretical findings of circularly-symmetric complex normal ratio distribution Yan and Ren (2016) [1,2] to transmissibility-based modal analysis from a statistical viewpoint. A probabilistic model of transmissibility function in the vicinity of the resonant frequency is formulated in modal domain, while some insightful comments are offered. It theoretically reveals that the statistics of transmissibility function around the resonant frequency is solely dependent on 'noise-to-signal' ratio and mode shapes. As a sequel to the development of the probabilistic model of transmissibility function in modal domain, this study poses the process of modal identification in the context of Bayesian framework by borrowing a novel paradigm. Implementation issues unique to the proposed approach are resolved by Lagrange multiplier approach. Also, this study explores the possibility of applying Bayesian analysis in distinguishing harmonic components and structural ones. The approaches are verified through simulated data and experimentally testing data. The uncertainty behavior due to variation of different factors is also discussed in detail.

Growth Type and Functional Trajectories: An Empirical Study of Urban Expansion in Nanjing, China

PubMed Central

Yuan, Feng

2016-01-01

Drawing upon the Landsat satellite images of Nanjing from 1985, 1995, 2001, 2007, and 2013, this paper integrates the convex hull analysis and common edge analysis at double scales, and develops a comprehensive matrix analysis to distinguish the different types of urban land expansion. The results show that Nanjing experienced rapid urban expansion, dominated by a mix of residential and manufacturing land from 1985 to 2013, which in turn has promoted Nanjing’s shift from a compact mononuclear city to a polycentric one. Spatial patterns of three specific types of growth, namely infilling, extension, and enclave were quite different in four consecutive periods. These patterns result primarily from the existing topographic constraints, as well as government-oriented urban planning and policies. By intersecting the function maps, we also reveal the functional evolution of newly-developed urban land. Moreover, both self-enhancing and mutual promotion of the newly developed functions are surveyed over the last decade. Our study confirms that the integration of a multi-scale method and multi-perspective analysis, such as the spatiotemporal patterns and functional evolution, helps us to better understand the rapid urban growth in China. PMID:26845155

Combining self-organizing mapping and supervised affinity propagation clustering approach to investigate functional brain networks involved in motor imagery and execution with fMRI measurements.

PubMed

Zhang, Jiang; Liu, Qi; Chen, Huafu; Yuan, Zhen; Huang, Jin; Deng, Lihua; Lu, Fengmei; Zhang, Junpeng; Wang, Yuqing; Wang, Mingwen; Chen, Liangyin

2015-01-01

Clustering analysis methods have been widely applied to identifying the functional brain networks of a multitask paradigm. However, the previously used clustering analysis techniques are computationally expensive and thus impractical for clinical applications. In this study a novel method, called SOM-SAPC that combines self-organizing mapping (SOM) and supervised affinity propagation clustering (SAPC), is proposed and implemented to identify the motor execution (ME) and motor imagery (MI) networks. In SOM-SAPC, SOM was first performed to process fMRI data and SAPC is further utilized for clustering the patterns of functional networks. As a result, SOM-SAPC is able to significantly reduce the computational cost for brain network analysis. Simulation and clinical tests involving ME and MI were conducted based on SOM-SAPC, and the analysis results indicated that functional brain networks were clearly identified with different response patterns and reduced computational cost. In particular, three activation clusters were clearly revealed, which include parts of the visual, ME and MI functional networks. These findings validated that SOM-SAPC is an effective and robust method to analyze the fMRI data with multitasks.

Resting state network topology of the ferret brain.

PubMed

Zhou, Zhe Charles; Salzwedel, Andrew P; Radtke-Schuller, Susanne; Li, Yuhui; Sellers, Kristin K; Gilmore, John H; Shih, Yen-Yu Ian; Fröhlich, Flavio; Gao, Wei

2016-12-01

Resting state functional magnetic resonance imaging (rsfMRI) has emerged as a versatile tool for non-invasive measurement of functional connectivity patterns in the brain. RsfMRI brain dynamics in rodents, non-human primates, and humans share similar properties; however, little is known about the resting state functional connectivity patterns in the ferret, an animal model with high potential for developmental and cognitive translational study. To address this knowledge-gap, we performed rsfMRI on anesthetized ferrets using a 9.4T MRI scanner, and subsequently performed group-level independent component analysis (gICA) to identify functionally connected brain networks. Group-level ICA analysis revealed distributed sensory, motor, and higher-order networks in the ferret brain. Subsequent connectivity analysis showed interconnected higher-order networks that constituted a putative default mode network (DMN), a network that exhibits altered connectivity in neuropsychiatric disorders. Finally, we assessed ferret brain topological efficiency using graph theory analysis and found that the ferret brain exhibits small-world properties. Overall, these results provide additional evidence for pan-species resting-state networks, further supporting ferret-based studies of sensory and cognitive function. Copyright © 2016 Elsevier Inc. All rights reserved.

Mining for hemicellulases in the fungus-growing termite Pseudacanthotermes militaris using functional metagenomics.

PubMed

Bastien, Géraldine; Arnal, Grégory; Bozonnet, Sophie; Laguerre, Sandrine; Ferreira, Fernando; Fauré, Régis; Henrissat, Bernard; Lefèvre, Fabrice; Robe, Patrick; Bouchez, Olivier; Noirot, Céline; Dumon, Claire; O'Donohue, Michael

2013-05-14

The metagenomic analysis of gut microbiomes has emerged as a powerful strategy for the identification of biomass-degrading enzymes, which will be no doubt useful for the development of advanced biorefining processes. In the present study, we have performed a functional metagenomic analysis on comb and gut microbiomes associated with the fungus-growing termite, Pseudacanthotermes militaris. Using whole termite abdomens and fungal-comb material respectively, two fosmid-based metagenomic libraries were created and screened for the presence of xylan-degrading enzymes. This revealed 101 positive clones, corresponding to an extremely high global hit rate of 0.49%. Many clones displayed either β-d-xylosidase (EC 3.2.1.37) or α-l-arabinofuranosidase (EC 3.2.1.55) activity, while others displayed the ability to degrade AZCL-xylan or AZCL-β-(1,3)-β-(1,4)-glucan. Using secondary screening it was possible to pinpoint clones of interest that were used to prepare fosmid DNA. Sequencing of fosmid DNA generated 1.46 Mbp of sequence data, and bioinformatics analysis revealed 63 sequences encoding putative carbohydrate-active enzymes, with many of these forming parts of sequence clusters, probably having carbohydrate degradation and metabolic functions. Taxonomic assignment of the different sequences revealed that Firmicutes and Bacteroidetes were predominant phyla in the gut sample, while microbial diversity in the comb sample resembled that of typical soil samples. Cloning and expression in E. coli of six enzyme candidates identified in the libraries provided access to individual enzyme activities, which all proved to be coherent with the primary and secondary functional screens. This study shows that the gut microbiome of P. militaris possesses the potential to degrade biomass components, such as arabinoxylans and arabinans. Moreover, the data presented suggests that prokaryotic microorganisms present in the comb could also play a part in the degradation of biomass within the termite mound, although further investigation will be needed to clarify the complex synergies that might exist between the different microbiomes that constitute the termitosphere of fungus-growing termites. This study exemplifies the power of functional metagenomics for the discovery of biomass-active enzymes and has provided a collection of potentially interesting biocatalysts for further study.

Laminar and dorsoventral molecular organization of the medial entorhinal cortex revealed by large-scale anatomical analysis of gene expression.

PubMed

Ramsden, Helen L; Sürmeli, Gülşen; McDonagh, Steven G; Nolan, Matthew F

2015-01-01

Neural circuits in the medial entorhinal cortex (MEC) encode an animal's position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. We propose a new molecular basis for distinguishing the deep layers of the MEC and show that their similarity to corresponding layers of neocortex is greater than that of superficial layers. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. We also reveal laminar organization of genes related to disease pathology and suggest that a high metabolic demand predisposes layer II to neurodegenerative pathology. In principle, our computational pipeline can be applied to high-throughput analysis of many forms of neuroanatomical data. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations.

Laminar and Dorsoventral Molecular Organization of the Medial Entorhinal Cortex Revealed by Large-scale Anatomical Analysis of Gene Expression

PubMed Central

Ramsden, Helen L.; Sürmeli, Gülşen; McDonagh, Steven G.; Nolan, Matthew F.

2015-01-01

Neural circuits in the medial entorhinal cortex (MEC) encode an animal’s position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. We propose a new molecular basis for distinguishing the deep layers of the MEC and show that their similarity to corresponding layers of neocortex is greater than that of superficial layers. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. We also reveal laminar organization of genes related to disease pathology and suggest that a high metabolic demand predisposes layer II to neurodegenerative pathology. In principle, our computational pipeline can be applied to high-throughput analysis of many forms of neuroanatomical data. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations. PMID:25615592

Oceanic protists with different forms of acquired phototrophy display contrasting biogeographies and abundance.

PubMed

Leles, S G; Mitra, A; Flynn, K J; Stoecker, D K; Hansen, P J; Calbet, A; McManus, G B; Sanders, R W; Caron, D A; Not, F; Hallegraeff, G M; Pitta, P; Raven, J A; Johnson, M D; Glibert, P M; Våge, S

2017-08-16

This first comprehensive analysis of the global biogeography of marine protistan plankton with acquired phototrophy shows these mixotrophic organisms to be ubiquitous and abundant; however, their biogeography differs markedly between different functional groups. These mixotrophs, lacking a constitutive capacity for photosynthesis (i.e. non-constitutive mixotrophs, NCMs), acquire their phototrophic potential through either integration of prey-plastids or through endosymbiotic associations with photosynthetic microbes. Analysis of field data reveals that 40-60% of plankton traditionally labelled as (non-phototrophic) microzooplankton are actually NCMs, employing acquired phototrophy in addition to phagotrophy. Specialist NCMs acquire chloroplasts or endosymbionts from specific prey, while generalist NCMs obtain chloroplasts from a variety of prey. These contrasting functional types of NCMs exhibit distinct seasonal and spatial global distribution patterns. Mixotrophs reliant on 'stolen' chloroplasts, controlled by prey diversity and abundance, dominate in high-biomass areas. Mixotrophs harbouring intact symbionts are present in all waters and dominate particularly in oligotrophic open ocean systems. The contrasting temporal and spatial patterns of distribution of different mixotroph functional types across the oceanic provinces, as revealed in this study, challenges traditional interpretations of marine food web structures. Mixotrophs with acquired phototrophy (NCMs) warrant greater recognition in marine research. © 2017 The Author(s).

Comparative and Evolutionary Analysis of the HES/HEY Gene Family Reveal Exon/Intron Loss and Teleost Specific Duplication Events

PubMed Central

Ma, Zhaowu; Zhou, Yang; Abbood, Nibras Najm; Liu, Jianfeng; Su, Li; Jia, Haibo; Guo, An-Yuan

2012-01-01

Background HES/HEY genes encode a family of basic helix-loop-helix (bHLH) transcription factors with both bHLH and Orange domain. HES/HEY proteins are direct targets of the Notch signaling pathway and play an essential role in developmental decisions, such as the developments of nervous system, somitogenesis, blood vessel and heart. Despite their important functions, the origin and evolution of this HES/HEY gene family has yet to be elucidated. Methods and Findings In this study, we identified genes of the HES/HEY family in representative species and performed evolutionary analysis to elucidate their origin and evolutionary process. Our results showed that the HES/HEY genes only existed in metazoans and may originate from the common ancestor of metazoans. We identified HES/HEY genes in more than 10 species representing the main lineages. Combining the bHLH and Orange domain sequences, we constructed the phylogenetic trees by different methods (Bayesian, ML, NJ and ME) and classified the HES/HEY gene family into four groups. Our results indicated that this gene family had undergone three expansions, which were along with the origins of Eumetazoa, vertebrate, and teleost. Gene structure analysis revealed that the HES/HEY genes were involved in exon and/or intron loss in different species lineages. Genes of this family were duplicated in bony fishes and doubled than other vertebrates. Furthermore, we studied the teleost-specific duplications in zebrafish and investigated the expression pattern of duplicated genes in different tissues by RT-PCR. Finally, we proposed a model to show the evolution of this gene family with processes of expansion, exon/intron loss, and motif loss. Conclusions Our study revealed the evolution of HES/HEY gene family, the expression and function divergence of duplicated genes, which also provide clues for the research of Notch function in development. This study shows a model of gene family analysis with gene structure evolution and duplication. PMID:22808219

Comparative and evolutionary analysis of the HES/HEY gene family reveal exon/intron loss and teleost specific duplication events.

PubMed

Zhou, Mi; Yan, Jun; Ma, Zhaowu; Zhou, Yang; Abbood, Nibras Najm; Liu, Jianfeng; Su, Li; Jia, Haibo; Guo, An-Yuan

2012-01-01

HES/HEY genes encode a family of basic helix-loop-helix (bHLH) transcription factors with both bHLH and Orange domain. HES/HEY proteins are direct targets of the Notch signaling pathway and play an essential role in developmental decisions, such as the developments of nervous system, somitogenesis, blood vessel and heart. Despite their important functions, the origin and evolution of this HES/HEY gene family has yet to be elucidated. In this study, we identified genes of the HES/HEY family in representative species and performed evolutionary analysis to elucidate their origin and evolutionary process. Our results showed that the HES/HEY genes only existed in metazoans and may originate from the common ancestor of metazoans. We identified HES/HEY genes in more than 10 species representing the main lineages. Combining the bHLH and Orange domain sequences, we constructed the phylogenetic trees by different methods (Bayesian, ML, NJ and ME) and classified the HES/HEY gene family into four groups. Our results indicated that this gene family had undergone three expansions, which were along with the origins of Eumetazoa, vertebrate, and teleost. Gene structure analysis revealed that the HES/HEY genes were involved in exon and/or intron loss in different species lineages. Genes of this family were duplicated in bony fishes and doubled than other vertebrates. Furthermore, we studied the teleost-specific duplications in zebrafish and investigated the expression pattern of duplicated genes in different tissues by RT-PCR. Finally, we proposed a model to show the evolution of this gene family with processes of expansion, exon/intron loss, and motif loss. Our study revealed the evolution of HES/HEY gene family, the expression and function divergence of duplicated genes, which also provide clues for the research of Notch function in development. This study shows a model of gene family analysis with gene structure evolution and duplication.

Journal entries facilitating preprofessional scientific literacy and mutualistic symbiotic relationships

NASA Astrophysics Data System (ADS)

Vander Vliet, Valerie J.

This study explored journal writing as an alternative assessment to promote the development of pre-professional scientific literacy and mutualistic symbiotic relationships between teaching and learning, instruction and assessment, and students and teachers. The larger context of this study is an action reaction project of the attempted transformation of a traditional first year undergraduate pre-professional biology class to sociocultural constructivist principles. The participants were commuter and residential, full and part-time students ranging in age from 18 to 27 and 18/21 were female. The backgrounds of the students varied considerably, ranging from low to upper middle income, including students of Black and Asian heritage. The setting was a medium-sized Midwestern university. The instructor has twenty years of experience teaching Biology at the college level. The data were analyzed using the constant comparative method and the development of grounded theory. The journal entries were analyzed as to their function and form in relationship to the development of multiple aspects of pre-professional scientific literacy. The perceptions of the students as to the significance of the use of journal entries were also determined through the analysis of their use of journal entries in their portfolios and statements in surveys and portfolios. The analysis revealed that journal entries promoted multiple aspects of pre-professional scientific literacy in both students and the instructor and facilitated the development of mutualistic symbiotic relationships between teaching and learning, instruction and assessment, and students and teachers. The function analysis revealed that the journal entries fulfilled the functions intended for the development of multiple aspects of pre-professional scientific literacy. The complexity of journal writing emerged from the form analysis, which revealed the multiple form elements inherent in journal entries. Students perceived journal entries to act as cognitive, affective, and social catalysts of pre-professional scientific literacy. This study has shown that journal entries facilitate the development of multiple aspects of scientific literacy and mutualistic symbiotic relationships between teaching and learning, instruction and assessment, and students and teachers.

Quantitative proteomic study of Aspergillus Fumigatus secretome revealed deamidation of secretory enzymes.

PubMed

Adav, Sunil S; Ravindran, Anita; Sze, Siu Kwan

2015-04-24

Aspergillus sp. plays an essential role in lignocellulosic biomass recycling and is also exploited as cell factories for the production of industrial enzymes. This study profiled the secretome of Aspergillus fumigatus when grown with cellulose, xylan and starch by high throughput quantitative proteomics using isobaric tags for relative and absolute quantification (iTRAQ). Post translational modifications (PTMs) of proteins play a critical role in protein functions. However, our understanding of the PTMs in secretory proteins is limited. Here, we present the identification of PTMs such as deamidation of secreted proteins of A. fumigatus. This study quantified diverse groups of extracellular secreted enzymes and their functional classification revealed cellulases and glycoside hydrolases (32.9%), amylases (0.9%), hemicellulases (16.2%), lignin degrading enzymes (8.1%), peptidases and proteases (11.7%), chitinases, lipases and phosphatases (7.6%), and proteins with unknown function (22.5%). The comparison of quantitative iTRAQ results revealed that cellulose and xylan stimulates expression of specific cellulases and hemicellulases, and their abundance level as a function of substrate. In-depth data analysis revealed deamidation as a major PTM of key cellulose hydrolyzing enzymes like endoglucanases, cellobiohydrolases and glucosidases. Hemicellulose degrading endo-1,4-beta-xylanase, monosidases, xylosidases, lignin degrading laccase, isoamyl alcohol oxidase and oxidoreductases were also found to be deamidated. The filamentous fungi play an essential role in lignocellulosic biomass recycling and fungal strains belonging to Aspergillus were also exploited as cell factories for the production of organic acids, pharmaceuticals, and industrially important enzymes. In this study, extracellular proteins secreted by thermophilic A. fumigatus when grown with cellulose, xylan and starch were profiled using isobaric tags for relative and absolute quantification (iTRAQ) by adopting liquid chromatography tandem mass spectrometry. The comparison of quantitative iTRAQ results revealed that cellulose and xylan stimulate expression of specific cellulases and hemicellulases, and expression level as a function of substrate. Post translational modifications revealed deamidation of key cellulases including endoglucanases, cellobiohydrolases and glucosidases; and hemicellulases and lignin degrading enzymes. The knowledge on deamidated enzymes along with specific sites of modifications could be crucial information for further functional studies of these enzymes of A. fumigatus. Copyright © 2015 Elsevier B.V. All rights reserved.

Computer-assisted image analysis of human cilia and Chlamydomonas flagella reveals both similarities and differences in axoneme structure.

PubMed

O'Toole, Eileen T; Giddings, Thomas H; Porter, Mary E; Ostrowski, Lawrence E

2012-08-01

In the past decade, investigations from several different fields have revealed the critical role of cilia in human health and disease. Because of the highly conserved nature of the basic axonemal structure, many different model systems have proven useful for the study of ciliopathies, especially the unicellular, biflagellate green alga Chlamydomonas reinhardtii. Although the basic axonemal structure of cilia and flagella is highly conserved, these organelles often perform specialized functions unique to the cell or tissue in which they are found. These differences in function are likely reflected in differences in structural organization. In this work, we directly compare the structure of isolated axonemes from human cilia and Chlamydomonas flagella to identify similarities and differences that potentially play key roles in determining their functionality. Using transmission electron microscopy and 2D image averaging techniques, our analysis has confirmed the overall structural similarity between these two species, but also revealed clear differences in the structure of the outer dynein arms, the central pair projections, and the radial spokes. We also show how the application of 2D image averaging can clarify the underlying structural defects associated with primary ciliary dyskinesia (PCD). Overall, our results document the remarkable similarity between these two structures separated evolutionarily by over a billion years, while highlighting several significant differences, and demonstrate the potential of 2D image averaging to improve the diagnosis and understanding of PCD. Copyright © 2012 Wiley Periodicals, Inc.

The use of dwell time cross-correlation functions to study single-ion channel gating kinetics.

PubMed Central

Ball, F G; Kerry, C J; Ramsey, R L; Sansom, M S; Usherwood, P N

1988-01-01

The derivation of cross-correlation functions from single-channel dwell (open and closed) times is described. Simulation of single-channel data for simple gating models, alongside theoretical treatment, is used to demonstrate the relationship of cross-correlation functions to underlying gating mechanisms. It is shown that time irreversibility of gating kinetics may be revealed in cross-correlation functions. Application of cross-correlation function analysis to data derived from the locust muscle glutamate receptor-channel provides evidence for multiple gateway states and time reversibility of gating. A model for the gating of this channel is used to show the effect of omission of brief channel events on cross-correlation functions. PMID:2462924

The Necessity of Functional Analysis for Space Exploration Programs

NASA Technical Reports Server (NTRS)

Morris, A. Terry; Breidenthal, Julian C.

2011-01-01

As NASA moves toward expanded commercial spaceflight within its human exploration capability, there is increased emphasis on how to allocate responsibilities between government and commercial organizations to achieve coordinated program objectives. The practice of program-level functional analysis offers an opportunity for improved understanding of collaborative functions among heterogeneous partners. Functional analysis is contrasted with the physical analysis more commonly done at the program level, and is shown to provide theoretical performance, risk, and safety advantages beneficial to a government-commercial partnership. Performance advantages include faster convergence to acceptable system solutions; discovery of superior solutions with higher commonality, greater simplicity and greater parallelism by substituting functional for physical redundancy to achieve robustness and safety goals; and greater organizational cohesion around program objectives. Risk advantages include avoidance of rework by revelation of some kinds of architectural and contractual mismatches before systems are specified, designed, constructed, or integrated; avoidance of cost and schedule growth by more complete and precise specifications of cost and schedule estimates; and higher likelihood of successful integration on the first try. Safety advantages include effective delineation of must-work and must-not-work functions for integrated hazard analysis, the ability to formally demonstrate completeness of safety analyses, and provably correct logic for certification of flight readiness. The key mechanism for realizing these benefits is the development of an inter-functional architecture at the program level, which reveals relationships between top-level system requirements that would otherwise be invisible using only a physical architecture. This paper describes the advantages and pitfalls of functional analysis as a means of coordinating the actions of large heterogeneous organizations for space exploration programs.

Dual role of wingless signaling in stem-like hematopoietic precursor maintenance in Drosophila.

PubMed

Sinenko, Sergey A; Mandal, Lolitika; Martinez-Agosto, Julian A; Banerjee, Utpal

2009-05-01

In Drosophila, blood development occurs in a specialized larval hematopoietic organ, the lymph gland (LG), within which stem-like hemocyte precursors or prohemocytes differentiate to multiple blood cell types. Here we show that components of the Wingless (Wg) signaling pathway are expressed in prohemocytes. Loss- and gain-of-function analysis indicates that canonical Wg signaling is required for maintenance of prohemocytes and negatively regulates their differentiation. Wg signals locally in a short-range fashion within different compartments of the LG. In addition, Wg signaling positively regulates the proliferation and maintenance of cells that function as a hematopoietic niche in Drosophila, the posterior signaling center (PSC), and in the proliferation of crystal cells. Our studies reveal a conserved function of Wg signaling in the maintenance of stem-like blood progenitors and reveal an involvement of this pathway in the regulation of hemocyte differentiation through its action in the hematopoietic niche.

Stratum corneum drying drives vertical compression and lipid organization and improves barrier function in vitro.

PubMed

Iwai, Ichiro; Kunizawa, Naomi; Yagi, Eiichiro; Hirao, Tetsuji; Hatta, Ichiro

2013-03-27

The stratum corneum dehydrates after exogenous hydration due to skincare or bathing. In this study, sheets of stratum corneum were isolated from reconstructed human epidermis and the barrier function and structure of these sheets were assessed during drying with the aim of improving our understanding of skincare. Water diffusion through the sheets of stratum corneum decreased with drying, accompanied by decreased thickness and increased visible light transmission through the sheets. Electron paramagnetic resonance revealed that the order parameter values of stratum corneum lipids increased with drying. X-ray diffraction analysis revealed increases in the diffraction intensity of lamellar structures, with an 11-12 nm periodicity and spacing of 0.42 nm for lattice structures with drying. These results suggest that the drying process improves the barrier function of the stratum corneum by organizing the intercellular lipids in a vertically compressed arrangement.

Functional-anatomic correlates of individual differences in memory.

PubMed

Kirchhoff, Brenda A; Buckner, Randy L

2006-07-20

Memory abilities differ greatly across individuals. To explore a source of these differences, we characterized the varied strategies people adopt during unconstrained encoding. Participants intentionally encoded object pairs during functional MRI. Principal components analysis applied to a strategy questionnaire revealed that participants variably used four main strategies to aid learning. Individuals' use of verbal elaboration and visual inspection strategies independently correlated with their memory performance. Verbal elaboration correlated with activity in a network of regions that included prefrontal regions associated with controlled verbal processing, while visual inspection correlated with activity in a network of regions that included an extrastriate region associated with object processing. Activity in regions associated with use of these strategies was also correlated with memory performance. This study reveals functional-anatomic correlates of verbal and perceptual strategies that are variably used by individuals during encoding. These strategies engage distinct brain regions and may separately influence memory performance.

Psychometrics of Multiple Choice Questions with Non-Functioning Distracters: Implications to Medical Education.

PubMed

Deepak, Kishore K; Al-Umran, Khalid Umran; AI-Sheikh, Mona H; Dkoli, B V; Al-Rubaish, Abdullah

2015-01-01

The functionality of distracters in a multiple choice question plays a very important role. We examined the frequency and impact of functioning and non-functioning distracters on psychometric properties of 5-option items in clinical disciplines. We analyzed item statistics of 1115 multiple choice questions from 15 summative assessments of undergraduate medical students and classified the items into five groups by their number of non-functioning distracters. We analyzed the effect of varying degree of non-functionality ranging from 0 to 4, on test reliability, difficulty index, discrimination index and point biserial correlation. The non-functionality of distracters inversely affected the test reliability and quality of items in a predictable manner. The non-functioning distracters made the items easier and lowered the discrimination index significantly. Three non-functional distracters in a 5-option MCQ significantly affected all psychometric properties (p < 0.5). The corrected point biserial correlation revealed that the items with 3 functional options were psychometrically as effective as 5-option items. Our study reveals that a multiple choice question with 3 functional options provides lower most limit of item format that has adequate psychometric property. The test containing items with less number of functioning options have significantly lower reliability. The distracter function analysis and revision of nonfunctioning distracters can serve as important methods to improve the psychometrics and reliability of assessment.

Nationwide analysis of adrenocortical carcinoma reveals higher perioperative morbidity in functional tumors.

