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  1. Cellular Dynamics Revealed by Digital Holographic Microscopy☆

    KAUST Repository

    Marquet, P.; Depeursinge, Christian; Jourdain, P.

    2016-01-01

    Digital holographic microscopy (DHM) is a new optical method that provides, without the use of any contrast agent, real-time, three-dimensional images of transparent living cells, with an axial sensitivity of a few tens of nanometers. They result from the hologram numerical reconstruction process, which permits a sub wavelength calculation of the phase shift, produced on the transmitted wave front, by the optically probed cells, namely the quantitative phase signal (QPS). Specifically, in addition to measurements of cellular surface morphometry and intracellular refractive index (RI), various biophysical cellular parameters including dry mass, absolute volume, membrane fluctuations at the nanoscale and biomechanical properties, transmembrane water permeability as swell as current, can be derived from the QPS. This article presents how quantitative phase DHM (QP-DHM) can explored cell dynamics at the nanoscale with a special attention to both the study of neuronal dynamics and the optical resolution of local neuronal network.

  2. Cellular Dynamics Revealed by Digital Holographic Microscopy☆

    KAUST Repository

    Marquet, P.

    2016-11-22

    Digital holographic microscopy (DHM) is a new optical method that provides, without the use of any contrast agent, real-time, three-dimensional images of transparent living cells, with an axial sensitivity of a few tens of nanometers. They result from the hologram numerical reconstruction process, which permits a sub wavelength calculation of the phase shift, produced on the transmitted wave front, by the optically probed cells, namely the quantitative phase signal (QPS). Specifically, in addition to measurements of cellular surface morphometry and intracellular refractive index (RI), various biophysical cellular parameters including dry mass, absolute volume, membrane fluctuations at the nanoscale and biomechanical properties, transmembrane water permeability as swell as current, can be derived from the QPS. This article presents how quantitative phase DHM (QP-DHM) can explored cell dynamics at the nanoscale with a special attention to both the study of neuronal dynamics and the optical resolution of local neuronal network.

  3. Quantitative proteomic assessment of very early cellular signaling events

    DEFF Research Database (Denmark)

    Dengjel, Joern; Akimov, Vyacheslav; Olsen, Jesper V

    2007-01-01

    Technical limitations have prevented proteomic analyses of events occurring less than 30 s after signal initiation. We developed an automated, continuous quench-flow system allowing quantitative proteomic assessment of very early cellular signaling events (qPACE) with a time resolution of 1 s...

  4. Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development

    Science.gov (United States)

    Hadel, Diana M.; Keller, Bradley B.; Sandell, Lisa L.

    2014-03-01

    Confocal microscopy has been an invaluable tool for studying cellular or sub-cellular biological processes. The study of vertebrate embryology is based largely on examination of whole embryos and organs. The application of confocal microscopy to immunostained whole mount embryos, combined with three dimensional (3D) image reconstruction technologies, opens new avenues for synthesizing molecular, cellular and anatomical analysis of vertebrate development. Optical cropping of the region of interest enables visualization of structures that are morphologically complex or obscured, and solid surface rendering of fluorescent signal facilitates understanding of 3D structures. We have applied these technologies to whole mount immunostained mouse embryos to visualize developmental morphogenesis of the mammalian inner ear and heart. Using molecular markers of neuron development and transgenic reporters of neural crest cell lineage we have examined development of inner ear neurons that originate from the otic vesicle, along with the supporting glial cells that derive from the neural crest. The image analysis reveals a previously unrecognized coordinated spatial organization between migratory neural crest cells and neurons of the cochleovestibular nerve. The images also enable visualization of early cochlear spiral nerve morphogenesis relative to the developing cochlea, demonstrating a heretofore unknown association of neural crest cells with extending peripheral neurite projections. We performed similar analysis of embryonic hearts in mouse and chick, documenting the distribution of adhesion molecules during septation of the outflow tract and remodeling of aortic arches. Surface rendering of lumen space defines the morphology in a manner similar to resin injection casting and micro-CT.

  5. Nuclear protein accumulation in cellular senescence and organismal aging revealed with a novel single-cell resolution fluorescence microscopy assay.

    Science.gov (United States)

    De Cecco, Marco; Jeyapalan, Jessie; Zhao, Xiaoai; Tamamori-Adachi, Mimi; Sedivy, John M

    2011-10-01

    Replicative cellular senescence was discovered some 50 years ago. The phenotypes of senescent cells have been investigated extensively in cell culture, and found to affect essentially all aspects of cellular physiology. The relevance of cellular senescence in the context of age-associated pathologies as well as normal aging is a topic of active and ongoing interest. Considerable effort has been devoted to biomarker discovery to enable the microscopic detection of single senescent cells in tissues. One characteristic of senescent cells documented very early in cell culture studies was an increase in cell size and total protein content, but whether this occurs in vivo is not known. A limiting factor for studies of protein content and localization has been the lack of suitable fluorescence microscopy tools. We have developed an easy and flexible method, based on the merocyanine dye known as NanoOrange, to visualize and quantitatively measure total protein levels by high resolution fluorescence microscopy. NanoOrange staining can be combined with antibody-based immunofluorescence, thus providing both specific target and total protein information in the same specimen. These methods are optimally combined with automated image analysis platforms for high throughput analysis. We document here increasing protein content and density in nuclei of senescent human and mouse fibroblasts in vitro, and in liver nuclei of aged mice in vivo. Additionally, in aged liver nuclei NanoOrange revealed protein-dense foci that colocalize with centromeric heterochromatin.

  6. Network analysis of oyster transcriptome revealed a cascade of cellular responses during recovery after heat shock.

    Directory of Open Access Journals (Sweden)

    Lingling Zhang

    Full Text Available Oysters, as a major group of marine bivalves, can tolerate a wide range of natural and anthropogenic stressors including heat stress. Recent studies have shown that oysters pretreated with heat shock can result in induced heat tolerance. A systematic study of cellular recovery from heat shock may provide insights into the mechanism of acquired thermal tolerance. In this study, we performed the first network analysis of oyster transcriptome by reanalyzing microarray data from a previous study. Network analysis revealed a cascade of cellular responses during oyster recovery after heat shock and identified responsive gene modules and key genes. Our study demonstrates the power of network analysis in a non-model organism with poor gene annotations, which can lead to new discoveries that go beyond the focus on individual genes.

  7. Cellular autofluorescence imaging for early diagnosis of cancers

    Science.gov (United States)

    Steenkeste, Karine; Deniset, Ariane; Lecart, Sandrine; Leveque-Fort, Sandrine; Fontaine-Aupart, Marie-Pierre; Ferlicot, Sophie; Eschwege, Pascal

    2005-08-01

    Urinary cytology is employed in diagnostic guidelines of bladder cancer in anatomo-pathological laboratories mostly for its ability to diagnose non detectable cancers using cystoscopy, but also because it is a non-invasive and non-constraining technique for a regular follow-up of the more exposed populations. The impossibility to detect such cancers is mainly due to their localization either in the bladder or in the upper urinary tract and the prostate. However, urinary cytology lacks sensitivity, especially for the detection of low grade low stage tumors due to inherent limitation of morphological criteria to distinguish low grade tumor cells from normal urothelial cells. For this purpose, we developed, in addition to urinary cytology, an original screening of these cytological slides by using spectrally-resolved and time-resolved fluorescence as a contrast factor, without changing any parameters in the cytological slide preparation. This method takes advantage of a femtosecond Ti:sapphire laser, continuously tunable in the spectral range 700-950 nm allowing the observation of most endogenous cellular chromophores by biphotonic excitation. A commercial confocal microscope was also used in the measurements allowing an excitation of the samples between 458 nm and 633 nm. We observed that the fluorescence emission is differentially distributed in normal and pathological urothelial cells. Spectral- and time-resolved measurements attested this difference over about one hundred cases which have been tested to confirm the high accuracy of this non-invasive technique.

  8. Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction.

    Science.gov (United States)

    Song, Lili; Zhuang, Pengwei; Lin, Mengya; Kang, Mingqin; Liu, Hongyue; Zhang, Yuping; Yang, Zhen; Chen, Yunlong; Zhang, Yanjun

    2017-09-01

    Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.

  9. Initial investigations of microscale cellular convection in an equatorial marine atmospheric boundary layer revealed by lidar

    Science.gov (United States)

    Cooper, D. I.; Eichinger, W. E.; Ecke, R. E.; Kao, J. C. Y.; Reisner, J. M.; Tellier, L. L.

    During the Combined Sensor Program (CSP) in March of 1996, the Los Alamos National Laboratory (LANL) fielded an advanced scanning Raman lidar. The lidar was part of a larger suite of micrometeorological sensors to quantify processes associated with the ocean-atmosphere interface, including intermittency and coherent atmospheric features in the “warm pool” of the Tropical Western Pacific (TWP) near Manus Island (2° S. lat, 147° E. long). Initial inspection of the data has revealed excellent information on the microscale vertical and horizontal spatial and temporal structure of the equatorial Marine Atmospheric Boundary Layer (MABL). The data from this experiment have added to the increasing body of measurements on surface layer convection and intermittency including, for the first time, the observation of microscale cellular convective structures such as hexagonal patterns associated with Rayleigh-Bénard cells.

  10. Assessment of Membrane Fluidity Fluctuations during Cellular Development Reveals Time and Cell Type Specificity

    KAUST Repository

    Noutsi, Bakiza Kamal; Gratton, Enrico; Chaieb, Saharoui

    2016-01-01

    Cell membrane is made up of a complex structure of lipids and proteins that diffuse laterally giving rise to what we call membrane fluidity. During cellular development, such as differentiation cell membranes undergo dramatic fluidity changes induced by proteins such as ARC and Cofilin among others. In this study we used the generalized polarization (GP) property of fluorescent probe Laurdan using two-photon microscopy to determine membrane fluidity as a function of time and for various cell lines. A low GP value corresponds to a higher fluidity and a higher GP value is associated with a more rigid membrane. Four different cell lines were monitored such as hN2, NIH3T3, HEK293 and L6 cells. Membrane fluidity was measured at 12h, 72h and 92 h. Our results show significant changes in membrane fluidity among all cell types at different time points. GP values tend to increase significantly within 92 h in hN2 cells and 72 h in NIH3T3 cells and only at 92 h in HEK293 cells. L6 showed a marked decrease in membrane fluidity at 72 h and starts to increase at 92 h. As expected, NIH3T3 cells have more rigid membrane at earlier time points. On the other hand, neurons tend to have the highest membrane fluidity at early time points emphasizing its correlation with plasticity and the need for this malleability during differentiation. This study sheds light on the involvement of membrane fluidity during neuronal differentiation and development of other cell lines.

  11. Assessment of Membrane Fluidity Fluctuations during Cellular Development Reveals Time and Cell Type Specificity

    KAUST Repository

    Noutsi, Bakiza Kamal

    2016-06-30

    Cell membrane is made up of a complex structure of lipids and proteins that diffuse laterally giving rise to what we call membrane fluidity. During cellular development, such as differentiation cell membranes undergo dramatic fluidity changes induced by proteins such as ARC and Cofilin among others. In this study we used the generalized polarization (GP) property of fluorescent probe Laurdan using two-photon microscopy to determine membrane fluidity as a function of time and for various cell lines. A low GP value corresponds to a higher fluidity and a higher GP value is associated with a more rigid membrane. Four different cell lines were monitored such as hN2, NIH3T3, HEK293 and L6 cells. Membrane fluidity was measured at 12h, 72h and 92 h. Our results show significant changes in membrane fluidity among all cell types at different time points. GP values tend to increase significantly within 92 h in hN2 cells and 72 h in NIH3T3 cells and only at 92 h in HEK293 cells. L6 showed a marked decrease in membrane fluidity at 72 h and starts to increase at 92 h. As expected, NIH3T3 cells have more rigid membrane at earlier time points. On the other hand, neurons tend to have the highest membrane fluidity at early time points emphasizing its correlation with plasticity and the need for this malleability during differentiation. This study sheds light on the involvement of membrane fluidity during neuronal differentiation and development of other cell lines.

  12. Telomere length and early severe social deprivation: linking early adversity and cellular aging

    Science.gov (United States)

    Drury, SS; Theall, K; Gleason, MM; Smyke, AT; De Vivo, I; Wong, JYY; Fox, NA; Zeanah, CH; Nelson, CA

    2012-01-01

    Accelerated telomere length attrition has been associated with psychological stress and early adversity in adults; however, no studies have examined whether telomere length in childhood is associated with early experiences. The Bucharest Early Intervention Project is a unique randomized controlled trial of foster care placement compared with continued care in institutions. As a result of the study design, participants were exposed to a quantified range of time in institutional care, and represented an ideal population in which to examine the association between a specific early adversity, institutional care and telomere length. We examined the association between average relative telomere length, telomere repeat copy number to single gene copy number (T/S) ratio and exposure to institutional care quantified as the percent of time at baseline (mean age 22 months) and at 54 months of age that each child lived in the institution. A significant negative correlation between T/S ratio and percentage of time was observed. Children with greater exposure to institutional care had significantly shorter relative telomere length in middle childhood. Gender modified this main effect. The percentage of time in institutional care at baseline significantly predicted telomere length in females, whereas the percentage of institutional care at 54 months was strongly predictive of telomere length in males. This is the first study to demonstrate an association between telomere length and institutionalization, the first study to find an association between adversity and telomere length in children, and contributes to the growing literature linking telomere length and early adversity. PMID:21577215

  13. Early Neolithic water wells reveal the world's oldest wood architecture.

    Science.gov (United States)

    Tegel, Willy; Elburg, Rengert; Hakelberg, Dietrich; Stäuble, Harald; Büntgen, Ulf

    2012-01-01

    The European Neolithization ~6000-4000 BC represents a pivotal change in human history when farming spread and the mobile style of life of the hunter-foragers was superseded by the agrarian culture. Permanent settlement structures and agricultural production systems required fundamental innovations in technology, subsistence, and resource utilization. Motivation, course, and timing of this transformation, however, remain debatable. Here we present annually resolved and absolutely dated dendroarchaeological information from four wooden water wells of the early Neolithic period that were excavated in Eastern Germany. A total of 151 oak timbers preserved in a waterlogged environment were dated between 5469 and 5098 BC and reveal unexpectedly refined carpentry skills. The recently discovered water wells enable for the first time a detailed insight into the earliest wood architecture and display the technological capabilities of humans ~7000 years ago. The timbered well constructions made of old oak trees feature an unopened tree-ring archive from which annually resolved and absolutely dated environmental data can be culled. Our results question the principle of continuous evolutionary development in prehistoric technology, and contradict the common belief that metal was necessary for complex timber constructions. Early Neolithic craftsmanship now suggests that the first farmers were also the first carpenters.

  14. Early Neolithic water wells reveal the world's oldest wood architecture.

    Directory of Open Access Journals (Sweden)

    Willy Tegel

    Full Text Available The European Neolithization ~6000-4000 BC represents a pivotal change in human history when farming spread and the mobile style of life of the hunter-foragers was superseded by the agrarian culture. Permanent settlement structures and agricultural production systems required fundamental innovations in technology, subsistence, and resource utilization. Motivation, course, and timing of this transformation, however, remain debatable. Here we present annually resolved and absolutely dated dendroarchaeological information from four wooden water wells of the early Neolithic period that were excavated in Eastern Germany. A total of 151 oak timbers preserved in a waterlogged environment were dated between 5469 and 5098 BC and reveal unexpectedly refined carpentry skills. The recently discovered water wells enable for the first time a detailed insight into the earliest wood architecture and display the technological capabilities of humans ~7000 years ago. The timbered well constructions made of old oak trees feature an unopened tree-ring archive from which annually resolved and absolutely dated environmental data can be culled. Our results question the principle of continuous evolutionary development in prehistoric technology, and contradict the common belief that metal was necessary for complex timber constructions. Early Neolithic craftsmanship now suggests that the first farmers were also the first carpenters.

  15. Time-resolved spectroscopic imaging reveals the fundamentals of cellular NADH fluorescence.

    Science.gov (United States)

    Li, Dong; Zheng, Wei; Qu, Jianan Y

    2008-10-15

    A time-resolved spectroscopic imaging system is built to study the fluorescence characteristics of nicotinamide adenine dinucleotide (NADH), an important metabolic coenzyme and endogenous fluorophore in cells. The system provides a unique approach to measure fluorescence signals in different cellular organelles and cytoplasm. The ratios of free over protein-bound NADH signals in cytosol and nucleus are slightly higher than those in mitochondria. The mitochondrial fluorescence contributes about 70% of overall cellular fluorescence and is not a completely dominant signal. Furthermore, NADH signals in mitochondria, cytosol, and the nucleus respond to the changes of cellular activity differently, suggesting that cytosolic and nuclear fluorescence may complicate the well-known relationship between mitochondrial fluorescence and cellular metabolism.

  16. Differential association with cellular substructures of pseudorabies virus DNA during early and late phases of replication

    International Nuclear Information System (INIS)

    Ben-Porat, T.; Veach, R.A.; Blankenship, M.L.; Kaplan, A.S.

    1984-01-01

    Pseudorabies virus DNA synthesis can be divided into two phases, early and late, which can be distinguished from each other on the basis of the structures of the replicating DNA. The two types of replicating virus DNA can also be distinguished from each other on the basis of the cellular substructures with which each is associated. Analysis by electron microscopic autoradiography showed that during the first round of replication, nascent virus DNA was found in the vicinity of the nuclear membrane; during later rounds of replication the nascent virus DNA was located centrally within the nucleus. The degree of association of virus DNA synthesized at early and late phases with the nuclear matrix fractions also differed; a larger proportion of late than of early nascent virus DNA was associated with this fraction. While nascent cellular DNA only was associated in significant amounts with the nuclear matrix fraction, a large part (up to 40%) of all the virus DNA remained associated with this fraction. However, no retention of specific virus proteins in this fraction was observed. Except for two virus proteins, which were preferentially extracted from the nuclear matrix, approximately 20% of all virus proteins remained in the nuclear matrix fraction. The large proportion of virus DNA associated with the nuclear fraction indicated that virus DNA may be intimately associated with some proteins

  17. Comparative genomics of neuroglobin reveals its early origins.

    Directory of Open Access Journals (Sweden)

    Jasmin Dröge

    Full Text Available Neuroglobin (Ngb is a hexacoordinated globin expressed mainly in the central and peripheral nervous system of vertebrates. Although several hypotheses have been put forward regarding the role of neuroglobin, its definite function remains uncertain. Ngb appears to have a neuro-protective role enhancing cell viability under hypoxia and other types of oxidative stress. Ngb is phylogenetically ancient and has a substitution rate nearly four times lower than that of other vertebrate globins, e.g. hemoglobin. Despite its high sequence conservation among vertebrates Ngb seems to be elusive in invertebrates.We determined candidate orthologs in invertebrates and identified a globin of the placozoan Trichoplax adhaerens that is most likely orthologous to vertebrate Ngb and confirmed the orthologous relationship of the polymeric globin of the sea urchin Strongylocentrotus purpuratus to Ngb. The putative orthologous globin genes are located next to genes orthologous to vertebrate POMT2 similarly to localization of vertebrate Ngb. The shared syntenic position of the globins from Trichoplax, the sea urchin and of vertebrate Ngb strongly suggests that they are orthologous. A search for conserved transcription factor binding sites (TFBSs in the promoter regions of the Ngb genes of different vertebrates via phylogenetic footprinting revealed several TFBSs, which may contribute to the specific expression of Ngb, whereas a comparative analysis with myoglobin revealed several common TFBSs, suggestive of regulatory mechanisms common to globin genes.Identification of the placozoan and echinoderm genes orthologous to vertebrate neuroglobin strongly supports the hypothesis of the early evolutionary origin of this globin, as it shows that neuroglobin was already present in the placozoan-bilaterian last common ancestor. Computational determination of the transcription factor binding sites repertoire provides on the one hand a set of transcriptional factors that are

  18. Coordination of cellular differentiation, polarity, mitosis and meiosis - New findings from early vertebrate oogenesis.

    Science.gov (United States)

    Elkouby, Yaniv M; Mullins, Mary C

    2017-10-15

    A mechanistic dissection of early oocyte differentiation in vertebrates is key to advancing our knowledge of germline development, reproductive biology, the regulation of meiosis, and all of their associated disorders. Recent advances in the field include breakthroughs in the identification of germline stem cells in Medaka, in the cellular architecture of the germline cyst in mice, in a mechanistic dissection of chromosomal pairing and bouquet formation in meiosis in mice, in tracing oocyte symmetry breaking to the chromosomal bouquet of meiosis in zebrafish, and in the biology of the Balbiani body, a universal oocyte granule. Many of the major events in early oogenesis are universally conserved, and some are co-opted for species-specific needs. The chromosomal events of meiosis are of tremendous consequence to gamete formation and have been extensively studied. New light is now being shed on other aspects of early oocyte differentiation, which were traditionally considered outside the scope of meiosis, and their coordination with meiotic events. The emerging theme is of meiosis as a common groundwork for coordinating multifaceted processes of oocyte differentiation. In an accompanying manuscript we describe methods that allowed for investigations in the zebrafish ovary to contribute to these breakthroughs. Here, we review these advances mostly from the zebrafish and mouse. We discuss oogenesis concepts across established model organisms, and construct an inclusive paradigm for early oocyte differentiation in vertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Early warning of illegal development for protected areas by integrating cellular automata with neural networks.

    Science.gov (United States)

    Li, Xia; Lao, Chunhua; Liu, Yilun; Liu, Xiaoping; Chen, Yimin; Li, Shaoying; Ai, Bing; He, Zijian

    2013-11-30

    Ecological security has become a major issue under fast urbanization in China. As the first two cities in this country, Shenzhen and Dongguan issued the ordinance of Eco-designated Line of Control (ELC) to "wire" ecologically important areas for strict protection in 2005 and 2009 respectively. Early warning systems (EWS) are a useful tool for assisting the implementation ELC. In this study, a multi-model approach is proposed for the early warning of illegal development by integrating cellular automata (CA) and artificial neural networks (ANN). The objective is to prevent the ecological risks or catastrophe caused by such development at an early stage. The integrated model is calibrated by using the empirical information from both remote sensing and handheld GPS (global positioning systems). The MAR indicator which is the ratio of missing alarms to all the warnings is proposed for better assessment of the model performance. It is found that the fast urban development has caused significant threats to natural-area protection in the study area. The integration of CA, ANN and GPS provides a powerful tool for describing and predicting illegal development which is in highly non-linear and fragmented forms. The comparison shows that this multi-model approach has much better performances than the single-model approach for the early warning. Compared with the single models of CA and ANN, this integrated multi-model can improve the value of MAR by 65.48% and 5.17% respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Prior acetaminophen consumption impacts the early adaptive cellular response of human skeletal muscle to resistance exercise.

    Science.gov (United States)

    D'Lugos, Andrew C; Patel, Shivam H; Ormsby, Jordan C; Curtis, Donald P; Fry, Christopher S; Carroll, Chad C; Dickinson, Jared M

    2018-04-01

    Resistance exercise (RE) is a powerful stimulus for skeletal muscle adaptation. Previous data demonstrate that cyclooxygenase (COX)-inhibiting drugs alter the cellular mechanisms regulating the adaptive response of skeletal muscle. The purpose of this study was to determine whether prior consumption of the COX inhibitor acetaminophen (APAP) alters the immediate adaptive cellular response in human skeletal muscle after RE. In a double-blinded, randomized, crossover design, healthy young men ( n = 8, 25 ± 1 yr) performed two trials of unilateral knee extension RE (8 sets, 10 reps, 65% max strength). Subjects ingested either APAP (1,000 mg/6 h) or placebo (PLA) for 24 h before RE (final dose consumed immediately after RE). Muscle biopsies (vastus lateralis) were collected at rest and 1 h and 3 h after exercise. Mammalian target of rapamycin (mTOR) complex 1 signaling was assessed through immunoblot and immunohistochemistry, and mRNA expression of myogenic genes was examined via RT-qPCR. At 1 h p-rpS6 Ser240/244 was increased in both groups but to a greater extent in PLA. At 3 h p-S6K1 Thr389 was elevated only in PLA. Furthermore, localization of mTOR to the lysosome (LAMP2) in myosin heavy chain (MHC) II fibers increased 3 h after exercise only in PLA. mTOR-LAMP2 colocalization in MHC I fibers was greater in PLA vs. APAP 1 h after exercise. Myostatin mRNA expression was reduced 1 h after exercise only in PLA. MYF6 mRNA expression was increased 1 h and 3 h after exercise only in APAP. APAP consumption appears to alter the early adaptive cellular response of skeletal muscle to RE. These findings further highlight the mechanisms through which COX-inhibiting drugs impact the adaptive response of skeletal muscle to exercise. NEW & NOTEWORTHY The extent to which the cellular reaction to acetaminophen impacts the mechanisms regulating the adaptive response of human skeletal muscle to resistance exercise is not well understood. Consumption of acetaminophen before

  1. Meta-Analysis of High-Throughput Datasets Reveals Cellular Responses Following Hemorrhagic Fever Virus Infection

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    Gavin C. Bowick

    2011-05-01

    Full Text Available The continuing use of high-throughput assays to investigate cellular responses to infection is providing a large repository of information. Due to the large number of differentially expressed transcripts, often running into the thousands, the majority of these data have not been thoroughly investigated. Advances in techniques for the downstream analysis of high-throughput datasets are providing additional methods for the generation of additional hypotheses for further investigation. The large number of experimental observations, combined with databases that correlate particular genes and proteins with canonical pathways, functions and diseases, allows for the bioinformatic exploration of functional networks that may be implicated in replication or pathogenesis. Herein, we provide an example of how analysis of published high-throughput datasets of cellular responses to hemorrhagic fever virus infection can generate additional functional data. We describe enrichment of genes involved in metabolism, post-translational modification and cardiac damage; potential roles for specific transcription factors and a conserved involvement of a pathway based around cyclooxygenase-2. We believe that these types of analyses can provide virologists with additional hypotheses for continued investigation.

  2. GEITLERINEMA SPECIES (OSCILLATORIALES, CYANOBACTERIA) REVEALED BY CELLULAR MORPHOLOGY, ULTRASTRUCTURE, AND DNA SEQUENCING(1).

    Science.gov (United States)

    Do Carmo Bittencourt-Oliveira, Maria; Do Nascimento Moura, Ariadne; De Oliveira, Mariana Cabral; Sidnei Massola, Nelson

    2009-06-01

    Geitlerinema amphibium (C. Agardh ex Gomont) Anagn. and G. unigranulatum (Rama N. Singh) Komárek et M. T. P. Azevedo are morphologically close species with characteristics frequently overlapping. Ten strains of Geitlerinema (six of G. amphibium and four of G. unigranulatum) were analyzed by DNA sequencing and transmission electronic and optical microscopy. Among the investigated strains, the two species were not separated with respect to cellular dimensions, and cellular width was the most varying characteristic. The number and localization of granules, as well as other ultrastructural characteristics, did not provide a means to discriminate between the two species. The two species were not separated either by geography or environment. These results were further corroborated by the analysis of the cpcB-cpcA intergenic spacer (PC-IGS) sequences. Given the fact that morphology is very uniform, plus the coexistence of these populations in the same habitat, it would be nearly impossible to distinguish between them in nature. On the other hand, two of the analyzed strains were distinct from all others based on the PC-IGS sequences, in spite of their morphological similarity. PC-IGS sequences indicate that these two strains could be a different species of Geitlerinema. Using morphology, cell ultrastructure, and PC-IGS sequences, it is not possible to distinguish G. amphibium and G. unigranulatum. Therefore, they should be treated as one species, G. unigranulatum as a synonym of G. amphibium. © 2009 Phycological Society of America.

  3. Detection of interferon alpha protein reveals differential levels and cellular sources in disease.

    Science.gov (United States)

    Rodero, Mathieu P; Decalf, Jérémie; Bondet, Vincent; Hunt, David; Rice, Gillian I; Werneke, Scott; McGlasson, Sarah L; Alyanakian, Marie-Alexandra; Bader-Meunier, Brigitte; Barnerias, Christine; Bellon, Nathalia; Belot, Alexandre; Bodemer, Christine; Briggs, Tracy A; Desguerre, Isabelle; Frémond, Marie-Louise; Hully, Marie; van den Maagdenberg, Arn M J M; Melki, Isabelle; Meyts, Isabelle; Musset, Lucile; Pelzer, Nadine; Quartier, Pierre; Terwindt, Gisela M; Wardlaw, Joanna; Wiseman, Stewart; Rieux-Laucat, Frédéric; Rose, Yoann; Neven, Bénédicte; Hertel, Christina; Hayday, Adrian; Albert, Matthew L; Rozenberg, Flore; Crow, Yanick J; Duffy, Darragh

    2017-05-01

    Type I interferons (IFNs) are essential mediators of antiviral responses. These cytokines have been implicated in the pathogenesis of autoimmunity, most notably systemic lupus erythematosus (SLE), diabetes mellitus, and dermatomyositis, as well as monogenic type I interferonopathies. Despite a fundamental role in health and disease, the direct quantification of type I IFNs has been challenging. Using single-molecule array (Simoa) digital ELISA technology, we recorded attomolar concentrations of IFNα in healthy donors, viral infection, and complex and monogenic interferonopathies. IFNα protein correlated well with functional activity and IFN-stimulated gene expression. High circulating IFNα levels were associated with increased clinical severity in SLE patients, and a study of the cellular source of IFNα protein indicated disease-specific mechanisms. Measurement of IFNα attomolar concentrations by digital ELISA will enhance our understanding of IFN biology and potentially improve the diagnosis and stratification of pathologies associated with IFN dysregulation. © 2017 Rodero et al.

  4. Using Cellular Proteins to Reveal Mechanisms of HIV Infection | Center for Cancer Research

    Science.gov (United States)

    A vital step in HIV infection is the insertion of viral DNA into the genome of the host cell. In order for the insertion to occur, viral nucleic acid must be transported through the membrane that separates the main cellular compartment (the cytoplasm) from the nucleus, where the host DNA is located. Scientists are actively studying the mechanism used to transport viral DNA into the nucleus in the hopes of targeting this step with future anti-HIV treatments. Up to this point, researchers have identified some of the viral components that play a role in nuclear transport, but they have not determined how viral interactions with other molecules in the cell contribute to the process.

  5. Early leaf senescence is associated with an altered cellular redox balance in Arabidopsis cpr5/old1 mutants

    OpenAIRE

    Jing, H. -C.; Hebeler, R.; Oeljeklaus, S.; Sitek, B.; Stuehler, K.; Meyer, H. E.; Sturre, M. J. G.; Hille, J.; Warscheid, B.; Dijkwel, P. P.; Stühler, K.

    2008-01-01

    Reactive oxygen species (ROS) are the inevitable by-products of essential cellular metabolic and physiological activities. Plants have developed sophisticated gene networks of ROS generation and scavenging systems. However, ROS regulation is still poorly understood. Here, we report that mutations in the Arabidopsis CPR5/OLD1 gene may cause early senescence through deregulation of the cellular redox balance. Genetic analysis showed that blocking stress-related hormonal signalling pathways, suc...

  6. The roles of cellular and molecular components of a hematoma at early stage of bone healing.

    Science.gov (United States)

    Shiu, Hoi Ting; Leung, Ping Chung; Ko, Chun Hay

    2018-04-01

    Bone healing is a complex repair process that commences with the formation of a blood clot at the injured bone, termed hematoma. It has evidenced that a lack of a stable hematoma causes delayed bone healing or non-union. The hematoma at the injured bone constitutes the early healing microenvironment. It appears to dictate healing pathways that ends in a regenerative bone. However, the hematoma is often clinically removed from the damaged site. Conversely, blood-derived products have been used in bone tissue engineering for treating critical sized defects, including fibrin gels and platelet-rich plasma. A second generation of platelet concentrate that is based on leukocyte and fibrin content has also been developed and introduced in market. Conflicting effect of these products in bone repair are reported. We propose that the bone healing response becomes dysregulated if the blood response and subsequent formation and properties of a hematoma are altered. This review focuses on the central structural, cellular, and molecular components of a fracture hematoma, with a major emphasis on their roles in regulating bone healing mechanism, and their interactions with mesenchymal stem cells. New angles towards a better understanding of these factors and relevant mechanisms involved at the beginning of bone healing may help to clarify limited or adverse effects of blood-derived products on bone repair. We emphasize that the recreation of an early hematoma niche with critical compositions might emerge as a viable therapeutic strategy for enhanced skeletal tissue engineering. Copyright © 2017 John Wiley & Sons, Ltd.

  7. The functional micro-organization of grid cells revealed by cellular-resolution imaging.

    Science.gov (United States)

    Heys, James G; Rangarajan, Krsna V; Dombeck, Daniel A

    2014-12-03

    Establishing how grid cells are anatomically arranged, on a microscopic scale, in relation to their firing patterns in the environment would facilitate a greater microcircuit-level understanding of the brain's representation of space. However, all previous grid cell recordings used electrode techniques that provide limited descriptions of fine-scale organization. We therefore developed a technique for cellular-resolution functional imaging of medial entorhinal cortex (MEC) neurons in mice navigating a virtual linear track, enabling a new experimental approach to study MEC. Using these methods, we show that grid cells are physically clustered in MEC compared to nongrid cells. Additionally, we demonstrate that grid cells are functionally micro-organized: the similarity between the environment firing locations of grid cell pairs varies as a function of the distance between them according to a "Mexican hat"-shaped profile. This suggests that, on average, nearby grid cells have more similar spatial firing phases than those further apart. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Two-Photon Autofluorescence Imaging Reveals Cellular Structures Throughout the Retina of the Living Primate Eye.

    Science.gov (United States)

    Sharma, Robin; Williams, David R; Palczewska, Grazyna; Palczewski, Krzysztof; Hunter, Jennifer J

    2016-02-01

    Although extrinsic fluorophores can be introduced to label specific cell types in the retina, endogenous fluorophores, such as NAD(P)H, FAD, collagen, and others, are present in all retinal layers. These molecules are a potential source of optical contrast and can enable noninvasive visualization of all cellular layers. We used a two-photon fluorescence adaptive optics scanning light ophthalmoscope (TPF-AOSLO) to explore the native autofluorescence of various cell classes spanning several layers in the unlabeled retina of a living primate eye. Three macaques were imaged on separate occasions using a custom TPF-AOSLO. Two-photon fluorescence was evoked by pulsed light at 730 and 920 nm excitation wavelengths, while fluorescence emission was collected in the visible range from several retinal layers and different locations. Backscattered light was recorded simultaneously in confocal modality and images were postprocessed to remove eye motion. All retinal layers yielded two-photon signals and the heterogeneous distribution of fluorophores provided optical contrast. Several structural features were observed, such as autofluorescence from vessel walls, Müller cell processes in the nerve fibers, mosaics of cells in the ganglion cell and other nuclear layers of the inner retina, as well as photoreceptor and RPE layers in the outer retina. This in vivo survey of two-photon autofluorescence throughout the primate retina demonstrates a wider variety of structural detail in the living eye than is available through conventional imaging methods, and broadens the use of two-photon imaging of normal and diseased eyes.

  9. Molecular and Cellular Profiling of Scalp Psoriasis Reveals Differences and Similarities Compared to Skin Psoriasis

    Science.gov (United States)

    Ruano, Juan; Suárez-Fariñas, Mayte; Shemer, Avner; Oliva, Margeaux

    2016-01-01

    Scalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis in other skin areas. We sought to determine the cellular and molecular phenotype of scalp psoriasis by performing a comparative analysis of scalp and skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement and 10 control subjects without psoriasis. Our results suggest that even in the scalp, psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprint were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with that of skin psoriasis, which was mainly associated with activation of TNFα/L-17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes. PMID:26849645

  10. Expression weighted cell type enrichments reveal genetic and cellular nature of major brain disorders

    Directory of Open Access Journals (Sweden)

    Nathan Gerald Skene

    2016-01-01

    Full Text Available The cell types that trigger the primary pathology in many brain diseases remain largely unknown. One route to understanding the primary pathological cell type for a particular disease is to identify the cells expressing susceptibility genes. Although this is straightforward for monogenic conditions where the causative mutation may alter expression of a cell type specific marker, methods are required for the common polygenic disorders. We developed the Expression Weighted Cell Type Enrichment (EWCE method that uses single cell transcriptomes to generate the probability distribution associated with a gene list having an average level of expression within a cell type. Following validation, we applied EWCE to human genetic data from cases of epilepsy, Schizophrenia, Autism, Intellectual Disability, Alzheimer’s disease, Multiple Sclerosis and anxiety disorders. Genetic susceptibility primarily affected microglia in Alzheimer’s and Multiple Sclerosis; was shared between interneurons and pyramidal neurons in Autism and Schizophrenia; while intellectual disabilities and epilepsy were attributable to a range of cell-types, with the strongest enrichment in interneurons. We hypothesised that the primary cell type pathology could trigger secondary changes in other cell types and these could be detected by applying EWCE to transcriptome data from diseased tissue. In Autism, Schizophrenia and Alzheimer’s disease we find evidence of pathological changes in all of the major brain cell types. These findings give novel insight into the cellular origins and progression in common brain disorders. The methods can be applied to any tissue and disorder and have applications in validating mouse models.

  11. Characterization of a Fasciola gigantica protein carrying two DM9 domains reveals cellular relocalization property.

    Science.gov (United States)

    Phadungsil, Wansika; Smooker, Peter M; Vichasri-Grams, Suksiri; Grams, Rudi

    2016-01-01

    Even at the present age of whole-organism analysis, e.g., genomics, transcriptomics, and proteomics, the biological roles of many proteins remain unresolved. Classified among the proteins of unknown function is a family of proteins harboring repeats of the DM9 domain, a 60-75 amino acids motif first described in a small number of Drosophila melanogaster proteins. Proteins may carry two or more DM9 domains either in combination with other domains or as their sole constituent. Here we have characterized a 16.8 kDa Fasciola gigantica protein comprising two tandem repeated DM9 domains (FgDM9-1). The protein was located in the parenchyma of the immature and mature parasite and consequently it was not detected in the ES product of the parasite but only in the whole worm extract. Interestingly, extraction with SDS yielded a substantially higher amount of the protein suggesting association with insoluble cell components. In Sf9 insect cells a heterologously expressed EGFP-FgDM9-1 chimera showed cell-wide distribution but relocated to vesicle-like structures in the cytoplasm after stimulating cellular stress by bacteria, heat shock or chloroquine. These structures did not colocalize with the markers of endocytosis/phagocytosis ubiquitin, RAB7, GABARAP. The same behavior was noted for Aedes aegypti PRS1, a homologous mosquito DM9 protein as a positive control while EGFP did not exhibit such relocation in the insect cells. Cross-linking experiments on soluble recombinant FgDM9-1 indicated that the protein can undergo specific oligomerization. It is speculated that proteins carrying the DM9 domain have a role in vesicular transport in flatworms and insects. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Genome sequencing reveals metabolic and cellular interdependence in an amoeba-kinetoplastid symbiosis

    Czech Academy of Sciences Publication Activity Database

    Tanifuji, G.; Cenci, U.; Moog, D.; Dean, S.; Nakayama, T.; David, Vojtěch; Fiala, Ivan; Curtis, B.A.; Sibbald, S. J.; Onodera, N. T.; Colp, M.; Flegontov, Pavel; Johnson-MacKinnon, J.; McPhee, M.; Inagaki, Y.; Hashimoto, T.; Kelly, S.; Gull, K.; Lukeš, Julius; Archibald, J.M.

    2017-01-01

    Roč. 7, SEP 15 (2017), č. článku 11688. ISSN 2045-2322 R&D Projects: GA ČR(CZ) GA14-23986S; GA MŠk LL1601 Institutional support: RVO:60077344 Keywords : trypanosoma-brucei reveals * hidden markov model * neoparamoeba-pemaquidensis * gill disease * phylogenetic analyses * ichthyobodo-necator * gene prediction * host control * evolution * proteomics Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 4.259, year: 2016

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

    Science.gov (United States)

    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.

  14. MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during Oropouche infection.

    Directory of Open Access Journals (Sweden)

    Victor Emmanuel Viana Geddes

    2018-05-01

    Full Text Available Oropouche Virus is the etiological agent of an arbovirus febrile disease that affects thousands of people and is widespread throughout Central and South American countries. Although isolated in 1950's, still there is scarce information regarding the virus biology and its prevalence is likely underestimated. In order to identify and elucidate interactions with host cells factors and increase the understanding about the Oropouche Virus biology, we performed microRNA (miRNA and target genes screening in human hepatocarcinoma cell line HuH-7. Cellular miRNAs are short non-coding RNAs that regulates gene expression post-transcriptionally and play key roles in several steps of viral infections. The large scale RT-qPCR based screening found 13 differentially expressed miRNAs in Oropouche infected cells. Further validation confirmed that miR-217 and miR-576-3p were 5.5 fold up-regulated at early stages of virus infection (6 hours post-infection. Using bioinformatics and pathway enrichment analysis, we predicted the cellular targets genes for miR-217 and miR-576-3p. Differential expression analysis of RNA from 95 selected targets revealed genes involved in innate immunity modulation, viral release and neurological disorder outcomes. Further analysis revealed the gene of decapping protein 2 (DCP2, a previous known restriction factor for bunyaviruses transcription, as a miR-217 candidate target that is progressively down-regulated during Oropouche infection. Our analysis also showed that activators genes involved in innate immune response through IFN-β pathway, as STING (Stimulator of Interferon Genes and TRAF3 (TNF-Receptor Associated Factor 3, were down-regulated as the infection progress. Inhibition of miR-217 or miR-576-3p restricts OROV replication, decreasing viral RNA (up to 8.3 fold and virus titer (3 fold. Finally, we showed that virus escape IFN-β mediated immune response increasing the levels of cellular miR-576-3p resulting in a decreasing of

  15. The hand of birds revealed by early ostrich embryos

    Science.gov (United States)

    Feduccia, Alan; Nowicki, Julie

    2002-08-01

    The problem of resolving the homology of the digits of the avian hand has been framed as a conflict between paleontological and embryological evidence, the former thought to support a hand composed of digits I, II, III, because of similarity of the phalangeal formulae of the earliest known bird Archaeopteryx to that of Mesozoic pentadactyl archosaurs, while embryological evidence has traditionally favored a II, III, IV avian hand. We have identified the critical developmental period for the major features of the avian skeleton in a primitive bird, the ostrich. Analysis of digit anlagen in the avian hand has revealed those for digits/metacarpals I and V, thus confirming previous embryological studies that indirectly suggested that the avian hand comprises digits II, III, IV, and was primitively pentadactyl.

  16. Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

    Science.gov (United States)

    Huang, Li-Tung

    2014-01-01

    Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed. PMID:24574961

  17. A New Natural Product Analog of Blasticidin S Reveals Cellular Uptake Facilitated by the NorA Multidrug Transporter.

    Science.gov (United States)

    Davison, Jack R; Lohith, Katheryn M; Wang, Xiaoning; Bobyk, Kostyantyn; Mandadapu, Sivakoteswara R; Lee, Su-Lin; Cencic, Regina; Nelson, Justin; Simpkins, Scott; Frank, Karen M; Pelletier, Jerry; Myers, Chad L; Piotrowski, Jeff; Smith, Harold E; Bewley, Carole A

    2017-06-01

    The permeation of antibiotics through bacterial membranes to their target site is a crucial determinant of drug activity but in many cases remains poorly understood. During screening efforts to discover new broad-spectrum antibiotic compounds from marine sponge samples, we identified a new analog of the peptidyl nucleoside antibiotic blasticidin S that exhibited up to 16-fold-improved potency against a range of laboratory and clinical bacterial strains which we named P10. Whole-genome sequencing of laboratory-evolved strains of Staphylococcus aureus resistant to blasticidin S and P10, combined with genome-wide assessment of the fitness of barcoded Escherichia coli knockout strains in the presence of the antibiotics, revealed that restriction of cellular access was a key feature in the development of resistance to this class of drug. In particular, the gene encoding the well-characterized multidrug efflux pump NorA was found to be mutated in 69% of all S. aureus isolates resistant to blasticidin S or P10. Unexpectedly, resistance was associated with inactivation of norA , suggesting that the NorA transporter facilitates cellular entry of peptidyl nucleosides in addition to its known role in the efflux of diverse compounds, including fluoroquinolone antibiotics. Copyright © 2017 American Society for Microbiology.