PubMed

Parikh, Punam P; Rubio, Gustavo A; Farra, Josefina C; Lew, John I

2017-08-25

Current adrenalectomy outcomes for functional adrenocortical carcinoma (ACC) remain unclear. This study examines nationwide in-hospital post-adrenalectomy outcomes for ACC. A retrospective analysis of the Nationwide Inpatient Sample database (2006-2011) to identify unilateral adrenalectomy patients for functional or nonfunctional ACC was performed. Patient demographics, comorbidities and postoperative outcomes were evaluated by t-test, Chi-square and multivariate regression. Of 2199 patients who underwent adrenalectomy, 87% had nonfunctional and 13% had functional ACC (86% hypercortisolism, 16% hyperaldosteronism, 4% hyperandrogenism). Functional ACC patients had significantly more comorbidities, and experienced certain postoperative complications more frequently including wound issues, adrenocortical insufficiency and acute kidney injury with longer hospital stay compared to nonfunctional ACC (P < 0.01). On multivariate analysis, functional ACC was an independent prognosticator for wound complications (28.1, 95%CI 4.59-176.6). Patients with functional ACC manifest significant comorbidities with certain in-hospital complications. Such high-risk patients require appropriate preoperative medical optimization prior to adrenalectomy. Patients with functional adrenocortical carcinoma (ACC) have significant preoperative comorbidities and experience higher rates of certain postoperative complications including wound complications, hematoma formation, adrenal insufficiency, pulmonary embolism and acute kidney injury. Functional ACC patients also necessitate longer hospitalizations. These patients should undergo appropriate preoperative counseling in preparation for adrenalectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

Growth and characterization of barium complex of 1,3,5-triazinane-2,4,6-trione in gel: a corrosion inhibiting material

NASA Astrophysics Data System (ADS)

Divya, R.; Nair, Lekshmi P.; Bijini, B. R.; Nair, C. M. K.; Babu, K. Rajendra

2018-05-01

Good quality prismatic crystals of industrially applicable corrosion inhibiting barium complex of 1,3,5-triazinane-2,4,6-trione have been grown by conventional gel method. The crystal structure, packing, and nature of bonds are revealed in the single crystal X-ray diffraction analysis. The crystal has a three-dimensional polymeric structure having a triclinic crystal system with the space group P-1. The powder X-ray diffraction analysis confirms its crystalline nature. The functional groups present in the crystal are identified by Fourier transform infrared spectroscopy. Elemental analysis confirms the stoichiometry of the elements present in the complex. Thermogravimetric analysis and differential thermal analysis reveal its good thermal stability. The optical properties like band gap, refractive index and extinction coefficient are evaluated from the UV-visible spectral analysis. The singular property of the material, corrosion inhibition efficiency achieved by the adsorption of the sample molecules is determined by the weight loss method.

Palaeogenetic analysis of (pre)historic artifacts and its significance for anthropology.

PubMed

Burger, J; Hummel, S; Pfeiffer, I; Herrmann, B

2000-03-01

The possibility of isolating ancient DNA (aDNA) from all kinds of (pre)historic anthropogenetic artifacts opens new perspectives. This study applies palaeogenetic techniques to three anthropological issues: 1. Palaeodiet. DNA sequences from organic residues in vessels identify Precolumbian Aztec diet. 2. (Pre)historic husbandry and economic structures. aDNA data can reveal the species and the genetic evolutionary stage of animals and plants and show the manner and the extent of their growth, cultivation, or domestication. 3. Production techniques, use, and functionality. Identification of the plant or animal source of an archaeological find can reveal the use or the function of the find. Examples from a Celtic "sausage-end" and an Aztec "eye salve" are given.

Surface regulated arsenenes as Dirac materials: From density functional calculations

NASA Astrophysics Data System (ADS)

Yuan, Junhui; Xie, Qingxing; Yu, Niannian; Wang, Jiafu

2017-02-01

Using first principle calculations based on density functional theory (DFT), we have systematically investigated the structure stability and electronic properties of chemically decorated arsenenes, AsX (X = CN, NC, NCO, NCS and NCSe). Phonon dispersion and formation energy analysis reveal that all the five chemically decorated buckled arsenenes are energetically favorable and could be synthesized. Our study shows that wide-bandgap arsenene would turn into Dirac materials when functionalized by -X (X = CN, NC, NCO, NCS and NCSe) groups, rendering new promises in next generation high-performance electronic devices.

On the Asymptotic Behavior of the Kernel Function in the Generalized Langevin Equation: A One-Dimensional Lattice Model

NASA Astrophysics Data System (ADS)

Chu, Weiqi; Li, Xiantao

2018-01-01

We present some estimates for the memory kernel function in the generalized Langevin equation, derived using the Mori-Zwanzig formalism from a one-dimensional lattice model, in which the particles interactions are through nearest and second nearest neighbors. The kernel function can be explicitly expressed in a matrix form. The analysis focuses on the decay properties, both spatially and temporally, revealing a power-law behavior in both cases. The dependence on the level of coarse-graining is also studied.

Principal Component Analysis reveals correlation of cavities evolution and functional motions in proteins.

PubMed

Desdouits, Nathan; Nilges, Michael; Blondel, Arnaud

2015-02-01

Protein conformation has been recognized as the key feature determining biological function, as it determines the position of the essential groups specifically interacting with substrates. Hence, the shape of the cavities or grooves at the protein surface appears to drive those functions. However, only a few studies describe the geometrical evolution of protein cavities during molecular dynamics simulations (MD), usually with a crude representation. To unveil the dynamics of cavity geometry evolution, we developed an approach combining cavity detection and Principal Component Analysis (PCA). This approach was applied to four systems subjected to MD (lysozyme, sperm whale myoglobin, Dengue envelope protein and EF-CaM complex). PCA on cavities allows us to perform efficient analysis and classification of the geometry diversity explored by a cavity. Additionally, it reveals correlations between the evolutions of the cavities and structures, and can even suggest how to modify the protein conformation to induce a given cavity geometry. It also helps to perform fast and consensual clustering of conformations according to cavity geometry. Finally, using this approach, we show that both carbon monoxide (CO) location and transfer among the different xenon sites of myoglobin are correlated with few cavity evolution modes of high amplitude. This correlation illustrates the link between ligand diffusion and the dynamic network of internal cavities. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Quantitative Analysis of the Human Milk Whey Proteome Reveals Developing Milk and Mammary-Gland Functions across the First Year of Lactation

PubMed Central

Zhang, Qiang; Cundiff, Judy K.; Maria, Sarah D.; McMahon, Robert J.; Woo, Jessica G.; Davidson, Barbara S.; Morrow, Ardythe L.

2013-01-01

In-depth understanding of the changing functions of human milk (HM) proteins and the corresponding physiological adaptions of the lactating mammary gland has been inhibited by incomplete knowledge of the HM proteome. We analyzed the HM whey proteome (n = 10 women with samples at 1 week and 1, 3, 6, 9 and 12 months) using a quantitative proteomic approach. One thousand three hundred and thirty three proteins were identified with 615 being quantified. Principal component analysis revealed a transition in the HM whey proteome-throughout the first year of lactation. Abundance changes in IgG, sIgA and sIgM display distinct features during the first year. Complement components and other acute-phase proteins are generally at higher levels in early lactation. Proteomic analysis further suggests that the sources of milk fatty acids (FA) shift from more direct blood influx to more de novo mammary synthesis over lactation. The abundances of the majority of glycoproteins decline over lactation, which is consistent with increased enzyme expression in glycoprotein degradation and decreased enzyme expression in glycoprotein synthesis. Cellular detoxification machinery may be transformed as well, thereby accommodating increased metabolic activities in late lactation. The multiple developing functions of HM proteins and the corresponding mammary adaption become more apparent from this study. PMID:28250401

Using Spatial Multiple Regression to Identify Intrinsic Connectivity Networks Involved in Working Memory Performance

PubMed Central

Gordon, Evan M.; Stollstorff, Melanie; Vaidya, Chandan J.

2012-01-01

Many researchers have noted that the functional architecture of the human brain is relatively invariant during task performance and the resting state. Indeed, intrinsic connectivity networks (ICNs) revealed by resting-state functional connectivity analyses are spatially similar to regions activated during cognitive tasks. This suggests that patterns of task-related activation in individual subjects may result from the engagement of one or more of these ICNs; however, this has not been tested. We used a novel analysis, spatial multiple regression, to test whether the patterns of activation during an N-back working memory task could be well described by a linear combination of ICNs delineated using Independent Components Analysis at rest. We found that across subjects, the cingulo-opercular Set Maintenance ICN, as well as right and left Frontoparietal Control ICNs, were reliably activated during working memory, while Default Mode and Visual ICNs were reliably deactivated. Further, involvement of Set Maintenance, Frontoparietal Control, and Dorsal Attention ICNs was sensitive to varying working memory load. Finally, the degree of left Frontoparietal Control network activation predicted response speed, while activation in both left Frontoparietal Control and Dorsal Attention networks predicted task accuracy. These results suggest that a close relationship between resting-state networks and task-evoked activation is functionally relevant for behavior, and that spatial multiple regression analysis is a suitable method for revealing that relationship. PMID:21761505

A Modified ABCDE Model of Flowering in Orchids Based on Gene Expression Profiling Studies of the Moth Orchid Phalaenopsis aphrodite

PubMed Central

Lee, Ann-Ying; Chen, Chun-Yi; Chang, Yao-Chien Alex; Chao, Ya-Ting; Shih, Ming-Che

2013-01-01

Previously we developed genomic resources for orchids, including transcriptomic analyses using next-generation sequencing techniques and construction of a web-based orchid genomic database. Here, we report a modified molecular model of flower development in the Orchidaceae based on functional analysis of gene expression profiles in Phalaenopsis aphrodite (a moth orchid) that revealed novel roles for the transcription factors involved in floral organ pattern formation. Phalaenopsis orchid floral organ-specific genes were identified by microarray analysis. Several critical transcription factors including AP3, PI, AP1 and AGL6, displayed distinct spatial distribution patterns. Phylogenetic analysis of orchid MADS box genes was conducted to infer the evolutionary relationship among floral organ-specific genes. The results suggest that gene duplication MADS box genes in orchid may have resulted in their gaining novel functions during evolution. Based on these analyses, a modified model of orchid flowering was proposed. Comparison of the expression profiles of flowers of a peloric mutant and wild-type Phalaenopsis orchid further identified genes associated with lip morphology and peloric effects. Large scale investigation of gene expression profiles revealed that homeotic genes from the ABCDE model of flower development classes A and B in the Phalaenopsis orchid have novel functions due to evolutionary diversification, and display differential expression patterns. PMID:24265826

Pyrcca: Regularized Kernel Canonical Correlation Analysis in Python and Its Applications to Neuroimaging.

PubMed

Bilenko, Natalia Y; Gallant, Jack L

2016-01-01

In this article we introduce Pyrcca, an open-source Python package for performing canonical correlation analysis (CCA). CCA is a multivariate analysis method for identifying relationships between sets of variables. Pyrcca supports CCA with or without regularization, and with or without linear, polynomial, or Gaussian kernelization. We first use an abstract example to describe Pyrcca functionality. We then demonstrate how Pyrcca can be used to analyze neuroimaging data. Specifically, we use Pyrcca to implement cross-subject comparison in a natural movie functional magnetic resonance imaging (fMRI) experiment by finding a data-driven set of functional response patterns that are similar across individuals. We validate this cross-subject comparison method in Pyrcca by predicting responses to novel natural movies across subjects. Finally, we show how Pyrcca can reveal retinotopic organization in brain responses to natural movies without the need for an explicit model.

Pyrcca: Regularized Kernel Canonical Correlation Analysis in Python and Its Applications to Neuroimaging

PubMed Central

Bilenko, Natalia Y.; Gallant, Jack L.

2016-01-01

In this article we introduce Pyrcca, an open-source Python package for performing canonical correlation analysis (CCA). CCA is a multivariate analysis method for identifying relationships between sets of variables. Pyrcca supports CCA with or without regularization, and with or without linear, polynomial, or Gaussian kernelization. We first use an abstract example to describe Pyrcca functionality. We then demonstrate how Pyrcca can be used to analyze neuroimaging data. Specifically, we use Pyrcca to implement cross-subject comparison in a natural movie functional magnetic resonance imaging (fMRI) experiment by finding a data-driven set of functional response patterns that are similar across individuals. We validate this cross-subject comparison method in Pyrcca by predicting responses to novel natural movies across subjects. Finally, we show how Pyrcca can reveal retinotopic organization in brain responses to natural movies without the need for an explicit model. PMID:27920675

Vibrational, spectroscopic, molecular docking and density functional theory studies on N-(5-aminopyridin-2-yl)acetamide

NASA Astrophysics Data System (ADS)

Asath, R. Mohamed; Rekha, T. N.; Premkumar, S.; Mathavan, T.; Benial, A. Milton Franklin

2016-12-01

Conformational analysis was carried out for N-(5-aminopyridin-2-yl)acetamide (APA) molecule. The most stable, optimized structure was predicted by the density functional theory calculations using the B3LYP functional with cc-pVQZ basis set. The optimized structural parameters and vibrational frequencies were calculated. The experimental and theoretical vibrational frequencies were assigned and compared. Ultraviolet-visible spectrum was simulated and validated experimentally. The molecular electrostatic potential surface was simulated. Frontier molecular orbitals and related molecular properties were computed, which reveals that the higher molecular reactivity and stability of the APA molecule and further density of states spectrum was simulated. The natural bond orbital analysis was also performed to confirm the bioactivity of the APA molecule. Antidiabetic activity was studied based on the molecular docking analysis and the APA molecule was identified that it can act as a good inhibitor against diabetic nephropathy.

Key Microbiota Identification Using Functional Gene Analysis during Pepper (Piper nigrum L.) Peeling.

PubMed

Zhang, Jiachao; Hu, Qisong; Xu, Chuanbiao; Liu, Sixin; Li, Congfa

2016-01-01

Pepper pericarp microbiota plays an important role in the pepper peeling process for the production of white pepper. We collected pepper samples at different peeling time points from Hainan Province, China, and used a metagenomic approach to identify changes in the pericarp microbiota based on functional gene analysis. UniFrac distance-based principal coordinates analysis revealed significant changes in the pericarp microbiota structure during peeling, which were attributed to increases in bacteria from the genera Selenomonas and Prevotella. We identified 28 core operational taxonomic units at each time point, mainly belonging to Selenomonas, Prevotella, Megasphaera, Anaerovibrio, and Clostridium genera. The results were confirmed by quantitative polymerase chain reaction. At the functional level, we observed significant increases in microbial features related to acetyl xylan esterase and pectinesterase for pericarp degradation during peeling. These findings offer a new insight into biodegradation for pepper peeling and will promote the development of the white pepper industry.

Key Microbiota Identification Using Functional Gene Analysis during Pepper (Piper nigrum L.) Peeling

PubMed Central

Xu, Chuanbiao; Liu, Sixin; Li, Congfa

2016-01-01

Pepper pericarp microbiota plays an important role in the pepper peeling process for the production of white pepper. We collected pepper samples at different peeling time points from Hainan Province, China, and used a metagenomic approach to identify changes in the pericarp microbiota based on functional gene analysis. UniFrac distance-based principal coordinates analysis revealed significant changes in the pericarp microbiota structure during peeling, which were attributed to increases in bacteria from the genera Selenomonas and Prevotella. We identified 28 core operational taxonomic units at each time point, mainly belonging to Selenomonas, Prevotella, Megasphaera, Anaerovibrio, and Clostridium genera. The results were confirmed by quantitative polymerase chain reaction. At the functional level, we observed significant increases in microbial features related to acetyl xylan esterase and pectinesterase for pericarp degradation during peeling. These findings offer a new insight into biodegradation for pepper peeling and will promote the development of the white pepper industry. PMID:27768750

Striatal changes in Parkinson disease: An investigation of morphology, functional connectivity and their relationship to clinical symptoms.

PubMed

Owens-Walton, Conor; Jakabek, David; Li, Xiaozhen; Wilkes, Fiona A; Walterfang, Mark; Velakoulis, Dennis; van Westen, Danielle; Looi, Jeffrey C L; Hansson, Oskar

2018-05-30

We sought to investigate morphological and resting state functional connectivity changes to the striatal nuclei in Parkinson disease (PD) and examine whether changes were associated with measures of clinical function. Striatal nuclei were manually segmented on 3T-T1 weighted MRI scans of 74 PD participants and 27 control subjects, quantitatively analysed for volume, shape and also functional connectivity using functional MRI data. Bilateral caudate nuclei and putamen volumes were significantly reduced in the PD cohort compared to controls. When looking at left and right hemispheres, the PD cohort had significantly smaller left caudate nucleus and right putamen volumes compared to controls. A significant correlation was found between greater atrophy of the caudate nucleus and poorer cognitive function, and between greater atrophy of the putamen and more severe motor symptoms. Resting-state functional MRI analysis revealed altered functional connectivity of the striatal structures in the PD group. This research demonstrates that PD involves atrophic changes to the caudate nucleus and putamen that are linked to clinical dysfunction. Our work reveals important information about a key structure-function relationship in the brain and provides support for caudate nucleus and putamen atrophy as neuroimaging biomeasures in PD. Copyright © 2018 Elsevier B.V. All rights reserved.

Executive functions predict conceptual learning of science.

PubMed

Rhodes, Sinéad M; Booth, Josephine N; Palmer, Lorna Elise; Blythe, Richard A; Delibegovic, Mirela; Wheate, Nial J

2016-06-01

We examined the relationship between executive functions and both factual and conceptual learning of science, specifically chemistry, in early adolescence. Sixty-three pupils in their second year of secondary school (aged 12-13 years) participated. Pupils completed tasks of working memory (Spatial Working Memory), inhibition (Stop-Signal), attention set-shifting (ID/ED), and planning (Stockings of Cambridge), from the CANTAB. They also participated in a chemistry teaching session, practical, and assessment on the topic of acids and alkalis designed specifically for this study. Executive function data were related to (1) the chemistry assessment which included aspects of factual and conceptual learning and (2) a recent school science exam. Correlational analyses between executive functions and both the chemistry assessment and science grades revealed that science achievements were significantly correlated with working memory. Linear regression analysis revealed that visuospatial working memory ability was predictive of chemistry performance. Interestingly, this relationship was observed solely in relation to the conceptual learning condition of the assessment highlighting the role of executive functions in understanding and applying knowledge about what is learned within science teaching. © 2016 The British Psychological Society.

Novel Functional Properties of Drosophila CNS Glutamate Receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yan; Dharkar, Poorva; Han, Tae-Hee

Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists. Surprisingly, the AMPA receptor DGluR1A shows weak activation bymore » its namesake agonist AMPA and also by quisqualate. Crystallization of the DGluR1A ligand-binding domain reveals amino acid exchanges that interfere with binding of these ligands. The unexpected ligand-binding profiles of insect iGluRs allows classical tools to be used in novel approaches for the study of synaptic regulation.« less

Novel Functional Properties of Drosophila CNS Glutamate Receptors.

PubMed

Li, Yan; Dharkar, Poorva; Han, Tae-Hee; Serpe, Mihaela; Lee, Chi-Hon; Mayer, Mark L

2016-12-07

Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists. Surprisingly, the AMPA receptor DGluR1A shows weak activation by its namesake agonist AMPA and also by quisqualate. Crystallization of the DGluR1A ligand-binding domain reveals amino acid exchanges that interfere with binding of these ligands. The unexpected ligand-binding profiles of insect iGluRs allows classical tools to be used in novel approaches for the study of synaptic regulation. VIDEO ABSTRACT. Published by Elsevier Inc.

Exon skipping of AGAMOUS homolog PrseAG in developing double flowers of Prunus lannesiana (Rosaceae).

PubMed

Liu, Zhixiong; Zhang, Dandan; Liu, Di; Li, Fenglan; Lu, Hai

2013-02-01

KEY MESSAGE : Two transcript isoforms of AGAMOUS homologs, from single and double flower Prunus lannesiana, respectively, showed different functions. The Arabidopsis floral homeotic C function gene AGAMOUS (AG) confers stamen and carpel identity. Loss of AG function results in homeotic conversions of stamens into petals and formation of double flowers. In order to present a molecular dissection of a double-flower cultivar in Prunus lannesiana (Rosaceae), we isolated and identified a single-copy gene, AG homolog from two genetically cognate P. lannesiana bearing single and double flowers, respectively. Sequence analysis revealed that the AG homolog, prseag-1, from double flowers showed a 170-bp exon skipping as compared to PrseAG (Prunus serrulata AGAMOUS) from the single flowers. Genomic DNA sequence revealed that abnormal splicing resulted in mutant prseag-1 protein with the C-terminal AG motifs I and II deletions. In addition, protein sequence alignment and phylogenetic analyses revealed that the PrseAG was grouped into the euAG lineage. A semi-quantitative PCR analysis showed that the expression of PrseAG was restricted to reproductive organs of stamens and carpels in single flowers of P. lannesiana 'speciosa', while the prseag-1 mRNA was highly transcribed throughout the petals, stamens, and carpels in double flowers from 'Albo-rosea'. The transgenic Arabidopsis containing 35S::PrseAG displayed extremely early flowering, bigger stamens and carpels and homeotic conversion of petals into staminoid organs, but ectopic expression of prseag-1 could not mimic the phenotypic ectopic expression of PrseAG in Arabidopsis. In general, this study provides evidences to show that double flower 'Albo-rosea' is a putative C functional ag mutant in P. lannesiana.

Mapping thalamocortical functional connectivity in chronic and early stages of psychotic disorders

PubMed Central

Woodward, Neil D.; Heckers, Stephan

2015-01-01

Objective There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state fMRI (RS-fMRI) has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis. Method RS-fMRI was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions-of-interest (ROIs) on the basis of connectivity with six a-priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxel-wise seed-based analyses to further localize thalamic dysconnectivity. Results ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early stages psychosis patients. PFC hypo-connectivity and motor cortex hyper-connectivity correlated in patients suggesting they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypo-connectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described ‘executive control’ network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory. Conclusions Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment. PMID:26248537

Association between the Type of Workplace and Lung Function in Copper Miners

PubMed Central

Gruszczyński, Leszek; Wojakowska, Anna; Ścieszka, Marek; Turczyn, Barbara; Schmidt, Edward

2016-01-01

The aim of the analysis was to retrospectively assess changes in lung function in copper miners depending on the type of workplace. In the groups of 225 operators, 188 welders, and 475 representatives of other jobs, spirometry was performed at the start of employment and subsequently after 10, 20, and 25 years of work. Spirometry Longitudinal Data Analysis software was used to estimate changes in group means for FEV1 and FVC. Multiple linear regression analysis was used to assess an association between workplace and lung function. Lung function assessed on the basis of calculation of longitudinal FEV1 (FVC) decline was similar in all studied groups. However, multiple linear regression model used in cross-sectional analysis revealed an association between workplace and lung function. In the group of welders, FEF75 was lower in comparison to operators and other miners as early as after 10 years of work. Simultaneously, in smoking welders, the FEV1/FVC ratio was lower than in nonsmokers (p < 0,05). The interactions between type of workplace and smoking (p < 0,05) in their effect on FVC, FEV1, PEF, and FEF50 were shown. Among underground working copper miners, the group of smoking welders is especially threatened by impairment of lung ventilatory function. PMID:27274987

Laterality effects in functional connectivity of the angular gyrus during rest and episodic retrieval.

PubMed

Bellana, Buddhika; Liu, Zhongxu; Anderson, John A E; Moscovitch, Morris; Grady, Cheryl L

2016-01-08

The angular gyrus (AG) is consistently reported in neuroimaging studies of episodic memory retrieval and is a fundamental node within the default mode network (DMN). Its specific contribution to episodic memory is debated, with some suggesting it is important for the subjective experience of episodic recollection, rather than retrieval of objective episodic details. Across studies of episodic retrieval, the left AG is recruited more reliably than the right. We explored functional connectivity of the right and left AG with the DMN during rest and retrieval to assess whether connectivity could provide insight into the nature of this laterality effect. Using data from the publically available 1000 Functional Connectome Project, 8min of resting fMRI data from 180 healthy young adults were analysed. Whole-brain functional connectivity at rest was measured using a seed-based Partial Least Squares (seed-PLS) approach (McIntosh and Lobaugh, 2004) with bilateral AG seeds. A subsequent analysis used 6-min of rest and 6-min of unconstrained, silent retrieval of autobiographical events from a new sample of 20 younger adults. Analysis of this dataset took a more targeted approach to functional connectivity analysis, consisting of univariate pairwise correlations restricted to nodes of the DMN. The seed-PLS analysis resulted in two Latent Variables that together explained ~86% of the shared cross-block covariance. The first LV revealed a common network consistent with the DMN and engaging the AG bilaterally, whereas the second LV revealed a less robust, yet significant, laterality effect in connectivity - the left AG was more strongly connected to the DMN. Univariate analyses of the second sample again revealed better connectivity between the left AG and the DMN at rest. However, during retrieval the left AG was more strongly connected than the right to non-medial temporal (MTL) nodes of the DMN, and MTL nodes were more strongly connected to the right AG. The multivariate analysis of resting connectivity revealed that the left and right AG show similar connectivity with the DMN. Only after accounting for this commonality were we able to detect a left laterality effect in DMN connectivity. Further probing with univariate connectivity analyses during retrieval demonstrates that the left preference we observe is restricted to the non-MTL regions of the DMN, whereas the right AG shows significantly better connectivity with the MTL. These data suggest bilateral involvement of the AG during retrieval, despite the focus on the left AG in the literature. Furthermore, the results suggest that the contribution of the left AG to retrieval may be separable from that of the MTL, consistent with a role for the left AG in the subjective aspects of recollection in memory, whereas the MTL and the right AG may contribute to objective recollection of specific memory details. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural, evolutionary and genetic analysis of the histidine biosynthetic "core" in the genus Burkholderia.

PubMed

Papaleo, Maria Cristiana; Russo, Edda; Fondi, Marco; Emiliani, Giovanni; Frandi, Antonio; Brilli, Matteo; Pastorelli, Roberta; Fani, Renato

2009-12-01

In this work a detailed analysis of the structure, the expression and the organization of his genes belonging to the core of histidine biosynthesis (hisBHAF) in 40 newly determined and 13 available sequences of Burkholderia strains was carried out. Data obtained revealed a strong conservation of the structure and organization of these genes through the entire genus. The phylogenetic analysis showed the monophyletic origin of this gene cluster and indicated that it did not undergo horizontal gene transfer events. The analysis of the intergenic regions, based on the substitution rate, entropy plot and bendability suggested the existence of a putative transcription promoter upstream of hisB, that was supported by the genetic analysis that showed that this cluster was able to complement Escherichia colihisA, hisB, and hisF mutations. Moreover, a preliminary transcriptional analysis and the analysis of microarray data revealed that the expression of the his core was constitutive. These findings are in agreement with the fact that the entire Burkholderiahis operon is heterogeneous, in that it contains "alien" genes apparently not involved in histidine biosynthesis. Besides, they also support the idea that the proteobacterial his operon was piece-wisely assembled, i.e. through accretion of smaller units containing only some of the genes (eventually together with their own promoters) involved in this biosynthetic route. The correlation existing between the structure, organization and regulation of his "core" genes and the function(s) they perform in cellular metabolism is discussed.

Quantitative protein localization signatures reveal an association between spatial and functional divergences of proteins.

PubMed

Loo, Lit-Hsin; Laksameethanasan, Danai; Tung, Yi-Ling

2014-03-01

Protein subcellular localization is a major determinant of protein function. However, this important protein feature is often described in terms of discrete and qualitative categories of subcellular compartments, and therefore it has limited applications in quantitative protein function analyses. Here, we present Protein Localization Analysis and Search Tools (PLAST), an automated analysis framework for constructing and comparing quantitative signatures of protein subcellular localization patterns based on microscopy images. PLAST produces human-interpretable protein localization maps that quantitatively describe the similarities in the localization patterns of proteins and major subcellular compartments, without requiring manual assignment or supervised learning of these compartments. Using the budding yeast Saccharomyces cerevisiae as a model system, we show that PLAST is more accurate than existing, qualitative protein localization annotations in identifying known co-localized proteins. Furthermore, we demonstrate that PLAST can reveal protein localization-function relationships that are not obvious from these annotations. First, we identified proteins that have similar localization patterns and participate in closely-related biological processes, but do not necessarily form stable complexes with each other or localize at the same organelles. Second, we found an association between spatial and functional divergences of proteins during evolution. Surprisingly, as proteins with common ancestors evolve, they tend to develop more diverged subcellular localization patterns, but still occupy similar numbers of compartments. This suggests that divergence of protein localization might be more frequently due to the development of more specific localization patterns over ancestral compartments than the occupation of new compartments. PLAST enables systematic and quantitative analyses of protein localization-function relationships, and will be useful to elucidate protein functions and how these functions were acquired in cells from different organisms or species. A public web interface of PLAST is available at http://plast.bii.a-star.edu.sg.