  18. Systematic screen for mutants resistant to TORC1 inhibition in fission yeast reveals genes involved in cellular ageing and growth

    Directory of Open Access Journals (Sweden)

    Charalampos Rallis

    2014-01-01

    Target of rapamycin complex 1 (TORC1, which controls growth in response to nutrients, promotes ageing in multiple organisms. The fission yeast Schizosaccharomyces pombe emerges as a valuable genetic model system to study TORC1 function and cellular ageing. Here we exploited the combinatorial action of rapamycin and caffeine, which inhibit fission yeast growth in a TORC1-dependent manner. We screened a deletion library, comprising ∼84% of all non-essential fission yeast genes, for drug-resistant mutants. This screen identified 33 genes encoding functions such as transcription, kinases, mitochondrial respiration, biosynthesis, intra-cellular trafficking, and stress response. Among the corresponding mutants, 5 showed shortened and 21 showed increased maximal chronological lifespans; 15 of the latter mutants showed no further lifespan increase with rapamycin and might thus represent key targets downstream of TORC1. We pursued the long-lived sck2 mutant with additional functional analyses, revealing that the Sck2p kinase functions within the TORC1 network and is required for normal cell growth, global protein translation, and ribosomal S6 protein phosphorylation in a nutrient-dependent manner. Notably, slow cell growth was associated with all long-lived mutants while oxidative-stress resistance was not.

  19. Real-time in vivo imaging of butterfly wing development: revealing the cellular dynamics of the pupal wing tissue.

    Directory of Open Access Journals (Sweden)

    Masaki Iwata

    Full Text Available Butterfly wings are covered with regularly arranged single-colored scales that are formed at the pupal stage. Understanding pupal wing development is therefore crucial to understand wing color pattern formation. Here, we successfully employed real-time in vivo imaging techniques to observe pupal hindwing development over time in the blue pansy butterfly, Junonia orithya. A transparent sheet of epithelial cells that were not yet regularly arranged was observed immediately after pupation. Bright-field imaging and autofluorescent imaging revealed free-moving hemocytes and tracheal branches of a crinoid-like structure underneath the epithelium. The wing tissue gradually became gray-white, epithelial cells were arranged regularly, and hemocytes disappeared, except in the bordering lacuna, after which scales grew. The dynamics of the epithelial cells and scale growth were also confirmed by fluorescent imaging. Fluorescent in vivo staining further revealed that these cells harbored many mitochondria at the surface of the epithelium. Organizing centers for the border symmetry system were apparent immediately after pupation, exhibiting a relatively dark optical character following treatment with fluorescent dyes, as well as in autofluorescent images. The wing tissue exhibited slow and low-frequency contraction pulses with a cycle of approximately 10 to 20 minutes, mainly occurring at 2 to 3 days postpupation. The pulses gradually became slower and weaker and eventually stopped. The wing tissue area became larger after contraction, which also coincided with an increase in the autofluorescence intensity that might have been caused by scale growth. Examination of the pattern of color development revealed that the black pigment was first deposited in patches in the central areas of an eyespot black ring and a parafocal element. These results of live in vivo imaging that covered wide wing area for a long time can serve as a foundation for studying the

  20. Real-time in vivo imaging of butterfly wing development: revealing the cellular dynamics of the pupal wing tissue.

    Science.gov (United States)

    Iwata, Masaki; Ohno, Yoshikazu; Otaki, Joji M

    2014-01-01

    Butterfly wings are covered with regularly arranged single-colored scales that are formed at the pupal stage. Understanding pupal wing development is therefore crucial to understand wing color pattern formation. Here, we successfully employed real-time in vivo imaging techniques to observe pupal hindwing development over time in the blue pansy butterfly, Junonia orithya. A transparent sheet of epithelial cells that were not yet regularly arranged was observed immediately after pupation. Bright-field imaging and autofluorescent imaging revealed free-moving hemocytes and tracheal branches of a crinoid-like structure underneath the epithelium. The wing tissue gradually became gray-white, epithelial cells were arranged regularly, and hemocytes disappeared, except in the bordering lacuna, after which scales grew. The dynamics of the epithelial cells and scale growth were also confirmed by fluorescent imaging. Fluorescent in vivo staining further revealed that these cells harbored many mitochondria at the surface of the epithelium. Organizing centers for the border symmetry system were apparent immediately after pupation, exhibiting a relatively dark optical character following treatment with fluorescent dyes, as well as in autofluorescent images. The wing tissue exhibited slow and low-frequency contraction pulses with a cycle of approximately 10 to 20 minutes, mainly occurring at 2 to 3 days postpupation. The pulses gradually became slower and weaker and eventually stopped. The wing tissue area became larger after contraction, which also coincided with an increase in the autofluorescence intensity that might have been caused by scale growth. Examination of the pattern of color development revealed that the black pigment was first deposited in patches in the central areas of an eyespot black ring and a parafocal element. These results of live in vivo imaging that covered wide wing area for a long time can serve as a foundation for studying the cellular dynamics of living

  1. Early vertebrate origin and diversification of small transmembrane regulators of cellular ion transport.

    Science.gov (United States)

    Pirkmajer, Sergej; Kirchner, Henriette; Lundell, Leonidas S; Zelenin, Pavel V; Zierath, Juleen R; Makarova, Kira S; Wolf, Yuri I; Chibalin, Alexander V

    2017-07-15

    Small transmembrane proteins such as FXYDs, which interact with Na + ,K + -ATPase, and the micropeptides that interact with sarco/endoplasmic reticulum Ca 2+ -ATPase play fundamental roles in regulation of ion transport in vertebrates. Uncertain evolutionary origins and phylogenetic relationships among these regulators of ion transport have led to inconsistencies in their classification across vertebrate species, thus hampering comparative studies of their functions. We discovered the first FXYD homologue in sea lamprey, a basal jawless vertebrate, which suggests small transmembrane regulators of ion transport emerged early in the vertebrate lineage. We also identified 13 gene subfamilies of FXYDs and propose a revised, phylogeny-based FXYD classification that is consistent across vertebrate species. These findings provide an improved framework for investigating physiological and pathophysiological functions of small transmembrane regulators of ion transport. Small transmembrane proteins are important for regulation of cellular ion transport. The most prominent among these are members of the FXYD family (FXYD1-12), which regulate Na + ,K + -ATPase, and phospholamban, sarcolipin, myoregulin and DWORF, which regulate the sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA). FXYDs and regulators of SERCA are present in fishes, as well as terrestrial vertebrates; however, their evolutionary origins and phylogenetic relationships are obscure, thus hampering comparative physiological studies. Here we discovered that sea lamprey (Petromyzon marinus), a representative of extant jawless vertebrates (Cyclostomata), expresses an FXYD homologue, which strongly suggests that FXYDs predate the emergence of fishes and other jawed vertebrates (Gnathostomata). Using a combination of sequence-based phylogenetic analysis and conservation of local chromosome context, we determined that FXYDs markedly diversified in the lineages leading to cartilaginous fishes (Chondrichthyes) and bony

  2. Revealing the sequence and resulting cellular morphology of receptor-ligand interactions during Plasmodium falciparum invasion of erythrocytes.

    Directory of Open Access Journals (Sweden)

    Greta E Weiss

    2015-02-01

    Full Text Available During blood stage Plasmodium falciparum infection, merozoites invade uninfected erythrocytes via a complex, multistep process involving a series of distinct receptor-ligand binding events. Understanding each element in this process increases the potential to block the parasite's life cycle via drugs or vaccines. To investigate specific receptor-ligand interactions, they were systematically blocked using a combination of genetic deletion, enzymatic receptor cleavage and inhibition of binding via antibodies, peptides and small molecules, and the resulting temporal changes in invasion and morphological effects on erythrocytes were filmed using live cell imaging. Analysis of the videos have shown receptor-ligand interactions occur in the following sequence with the following cellular morphologies; 1 an early heparin-blockable interaction which weakly deforms the erythrocyte, 2 EBA and PfRh ligands which strongly deform the erythrocyte, a process dependant on the merozoite's actin-myosin motor, 3 a PfRh5-basigin binding step which results in a pore or opening between parasite and host through which it appears small molecules and possibly invasion components can flow and 4 an AMA1-RON2 interaction that mediates tight junction formation, which acts as an anchor point for internalization. In addition to enhancing general knowledge of apicomplexan biology, this work provides a rational basis to combine sequentially acting merozoite vaccine candidates in a single multi-receptor-blocking vaccine.

  3. Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function.

    Directory of Open Access Journals (Sweden)

    Yana Sandlers

    Full Text Available Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of individuals with Barth Syndrome and controls was observed, and was defined by an array of metabolite classes including amino acids and lipids. Pathway analysis of these discriminating metabolites revealed involvement of mitochondrial and extra-mitochondrial biochemical pathways including: insulin regulation of fatty acid metabolism, lipid metabolism, biogenic amine metabolism, amino acid metabolism, endothelial nitric oxide synthase signaling, and tRNA biosynthesis. Taken together, this data indicates broad metabolic dysregulation in Barth Syndrome with wide cellular effects.

  4. Semen modulated secretory activity of oviductal epithelial cells is linked to cellular proteostasis network remodeling: Proteomic insights into the early phase of interaction in the oviduct in vivo.

    Science.gov (United States)

    Steinberger, Birgit; Yu, Hans; Brodmann, Theodor; Milovanovic, Daniela; Reichart, Ursula; Besenfelder, Urban; Artemenko, Konstantin; Razzazi-Fazeli, Ebrahim; Brem, Gottfried; Mayrhofer, Corina

    2017-06-23

    The oviductal epithelium is crucial for the integrity of the female organ. Previously we got evidence that the surface proteome of oviductal epithelial cells (Oecs) is promptly altered in response to insemination and thus suggested that this early phase plays a notable regulatory role in maintaining cellular function. This study further aimed to assess the effect of semen on the cellular and molecular mechanisms in rabbit Oecs. A quantitative gel-based proteomic approach was applied to analyze changes at three time points (0h, 1h, 2h) after intrauterine insemination (IUI) compared to time matched controls. Within two hours the abundance of 22 protein species was evidently altered in the intracellular fraction. Functional analysis revealed that the proteins were primarily involved in proteostasis as well as metabolic processes. The analysis of phosphoproteins specified a role of mitogen-activated protein kinase (MAPK) signaling molecules. Concurrently, semen increased oviduct-specific glycoprotein (OVGP1) secretion. A correlation between OVGP1 abundance and microtubule-associated proteins 1A/1B-light chain 3 lipidation was observed. The localization and changes in abundance of selected proteins were corroborated by antibody-based methods. These results clearly show that the early phase of interaction acts as a trigger for cellular adaptation to meet an altered demand in the female organ. The oviductal epithelium and its secreted proteins exert a pivotal role in reproductive processes, including the final maturation of male gametes. Thereby, the regulation and subsequently the functionality of the oviductal epithelial cell layer are important factors for the establishment of the appropriate milieu in the female reproductive tract. Notably, male gametes themselves have been shown to be an extrinsic modulatory factor of the oviductal epithelium. Accordingly a comprehensive knowledge about the underlying cellular and molecular mechanisms in the epithelial cells is of

  5. Reviewing the current evidence supporting early B-cells as the cellular origin of Merkel cell carcinoma.

    Science.gov (United States)

    Sauer, C M; Haugg, A M; Chteinberg, E; Rennspiess, D; Winnepenninckx, V; Speel, E-J; Becker, J C; Kurz, A K; Zur Hausen, A

    2017-08-01

    Merkel cell carcinoma (MCC) is a highly malignant skin cancer characterized by early metastases and poor survival. Although MCC is a rare malignancy, its incidence is rapidly increasing in the U.S. and Europe. The discovery of the Merkel cell polyomavirus (MCPyV) has enormously impacted our understanding of its etiopathogenesis and biology. MCCs are characterized by trilinear differentiation, comprising the expression of neuroendocrine, epithelial and B-lymphoid lineage markers. To date, it is generally accepted that the initial assumption of MCC originating from Merkel cells (MCs) is unlikely. This is owed to their post-mitotic character, absence of MCPyV in MCs and discrepant protein expression pattern in comparison to MCC. Evidence from mouse models suggests that epidermal/dermal stem cells might be of cellular origin in MCC. The recently formulated hypothesis of MCC originating from early B-cells is based on morphology, the consistent expression of early B-cell lineage markers and the finding of clonal immunoglobulin chain rearrangement in MCC cells. In this review we elaborate on the cellular ancestry of MCC, the identification of which could pave the way for novel and more effective therapeutic regimens. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression.

    Directory of Open Access Journals (Sweden)

    Victoria Wahl-Jensen

    2011-10-01

    Full Text Available Zaire ebolavirus (ZEBOV infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP(1,2 is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP(1,2 (VLP(VP40-GP triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLP(VP40 (particles lacking GP(1,2 caused an aberrant response. This suggests that GP(1,2 binding to macrophages plays an important role in the immediate cellular response.

  7. Genome-wide allelotyping of a new in vitro model system reveals early events in breast cancer progression.

    Science.gov (United States)

    Li, Zheng; Meng, Zhen Hang; Sayeed, Aejaz; Shalaby, Refaat; Ljung, Britt-Marie; Dairkee, Shanaz H

    2002-10-15

    Toward the goal of identifying early genetic losses, which mediate the release of human breast epithelium from replicative suppression leading to cellular immortalization, we have used a newly developed in vitro model system. This system consists of epithelial cultures derived from noncancerous breast tissue, treated with the chemical carcinogen N-ethyl-N-nitrosourea, and continuously passaged to yield cell populations culminating in the immortal phenotype. Genome-wide allelotyping of early passage N-ethyl-N-nitrosourea-exposed cell populations revealed aberrations at >10% (18 of 169) loci examined. Allelic losses encompassing chromosomes 6q24-6q27, implicating immortalization-associated candidate genes, hZAC and SEN6, occurred in two independently derived cell lines before the Hayflick limit. Additional LOH sites were present in one cell line at 3p11-3p26, 11p15, and 20p12-13. Allelic losses reported in this cell line preceded detectable levels of telomerase activity and the occurrence of p53-related aberrations. Information gained from the search for early immortalization-associated genetic deletions in cultured cells was applied in a novel approach toward the analysis of morphologically normal terminal ductal lobular units microdissected from 20 cases of ductal carcinoma in situ. Notably, clonal allelic losses at chromosome 3p24 and 6q24 were an early occurrence in adjoining terminal ductal lobular units of a proportion of primary tumors, which displayed loss of heterozygosity (3 of 11 and 3 of 6, respectively). The biological insights provided by the new model system reported here strongly suggest that early allelic losses delineated in immortalized cultures and validated in vivo could serve as surrogate endpoints to assist in the identification and intervention of high-risk benign breast tissue, which sustains the potential for continuous proliferation.

  8. Accelerated telomere shortening: Tracking the lasting impact of early institutional care at the cellular level.

    Science.gov (United States)

    Humphreys, Kathryn L; Esteves, Kyle; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A; Drury, Stacy S

    2016-12-30

    Studies examining the association between early adversity and longitudinal changes in telomere length within the same individual are rare, yet are likely to provide novel insight into the subsequent lasting effects of negative early experiences. We sought to examine the association between institutional care history and telomere shortening longitudinally across middle childhood and into adolescence. Buccal DNA was collected 2-4 times, between the ages of 6 and 15 years, in 79 children enrolled in the Bucharest Early Intervention Project (BEIP), a longitudinal study exploring the impact of early institutional rearing on child health and development. Children with a history of early institutional care (n=50) demonstrated significantly greater telomere shortening across middle childhood and adolescence compared to never institutionalized children (n=29). Among children with a history of institutional care, randomization to high quality foster care was not associated with differential telomere attrition across development. Cross-sectional analysis of children randomized to the care as usual group indicated shorter telomere length was associated with greater percent of the child's life spent in institutional care up to age 8. These results suggest that early adverse care from severe psychosocial deprivation may be embedded at the molecular genetic level through accelerated telomere shortening. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. The induced expression of heat shock proteins as a part of the early cellular response to gamma radiation

    International Nuclear Information System (INIS)

    Stankova, K.; Ivanova, K.; Georgieva, R.; Rupova, I.; Boteva, R.

    2008-01-01

    A variety of stressful stimuli including gamma radiation can induce increase in the synthesis of heat shock proteins (Hsp). This family of molecular chaperones includes members with molecular masses ranging from 10 to 150 kDa and has been identified in all organisms from bacteria to humans. Hsp70 chaperones are very important. The present study aimed to characterize the radiation-induced changes in Hsp70 synthesis in human lymphocytes as a part of the early cellular response to gamma irradiation. The expression of Hsp70 was determined with Western blot and the radiation-induced apoptotic changes were registered by staining with fluorescent dyes. Part of the experiments were performed in the presence of the organic solvent DMSO. At low concentrations this reagent shows antioxidant activity and can reduce the level of the radiation-induced oxidant stress which determines the predominant biological effects of the ionizing radiation. Irradiation with 0.5 to 8 Gy caused statistically significant increase in the synthesis of Hsp70 which was strongest after irradiation with 4 Gy. In the range 0.5-2 Gy the enhancement of the radiation-induced synthesis of Hsp70 reached 60%. Our experimental results characterize changes in the Hsp70 synthesis after gamma irradiation as a part of the early cellular stress response in lymphocytes. (authors)

  10. Quantification of nanoscale density fluctuations by electron microscopy: probing cellular alterations in early carcinogenesis

    International Nuclear Information System (INIS)

    Pradhan, Prabhakar; Damania, Dhwanil; Turzhitsky, Vladimir; Subramanian, Hariharan; Backman, Vadim; Joshi, Hrushikesh M; Dravid, Vinayak P; Roy, Hemant K; Taflove, Allen

    2011-01-01

    Most cancers are curable if they are diagnosed and treated at an early stage. Recent studies suggest that nanoarchitectural changes occur within cells during early carcinogenesis and that such changes precede microscopically evident tissue alterations. It follows that the ability to comprehensively interrogate cell nanoarchitecture (e.g., macromolecular complexes, DNA, RNA, proteins and lipid membranes) could be critical to the diagnosis of early carcinogenesis. We present a study of the nanoscale mass-density fluctuations of biological tissues by quantifying their degree of disorder at the nanoscale. Transmission electron microscopy images of human tissues are used to construct corresponding effective disordered optical lattices. The properties of nanoscale disorder are then studied by statistical analysis of the inverse participation ratio (IPR) of the spatially localized eigenfunctions of these optical lattices at the nanoscale. Our results show an increase in the disorder of human colonic epithelial cells in subjects harboring early stages of colon neoplasia. Furthermore, our findings strongly suggest that increased nanoscale disorder correlates with the degree of tumorigenicity. Therefore, the IPR technique provides a practicable tool for the detection of nanoarchitectural alterations in the earliest stages of carcinogenesis. Potential applications of the technique for early cancer screening and detection are also discussed

  11. Nuclear and cellular expression data from the whole 16-cell stage Arabidopsis thaliana embryo and a cell type-specific expression atlas of the early Arabidopsis embryo

    NARCIS (Netherlands)

    Palovaara, J.P.J.

    2017-01-01

    SuperSeries contain expression data from the nuclei of cell types involved in patterning events, with focus on root apical stem cell formation, at 16-cell stage, early globular stage and late globular stage in the early Arabidopsis embryo (atlas). Expression data comparing nuclear and cellular RNA

  12. Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics

    Science.gov (United States)

    Yang, Jae-Seong; Kwon, Oh Sung; Kim, Sanguk; Jang, Sung Key

    2013-01-01

    Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets. PMID:23593195

  13. Comparative studies on cellular behaviour of carnation (Dianthus caryophyllus Linn. cv. Grenadin) grown in vivo and in vitro for early detection of somaclonal variation.

    Science.gov (United States)

    Yaacob, Jamilah Syafawati; Taha, Rosna Mat; Khorasani Esmaeili, Arash

    2013-01-01

    The present study deals with the cytological investigations on the meristematic root cells of carnation (Dianthus caryophyllus Linn.) grown in vivo and in vitro. Cellular parameters including the mitotic index (MI), chromosome count, ploidy level (nuclear DNA content), mean cell and nuclear areas, and cell doubling time (Cdt) were determined from the 2 mm root tip segments of this species. The MI value decreased when cells were transferred from in vivo to in vitro conditions, perhaps due to early adaptations of the cells to the in vitro environment. The mean chromosome number was generally stable (2n = 2x = 30) throughout the 6-month culture period, indicating no occurrence of early somaclonal variation. Following the transfer to the in vitro environment, a significant increase was recorded for mean cell and nuclear areas, from 26.59 ± 0.09  μm² to 35.66 ± 0.10  μm² and 142.90 ± 0.59  μm² to 165.05 ± 0.58  μm², respectively. However, the mean cell and nuclear areas of in vitro grown D. caryophyllus were unstable and fluctuated throughout the tissue culture period, possibly due to organogenesis or rhizogenesis. Ploidy level analysis revealed that D. caryophyllus root cells contained high percentage of polyploid cells when grown in vivo and maintained high throughout the 6-month culture period.

  14. DIGE proteome analysis reveals suitability of ischemic cardiac in vitro model for studying cellular response to acute ischemia and regeneration.

    Directory of Open Access Journals (Sweden)

    Sina Haas

    Full Text Available Proteomic analysis of myocardial tissue from patient population is suited to yield insights into cellular and molecular mechanisms taking place in cardiovascular diseases. However, it has been limited by small sized biopsies and complicated by high variances between patients. Therefore, there is a high demand for suitable model systems with the capability to simulate ischemic and cardiotoxic effects in vitro, under defined conditions. In this context, we established an in vitro ischemia/reperfusion cardiac disease model based on the contractile HL-1 cell line. To identify pathways involved in the cellular alterations induced by ischemia and thereby defining disease-specific biomarkers and potential target structures for new drug candidates we used fluorescence 2D-difference gel electrophoresis. By comparing spot density changes in ischemic and reperfusion samples we detected several protein spots that were differentially abundant. Using MALDI-TOF/TOF-MS and ESI-MS the proteins were identified and subsequently grouped by functionality. Most prominent were changes in apoptosis signalling, cell structure and energy-metabolism. Alterations were confirmed by analysis of human biopsies from patients with ischemic cardiomyopathy.With the establishment of our in vitro disease model for ischemia injury target identification via proteomic research becomes independent from rare human material and will create new possibilities in cardiac research.

  15. Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

    Science.gov (United States)

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2012-01-01

    Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

  16. Coordination of early cellular reactions during activation of bone resorption in the rat mandible periosteum: An immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Bassam Hassan

    2017-10-01

    Full Text Available The activation step of bone remodeling remains poorly characterized. Activation comprises determination of the site to be remodeled, osteoclast precursor recruitment, their migration to the site of remodeling, and differentiation. These actions involve different compartments and cell types. The aim of this study was to investigate events and cell types involved during activation. We used a bone remodeling model in rats where extractions of the upper jaw molars initiate remodeling of the antagonist lower jaw (mandible cortex along the periosteum. In this model osteoclastic resorption peaks 4 days after extractions. We previously reported that mast cell activation in the periosteum fibrous compartment is an early event of activation, associated with recruitment of circulating monocyte osteoclast precursors. By using immunohistochemistry, we observed 9 hours after induction a spatially oriented expression of InterCellular Adhesion Molecule-1 in the vessels that was inhibited by antagonists of histamine receptors 1 and 2. It was followed at 12 hours by the recruitment of ED1+ monocytes. In parallel, at 9 hours, Vascular Cellular Adhesion Molecule-1+ fibroblast-like cells scattered in the fibrous compartment of the periosteum between the vessels and the osteogenic compartment increased; these cells may be implicated in osteoclast precursor migration. Receptor Activator of NF KappaB Ligand+ cells increased at 12 hours in the osteogenic compartment and reached a peak at 18 hours. At 24 hours the numbers of osteogenic cells and subjacent osteocytes expressing semaphorin 3a, a repulsive for osteoclast precursors, decreased before returning to baseline at 48 hours. These data show that during activation the two periosteum compartments and several cell types are coordinated to recruit and guide osteoclast precursors towards the bone surface. Keywords: Biological sciences, Cell biology, Physiology, Dentistry

  17. Quantitative Tissue Proteomics Analysis Reveals Versican as Potential Biomarker for Early-Stage Hepatocellular Carcinoma.

    Science.gov (United States)

    Naboulsi, Wael; Megger, Dominik A; Bracht, Thilo; Kohl, Michael; Turewicz, Michael; Eisenacher, Martin; Voss, Don Marvin; Schlaak, Jörg F; Hoffmann, Andreas-Claudius; Weber, Frank; Baba, Hideo A; Meyer, Helmut E; Sitek, Barbara

    2016-01-04

    Hepatocellular carcinoma (HCC) is one of the most aggressive tumors, and the treatment outcome of this disease is improved when the cancer is diagnosed at an early stage. This requires biomarkers allowing an accurate and early tumor diagnosis. To identify potential markers for such applications, we analyzed a patient cohort consisting of 50 patients (50 HCC and 50 adjacent nontumorous tissue samples as controls) using two independent proteomics approaches. We performed label-free discovery analysis on 19 HCC and corresponding tissue samples. The data were analyzed considering events known to take place in early events of HCC development, such as abnormal regulation of Wnt/b-catenin and activation of receptor tyrosine kinases (RTKs). 31 proteins were selected for verification experiments. For this analysis, the second set of the patient cohort (31 HCC and corresponding tissue samples) was analyzed using selected (multiple) reaction monitoring (SRM/MRM). We present the overexpression of ATP-dependent RNA helicase (DDX39), Fibulin-5 (FBLN5), myristoylated alanine-rich C-kinase substrate (MARCKS), and Serpin H1 (SERPINH1) in HCC for the first time. We demonstrate Versican core protein (VCAN) to be significantly associated with well differentiated and low-stage HCC. We revealed for the first time the evidence of VCAN as a potential biomarker for early-HCC diagnosis.

  18. A Stochastic Model of the Yeast Cell Cycle Reveals Roles for Feedback Regulation in Limiting Cellular Variability.

    Science.gov (United States)

    Barik, Debashis; Ball, David A; Peccoud, Jean; Tyson, John J

    2016-12-01

    The cell division cycle of eukaryotes is governed by a complex network of cyclin-dependent protein kinases (CDKs) and auxiliary proteins that govern CDK activities. The control system must function reliably in the context of molecular noise that is inevitable in tiny yeast cells, because mistakes in sequencing cell cycle events are detrimental or fatal to the cell or its progeny. To assess the effects of noise on cell cycle progression requires not only extensive, quantitative, experimental measurements of cellular heterogeneity but also comprehensive, accurate, mathematical models of stochastic fluctuations in the CDK control system. In this paper we provide a stochastic model of the budding yeast cell cycle that accurately accounts for the variable phenotypes of wild-type cells and more than 20 mutant yeast strains simulated in different growth conditions. We specifically tested the role of feedback regulations mediated by G1- and SG2M-phase cyclins to minimize the noise in cell cycle progression. Details of the model are informed and tested by quantitative measurements (by fluorescence in situ hybridization) of the joint distributions of mRNA populations in yeast cells. We use the model to predict the phenotypes of ~30 mutant yeast strains that have not yet been characterized experimentally.

  19. A Stochastic Model of the Yeast Cell Cycle Reveals Roles for Feedback Regulation in Limiting Cellular Variability.

    Directory of Open Access Journals (Sweden)

    Debashis Barik

    2016-12-01

    Full Text Available The cell division cycle of eukaryotes is governed by a complex network of cyclin-dependent protein kinases (CDKs and auxiliary proteins that govern CDK activities. The control system must function reliably in the context of molecular noise that is inevitable in tiny yeast cells, because mistakes in sequencing cell cycle events are detrimental or fatal to the cell or its progeny. To assess the effects of noise on cell cycle progression requires not only extensive, quantitative, experimental measurements of cellular heterogeneity but also comprehensive, accurate, mathematical models of stochastic fluctuations in the CDK control system. In this paper we provide a stochastic model of the budding yeast cell cycle that accurately accounts for the variable phenotypes of wild-type cells and more than 20 mutant yeast strains simulated in different growth conditions. We specifically tested the role of feedback regulations mediated by G1- and SG2M-phase cyclins to minimize the noise in cell cycle progression. Details of the model are informed and tested by quantitative measurements (by fluorescence in situ hybridization of the joint distributions of mRNA populations in yeast cells. We use the model to predict the phenotypes of ~30 mutant yeast strains that have not yet been characterized experimentally.

  20. An immunoproteomic approach revealing peptides from Sporothrix brasiliensis that induce a cellular immune response in subcutaneous sporotrichosis.

    Science.gov (United States)

    de Almeida, José Roberto Fogaça; Jannuzzi, Grasielle Pereira; Kaihami, Gilberto Hideo; Breda, Leandro Carvalho Dantas; Ferreira, Karen Spadari; de Almeida, Sandro Rogério

    2018-03-08

    Sporothrix brasiliensis is the most virulent fungus of the Sporothrix complex and is the main species recovered in the sporotrichosis zoonotic hyperendemic area in Rio de Janeiro. A vaccine against S. brasiliensis could improve the current sporotrichosis situation. Here, we show 3 peptides from S. brasiliensis immunogenic proteins that have a higher likelihood for engaging MHC-class II molecules. We investigated the efficiency of the peptides as vaccines for preventing subcutaneous sporotrichosis. In this study, we observed a decrease in lesion diameters in peptide-immunized mice, showing that the peptides could induce a protective immune response against subcutaneous sporotrichosis. ZR8 peptide is from the GP70 protein, the main antigen of the Sporothrix complex, and was the best potential vaccine candidate by increasing CD4 + T cells and higher levels of IFN-γ, IL-17A and IL-1β characterizing a strong cellular immune response. This immune environment induced a higher number of neutrophils in lesions that are associated with fungus clearance. These results indicated that the ZR8 peptide induces a protective immune response against subcutaneous sporotrichosis and is a vaccine candidate against S. brasiliensis infection.

  1. A chimera embryo assay reveals a decrease in embryonic cellular proliferation induced by sperm from X-irradiated male mice

    International Nuclear Information System (INIS)

    Obasaju, M.F.; Wiley, L.M.; Oudiz, D.J.; Raabe, O.; Overstreet, J.W.

    1989-01-01

    Male mice were divided into three experimental groups and a control group. Mice in the experimental groups received one of three doses of acute X irradiation (1.73, 0.29, and 0.05 Gy) and together with the control unirradiated mice were then mated weekly to unirradiated female mice for a 9-week experimental period. Embryos were recovered from the weekly matings at the four-cell stage and examined by the chimera assay for proliferative disadvantage. Aggregation chimeras were constructed of embryos from female mice mated to irradiated males (experimental embryos) and embryos from females mated to unexposed males (control embryos) and contained either one experimental embryo and one control embryo (heterologous chimera) or two control embryos (control chimera). The control embryo in heterologous chimeras and either embryo in control chimeras were prelabeled with the vital dye fluorescein isothiocyanate (FITC), and the chimeras were cultured for 40 h and viewed under phase-contrast and epifluorescence microscopy to obtain total embryo cell number and the cellular contribution from the FITC-labeled embryo. Experimental and control embryos that were cultured singly were also examined for embryo cell number at the end of the 40-h culture period. In control chimeras, the mean ratio of the unlabeled cells:total chimera cell number (henceforth referred to as ''mean ratio'') was 0.50 with little or no weekly variation over the 9-week experimental period. During Weeks 4-7, the mean ratios of heterologous chimeras differed significantly from the mean ratio of control chimeras with the greatest differences occurring during Week 7 (0.41 for chimeras of 0.05 Gy dose group, 0.40 for chimeras of the 0.29 Gy dose group, and 0.17 for chimeras of the 1.73 Gy dose group)

  2. NAXE Mutations Disrupt the Cellular NAD(P)HX Repair System and Cause a Lethal Neurometabolic Disorder of Early Childhood.

    Science.gov (United States)

    Kremer, Laura S; Danhauser, Katharina; Herebian, Diran; Petkovic Ramadža, Danijela; Piekutowska-Abramczuk, Dorota; Seibt, Annette; Müller-Felber, Wolfgang; Haack, Tobias B; Płoski, Rafał; Lohmeier, Klaus; Schneider, Dominik; Klee, Dirk; Rokicki, Dariusz; Mayatepek, Ertan; Strom, Tim M; Meitinger, Thomas; Klopstock, Thomas; Pronicka, Ewa; Mayr, Johannes A; Baric, Ivo; Distelmaier, Felix; Prokisch, Holger

    2016-10-06

    To safeguard the cell from the accumulation of potentially harmful metabolic intermediates, specific repair mechanisms have evolved. APOA1BP, now renamed NAXE, encodes an epimerase essential in the cellular metabolite repair for NADHX and NADPHX. The enzyme catalyzes the epimerization of NAD(P)HX, thereby avoiding the accumulation of toxic metabolites. The clinical importance of the NAD(P)HX repair system has been unknown. Exome sequencing revealed pathogenic biallelic mutations in NAXE in children from four families with (sub-) acute-onset ataxia, cerebellar edema, spinal myelopathy, and skin lesions. Lactate was elevated in cerebrospinal fluid of all affected individuals. Disease onset was during the second year of life and clinical signs as well as episodes of deterioration were triggered by febrile infections. Disease course was rapidly progressive, leading to coma, global brain atrophy, and finally to death in all affected individuals. NAXE levels were undetectable in fibroblasts from affected individuals of two families. In these fibroblasts we measured highly elevated concentrations of the toxic metabolite cyclic-NADHX, confirming a deficiency of the mitochondrial NAD(P)HX repair system. Finally, NAD or nicotinic acid (vitamin B3) supplementation might have therapeutic implications for this fatal disorder. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. Long-term In Vivo Calcium Imaging of Astrocytes Reveals Distinct Cellular Compartment Responses to Sensory Stimulation.

    Science.gov (United States)

    Stobart, Jillian L; Ferrari, Kim David; Barrett, Matthew J P; Stobart, Michael J; Looser, Zoe J; Saab, Aiman S; Weber, Bruno

    2018-01-01

    Localized, heterogeneous calcium transients occur throughout astrocytes, but the characteristics and long-term stability of these signals, particularly in response to sensory stimulation, remain unknown. Here, we used a genetically encoded calcium indicator and an activity-based image analysis scheme to monitor astrocyte calcium activity in vivo. We found that different subcellular compartments (processes, somata, and endfeet) displayed distinct signaling characteristics. Closer examination of individual signals showed that sensory stimulation elevated the number of specific types of calcium peaks within astrocyte processes and somata, in a cortical layer-dependent manner, and that the signals became more synchronous upon sensory stimulation. Although mice genetically lacking astrocytic IP3R-dependent calcium signaling (Ip3r2-/-) had fewer signal peaks, the response to sensory stimulation was sustained, suggesting other calcium pathways are also involved. Long-term imaging of astrocyte populations revealed that all compartments reliably responded to stimulation over several months, but that the location of the response within processes may vary. These previously unknown characteristics of subcellular astrocyte calcium signals provide new insights into how astrocytes may encode local neuronal circuit activity. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Host and Non-Host roots in rice: cellular and molecular approaches reveal differential responses to arbuscular mycorrhizal fungi.

    Directory of Open Access Journals (Sweden)

    Valentina eFiorilli

    2015-08-01

    Full Text Available Oryza sativa, a model plant for Arbuscular Mycorrhizal (AM symbiosis, has both host and non-host roots. Large lateral (LLR and fine lateral (FLR roots display opposite responses: LLR support AM colonization, but FLR do not. Our research aimed to study the molecular, morphological and physiological aspects related to the non-host behavior of FLR. RNA-seq analysis revealed that LLR and FLR displayed divergent expression profiles, including changes in many metabolic pathways. Compared with LLR, FLR showed down-regulation of genes instrumental for AM establishment and gibberellin signaling, and a higher expression of nutrient transporters. Consistent with the transcriptomic data, FLR had higher phosphorus content. Light and electron microscopy demonstrated that, surprisingly, in the Selenio cultivar, FLR have a two-layered cortex, which is theoretically compatible with AM colonization. According to RNA-seq, a gibberellin inhibitor treatment increased anticlinal divisions leading to a higher number of cortex cells in FLR.We propose that some of the differentially regulated genes that lead to the anatomical and physiological properties of the two root types also function as genetic factors regulating fungal colonization. The rice root apparatus offers a unique tool to study AM symbiosis, allowing direct comparisons of host and non-host roots in the same individual plant.

  5. EEG reveals an early influence of social conformity on visual processing in group pressure situations.

    Science.gov (United States)

    Trautmann-Lengsfeld, Sina Alexa; Herrmann, Christoph Siegfried

    2013-01-01

    Humans are social beings and often have to perceive and perform within groups. In conflict situations, this puts them under pressure to either adhere to the group opinion or to risk controversy with the group. Psychological experiments have demonstrated that study participants adapt to erroneous group opinions in visual perception tasks, which they can easily solve correctly when performing on their own. Until this point, however, it is unclear whether this phenomenon of social conformity influences early stages of perception that might not even reach awareness or later stages of conscious decision-making. Using electroencephalography, this study has revealed that social conformity to the wrong group opinion resulted in a decrease of the posterior-lateral P1 in line with a decrease of the later centro-parietal P3. These results suggest that group pressure situations impact early unconscious visual perceptual processing, which results in a later diminished stimulus discrimination and an adaptation even to the wrong group opinion. These findings might have important implications for understanding social behavior in group settings and are discussed within the framework of social influence on eyewitness testimony.

  6. Quantitative proteomic analysis of human testis reveals system-wide molecular and cellular pathways associated with non-obstructive azoospermia.

    Science.gov (United States)

    Alikhani, Mehdi; Mirzaei, Mehdi; Sabbaghian, Marjan; Parsamatin, Pouria; Karamzadeh, Razieh; Adib, Samane; Sodeifi, Niloofar; Gilani, Mohammad Ali Sadighi; Zabet-Moghaddam, Masoud; Parker, Lindsay; Wu, Yunqi; Gupta, Vivek; Haynes, Paul A; Gourabi, Hamid; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

    2017-06-06

    Male infertility accounts for half of the infertility problems experienced by couples. Azoospermia, having no measurable level of sperm in seminal fluid, is one of the known conditions resulting in male infertility. In order to elucidate the complex molecular mechanisms causing male azoospermia, label-free quantitative shotgun proteomics was carried out on testicular tissue specimens from patients with obstructive azoospermia and non-obstructive azoospermia, including maturation arrest (MA) and Sertoli cell only syndrome (SCOS). The abundance of 520 proteins was significantly changed across three groups of samples. We were able to identify several functional biological pathways enriched in azoospermia samples and confirm selected differentially abundant proteins, using multiple histological methods. The results revealed that cell cycle and proteolysis, and RNA splicing were the most significant biological processes impaired by the substantial suppression of proteins related to the aforementioned categories in SCOS tissues. In the MA patient testes, generation of precursor metabolites and energy as well as oxidation-reduction were the most significantly altered processes. Novel candidate proteins identified in this study include key transcription factors, many of which have not previously been shown to be associated with azoospermia. Our findings can provide substantial insights into the molecular regulation of spermatogenesis and human reproduction. The obtained data showed a drastic suppression of proteins involved in spliceosome, cell cycle and proteasome proteins, as well as energy and metabolic production in Sertoli cell only syndrome testis tissue, and to a lesser extent in maturation arrest samples. Moreover, we identified new transcription factors that are highly down-regulated in SCOS and MA patients, thus helping to understand the molecular complexity of spermatogenesis in male infertility. Our findings provide novel candidate protein targets associated

  7. Proteomic analysis of HIV-1 Nef cellular binding partners reveals a role for exocyst complex proteins in mediating enhancement of intercellular nanotube formation

    Directory of Open Access Journals (Sweden)

    Mukerji Joya

    2012-06-01

    Full Text Available Abstract Background HIV-1 Nef protein contributes to pathogenesis via multiple functions that include enhancement of viral replication and infectivity, alteration of intracellular trafficking, and modulation of cellular signaling pathways. Nef stimulates formation of tunneling nanotubes and virological synapses, and is transferred to bystander cells via these intercellular contacts and secreted microvesicles. Nef associates with and activates Pak2, a kinase that regulates T-cell signaling and actin cytoskeleton dynamics, but how Nef promotes nanotube formation is unknown. Results To identify Nef binding partners involved in Pak2-association dependent Nef functions, we employed tandem mass spectrometry analysis of Nef immunocomplexes from Jurkat cells expressing wild-type Nef or Nef mutants defective for the ability to associate with Pak2 (F85L, F89H, H191F and A72P, A75P in NL4-3. We report that wild-type, but not mutant Nef, was associated with 5 components of the exocyst complex (EXOC1, EXOC2, EXOC3, EXOC4, and EXOC6, an octameric complex that tethers vesicles at the plasma membrane, regulates polarized exocytosis, and recruits membranes and proteins required for nanotube formation. Additionally, Pak2 kinase was associated exclusively with wild-type Nef. Association of EXOC1, EXOC2, EXOC3, and EXOC4 with wild-type, but not mutant Nef, was verified by co-immunoprecipitation assays in Jurkat cells. Furthermore, shRNA-mediated depletion of EXOC2 in Jurkat cells abrogated Nef-mediated enhancement of nanotube formation. Using bioinformatic tools, we visualized protein interaction networks that reveal functional linkages between Nef, the exocyst complex, and the cellular endocytic and exocytic trafficking machinery. Conclusions Exocyst complex proteins are likely a key effector of Nef-mediated enhancement of nanotube formation, and possibly microvesicle secretion. Linkages revealed between Nef and the exocyst complex suggest a new paradigm of

  8. A short-time scale colloidal system reveals early bacterial adhesion dynamics.

    Directory of Open Access Journals (Sweden)

    Christophe Beloin

    2008-07-01

    Full Text Available The development of bacteria on abiotic surfaces has important public health and sanitary consequences. However, despite several decades of study of bacterial adhesion to inert surfaces, the biophysical mechanisms governing this process remain poorly understood, due, in particular, to the lack of methodologies covering the appropriate time scale. Using micrometric colloidal surface particles and flow cytometry analysis, we developed a rapid multiparametric approach to studying early events in adhesion of the bacterium Escherichia coli. This approach simultaneously describes the kinetics and amplitude of early steps in adhesion, changes in physicochemical surface properties within the first few seconds of adhesion, and the self-association state of attached and free-floating cells. Examination of the role of three well-characterized E. coli surface adhesion factors upon attachment to colloidal surfaces--curli fimbriae, F-conjugative pilus, and Ag43 adhesin--showed clear-cut differences in the very initial phases of surface colonization for cell-bearing surface structures, all known to promote biofilm development. Our multiparametric analysis revealed a correlation in the adhesion phase with cell-to-cell aggregation properties and demonstrated that this phenomenon amplified surface colonization once initial cell-surface attachment was achieved. Monitoring of real-time physico-chemical particle surface properties showed that surface-active molecules of bacterial origin quickly modified surface properties, providing new insight into the intricate relations connecting abiotic surface physicochemical properties and bacterial adhesion. Hence, the biophysical analytical method described here provides a new and relevant approach to quantitatively and kinetically investigating bacterial adhesion and biofilm development.

  9. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

    Science.gov (United States)

    Devchand, Pallavi R; Schmidt, Birgitta A; Primo, Valeria C; Zhang, Qing-yin; Arnaout, M Amin; Serhan, Charles N; Nikolic, Boris

    2005-02-01

    Lipoxin A(4) (LXA(4)) and aspirin-triggered 15-epi-LXA(4) are potent endogenous lipid mediators thought to define the inflammatory set-point. We used single prophylactic administrations of a synthetic aspirin-triggered lipoxin A(4) signal mimetic, ATLa, to probe dynamics of early host-donor interactions in a mouse model for the inflammation-associated multifactorial disease of allogeneic bone marrow transplant (BMT) -induced graft-vs.-host disease (GvHD). We first demonstrated that both host and donor are responsive to the ATLa signals. The simple and restricted regimen of a single prophylactic administration of ATLa [100 ng/mL to donor cells or 1 microg (approximately 50 microg/kg) i.v. to host] was sufficient to delay death. Clinical indicators of weight, skin lesions, diarrhea and eye inflammation were monitored. Histological analyses on day 45 post-BMT showed that the degree of cellular trafficking, particularly neutrophil infiltrate, and protection of end-organ target pathology are different, depending on whether the host or donor was treated with ATLa. Taken together, these results chart some ATLa protective effects on GvHD cellular dynamics over time and identify a previously unrecognized effect of host neutrophils in the early phase post-BMT as important determinants in the dynamics of GvHD onset and progression.-Devchand, P. R., Schmidt, B. A., Primo, V. C., Zhang, Q.-y., Arnaout, M. A., Serhan, C. N., Nikolic, B. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

  10. Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum.

    Science.gov (United States)

    Kenyon, Amy; Gavriouchkina, Daria; Zorman, Jernej; Napolitani, Giorgio; Cerundolo, Vincenzo; Sauka-Spengler, Tatjana

    2017-07-26

    The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic processing of il1β, results in increased bacterial burden and less infiltration of macrophages to sites of mycobacterial infection, thus impairing granuloma development. We also show that a number of immediate early response genes (IEGs) are responsible for orchestrating the initial neutrophil response to mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key transcriptional regulator controlling il1β transcription.

  11. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma.

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    Mathieu Salaün

    Full Text Available Several matrix metalloproteinases (MMPs are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging.To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma.K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors.In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27, but in none of the non-invasive (0/4 (p=0.001.MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer.