Parallel Alterations of Functional Connectivity during Execution and Imagination after Motor Imagery Learning

PubMed Central

Zhang, Rushao; Hui, Mingqi; Long, Zhiying; Zhao, Xiaojie; Yao, Li

2012-01-01

Background Neural substrates underlying motor learning have been widely investigated with neuroimaging technologies. Investigations have illustrated the critical regions of motor learning and further revealed parallel alterations of functional activation during imagination and execution after learning. However, little is known about the functional connectivity associated with motor learning, especially motor imagery learning, although benefits from functional connectivity analysis attract more attention to the related explorations. We explored whether motor imagery (MI) and motor execution (ME) shared parallel alterations of functional connectivity after MI learning. Methodology/Principal Findings Graph theory analysis, which is widely used in functional connectivity exploration, was performed on the functional magnetic resonance imaging (fMRI) data of MI and ME tasks before and after 14 days of consecutive MI learning. The control group had no learning. Two measures, connectivity degree and interregional connectivity, were calculated and further assessed at a statistical level. Two interesting results were obtained: (1) The connectivity degree of the right posterior parietal lobe decreased in both MI and ME tasks after MI learning in the experimental group; (2) The parallel alterations of interregional connectivity related to the right posterior parietal lobe occurred in the supplementary motor area for both tasks. Conclusions/Significance These computational results may provide the following insights: (1) The establishment of motor schema through MI learning may induce the significant decrease of connectivity degree in the posterior parietal lobe; (2) The decreased interregional connectivity between the supplementary motor area and the right posterior parietal lobe in post-test implicates the dissociation between motor learning and task performing. These findings and explanations further revealed the neural substrates underpinning MI learning and supported that the potential value of MI learning in motor function rehabilitation and motor skill learning deserves more attention and further investigation. PMID:22629308

Quantitative Protein Localization Signatures Reveal an Association between Spatial and Functional Divergences of Proteins

PubMed Central

Loo, Lit-Hsin; Laksameethanasan, Danai; Tung, Yi-Ling

2014-01-01

Protein subcellular localization is a major determinant of protein function. However, this important protein feature is often described in terms of discrete and qualitative categories of subcellular compartments, and therefore it has limited applications in quantitative protein function analyses. Here, we present Protein Localization Analysis and Search Tools (PLAST), an automated analysis framework for constructing and comparing quantitative signatures of protein subcellular localization patterns based on microscopy images. PLAST produces human-interpretable protein localization maps that quantitatively describe the similarities in the localization patterns of proteins and major subcellular compartments, without requiring manual assignment or supervised learning of these compartments. Using the budding yeast Saccharomyces cerevisiae as a model system, we show that PLAST is more accurate than existing, qualitative protein localization annotations in identifying known co-localized proteins. Furthermore, we demonstrate that PLAST can reveal protein localization-function relationships that are not obvious from these annotations. First, we identified proteins that have similar localization patterns and participate in closely-related biological processes, but do not necessarily form stable complexes with each other or localize at the same organelles. Second, we found an association between spatial and functional divergences of proteins during evolution. Surprisingly, as proteins with common ancestors evolve, they tend to develop more diverged subcellular localization patterns, but still occupy similar numbers of compartments. This suggests that divergence of protein localization might be more frequently due to the development of more specific localization patterns over ancestral compartments than the occupation of new compartments. PLAST enables systematic and quantitative analyses of protein localization-function relationships, and will be useful to elucidate protein functions and how these functions were acquired in cells from different organisms or species. A public web interface of PLAST is available at http://plast.bii.a-star.edu.sg. PMID:24603469

Unraveling Core Functional Microbiota in Traditional Solid-State Fermentation by High-Throughput Amplicons and Metatranscriptomics Sequencing.

PubMed

Song, Zhewei; Du, Hai; Zhang, Yan; Xu, Yan

2017-01-01

Fermentation microbiota is specific microorganisms that generate different types of metabolites in many productions. In traditional solid-state fermentation, the structural composition and functional capacity of the core microbiota determine the quality and quantity of products. As a typical example of food fermentation, Chinese Maotai-flavor liquor production involves a complex of various microorganisms and a wide variety of metabolites. However, the microbial succession and functional shift of the core microbiota in this traditional food fermentation remain unclear. Here, high-throughput amplicons (16S rRNA gene amplicon sequencing and internal transcribed space amplicon sequencing) and metatranscriptomics sequencing technologies were combined to reveal the structure and function of the core microbiota in Chinese soy sauce aroma type liquor production. In addition, ultra-performance liquid chromatography and headspace-solid phase microextraction-gas chromatography-mass spectrometry were employed to provide qualitative and quantitative analysis of the major flavor metabolites. A total of 10 fungal and 11 bacterial genera were identified as the core microbiota. In addition, metatranscriptomic analysis revealed pyruvate metabolism in yeasts (genera Pichia, Schizosaccharomyces, Saccharomyces , and Zygosaccharomyces ) and lactic acid bacteria (genus Lactobacillus ) classified into two stages in the production of flavor components. Stage I involved high-level alcohol (ethanol) production, with the genus Schizosaccharomyces serving as the core functional microorganism. Stage II involved high-level acid (lactic acid and acetic acid) production, with the genus Lactobacillus serving as the core functional microorganism. The functional shift from the genus Schizosaccharomyces to the genus Lactobacillus drives flavor component conversion from alcohol (ethanol) to acid (lactic acid and acetic acid) in Chinese Maotai-flavor liquor production. Our findings provide insight into the effects of the core functional microbiota in soy sauce aroma type liquor production and the characteristics of the fermentation microbiota under different environmental conditions.

Development of a fermented ice-cream as influenced by in situ exopolysaccharide production: Rheological, molecular, microstructural and sensory characterization.

PubMed

Dertli, Enes; Toker, Omer S; Durak, M Zeki; Yilmaz, Mustafa T; Tatlısu, Nevruz Berna; Sagdic, Osman; Cankurt, Hasan

2016-01-20

This study aimed to investigate the role of in situ exopolysaccharide (EPS) production by EPS(+)Streptococcus thermophilus strains on physicochemical, rheological, molecular, microstructural and sensory properties of ice cream in order to develop a fermented and consequently functional ice-cream in which no stabilizers would be required in ice-cream production. For this purpose, the effect of EPS producing strains (control, strain 1, strain 2 and mixture) and fermentation conditions (fermentation temperature; 32, 37 and 42 °C and time; 2, 3 and 4h) on pH, S. thermophilus count, EPS amount, consistency coefficient (K), and apparent viscosity (η50) were investigated and optimized using single and multiple response optimization tools of response surface methodology. Optimization analyses indicated that functional ice-cream should be fermented with strain 1 or strain mixture at 40-42 °C for 4h in order to produce the most viscous ice-cream with maximum EPS content. Optimization analysis results also revealed that strain specific conditions appeared to be more effective factor on in situ EPS production amount, K and η50 parameters than did fermentation temperature and time. The rheological analysis of the ice-cream produced by EPS(+) strains revealed its high viscous and pseudoplastic non-Newtonian fluid behavior, which demonstrates potential of S. thermophilus EPS as thickening and gelling agent in dairy industry. FTIR analysis proved that the EPS in ice-cream corresponded to a typical EPS, as revealed by the presence of carboxyl, hydroxyl and amide groups with additional α-glycosidic linkages. SEM studies demonstrated that it had a web-like compact microstructure with pores in ice-cream, revealing its application possibility in dairy products to improve their rheological properties. Copyright © 2015. Published by Elsevier Ltd.

Characterization of the telomere complex, TERF1 and TERF2 genes in muntjac species with fusion karyotypes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartmann, Nils; Scherthan, Harry

The telomere binding proteins TRF1 and TRF2 maintain and protect chromosome ends and confer karyotypic stability. Chromosome evolution in the genus Muntiacus is characterized by numerous tandem (end-to-end) fusions. To study TRF1 and TRF2 telomere binding proteins in Muntiacus species, we isolated and characterized the TERF1 and -2 genes from Indian muntjac (Muntiacus muntjak vaginalis; 2n = 6 female) and from Chinese muntjac (Muntiacus reveesi; 2n = 46). Expression analysis revealed that both genes are ubiquitously expressed and sequence analysis identified several transcript variants of both TERF genes. Control experiments disclosed a novel testis-specific splice variant of TERF1 in humanmore » testes. Amino acid sequence comparisons demonstrate that Muntiacus TRF1 and in particular TRF2 are highly conserved between muntjac and human. In vivo TRF2-GFP and immuno-staining studies in muntjac cell lines revealed telomeric TRF2 localization, while deletion of the DNA binding domain abrogated this localization, suggesting muntjac TRF2 represents a functional telomere protein. Finally, expression analysis of a set of telomere-related genes revealed their presence in muntjac fibroblasts and testis tissue, which suggests the presence of a conserved telomere complex in muntjacs. However, a deviation from the common theme was noted for the TERT gene, encoding the catalytic subunit of telomerase; TERT expression could not be detected in Indian or Chinese muntjac cDNA or genomic DNA using a series of conserved primers, while TRAP assay revealed functional telomerase in Chinese muntjac testis tissues. This suggests muntjacs may harbor a diverged telomerase sequence.« less

Low-frequency dynamics of autonomic regulation of circulatory system in healthy subjects

NASA Astrophysics Data System (ADS)

Skazkina, V. V.; Borovkova, E. I.; Galushko, T. A.; Khorev, V. S.; Kiselev, A. R.

2018-04-01

The paper is devoted to the analysis of dynamic of interactions between signals of autonomic circulatory regulation. We investigated two-hour experimental records of 30 healthy people. Phase synchronization was studied using the signals of the electrocardiogram and the photoplethysmogram of vessels. We found the presence of long synchronous intervals in some subjects. For analysis of the dynamic we calculated autocorrelation functions. The analysis made it possible to reveal indirect signs of the influence of the humoral regulation system.

A Comparison of Preservice and Experienced Teachers' Perceptions of the School Psychologist.

ERIC Educational Resources Information Center

Dean, Raymond S.

1980-01-01

Experienced and preservice teachers agreed about the importance of the school psychologist and the appropriateness of referral problems. Analysis of ratings revealed that experienced teachers had a more negative opinion of the school psychologist's functioning when compared to their novice counterparts. (Author)

Predictors of Sex Offender Treatment Completion.

ERIC Educational Resources Information Center

Moore, Donna L.; Bergman, Barbara A.; Knox, Pamela L.

1999-01-01

Reviews records of 126 incarcerated offenders who participated in a prison-based sex offender treatment program. Discriminate function analysis reveals that offenders who completed treatment were more often diagnosed with a substance disorder, had a history of nonviolence offenses, and were less often diagnosed as having an antisocial personality…

Actin motility: formin a SCAry tail.

PubMed

Alberts, Art; Way, Michael

2011-01-11

A new biochemical analysis has revealed that the Rickettsia bacterial protein Sca2--recently shown to be essential for virulence and actin-dependent motility--assembles actin filaments using a mechanism that functionally resembles the processive elongation tactics used by formins. Copyright © 2011 Elsevier Ltd. All rights reserved.

Metagenome Analyses of Corroded Concrete Wastewater Pipe Biofilms Reveals a Complex Microbial System

EPA Science Inventory

Analysis of whole-metagenome pyrosequencing data and 16S rRNA gene clone libraries was used to determine microbial composition and functional genes associated with biomass harvested from crown (top) and invert (bottom) sections of a corroded wastewater pipe. Taxonomic and functio...

3D printing of graphene-doped target for "matrix-free" laser desorption/ionization mass spectrometry.

PubMed

Wang, Dingyi; Huang, Xiu; Li, Jie; He, Bin; Liu, Qian; Hu, Ligang; Jiang, Guibin

2018-03-13

We report a graphene-doped resin target fabricated via a 3D printing technique for laser desorption/ionization mass spectrometry analysis. The graphene doped in the target acts as an inherent laser absorber and ionization promoter, thus permitting the direct analysis of samples without adding matrix. This work reveals a new strategy for easy designing and fabrication of functional mass spectrometry devices.

Characterization and Expression Analysis of Receptor for Activated C Kinase from Silk-producing Insect Antheraea pernyi.

PubMed

Zhu, Bao-Jian; Yu, Hao; Tian, Sen; Dai, Li-Shang; Sun, Yu; Liu, Chao-Liang

2016-01-01

The receptor for activated C kinase (RACK) is an important scaffold protein with regulatory functions in cells. However, its role in the immune response of Antheraea pernyi to pathogen challenge remains unclear. To investigate the biological functions of RACK in the wild silkworm A. pernyi, cloning was performed and the expression patterns of the RACK gene were analyzed. Sequence analysis revealed that the RACK gene was 1120 bp containing a 960-bp open reading frame. The deduced RACK protein sequence reveals the higher identity with its homologs from other insects. SDS-PAGE and western blot analysis demonstrated successful expression of a 36-kDa recombinant RACK protein in Escherichia coli. The titer of a rabbit-raised antibody against recombinant RACK protein was about 1: 20000, determined by ELISA. Real-time PCR analysis showed that RACK expression was higher in fat bodies than in other examined A. pernyi tissues. The expression of RACK mRNA in fat bodies of fifth larvae of A. pernyi was obviously induced after nucleopolyhedrovirus, E. coli or Beauveria bassiana challenge. However, the expression patterns of RACK were different in response to these pathogens. Our data suggest that RACK may play a role in the innate immune responses of A. pernyi.

Network analysis reveals that bacteria and fungi form modules that correlate independently with soil parameters.

PubMed

de Menezes, Alexandre B; Prendergast-Miller, Miranda T; Richardson, Alan E; Toscas, Peter; Farrell, Mark; Macdonald, Lynne M; Baker, Geoff; Wark, Tim; Thrall, Peter H

2015-08-01

Network and multivariate statistical analyses were performed to determine interactions between bacterial and fungal community terminal restriction length polymorphisms as well as soil properties in paired woodland and pasture sites. Canonical correspondence analysis (CCA) revealed that shifts in woodland community composition correlated with soil dissolved organic carbon, while changes in pasture community composition correlated with moisture, nitrogen and phosphorus. Weighted correlation network analysis detected two distinct microbial modules per land use. Bacterial and fungal ribotypes did not group separately, rather all modules comprised of both bacterial and fungal ribotypes. Woodland modules had a similar fungal : bacterial ribotype ratio, while in the pasture, one module was fungal dominated. There was no correspondence between pasture and woodland modules in their ribotype composition. The modules had different relationships to soil variables, and these contrasts were not detected without the use of network analysis. This study demonstrated that fungi and bacteria, components of the soil microbial communities usually treated as separate functional groups as in a CCA approach, were co-correlated and formed distinct associations in these adjacent habitats. Understanding these distinct modular associations may shed more light on their niche space in the soil environment, and allow a more realistic description of soil microbial ecology and function. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Cloning and expression profile of ionotropic receptors in the parasitoid wasp Microplitis mediator (Hymenoptera: Braconidae).

PubMed

Wang, Shan-Ning; Peng, Yong; Lu, Zi-Yun; Dhiloo, Khalid Hussain; Zheng, Yao; Shan, Shuang; Li, Rui-Jun; Zhang, Yong-Jun; Guo, Yu-Yuan

2016-07-01

Ionotropic receptors (IRs) mainly detect the acids and amines having great importance in many insect species, representing an ancient olfactory receptor family in insects. In the present work, we performed RNAseq of Microplitis mediator antennae and identified seventeen IRs. Full-length MmedIRs were cloned and sequenced. Phylogenetic analysis of the Hymenoptera IRs revealed that ten MmedIR genes encoded "antennal IRs" and seven encoded "divergent IRs". Among the IR25a orthologous groups, two genes, MmedIR25a.1 and MmedIR25a.2, were found in M. mediator. Gene structure analysis of MmedIR25a revealed a tandem duplication of IR25a in M. mediator. The tissue distribution and development specific expression of the MmedIR genes suggested that these genes showed a broad expression profile. Quantitative gene expression analysis showed that most of the genes are highly enriched in adult antennae, indicating the candidate chemosensory function of this family in parasitic wasps. Using immunocytochemistry, we confirmed that one co-receptor, MmedIR8a, was expressed in the olfactory sensory neurons. Our data will supply fundamental information for functional analysis of the IRs in parasitoid wasp chemoreception. Copyright © 2016 Elsevier Ltd. All rights reserved.

Engineering of a conditional allele reveals multiple roles of XRN2 in Caenorhabditis elegans development and substrate specificity in microRNA turnover.

PubMed

Miki, Takashi S; Rüegger, Stefan; Gaidatzis, Dimos; Stadler, Michael B; Großhans, Helge

2014-04-01

Although XRN2 proteins are highly conserved eukaryotic 5'→3' exonucleases, little is known about their function in animals. Here, we characterize Caenorhabditis elegans XRN2, which we find to be a broadly and constitutively expressed nuclear protein. An xrn-2 null mutation or loss of XRN2 catalytic activity causes a molting defect and early larval arrest. However, by generating a conditionally mutant xrn-2ts strain de novo through an approach that may be also applicable to other genes of interest, we reveal further functions in fertility, during embryogenesis and during additional larval stages. Consistent with the known role of XRN2 in controlling microRNA (miRNA) levels, we can demonstrate that loss of XRN2 activity stabilizes some rapidly decaying miRNAs. Surprisingly, however, other miRNAs continue to decay rapidly in xrn-2ts animals. Thus, XRN2 has unanticipated miRNA specificity in vivo, and its diverse developmental functions may relate to distinct substrates. Finally, our global analysis of miRNA stability during larval stage 1 reveals that miRNA passenger strands (miR*s) are substantially less stable than guide strands (miRs), supporting the notion that the former are mostly byproducts of biogenesis rather than a less abundant functional species.

Abnormal cardiac autonomic regulation in mice lacking ASIC3.

PubMed

Cheng, Ching-Feng; Kuo, Terry B J; Chen, Wei-Nan; Lin, Chao-Chieh; Chen, Chih-Cheng

2014-01-01

Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3) is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function using Asic3(-/-) mice. Asic3(-/-) mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore, Asic3(-/-) mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found in Asic3(-/-) mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases.

Pulse gas chromatographic study of adsorption of substituted aromatics and heterocyclic molecules on MIL-47 at zero coverage.

PubMed

Duerinck, Tim; Couck, Sarah; Vermoortele, Frederik; De Vos, Dirk E; Baron, Gino V; Denayer, Joeri F M

2012-10-02

The low coverage adsorptive properties of the MIL-47 metal organic framework toward aromatic and heterocyclic molecules are reported in this paper. The effect of molecular functionality and size on Henry adsorption constants and adsorption enthalpies of alkyl and heteroatom functionalized benzene derivates and heterocyclic molecules was studied using pulse gas chromatography. By means of statistical analysis, experimental data was analyzed and modeled using principal component analysis and partial least-squares regression. Structure-property relationships were established, revealing and confirming several trends. Among the molecular properties governing the adsorption process, vapor pressure, mean polarizability, and dipole moment play a determining role.

Vibrational Spectra and Density functional calculation of Organic Nonlinear Optic Crystal p-Amino Acetanilide

NASA Astrophysics Data System (ADS)

Saja, D.; Joe, I. Hubert; Jayakumar, V. S.

2006-01-01

The NIR-FT Raman, FT-IR spectral analysis of potential NLO material P-Amino Acetanilide is carried out by density functional computations. The optimized geometry shows that NH2 and NHCOCH3 groups substituted in para position of phenyl ring are non-planar which predicts maximum conjugation of molecule with donor and acceptor groups. Vibrational analysis reveals that simultaneous IR and Raman activation of the phenyl ring modes also provide evidence for the charge transfer interaction between the donors and the acceptor can make the molecule highly polarized and the intra molecular charge transfer interaction must be responsible for the NLO properties of PAA.

Evaluation of biodegradable electric conductive tube-guides and mesenchymal stem cells

PubMed Central

Ribeiro, Jorge; Pereira, Tiago; Caseiro, Ana Rita; Armada-da-Silva, Paulo; Pires, Isabel; Prada, Justina; Amorim, Irina; Amado, Sandra; França, Miguel; Gonçalves, Carolina; Lopes, Maria Ascensão; Santos, José Domingos; Silva, Dina Morais; Geuna, Stefano; Luís, Ana Lúcia; Maurício, Ana Colette

2015-01-01

AIM: To study the therapeutic effect of three tube-guides with electrical conductivity associated to mesenchymal stem cells (MSCs) on neuro-muscular regeneration after neurotmesis. METHODS: Rats with 10-mm gap nerve injury were tested using polyvinyl alcohol (PVA), PVA-carbon nanotubes (CNTs) and MSCs, and PVA-polypyrrole (PPy). The regenerated nerves and tibialis anterior muscles were processed for stereological studies after 20 wk. The functional recovery was assessed serially for gait biomechanical analysis, by extensor postural thrust, sciatic functional index and static sciatic functional index (SSI), and by withdrawal reflex latency (WRL). In vitro studies included cytocompatibility, flow cytometry, reverse transcriptase polymerase chain reaction and karyotype analysis of the MSCs. Histopathology of lung, liver, kidneys, and regional lymph nodes ensured the biomaterials biocompatibility. RESULTS: SSI remained negative throughout and independently from treatment. Differences between treted groups in the severity of changes in WRL existed, showing a faster regeneration for PVA-CNTs-MSCs (P < 0.05). At toe-off, less acute ankle joint angles were seen for PVA-CNTs-MSCs group (P = 0.051) suggesting improved ankle muscles function during the push off phase of the gait cycle. In PVA-PPy and PVA-CNTs groups, there was a 25% and 42% increase of average fiber area and a 13% and 21% increase of the “minimal Feret’s diameter” respectively. Stereological analysis disclosed a significantly (P < 0.05) increased myelin thickness (M), ratio myelin thickness/axon diameter (M/d) and ratio axon diameter/fiber diameter (d/D; g-ratio) in PVA-CNT-MSCs group (P < 0.05). CONCLUSION: Results revealed that treatment with MSCs and PVA-CNTs tube-guides induced better nerve fiber regeneration. Functional and kinematics analysis revealed positive synergistic effects brought by MSCs and PVA-CNTs. The PVA-CNTs and PVA-PPy are promising scaffolds with electric conductive properties, bio- and cytocompatible that might prevent the secondary neurogenic muscular atrophy by improving the reestablishment of the neuro-muscular junction. PMID:26240682

Insight into pattern of codon biasness and nucleotide base usage in serotonin receptor gene family from different mammalian species.

PubMed

Dass, J Febin Prabhu; Sudandiradoss, C

2012-07-15

5-HT (5-Hydroxy-tryptamine) or serotonin receptors are found both in central and peripheral nervous system as well as in non-neuronal tissues. In the animal and human nervous system, serotonin produces various functional effects through a variety of membrane bound receptors. In this study, we focus on 5-HT receptor family from different mammals and examined the factors that account for codon and nucleotide usage variation. A total of 110 homologous coding sequences from 11 different mammalian species were analyzed using relative synonymous codon usage (RSCU), correspondence analysis (COA) and hierarchical cluster analysis together with nucleotide base usage frequency of chemically similar amino acid codons. The mean effective number of codon (ENc) value of 37.06 for 5-HT(6) shows very high codon bias within the family and may be due to high selective translational efficiency. The COA and Spearman's rank correlation reveals that the nucleotide compositional mutation bias as the major factors influencing the codon usage in serotonin receptor genes. The hierarchical cluster analysis suggests that gene function is another dominant factor that affects the codon usage bias, while species is a minor factor. Nucleotide base usage was reported using Goldman, Engelman, Stietz (GES) scale reveals the presence of high uracil (>45%) content at functionally important hydrophobic regions. Our in silico approach will certainly help for further investigations on critical inference on evolution, structure, function and gene expression aspects of 5-HT receptors family which are potential antipsychotic drug targets. Copyright © 2012 Elsevier B.V. All rights reserved.

RNA-Seq Analysis Reveals MAPKKK Family Members Related to Drought Tolerance in Maize

PubMed Central

Ren, Wen; Yang, Fengling; He, Hang; Zhao, Jiuran

2015-01-01

The mitogen-activated protein kinase (MAPK) cascade is an evolutionarily conserved signal transduction pathway that is involved in plant development and stress responses. As the first component of this phosphorelay cascade, mitogen-activated protein kinase kinase kinases (MAPKKKs) act as adaptors linking upstream signaling steps to the core MAPK cascade to promote the appropriate cellular responses; however, the functions of MAPKKKs in maize are unclear. Here, we identified 71 MAPKKK genes, of which 14 were novel, based on a computational analysis of the maize (Zea mays L.) genome. Using an RNA-seq analysis in the leaf, stem and root of maize under well-watered and drought-stress conditions, we identified 5,866 differentially expressed genes (DEGs), including 8 MAPKKK genes responsive to drought stress. Many of the DEGs were enriched in processes such as drought stress, abiotic stimulus, oxidation-reduction, and metabolic processes. The other way round, DEGs involved in processes such as oxidation, photosynthesis, and starch, proline, ethylene, and salicylic acid metabolism were clearly co-expressed with the MAPKKK genes. Furthermore, a quantitative real-time PCR (qRT-PCR) analysis was performed to assess the relative expression levels of MAPKKKs. Correlation analysis revealed that there was a significant correlation between expression levels of two MAPKKKs and relative biomass responsive to drought in 8 inbred lines. Our results indicate that MAPKKKs may have important regulatory functions in drought tolerance in maize. PMID:26599013

Treating conduct disorder: An effectiveness and natural language analysis study of a new family-centred intervention program.

PubMed

Stevens, Kimberly A; Ronan, Prof Kevin; Davies, Gene

2017-05-01

This paper reports on a new family-centred, feedback-informed intervention focused on evaluating therapeutic outcomes and language changes across treatment for conduct disorder (CD). The study included 26 youth and families from a larger randomised, controlled trial (Ronan et al., in preparation). Outcome measures reflected family functioning/youth compliance, delinquency, and family goal attainment. First- and last-treatment session audio files were transcribed into more than 286,000 words and evaluated through the Linguistic Inquiry and Word Count Analysis program (Pennebaker et al., 2007). Significant outcomes across family functioning/youth compliance, delinquency, goal attainment and word usage reflected moderate-strong effect sizes. Benchmarking findings also revealed reduced time of treatment delivery compared to a gold standard approach. Linguistic analysis revealed specific language changes across treatment. For caregivers, increased first person, action-oriented, present tense, and assent type words and decreased sadness words were found; for youth, significant reduction in use of leisure words. This study is the first using lexical analyses of natural language to assess change across treatment for conduct disordered youth and families. Such findings provided strong support for program tenets; others, more speculative support. Copyright © 2016. Published by Elsevier B.V.

Revealing the Hidden Relationship by Sparse Modules in Complex Networks with a Large-Scale Analysis

PubMed Central

Jiao, Qing-Ju; Huang, Yan; Liu, Wei; Wang, Xiao-Fan; Chen, Xiao-Shuang; Shen, Hong-Bin

2013-01-01

One of the remarkable features of networks is module that can provide useful insights into not only network organizations but also functional behaviors between their components. Comprehensive efforts have been devoted to investigating cohesive modules in the past decade. However, it is still not clear whether there are important structural characteristics of the nodes that do not belong to any cohesive module. In order to answer this question, we performed a large-scale analysis on 25 complex networks with different types and scales using our recently developed BTS (bintree seeking) algorithm, which is able to detect both cohesive and sparse modules in the network. Our results reveal that the sparse modules composed by the cohesively isolated nodes widely co-exist with the cohesive modules. Detailed analysis shows that both types of modules provide better characterization for the division of a network into functional units than merely cohesive modules, because the sparse modules possibly re-organize the nodes in the so-called cohesive modules, which lack obvious modular significance, into meaningful groups. Compared with cohesive modules, the sizes of sparse ones are generally smaller. Sparse modules are also found to have preferences in social and biological networks than others. PMID:23762457

Default and Executive Network Coupling Supports Creative Idea Production

PubMed Central

Beaty, Roger E.; Benedek, Mathias; Barry Kaufman, Scott; Silvia, Paul J.

2015-01-01

The role of attention in creative cognition remains controversial. Neuroimaging studies have reported activation of brain regions linked to both cognitive control and spontaneous imaginative processes, raising questions about how these regions interact to support creative thought. Using functional magnetic resonance imaging (fMRI), we explored this question by examining dynamic interactions between brain regions during a divergent thinking task. Multivariate pattern analysis revealed a distributed network associated with divergent thinking, including several core hubs of the default (posterior cingulate) and executive (dorsolateral prefrontal cortex) networks. The resting-state network affiliation of these regions was confirmed using data from an independent sample of participants. Graph theory analysis assessed global efficiency of the divergent thinking network, and network efficiency was found to increase as a function of individual differences in divergent thinking ability. Moreover, temporal connectivity analysis revealed increased coupling between default and salience network regions (bilateral insula) at the beginning of the task, followed by increased coupling between default and executive network regions at later stages. Such dynamic coupling suggests that divergent thinking involves cooperation between brain networks linked to cognitive control and spontaneous thought, which may reflect focused internal attention and the top-down control of spontaneous cognition during creative idea production. PMID:26084037

Molecular cloning and expression analysis of five heat shock protein 70 (HSP70) family members in Lateolabrax maculatus with Vibrio harveyi infection.

PubMed

Han, Ying-Li; Hou, Cong-Cong; Du, Chen; Zhu, Jun-Quan

2017-01-01

Heat shock proteins 70 (HSP70s) are molecular chaperones that aid in protection against environmental stress. In this study, we cloned and characterized five members of the HSP70 family (designated as HSPa1a, HSC70-1, HSC70-2, HSPa4 and HSPa14) from Lateolabrax maculatus using rapid amplification cDNA ends (RACE). Multiple sequence alignment and structural analysis revealed that all members of the HSP70 family had a conserved domain architecture, with some distinguishing features unique to each HSP70. Quantitative real-time (qPCR) analysis revealed that all members of the HSP70 family were ubiquitously and differentially expressed in all major types of tissues, including testicular tissue. This indicated that HSP70s have vital and conserved biological functions, and may also function in the development of germinal cells. The expression of mRNA of the five HSP70 family members mRNA expression was significantly increased in the head kidney, intestine and gill after Vibrio harveyi challenge, suggesting that HSP70s play an important role in the immune response. Copyright © 2016 Elsevier Ltd. All rights reserved.

Peptidomic analysis of human cell lines

PubMed Central

Gelman, Julia S.; Sironi, Juan; Castro, Leandro M.; Ferro, Emer S.; Fricker, Lloyd D.

2011-01-01

Peptides have been proposed to function in intracellular signaling within the cytosol. Although cytosolic peptides are considered to be highly unstable, a large number of peptides have been detected in mouse brain and other biological samples. In the present study, we evaluated the peptidome of three diverse cell lines: SH-SY5Y, MCF7, and HEK293 cells. A comparison of the peptidomes revealed considerable overlap in the identity of the peptides found in each cell line. The majority of the observed peptides are not derived from the most abundant or least stable proteins in the cell, and approximately half of the cellular peptides correspond to the N- or C- termini of the precursor proteins. Cleavage site analysis revealed a preference for hydrophobic residues in the P1 position. Quantitative peptidomic analysis indicated that the levels of most cellular peptides are not altered in response to elevated intracellular calcium, suggesting that calpain is not responsible for their production. The similarity of the peptidomes of the three cell lines and the lack of correlation with the predicted cellular degradome implies the selective formation or retention of these peptides, consistent with the hypothesis that they are functional in the cells. PMID:21204522

Flexible modulation of network connectivity related to cognition in Alzheimer's disease.

PubMed

McLaren, Donald G; Sperling, Reisa A; Atri, Alireza

2014-10-15

Functional neuroimaging tools, such as fMRI methods, may elucidate the neural correlates of clinical, behavioral, and cognitive performance. Most functional imaging studies focus on regional task-related activity or resting state connectivity rather than how changes in functional connectivity across conditions and tasks are related to cognitive and behavioral performance. To investigate the promise of characterizing context-dependent connectivity-behavior relationships, this study applies the method of generalized psychophysiological interactions (gPPI) to assess the patterns of associative-memory-related fMRI hippocampal functional connectivity in Alzheimer's disease (AD) associated with performance on memory and other cognitively demanding neuropsychological tests and clinical measures. Twenty-four subjects with mild AD dementia (ages 54-82, nine females) participated in a face-name paired-associate encoding memory study. Generalized PPI analysis was used to estimate the connectivity between the hippocampus and the whole brain during encoding. The difference in hippocampal-whole brain connectivity between encoding novel and encoding repeated face-name pairs was used in multiple-regression analyses as an independent predictor for 10 behavioral, neuropsychological and clinical tests. The analysis revealed connectivity-behavior relationships that were distributed, dynamically overlapping, and task-specific within and across intrinsic networks; hippocampal-whole brain connectivity-behavior relationships were not isolated to single networks, but spanned multiple brain networks. Importantly, these spatially distributed performance patterns were unique for each measure. In general, out-of-network behavioral associations with encoding novel greater than repeated face-name pairs hippocampal-connectivity were observed in the default-mode network, while correlations with encoding repeated greater than novel face-name pairs hippocampal-connectivity were observed in the executive control network (p<0.05, cluster corrected). Psychophysiological interactions revealed significantly more extensive and robust associations between paired-associate encoding task-dependent hippocampal-whole brain connectivity and performance on memory and behavioral/clinical measures than previously revealed by standard activity-behavior analysis. Compared to resting state and task-activation methods, gPPI analyses may be more sensitive to reveal additional complementary information regarding subtle within- and between-network relations. The patterns of robust correlations between hippocampal-whole brain connectivity and behavioral measures identified here suggest that there are 'coordinated states' in the brain; that the dynamic range of these states is related to behavior and cognition; and that these states can be observed and quantified, even in individuals with mild AD. Copyright © 2014 Elsevier Inc. All rights reserved.

Skeletal effects in Angle Class II/1 patients treated with the functional regulator type II : Cephalometric and tensor analysis.

PubMed

Schulz, Simone; Koos, Bernd; Duske, Kathrin; Stahl, Franka

2016-11-01

The purpose of this work was to employ both cephalometric and tensor analysis in characterizing the skeletal changes experienced by patients with Angle Class II/1 malocclusion during functional orthodontic treatment with the functional regulator type II. A total of 23 patients with Class II/1 malocclusion based on lateral cephalograms obtained before and after treatment with the functional regulator type II were analyzed. Another 23 patients with Angle Class II/1 malocclusion who had not undergone treatment were included as controls. Our cephalometric data attest to significant therapeutic effects of the functional regulator type II on the skeletal mandibular system, including significant advancement of the mandible, increases in effective mandibular length with enhancement of the chin profile, and reduction of growth-related bite deepening. No treatment-related effects were observed at the cranial-base and midface levels. In addition, tensor analysis revealed significant stimulation of mandibular growth in sagittal directions, without indications of growth effects on the maxilla. Its growth-pattern findings differed from those of cephalometric analysis by indicating that the appliance did promote horizontal development, which supports the functional orthodontic treatment effect in Angle Class II/1 cases. Tensor analysis yielded additional insights into sagittal and vertical growth changes not identifiable by strictly cephalometric means. The functional regulator type II was an effective treatment modality for Angle Class II/1 malocclusion and influenced the skeletal development of these patients in favorable ways.

Left dorsolateral prefrontal cortex atrophy is associated with frontal lobe function in Alzheimer's disease and contributes to caregiver burden.

PubMed

Matsuoka, Kiwamu; Yasuno, Fumihiko; Hashimoto, Akiko; Miyasaka, Toshiteru; Takahashi, Masato; Kiuchi, Kuniaki; Iida, Junzo; Kichikawa, Kimihiko; Kishimoto, Toshifumi

2018-05-01

Caregivers of patients with dementia experience physical and mental deterioration. We have previously reported a correlation between caregiver burden and the Frontal Assessment Battery (FAB) total scores of patients with Alzheimer's disease (AD), especially regarding the dependency factor from the Zarit Burden Interview. The present study aimed to identify an objective biomarker for predicting caregiver burden. The participants were 26 pairs of caregivers and patients with AD and mild-to-moderate dementia. Correlations between regional gray matter volumes in the patients with AD and the FAB total scores were explored by using whole-brain voxel-based morphometric analysis. Path analysis was used to estimate the relationships between regional gray matter volumes, FAB total scores, and caregiver burden based on the Zarit Burden Interview. The voxel-based morphometric revealed a significant positive correlation between the FAB total scores and the volume of the left dorsolateral prefrontal cortex. This positive correlation persisted after controlling for the effect of general cognitive dysfunction, which was assessed by using the Mini-Mental State Examination. Path analysis revealed that decreases in FAB scores, caused by reduced frontal lobe volumes, negatively affected caregiver burden. The present study revealed that frontal lobe function, based on FAB scores, was affected by the volume of the left dorsolateral prefrontal cortex. Decreased scores were associated with greater caregiver burden, especially for the dependency factor. These findings may facilitate the development of an objective biomarker for predicting caregiver burden. Copyright © 2017 John Wiley & Sons, Ltd.

Abundance and Diversity of Bacterial Nitrifiers and Denitrifiers and Their Functional Genes in Tannery Wastewater Treatment Plants Revealed by High-Throughput Sequencing

PubMed Central

Wang, Zhu; Zhang, Xu-Xiang; Lu, Xin; Liu, Bo; Li, Yan; Long, Chao; Li, Aimin

2014-01-01

Biological nitrification/denitrification is frequently used to remove nitrogen from tannery wastewater containing high concentrations of ammonia. However, information is limited about the bacterial nitrifiers and denitrifiers and their functional genes in tannery wastewater treatment plants (WWTPs) due to the low-throughput of the previously used methods. In this study, 454 pyrosequencing and Illumina high-throughput sequencing, combined with molecular methods, were used to comprehensively characterize structures and functions of nitrification and denitrification bacterial communities in aerobic and anaerobic sludge of two full-scale tannery WWTPs. Pyrosequencing of 16S rRNA genes showed that Proteobacteria and Synergistetes dominated in the aerobic and anaerobic sludge, respectively. Ammonia-oxidizing bacteria (AOB) amoA gene cloning revealed that Nitrosomonas europaea dominated the ammonia-oxidizing community in the WWTPs. Metagenomic analysis showed that the denitrifiers mainly included the genera of Thauera, Paracoccus, Hyphomicrobium, Comamonas and Azoarcus, which may greatly contribute to the nitrogen removal in the two WWTPs. It is interesting that AOB and ammonia-oxidizing archaea had low abundance although both WWTPs demonstrated high ammonium removal efficiency. Good correlation between the qPCR and metagenomic analysis is observed for the quantification of functional genes amoA, nirK, nirS and nosZ, indicating that the metagenomic approach may be a promising method used to comprehensively investigate the abundance of functional genes of nitrifiers and denitrifiers in the environment. PMID:25420093

[EMD Time-Frequency Analysis of Raman Spectrum and NIR].

PubMed

Zhao, Xiao-yu; Fang, Yi-ming; Tan, Feng; Tong, Liang; Zhai, Zhe

2016-02-01

This paper analyzes the Raman spectrum and Near Infrared Spectrum (NIR) with time-frequency method. The empirical mode decomposition spectrum becomes intrinsic mode functions, which the proportion calculation reveals the Raman spectral energy is uniform distributed in each component, while the NIR's low order intrinsic mode functions only undertakes fewer primary spectroscopic effective information. Both the real spectrum and numerical experiments show that the empirical mode decomposition (EMD) regard Raman spectrum as the amplitude-modulated signal, which possessed with high frequency adsorption property; and EMD regards NIR as the frequency-modulated signal, which could be preferably realized high frequency narrow-band demodulation during first-order intrinsic mode functions. The first-order intrinsic mode functions Hilbert transform reveals that during the period of empirical mode decomposes Raman spectrum, modal aliasing happened. Through further analysis of corn leaf's NIR in time-frequency domain, after EMD, the first and second orders components of low energy are cut off, and reconstruct spectral signal by using the remaining intrinsic mode functions, the root-mean-square error is 1.001 1, and the correlation coefficient is 0.981 3, both of these two indexes indicated higher accuracy in re-construction; the decomposition trend term indicates the absorbency is ascending along with the decreasing to wave length in the near-infrared light wave band; and the Hilbert transform of characteristic modal component displays, 657 cm⁻¹ is the specific frequency by the corn leaf stress spectrum, which could be regarded as characteristic frequency for identification.

Deep transcriptome sequencing provides new insights into the structural and functional organization of the wheat genome.

PubMed

Pingault, Lise; Choulet, Frédéric; Alberti, Adriana; Glover, Natasha; Wincker, Patrick; Feuillet, Catherine; Paux, Etienne

2015-02-10

Because of its size, allohexaploid nature, and high repeat content, the bread wheat genome is a good model to study the impact of the genome structure on gene organization, function, and regulation. However, because of the lack of a reference genome sequence, such studies have long been hampered and our knowledge of the wheat gene space is still limited. The access to the reference sequence of the wheat chromosome 3B provided us with an opportunity to study the wheat transcriptome and its relationships to genome and gene structure at a level that has never been reached before. By combining this sequence with RNA-seq data, we construct a fine transcriptome map of the chromosome 3B. More than 8,800 transcription sites are identified, that are distributed throughout the entire chromosome. Expression level, expression breadth, alternative splicing as well as several structural features of genes, including transcript length, number of exons, and cumulative intron length are investigated. Our analysis reveals a non-monotonic relationship between gene expression and structure and leads to the hypothesis that gene structure is determined by its function, whereas gene expression is subject to energetic cost. Moreover, we observe a recombination-based partitioning at the gene structure and function level. Our analysis provides new insights into the relationships between gene and genome structure and function. It reveals mechanisms conserved with other plant species as well as superimposed evolutionary forces that shaped the wheat gene space, likely participating in wheat adaptation.

Investigation of phonon transport and thermal boundary conductance at the interface of functionalized SWCNT and poly (ether-ketone)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Haoxiang; Kumar, Satish, E-mail: satish.kumar@me.gatech.edu; Chen, Liang

2016-09-07

Carbon nanostructures such as carbon nanotube (CNT), graphene, and carbon fibers can be used as fillers in amorphous polymers to improve their thermal properties. In this study, the effect of covalent bonding of CNT with poly(ether ketone) (PEK) on interfacial thermal interactions is investigated using non-equilibrium molecular dynamics simulations. The number of covalent bonds between (20, 20) CNT and PEK is varied in the range of 0–80 (0%–6.25%), and the thermal boundary conductance is computed. The analysis reveals that covalent functionalization of CNT atoms can enhance the thermal boundary conductance by an order of magnitude compared to the non-functionalized CNT-PEKmore » interface at a high degree of CNT functionalization. Besides strengthening the thermal coupling, covalent functionalization is also shown to modify the phonon spectra of CNT. The transient spectral energy analysis shows that the crosslinks cause faster energy exchange from CNT to PEK in different frequency bands. The oxygen atom of hydroxyl group of PEK contributes energy transfer in the low frequency band, while aromatic and carbonyl carbon atoms play a more significant role in high frequency bands. In addition, by analyzing the relaxation time of the spectral temperature of different frequency bands of CNT, it is revealed that with increasing number of bonds, both lower frequency vibrational modes and higher frequency modes efficiently couple across the CNT-PEK interface and contribute in thermal energy transfer from CNT to the matrix.« less

A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma.

PubMed

Palumbo, Tiziana; Poultsides, George A; Kouraklis, Grigorios; Liakakos, Theodore; Drakaki, Alexandra; Peros, George; Hatziapostolou, Maria; Iliopoulos, Dimitrios

2016-06-03

Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo. A functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors. The screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas. Taken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma.

Aberrant functional brain connectome in people with antisocial personality disorder

PubMed Central

Tang, Yan; Long, Jun; Wang, Wei; Liao, Jian; Xie, Hua; Zhao, Guihu; Zhang, Hao

2016-01-01

Antisocial personality disorder (ASPD) is characterised by a disregard for social obligations and callous unconcern for the feelings of others. Studies have demonstrated that ASPD is associated with abnormalities in brain regions and aberrant functional connectivity. In this paper, topological organisation was examined in resting-state fMRI data obtained from 32 ASPD patients and 32 non-ASPD controls. The frequency-dependent functional networks were constructed using wavelet-based correlations over 90 brain regions. The topology of the functional networks of ASPD subjects was analysed via graph theoretical analysis. Furthermore, the abnormal functional connectivity was determined with a network-based statistic (NBS) approach. Our results revealed that, compared with the controls, the ASPD patients exhibited altered topological configuration of the functional connectome in the frequency interval of 0.016–0.031 Hz, as indicated by the increased clustering coefficient and decreased betweenness centrality in the medial superior frontal gyrus, precentral gyrus, Rolandic operculum, superior parietal gyrus, angular gyrus, and middle temporal pole. In addition, the ASPD patients showed increased functional connectivity mainly located in the default-mode network. The present study reveals an aberrant topological organisation of the functional brain network in individuals with ASPD. Our findings provide novel insight into the neuropathological mechanisms of ASPD. PMID:27257047

Aberrant functional brain connectome in people with antisocial personality disorder.

PubMed

Tang, Yan; Long, Jun; Wang, Wei; Liao, Jian; Xie, Hua; Zhao, Guihu; Zhang, Hao

2016-06-03

Antisocial personality disorder (ASPD) is characterised by a disregard for social obligations and callous unconcern for the feelings of others. Studies have demonstrated that ASPD is associated with abnormalities in brain regions and aberrant functional connectivity. In this paper, topological organisation was examined in resting-state fMRI data obtained from 32 ASPD patients and 32 non-ASPD controls. The frequency-dependent functional networks were constructed using wavelet-based correlations over 90 brain regions. The topology of the functional networks of ASPD subjects was analysed via graph theoretical analysis. Furthermore, the abnormal functional connectivity was determined with a network-based statistic (NBS) approach. Our results revealed that, compared with the controls, the ASPD patients exhibited altered topological configuration of the functional connectome in the frequency interval of 0.016-0.031 Hz, as indicated by the increased clustering coefficient and decreased betweenness centrality in the medial superior frontal gyrus, precentral gyrus, Rolandic operculum, superior parietal gyrus, angular gyrus, and middle temporal pole. In addition, the ASPD patients showed increased functional connectivity mainly located in the default-mode network. The present study reveals an aberrant topological organisation of the functional brain network in individuals with ASPD. Our findings provide novel insight into the neuropathological mechanisms of ASPD.

Differential expression pattern of UBX family genes in Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamauchi, Seiji; Sasagawa, Yohei; Ogura, Teru

2007-06-29

UBX (ubiquitin regulatory X)-containing proteins belong to an evolutionary conserved protein family and determine the specificity of p97/VCP/Cdc48p function by binding as its adaptors. Caenorhabditis elegans was found to possess six UBX-containing proteins, named UBXN-1 to -6. However, no general or specific function of them has been revealed. During the course of understanding not only their function but also specified function of p97, we investigated spatial and temporal expression patterns of six ubxn genes in this study. Transcript analyses showed that the expression pattern of each ubxn gene was different throughout worm's development and may show potential developmental dynamics inmore » their function, especially ubxn-5 was expressed specifically in the spermatogenic germline, suggesting a crucial role in spermatogenesis. In addition, as ubxn-4 expression was induced by ER stress, it would function as an ERAD factor in C. elegans. In vivo expression analysis by using GFP translational fusion constructs revealed that six ubxn genes show distinct expression patterns. These results altogether demonstrate that the expression of all six ubxn genes of C. elegans is differently regulated.« less

A high throughput mutagenic analysis of yeast sumo structure and function

PubMed Central

Newman, Heather A.; Lu, Jian; Carson, Caryn; Boeke, Jef D.

2017-01-01

Sumoylation regulates a wide range of essential cellular functions through diverse mechanisms that remain to be fully understood. Using S. cerevisiae, a model organism with a single essential SUMO gene (SMT3), we developed a library of >250 mutant strains with single or multiple amino acid substitutions of surface or core residues in the Smt3 protein. By screening this library using plate-based assays, we have generated a comprehensive structure-function based map of Smt3, revealing essential amino acid residues and residues critical for function under a variety of genotoxic and proteotoxic stress conditions. Functionally important residues mapped to surfaces affecting Smt3 precursor processing and deconjugation from protein substrates, covalent conjugation to protein substrates, and non-covalent interactions with E3 ligases and downstream effector proteins containing SUMO-interacting motifs. Lysine residues potentially involved in formation of polymeric chains were also investigated, revealing critical roles for polymeric chains, but redundancy in specific chain linkages. Collectively, our findings provide important insights into the molecular basis of signaling through sumoylation. Moreover, the library of Smt3 mutants represents a valuable resource for further exploring the functions of sumoylation in cellular stress response and other SUMO-dependent pathways. PMID:28166236

Psychosocial functioning in adolescents with complex partial seizures.

PubMed

Elliott, I

1992-03-01

This pilot study examined psychosocial functioning in adolescents (age 12.5-18.5 years) with complex partial seizures. Twenty-five subjects were divided into three groups: Group I (N = 11), medically treated with uncontrolled seizures; Group II (N = 6), medically managed with controlled seizures; and Group III (N = 8), epilepsy refractory to medical management with seizure control following surgery. Psychosocial functioning was measured using the "Adolescent Psychosocial Inventory" of Batzel and Dodrill. Findings revealed significant differences (F 4.80. p less than 0.02) in psychosocial functioning between the three groups. Group I showed the poorest overall adjustment; Group II, the best adjustment; Group III was better adjusted than Group I, but less than Group II. Significant difficulties were evident in the areas of school, interpersonal, emotional, seizure adjustment and overall psychosocial functioning in Group III. No problems were evident in Group II. School, emotional and overall adjustment were moderately problematic in Group III. Analysis of biological and demographic data revealed a significant association between increased numbers of medications and poorer psychosocial functioning (r = 58, p less than 0.02). The study results provide direction for clinic and community nurse specialists to set priorities with regard to assessment and supportive interventions.

Drosophila Pelle phosphorylates Dichaete protein and influences its subcellular distribution in developing oocytes.

PubMed

Mutsuddi, Mousumi; Mukherjee, Ashim; Shen, Baohe; Manley, James L; Nambu, John R

2010-01-01

The Drosophila Dichaete gene encodes a member of the Sox family of high mobility group (HMG) domain proteins that have crucial gene regulatory functions in diverse developmental processes. The subcellular localization and transcriptional regulatory activities of Sox proteins can be regulated by several post-translational modifications. To identify genes that functionally interact with Dichaete, we undertook a genetic modifier screen based on a Dichaete gain-of-function phenotype in the adult eye. Mutations in several genes, including decapentaplegic, engrailed and pelle, behaved as dominant modifiers of this eye phenotype. Further analysis of pelle mutants revealed that loss of pelle function results in alterations in the distinctive cytoplasmic distribution of Dichaete protein within the developing oocyte, as well as defects in the elaboration of individual egg chambers. The death domain-containing region of the Pelle protein kinase was found to associate with both Dichaete and mouse Sox2 proteins, and Pelle can phosphorylate Dichaete protein in vitro. Overall, these findings reveal that maternal functions of pelle are essential for proper localization of Dichaete protein in the oocyte and normal egg chamber formation. Dichaete appears to be a novel phosphorylation substrate for Pelle and may function in a Pelle-dependent signaling pathway during oogenesis.

IFN-γ-mediated induction of an apical IL-10 receptor on polarized intestinal epithelia.

PubMed

Kominsky, Douglas J; Campbell, Eric L; Ehrentraut, Stefan F; Wilson, Kelly E; Kelly, Caleb J; Glover, Louise E; Collins, Colm B; Bayless, Amanda J; Saeedi, Bejan; Dobrinskikh, Evgenia; Bowers, Brittelle E; MacManus, Christopher F; Müller, Werner; Colgan, Sean P; Bruder, Dunja

2014-02-01

Cytokines secreted at sites of inflammation impact the onset, progression, and resolution of inflammation. In this article, we investigated potential proresolving mechanisms of IFN-γ in models of inflammatory bowel disease. Guided by initial microarray analysis, in vitro studies revealed that IFN-γ selectively induced the expression of IL-10R1 on intestinal epithelia. Further analysis revealed that IL-10R1 was expressed predominantly on the apical membrane of polarized epithelial cells. Receptor activation functionally induced canonical IL-10 target gene expression in epithelia, concomitant with enhanced barrier restitution. Furthermore, knockdown of IL-10R1 in intestinal epithelial cells results in impaired barrier function in vitro. Colonic tissue isolated from murine colitis revealed that levels of IL-10R1 and suppressor of cytokine signaling 3 were increased in the epithelium and coincided with increased tissue IFN-γ and IL-10 cytokines. In parallel, studies showed that treatment of mice with rIFN-γ was sufficient to drive expression of IL-10R1 in the colonic epithelium. Studies of dextran sodium sulfate colitis in intestinal epithelial-specific IL-10R1-null mice revealed a remarkable increase in disease susceptibility associated with increased intestinal permeability. Together, these results provide novel insight into the crucial and underappreciated role of epithelial IL-10 signaling in the maintenance and restitution of epithelial barrier and of the temporal regulation of these pathways by IFN-γ.

Impact of medications on cognitive function in obstructive sleep apnea syndrome.

PubMed

Lal, Chitra; Siddiqi, Nasar; Kumbhare, Suchit; Strange, Charlie

2015-09-01

Medications can impact cognitive function. Obstructive sleep apnea syndrome (OSAS) is associated with cognitive impairment. There is currently a paucity of data evaluating the impact of medications on sleep architecture and cognition in untreated OSAS. Our objective was to evaluate the impact of obstructive sleep apnea syndrome (OSAS) and medications on cognition by a screening questionnaire called the Mail-In Cognitive Function Screening Instrument (MCFSI). We conducted a retrospective chart review on consecutive adults (age > 18 years) with OSAS seen in Medical University of South Carolina Sleep Clinic between January 1, 2012 and May 8, 2013, for whom the Mail-In Cognitive Function Screening Instrument (MCFSI) score was available and who were not on continuous positive airway pressure (CPAP). The correlation between different medications, sleep study variables, and MCFSI scores was studied. Univariate analysis revealed that many medications had significant correlations with MCFSI scores, including antidepressants (p = 0.05), antipsychotics (p = 0.01), anxiolytics (p = 0.005), statins (p = 0.077) and narcotics (p = 0.006). The mean percentage of rapid eye movement (REM) sleep (p = 0.04) and Epworth Sleepiness Scale (p = 0.01) were also significantly correlated with MCFSI scores. Multivariate analysis revealed that Epworth Sleepiness Scale and use of antipsychotics, narcotics, and anxiolytics correlated with higher MCFSI scores (worse cognition) and conversely that statin use was associated with improved cognition. Medications have a significant impact on cognitive function in OSAS. Thus, medication use should be considered in future studies of cognitive function in patients with OSAS.

Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity*

PubMed Central

Chen, Ying; Yang, Li-Na; Cheng, Li; Tu, Shun; Guo, Shu-Juan; Le, Huang-Ying; Xiong, Qian; Mo, Ran; Li, Chong-Yang; Jeong, Jun-Seop; Jiang, Lizhi; Blackshaw, Seth; Bi, Li-Jun; Zhu, Heng; Tao, Sheng-Ce; Ge, Feng

2013-01-01

Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach. PMID:23824909

Functional Relationships for Investigating Cognitive Processes

PubMed Central

Wright, Anthony A.

2013-01-01

Functional relationships (from systematic manipulation of critical variables) are advocated for revealing fundamental processes of (comparative) cognition—through examples from my work in psychophysics, learning, and memory. Functional relationships for pigeon wavelength (hue) discrimination revealed best discrimination at the spectral points of hue transition for pigeons—a correspondence (i.e., functional relationship) similar to that for humans. Functional relationships for learning revealed: Item-specific or relational learning in matching to sample as a function of the pigeons’ sample-response requirement, and same/different abstract-concept learning as a function of the training set size for rhesus monkeys, capuchin monkeys, and pigeons. Functional relationships for visual memory revealed serial position functions (a 1st order functional relationship) that changed systematically with retention delay (a 2nd order relationship) for pigeons, capuchin monkeys, rhesus monkeys, and humans. Functional relationships for rhesus-monkey auditory memory also revealed systematic changes in serial position functions with delay, but these changes were opposite to those for visual memory. Functional relationships for proactive interference revealed interference that varied as a function of a ratio of delay times. Functional relationships for change detection memory revealed (qualitative) similarities and (quantitative) differences in human and monkey visual short term memory as a function of the number of memory items. It is concluded that these findings were made possible by varying critical variables over a substantial portion of the manipulable range to generate functions and derive relationships. PMID:23174335

Striatal functional connectivity changes following specific balance training in elderly people: MRI results of a randomized controlled pilot study.

PubMed

Magon, Stefano; Donath, Lars; Gaetano, Laura; Thoeni, Alain; Radue, Ernst-Wilhelm; Faude, Oliver; Sprenger, Till

2016-09-01

Practice-induced effects of specific balance training on brain structure and activity in elderly people are largely unknown. In the present study, we investigated morphological and functional brain changes following slacking training (balancing over nylon ribbons) in a group of elderly people. Twenty-eight healthy volunteers were recruited and randomly assigned to the intervention (mean age: 62.3±5.4years) or control group (mean age: 61.8±5.3years). The intervention group completed six-weeks of slackline training. Brain morphological changes were investigated using voxel-based morphometry and functional connectivity changes were computed via independent component analysis and seed-based analyses. All analyses were applied to the whole sample and to a subgroup of participants who improved in slackline performance. The repeated measures analysis of variance showed a significant interaction effect between groups and sessions. Specifically, the Tukey post-hoc analysis revealed a significantly improved slackline standing performance after training for the left leg stance time (pre: 4.5±3.6s vs. 26.0±30.0s, p<0.038) as well as for tandem stance time (pre: 1.4±0.6s vs. post: 4.5±4.0s, p=0.003) in the intervention group. No significant changes in balance performance were observed in the control group. The MRI analysis did not reveal morphological or functional connectivity differences before or after the training between the intervention and control groups (whole sample). However, subsequent analysis in subjects with improved slackline performance showed a decrease of connectivity between the striatum and other brain areas during the training period. These preliminary results suggest that improved balance performance with slackline training goes along with an increased efficiency of the striatal network. Copyright © 2016 Elsevier B.V. All rights reserved.

Systems Genetics Analysis of GWAS reveals Novel Associations between Key Biological Processes and Coronary Artery Disease

PubMed Central

Ghosh, Sujoy; Vivar, Juan; Nelson, Christopher P; Willenborg, Christina; Segrè, Ayellet V; Mäkinen, Ville-Petteri; Nikpay, Majid; Erdmann, Jeannette; Blankenberg, Stefan; O'Donnell, Christopher; März, Winfried; Laaksonen, Reijo; Stewart, Alexandre FR; Epstein, Stephen E; Shah, Svati H; Granger, Christopher B; Hazen, Stanley L; Kathiresan, Sekar; Reilly, Muredach P; Yang, Xia; Quertermous, Thomas; Samani, Nilesh J; Schunkert, Heribert; Assimes, Themistocles L; McPherson, Ruth

2016-01-01

Objective Genome-wide association (GWA) studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks. Approaches and Results Employing pathways (gene sets) from Reactome, we carried out a two-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CADGWAS data sets (9,889 cases/11,089 controls), nominally significant gene-sets were tested for replication in a meta-analysis of 9 additional studies (15,502 cases/55,730 controls) from the CARDIoGRAM Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication p<0.05). These pathways resided in 9 of 21 core biological processes represented in Reactome, and included pathways relevant to extracellular matrix integrity, innate immunity, axon guidance, and signaling by PDRF, NOTCH, and the TGF-β/SMAD receptor complex. Many of these pathways had strengths of association comparable to those observed in lipid transport pathways. Network analysis of unique genes within the replicated pathways further revealed several interconnected functional and topologically interacting modules representing novel associations (e.g. semaphorin regulated axonal guidance pathway) besides confirming known processes (lipid metabolism). The connectivity in the observed networks was statistically significant compared to random networks (p<0.001). Network centrality analysis (‘degree’ and ‘betweenness’) further identified genes (e.g. NCAM1, FYN, FURIN etc.) likely to play critical roles in the maintenance and functioning of several of the replicated pathways. Conclusions These findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD. PMID:25977570

Feminist Research Methodology Groups: Origins, Forms, Functions.

ERIC Educational Resources Information Center

Reinharz, Shulamit

Feminist Research Methodology Groups (FRMGs) have developed as a specific type of women's group in which feminist academics can find supportive audiences for their work while contributing to a feminist redefinition of research methods. An analysis of two FRMGs reveals common characteristics, dynamics, and outcomes. Both were limited to small…

Phylogenetic and Protein Sequence Analysis of Bacterial Chemoreceptors.

PubMed

Ortega, Davi R; Zhulin, Igor B

2018-01-01

Identifying chemoreceptors in sequenced bacterial genomes, revealing their domain architecture, inferring their evolutionary relationships, and comparing them to chemoreceptors of known function become important steps in genome annotation and chemotaxis research. Here, we describe bioinformatics procedures that enable such analyses, using two closely related bacterial genomes as examples.

Analysis of Globodera rostochiensis effectors reveals conserved functions of SPRYSEC proteins in suppressing and eliciting plant immune responses

USDA-ARS?s Scientific Manuscript database

Potato cyst nematodes (PCNs), including Globodera rostochiensis (Woll.), are important pests of potato. Plant parasitic nematodes produce multiple effector proteins, secreted from their stylets, to successfully infect their hosts. These include proteins that are delivered to the apoplast, as well as...

Meta-analysis of Gene Expression in the Mouse Liver Reveals Biomarkers Associated with Inflammation Increased Early During Aging

EPA Science Inventory

Aging is associated with a predictable loss of cellular homeostasis, a decline in physiological function and an increase in various diseases. We hypothesized that similar age-related gene expression profiles would be observed in mice across independent studies. Employing a metaan...

Transcriptome analysis revealed anti-obesity effects of the alginate polysaccharide in high-fat diet-induced obese mice

USDA-ARS?s Scientific Manuscript database

The polysaccharide alginate (Alg) extracted from brown seaweeds possesses numerous bioactivities. We hypothesized that Alg intake may alleviate high-fat diet (HFD)- induced obesity and chronic metabolism symptoms by strengthening the bio-functionality of the intestine, especially in the colon. A tot...

Pichia stipitis genomics, transcriptomics, and gene clusters

Treesearch

Thomas W. Jeffries; Jennifer R. Headman Van Vleet

2009-01-01

Genome sequencing and subsequent global gene expression studies have advanced our understanding of the lignocellulose-fermenting yeast Pichia stipitis. These studies have provided an insight into its central carbon metabolism, and analysis of its genome has revealed numerous functional gene clusters and tandem repeats. Specialized physiological traits are often the...

Improvement of endothelial function by pitavastatin: a meta-analysis.

PubMed

Katsiki, Niki; Reiner, Željko; Tedeschi Reiner, Eugenia; Al-Rasadi, Khalid; Pirro, Matteo; Mikhailidis, Dimitri P; Sahebkar, Amirhossein

2018-02-01

Dyslipidemia is commonly associated with endothelial dysfunction and increased cardiovascular risk. Pitavastatin has been shown to reduce total and low-density lipoprotein cholesterol, to increase high-density lipoprotein (HDL)-cholesterol and improve HDL function. Furthermore, several trials explored its effects on flow-mediated dilation (FMD), as an index of endothelial function. The authors evaluated the effect of pitavastatin therapy on FMD. The authors performed a systematic review and meta-analysis of all clinical trials exploring the impact of pitavastatin on FMD. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Six eligible studies comprising 7 treatment arms were selected for this meta-analysis. Overall, WMD was significant for the effect of pitavastatin on FMD (2.45%, 95% CI: 1.31, 3.60, p < 0.001) and the effect size was robust in the leave-one-out sensitivity analysis. This meta-analysis of all available clinical trials revealed a significant increase of FMD induced by pitavastatin.

Interpreting Mammalian Evolution using Fugu Genome Comparisons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stubbs, L; Ovcharenko, I; Loots, G G

2004-04-02

Comparative sequence analysis of the human and the pufferfish Fugu rubripes (fugu) genomes has revealed several novel functional coding and noncoding regions in the human genome. In particular, the fugu genome has been extremely valuable for identifying transcriptional regulatory elements in human loci harboring unusually high levels of evolutionary conservation to rodent genomes. In such regions, the large evolutionary distance between human and fishes provides an additional filter through which functional noncoding elements can be detected with high efficiency.

Crystal structures of the F and pSLT plasmid TraJ N-terminal regions reveal similar homodimeric PAS folds with functional interchangeability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Jun; Wu, Ruiying; Adkins, Joshua N.

2014-09-16

In the F-family of conjugative plasmids, TraJ is an essential transcriptional activator of the tra operon that encodes most of the proteins required for conjugation. Here we report for the first time the X-ray crystal structures of the TraJ N-terminal regions from the prototypic F plasmid (TraJF11-130) and from the Salmonella virulence plasmid pSLT (TraJpSLT 1-128). Both proteins form similar homodimeric Per-ARNT-Sim (PAS) fold structures. Mutational analysis reveals that the observed dimeric interface is critical for TraJF transcriptional activation, indicating that dimerization of TraJ is required for its in vivo function. An artificial ligand (oxidized dithiothreitol) occupies a cavity inmore » the TraJF dimer interface, while a smaller cavity in corresponding region of the TraJpSLT structure lacks a ligand. Gas chromatography/mass spectrometry-electron ionization analysis of dithiothreitol-free TraJF suggests indole may be the natural TraJ ligand; however, disruption of the indole biosynthetic pathway does not affect TraJF function. Heterologous PAS domains from pSLT and R100 TraJ can functionally replace the TraJF PAS domain, suggesting that TraJ allelic specificity is mediated by the region C-terminal to the PAS domain.« less

Genome-wide expression analysis of soybean NF-Y genes reveals potential function in development and drought response.

PubMed

Quach, Truyen N; Nguyen, Hanh T M; Valliyodan, Babu; Joshi, Trupti; Xu, Dong; Nguyen, Henry T

2015-06-01

Nuclear factor-Y (NF-Y), a heterotrimeric transcription factor, is composed of NF-YA, NF-YB and NF-YC proteins. In plants, there are usually more than 10 genes for each family and their members have been identified to be key regulators in many developmental and physiological processes controlling gametogenesis, embryogenesis, nodule development, seed development, abscisic acid (ABA) signaling, flowering time, primary root elongation, blue light responses, endoplasmic reticulum (ER) stress response and drought tolerance. Taking the advantages of the recent soybean genome draft and information on functional characterizations of nuclear factor Y (NF-Y) transcription factor family in plants, we identified 21 GmNF-YA, 32 GmNF-YB, and 15 GmNF-YC genes in the soybean (Glycine max) genome. Phylogenetic analyses show that soybean's proteins share strong homology to Arabidopsis and many of them are closely related to functionally characterized NF-Y in plants. Expression analysis in various tissues of flower, leaf, root, seeds of different developmental stages, root hairs under rhizobium inoculation, and drought-treated roots and leaves revealed that certain groups of soybean NF-Y are likely involved in specific developmental and stress responses. This study provides extensive evaluation of the soybean NF-Y family and is particularly useful for further functional characterization of GmNF-Y proteins in seed development, nodulation and drought adaptation of soybean.

Polycomb purification by in vivo biotinylation tagging reveals cohesin and Trithorax group proteins as interaction partners

PubMed Central

Strübbe, Gero; Popp, Christian; Schmidt, Alexander; Pauli, Andrea; Ringrose, Leonie; Beisel, Christian; Paro, Renato

2011-01-01

The maintenance of specific gene expression patterns during cellular proliferation is crucial for the identity of every cell type and the development of tissues in multicellular organisms. Such a cellular memory function is conveyed by the complex interplay of the Polycomb and Trithorax groups of proteins (PcG/TrxG). These proteins exert their function at the level of chromatin by establishing and maintaining repressed (PcG) and active (TrxG) chromatin domains. Past studies indicated that a core PcG protein complex is potentially associated with cell type or even cell stage-specific sets of accessory proteins. In order to better understand the dynamic aspects underlying PcG composition and function we have established an inducible version of the biotinylation tagging approach to purify Polycomb and associated factors from Drosophila embryos. This system enabled fast and efficient isolation of Polycomb containing complexes under near physiological conditions, thereby preserving substoichiometric interactions. Novel interacting proteins were identified by highly sensitive mass spectrometric analysis. We found many TrxG related proteins, suggesting a previously unrecognized extent of molecular interaction of the two counteracting chromatin regulatory protein groups. Furthermore, our analysis revealed an association of PcG protein complexes with the cohesin complex and showed that Polycomb-dependent silencing of a transgenic reporter depends on cohesin function. PMID:21415365

Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.

PubMed

Zhang, Qunfeng; Liu, Meiya; Ruan, Jianyun

2017-03-20

As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.

Family functioning and trait emotional intelligence among youth.

PubMed

Alavi, Masoumeh; Mehrinezhad, Seyed Abolghasem; Amini, Mansour; Parthaman Singh, Minder Kaur A/P

2017-01-01

This study explored the relationship between family functioning and trait emotional intelligence among 547 respondents, between the age of 16 and 24 years from Malaysia, Iran, China, Sudan, Somalia, Morocco, the United Kingdom, Germany and the Netherlands. The questionnaires were Family Adaptability and Cohesion Evaluation Scale III and Trait Emotional Intelligence Questionnaire Short Form. Pearson correlation analysis revealed a significant relationship between family functioning and trait emotional intelligence. The higher the family functioning, the higher the trait emotional intelligence among youths. The findings provide a deeper understanding in the field of family functioning and trait emotional intelligence and have implications for parents, administrators and child relationships dealing with trait emotional intelligence.

Bioinformatic analysis of microRNA biogenesis and function related proteins in eleven animal genomes.

PubMed

Liu, Xiuying; Luo, GuanZheng; Bai, Xiujuan; Wang, Xiu-Jie

2009-10-01

MicroRNAs are approximately 22 nt long small non-coding RNAs that play important regulatory roles in eukaryotes. The biogenesis and functional processes of microRNAs require the participation of many proteins, of which, the well studied ones are Dicer, Drosha, Argonaute and Exportin 5. To systematically study these four protein families, we screened 11 animal genomes to search for genes encoding above mentioned proteins, and identified some new members for each family. Domain analysis results revealed that most proteins within the same family share identical or similar domains. Alternative spliced transcript variants were found for some proteins. We also examined the expression patterns of these proteins in different human tissues and identified other proteins that could potentially interact with these proteins. These findings provided systematic information on the four key proteins involved in microRNA biogenesis and functional pathways in animals, and will shed light on further functional studies of these proteins.

Integrated analysis of microRNA and gene expression profiles reveals a functional regulatory module associated with liver fibrosis.

PubMed

Chen, Wei; Zhao, Wenshan; Yang, Aiting; Xu, Anjian; Wang, Huan; Cong, Min; Liu, Tianhui; Wang, Ping; You, Hong

2017-12-15

Liver fibrosis, characterized with the excessive accumulation of extracellular matrix (ECM) proteins, represents the final common pathway of chronic liver inflammation. Ever-increasing evidence indicates microRNAs (miRNAs) dysregulation has important implications in the different stages of liver fibrosis. However, our knowledge of miRNA-gene regulation details pertaining to such disease remains unclear. The publicly available Gene Expression Omnibus (GEO) datasets of patients suffered from cirrhosis were extracted for integrated analysis. Differentially expressed miRNAs (DEMs) and genes (DEGs) were identified using GEO2R web tool. Putative target gene prediction of DEMs was carried out using the intersection of five major algorithms: DIANA-microT, TargetScan, miRanda, PICTAR5 and miRWalk. Functional miRNA-gene regulatory network (FMGRN) was constructed based on the computational target predictions at the sequence level and the inverse expression relationships between DEMs and DEGs. DAVID web server was selected to perform KEGG pathway enrichment analysis. Functional miRNA-gene regulatory module was generated based on the biological interpretation. Internal connections among genes in liver fibrosis-related module were determined using String database. MiRNA-gene regulatory modules related to liver fibrosis were experimentally verified in recombinant human TGFβ1 stimulated and specific miRNA inhibitor treated LX-2 cells. We totally identified 85 and 923 dysregulated miRNAs and genes in liver cirrhosis biopsy samples compared to their normal controls. All evident miRNA-gene pairs were identified and assembled into FMGRN which consisted of 990 regulations between 51 miRNAs and 275 genes, forming two big sub-networks that were defined as down-network and up-network, respectively. KEGG pathway enrichment analysis revealed that up-network was prominently involved in several KEGG pathways, in which "Focal adhesion", "PI3K-Akt signaling pathway" and "ECM-receptor interaction" were remarked significant (adjusted p<0.001). Genes enriched in these pathways coupled with their regulatory miRNAs formed a functional miRNA-gene regulatory module that contains 7 miRNAs, 22 genes and 42 miRNA-gene connections. Gene interaction analysis based on String database revealed that 8 out of 22 genes were highly clustered. Finally, we experimentally confirmed a functional regulatory module containing 5 miRNAs (miR-130b-3p, miR-148a-3p, miR-345-5p, miR-378a-3p, and miR-422a) and 6 genes (COL6A1, COL6A2, COL6A3, PIK3R3, COL1A1, CCND2) associated with liver fibrosis. Our integrated analysis of miRNA and gene expression profiles highlighted a functional miRNA-gene regulatory module associated with liver fibrosis, which, to some extent, may provide important clues to better understand the underlying pathogenesis of liver fibrosis. Copyright © 2017. Published by Elsevier B.V.

Multivariate functional response regression, with application to fluorescence spectroscopy in a cervical pre-cancer study.

PubMed

Zhu, Hongxiao; Morris, Jeffrey S; Wei, Fengrong; Cox, Dennis D

2017-07-01

Many scientific studies measure different types of high-dimensional signals or images from the same subject, producing multivariate functional data. These functional measurements carry different types of information about the scientific process, and a joint analysis that integrates information across them may provide new insights into the underlying mechanism for the phenomenon under study. Motivated by fluorescence spectroscopy data in a cervical pre-cancer study, a multivariate functional response regression model is proposed, which treats multivariate functional observations as responses and a common set of covariates as predictors. This novel modeling framework simultaneously accounts for correlations between functional variables and potential multi-level structures in data that are induced by experimental design. The model is fitted by performing a two-stage linear transformation-a basis expansion to each functional variable followed by principal component analysis for the concatenated basis coefficients. This transformation effectively reduces the intra-and inter-function correlations and facilitates fast and convenient calculation. A fully Bayesian approach is adopted to sample the model parameters in the transformed space, and posterior inference is performed after inverse-transforming the regression coefficients back to the original data domain. The proposed approach produces functional tests that flag local regions on the functional effects, while controlling the overall experiment-wise error rate or false discovery rate. It also enables functional discriminant analysis through posterior predictive calculation. Analysis of the fluorescence spectroscopy data reveals local regions with differential expressions across the pre-cancer and normal samples. These regions may serve as biomarkers for prognosis and disease assessment.

Single-trial EEG-informed fMRI analysis of emotional decision problems in hot executive function.

PubMed

Guo, Qian; Zhou, Tiantong; Li, Wenjie; Dong, Li; Wang, Suhong; Zou, Ling

2017-07-01

Executive function refers to conscious control in psychological process which relates to thinking and action. Emotional decision is a part of hot executive function and contains emotion and logic elements. As a kind of important social adaptation ability, more and more attention has been paid in recent years. Gambling task can be well performed in the study of emotional decision. As fMRI researches focused on gambling task show not completely consistent brain activation regions, this study adopted EEG-fMRI fusion technology to reveal brain neural activity related with feedback stimuli. In this study, an EEG-informed fMRI analysis was applied to process simultaneous EEG-fMRI data. First, relative power-spectrum analysis and K-means clustering method were performed separately to extract EEG-fMRI features. Then, Generalized linear models were structured using fMRI data and using different EEG features as regressors. The results showed that in the win versus loss stimuli, the activated regions almost covered the caudate, the ventral striatum (VS), the orbital frontal cortex (OFC), and the cingulate. Wide activation areas associated with reward and punishment were revealed by the EEG-fMRI integration analysis than the conventional fMRI results, such as the posterior cingulate and the OFC. The VS and the medial prefrontal cortex (mPFC) were found when EEG power features were performed as regressors of GLM compared with results entering the amplitudes of feedback-related negativity (FRN) as regressors. Furthermore, the brain region activation intensity was the strongest when theta-band power was used as a regressor compared with the other two fusion results. The EEG-based fMRI analysis can more accurately depict the whole-brain activation map and analyze emotional decision problems.

[Relationships between venomous function and innate immune function].

PubMed

Goyffon, Max; Saul, Frederick; Faure, Grazyna

2015-01-01

Venomous function is investigated in relation to innate immune function in two cases selected from scorpion venom and serpent venom. In the first case, structural analysis of scorpion toxins and defensins reveals a close interrelation between both functions (toxic and innate immune system function). In the second case, structural and functional studies of natural inhibitors of toxic snake venom phospholipases A2 reveal homology with components of the innate immune system, leading to a similar conclusion. Although there is a clear functional distinction between neurotoxins, which act by targeting membrane ion channels, and the circulating defensins which protect the organism from pathogens, the scorpion short toxins and defensins share a common protein folding scaffold with a conserved cysteine-stabilized alpha-beta motif of three disulfide bridges linking a short alpha helix and an antiparallel beta sheet. Genomic analysis suggests that these proteins share a common ancestor (long venom toxins were separated from an early gene family which gave rise to separate short toxin and defensin families). Furthermore, a scorpion toxin has been experimentally synthetized from an insect defensin, and an antibacterial scorpion peptide, androctonin (whose structure is similar to that of a cone snail venom toxin), was shown to have a similar high affinity for the postsynaptic acetylcholine receptor of Torpedo sp. Natural inhibitors of phospholipase A2 found in the blood of snakes are associated with the resistance of venomous snakes to their own highly neurotoxic venom proteins. Three classes of phospholipases A2 inhibitors (PLI-α, PLI-β, PLI-γ) have been identified. These inhibitors display diverse structural motifs related to innate immune proteins including carbohydrate recognition domains (CRD), leucine rich repeat domains (found in Toll-like receptors) and three finger domains, which clearly differentiate them from components of the adaptive immune system. Thus, in structure, function and phylogeny, venomous function in both vertebrates and invertebrates are clearly interrelated with innate immune function. © Société de Biologie, 2016.

Acetylome analysis reveals the involvement of lysine acetylation in photosynthesis and carbon metabolism in the model cyanobacterium Synechocystis sp. PCC 6803.

PubMed

Mo, Ran; Yang, Mingkun; Chen, Zhuo; Cheng, Zhongyi; Yi, Xingling; Li, Chongyang; He, Chenliu; Xiong, Qian; Chen, Hui; Wang, Qiang; Ge, Feng

2015-02-06

Cyanobacteria are the oldest known life form inhabiting Earth and the only prokaryotes capable of performing oxygenic photosynthesis. Synechocystis sp. PCC 6803 (Synechocystis) is a model cyanobacterium used extensively in research on photosynthesis and environmental adaptation. Posttranslational protein modification by lysine acetylation plays a critical regulatory role in both eukaryotes and prokaryotes; however, its extent and function in cyanobacteria remain unexplored. Herein, we performed a global acetylome analysis on Synechocystis through peptide prefractionation, antibody enrichment, and high accuracy LC-MS/MS analysis; identified 776 acetylation sites on 513 acetylated proteins; and functionally categorized them into an interaction map showing their involvement in various biological processes. Consistent with previous reports, a large fraction of the acetylation sites are present on proteins involved in cellular metabolism. Interestingly, for the first time, many proteins involved in photosynthesis, including the subunits of phycocyanin (CpcA, CpcB, CpcC, and CpcG) and allophycocyanin (ApcA, ApcB, ApcD, ApcE, and ApcF), were found to be lysine acetylated, suggesting that lysine acetylation may play regulatory roles in the photosynthesis process. Six identified acetylated proteins associated with photosynthesis and carbon metabolism were further validated by immunoprecipitation and Western blotting. Our data provide the first global survey of lysine acetylation in cyanobacteria and reveal previously unappreciated roles of lysine acetylation in the regulation of photosynthesis. The provided data set may serve as an important resource for the functional analysis of lysine acetylation in cyanobacteria and facilitate the elucidation of the entire metabolic networks and photosynthesis process in this model cyanobacterium.

Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects.

PubMed

Jiang, Feng; Liu, Qing; Wang, Yanli; Zhang, Jie; Wang, Huimin; Song, Tianqi; Yang, Meiling; Wang, Xianhui; Kang, Le

2017-06-01

The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain-containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution. © The Authors 2017. Published by Oxford University Press.

Regulatory network analysis of Epstein-Barr virus identifies functional modules and hub genes involved in infectious mononucleosis.