  12. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma

    Science.gov (United States)

    Salaün, Mathieu; Peng, Jing; Hensley, Harvey H.; Roder, Navid; Flieder, Douglas B.; Houlle-Crépin, Solène; Abramovici-Roels, Olivia; Sabourin, Jean-Christophe; Thiberville, Luc; Clapper, Margie L.

    2015-01-01

    Introduction Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging. Objective To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. Methods K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. Results In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). Conclusion MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer. PMID:26193700

  13. Ligand Binding Induces Conformational Changes in Human Cellular Retinol-binding Protein 1 (CRBP1) Revealed by Atomic Resolution Crystal Structures.

    Science.gov (United States)

    Silvaroli, Josie A; Arne, Jason M; Chelstowska, Sylwia; Kiser, Philip D; Banerjee, Surajit; Golczak, Marcin

    2016-04-15

    Important in regulating the uptake, storage, and metabolism of retinoids, cellular retinol-binding protein 1 (CRBP1) is essential for trafficking vitamin A through the cytoplasm. However, the molecular details of ligand uptake and targeted release by CRBP1 remain unclear. Here we report the first structure of CRBP1 in a ligand-free form as well as ultra-high resolution structures of this protein bound to either all-trans-retinol or retinylamine, the latter a therapeutic retinoid that prevents light-induced retinal degeneration. Superpositioning of human apo- and holo-CRBP1 revealed major differences within segments surrounding the entrance to the retinoid-binding site. These included α-helix II and hairpin turns between β-strands βC-βD and βE-βF as well as several side chains, such as Phe-57, Tyr-60, and Ile-77, that change their orientations to accommodate the ligand. Additionally, we mapped hydrogen bond networks inside the retinoid-binding cavity and demonstrated their significance for the ligand affinity. Analyses of the crystallographic B-factors indicated several regions with higher backbone mobility in the apoprotein that became more rigid upon retinoid binding. This conformational flexibility of human apo-CRBP1 facilitates interaction with the ligands, whereas the more rigid holoprotein structure protects the labile retinoid moiety during vitamin A transport. These findings suggest a mechanism of induced fit upon ligand binding by mammalian cellular retinol-binding proteins. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. A systems biology approach reveals that tissue tropism to West Nile virus is regulated by antiviral genes and innate immune cellular processes.

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    Mehul S Suthar

    2013-02-01

    Full Text Available The actions of the RIG-I like receptor (RLR and type I interferon (IFN signaling pathways are essential for a protective innate immune response against the emerging flavivirus West Nile virus (WNV. In mice lacking RLR or IFN signaling pathways, WNV exhibits enhanced tissue tropism, indicating that specific host factors of innate immune defense restrict WNV infection and dissemination in peripheral tissues. However, the immune mechanisms by which the RLR and IFN pathways coordinate and function to impart restriction of WNV infection are not well defined. Using a systems biology approach, we defined the host innate immune response signature and actions that restrict WNV tissue tropism. Transcriptional profiling and pathway modeling to compare WNV-infected permissive (spleen and nonpermissive (liver tissues showed high enrichment for inflammatory responses, including pattern recognition receptors and IFN signaling pathways, that define restriction of WNV replication in the liver. Assessment of infected livers from Mavs(-/- × Ifnar(-/- mice revealed the loss of expression of several key components within the natural killer (NK cell signaling pathway, including genes associated with NK cell activation, inflammatory cytokine production, and NK cell receptor signaling. In vivo analysis of hepatic immune cell infiltrates from WT mice demonstrated that WNV infection leads to an increase in NK cell numbers with enhanced proliferation, maturation, and effector action. In contrast, livers from Mavs(-/- × Ifnar(-/- infected mice displayed reduced immune cell infiltration, including a significant reduction in NK cell numbers. Analysis of cocultures of dendritic and NK cells revealed both cell-intrinsic and -extrinsic roles for the RLR and IFN signaling pathways to regulate NK cell effector activity. Taken together, these observations reveal a complex innate immune signaling network, regulated by the RLR and IFN signaling pathways, that drives tissue

  15. Ancient DNA from European Early Neolithic Farmers Reveals Their Near Eastern Affinities

    Science.gov (United States)

    Haak, Wolfgang; Balanovsky, Oleg; Sanchez, Juan J.; Koshel, Sergey; Zaporozhchenko, Valery; Adler, Christina J.; Der Sarkissian, Clio S. I.; Brandt, Guido; Schwarz, Carolin; Nicklisch, Nicole; Dresely, Veit; Fritsch, Barbara; Balanovska, Elena; Villems, Richard; Meller, Harald; Alt, Kurt W.; Cooper, Alan

    2010-01-01

    In Europe, the Neolithic transition (8,000–4,000 b.c.) from hunting and gathering to agricultural communities was one of the most important demographic events since the initial peopling of Europe by anatomically modern humans in the Upper Paleolithic (40,000 b.c.). However, the nature and speed of this transition is a matter of continuing scientific debate in archaeology, anthropology, and human population genetics. To date, inferences about the genetic make up of past populations have mostly been drawn from studies of modern-day Eurasian populations, but increasingly ancient DNA studies offer a direct view of the genetic past. We genetically characterized a population of the earliest farming culture in Central Europe, the Linear Pottery Culture (LBK; 5,500–4,900 calibrated b.c.) and used comprehensive phylogeographic and population genetic analyses to locate its origins within the broader Eurasian region, and to trace potential dispersal routes into Europe. We cloned and sequenced the mitochondrial hypervariable segment I and designed two powerful SNP multiplex PCR systems to generate new mitochondrial and Y-chromosomal data from 21 individuals from a complete LBK graveyard at Derenburg Meerenstieg II in Germany. These results considerably extend the available genetic dataset for the LBK (n = 42) and permit the first detailed genetic analysis of the earliest Neolithic culture in Central Europe (5,500–4,900 calibrated b.c.). We characterized the Neolithic mitochondrial DNA sequence diversity and geographical affinities of the early farmers using a large database of extant Western Eurasian populations (n = 23,394) and a wide range of population genetic analyses including shared haplotype analyses, principal component analyses, multidimensional scaling, geographic mapping of genetic distances, and Bayesian Serial Simcoal analyses. The results reveal that the LBK population shared an affinity with the modern-day Near East and Anatolia, supporting a major

  16. Ancient DNA from European early neolithic farmers reveals their near eastern affinities.

    Directory of Open Access Journals (Sweden)

    Wolfgang Haak

    Full Text Available In Europe, the Neolithic transition (8,000-4,000 B.C. from hunting and gathering to agricultural communities was one of the most important demographic events since the initial peopling of Europe by anatomically modern humans in the Upper Paleolithic (40,000 B.C.. However, the nature and speed of this transition is a matter of continuing scientific debate in archaeology, anthropology, and human population genetics. To date, inferences about the genetic make up of past populations have mostly been drawn from studies of modern-day Eurasian populations, but increasingly ancient DNA studies offer a direct view of the genetic past. We genetically characterized a population of the earliest farming culture in Central Europe, the Linear Pottery Culture (LBK; 5,500-4,900 calibrated B.C. and used comprehensive phylogeographic and population genetic analyses to locate its origins within the broader Eurasian region, and to trace potential dispersal routes into Europe. We cloned and sequenced the mitochondrial hypervariable segment I and designed two powerful SNP multiplex PCR systems to generate new mitochondrial and Y-chromosomal data from 21 individuals from a complete LBK graveyard at Derenburg Meerenstieg II in Germany. These results considerably extend the available genetic dataset for the LBK (n = 42 and permit the first detailed genetic analysis of the earliest Neolithic culture in Central Europe (5,500-4,900 calibrated B.C.. We characterized the Neolithic mitochondrial DNA sequence diversity and geographical affinities of the early farmers using a large database of extant Western Eurasian populations (n = 23,394 and a wide range of population genetic analyses including shared haplotype analyses, principal component analyses, multidimensional scaling, geographic mapping of genetic distances, and Bayesian Serial Simcoal analyses. The results reveal that the LBK population shared an affinity with the modern-day Near East and Anatolia, supporting

  17. Early leaf senescence is associated with an altered cellular redox balance in Arabidopsis cpr5/old1 mutants

    NARCIS (Netherlands)

    Jing, H. -C.; Hebeler, R.; Oeljeklaus, S.; Sitek, B.; Stuehler, K.; Meyer, H. E.; Sturre, M. J. G.; Hille, J.; Warscheid, B.; Dijkwel, P. P.; Stühler, K.

    Reactive oxygen species (ROS) are the inevitable by-products of essential cellular metabolic and physiological activities. Plants have developed sophisticated gene networks of ROS generation and scavenging systems. However, ROS regulation is still poorly understood. Here, we report that mutations in

  18. Early herding practices revealed through organic residue analysis of pottery from the early Neolithic rock shelter of Mala Triglavca, Slovenia

    Directory of Open Access Journals (Sweden)

    Lucija Šoberl

    2008-12-01

    Full Text Available A collection of pottery from the early Neolithic site of Mala Triglavca was analysed with the aim of obtaining insights into vessel use and early animal domestication and husbandry practices in the Adriatic region. Total lipid extracts were submitted to gas chromatography (GC, GC-mass spectrometry (GC-MS and GC-combustion-isotope ratio MS (GC-C-IRMS in order to obtain molecular and stable carbon isotope signatures as the basis for determining the nature and origins of the residues. The extracts were dominated by degraded animal fats. The majority (70% of the total lipid extracts displayed intact triacylglycerol distributions attributable to ruminant adipose and dairy fats, which were subsequently confirmed through C16:0 and C18:0 fatty acid δ13C values.

  19. Intramolecular dynamics within the N-Cap-SH3-SH2 regulatory unit of the c-Abl tyrosine kinase reveal targeting to the cellular membrane.

    Science.gov (United States)

    de Oliveira, Guilherme A P; Pereira, Elen G; Ferretti, Giulia D S; Valente, Ana Paula; Cordeiro, Yraima; Silva, Jerson L

    2013-09-27

    c-Abl is a key regulator of cell signaling and is under strict control via intramolecular interactions. In this study, we address changes in the intramolecular dynamics coupling within the c-Abl regulatory unit by presenting its N-terminal segment (N-Cap) with an alternative function in the cell as c-Abl becomes activated. Using small angle x-ray scattering, nuclear magnetic resonance, and confocal microscopy, we demonstrate that the N-Cap and the Src homology (SH) 3 domain acquire μs-ms motions upon N-Cap association with the SH2-L domain, revealing a stabilizing synergy between these segments. The N-Cap-myristoyl tether likely triggers the protein to anchor to the membrane because of these flip-flop dynamics, which occur in the μs-ms time range. This segment not only presents the myristate during c-Abl inhibition but may also trigger protein localization inside the cell in a functional and stability-dependent mechanism that is lost in Bcr-Abl(+) cells, which underlie chronic myeloid leukemia. This loss of intramolecular dynamics and binding to the cellular membrane is a potential therapeutic target.

  20. Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

    Science.gov (United States)

    Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

    2010-01-01

    Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

  1. Oxygen restriction as challenge test reveals early high-fat-diet-induced changes in glucose and lipid metabolism

    NARCIS (Netherlands)

    Duivenvoorde, L.P.M.; Schothorst, van E.M.; Derous, D.; Stelt, van der I.; Masania, J.; Rabbani, N.; Thornalley, P.J.; Keijer, J.

    2015-01-01

    Challenge tests stress homeostasis and may reveal deviations in health that remain masked under unchallenged conditions. Ideally, challenge tests are non-invasive and applicable in an early phase of an animal experiment. Oxygen restriction (OxR; based on ambient, mild normobaric hypoxia) is a

  2. A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds.

    Science.gov (United States)

    Knoll, Fabien; Chiappe, Luis M; Sanchez, Sophie; Garwood, Russell J; Edwards, Nicholas P; Wogelius, Roy A; Sellers, William I; Manning, Phillip L; Ortega, Francisco; Serrano, Francisco J; Marugán-Lobón, Jesús; Cuesta, Elena; Escaso, Fernando; Sanz, Jose Luis

    2018-03-05

    Fossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages of development. Comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.

  3. Early differential cell death and survival mechanisms initiate and contribute to the development of OPIDN: A study of molecular, cellular, and anatomical parameters

    International Nuclear Information System (INIS)

    Damodaran, T.V.; Attia, M.K.; Abou-Donia, M.B.

    2011-01-01

    analysis revealed that the order of severity of damage declines from the spino-cerebellar, ventral, and dorsal tract respectively, suggesting neuroanatomical specificity. Thus, early activation of cell death and cell survival processes may play significant role in the clinical progression and syndromic clinical feature presentation of OPIDN. -- Highlights: ► Multiple mechanisms of neurodegeneration were indicated in a study on OPIDN model. ► Altered expressions of BCL2 and GADD45 were recorded in various tissues of CNS. ► Multiple anomalous cellular (neuronal and astroglial) features were recorded. ► Anatomical specificity of the neurodegeneration was described.

  4. Large-scale Metabolomic Analysis Reveals Potential Biomarkers for Early Stage Coronary Atherosclerosis.

    Science.gov (United States)

    Gao, Xueqin; Ke, Chaofu; Liu, Haixia; Liu, Wei; Li, Kang; Yu, Bo; Sun, Meng

    2017-09-18

    Coronary atherosclerosis (CAS) is the pathogenesis of coronary heart disease, which is a prevalent and chronic life-threatening disease. Initially, this disease is not always detected until a patient presents with seriously vascular occlusion. Therefore, new biomarkers for appropriate and timely diagnosis of early CAS is needed for screening to initiate therapy on time. In this study, we used an untargeted metabolomics approach to identify potential biomarkers that could enable highly sensitive and specific CAS detection. Score plots from partial least-squares discriminant analysis clearly separated early-stage CAS patients from controls. Meanwhile, the levels of 24 metabolites increased greatly and those of 18 metabolites decreased markedly in early CAS patients compared with the controls, which suggested significant metabolic dysfunction in phospholipid, sphingolipid, and fatty acid metabolism in the patients. Furthermore, binary logistic regression showed that nine metabolites could be used as a combinatorial biomarker to distinguish early-stage CAS patients from controls. The panel of nine metabolites was then tested with an independent cohort of samples, which also yielded satisfactory diagnostic accuracy (AUC = 0.890). In conclusion, our findings provide insight into the pathological mechanism of early-stage CAS and also supply a combinatorial biomarker to aid clinical diagnosis of early-stage CAS.

  5. Receptor complementation and mutagenesis reveal SR-BI as an essential HCV entry factor and functionally imply its intra- and extra-cellular domains.

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    Marlène Dreux

    2009-02-01

    Full Text Available HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI, a major receptor of high-density lipoprotein (HDL, the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection.

  6. Pure versus combined Merkel cell carcinomas: immunohistochemical evaluation of cellular proteins (p53, Bcl-2, and c-kit) reveals significant overexpression of p53 in combined tumors.

    Science.gov (United States)

    Lai, Jonathan H; Fleming, Kirsten E; Ly, Thai Yen; Pasternak, Sylvia; Godlewski, Marek; Doucette, Steve; Walsh, Noreen M

    2015-09-01

    Merkel cell polyomavirus is of oncogenic significance in approximately 80% of Merkel cell carcinomas. Morphological subcategories of the tumor differ in regard to viral status, the rare combined type being uniformly virus negative and the predominant pure type being mainly virus positive. Indications that different biological subsets of the tumor exist led us to explore this diversity. In an Eastern Canadian cohort of cases (75 patients; mean age, 76 years [range, 43-91]; male/female ratio, 43:32; 51 [68%] pure and 24 [34%] combined tumors), we semiquantitatively compared the immunohistochemical expression of 3 cellular proteins (p53, Bcl-2, and c-kit) in pure versus combined groups. Viral status was known in a subset of cases. The significant overexpression of p53 in the combined group (mean [SD], 153.8 [117.8] versus 121.6 [77.9]; P = .01) and the increased epidermal expression of this protein (p53 patches) in the same group lend credence to a primary etiologic role for sun damage in these cases. Expression of Bcl-2 and c-kit did not differ significantly between the 2 morphological groups. A relative increase in c-kit expression was significantly associated with a virus-negative status (median [interquartile range], 100 [60-115] versus 70 [0-100]; P = .03). Emerging data reveal divergent biological pathways in Merkel cell carcinoma, each with a characteristic immunohistochemical profile. Virus-positive tumors (all pure) exhibit high retinoblastoma protein and low p53 expression, whereas virus-negative cases (few pure and all combined) show high p53 and relatively high c-kit expression. The potential biological implications of this dichotomy call for consistent stratification of these tumors in future studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Single-cell analysis reveals early manifestation of cancerous phenotype in pre-malignant esophageal cells.

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    Jiangxin Wang

    Full Text Available Cellular heterogeneity plays a pivotal role in a variety of functional processes in vivo including carcinogenesis. However, our knowledge about cell-to-cell diversity and how differences in individual cells manifest in alterations at the population level remains very limited mainly due to the lack of appropriate tools enabling studies at the single-cell level. We present a study on changes in cellular heterogeneity in the context of pre-malignant progression in response to hypoxic stress. Utilizing pre-malignant progression of Barrett's esophagus (BE as a disease model system we studied molecular mechanisms underlying the progression from metaplastic to dysplastic (pre-cancerous stage. We used newly developed methods enabling measurements of cell-to-cell differences in copy numbers of mitochondrial DNA, expression levels of a set of mitochondrial and nuclear genes involved in hypoxia response pathways, and mitochondrial membrane potential. In contrast to bulk cell studies reported earlier, our study shows significant differences between metaplastic and dysplastic BE cells in both average values and single-cell parameter distributions of mtDNA copy numbers, mitochondrial function, and mRNA expression levels of studied genes. Based on single-cell data analysis, we propose that mitochondria may be one of the key factors in pre-malignant progression in BE.

  8. Cellular homeoproteins, SATB1 and CDP, bind to the unique region between the human cytomegalovirus UL127 and major immediate-early genes

    International Nuclear Information System (INIS)

    Lee Jialing; Klase, Zachary; Gao Xiaoqi; Caldwell, Jeremy S.; Stinski, Mark F.; Kashanchi, Fatah; Chao, S.-H.

    2007-01-01

    An AT-rich region of the human cytomegalovirus (CMV) genome between the UL127 open reading frame and the major immediate-early (MIE) enhancer is referred to as the unique region (UR). It has been shown that the UR represses activation of transcription from the UL127 promoter and functions as a boundary between the divergent UL127 and MIE genes during human CMV infection [Angulo, A., Kerry, D., Huang, H., Borst, E.M., Razinsky, A., Wu, J., Hobom, U., Messerle, M., Ghazal, P., 2000. Identification of a boundary domain adjacent to the potent human cytomegalovirus enhancer that represses transcription of the divergent UL127 promoter. J. Virol. 74 (6), 2826-2839; Lundquist, C.A., Meier, J.L., Stinski, M.F., 1999. A strong negative transcriptional regulatory region between the human cytomegalovirus UL127 gene and the major immediate-early enhancer. J. Virol. 73 (11), 9039-9052]. A putative forkhead box-like (FOX-like) site, AAATCAATATT, was identified in the UR and found to play a key role in repression of the UL127 promoter in recombinant virus-infected cells [Lashmit, P.E., Lundquist, C.A., Meier, J.L., Stinski, M.F., 2004. Cellular repressor inhibits human cytomegalovirus transcription from the UL127 promoter. J. Virol. 78 (10), 5113-5123]. However, the cellular factors which associate with the UR and FOX-like region remain to be determined. We reported previously that pancreatic-duodenal homeobox factor-1 (PDX1) bound to a 45-bp element located within the UR [Chao, S.H., Harada, J.N., Hyndman, F., Gao, X., Nelson, C.G., Chanda, S.K., Caldwell, J.S., 2004. PDX1, a Cellular Homeoprotein, Binds to and Regulates the Activity of Human Cytomegalovirus Immediate Early Promoter. J. Biol. Chem. 279 (16), 16111-16120]. Here we demonstrate that two additional cellular homeoproteins, special AT-rich sequence binding protein 1 (SATB1) and CCAAT displacement protein (CDP), bind to the human CMV UR in vitro and in vivo. Furthermore, CDP is identified as a FOX-like binding protein

  9. Transcriptomic profiling of bovine IVF embryos revealed candidate genes and pathways involved in early embryonic development

    Directory of Open Access Journals (Sweden)

    Yandell Brian S

    2010-01-01

    Full Text Available Abstract Background Early embryonic loss is a large contributor to infertility in cattle. Although genetic factors are known to affect early embryonic development, the discovery of such factors has been a serious challenge. The objective of this study was to identify genes differentially expressed between blastocysts and degenerative embryos at early stages of development. Results Using microarrays, genome-wide RNA expression was profiled and compared for in vitro fertilization (IVF - derived blastocysts and embryos undergoing degenerative development up to the same time point. Surprisingly similar transcriptomic profiles were found in degenerative embryos and blastocysts. Nonetheless, we identified 67 transcripts that significantly differed between these two groups of embryos at a 15% false discovery rate, including 33 transcripts showing at least a two-fold difference. Several signaling and metabolic pathways were found to be associated with the developmental status of embryos, among which were previously known important steroid biosynthesis and cell communication pathways in early embryonic development. Conclusions This study presents the first direct and comprehensive comparison of transcriptomes between IVF blastocysts and degenerative embryos, providing important information for potential genes and pathways associated with early embryonic development.

  10. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis

    Science.gov (United States)

    Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

    2014-01-01

    Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (PM. R., Samiei, S., Soheili, Z.-S., Frimmel, S., Zhang, Z., Ablonczy, Z., Ahmadieh, H., Hafezi-Moghadam, A. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis. PMID:24903276

  11. Early Top-Down Influences on Bistable Perception Revealed by Event-Related Potentials

    Science.gov (United States)

    Pitts, Michael A.; Gavin, William J.; Nerger, Janice L.

    2008-01-01

    A longstanding debate exists in the literature concerning bottom-up vs. top-down influences on bistable perception. Recently, a technique has been developed to measure early changes in brain activity (via ERPs) related to perceptual reversals (Kornmeier & Bach, 2004). An ERP component, the reversal negativity (RN) has been identified, and is…

  12. Barium distributions in teeth reveal early-life dietary transitions in primates.

    Science.gov (United States)

    Austin, Christine; Smith, Tanya M; Bradman, Asa; Hinde, Katie; Joannes-Boyau, Renaud; Bishop, David; Hare, Dominic J; Doble, Philip; Eskenazi, Brenda; Arora, Manish

    2013-06-13

    Early-life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth. Uncovering early-life dietary history in fossils is hampered by the absence of prospectively validated biomarkers that are not modified during fossilization. Here we show that large dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother's milk through the weaning process. We also document dietary transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, indicating an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history.