PubMed

Poorebrahim, Mansour; Salarian, Ali; Najafi, Saeideh; Abazari, Mohammad Foad; Aleagha, Maryam Nouri; Dadras, Mohammad Nasr; Jazayeri, Seyed Mohammad; Ataei, Atousa; Poortahmasebi, Vahdat

2017-05-01

Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis (IM) and establishes lifetime infection associated with a variety of cancers and autoimmune diseases. The aim of this study was to develop an integrative gene regulatory network (GRN) approach and overlying gene expression data to identify the representative subnetworks for IM and EBV latent infection (LI). After identifying differentially expressed genes (DEGs) in both IM and LI gene expression profiles, functional annotations were applied using gene ontology (GO) and BiNGO tools, and construction of GRNs, topological analysis and identification of modules were carried out using several plugins of Cytoscape. In parallel, a human-EBV GRN was generated using the Hu-Vir database for further analyses. Our analysis revealed that the majority of DEGs in both IM and LI were involved in cell-cycle and DNA repair processes. However, these genes showed a significant negative correlation in the IM and LI states. Furthermore, cyclin-dependent kinase 2 (CDK2) - a hub gene with the highest centrality score - appeared to be the key player in cell cycle regulation in IM disease. The most significant functional modules in the IM and LI states were involved in the regulation of the cell cycle and apoptosis, respectively. Human-EBV network analysis revealed several direct targets of EBV proteins during IM disease. Our study provides an important first report on the response to IM/LI EBV infection in humans. An important aspect of our data was the upregulation of genes associated with cell cycle progression and proliferation.

Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects

PubMed Central

Jiang, Feng; Liu, Qing; Wang, Yanli; Zhang, Jie; Wang, Huimin; Song, Tianqi; Yang, Meiling

2017-01-01

Abstract The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain–containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution. PMID:28444351

Population Pharmacokinetics and Therapeutic Efficacy of Febuxostat in Patients with Severe Renal Impairment.

PubMed

Hira, Daiki; Chisaki, Yugo; Noda, Satoshi; Araki, Hisazumi; Uzu, Takashi; Maegawa, Hiroshi; Yano, Yoshitaka; Morita, Shin-Ya; Terada, Tomohiro

2015-01-01

The aim of the present study was to determine the influence of severe renal dysfunction (estimated glomerular filtration rate <30 ml/min/1.73 m(2), including hemodialysis) on the pharmacokinetics and therapeutic effects of febuxostat using a population pharmacokinetic analysis. This study recruited patients with hyperuricemia who were initially treated with allopurinol, but were switched to febuxostat, and it consists of 2 sub-studies: a pharmacokinetic study (26 patients) and retrospective efficacy evaluation study (51 patients). The demographic and clinical data of patients were collected from electronic medical records. Plasma febuxostat concentrations were obtained at each hospital visit. Population pharmacokinetic modeling was performed with NONMEM version 7.2. A total of 128 plasma febuxostat concentrations from 26 patients were used in the population pharmacokinetic analysis. The data were best described by a 1-compartment model with first order absorption. Covariate analysis revealed that renal function did not influence the pharmacokinetics of febuxostat, whereas actual body weight significantly influenced apparent clearance and apparent volume of distribution. The retrospective efficacy analysis showed the favorable therapeutic response of febuxostat switched from allopurinol in patients with moderate to severe renal impairment. No serious adverse event associated with febuxostat was observed irrespective of renal function. The population pharmacokinetic analysis and therapeutic analysis of febuxostat revealed that severe renal dysfunction had no influence on the pharmacokinetic parameters of febuxostat. These results suggest that febuxostat is tolerated well by patients with severe renal impairment. © 2015 S. Karger AG, Basel.

A genome-wide analysis of the expansin genes in Malus × Domestica.

PubMed

Zhang, Shizhong; Xu, Ruirui; Gao, Zheng; Chen, Changtian; Jiang, Zesheng; Shu, Huairui

2014-04-01

Expansins were first identified as cell wall-loosening proteins; they are involved in regulating cell expansion, fruits softening and many other physiological processes. However, our knowledge about the expansin family members and their evolutionary relationships in fruit trees, such as apple, is limited. In this study, we identified 41 members of the expansin gene family in the genome of apple (Malus × Domestica L. Borkh). Phylogenetic analysis revealed that expansin genes in apple could be divided into four subfamilies according to their gene structures and protein motifs. By phylogenetic analysis of the expansins in five plants (Arabidopsis, rice, poplar, grape and apple), the expansins were divided into 17 subgroups. Our gene duplication analysis revealed that whole-genome and chromosomal-segment duplications contributed to the expansion of Mdexpansins. The microarray and expressed sequence tag (EST) data showed that 34 Mdexpansin genes could be divided into five groups by the EST analysis; they may also play different roles during fruit development. An expression model for MdEXPA16 and MdEXPA20 showed their potential role in developing fruit. Overall, our study provides useful data and novel insights into the functions and regulatory mechanisms of the expansin genes in apple, as well as their evolution and divergence. As the first step towards genome-wide analysis of the expansin genes in apple, our results have established a solid foundation for future studies on the function of the expansin genes in fruit development.

Trophic Mode-Dependent Proteomic Analysis Reveals Functional Significance of Light-Independent Chlorophyll Synthesis in Synechocystis sp. PCC 6803.

PubMed

Fang, Longfa; Ge, Haitao; Huang, Xiahe; Liu, Ye; Lu, Min; Wang, Jinlong; Chen, Weiyang; Xu, Wu; Wang, Yingchun

2017-01-09

The photosynthetic model organism Synechocystis sp. PCC 6803 can grow in different trophic modes, depending on the availability of light and exogenous organic carbon source. However, how the protein profile changes to facilitate the cells differentially propagate in different modes has not been comprehensively investigated. Using isobaric labeling-based quantitative proteomics, we simultaneously identified and quantified 45% Synechocystis proteome across four different trophic modes, i.e., autotrophic, heterotrophic, photoheterotrophic, and mixotrophic modes. Among the 155 proteins that are differentially expressed across four trophic modes, proteins involved in nitrogen assimilation and light-independent chlorophyll synthesis are dramatically upregulated in the mixotrophic mode, concomitant with a dramatic increase of P II phosphorylation that senses carbon and nitrogen assimilation status. Moreover, functional study using a mutant defective in light-independent chlorophyll synthesis revealed that this pathway is important for chlorophyll accumulation under a cycled light/dark illumination regime, a condition mimicking day/night cycles in certain natural habitats. Collectively, these results provide the most comprehensive information on trophic mode-dependent protein expression in cyanobacterium, and reveal the functional significance of light-independent chlorophyll synthesis in trophic growth. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

ERP evidence suggests executive dysfunction in ecstasy polydrug users.

PubMed

Roberts, C A; Fairclough, S H; Fisk, J E; Tames, F; Montgomery, C

2013-08-01

Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research. Equally, there have been many reports of equivocal findings in this area. The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users. Twenty ecstasy-polydrug users, 20 non-ecstasy-polydrug users and 20 drug-naïve controls were recruited. Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded. Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task. Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component. Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-naïve controls. Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy-polydrug users.

End-to-side neurorraphy: a long-term study of neural regeneration in a rat model.

PubMed

Tarasidis, G; Watanabe, O; Mackinnon, S E; Strasberg, S R; Haughey, B H; Hunter, D A

1998-10-01

This study evaluated long-term reinnervation of an end-to-side neurorraphy and the resultant functional recovery in a rat model. The divided distal posterior tibial nerve was repaired to the side of an intact peroneal nerve. Control groups included a cut-and-repair of the posterior tibial nerve and an end-to-end repair of the peroneal nerve to the posterior tibial nerve. Evaluations included walking-track analysis, nerve conduction studies, muscle mass measurements, retrograde nerve tracing, and histologic evaluation. Walking tracks indicated poor recovery of posterior tibial nerve function in the experimental group. No significant difference in nerve conduction velocities was seen between the experimental and control groups. Gastrocnemius muscle mass measurements revealed no functional recovery in the experimental group. Similarly, retrograde nerve tracing revealed minimal motor neuron staining in the experimental group. However, some sensory staining was seen within the dorsal root ganglia of the end-to-side group. Histologic study revealed minimal myelinated axonal regeneration in the experimental group as compared with findings in the other groups. These results suggest that predominantly sensory regeneration occurs in an end-to-side neurorraphy at an end point of 6 months.

Multimodal and Multi-tissue Measures of Connectivity Revealed by Joint Independent Component Analysis.

PubMed

Franco, Alexandre R; Ling, Josef; Caprihan, Arvind; Calhoun, Vince D; Jung, Rex E; Heileman, Gregory L; Mayer, Andrew R

2008-12-01

The human brain functions as an efficient system where signals arising from gray matter are transported via white matter tracts to other regions of the brain to facilitate human behavior. However, with a few exceptions, functional and structural neuroimaging data are typically optimized to maximize the quantification of signals arising from a single source. For example, functional magnetic resonance imaging (FMRI) is typically used as an index of gray matter functioning whereas diffusion tensor imaging (DTI) is typically used to determine white matter properties. While it is likely that these signals arising from different tissue sources contain complementary information, the signal processing algorithms necessary for the fusion of neuroimaging data across imaging modalities are still in a nascent stage. In the current paper we present a data-driven method for combining measures of functional connectivity arising from gray matter sources (FMRI resting state data) with different measures of white matter connectivity (DTI). Specifically, a joint independent component analysis (J-ICA) was used to combine these measures of functional connectivity following intensive signal processing and feature extraction within each of the individual modalities. Our results indicate that one of the most predominantly used measures of functional connectivity (activity in the default mode network) is highly dependent on the integrity of white matter connections between the two hemispheres (corpus callosum) and within the cingulate bundles. Importantly, the discovery of this complex relationship of connectivity was entirely facilitated by the signal processing and fusion techniques presented herein and could not have been revealed through separate analyses of both data types as is typically performed in the majority of neuroimaging experiments. We conclude by discussing future applications of this technique to other areas of neuroimaging and examining potential limitations of the methods.

Functional and motor outcome 5 years after stroke is equivalent to outcome at 2 months: follow-up of the collaborative evaluation of rehabilitation in stroke across Europe.

PubMed

Meyer, Sarah; Verheyden, Geert; Brinkmann, Nadine; Dejaeger, Eddy; De Weerdt, Willy; Feys, Hilde; Gantenbein, Andreas R; Jenni, Walter; Laenen, Annouschka; Lincoln, Nadina; Putman, Koen; Schuback, Birgit; Schupp, Wilfried; Thijs, Vincent; De Wit, Liesbet

2015-06-01

Recovery of patients within the first 6 months after stroke is well documented, but there has been little research on long-term recovery. The aim of this study was to analyze functional and motor recovery between admission to rehabilitation centres and 5 years after stroke. This follow-up of the Collaborative Evaluation of Rehabilitation in Stroke Across Europe study, included patients from 4 European rehabilitation centres. Patients were assessed on admission, at 2 and 6 months, and 5 years after stroke, using the Barthel Index, Rivermead Motor Assessment Gross Function, Leg and Trunk function, and Arm function. Linear mixed models were used, corrected for baseline characteristics. To account for the drop-out during follow-up, the analysis is likelihood-based (assumption of missingness at random). A total of 532 patients were included in this study, of which 238 were followed up at 5 years post stroke. Mean age at stroke onset was 69 (±10 SD) years, 53% were men, 84% had ischemic strokes, and 53% had left-sided motor impairment. Linear mixed model analysis revealed a significant deterioration for all 4 outcomes between 6 months and 5 years (P<0.0001). Scores at 2 months were not statistically significant different from scores at 5 years after stroke. Higher age (P<0.0001) and increasing stroke severity on admission (P<0.0001) negatively affected long-term functional and motor recovery. Five-year follow-up revealed deterioration in functional and motor outcome, with a return to the level measured at 2 months. Increasing age and increasing stroke severity negatively affected recovery up to 5 years after stroke. © 2015 American Heart Association, Inc.

Sparse dictionary learning for resting-state fMRI analysis

NASA Astrophysics Data System (ADS)

Lee, Kangjoo; Han, Paul Kyu; Ye, Jong Chul

2011-09-01

Recently, there has been increased interest in the usage of neuroimaging techniques to investigate what happens in the brain at rest. Functional imaging studies have revealed that the default-mode network activity is disrupted in Alzheimer's disease (AD). However, there is no consensus, as yet, on the choice of analysis method for the application of resting-state analysis for disease classification. This paper proposes a novel compressed sensing based resting-state fMRI analysis tool called Sparse-SPM. As the brain's functional systems has shown to have features of complex networks according to graph theoretical analysis, we apply a graph model to represent a sparse combination of information flows in complex network perspectives. In particular, a new concept of spatially adaptive design matrix has been proposed by implementing sparse dictionary learning based on sparsity. The proposed approach shows better performance compared to other conventional methods, such as independent component analysis (ICA) and seed-based approach, in classifying the AD patients from normal using resting-state analysis.

A malignant cause of hypoglycaemia: a metastatic insulin-secreting pancreatic neuroendocrine carcinoma.

PubMed

Sandoval, Mark Anthony; Pagsisihan, Daveric; Berberabe, A'Ericson; Palugod-Lopez, Elaine Gayle

2016-03-18

Most cases of insulinomas are benign. We report a case of a malignant form of insulinoma. A 46-year-old man presented with behavioural changes associated with hypoglycaemia. Diagnostic work up revealed high serum insulin, high C-peptide and low glucose levels, compatible with endogenous hyperinsulinaemic hypoglycaemia. CT imaging of the abdomen revealed a pancreatic head mass and multiple liver masses. Biopsy of the pancreatic mass revealed a grade three pancreatic neuroendocrine carcinoma. Histological analysis of a liver mass showed that it was identical to the pancreatic mass, confirming its metastatic nature. The patient underwent distal pancreatectomy with en bloc splenectomy. There was persistence of hypoglycaemic symptoms after removal of the pancreatic mass, suggesting that the liver metastases were also functioning. Symptoms were controlled by diazoxide and octreotide long-acting release. The patient is already 1 year postsurgery with no recurrence of severe hypoglycaemia, and he has good functional capacity and has returned to his office job. 2016 BMJ Publishing Group Ltd.

A malignant cause of hypoglycaemia: a metastatic insulin-secreting pancreatic neuroendocrine carcinoma

PubMed Central

Sandoval, Mark Anthony; Pagsisihan, Daveric; Berberabe, A'Ericson; Palugod-Lopez, Elaine Gayle

2016-01-01

Most cases of insulinomas are benign. We report a case of a malignant form of insulinoma. A 46-year-old man presented with behavioural changes associated with hypoglycaemia. Diagnostic work up revealed high serum insulin, high C-peptide and low glucose levels, compatible with endogenous hyperinsulinaemic hypoglycaemia. CT imaging of the abdomen revealed a pancreatic head mass and multiple liver masses. Biopsy of the pancreatic mass revealed a grade three pancreatic neuroendocrine carcinoma. Histological analysis of a liver mass showed that it was identical to the pancreatic mass, confirming its metastatic nature. The patient underwent distal pancreatectomy with en bloc splenectomy. There was persistence of hypoglycaemic symptoms after removal of the pancreatic mass, suggesting that the liver metastases were also functioning. Symptoms were controlled by diazoxide and octreotide long-acting release. The patient is already 1 year postsurgery with no recurrence of severe hypoglycaemia, and he has good functional capacity and has returned to his office job. PMID:26994053

Photoelectron spectra and biological activity of cinnamic acid derivatives revisited.

PubMed

Novak, Igor; Klasinc, Leo; McGlynn, Sean P

2018-01-15

The electronic structures of several derivatives of cinnamic acid have been studied by UV photoelectron spectroscopy (UPS) and Green's function quantum chemical calculations. The spectra reveal the presence of dimers in the gas phase for p-coumaric and ferulic acids. The electronic structure analysis has been related to the biological properties of these compounds through the analysis of some structure-activity relationships (SAR). Copyright © 2017 Elsevier B.V. All rights reserved.

A protein domain-centric approach for the comparative analysis of human and yeast phenotypically relevant mutations

PubMed Central

2013-01-01

Background The body of disease mutations with known phenotypic relevance continues to increase and is expected to do so even faster with the advent of new experimental techniques such as whole-genome sequencing coupled with disease association studies. However, genomic association studies are limited by the molecular complexity of the phenotype being studied and the population size needed to have adequate statistical power. One way to circumvent this problem, which is critical for the study of rare diseases, is to study the molecular patterns emerging from functional studies of existing disease mutations. Current gene-centric analyses to study mutations in coding regions are limited by their inability to account for the functional modularity of the protein. Previous studies of the functional patterns of known human disease mutations have shown a significant tendency to cluster at protein domain positions, namely position-based domain hotspots of disease mutations. However, the limited number of known disease mutations remains the main factor hindering the advancement of mutation studies at a functional level. In this paper, we address this problem by incorporating mutations known to be disruptive of phenotypes in other species. Focusing on two evolutionarily distant organisms, human and yeast, we describe the first inter-species analysis of mutations of phenotypic relevance at the protein domain level. Results The results of this analysis reveal that phenotypic mutations from yeast cluster at specific positions on protein domains, a characteristic previously revealed to be displayed by human disease mutations. We found over one hundred domain hotspots in yeast with approximately 50% in the exact same domain position as known human disease mutations. Conclusions We describe an analysis using protein domains as a framework for transferring functional information by studying domain hotspots in human and yeast and relating phenotypic changes in yeast to diseases in human. This first-of-a-kind study of phenotypically relevant yeast mutations in relation to human disease mutations demonstrates the utility of a multi-species analysis for advancing the understanding of the relationship between genetic mutations and phenotypic changes at the organismal level. PMID:23819456

[Soft tissue sarcoma of the upper extremities. Analysis of factors relevant for prognosis in 160 patients].

PubMed

Lehnhardt, M; Hirche, C; Daigeler, A; Goertz, O; Ring, A; Hirsch, T; Drücke, D; Hauser, J; Steinau, H U

2012-02-01

Soft tissue sarcomas (STS) are a rare entity with reduced prognosis due to their aggressive biology. For an optimal treatment of STS identification of independent prognostic factors is crucial in order to reduce tumor-related mortality and recurrence rates. The surgical oncological concept includes wide excisions with resection safety margins >1 cm which enables acceptable functional results and reduced rates of amputation of the lower extremities. In contrast, individual anatomy of the upper extremities, in particular of the hand, leads to an intentional reduction of resection margins in order to preserve the extremity and its function with the main intention of tumor-free resection margins. In this study, the oncological safety and outcome as well as functional results were validated by a retrospective analysis of survival rate, recurrence rate and potential prognostic factors. A total of 160 patients who had been treated for STS of the upper extremities were retrospectively included. Independent prognostic factors were analyzed (primary versus recurrent tumor, tumor size, resection status, grade of malignancy, additional therapy, localization in the upper extremity). Kaplan-Meier analyses for survival rate and local control were calculated. Further outcome measures were functional results validated by the DASH score and rate of amputation. In 130 patients (81%) wide tumor excision (R0) was performed and in 19 patients (12%) an amputation was necessary. The 5-year overall survival rate was 70% and the 5-year survival rate in primary tumors was 81% whereas in recurrences 55% relapsed locally. The 10-year overall survival rate was 45% and the 5-year recurrence rate was 18% for primary STS and 43% for recurrent STS. Variance analysis revealed primary versus recurrent tumor, tumor size, resection status and grade of malignancy as independent prognostic factors. Analysis of functional results showed a median DASH score of 37 (0-100; 0=contralateral extremity). The 5-year survival and local recurrence rates are comparable to STS wide resections with safety margins >1 cm for the lower extremities and the trunk. Analysis of prognostic factors revealed resection status and the tumor-free resection margins to be the main goals in STS resection of upper extremity.

Comparative analysis of Hibiscus sabdariffa (roselle) hot and cold extracts in respect to their potential for α-glucosidase inhibition.

PubMed

Rasheed, Dalia M; Porzel, Andrea; Frolov, Andrei; El Seedi, Hesham R; Wessjohann, Ludger A; Farag, Mohamed A

2018-06-01

Roselle (Hibiscus sabdariffa) is a functional food with potential health benefits, consumed either as hot or cold beverage. To ensure quality control of its various products, accurate measurement of active metabolites is warranted. Herein, we propose a combination of ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and nuclear magnetic resonance (NMR) analytical platforms for the untargeted characterization of metabolites in two roselle cultivars, Aswan and Sudan-1. The analyses revealed 33 metabolites, including sugars, flavonoids, anthocyanins, phenolic and aliphatic organic acids. Their relative contents in cultivars were assessed via principle component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS). Impact of the different extraction methods (decoction, infusion and maceration) was compared by quantitative 1 H NMR spectroscopy, revealing cold maceration to be optimal for preserving anthocyanins, whereas infusion was more suited for recovering organic acids. The metabolite pattern revealed by the different extraction methods was found in good correlation for their ability to inhibit α-glucosidase enzyme. Copyright © 2018 Elsevier Ltd. All rights reserved.

Creativity and the default network: A functional connectivity analysis of the creative brain at rest☆

PubMed Central

Beaty, Roger E.; Benedek, Mathias; Wilkins, Robin W.; Jauk, Emanuel; Fink, Andreas; Silvia, Paul J.; Hodges, Donald A.; Koschutnig, Karl; Neubauer, Aljoscha C.

2014-01-01

The present research used resting-state functional magnetic resonance imaging (fMRI) to examine whether the ability to generate creative ideas corresponds to differences in the intrinsic organization of functional networks in the brain. We examined the functional connectivity between regions commonly implicated in neuroimaging studies of divergent thinking, including the inferior prefrontal cortex and the core hubs of the default network. Participants were prescreened on a battery of divergent thinking tests and assigned to high- and low-creative groups based on task performance. Seed-based functional connectivity analysis revealed greater connectivity between the left inferior frontal gyrus (IFG) and the entire default mode network in the high-creative group. The right IFG also showed greater functional connectivity with bilateral inferior parietal cortex and the left dorsolateral prefrontal cortex in the high-creative group. The results suggest that the ability to generate creative ideas is characterized by increased functional connectivity between the inferior prefrontal cortex and the default network, pointing to a greater cooperation between brain regions associated with cognitive control and low-level imaginative processes. PMID:25245940

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders

PubMed Central

2012-01-01

Background Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD. We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Result Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex–MTG–IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. Conclusions These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD. PMID:22889284

Genome-wide profiling of 24 hr diel rhythmicity in the water flea, Daphnia pulex: network analysis reveals rhythmic gene expression and enhances functional gene annotation.

PubMed

Rund, Samuel S C; Yoo, Boyoung; Alam, Camille; Green, Taryn; Stephens, Melissa T; Zeng, Erliang; George, Gary F; Sheppard, Aaron D; Duffield, Giles E; Milenković, Tijana; Pfrender, Michael E

2016-08-18

Marine and freshwater zooplankton exhibit daily rhythmic patterns of behavior and physiology which may be regulated directly by the light:dark (LD) cycle and/or a molecular circadian clock. One of the best-studied zooplankton taxa, the freshwater crustacean Daphnia, has a 24 h diel vertical migration (DVM) behavior whereby the organism travels up and down through the water column daily. DVM plays a critical role in resource tracking and the behavioral avoidance of predators and damaging ultraviolet radiation. However, there is little information at the transcriptional level linking the expression patterns of genes to the rhythmic physiology/behavior of Daphnia. Here we analyzed genome-wide temporal transcriptional patterns from Daphnia pulex collected over a 44 h time period under a 12:12 LD cycle (diel) conditions using a cosine-fitting algorithm. We used a comprehensive network modeling and analysis approach to identify novel co-regulated rhythmic genes that have similar network topological properties and functional annotations as rhythmic genes identified by the cosine-fitting analyses. Furthermore, we used the network approach to predict with high accuracy novel gene-function associations, thus enhancing current functional annotations available for genes in this ecologically relevant model species. Our results reveal that genes in many functional groupings exhibit 24 h rhythms in their expression patterns under diel conditions. We highlight the rhythmic expression of immunity, oxidative detoxification, and sensory process genes. We discuss differences in the chronobiology of D. pulex from other well-characterized terrestrial arthropods. This research adds to a growing body of literature suggesting the genetic mechanisms governing rhythmicity in crustaceans may be divergent from other arthropod lineages including insects. Lastly, these results highlight the power of using a network analysis approach to identify differential gene expression and provide novel functional annotation.

DNA microarray‐based analysis of voluntary resistance wheel running reveals novel transcriptome leading robust hippocampal plasticity

PubMed Central

Lee, Min Chul; Rakwal, Randeep; Shibato, Junko; Inoue, Koshiro; Chang, Hyukki; Soya, Hideaki

2014-01-01

Abstract In two separate experiments, voluntary resistance wheel running with 30% of body weight (RWR), rather than wheel running (WR), led to greater enhancements, including adult hippocampal neurogenesis and cognitive functions, in conjunction with hippocampal brain‐derived neurotrophic factor (BDNF) signaling (Lee et al., J Appl Physiol, 2012; Neurosci Lett., 2013). Here we aimed to unravel novel molecular factors and gain insight into underlying molecular mechanisms for RWR‐enhanced hippocampal functions; a high‐throughput whole‐genome DNA microarray approach was applied to rats performing voluntary running for 4 weeks. RWR rats showed a significant decrease in average running distances although average work levels increased immensely, by about 11‐fold compared to WR, resulting in muscular adaptation for the fast‐twitch plantaris muscle. Global transcriptome profiling analysis identified 128 (sedentary × WR) and 169 (sedentary × RWR) up‐regulated (>1.5‐fold change), and 97 (sedentary × WR) and 468 (sedentary × RWR) down‐regulated (<0.75‐fold change) genes. Functional categorization using both pathway‐ or specific‐disease‐state‐focused gene classifications and Ingenuity Pathway Analysis (IPA) revealed expression pattern changes in the major categories of disease and disorders, molecular functions, and physiological system development and function. Genes specifically regulated with RWR include the newly identified factors of NFATc1, AVPR1A, and FGFR4, as well as previously known factors, BDNF and CREB mRNA. Interestingly, RWR down‐regulated multiple inflammatory cytokines (IL1B, IL2RA, and TNF) and chemokines (CXCL1, CXCL10, CCL2, and CCR4) with the SYCP3, PRL genes, which are potentially involved in regulating hippocampal neuroplastic changes. These results provide understanding of the voluntary‐RWR‐related hippocampal transcriptome, which will open a window to the underlying mechanisms of the positive effects of exercise, with therapeutic value for enhancing hippocampal functions. PMID:25413326

Functional Genomics Analysis of Big Data Identifies Novel Peroxisome Proliferator-Activated Receptor γ Target Single Nucleotide Polymorphisms Showing Association With Cardiometabolic Outcomes.

PubMed

Richardson, Kris; Schnitzler, Gavin R; Lai, Chao-Qiang; Ordovas, Jose M

2015-12-01

Cardiovascular disease and type 2 diabetes mellitus represent overlapping diseases where a large portion of the variation attributable to genetics remains unexplained. An important player in their pathogenesis is peroxisome proliferator-activated receptor γ (PPARγ) that is involved in lipid and glucose metabolism and maintenance of metabolic homeostasis. We used a functional genomics methodology to interrogate human chromatin immunoprecipitation-sequencing, genome-wide association studies, and expression quantitative trait locus data to inform selection of candidate functional single nucleotide polymorphisms (SNPs) falling in PPARγ motifs. We derived 27 328 chromatin immunoprecipitation-sequencing peaks for PPARγ in human adipocytes through meta-analysis of 3 data sets. The PPARγ consensus motif showed greatest enrichment and mapped to 8637 peaks. We identified 146 SNPs in these motifs. This number was significantly less than would be expected by chance, and Inference of Natural Selection from Interspersed Genomically coHerent elemenTs analysis indicated that these motifs are under weak negative selection. A screen of these SNPs against genome-wide association studies for cardiometabolic traits revealed significant enrichment with 16 SNPs. A screen against the MuTHER expression quantitative trait locus data revealed 8 of these were significantly associated with altered gene expression in human adipose, more than would be expected by chance. Several SNPs fall close, or are linked by expression quantitative trait locus to lipid-metabolism loci including CYP26A1. We demonstrated the use of functional genomics to identify SNPs of potential function. Specifically, that SNPs within PPARγ motifs that bind PPARγ in adipocytes are significantly associated with cardiometabolic disease and with the regulation of transcription in adipose. This method may be used to uncover functional SNPs that do not reach significance thresholds in the agnostic approach of genome-wide association studies. © 2015 American Heart Association, Inc.