  13. Barium distributions in teeth reveal early life dietary transitions in primates

    Science.gov (United States)

    Austin, Christine; Smith, Tanya M.; Bradman, Asa; Hinde, Katie; Joannes-Boyau, Renaud; Bishop, David; Hare, Dominic J.; Doble, Philip; Eskenazi, Brenda; Arora, Manish

    2013-01-01

    Early life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations1,2. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth3. Uncovering early life dietary history in fossils is hampered by the absence of prospectively-validated biomarkers that are not modified during fossilisation4. Here we show that major dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively-recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother’s milk and through the weaning process. We also document transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, suggesting an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history. PMID:23698370

  14. Dynamic locomotor capabilities revealed by early dinosaur trackmakers from southern Africa.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Wilson

    Full Text Available BACKGROUND: A new investigation of the sedimentology and ichnology of the Early Jurassic Moyeni tracksite in Lesotho, southern Africa has yielded new insights into the behavior and locomotor dynamics of early dinosaurs. METHODOLOGY/PRINCIPAL FINDINGS: The tracksite is an ancient point bar preserving a heterogeneous substrate of varied consistency and inclination that includes a ripple-marked riverbed, a bar slope, and a stable algal-matted bar top surface. Several basal ornithischian dinosaurs and a single theropod dinosaur crossed its surface within days or perhaps weeks of one another, but responded to substrate heterogeneity differently. Whereas the theropod trackmaker accommodated sloping and slippery surfaces by gripping the substrate with its pedal claws, the basal ornithischian trackmakers adjusted to the terrain by changing between quadrupedal and bipedal stance, wide and narrow gauge limb support (abduction range = 31 degrees , and plantigrade and digitigrade foot posture. CONCLUSIONS/SIGNIFICANCE: The locomotor adjustments coincide with changes in substrate consistency along the trackway and appear to reflect 'real time' responses to a complex terrain. It is proposed that these responses foreshadow important locomotor transformations characterizing the later evolution of the two main dinosaur lineages. Ornithischians, which shifted from bipedal to quadrupedal posture at least three times in their evolutionary history, are shown to have been capable of adopting both postures early in their evolutionary history. The substrate-gripping behavior demonstrated by the early theropod, in turn, is consistent with the hypothesized function of pedal claws in bird ancestors.

  15. FINE SPECIFICITY OF CELLULAR IMMUNE-RESPONSES IN HUMANS TO HUMAN CYTOMEGALOVIRUS IMMEDIATE-EARLY 1-PROTEIN

    NARCIS (Netherlands)

    ALP, NJ; ALLPORT, TD; VANZANTEN, J; RODGERS, B; SISSONS, JGP; BORYSIEWICZ, LK

    Cell-mediated immunity is important in maintaining the virus-host equilibrium in persistent human cytomegalovirus (HCMV) infection. The HCMV 72-kDa major immediate early 1 protein (IE1) is a target for CD8+ cytotoxic T cells in humans, as is the equivalent 89-kDa protein in mouse. Less is known

  16. Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea.

    Science.gov (United States)

    Francis, J P; Richmond, P C; Strickland, D; Prescott, S L; Pomat, W S; Michael, A; Nadal-Sims, M A; Edwards-Devitt, C J; Holt, P G; Lehmann, D; van den Biggelaar, A H J

    2017-03-01

    In areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high-risk areas have pre-existing pneumococcal-specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA-induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA-specific interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-10 and IL-13 responses, and lower dPly-IL-6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA-IL-5 and PspA-IL-13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly-IL-6 responses with a higher frequency of cord antigen-presenting cells. In the PNG cohort, higher PspA-specific IL-5 and IL-6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA-IL-10 CBMC responses. Pneumococcus-specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease. © 2016 British Society for Immunology.

  17. Gene expression profiling reveals underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis

    International Nuclear Information System (INIS)

    Pogribny, Igor P.; Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.; Muskhelishvili, Levan; Rodriguez-Juarez, Rocio; Kovalchuk, Olga; Han Tao; Fuscoe, James C.; Ross, Sharon A.; Beland, Frederick A.

    2007-01-01

    Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the molecular mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. In the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during early stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that early stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during early stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G 1 to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt1/2, Akt3, and cyclin B, D1, and D3 proteins. The early appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen

  18. Chinese characters reveal impacts of prior experience on very early stages of perception

    Directory of Open Access Journals (Sweden)

    Stollhoff Rainer

    2011-01-01

    Full Text Available Abstract Background Visual perception is strongly determined by accumulated experience with the world, which has been shown for shape, color, and position perception, in the field of visuomotor learning, and in neural computation. In addition, visual perception is tuned to statistics of natural scenes. Such prior experience is modulated by neuronal top-down control the temporal properties of which had been subject to recent studies. Here, we deal with these temporal properties and address the question how early in time accumulated past experience can modulate visual perception. Results We performed stimulus discrimination experiments and compared a group of Chinese participants with a German control group. The perception of our briefly presented visual objects (targets was disturbed by masking stimuli which appeared in close spatiotemporal proximity. These masking stimuli were either intact or scrambled Chinese characters and did not overlap with the targets. In contrast to German controls, Chinese participants show substantial performance differences for real versus scrambled Chinese characters if these masking stimuli were presented as early as less than 100 milliseconds after the onset of the target. For Chinese observers, it even occured that meaningful masking stimuli enhanced target identification if they were shown at least 100 milliseconds after target onset while the same stimuli impaired recognition if presented in close temporal proximity to the target. The latter finding challenges interpretations of our data that solely rely on stimulus contours or geometric properties and emphasizes the impact of prior experience on the very early temporal dynamics of the visual system. Conclusions Our findings demonstrate that prior experience which had been accummulated long before the experiments can modulate the time course of perception intriguingly early, namely already immediately after the perceptual onset of a visual event. This modulation

  19. Bird-like anatomy, posture, and behavior revealed by an early jurassic theropod dinosaur resting trace

    Science.gov (United States)

    Milner, Andrew R.C.; Harris, J.D.; Lockley, M.G.; Kirkland, J.I.; Matthews, N.A.

    2009-01-01

    Background: Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. Methodology/Principal Findings: Here we describe a well-preserved theropod trackway in a Lower Jurassic (???198 millionyear- old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. Conclusions/Significance: The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods.

  20. The TESIS Project: Revealing Massive Early-Type Galaxies at z > 1

    Science.gov (United States)

    Saracco, P.; Longhetti, M.; Severgnini, P.; Della Ceca, R.; Braito, V.; Bender, R.; Drory, N.; Feulner, G.; Hopp, U.; Mannucci, F.; Maraston, C.

    How and when present-day massive early-type galaxies built up and what type of evolution has characterized their growth (star formation and/or merging) still remain open issues. The different competing scenarios of galaxy formation predict much different properties of early-type galaxies at z > 1. The "monolithic" collapse predicts that massive spheroids formed at high redshift (z > 2.5-3) and that their comoving density is constant at z 1, their comoving density decreases from z = 0 to z ~ 1.5 and they should experience their last burst of star formation at z 1 can be probed observationally once a well defined sample of massive early-types at z > 1 is available. We are constructing such a sample through a dedicated near-IR very low resolution (λ/Δλ≃50) spectroscopic survey (TNG EROs Spectroscopic Identification Survey, TESIS, [6]) of a complete sample of 30 bright (K < 18.5) Extremely Red Objects (EROs).

  1. Bird-like anatomy, posture, and behavior revealed by an early jurassic theropod dinosaur resting trace.

    Directory of Open Access Journals (Sweden)

    Andrew R C Milner

    Full Text Available BACKGROUND: Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-year-old lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. CONCLUSIONS/SIGNIFICANCE: The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods.

  2. Bird-like anatomy, posture, and behavior revealed by an early jurassic theropod dinosaur resting trace.

    Science.gov (United States)

    Milner, Andrew R C; Harris, Jerald D; Lockley, Martin G; Kirkland, James I; Matthews, Neffra A

    2009-01-01

    Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-year-old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods.

  3. A novel method for measuring cellular antibody uptake using imaging flow cytometry reveals distinct uptake rates for two different monoclonal antibodies targeting L1.

    Science.gov (United States)

    Hazin, John; Moldenhauer, Gerhard; Altevogt, Peter; Brady, Nathan R

    2015-08-01

    Monoclonal antibodies (mAbs) have emerged as a promising tool for cancer therapy. Differing approaches utilize mAbs to either deliver a drug to the tumor cells or to modulate the host's immune system to mediate tumor kill. The rate by which a therapeutic antibody is being internalized by tumor cells is a decisive feature for choosing the appropriate treatment strategy. We herein present a novel method to effectively quantitate antibody uptake of tumor cells by using image-based flow cytometry, which combines image analysis with high throughput of sample numbers and sample size. The use of this method is established by determining uptake rate of an anti-EpCAM antibody (HEA125), from single cell measurements of plasma membrane versus internalized antibody, in conjunction with inhibitors of endocytosis. The method is then applied to two mAbs (L1-9.3, L1-OV52.24) targeting the neural cell adhesion molecule L1 (L1CAM) at two different epitopes. Based on median cell population responses, we find that mAb L1-OV52.24 is rapidly internalized by the ovarian carcinoma cell line SKOV3ip while L1 mAb 9.3 is mainly retained at the cell surface. These findings suggest the L1 mAb OV52.24 as a candidate to be further developed for drug-delivery to cancer cells, while L1-9.3 may be optimized to tag the tumor cells and stimulate immunogenic cancer cell killing. Furthermore, when analyzing cell-to-cell variability, we observed L1 mAb OV52.24 rapidly transition into a subpopulation with high-internalization capacity. In summary, this novel high-content method for measuring antibody internalization rate provides a high level of accuracy and sensitivity for cell population measurements and reveals further biologically relevant information when taking into account cellular heterogeneity. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Reworked crustal of early Paleozoic WuYi Orogen revealed by receiver function data

    Science.gov (United States)

    Wei, Y.; Duan, Y.; Tian, X.; Zhao, Y.

    2017-12-01

    Intraplate orogenic belt, which occurs at the rigid and undeformable plate interiors, is a distinct new type of orogen rather than an interplate or plate marginal orogenic belt, whose deformation occurs exclusively at plate margins. Therefore, intraplate orogenic belts are the most obvious exception to the plate-tectonic paradigm, they are uncommon in Earth's history. The early Paleozoic Wuyi orogen in South China is one of the few examples of intraplate orogen, and is a key to understanding the process of intraplate orogenesis and global early Paleozoic geodynamics. In this study, we select teleseismic records from 45 mobile linear seismic stations deployed in Wuyi Mountain and 58 permanent stations setting in Jiangxi and Fujian provinces, from January 2011 to December 2012, and calculate the crustal thickness and average crustal Vp/Vs ratio using the H-κ stacking method. The main results include the following: 1) the crustal average Poission's ratio shows an increase tendency from land to sea, the interior of Wuyi orogen belt with an low ration less than 0.23, and the coastline with high ration which is up to 0.28, which indicate a very heterogeneous crustal structure and composition in Wuyi orogen and coast belt. 2) the crustal thickness ranges 28-34 km and shows a tendency of thinning from inland to coast in the region of SE China margin, which maight mean the eastern Eurasia lithospheric is extension and thinning induced by the subducted paleo-Pacific slab. To conclusion, we assume that Wuyi orogen experienced upper crustal thickening, lower crust and lithosphere delamination during the early Paleozoic orogeny, and lithosphere extension in Mesozoic. This research is founded by the Natural Science Foundation of China (41174052 and 41604048).

  5. Classification tree analyses reveal limited potential for early targeted prevention against childhood overweight.

    Science.gov (United States)

    Beyerlein, Andreas; Kusian, Dennis; Ziegler, Anette-Gabriele; Schaffrath-Rosario, Angelika; von Kries, Rüdiger

    2014-02-01

    Whether specific combinations of risk factors in very early life might allow identification of high-risk target groups for overweight prevention programs was examined. Data of n = 8981 children from the German KiGGS study were analyzed. Using a classification tree approach, predictive risk factor combinations were assessed for overweight in 3-6, 7-10, and 11-17-year-old children. In preschool children, the subgroup with the highest overweight risk were migrant children with at least one obese parent, with a prevalence of 36.6 (95% confidence interval or CI: 22.9, 50.4)%, compared to an overall prevalence of 10.0 (8.9, 11.2)%. The prevalence of overweight increased from 18.3 (16.8, 19.8)% to 57.9 (46.6, 69.3)% in 7-10-year-old children, if at least one parent was obese and the child had been born large-for-gestational-age. In 11-17-year-olds, the overweight risk increased from 20.1 (18.9, 21.3)% to 63.0 (46.4, 79.7)% in the highest risk group. However, high prevalence ratios were found only in small subgroups, containing <10% of all overweight cases in the respective age group. Our results indicate only a limited potential for early targeted preventions against overweight in children and adolescents. Copyright © 2013 The Obesity Society.

  6. Starch grains reveal early root crop horticulture in the Panamanian tropical forest.

    Science.gov (United States)

    Piperno, D R; Ranere, A J; Holst, I; Hansell, P

    2000-10-19

    Native American populations are known to have cultivated a large number of plants and domesticated them for their starch-rich underground organs. Suggestions that the likely source of many of these crops, the tropical forest, was an early and influential centre of plant husbandry have long been controversial because the organic remains of roots and tubers are poorly preserved in archaeological sediments from the humid tropics. Here we report the occurrence of starch grains identifiable as manioc (Manihot esculenta Crantz), yams (Dioscorea sp.) and arrowroot (Maranta arundinacea L.) on assemblages of plant milling stones from preceramic horizons at the Aguadulce Shelter, Panama, dated between 7,000 and 5,000 years before present (BP). The artefacts also contain maize starch (Zea mays L.), indicating that early horticultural systems in this region were mixtures of root and seed crops. The data provide the earliest direct evidence for root crop cultivation in the Americas, and support an ancient and independent emergence of plant domestication in the lowland Neotropical forest.

  7. Synchrotron Reveals Early Triassic Odd Couple: Injured Amphibian and Aestivating Therapsid Share Burrow.

    Directory of Open Access Journals (Sweden)

    Vincent Fernandez

    Full Text Available Fossorialism is a beneficial adaptation for brooding, predator avoidance and protection from extreme climate. The abundance of fossilised burrow casts from the Early Triassic of southern Africa is viewed as a behavioural response by many tetrapods to the harsh conditions following the Permo-Triassic mass-extinction event. However, scarcity of vertebrate remains associated with these burrows leaves many ecological questions unanswered. Synchrotron scanning of a lithified burrow cast from the Early Triassic of the Karoo unveiled a unique mixed-species association: an injured temnospondyl amphibian (Broomistega that sheltered in a burrow occupied by an aestivating therapsid (Thrinaxodon. The discovery of this rare rhinesuchid represents the first occurrence in the fossil record of a temnospondyl in a burrow. The amphibian skeleton shows signs of a crushing trauma with partially healed fractures on several consecutive ribs. The presence of a relatively large intruder in what is interpreted to be a Thrinaxodon burrow implies that the therapsid tolerated the amphibian's presence. Among possible explanations for such unlikely cohabitation, Thrinaxodon aestivation is most plausible, an interpretation supported by the numerous Thrinaxodon specimens fossilised in curled-up postures. Recent advances in synchrotron imaging have enabled visualization of the contents of burrow casts, thus providing a novel tool to elucidate not only anatomy but also ecology and biology of ancient tetrapods.

  8. Immediate relativity: EEG reveals early engagement of comparison in social information processing.

    Science.gov (United States)

    Ohmann, Katharina; Stahl, Jutta; Mussweiler, Thomas; Kedia, Gayannée

    2016-11-01

    A wide array of social decisions relies on social comparisons. As such, these decisions require fast access to relative information. Therefore, we expect that signatures of the comparative process should be observable in electrophysiological components at an early stage of information processing. However, to date, little is known about the neural time course of social target comparisons. Therefore, we tested this hypothesis in 2 electroencephalography (EEG) studies using a social distance effect paradigm. The distance effect capitalizes on the fact that stimuli close on a certain dimension take longer to compare than stimuli clearly differing on this dimension. Here, we manipulated the distance of face characteristics regarding their levels of attractiveness (Study 1) and trustworthiness (Study 2), 2 essential social dimensions. In both studies, size comparisons served as a nonsocial control condition. In Study 1, distance related effects were apparent 170 ms (vertex positive potential, VPP) and 200 ms (N2) after stimulus onset for attractiveness comparisons. In Study 2, trustworthiness comparisons took effect already after 100 ms (N1) and likewise carried over to an event-related N2. Remarkably, we observed a similar temporal pattern for social (attractiveness, trustworthiness) and nonsocial (size) dimensions. These results speak in favor of an early encoding of comparative information and emphasize the primary role of comparison in social information processing. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  9. Ancient igneous intrusions and early expansion of the Moon revealed by GRAIL gravity gradiometry.

    Science.gov (United States)

    Andrews-Hanna, Jeffrey C; Asmar, Sami W; Head, James W; Kiefer, Walter S; Konopliv, Alexander S; Lemoine, Frank G; Matsuyama, Isamu; Mazarico, Erwan; McGovern, Patrick J; Melosh, H Jay; Neumann, Gregory A; Nimmo, Francis; Phillips, Roger J; Smith, David E; Solomon, Sean C; Taylor, G Jeffrey; Wieczorek, Mark A; Williams, James G; Zuber, Maria T

    2013-02-08

    The earliest history of the Moon is poorly preserved in the surface geologic record due to the high flux of impactors, but aspects of that history may be preserved in subsurface structures. Application of gravity gradiometry to observations by the Gravity Recovery and Interior Laboratory (GRAIL) mission results in the identification of a population of linear gravity anomalies with lengths of hundreds of kilometers. Inversion of the gravity anomalies indicates elongated positive-density anomalies that are interpreted to be ancient vertical tabular intrusions or dikes formed by magmatism in combination with extension of the lithosphere. Crosscutting relationships support a pre-Nectarian to Nectarian age, preceding the end of the heavy bombardment of the Moon. The distribution, orientation, and dimensions of the intrusions indicate a globally isotropic extensional stress state arising from an increase in the Moon's radius by 0.6 to 4.9 kilometers early in lunar history, consistent with predictions of thermal models.

  10. Infrasound reveals transition to oscillatory discharge regime during lava fountaining: Implication for early warning

    Science.gov (United States)

    Ulivieri, Giacomo; Ripepe, Maurizio; Marchetti, Emanuele

    2013-06-01

    present the analysis of ~4 million infrasonic signals which include 39 episodes of lava fountains recorded at 5.5 km from the active vents. We show that each eruptive episode is characterized by a distinctive trend in the amplitude, waveform, and frequency content of the acoustic signals, reflecting different explosive levels. Lava fountain starts with an ~93 min long violent phase of acoustic transients at ~1.25 Hz repeating every 2-5 s. Infrasound suddenly evolves into a persistent low-frequency quasi-monochromatic pressure oscillation at ~0.4 Hz. We interpret this shift as induced by the transition from the slug (discrete Strombolian) to churn flow (sustained lava fountain) regime that is reflecting an increase in the gas discharge rate. We calculate that infrasonic transition can occur at a gas superficial velocity of ≤76 m/s and it can be used to define infrasonic-based thresholds for an efficient early warning system.

  11. The behavior of larval zebrafish reveals stressor-mediated anorexia during early vertebrate development

    Science.gov (United States)

    De Marco, Rodrigo J.; Groneberg, Antonia H.; Yeh, Chen-Min; Treviño, Mario; Ryu, Soojin

    2014-01-01

    The relationship between stress and food consumption has been well documented in adults but less so in developing vertebrates. Here we demonstrate that an encounter with a stressor can suppress food consumption in larval zebrafish. Furthermore, we provide indication that food intake suppression cannot be accounted for by changes in locomotion, oxygen consumption and visual responses, as they remain unaffected after exposure to a potent stressor. We also show that feeding reoccurs when basal levels of cortisol (stress hormone in humans and teleosts) are re-established. The results present evidence that the onset of stress can switch off the drive for feeding very early in vertebrate development, and add a novel endpoint for analyses of metabolic and behavioral disorders in an organism suitable for high-throughput genetics and non-invasive brain imaging. PMID:25368561

  12. Ancient DNA reveals genetic connections between early Di-Qiang and Han Chinese.

    Science.gov (United States)

    Li, Jiawei; Zeng, Wen; Zhang, Ye; Ko, Albert Min-Shan; Li, Chunxiang; Zhu, Hong; Fu, Qiaomei; Zhou, Hui

    2017-12-04

    Ancient Di-Qiang people once resided in the Ganqing region of China, adjacent to the Central Plain area from where Han Chinese originated. While gene flow between the Di-Qiang and Han Chinese has been proposed, there is no evidence to support this view. Here we analyzed the human remains from an early Di-Qiang site (Mogou site dated ~4000 years old) and compared them to other ancient DNA across China, including an early Han-related site (Hengbei site dated ~3000 years old) to establish the underlying genetic relationship between the Di-Qiang and ancestors of Han Chinese. We found Mogou mtDNA haplogroups were highly diverse, comprising 14 haplogroups: A, B, C, D (D*, D4, D5), F, G, M7, M8, M10, M13, M25, N*, N9a, and Z. In contrast, Mogou males were all Y-DNA haplogroup O3a2/P201; specifically one male was further assigned to O3a2c1a/M117 using targeted unique regions on the non-recombining region of the Y-chromosome. We compared Mogou to 7 other ancient and 38 modern Chinese groups, in a total of 1793 individuals, and found that Mogou shared close genetic distances with Taojiazhai (a more recent Di-Qiang population), Hengbei, and Northern Han. We modeled their interactions using Approximate Bayesian Computation, and support was given to a potential admixture of ~13-18% between the Mogou and Northern Han around 3300-3800 years ago. Mogou harbors the earliest genetically identifiable Di-Qiang, ancestral to the Taojiazhai, and up to ~33% paternal and ~70% of its maternal haplogroups could be found in present-day Northern Han Chinese.

  13. Gene expression profiles reveal key genes for early diagnosis and treatment of adamantinomatous craniopharyngioma.

    Science.gov (United States)

    Yang, Jun; Hou, Ziming; Wang, Changjiang; Wang, Hao; Zhang, Hongbing

    2018-04-23

    Adamantinomatous craniopharyngioma (ACP) is an aggressive brain tumor that occurs predominantly in the pediatric population. Conventional diagnosis method and standard therapy cannot treat ACPs effectively. In this paper, we aimed to identify key genes for ACP early diagnosis and treatment. Datasets GSE94349 and GSE68015 were obtained from Gene Expression Omnibus database. Consensus clustering was applied to discover the gene clusters in the expression data of GSE94349 and functional enrichment analysis was performed on gene set in each cluster. The protein-protein interaction (PPI) network was built by the Search Tool for the Retrieval of Interacting Genes, and hubs were selected. Support vector machine (SVM) model was built based on the signature genes identified from enrichment analysis and PPI network. Dataset GSE94349 was used for training and testing, and GSE68015 was used for validation. Besides, RT-qPCR analysis was performed to analyze the expression of signature genes in ACP samples compared with normal controls. Seven gene clusters were discovered in the differentially expressed genes identified from GSE94349 dataset. Enrichment analysis of each cluster identified 25 pathways that highly associated with ACP. PPI network was built and 46 hubs were determined. Twenty-five pathway-related genes that overlapped with the hubs in PPI network were used as signatures to establish the SVM diagnosis model for ACP. The prediction accuracy of SVM model for training, testing, and validation data were 94, 85, and 74%, respectively. The expression of CDH1, CCL2, ITGA2, COL8A1, COL6A2, and COL6A3 were significantly upregulated in ACP tumor samples, while CAMK2A, RIMS1, NEFL, SYT1, and STX1A were significantly downregulated, which were consistent with the differentially expressed gene analysis. SVM model is a promising classification tool for screening and early diagnosis of ACP. The ACP-related pathways and signature genes will advance our knowledge of ACP pathogenesis

  14. Early Gene Expression in Wounded Human Keratinocytes Revealed by DNA Microarray Analysis

    Directory of Open Access Journals (Sweden)

    Pascal Barbry

    2006-04-01

    Full Text Available Wound healing involves several steps: spreading of the cells, migration and proliferation. We have profiled gene expression during the early events of wound healing in normal human keratinocytes with a home-made DNA microarray containing about 1000 relevant human probes. An original wounding machine was used, that allows the wounding of up to 40% of the surface of a confluent monolayer of cultured cells grown on a Petri dish (compared with 5% with a classical ‘scratch’ method. The two aims of the present study were: (a to validate a limited number of genes by comparing the expression levels obtained with this technique with those found in the literature; (b to combine the use of the wounding machine with DNA microarray analysis for large-scale detection of the molecular events triggered during the early stages of the wound-healing process. The time-courses of RNA expression observed at 0.5, 1.5, 3, 6 and 15 h after wounding for genes such as c-Fos, c-Jun, Egr1, the plasminogen activator PLAU (uPA and the signal transducer and transcription activator STAT3, were consistent with previously published data. This suggests that our methodologies are able to perform quantitative measurement of gene expression. Transcripts encoding two zinc finger proteins, ZFP36 and ZNF161, and the tumour necrosis factor α-induced protein TNFAIP3, were also overexpressed after wounding. The role of the p38 mitogen-activated protein kinase (p38MAPK in wound healing was shown after the inhibition of p38 by SB203580, but our results also suggest the existence of surrogate activating pathways.

  15. Integrative analyses reveal novel strategies in HPV11,-16 and-45 early infection

    DEFF Research Database (Denmark)

    Kaczkowski, Bogumil; Rossing, Maria; Andersen, Ditte

    2012-01-01

    of genes not previously implicated in HPV biology, such as the PSG family and ANKRD1, and of genes implicated in the biology of other viruses, e. g. MX1, IFI44 and DDX60. Carcinogenesis-related genes, e. g. ABL2, MGLL and CYR61, were upregulated by high-risk HPV16 and -45. The integrative analysis revealed...... the suppression of DNA repair by HPV11 and -16, and downregulation of cytoskeleton genes by all HPV types. Various signalling pathways were affected by the HPVs: IL-2 by HPV11; JAK-STAT by HPV16; and TGF-beta, NOTCH and tyrosine kinase signalling by HPV45. This study uncovered novel strategies employed by HPV...... to establish infection and promote uncontrolled growth....

  16. Early Miocene amber inclusions from Mexico reveal antiquity of mangrove-associated copepods.

    Science.gov (United States)

    Huys, Rony; Suárez-Morales, Eduardo; Serrano-Sánchez, María de Lourdes; Centeno-García, Elena; Vega, Francisco J

    2016-10-12

    Copepods are aquatic microcrustaceans and represent the most abundant metazoans on Earth, outnumbering insects and nematode worms. Their position of numerical world predominance can be attributed to three principal radiation events, i.e. their major habitat shift into the marine plankton, the colonization of freshwater and semiterrestrial environments, and the evolution of parasitism. Their variety of life strategies has generated an incredible morphological plasticity and disparity in body form and shape that are arguably unrivalled among the Crustacea. Although their chitinous exoskeleton is largely resistant to chemical degradation copepods are exceedingly scarce in the geological record with limited body fossil evidence being available for only three of the eight currently recognized orders. The preservation of aquatic arthropods in amber is unusual but offers a unique insight into ancient subtropical and tropical ecosystems. Here we report the first discovery of amber-preserved harpacticoid copepods, represented by ten putative species belonging to five families, based on Early Miocene (22.8 million years ago) samples from Chiapas, southeast Mexico. Their close resemblance to Recent mangrove-associated copepods highlights the antiquity of the specialized harpacticoid fauna living in this habitat. With the taxa reported herein, the Mexican amber holds the greatest diversity of fossil copepods worldwide.

  17. Adaptive genomic evolution of opsins reveals that early mammals flourished in nocturnal environments.

    Science.gov (United States)

    Borges, Rui; Johnson, Warren E; O'Brien, Stephen J; Gomes, Cidália; Heesy, Christopher P; Antunes, Agostinho

    2018-02-05

    Based on evolutionary patterns of the vertebrate eye, Walls (1942) hypothesized that early placental mammals evolved primarily in nocturnal habitats. However, not only Eutheria, but all mammals show photic characteristics (i.e. dichromatic vision, rod-dominated retina) suggestive of a scotopic eye design. Here, we used integrative comparative genomic and phylogenetic methodologies employing the photoreceptive opsin gene family in 154 mammals to test the likelihood of a nocturnal period in the emergence of all mammals. We showed that mammals possess genomic patterns concordant with a nocturnal ancestry. The loss of the RH2, VA, PARA, PARIE and OPN4x opsins in all mammals led us to advance a probable and most-parsimonious hypothesis of a global nocturnal bottleneck that explains the loss of these genes in the emerging lineage (> > 215.5 million years ago). In addition, ancestral character reconstruction analyses provided strong evidence that ancestral mammals possessed a nocturnal lifestyle, ultra-violet-sensitive vision, low visual acuity and low orbit convergence (i.e. panoramic vision). Overall, this study provides insight into the evolutionary history of the mammalian eye while discussing important ecological aspects of the photic paleo-environments ancestral mammals have occupied.

  18. Comparative Genomics of Early-Diverging Brucella Strains Reveals a Novel Lipopolysaccharide Biosynthesis Pathway

    Science.gov (United States)

    Wattam, Alice R.; Inzana, Thomas J.; Williams, Kelly P.; Mane, Shrinivasrao P.; Shukla, Maulik; Almeida, Nalvo F.; Dickerman, Allan W.; Mason, Steven; Moriyón, Ignacio; O’Callaghan, David; Whatmore, Adrian M.; Sobral, Bruno W.; Tiller, Rebekah V.; Hoffmaster, Alex R.; Frace, Michael A.; De Castro, Cristina; Molinaro, Antonio; Boyle, Stephen M.; De, Barun K.; Setubal, João C.

    2012-01-01

    ABSTRACT Brucella species are Gram-negative bacteria that infect mammals. Recently, two unusual strains (Brucella inopinata BO1T and B. inopinata-like BO2) have been isolated from human patients, and their similarity to some atypical brucellae isolated from Australian native rodent species was noted. Here we present a phylogenomic analysis of the draft genome sequences of BO1T and BO2 and of the Australian rodent strains 83-13 and NF2653 that shows that they form two groups well separated from the other sequenced Brucella spp. Several important differences were noted. Both BO1T and BO2 did not agglutinate significantly when live or inactivated cells were exposed to monospecific A and M antisera against O-side chain sugars composed of N-formyl-perosamine. While BO1T maintained the genes required to synthesize a typical Brucella O-antigen, BO2 lacked many of these genes but still produced a smooth LPS (lipopolysaccharide). Most missing genes were found in the wbk region involved in O-antigen synthesis in classic smooth Brucella spp. In their place, BO2 carries four genes that other bacteria use for making a rhamnose-based O-antigen. Electrophoretic, immunoblot, and chemical analyses showed that BO2 carries an antigenically different O-antigen made of repeating hexose-rich oligosaccharide units that made the LPS water-soluble, which contrasts with the homopolymeric O-antigen of other smooth brucellae that have a phenol-soluble LPS. The results demonstrate the existence of a group of early-diverging brucellae with traits that depart significantly from those of the Brucella species described thus far. PMID:22930339

  19. Mathematical Modeling of Early Cellular Innate and Adaptive Immune Responses to Ischemia/Reperfusion Injury and Solid Organ Allotransplantation

    Science.gov (United States)

    Day, Judy D.; Metes, Diana M.; Vodovotz, Yoram

    2015-01-01

    A mathematical model of the early inflammatory response in transplantation is formulated with ordinary differential equations. We first consider the inflammatory events associated only with the initial surgical procedure and the subsequent ischemia/reperfusion (I/R) events that cause tissue damage to the host as well as the donor graft. These events release damage-associated molecular pattern molecules (DAMPs), thereby initiating an acute inflammatory response. In simulations of this model, resolution of inflammation depends on the severity of the tissue damage caused by these events and the patient’s (co)-morbidities. We augment a portion of a previously published mathematical model of acute inflammation with the inflammatory effects of T cells in the absence of antigenic allograft mismatch (but with DAMP release proportional to the degree of graft damage prior to transplant). Finally, we include the antigenic mismatch of the graft, which leads to the stimulation of potent memory T cell responses, leading to further DAMP release from the graft and concomitant increase in allograft damage. Regulatory mechanisms are also included at the final stage. Our simulations suggest that surgical injury and I/R-induced graft damage can be well-tolerated by the recipient when each is present alone, but that their combination (along with antigenic mismatch) may lead to acute rejection, as seen clinically in a subset of patients. An emergent phenomenon from our simulations is that low-level DAMP release can tolerize the recipient to a mismatched allograft, whereas different restimulation regimens resulted in an exaggerated rejection response, in agreement with published studies. We suggest that mechanistic mathematical models might serve as an adjunct for patient- or sub-group-specific predictions, simulated clinical studies, and rational design of immunosuppression. PMID:26441988

  20. Liquefaction along Late Pleistocene to early Holocene Faults as Revealed by Lidar in Northwest Tasmania, Australia

    Science.gov (United States)

    Webb, J.; Gardner, T.

    2016-12-01

    In northwest Tasmania well-preserved mid-Holocene beach ridges with maximum radiocarbon ages of 5.25 ka occur along the coast; inland are a parallel set of lower relief beach ridges of probable MIS 5e age. The latter are cut by northeast-striking faults clearly visible on LIDAR images, with a maximum vertical displacement (evident as difference in topographic elevation) of 3 m. Also distinct on the LIDAR images are large sand boils along the fault lines; they are up to 5 m in diameter and 2-3 m high and mostly occur on the hanging wall close to the fault traces. Without LIDAR it would have been almost impossible to distinguish either the fault scarps or the sand boils. Excavations through the sand boils show that they are massive, with no internal structure, suggesting that they formed in a single event. They are composed of well-sorted, very fine white sand, identical to the sand in the underlying beach ridges. The sand boils overlie a peaty paleosol; this formed in the tea-tree swamp that formerly covered the area, and has been offset along the faults. Radiocarbon dating of the buried organic-rich paleosol gave ages of 14.8-7.2 ka, suggesting that the faulting is latest Pleistocene to early Holocene in age; it occurred prior to deposition of the mid-Holocene beach ridges, which are not offset. The beach ridge sediments are up to 7 m thick and contain an iron-cemented hard pan 1-3 m below the surface. The water table is very shallow and close to the ground surface, so the sands of the beach ridges are mostly saturated. During faulting these sands experienced extensive liquefaction. The resulting sand boils rose to a substantial height of 2-3 m, probably possibly reflecting the elevation of the potentiometric surface within the confined part of the beach ridge sediments below the iron-cemented hard pan. Motion on the faults was predominantly dip slip (shown by an absence of horizontal offset) and probably reverse, which is consistent with the present-day northwest

  1. A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides.

    Science.gov (United States)

    Voelz, Kerstin; Gratacap, Remi L; Wheeler, Robert T

    2015-11-01

    Mucormycosis is an emerging fungal infection that is clinically difficult to manage, with increasing incidence and extremely high mortality rates. Individuals with diabetes, suppressed immunity or traumatic injury are at increased risk of developing disease. These individuals often present with defects in phagocytic effector cell function. Research using mammalian models and phagocytic effector cell lines has attempted to decipher the importance of the innate immune system in host defence against mucormycosis. However, these model systems have not been satisfactory for direct analysis of the interaction between innate immune effector cells and infectious sporangiospores in vivo. Here, we report the first real-time in vivo analysis of the early innate immune response to mucormycete infection using a whole-animal zebrafish larval model system. We identified differential host susceptibility, dependent on the site of infection (hindbrain ventricle and swim bladder), as well as differential functions of the two major phagocyte effector cell types in response to viable and non-viable spores. Larval susceptibility to mucormycete spore infection was increased upon immunosuppressant treatment. We showed for the first time that macrophages and neutrophils were readily recruited in vivo to the site of infection in an intact host and that spore phagocytosis can be observed in real-time in vivo. While exploring innate immune effector recruitment dynamics, we discovered the formation of phagocyte clusters in response to fungal spores that potentially play a role in fungal spore dissemination. Spores failed to activate pro-inflammatory gene expression by 6 h post-infection in both infection models. After 24 h, induction of a pro-inflammatory response was observed only in hindbrain ventricle infections. Only a weak pro-inflammatory response was initiated after spore injection into the swim bladder during the same time frame. In the future, the zebrafish larva as a live whole

  2. Correlation of transcriptomic responses and metal bioaccumulation in Mytilus edulis L. reveals early indicators of stress

    Energy Technology Data Exchange (ETDEWEB)

    Poynton, Helen C., E-mail: helen.poynton@umb.edu; Robinson, William E.; Blalock, Bonnie J.; Hannigan, Robyn E.

    2014-10-15

    , three transcripts directly involved in the unfolded protein response (UPR) were induced in the metal treatments at 2 weeks and were further up-regulated at 4 weeks. Overall, correlation of tissue concentrations and gene expression responses indicates that as mussels accumulate higher concentrations of metals, initial stress responses are mobilized to protect tissues. However, given the role of UPR in apoptosis, it serves as an early indicator of stress, which once overwhelmed will result in adverse physiological effects.

  3. Methods of early revealing, prognosis of further course and complications of pollinosis

    Directory of Open Access Journals (Sweden)

    Chukhrienko N.D.

    2013-10-01

    Full Text Available Under our observation there were 59 patients with pollinosis – 39 females and 20 males at the age from 18 to 68 years. All patients were in the phase of disease exacerbation. General clinical symptoms were: rhinitis, conjunctivitis and bronchial spasm. The results showed that first clinical manifestations appear in persons of young age. Half of the patients had aggravated allergologic anamnesis. Taking into account that pollinosis is a typical representative of diseases having mechanism of immunoglobulin E (IgE-dependent allergic reactions of the first type, the authors have studied in detail level of IgE and its link with other factors. Practically in all patients with pollinosis level of total IgE exceeded the norm. As a result of studies performed, it was established that high IgE level, presence of phagocytosis defect and prolong duration of illness are the criteria which affect disease progress, aggravation of patients’ state, less efficacy of treatment. Due to the fact that development of bronchial obstruction and transformation of pollinosis into bronchial asthma is the most topical issue nowadays, the authors studied its link with other factors and findings. It was established that risk of pollinosis transformation into pollen bronchial asthma increases in the presence of high level of total IgE, aggravation of allergologic anamnesis, decrease of forced expiration volume (FEV, significant duration of disease course. In the course of investigation it was revealed that the highest efficacy of treatment is noted in patients receiving allergen-specific therapy; this confirms data of world scientific literature. The best treatment results are observed in pollinosis patients, with aggravated family history not in parents but in grandparents.

  4. Molecular and cellular effects of chemicals disrupting steroidogenesis during early ovarian development of brown trout (Salmo trutta fario).

    Science.gov (United States)

    a Marca Pereira, M L; Eppler, E; Thorpe, K L; Wheeler, J R; Burkhardt-Holm, P

    2014-02-01

    A range of chemicals found in the aquatic environment have the potential to influence endocrine function and affect sexual development by mimicking or antagonizing the effects of hormones, or by altering the synthesis and metabolism of hormones. The aim of this study was to evaluate whether the effects of chemicals interfering with sex hormone synthesis may affect the regulation of early ovarian development via the modulation of sex steroid and insulin-like growth factor (IGF) systems. To this end, ex vivo ovary cultures of juvenile brown trout (Salmo trutta fario) were exposed for 2 days to either 1,4,6-androstatriene-3,17-dione (ATD, a specific aromatase inhibitor), prochloraz (an imidazole fungicide), or tributyltin (TBT, a persistent organic pollutant). Further, juvenile female brown trout were exposed in vivo for 2 days to prochloraz or TBT. The ex vivo and in vivo ovarian gene expression of the aromatase (CYP19), responsible for estrogen production, and of IGF1 and 2 were compared. Moreover, 17β-estradiol (E2) and testosterone (T) production from ex vivo ovary cultures was assessed. Ex vivo exposure to ATD inhibited ovarian E2 synthesis, while T levels accumulated. However, ATD did not affect ex vivo expression of cyp19, igf1, or igf2. Ex vivo exposure to prochloraz inhibited ovarian E2 production, but did not affect T levels. Further prochloraz up-regulated igf1 expression in both ex vivo and in vivo exposures. TBT exposure did not modify ex vivo synthesis of either E2 or T. However, in vivo exposure to TBT down-regulated igf2 expression. The results indicate that ovarian inhibition of E2 production in juvenile brown trout might not directly affect cyp19 and igf gene expression. Thus, we suggest that the test chemicals may interfere with both sex steroid and IGF systems in an independent manner, and based on published literature, potentially lead to endocrine dysfunction and altered sexual development. Copyright © 2011 Wiley Periodicals, Inc., A Wiley

  5. Steroidogenesis and early response gene expression in MA-10 Leydig tumor cells following heterologous receptor down-regulation and cellular desensitization

    Directory of Open Access Journals (Sweden)

    Tsuey-Ming Chen

    2016-03-01

    Full Text Available The Leydig tumor cell line, MA-10, expresses the luteinizing hormone receptor, a G protein-coupled receptor that, when activated with luteinizing hormone or chorionic gonadotropin (CG, stimulates cAMP production and subsequent steroidogenesis, notably progesterone. These cells also respond to epidermal growth factor (EGF and phorbol esters with increased steroid biosynthesis. In order to probe the intracellular pathways along with heterologous receptor down-regulation and cellular desensitization, cells were preincubated with EGF or phorbol esters and then challenged with CG, EGF, dibutryl-cyclic AMP, and a phorbol ester. Relative receptor numbers, steroid biosynthesis, and expression of the early response genes, JUNB and c-FOS, were measured. It was found that in all cases but one receptor down-regulation and decreased progesterone production were closely coupled under the conditions used; the exception involved preincubation of the cells with EGF followed by addition of CG where the CG-mediated stimulation of steroidogenesis was considerably lower than the level of receptor down-regulation. In a number of instances JUNB and c-FOS expression paralleled the decreases in receptor number and progesterone production, while in some cases these early response genes were affected little if at all by the changes in receptor number. This finding may indicate that even low levels of activated signaling kinases, e.g. protein kinase A, protein kinase C, or receptor tyrosine kinase, may suffice to yield good expression of JUNB and c-FOS, or it may suggest alternative pathways for regulating expression of these two early response genes.

  6. Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes.

    Directory of Open Access Journals (Sweden)

    Mohammad F Saeed

    2010-09-01

    Full Text Available Zaire ebolavirus (ZEBOV, a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new

  7. New features on the environmental regulation of metabolism revealed by modeling the cellular proteomic adaptations induced by light, carbon and inorganic nitrogen in Chlamydomonas reinhardtii

    Directory of Open Access Journals (Sweden)

    Stéphanie Gérin

    2016-08-01

    Full Text Available Microalgae are currently emerging to be very promising organisms for the production of biofuels and high-added value compounds. Understanding the influence of environmental alterations on their metabolism is a crucial issue. Light, carbon and nitrogen availability have been reported to induce important metabolic adaptations. So far, the influence of these variables has essentially been studied while varying only one or two environmental factors at the same time. The goal of the present work was to model the cellular proteomic adaptations of the green microalga Chlamydomonas reinhardtii upon the simultaneous changes of light intensity, carbon concentrations (CO2 and acetate and inorganic nitrogen concentrations (nitrate and ammonium in the culture medium. Statistical design of experiments (DOE enabled to define 32 culture conditions to be tested experimentally. Relative protein abundance was quantified by two dimensional differential in-gel electrophoresis (2D-DIGE. Additional assays for respiration, photosynthesis, and lipid and pigment concentrations were also carried out. A hierarchical clustering survey enabled to partition biological variables (proteins + assays into eight co-regulated clusters. In most cases, the biological variables partitioned in the same cluster had already been reported to participate to common biological functions (acetate assimilation, bioenergetic processes, light harvesting, Calvin cycle and protein metabolism. The environmental regulation within each cluster was further characterized by a series of multivariate methods including principal component analysis and multiple linear regressions. This metadata analysis enabled to highlight the existence of a clear regulatory pattern for every cluster and to mathematically simulate the effects of light, carbon and nitrogen. The influence of these environmental variables on cellular metabolism is described in details and thoroughly discussed. This work provides an overview

  8. Epigenetics and Cellular Metabolism

    OpenAIRE

    Wenyi Xu; Fengzhong Wang; Zhongsheng Yu; Fengjiao Xin

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the proce...