Dynamic biochemical tissue analysis detects functional L-selectin ligands on colon cancer tissues

PubMed Central

Carlson, Grady E.; Martin, Eric W.; Shirure, Venktesh S.; Malgor, Ramiro; Resto, Vicente A.; Goetz, Douglas J.; Burdick, Monica M.

2017-01-01

A growing body of evidence suggests that L-selectin ligands presented on circulating tumor cells facilitate metastasis by binding L-selectin presented on leukocytes. Commonly used methods for detecting L-selectin ligands on tissues, e.g., immunostaining, are performed under static, no-flow conditions. However, such analysis does not assay for functional L-selectin ligands, specifically those ligands that promote adhesion under shear flow conditions. Recently our lab developed a method, termed dynamic biochemical tissue analysis (DBTA), to detect functional selectin ligands in situ by probing tissues with L-selectin-coated microspheres under hemodynamic flow conditions. In this investigation, DBTA was used to probe human colon tissues for L-selectin ligand activity. The detection of L-selectin ligands using DBTA was highly specific. Furthermore, DBTA reproducibly detected functional L-selectin ligands on diseased, e.g., cancerous or inflamed, tissues but not on noncancerous tissues. In addition, DBTA revealed a heterogeneous distribution of functional L-selectin ligands on colon cancer tissues. Most notably, detection of L-selectin ligands by immunostaining using HECA-452 antibody only partially correlated with functional L-selectin ligands detected by DBTA. In summation, the results of this study demonstrate that DBTA detects functional selectin ligands to provide a unique characterization of pathological tissue. PMID:28282455

Dynamic biochemical tissue analysis detects functional L-selectin ligands on colon cancer tissues.

PubMed

Carlson, Grady E; Martin, Eric W; Shirure, Venktesh S; Malgor, Ramiro; Resto, Vicente A; Goetz, Douglas J; Burdick, Monica M

2017-01-01

A growing body of evidence suggests that L-selectin ligands presented on circulating tumor cells facilitate metastasis by binding L-selectin presented on leukocytes. Commonly used methods for detecting L-selectin ligands on tissues, e.g., immunostaining, are performed under static, no-flow conditions. However, such analysis does not assay for functional L-selectin ligands, specifically those ligands that promote adhesion under shear flow conditions. Recently our lab developed a method, termed dynamic biochemical tissue analysis (DBTA), to detect functional selectin ligands in situ by probing tissues with L-selectin-coated microspheres under hemodynamic flow conditions. In this investigation, DBTA was used to probe human colon tissues for L-selectin ligand activity. The detection of L-selectin ligands using DBTA was highly specific. Furthermore, DBTA reproducibly detected functional L-selectin ligands on diseased, e.g., cancerous or inflamed, tissues but not on noncancerous tissues. In addition, DBTA revealed a heterogeneous distribution of functional L-selectin ligands on colon cancer tissues. Most notably, detection of L-selectin ligands by immunostaining using HECA-452 antibody only partially correlated with functional L-selectin ligands detected by DBTA. In summation, the results of this study demonstrate that DBTA detects functional selectin ligands to provide a unique characterization of pathological tissue.

Widespread occurrence of lysine methylation in Plasmodium falciparum proteins at asexual blood stages.

PubMed

Kaur, Inderjeet; Zeeshan, Mohammad; Saini, Ekta; Kaushik, Abhinav; Mohmmed, Asif; Gupta, Dinesh; Malhotra, Pawan

2016-10-20

Post-transcriptional and post-translational modifications play a major role in Plasmodium life cycle regulation. Lysine methylation of histone proteins is well documented in several organisms, however in recent years lysine methylation of proteins outside histone code is emerging out as an important post-translational modification (PTM). In the present study we have performed global analysis of lysine methylation of proteins in asexual blood stages of Plasmodium falciparum development. We immunoprecipitated stage specific Plasmodium lysates using anti-methyl lysine specific antibodies that immunostained the asexual blood stage parasites. Using liquid chromatography and tandem mass spectrometry analysis, 570 lysine methylated proteins at three different blood stages were identified. Analysis of the peptide sequences identified 605 methylated sites within 422 proteins. Functional classification of the methylated proteins revealed that the proteins are mainly involved in nucleotide metabolic processes, chromatin organization, transport, homeostatic processes and protein folding. The motif analysis of the methylated lysine peptides reveals novel motifs. Many of the identified lysine methylated proteins are also interacting partners/substrates of PfSET domain proteins as revealed by STRING database analysis. Our findings suggest that the protein methylation at lysine residues is widespread in Plasmodium and plays an important regulatory role in diverse set of the parasite pathways.

Blind source separation in retinal videos

NASA Astrophysics Data System (ADS)

Barriga, Eduardo S.; Truitt, Paul W.; Pattichis, Marios S.; Tüso, Dan; Kwon, Young H.; Kardon, Randy H.; Soliz, Peter

2003-05-01

An optical imaging device of retina function (OID-RF) has been developed to measure changes in blood oxygen saturation due to neural activity resulting from visual stimulation of the photoreceptors in the human retina. The video data that are collected represent a mixture of the functional signal in response to the retinal activation and other signals from undetermined physiological activity. Measured changes in reflectance in response to the visual stimulus are on the order of 0.1% to 1.0% of the total reflected intensity level which makes the functional signal difficult to detect by standard methods since it is masked by the other signals that are present. In this paper, we apply principal component analysis (PCA), blind source separation (BSS), using Extended Spatial Decorrelation (ESD) and independent component analysis (ICA) using the Fast-ICA algorithm to extract the functional signal from the retinal videos. The results revealed that the functional signal in a stimulated retina can be detected through the application of some of these techniques.

Genetic deletion of the EGFR ligand epigen does not affect mouse embryonic development and tissue homeostasis.

PubMed

Dahlhoff, Maik; Schäfer, Matthias; Wolf, Eckhard; Schneider, Marlon R

2013-02-15

The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor with manifold functions during development, tissue homeostasis and disease. EGFR activation, the formation of homodimers or heterodimers (with the related ERBB2-4 receptors) and downstream signaling is initiated by the binding of a family of structurally related growth factors, the EGFR ligands. Genetic deletion experiments clarified the biological function of all family members except for the last characterized ligand, epigen. We employed gene targeting in mouse embryonic stem cells to generate mice lacking epigen expression. Loss of epigen did not affect mouse development, fertility, or organ physiology. Quantitative RT-PCR analysis revealed increased expression of betacellulin and EGF in a few organs of epigen-deficient mice, suggesting a functional compensation by these ligands. In conclusion, we completed the genetic analysis of EGFR ligands and show that epigen has non-essential functions or functions that can be compensated by other EGFR ligands during growth and tissue homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.

Morphological and functional diversity in therizinosaur claws and the implications for theropod claw evolution.

PubMed

Lautenschlager, Stephan

2014-06-22

Therizinosaurs are a group of herbivorous theropod dinosaurs from the Cretaceous of North America and Asia, best known for their iconically large and elongate manual claws. However, among Therizinosauria, ungual morphology is highly variable, reflecting a general trend found in derived theropod dinosaurs (Maniraptoriformes). A combined approach of shape analysis to characterize changes in manual ungual morphology across theropods and finite-element analysis to assess the biomechanical properties of different ungual shapes in therizinosaurs reveals a functional diversity related to ungual morphology. While some therizinosaur taxa used their claws in a generalist fashion, other taxa were functionally adapted to use the claws as grasping hooks during foraging. Results further indicate that maniraptoriform dinosaurs deviated from the plesiomorphic theropod ungual morphology resulting in increased functional diversity. This trend parallels modifications of the cranial skeleton in derived theropods in response to dietary adaptation, suggesting that dietary diversification was a major driver for morphological and functional disparity in theropod evolution.

Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders.

PubMed

Novarino, Gaia; Fenstermaker, Ali G; Zaki, Maha S; Hofree, Matan; Silhavy, Jennifer L; Heiberg, Andrew D; Abdellateef, Mostafa; Rosti, Basak; Scott, Eric; Mansour, Lobna; Masri, Amira; Kayserili, Hulya; Al-Aama, Jumana Y; Abdel-Salam, Ghada M H; Karminejad, Ariana; Kara, Majdi; Kara, Bulent; Bozorgmehri, Bita; Ben-Omran, Tawfeg; Mojahedi, Faezeh; El Din Mahmoud, Iman Gamal; Bouslam, Naima; Bouhouche, Ahmed; Benomar, Ali; Hanein, Sylvain; Raymond, Laure; Forlani, Sylvie; Mascaro, Massimo; Selim, Laila; Shehata, Nabil; Al-Allawi, Nasir; Bindu, P S; Azam, Matloob; Gunel, Murat; Caglayan, Ahmet; Bilguvar, Kaya; Tolun, Aslihan; Issa, Mahmoud Y; Schroth, Jana; Spencer, Emily G; Rosti, Rasim O; Akizu, Naiara; Vaux, Keith K; Johansen, Anide; Koh, Alice A; Megahed, Hisham; Durr, Alexandra; Brice, Alexis; Stevanin, Giovanni; Gabriel, Stacy B; Ideker, Trey; Gleeson, Joseph G

2014-01-31

Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease.

Mutual connectivity analysis (MCA) using generalized radial basis function neural networks for nonlinear functional connectivity network recovery in resting-state functional MRI

NASA Astrophysics Data System (ADS)

D'Souza, Adora M.; Abidin, Anas Zainul; Nagarajan, Mahesh B.; Wismüller, Axel

2016-03-01

We investigate the applicability of a computational framework, called mutual connectivity analysis (MCA), for directed functional connectivity analysis in both synthetic and resting-state functional MRI data. This framework comprises of first evaluating non-linear cross-predictability between every pair of time series prior to recovering the underlying network structure using community detection algorithms. We obtain the non-linear cross-prediction score between time series using Generalized Radial Basis Functions (GRBF) neural networks. These cross-prediction scores characterize the underlying functionally connected networks within the resting brain, which can be extracted using non-metric clustering approaches, such as the Louvain method. We first test our approach on synthetic models with known directional influence and network structure. Our method is able to capture the directional relationships between time series (with an area under the ROC curve = 0.92 +/- 0.037) as well as the underlying network structure (Rand index = 0.87 +/- 0.063) with high accuracy. Furthermore, we test this method for network recovery on resting-state fMRI data, where results are compared to the motor cortex network recovered from a motor stimulation sequence, resulting in a strong agreement between the two (Dice coefficient = 0.45). We conclude that our MCA approach is effective in analyzing non-linear directed functional connectivity and in revealing underlying functional network structure in complex systems.

Factors Associated with Postpartum Maternal Functioning in Women with Positive Screens for Depression.

PubMed

Barkin, Jennifer L; Wisner, Katherine L; Bromberger, Joyce T; Beach, Scott R; Wisniewski, Stephen R

2016-07-01

Functional assessment may represent a valuable addition to postpartum depression screening, providing a more thorough characterization of the mother's health and quality of life. To the authors' knowledge, this analysis represents the first examination of postpartum maternal functioning, as measured by a patient-centered validated tool aimed at ascertainment of functional status explicitly, and its clinical and sociodemographic correlates. A total of 189 women recruited from a large, urban women's hospital in the northeastern United States who both (1) screened positive for depression between 4 and 6 weeks postpartum and (2) completed a subsequent home (baseline) visit between October 1, 2008, and September 4, 2009, were included in this analysis. Multiple linear regression was conducted to ascertain which clinical and sociodemographic variables were independently associated with maternal functioning. The multivariate analysis revealed independent associations between bipolar status, atypical depression, depression score (17-item Hamilton Rating Scale for Depression), and insurance type with postpartum maternal functioning. The beta coefficient for bipolar status indicates that on average we would expect those with bipolar disorder to have maternal functioning scores that are 5.6 points less than those without bipolar disorder. Healthcare providers treating postpartum women with complicating mental health conditions should be cognizant of the potential ramifications on maternal functioning. Impaired functioning in the maternal role is likely to impact child development, although the precise nature of this relationship is yet to be elucidated.

Mutual Connectivity Analysis (MCA) Using Generalized Radial Basis Function Neural Networks for Nonlinear Functional Connectivity Network Recovery in Resting-State Functional MRI.

PubMed

DSouza, Adora M; Abidin, Anas Zainul; Nagarajan, Mahesh B; Wismüller, Axel

2016-03-29

We investigate the applicability of a computational framework, called mutual connectivity analysis (MCA), for directed functional connectivity analysis in both synthetic and resting-state functional MRI data. This framework comprises of first evaluating non-linear cross-predictability between every pair of time series prior to recovering the underlying network structure using community detection algorithms. We obtain the non-linear cross-prediction score between time series using Generalized Radial Basis Functions (GRBF) neural networks. These cross-prediction scores characterize the underlying functionally connected networks within the resting brain, which can be extracted using non-metric clustering approaches, such as the Louvain method. We first test our approach on synthetic models with known directional influence and network structure. Our method is able to capture the directional relationships between time series (with an area under the ROC curve = 0.92 ± 0.037) as well as the underlying network structure (Rand index = 0.87 ± 0.063) with high accuracy. Furthermore, we test this method for network recovery on resting-state fMRI data, where results are compared to the motor cortex network recovered from a motor stimulation sequence, resulting in a strong agreement between the two (Dice coefficient = 0.45). We conclude that our MCA approach is effective in analyzing non-linear directed functional connectivity and in revealing underlying functional network structure in complex systems.

Genome-Wide Survey and Expression Profiling of CCCH-Zinc Finger Family Reveals a Functional Module in Macrophage Activation

PubMed Central

Liang, Jian; Song, Wenjun; Tromp, Gail; Kolattukudy, Pappachan E.; Fu, Mingui

2008-01-01

Previously, we have identified a novel CCCH zinc finger protein family as negative regulators of macrophage activation. To gain an overall insight into the entire CCCH zinc finger gene family and to evaluate their potential role in macrophage activation, here we performed a genome-wide survey of CCCH zinc finger genes in mouse and human. Totally 58 CCCH zinc finger genes in mouse and 55 in human were identified and most of them have not been reported previously. Phylogenetic analysis revealed that the mouse CCCH family was divided into 6 groups. Meanwhile, we employed quantitative real-time PCR to profile their tissue expression patterns in adult mice. Clustering analysis showed that most of CCCH genes were broadly expressed in all of tissues examined with various levels. Interestingly, several CCCH genes Mbnl3, Zfp36l2, Zfp36, Zc3h12a, Zc3h12d, Zc3h7a and Leng9 were enriched in macrophage-related organs such as thymus, spleen, lung, intestine and adipose. Consistently, a comprehensive assessment of changes in expression of the 58 members of the mouse CCCH family during macrophage activation also revealed that these CCCH zinc finger genes were associated with the activation of bone marrow-derived macrophages by lipopolysaccharide. Taken together, this study not only identified a functional module of CCCH zinc finger genes in the regulation of macrophage activation but also provided the framework for future studies to dissect the function of this emerging gene family. PMID:18682727

The Association Between Cognitive Function and Subsequent Depression: A Systematic Review and Meta-Analysis

PubMed Central

Scult, Matthew A.; Paulli, Athelia R.; Mazure, Emily S.; Moffitt, Terrie E.; Hariri, Ahmad R.; Strauman, Timothy J.

2016-01-01

Despite a growing interest in understanding the cognitive deficits associated with major depressive disorder (MDD), it is largely unknown whether such deficits exist before disorder onset or how they might influence the severity of subsequent illness. The purpose of the present study was to conduct a systematic review and meta-analysis of longitudinal datasets to determine whether cognitive function acts as a predictor of later MDD diagnosis or change in depression symptoms. Eligible studies included longitudinal designs with baseline measures of cognitive functioning, and later unipolar MDD diagnosis or symptom assessment. The systematic review identified 29 publications, representing 34 unique samples, and 121,749 participants, that met the inclusion/exclusion criteria. Quantitative meta-analysis demonstrated that higher cognitive function was associated with decreased levels of subsequent depression (r=−0.088; 95% CI: −0.121, −0.054; p<0.001). However, sensitivity analyses revealed that this association is likely driven by concurrent depression symptoms at the time of cognitive assessment. Our review and meta-analysis indicate that the association between lower cognitive function and later depression is confounded by the presence of contemporaneous depression symptoms at the time of cognitive assessment. Thus, cognitive deficits predicting MDD likely represent deleterious effects of subclinical depression symptoms on performance rather than premorbid risk factors for disorder. PMID:27624847

Electromagnetic scaling functions within the Green's function Monte Carlo approach

DOE PAGES

Rocco, N.; Alvarez-Ruso, L.; Lovato, A.; ...

2017-07-24

We have studied the scaling properties of the electromagnetic response functions of 4He and 12C nuclei computed by the Green's function Monte Carlo approach, retaining only the one-body current contribution. Longitudinal and transverse scaling functions have been obtained in the relativistic and nonrelativistic cases and compared to experiment for various kinematics. The characteristic asymmetric shape of the scaling function exhibited by data emerges in the calculations in spite of the nonrelativistic nature of the model. The results are mostly consistent with scaling of zeroth, first, and second kinds. Our analysis reveals a direct correspondence between the scaling and the nucleon-densitymore » response functions. In conclusion, the scaling function obtained from the proton-density response displays scaling of the first kind, even more evidently than the longitudinal and transverse scaling functions« less

Electromagnetic scaling functions within the Green's function Monte Carlo approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rocco, N.; Alvarez-Ruso, L.; Lovato, A.

We have studied the scaling properties of the electromagnetic response functions of 4He and 12C nuclei computed by the Green's function Monte Carlo approach, retaining only the one-body current contribution. Longitudinal and transverse scaling functions have been obtained in the relativistic and nonrelativistic cases and compared to experiment for various kinematics. The characteristic asymmetric shape of the scaling function exhibited by data emerges in the calculations in spite of the nonrelativistic nature of the model. The results are mostly consistent with scaling of zeroth, first, and second kinds. Our analysis reveals a direct correspondence between the scaling and the nucleon-densitymore » response functions. In conclusion, the scaling function obtained from the proton-density response displays scaling of the first kind, even more evidently than the longitudinal and transverse scaling functions« less

Neurotactin functions in concert with other identified CAMs in growth cone guidance in Drosophila.

PubMed

Speicher, S; García-Alonso, L; Carmena, A; Martín-Bermudo, M D; de la Escalera, S; Jiménez, F

1998-02-01

We have isolated and characterized mutations in Drosophila neurotactin, a gene that encodes a cell adhesion protein widely expressed during neural development. Analysis of both loss and gain of gene function conditions during embryonic and postembryonic development revealed specific requirements for neurotactin during axon outgrowth, fasciculation, and guidance. Furthermore, embryos of some double mutant combinations of neurotactin and other genes encoding adhesion/signaling molecules, including neuroglian, derailed, and kekkon1, displayed phenotypic synergy. This result provides evidence for functional cooperativity in vivo between the adhesion and signaling pathways controlled by neurotactin and the other three genes.

Imposture, inauthenticity, and feeling fraudulent.

PubMed

Gediman, H K

1985-01-01

This paper deals with imposturous tendencies as ubiquitous and heterogeneous. They may enter into neurotic conflict and compromise, and also reflect an ego function disturbance involving multiple, shifting identities and subsequent problems in the subjective sense of reality of the self and objects. Imposture in a person undergoing analysis is, however, not only a function of individual character and psychopathology; it is also a function of certain inevitable requirements of the analytic situation which constitute a "pull" for its emergence. Vulnerable individuals will respond to this pull in revealing ways. Three case summaries illustrate the spectrum of imposturous tendencies.

Comparative bioinformatics analyses and profiling of lysosome-related organelle proteomes

NASA Astrophysics Data System (ADS)

Hu, Zhang-Zhi; Valencia, Julio C.; Huang, Hongzhan; Chi, An; Shabanowitz, Jeffrey; Hearing, Vincent J.; Appella, Ettore; Wu, Cathy

2007-01-01

Complete and accurate profiling of cellular organelle proteomes, while challenging, is important for the understanding of detailed cellular processes at the organelle level. Mass spectrometry technologies coupled with bioinformatics analysis provide an effective approach for protein identification and functional interpretation of organelle proteomes. In this study, we have compiled human organelle reference datasets from large-scale proteomic studies and protein databases for seven lysosome-related organelles (LROs), as well as the endoplasmic reticulum and mitochondria, for comparative organelle proteome analysis. Heterogeneous sources of human organelle proteins and rodent homologs are mapped to human UniProtKB protein entries based on ID and/or peptide mappings, followed by functional annotation and categorization using the iProXpress proteomic expression analysis system. Cataloging organelle proteomes allows close examination of both shared and unique proteins among various LROs and reveals their functional relevance. The proteomic comparisons show that LROs are a closely related family of organelles. The shared proteins indicate the dynamic and hybrid nature of LROs, while the unique transmembrane proteins may represent additional candidate marker proteins for LROs. This comparative analysis, therefore, provides a basis for hypothesis formulation and experimental validation of organelle proteins and their functional roles.

A Trans-omics Mathematical Analysis Reveals Novel Functions of the Ornithine Metabolic Pathway in Cancer Stem Cells

NASA Astrophysics Data System (ADS)

Koseki, Jun; Matsui, Hidetoshi; Konno, Masamitsu; Nishida, Naohiro; Kawamoto, Koichi; Kano, Yoshihiro; Mori, Masaki; Doki, Yuichiro; Ishii, Hideshi

2016-02-01

Bioinformatics and computational modelling are expected to offer innovative approaches in human medical science. In the present study, we performed computational analyses and made predictions using transcriptome and metabolome datasets obtained from fluorescence-based visualisations of chemotherapy-resistant cancer stem cells (CSCs) in the human oesophagus. This approach revealed an uncharacterized role for the ornithine metabolic pathway in the survival of chemotherapy-resistant CSCs. The present study fastens this rationale for further characterisation that may lead to the discovery of innovative drugs against robust CSCs.

Analysis of Tryptophan Residues in the Staphylococcal Multidrug Transporter QacA Reveals Long-Distance Functional Associations of Residues on Opposite Sides of the Membrane▿

PubMed Central

Hassan, Karl A.; Souhani, Talal; Skurray, Ronald A.; Brown, Melissa H.

2008-01-01

Tryptophan residues can possess a multitude of functions within a multidrug transport protein, e.g., mediating interactions with substrates or distal parts of the protein, or fulfilling a structural requirement, such as guiding the depth of membrane insertion. In this study, the nine tryptophan residues of the staphylococcal QacA multidrug efflux protein were individually mutated to alanine and phenylalanine, and the functional consequences of these changes were determined. Phenylalanine substitutions for each tryptophan residue were functionally tolerated. However, alanine modifications revealed an important functional role for three tryptophan residues, W58, W149, and W173, each of which is well conserved among QacA-related transport proteins in the major facilitator superfamily. The most functionally compromising mutation, an alanine substitution for W58, likely to be located at the extracellular interface of transmembrane segment 2, abolished all detectable QacA-mediated resistance and transport function. Second-site suppressor analyses identified several mutations that rescued the function of the W58A QacA mutant. Remarkably, all of these suppressor mutations were shown to be located in cytoplasmic loops between transmembrane helices 2 and 3 or 12 and 13, demonstrating novel functional associations between amino acid positions on opposite sides of the membrane and in distal N- and C-terminal regions of the QacA protein. PMID:18223078

[Factor structure of regional CBF and CMRglu values as a tool for the study of default mode of the brain].

PubMed

Kataev, G V; Korotkov, A D; Kireev, M V; Medvedev, S V

2013-01-01

In the present article it was shown that the functional connectivity of brain structures, revealed by factor analysis of resting PET CBF and rCMRglu data, is an adequate tool to study the default mode of the human brain. The identification of neuroanatomic systems of default mode (default mode network) during routine clinical PET investigations is important for further studying the functional organization of the normal brain and its reorganizations in pathological conditions.

Analysis of nucleotide diversity among alleles of the major bacterial blight resistance gene Xa27 in cultivars of rice (Oryza sativa) and its wild relatives.

PubMed

Bimolata, Waikhom; Kumar, Anirudh; Sundaram, Raman Meenakshi; Laha, Gouri Shankar; Qureshi, Insaf Ahmed; Reddy, Gajjala Ashok; Ghazi, Irfan Ahmad

2013-08-01

Xa27 is one of the important R-genes, effective against bacterial blight disease of rice caused by Xanthomonas oryzae pv. oryzae (Xoo). Using natural population of Oryza, we analyzed the sequence variation in the functionally important domains of Xa27 across the Oryza species. DNA sequences of Xa27 alleles from 27 rice accessions revealed higher nucleotide diversity among the reported R-genes of rice. Sequence polymorphism analysis revealed synonymous and non-synonymous mutations in addition to a number of InDels in non-coding regions of the gene. High sequence variation was observed in the promoter region including the 5'UTR with 'π' value 0.00916 and 'θ w ' = 0.01785. Comparative analysis of the identified Xa27 alleles with that of IRBB27 and IR24 indicated the operation of both positive selection (Ka/Ks > 1) and neutral selection (Ka/Ks ≈ 0). The genetic distances of alleles of the gene from Oryza nivara were nearer to IRBB27 as compared to IR24. We also found the presence of conserved and null UPT (upregulated by transcriptional activator) box in the isolated alleles. Considerable amino acid polymorphism was localized in the trans-membrane domain for which the functional significance is yet to be elucidated. However, the absence of functional UPT box in all the alleles except IRBB27 suggests the maintenance of single resistant allele throughout the natural population.

Phylogenetic and Functional Analysis of Metagenome Sequence from High-Temperature Archaeal Habitats Demonstrate Linkages between Metabolic Potential and Geochemistry

PubMed Central

Inskeep, William P.; Jay, Zackary J.; Herrgard, Markus J.; Kozubal, Mark A.; Rusch, Douglas B.; Tringe, Susannah G.; Macur, Richard E.; Jennings, Ryan deM.; Boyd, Eric S.; Spear, John R.; Roberto, Francisco F.

2013-01-01

Geothermal habitats in Yellowstone National Park (YNP) provide an unparalleled opportunity to understand the environmental factors that control the distribution of archaea in thermal habitats. Here we describe, analyze, and synthesize metagenomic and geochemical data collected from seven high-temperature sites that contain microbial communities dominated by archaea relative to bacteria. The specific objectives of the study were to use metagenome sequencing to determine the structure and functional capacity of thermophilic archaeal-dominated microbial communities across a pH range from 2.5 to 6.4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (∼40–45 Mb Sanger sequencing per site) was obtained from environmental DNA extracted from high-temperature sediments and/or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G + C content) and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport, and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.g., sulfide, oxygen, pH). These observations provide an ecological basis for understanding the distribution of indigenous archaeal lineages across high-temperature systems of YNP. PMID:23720654

Metagenomic analysis of the microbiota in the highly compartmented hindguts of six wood- or soil-feeding higher termites.

PubMed

Rossmassler, Karen; Dietrich, Carsten; Thompson, Claire; Mikaelyan, Aram; Nonoh, James O; Scheffrahn, Rudolf H; Sillam-Dussès, David; Brune, Andreas

2015-11-26

Termites are important contributors to carbon and nitrogen cycling in tropical ecosystems. Higher termites digest lignocellulose in various stages of humification with the help of an entirely prokaryotic microbiota housed in their compartmented intestinal tract. Previous studies revealed fundamental differences in community structure between compartments, but the functional roles of individual lineages in symbiotic digestion are mostly unknown. Here, we conducted a highly resolved analysis of the gut microbiota in six species of higher termites that feed on plant material at different levels of humification. Combining amplicon sequencing and metagenomics, we assessed similarities in community structure and functional potential between the major hindgut compartments (P1, P3, and P4). Cluster analysis of the relative abundances of orthologous gene clusters (COGs) revealed high similarities among wood- and litter-feeding termites and strong differences to humivorous species. However, abundance estimates of bacterial phyla based on 16S rRNA genes greatly differed from those based on protein-coding genes. Community structure and functional potential of the microbiota in individual gut compartments are clearly driven by the digestive strategy of the host. The metagenomics libraries obtained in this study provide the basis for future studies that elucidate the fundamental differences in the symbiont-mediated breakdown of lignocellulose and humus by termites of different feeding groups. The high proportion of uncultured bacterial lineages in all samples calls for a reference-independent approach for the correct taxonomic assignment of protein-coding genes.

Team talk and team activity in simulated medical emergencies: a discourse analytical approach.

PubMed

Gundrosen, Stine; Andenæs, Ellen; Aadahl, Petter; Thomassen, Gøril

2016-11-14

Communication errors can reduce patient safety, especially in emergency situations that require rapid responses by experts in a number of medical specialties. Talking to each other is crucial for utilizing the collective expertise of the team. Here we explored the functions of "team talk" (talking between team members) with an emphasis on the talk-work relationship in interdisciplinary emergency teams. Five interdisciplinary medical emergency teams were observed and videotaped during in situ simulations at an emergency department at a university hospital in Norway. Team talk and simultaneous actions were transcribed and analysed. We used qualitative discourse analysis to perform structural mapping of the team talk and to analyse the function of online commentaries (real-time observations and assessments of observations based on relevant cues in the clinical situation). Structural mapping revealed recurring and diverse patterns. Team expansion stood out as a critical phase in the teamwork. Online commentaries that occurred during the critical phase served several functions and demonstrated the inextricable interconnections between team talk and actions. Discourse analysis allowed us to capture the dynamics and complexity of team talk during a simulated emergency situation. Even though the team talk did not follow a predefined structure, the team members managed to manoeuvre safely within the complex situation. Our results support that online commentaries contributes to shared team situation awareness. Discourse analysis reveals naturally occurring communication strategies that trigger actions relevant for safe practice and thus provides supplemental insights into what comprises "good" team communication in medical emergencies.

Contributions of structural connectivity and cerebrovascular parameters to functional magnetic resonance imaging signals in mice at rest and during sensory paw stimulation.

PubMed

Schroeter, Aileen; Grandjean, Joanes; Schlegel, Felix; Saab, Bechara J; Rudin, Markus

2017-07-01

Previously, we reported widespread bilateral increases in stimulus-evoked functional magnetic resonance imaging signals in mouse brain to unilateral sensory paw stimulation. We attributed the pattern to arousal-related cardiovascular changes overruling cerebral autoregulation thereby masking specific signal changes elicited by local neuronal activity. To rule out the possibility that interhemispheric neuronal communication might contribute to bilateral functional magnetic resonance imaging responses, we compared stimulus-evoked functional magnetic resonance imaging responses to unilateral hindpaw stimulation in acallosal I/LnJ, C57BL/6, and BALB/c mice. We found bilateral blood-oxygenation-level dependent signal changes in all three strains, ruling out a dominant contribution of transcallosal communication as reason for bilaterality. Analysis of functional connectivity derived from resting-state functional magnetic resonance imaging, revealed that bilateral cortical functional connectivity is largely abolished in I/LnJ animals. Cortical functional connectivity in all strains correlated with structural connectivity in corpus callosum as revealed by diffusion tensor imaging. Given the profound influence of systemic hemodynamics on stimulus-evoked functional magnetic resonance imaging outcomes, we evaluated whether functional connectivity data might be affected by cerebrovascular parameters, i.e. baseline cerebral blood volume, vascular reactivity, and reserve. We found that effects of cerebral hemodynamics on functional connectivity are largely outweighed by dominating contributions of structural connectivity. In contrast, contributions of transcallosal interhemispheric communication to the occurrence of ipsilateral functional magnetic resonance imaging response of equal amplitude to unilateral stimuli seem negligible.

Comprehensive Analysis of DWARF14-LIKE2 (DLK2) Reveals Its Functional Divergence from Strigolactone-Related Paralogs

PubMed Central

Végh, Attila; Incze, Norbert; Fábián, Attila; Huo, Heqiang; Bradford, Kent J.; Balázs, Ervin; Soós, Vilmos

2017-01-01

Strigolactones (SLs) and related butenolides, originally identified as active seed germination stimulants of parasitic weeds, play important roles in many aspects of plant development. Two members of the D14 α/β hydrolase protein family, DWARF14 (D14) and KARRIKIN INSENSITIVE2 (KAI2) are essential for SL/butenolide signaling. The third member of the family in Arabidopsis, DWARF 14-LIKE2 (DLK2) is structurally very similar to D14 and KAI2, but its function is unknown. We demonstrated that DLK2 does not bind nor hydrolyze natural (+)5-deoxystrigol [(+)5DS], and weakly hydrolyzes non-natural strigolactone (-)5DS. A detailed genetic analysis revealed that DLK2 does not affect SL responses and can regulate seedling photomorphogenesis. DLK2 is upregulated in the dark dependent upon KAI2 and PHYTOCHROME INTERACTING FACTORS (PIFs), indicating that DLK2 might function in light signaling pathways. In addition, unlike its paralog proteins, DLK2 is not subject to rac-GR24-induced degradation, suggesting that DLK2 acts independently of MORE AXILLARY GROWTH2 (MAX2); however, regulation of DLK2 transcription is mostly accomplished through MAX2. In conclusion, these data suggest that DLK2 represents a divergent member of the DWARF14 family. PMID:28970845

Comprehensive Analysis of DWARF14-LIKE2 (DLK2) Reveals Its Functional Divergence from Strigolactone-Related Paralogs.

PubMed

Végh, Attila; Incze, Norbert; Fábián, Attila; Huo, Heqiang; Bradford, Kent J; Balázs, Ervin; Soós, Vilmos

2017-01-01

Strigolactones (SLs) and related butenolides, originally identified as active seed germination stimulants of parasitic weeds, play important roles in many aspects of plant development. Two members of the D14 α/β hydrolase protein family, DWARF14 (D14) and KARRIKIN INSENSITIVE2 (KAI2) are essential for SL/butenolide signaling. The third member of the family in Arabidopsis, DWARF 14-LIKE2 (DLK2) is structurally very similar to D14 and KAI2, but its function is unknown. We demonstrated that DLK2 does not bind nor hydrolyze natural (+)5-deoxystrigol [(+)5DS], and weakly hydrolyzes non-natural strigolactone (-)5DS. A detailed genetic analysis revealed that DLK2 does not affect SL responses and can regulate seedling photomorphogenesis. DLK2 is upregulated in the dark dependent upon KAI2 and PHYTOCHROME INTERACTING FACTORS (PIFs), indicating that DLK2 might function in light signaling pathways. In addition, unlike its paralog proteins, DLK2 is not subject to rac -GR24-induced degradation, suggesting that DLK2 acts independently of MORE AXILLARY GROWTH2 (MAX2); however, regulation of DLK2 transcription is mostly accomplished through MAX2. In conclusion, these data suggest that DLK2 represents a divergent member of the DWARF14 family.

Alpharetroviral Vector-mediated Gene Therapy for X-CGD: Functional Correction and Lack of Aberrant Splicing

PubMed Central

Kaufmann, Kerstin B.; Brendel, Christian; Suerth, Julia D.; Mueller-Kuller, Uta; Chen-Wichmann, Linping; Schwäble, Joachim; Pahujani, Shweta; Kunkel, Hana; Schambach, Axel; Baum, Christopher; Grez, Manuel

2013-01-01

Comparative integrome analysis has revealed that the most neutral integration pattern among retroviruses is attributed to alpharetroviruses. We chose X-linked chronic granulomatous disease (X-CGD) as model to evaluate the potential of self-inactivating (SIN) alpharetroviral vectors for gene therapy of monogenic diseases. Therefore, we combined the alpharetroviral vector backbone with the elongation factor-1α short promoter, both considered to possess a low genotoxic profile, to drive transgene (gp91phox) expression. Following efficient transduction transgene expression was sustained and provided functional correction of the CGD phenotype in a cell line model at low vector copy number. Further analysis in a murine X-CGD transplantation model revealed gene-marking of bone marrow cells and oxidase positive granulocytes in peripheral blood. Transduction of human X-CGD CD34+ cells provided functional correction up to wild-type levels and long-term expression upon transplantation into a humanized mouse model. In contrast to lentiviral vectors, no aberrantly spliced transcripts containing cellular exons fused to alpharetroviral sequences were found in transduced cells, implying that the safety profile of alpharetroviral vectors may extend beyond their neutral integration profile. Taken together, this highlights the potential of this SIN alpharetroviral system as a platform for new candidate vectors for future gene therapy of hematopoietic disorders. PMID:23207695

Global Proteomic Analysis in Trypanosomes Reveals Unique Proteins and Conserved Cellular Processes Impacted by Arginine Methylation

PubMed Central

Lott, Kaylen; Li, Jun; Fisk, John C.; Wang, Hao; Aletta, John M.; Qu, Jun; Read, Laurie K.

2013-01-01

Arginine methylation is a common posttranslational modification with reported functions in transcription, RNA processing and translation, and DNA repair. Trypanosomes encode five protein arginine methyltransferases, suggesting that arginine methylation exerts widespread impacts on the biology of these organisms. Here, we performed a global proteomic analysis of T. brucei to identify arginine methylated proteins and their sites of modification. Using an approach entailing two-dimensional chromatographic separation, and alternating electron transfer dissociation and collision induced dissociation, we identified 1332 methylarginines in 676 proteins. The resulting data set represents the largest compilation of arginine methylated proteins in any organism to date. Functional classification revealed numerous arginine methylated proteins involved in flagellar function, RNA metabolism, DNA replication and repair, and intracellular protein trafficking. Thus, arginine methylation has the potential to impact aspects of T. brucei gene expression, cell biology, and pathogenesis. Interestingly, pathways with known methylated proteins in higher eukaryotes were identified in this study, but often different components of the pathway were methylated in trypanosomes. Methylarginines were often identified in glycine rich contexts, although exceptions to this rule were detected. Collectively, these data inform on a multitude of aspects of trypanosome biology and serve as a guide for the identification of homologous arginine methylated proteins in higher eukaryotes. PMID:23872088

Electrical Neuroimaging of Music Processing Reveals Mid-Latency Changes with Level of Musical Expertise

PubMed Central

James, Clara E.; Oechslin, Mathias S.; Michel, Christoph M.; De Pretto, Michael

2017-01-01

This original research focused on the effect of musical training intensity on cerebral and behavioral processing of complex music using high-density event-related potential (ERP) approaches. Recently we have been able to show progressive changes with training in gray and white matter, and higher order brain functioning using (f)MRI [(functional) Magnetic Resonance Imaging], as well as changes in musical and general cognitive functioning. The current study investigated the same population of non-musicians, amateur pianists and expert pianists using spatio-temporal ERP analysis, by means of microstate analysis, and ERP source imaging. The stimuli consisted of complex musical compositions containing three levels of transgression of musical syntax at closure that participants appraised. ERP waveforms, microstates and underlying brain sources revealed gradual differences according to musical expertise in a 300–500 ms window after the onset of the terminal chords of the pieces. Within this time-window, processing seemed to concern context-based memory updating, indicated by a P3b-like component or microstate for which underlying sources were localized in the right middle temporal gyrus, anterior cingulate and right parahippocampal areas. Given that the 3 expertise groups were carefully matched for demographic factors, these results provide evidence of the progressive impact of training on brain and behavior. PMID:29163017

Synthesis of functional ceramic supports by ice templating and atomic layer deposition

NASA Astrophysics Data System (ADS)

Klotz, Michaela; Weber, Matthieu; Deville, Sylvain; Oison, Didier; Iatsunskyi, Igor; Coy, Emerson; Bechelany, Mikhael

2018-05-01

In this work, we report an innovative route for the manufacturing of functional ceramic supports, by combining ice templating of yttria stabilized zirconia (YSZ) and atomic layer deposition (ALD) of Al2O3 processes. Ceramic YSZ monoliths are prepared using the ice-templating process, which is based on the controlled crystallization of water following a thermal gradient. Sublimation of the ice and the sintering of the material reveal the straight micrometer sized pores shaped by the ice crystal growth. The high temperature sintering allows for the ceramic materials to present excellent mechanical strength and porosities of 67%. Next, the conformality benefit of ALD is used to deposit an alumina coating at the surface of the YSZ pores, in order to obtain a functional material. The Al2O3 thin films obtained by ALD are 100 nm thick and conformally deposited within the macroporous ceramic supports, as shown by SEM and EDS analysis. Mercury intrusion experiments revealed a reduction of the entrance pore diameter, in line with the growth per cycle of 2 Å of the ALD process. In addition to the manufacture of the innovative ceramic nanomaterials, this article also describes the fine characterization of the coatings obtained using mercury intrusion, SEM and XRD analysis.

Successive chlorothalonil applications inhibit soil nitrification and discrepantly affect abundances of functional genes in soil nitrogen cycling.

PubMed

Teng, Ying; Zhang, Manyun; Yang, Guangmei; Wang, Jun; Christie, Peter; Luo, Yongming

2017-02-01

Broad-spectrum fungicide chlorothalonil (CTN) is successively applied into intensive agriculture soil. However, the impacts of successive CTN applications on soil nitrification and related microorganisms remain poorly understood. A microcosm study was conducted to reveal the effects of successive CTN applications on soil nitrification and functional genes involved in soil nitrogen (N) cycling. The CTN at the dosages of 5 mg kg -1 dry soil (RD) and 25 mg kg -1 dry soil (5RD) was successively applied into the test soil at 7-day intervals which resulted in the accumulations of CTN residues. After 28 days of incubation, CTN residues in the RD and 5RD treatments were 3.14 and 69.7 mg kg -1 dry soil respectively. Net nitrification rates in the RD and 5RD treatments were lower than that obtained from the blank control (CK). Real-time PCR analysis revealed that AOA and AOB amoA gene abundances were significantly decreased by CTN applications. Moreover, CTN applications also discrepantly decreased the abundances of functional genes involved in soil denitrification, with the exception of nosZ gene. Principal component analysis further supported the observation that successive CTN applications could result in enhanced ecological toxicity.

Transcriptomic basis for drought-resistance in Brassica napus L.

NASA Astrophysics Data System (ADS)

Wang, Pei; Yang, Cuiling; Chen, Hao; Song, Chunpeng; Zhang, Xiao; Wang, Daojie

2017-01-01

Based on transcriptomic data from four experimental settings with drought-resistant and drought-sensitive cultivars under drought and well-watered conditions, statistical analysis revealed three categories encompassing 169 highly differentially expressed genes (DEGs) in response to drought in Brassica napus L., including 37 drought-resistant cultivar-related genes, 35 drought-sensitive cultivar-related genes and 97 cultivar non-specific ones. We provide evidence that the identified DEGs were fairly uniformly distributed on different chromosomes and their expression patterns are variety specific. Except commonly enriched in response to various stimuli or stresses, different categories of DEGs show specific enrichment in certain biological processes or pathways, which indicated the possibility of functional differences among the three categories. Network analysis revealed relationships among the 169 DEGs, annotated biological processes and pathways. The 169 DEGs can be classified into different functional categories via preferred pathways or biological processes. Some pathways might simultaneously involve a large number of shared DEGs, and these pathways are likely to cross-talk and have overlapping biological functions. Several members of the identified DEGs fit to drought stress signal transduction pathway in Arabidopsis thaliana. Finally, quantitative real-time PCR validations confirmed the reproducibility of the RNA-seq data. These investigations are profitable for the improvement of crop varieties through transgenic engineering.

Multidisciplinary and biodanza intervention for the management of fibromyalgia.

PubMed

Carbonell-Baeza, Ana; Ruiz, Jonatan R; Aparicio, Virginia A; Martins-Pereira, Clelia M; Gatto-Cardia, M Claudia; Martinez, Jose M; Ortega, Francisco B; Delgado-Fernandez, Manuel

2012-01-01

To evaluate and compare the effectiveness of a 16-week multidisciplinary (exercise plus psychological therapy) and biodanza intervention in women with fibromyalgia. Thirty-eight women with fibromyalgia were distributed to a 16-week multidisciplinary (3-times/week) intervention (n=21) or Biodanza (1-time/week) intervention (n=17). We assessed tender point, body composition, physical fitness and psychological outcomes (Fibromyalgia Impact Questionnaire, the Short-Form Health Survey 36 questionnaire (SF-36), the Hospital Anxiety and Depression Scale, Vanderbilt Pain Management Inventory (VPMI), Rosenberg Self-Esteem Scale and General Self-Efficacy Scale). We observed a significant group*time interaction effect for the scales of SF-36 physical role (P=0.038) and social functioning (P=0.030) and for the passive coping scale in VPMI (P=0.043). Post hoc analysis revealed a significant improvement on social functioning (P=0.030) in the multidisciplinary group whereas it did not change in the Biodanza group. Post hoc analysis revealed a reduction in the use of passive coping (positive) (P less than 0.001) in the multidisciplinary group. There was no significant interaction or time effect in body composition and physical fitness. 16 weeks of multidisciplinary intervention induced greater benefits than a Biodanza intervention for social functioning and the use of passive coping strategies in women with fibromyalgia.

Electrical Neuroimaging of Music Processing Reveals Mid-Latency Changes with Level of Musical Expertise.

PubMed

James, Clara E; Oechslin, Mathias S; Michel, Christoph M; De Pretto, Michael

2017-01-01

This original research focused on the effect of musical training intensity on cerebral and behavioral processing of complex music using high-density event-related potential (ERP) approaches. Recently we have been able to show progressive changes with training in gray and white matter, and higher order brain functioning using (f)MRI [(functional) Magnetic Resonance Imaging], as well as changes in musical and general cognitive functioning. The current study investigated the same population of non-musicians, amateur pianists and expert pianists using spatio-temporal ERP analysis, by means of microstate analysis, and ERP source imaging. The stimuli consisted of complex musical compositions containing three levels of transgression of musical syntax at closure that participants appraised. ERP waveforms, microstates and underlying brain sources revealed gradual differences according to musical expertise in a 300-500 ms window after the onset of the terminal chords of the pieces. Within this time-window, processing seemed to concern context-based memory updating, indicated by a P3b-like component or microstate for which underlying sources were localized in the right middle temporal gyrus, anterior cingulate and right parahippocampal areas. Given that the 3 expertise groups were carefully matched for demographic factors, these results provide evidence of the progressive impact of training on brain and behavior.

Qualitative ubiquitome unveils the potential significances of protein lysine ubiquitination in hyphal growth of Aspergillus nidulans.

PubMed

Chu, Xin-Ling; Feng, Ming-Guang; Ying, Sheng-Hua

2016-02-01

Protein ubiquitination is an evolutionarily conserved post-translational modification process in eukaryotes, and it plays an important role in many biological processes. Aspergillus nidulans, a model filamentous fungus, contributes to our understanding of cellular physiology, metabolism and genetics, but its ubiquitination is not completely revealed. In this study, the ubiquitination sites in the proteome of A. nidulans were identified using a highly sensitive mass spectrometry combined with immuno-affinity enrichment of the ubiquitinated peptides. The 4816 ubiquitination sites were identified in 1913 ubiquitinated proteins, accounting for 18.1% of total proteins in A. nidulans. Bioinformatic analysis suggested that the ubiquitinated proteins associated with a number of biological functions and displayed various sub-cellular localisations. Meanwhile, seven motifs were revealed from the ubiquitinated peptides, and significantly over-presented in the different pathways. Comparison of the enriched functional catalogues indicated that the ubiquitination functions divergently during growth of A. nidulans and Saccharomyces cerevisiae. Additionally, the proteins in A. nidulans-specific sub-category (cell growth/morphogenesis) were subjected to the protein interaction analysis which demonstrated that ubiquitination is involved in the comprehensive protein interactions. This study presents a first proteomic view of ubiquitination in the filamentous fungus, and provides an initial framework for exploring the physiological roles of ubiquitination in A. nidulans.

EELS Analysis of Nylon 6 Nanofibers Reinforced with Nitroxide-Functionalized Graphene Oxide.

PubMed

Leyva-Porras, César; Ornelas-Gutiérrez, C; Miki-Yoshida, M; Avila-Vega, Yazmín I; Macossay, Javier; Bonilla-Cruz, José

2014-01-01

A detailed analysis by transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) of nitroxide-functionalized graphene oxide layers (GOFT) dispersed in Nylon 6 nanofibers is reported herein. The functionalization and exfoliation process of graphite oxide to GOFT was confirmed by TEM using electron diffraction patterns (EDP), wherein 1 to 4 graphene layers of GOFT were observed. The distribution and alignment of GOFT layers within a sample of Nylon 6 nanofiber reveals that GOFT platelets are mainly within the fiber, but some were partially protruding from it. Furthermore, Nylon 6 nanofibers exhibit an average diameter of 225 nm with several microns in length. GOFT platelets embedded into the fiber, the pristine fiber, and amorphous carbon were analyzed by EELS where each spectra [corresponding to the carbon edge (C-K)] exhibited changes in the fine structure, allowing a clear distinction between: i) GOFT single-layers, ii) Nylon-6 nanofibers, and iii) the carbon substrate. EELS analysis is presented here for the first time as a powerful tool to identify functionalized graphene single-layers (< 4 layers of GOFT) into a Nylon 6 nanofiber composite.

EELS Analysis of Nylon 6 Nanofibers Reinforced with Nitroxide-Functionalized Graphene Oxide

PubMed Central

Leyva-Porras, César; Ornelas-Gutiérrez, C.; Miki-Yoshida, M.; Avila-Vega, Yazmín I.; Macossay, Javier; Bonilla-Cruz, José

2014-01-01

A detailed analysis by transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) of nitroxide-functionalized graphene oxide layers (GOFT) dispersed in Nylon 6 nanofibers is reported herein. The functionalization and exfoliation process of graphite oxide to GOFT was confirmed by TEM using electron diffraction patterns (EDP), wherein 1 to 4 graphene layers of GOFT were observed. The distribution and alignment of GOFT layers within a sample of Nylon 6 nanofiber reveals that GOFT platelets are mainly within the fiber, but some were partially protruding from it. Furthermore, Nylon 6 nanofibers exhibit an average diameter of 225 nm with several microns in length. GOFT platelets embedded into the fiber, the pristine fiber, and amorphous carbon were analyzed by EELS where each spectra [corresponding to the carbon edge (C-K)] exhibited changes in the fine structure, allowing a clear distinction between: i) GOFT single-layers, ii) Nylon-6 nanofibers, and iii) the carbon substrate. EELS analysis is presented here for the first time as a powerful tool to identify functionalized graphene single-layers (< 4 layers of GOFT) into a Nylon 6 nanofiber composite. PMID:24634536

Occupational activity and cognitive reserve: implications in terms of prevention of cognitive aging and Alzheimer’s disease

PubMed Central

Adam, Stéphane; Bonsang, Eric; Grotz, Catherine; Perelman, Sergio

2013-01-01

This paper investigates the relationship between the concept of activity (including both professional and nonprofessional) and cognitive functioning among older European individuals. In this research, we used data collected during the first wave of SHARE (Survey on Health, Ageing and Retirement in Europe), and a measurement approach known as stochastic frontier analysis, derived from the economic literature. SHARE includes a large population (n > 25,000) geographically distributed across Europe, and analyzes several dimensions simultaneously, including physical and mental health activity. The main advantages of stochastic frontier analysis are that it allows estimation of parametric function relating cognitive scores and driving factors at the boundary and disentangles frontier noise and distance to frontier components, as well as testing the effect of potential factors on these distances simultaneously. The analysis reveals that all activities are positively related to cognitive functioning in elderly people. Our results are discussed in terms of prevention of cognitive aging and Alzheimer’s disease, and regarding the potential impact that some retirement programs might have on cognitive functioning in individuals across Europe. PMID:23671387

Runx2 contributes to the regenerative potential of the mammary epithelium.

PubMed

Ferrari, Nicola; Riggio, Alessandra I; Mason, Susan; McDonald, Laura; King, Ayala; Higgins, Theresa; Rosewell, Ian; Neil, James C; Smalley, Matthew J; Sansom, Owen J; Morris, Joanna; Cameron, Ewan R; Blyth, Karen

2015-10-22

Although best known for its role in bone development and associated structures the transcription factor RUNX2 is expressed in a wide range of lineages, including those of the mammary gland. Previous studies have indicated that Runx2 can regulate aspects of mammary cell function and influence the properties of cancer cells. In this study we investigate the role of Runx2 in the mammary stem/progenitor population and its relationship with WNT signalling. Results show that RUNX2 protein is differentially expressed throughout embryonic and adult development of the murine mammary gland with high levels of expression in mammary stem-cell enriched cultures. Importantly, functional analysis reveals a role for Runx2 in mammary stem/progenitor cell function in in vitro and in vivo regenerative assays. Furthermore, RUNX2 appears to be associated with WNT signalling in the mammary epithelium and is specifically upregulated in mouse models of WNT-driven breast cancer. Overall our studies reveal a novel function for Runx2 in regulating mammary epithelial cell regenerative potential, possibly acting as a downstream target of WNT signalling.

Runx2 contributes to the regenerative potential of the mammary epithelium

PubMed Central

Ferrari, Nicola; Riggio, Alessandra I.; Mason, Susan; McDonald, Laura; King, Ayala; Higgins, Theresa; Rosewell, Ian; Neil, James C.; Smalley, Matthew J.; Sansom, Owen J.; Morris, Joanna; Cameron, Ewan R.; Blyth, Karen

2015-01-01

Although best known for its role in bone development and associated structures the transcription factor RUNX2 is expressed in a wide range of lineages, including those of the mammary gland. Previous studies have indicated that Runx2 can regulate aspects of mammary cell function and influence the properties of cancer cells. In this study we investigate the role of Runx2 in the mammary stem/progenitor population and its relationship with WNT signalling. Results show that RUNX2 protein is differentially expressed throughout embryonic and adult development of the murine mammary gland with high levels of expression in mammary stem-cell enriched cultures. Importantly, functional analysis reveals a role for Runx2 in mammary stem/progenitor cell function in in vitro and in vivo regenerative assays. Furthermore, RUNX2 appears to be associated with WNT signalling in the mammary epithelium and is specifically upregulated in mouse models of WNT-driven breast cancer. Overall our studies reveal a novel function for Runx2 in regulating mammary epithelial cell regenerative potential, possibly acting as a downstream target of WNT signalling. PMID:26489514