  9. Cellular gravity

    NARCIS (Netherlands)

    F.C. Gruau; J.T. Tromp (John)

    1999-01-01

    textabstractWe consider the problem of establishing gravity in cellular automata. In particular, when cellular automata states can be partitioned into empty, particle, and wall types, with the latter enclosing rectangular areas, we desire rules that will make the particles fall down and pile up on

  10. Multimodal MR-imaging reveals large-scale structural and functional connectivity changes in profound early blindness

    Science.gov (United States)

    Bauer, Corinna M.; Hirsch, Gabriella V.; Zajac, Lauren; Koo, Bang-Bon; Collignon, Olivier

    2017-01-01

    In the setting of profound ocular blindness, numerous lines of evidence demonstrate the existence of dramatic anatomical and functional changes within the brain. However, previous studies based on a variety of distinct measures have often provided inconsistent findings. To help reconcile this issue, we used a multimodal magnetic resonance (MR)-based imaging approach to provide complementary structural and functional information regarding this neuroplastic reorganization. This included gray matter structural morphometry, high angular resolution diffusion imaging (HARDI) of white matter connectivity and integrity, and resting state functional connectivity MRI (rsfcMRI) analysis. When comparing the brains of early blind individuals to sighted controls, we found evidence of co-occurring decreases in cortical volume and cortical thickness within visual processing areas of the occipital and temporal cortices respectively. Increases in cortical volume in the early blind were evident within regions of parietal cortex. Investigating white matter connections using HARDI revealed patterns of increased and decreased connectivity when comparing both groups. In the blind, increased white matter connectivity (indexed by increased fiber number) was predominantly left-lateralized, including between frontal and temporal areas implicated with language processing. Decreases in structural connectivity were evident involving frontal and somatosensory regions as well as between occipital and cingulate cortices. Differences in white matter integrity (as indexed by quantitative anisotropy, or QA) were also in general agreement with observed pattern changes in the number of white matter fibers. Analysis of resting state sequences showed evidence of both increased and decreased functional connectivity in the blind compared to sighted controls. Specifically, increased connectivity was evident between temporal and inferior frontal areas. Decreases in functional connectivity were observed

  11. A zebrafish model of congenital disorders of glycosylation with phosphomannose isomerase deficiency reveals an early opportunity for corrective mannose supplementation

    Directory of Open Access Journals (Sweden)

    Jaime Chu

    2013-01-01

    Individuals with congenital disorders of glycosylation (CDG have recessive mutations in genes required for protein N-glycosylation, resulting in multi-systemic disease. Despite the well-characterized biochemical consequences in these individuals, the underlying cellular defects that contribute to CDG are not well understood. Synthesis of the lipid-linked oligosaccharide (LLO, which serves as the sugar donor for the N-glycosylation of secretory proteins, requires conversion of fructose-6-phosphate to mannose-6-phosphate via the phosphomannose isomerase (MPI enzyme. Individuals who are deficient in MPI present with bleeding, diarrhea, edema, gastrointestinal bleeding and liver fibrosis. MPI-CDG patients can be treated with oral mannose supplements, which is converted to mannose-6-phosphate through a minor complementary metabolic pathway, restoring protein glycosylation and ameliorating most symptoms, although liver disease continues to progress. Because Mpi deletion in mice causes early embryonic lethality and thus is difficult to study, we used zebrafish to establish a model of MPI-CDG. We used a morpholino to block mpi mRNA translation and established a concentration that consistently yielded 13% residual Mpi enzyme activity at 4 days post-fertilization (dpf, which is within the range of MPI activity detected in fibroblasts from MPI-CDG patients. Fluorophore-assisted carbohydrate electrophoresis detected decreased LLO and N-glycans in mpi morphants. These deficiencies resulted in 50% embryonic lethality by 4 dpf. Multi-systemic abnormalities, including small eyes, dysmorphic jaws, pericardial edema, a small liver and curled tails, occurred in 82% of the surviving larvae. Importantly, these phenotypes could be rescued with mannose supplementation. Thus, parallel processes in fish and humans contribute to the phenotypes caused by Mpi depletion. Interestingly, mannose was only effective if provided prior to 24 hpf. These data provide insight into treatment efficacy

  12. Overexpression of FurA in Anabaena sp. PCC 7120 reveals new targets for this regulator involved in photosynthesis, iron uptake and cellular morphology.

    Science.gov (United States)

    González, Andrés; Bes, M Teresa; Barja, François; Peleato, M Luisa; Fillat, María F

    2010-11-01

    Previous genomic analyses of the filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 have identified three ferric uptake regulator (Fur) homologs with low sequence identities and probably different functions in the cell. FurA is a constitutive protein that shares the highest homology with Fur from heterotrophic bacteria and appears to be essential for in vitro growth. In this study, we have analysed the effects of FurA overexpression on the Anabaena sp. phenotype and investigated which of the observed alterations were directly operated by FurA. Overexpression of the regulator led to changes in cellular morphology, resulting in shorter filaments with rounded cells of different sizes. The furA-overexpressing strain showed a slower photoautotrophic growth and a marked decrease in the oxygen evolution rate. Overexpression of the regulator also decreased both catalase and superoxide dismutase activities, but did not lead to an increase in the levels of intracellular reactive oxygen species. By combining phenotypic studies, reverse transcription-PCR analyses and electrophoretic mobility shift assays, we identified three novel direct targets of FurA, including genes encoding a siderophore outer membrane transporter (schT), bacterial actins (mreBCD) and the PSII reaction center protein D1 (psbA). The affinity of FurA for these novel targets was markedly affected by the absence of divalent metal ions, confirming previous evidence of a critical role for the metal co-repressor in the function of the regulator in vivo. The results unravel new cellular processes modulated by FurA, supporting its role as a global transcriptional regulator in Anabaena sp. PCC 7120.

  13. Structural analysis and mutant growth properties reveal distinctive enzymatic and cellular roles for the three major L-alanine transaminases of Escherichia coli.

    Science.gov (United States)

    Peña-Soler, Esther; Fernandez, Francisco J; López-Estepa, Miguel; Garces, Fernando; Richardson, Andrew J; Quintana, Juan F; Rudd, Kenneth E; Coll, Miquel; Vega, M Cristina

    2014-01-01

    In order to maintain proper cellular function, the metabolism of the bacterial microbiota presents several mechanisms oriented to keep a correctly balanced amino acid pool. Central components of these mechanisms are enzymes with alanine transaminase activity, pyridoxal 5'-phosphate-dependent enzymes that interconvert alanine and pyruvate, thereby allowing the precise control of alanine and glutamate concentrations, two of the most abundant amino acids in the cellular amino acid pool. Here we report the 2.11-Å crystal structure of full-length AlaA from the model organism Escherichia coli, a major bacterial alanine aminotransferase, and compare its overall structure and active site composition with detailed atomic models of two other bacterial enzymes capable of catalyzing this reaction in vivo, AlaC and valine-pyruvate aminotransferase (AvtA). Apart from a narrow entry channel to the active site, a feature of this new crystal structure is the role of an active site loop that closes in upon binding of substrate-mimicking molecules, and which has only been previously reported in a plant enzyme. Comparison of the available structures indicates that beyond superficial differences, alanine aminotransferases of diverse phylogenetic origins share a universal reaction mechanism that depends on an array of highly conserved amino acid residues and is similarly regulated by various unrelated motifs. Despite this unifying mechanism and regulation, growth competition experiments demonstrate that AlaA, AlaC and AvtA are not freely exchangeable in vivo, suggesting that their functional repertoire is not completely redundant thus providing an explanation for their independent evolutionary conservation.

  14. Comparative proteomic analysis of Xanthomonas citri ssp. citri periplasmic proteins reveals changes in cellular envelope metabolism during in vitro pathogenicity induction.

    Science.gov (United States)

    Artier, Juliana; da Silva Zandonadi, Flávia; de Souza Carvalho, Flávia Maria; Pauletti, Bianca Alves; Leme, Adriana Franco Paes; Carnielli, Carolina Moretto; Selistre-de-Araujo, Heloisa Sobreiro; Bertolini, Maria Célia; Ferro, Jesus Aparecido; Belasque Júnior, José; de Oliveira, Julio Cezar Franco; Novo-Mansur, Maria Teresa Marques

    2018-01-01

    Citrus canker is a plant disease caused by Gram-negative bacteria from the genus Xanthomonas. The most virulent species is Xanthomonas citri ssp. citri (XAC), which attacks a wide range of citrus hosts. Differential proteomic analysis of the periplasm-enriched fraction was performed for XAC cells grown in pathogenicity-inducing (XAM-M) and pathogenicity-non-inducing (nutrient broth) media using two-dimensional electrophoresis combined with liquid chromatography-tandem mass spectrometry. Amongst the 40 proteins identified, transglycosylase was detected in a highly abundant spot in XAC cells grown under inducing condition. Additional up-regulated proteins related to cellular envelope metabolism included glucose-1-phosphate thymidylyltransferase, dTDP-4-dehydrorhamnose-3,5-epimerase and peptidyl-prolyl cis-trans-isomerase. Phosphoglucomutase and superoxide dismutase proteins, known to be involved in pathogenicity in other Xanthomonas species or organisms, were also detected. Western blot and quantitative real-time polymerase chain reaction analyses for transglycosylase and superoxide dismutase confirmed that these proteins were up-regulated under inducing condition, consistent with the proteomic results. Multiple spots for the 60-kDa chaperonin and glyceraldehyde-3-phosphate dehydrogenase were identified, suggesting the presence of post-translational modifications. We propose that substantial alterations in cellular envelope metabolism occur during the XAC infectious process, which are related to several aspects, from defence against reactive oxygen species to exopolysaccharide synthesis. Our results provide new candidates for virulence-related proteins, whose abundance correlates with the induction of pathogenicity and virulence genes, such as hrpD6, hrpG, hrpB7, hpa1 and hrpX. The results present new potential targets against XAC to be investigated in further functional studies. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  15. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis.

    Science.gov (United States)

    Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

    2014-09-01

    Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients. © FASEB.

  16. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

    Science.gov (United States)

    Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

    2014-01-01

    Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

  17. The use of global transcriptional analysis to reveal the biological and cellular events involved in distinct development phases of Trichophyton rubrum conidial germination

    Directory of Open Access Journals (Sweden)

    Ding Guohui

    2007-04-01

    Full Text Available Abstract Background Conidia are considered to be the primary cause of infections by Trichophyton rubrum. Results We have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the Saccharomyces Genome Database (SGD. A number of homologues of Saccharomyces cerevisiae genes related to signalling pathways and some important cellular processes were found to be involved in T. rubrum germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions. Conclusion Our results may provide insights into molecular mechanisms of conidial germination at the cell level, and may enhance our understanding of regulation of gene expression related to the morphological construction of T. rubrum.

  18. Proteomic investigation of Vibrio alginolyticus challenged Caenorhabditis elegans revealed regulation of cellular homeostasis proteins and their role in supporting innate immune system.

    Science.gov (United States)

    Durai, Sellegounder; Singh, Nirpendra; Kundu, Suman; Balamurugan, Krishnaswamy

    2014-08-01

    Caenorhabditis elegans has been the preferred model system for many investigators to study pathogenesis. In the present investigation, regulation of C. elegans proteome was explored against V. alginolyticus infection using quantitative proteomics approach. Proteins were separated using 2D-DIGE and the differentially regulated proteins were identified using PMF and MALDI TOF/TOF analysis. The results thus obtained were validated using Western blotting for candidate proteins. The corresponding transcriptional regulation was quantified subsequently using real-time PCR. Interaction network for candidate proteins was predicted using search tool for the retrieval of interacting genes/proteins (STRING) and functional validation was performed using respective mutant strains. Out of the 25 proteins identified, 21 proteins appeared to be upregulated while four were downregulated. Upregulated proteins included those involved in stress-response (PDI-2, HSP-6), immune-response (protein kinase -18, GST-8) and energy-production (ATP-2) while proteins involved in structural maintenance (IFB-2) and lipid metabolism (SODH-1) were downregulated. The roles of these players in the host system during Vibrio infection was analyzed in vivo using wild type and mutant C. elegans. Survival assays using mutants lacking pdi-2, ire-1, and xbp-1 displayed enhanced susceptibility to V. alginolyticus. Cellular stress generated by V. alginolyticus was determined using ROS assay. This is the first report of proteome changes in C. elegans against V. alginolyticus challenge and highlights the significance of unfolded protein response (UPR) pathway during bacterial infection. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Cellular Mechanism Underlying Hypothermia-Induced VT/VF in the Setting of Early Repolarization and the Protective Effect of Quinidine, Cilostazol and Milrinone

    Science.gov (United States)

    Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V.; Antzelevitch, Charles

    2014-01-01

    Background Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome (ERS) and examines the effectiveness of quinidine, cilostazol and milrinone to prevent hypothermia-induced arrhythmias. Method and Results Transmembrane action potentials (AP) were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left-ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3–10 µM) and verapamil (1µM) was used to pharmacologically model the genetic mutations responsible for ERS. Acetylcholine (3µM) was used to simulate increased parasympathetic tone, which is known to promote ER. In control, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J wave area on the ECG and accentuated epicardial AP notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial AP notch, leading to loss of the AP dome at some sites but not others, thus creating the substrate for development of phase-2-reentry and VT/VF. Addition of the Ito antagonist quinidine (5 µM) or the phosphodiesterase III inhibitors cilostazol (10 µM) or milrinone (5 µM), diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Conclusions Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase-2-reentry. Quinidine, cilostazol and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities. PMID:24429494

  20. Cellular mechanism underlying hypothermia-induced ventricular tachycardia/ventricular fibrillation in the setting of early repolarization and the protective effect of quinidine, cilostazol, and milrinone.

    Science.gov (United States)

    Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V; Antzelevitch, Charles

    2014-02-01

    Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome and examines the effectiveness of quinidine, cilostazol, and milrinone to prevent hypothermia-induced arrhythmias. Transmembrane action potentials were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3-10 μmol/L) and verapamil (1 μmol/L) was used to pharmacologically model the genetic mutations responsible for ER syndrome. Acetylcholine (3 μmol/L) was used to simulate increased parasympathetic tone, which is known to promote ER. In controls, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J-wave area on the ECG and accentuated epicardial action potential notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial action potential notch, leading to loss of the action potential dome at some sites but not others, thus creating the substrate for development of phase 2 reentry and VT/VF. Addition of the transient outward current antagonist quinidine (5 μmol/L) or the phosphodiesterase III inhibitors cilostazol (10 μmol/L) or milrinone (5 μmol/L) diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase 2 reentry. Quinidine, cilostazol, and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities.

  1. Sulfur Geochemistry of a Lacustrine Record from Taiwan Reveals Enhanced Marine Aerosol Input during the Early Holocene.

    Science.gov (United States)

    Ding, Xiaodong; Li, Dawei; Zheng, Liwei; Bao, Hongyan; Chen, Huei-Fen; Kao, Shuh-Ji

    2016-12-12

    Lacustrine record of marine aerosol input has rarely been documented. Here, we present the sulfur geochemistry during the last deglaciation and early Holocene of a sediment core retrieved from the Dongyuan Lake in southern Taiwan. An unusually high sulfur peak accompanying pyrite presence is observed at 10.5 ka BP. Such high sulfur content in lacustrine record is unusual. The δ 34 S of sulfur varied from +9.5 to + 17.1‰ with two significant positive shifts at 10.5 and 9.4 ka BP. The sources of sulfur and potential processes involving the sulfur isotope variation including bacterial sulfate reduction, volcanic emissions, in-catchment sulfide oxidation and marine aerosol input are discussed. Enhanced marine aerosol input is the most likely explanation for such sulfur peaks and δ 34 S shifts. The positive δ 34 S shifts appeared concurrently with the maximum landslide events over Taiwan resulted from enhanced typhoon activities. The synchronicity among records suggests that increased typhoon activities promoted sea spray, and consequently enhanced the marine aerosol input with 34 S-enriched sulfate. Our sulfur geochemistry data revealed sea spray history and marine influence onto terrestrial environment at coastal regions. Wider coverage of spatial-temporal lacustrine sulfur geochemistry record is needed to validate the applicability of sulfur proxy in paleoenvironmental research.

  2. High sequence variations in the region containing genes encoding a cellular morphogenesis protein and the repressor of sexual development help to reveal origins of Aspergillus oryzae.

    Science.gov (United States)

    Chang, Perng-Kuang; Scharfenstein, Leslie L; Solorzano, Cesar D; Abbas, Hamed K; Hua, Sui-Sheng T; Jones, Walker A; Zablotowicz, Robert M

    2015-05-04

    Aspergillus oryzae and Aspergillus flavus are closely related fungal species. The A. flavus morphotype that produces numerous small sclerotia (S strain) and aflatoxin has a unique 1.5 kb deletion in the norB-cypA region of the aflatoxin gene cluster (i.e. the S genotype). Phylogenetic studies have indicated that an isolate of the nonaflatoxigenic A. flavus with the S genotype is the ancestor of A. oryzae. Genome sequence comparison between A. flavus NRRL3357, which produces large sclerotia (L strain), and S-strain A. flavus 70S identified a region (samA-rosA) that was highly variable in the two morphotypes. A third type of samA-rosA region was found in A. oryzae RIB40. The three samA-rosA types were later revealed to be commonly present in A. flavus L-strain populations. Of the 182 L-strain A. flavus field isolates examined, 46%, 15% and 39% had the samA-rosA type of NRRL3357, 70S and RIB40, respectively. The three types also were found in 18 S-strain A. flavus isolates with different proportions. For A. oryzae, however, the majority (80%) of the 16 strains examined had the RIB40 type and none had the NRRL3357 type. The results suggested that A. oryzae strains in the current culture collections were mostly derived from the samA-rosA/RIB40 lineage of the nonaflatoxigenic A. flavus with the S genotype. Published by Elsevier B.V.

  3. δ- and γ-tocopherols inhibit phIP/DSS-induced colon carcinogenesis by protection against early cellular and DNA damages.

    Science.gov (United States)

    Chen, Jayson X; Liu, Anna; Lee, Mao-Jung; Wang, Hong; Yu, Siyuan; Chi, Eric; Reuhl, Kenneth; Suh, Nanjoo; Yang, Chung S

    2017-01-01

    Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T), and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α-T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ-T, γ-T, and α-T (0.2% in diet) in a novel colon cancer model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)-induced colitis in CYP1A-humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 wk. Dietary supplementation with δ-T and γ-T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory mediators (i.e., NF-κB p65 and p-STAT3) in tumors and adjacent tissues. By administering δ-T at different time periods, we obtained results suggesting that the inhibitory effect of δ-T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α-T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ-T and γ-T in a physiologically relevant model of human colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Dynamic contrast enhanced MRI detects early response to adoptive NK cellular immunotherapy targeting the NG2 proteoglycan in a rat model of glioblastoma.

    Directory of Open Access Journals (Sweden)

    Cecilie Brekke Rygh

    Full Text Available There are currently no established radiological parameters that predict response to immunotherapy. We hypothesised that multiparametric, longitudinal magnetic resonance imaging (MRI of physiological parameters and pharmacokinetic models might detect early biological responses to immunotherapy for glioblastoma targeting NG2/CSPG4 with mAb9.2.27 combined with natural killer (NK cells. Contrast enhanced conventional T1-weighted MRI at 7±1 and 17±2 days post-treatment failed to detect differences in tumour size between the treatment groups, whereas, follow-up scans at 3 months demonstrated diminished signal intensity and tumour volume in the surviving NK+mAb9.2.27 treated animals. Notably, interstitial volume fraction (ve, was significantly increased in the NK+mAb9.2.27 combination therapy group compared mAb9.2.27 and NK cell monotherapy groups (p = 0.002 and p = 0.017 respectively in cohort 1 animals treated with 1 million NK cells. ve was reproducibly increased in the combination NK+mAb9.2.27 compared to NK cell monotherapy in cohort 2 treated with increased dose of 2 million NK cells (p<0.0001, indicating greater cell death induced by NK+mAb9.2.27 treatment. The interstitial volume fraction in the NK monotherapy group was significantly reduced compared to mAb9.2.27 monotherapy (p<0.0001 and untreated controls (p = 0.014 in the cohort 2 animals. NK cells in monotherapy were unable to kill the U87MG cells that highly expressed class I human leucocyte antigens, and diminished stress ligands for activating receptors. A significant association between apparent diffusion coefficient (ADC of water and ve in combination NK+mAb9.2.27 and NK monotherapy treated tumours was evident, where increased ADC corresponded to reduced ve in both cases. Collectively, these data support histological measures at end-stage demonstrating diminished tumour cell proliferation and pronounced apoptosis in the NK+mAb9.2.27 treated tumours compared to the other

  5. Meta-analysis of Gene Expression in the Mouse Liver Reveals Biomarkers Associated with Inflammation Increased Early During Aging

    Science.gov (United States)

    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...

  6. The complete mitochondrial genome of Pauropus longiramus (Myriapoda: Pauropoda): implications on early diversification of the myriapods revealed from comparative analysis.

    Science.gov (United States)

    Dong, Yan; Sun, Hongying; Guo, Hua; Pan, Da; Qian, Changyuan; Hao, Sijing; Zhou, Kaiya

    2012-08-15

    Myriapods are among the earliest arthropods and may have evolved to become part of the terrestrial biota more than 400 million years ago. A noticeable lack of mitochondrial genome data from Pauropoda hampers phylogenetic and evolutionary studies within the subphylum Myriapoda. We sequenced the first complete mitochondrial genome of a microscopic pauropod, Pauropus longiramus (Arthropoda: Myriapoda), and conducted comprehensive mitogenomic analyses across the Myriapoda. The pauropod mitochondrial genome is a circular molecule of 14,487 bp long and contains the entire set of thirty-seven genes. Frequent intergenic overlaps occurred between adjacent tRNAs, and between tRNA and protein-coding genes. This is the first example of a mitochondrial genome with multiple intergenic overlaps and reveals a strategy for arthropods to effectively compact the mitochondrial genome by overlapping and truncating tRNA genes with neighbor genes, instead of only truncating tRNAs. Phylogenetic analyses based on protein-coding genes provide strong evidence that the sister group of Pauropoda is Symphyla. Additionally, approximately unbiased (AU) tests strongly support the Progoneata and confirm the basal position of Chilopoda in Myriapoda. This study provides an estimation of myriapod origins around 555 Ma (95% CI: 444-704 Ma) and this date is comparable with that of the Cambrian explosion and candidate myriapod-like fossils. A new time-scale suggests that deep radiations during early myriapod diversification occurred at least three times, not once as previously proposed. A Carboniferous origin of pauropods is congruent with the idea that these taxa are derived, rather than basal, progoneatans. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. The early asthmatic response is associated with glycolysis, calcium binding and mitochondria activity as revealed by proteomic analysis in rats

    Directory of Open Access Journals (Sweden)

    Xu Yu-Dong

    2010-08-01

    Full Text Available Abstract Background The inhalation of allergens by allergic asthmatics results in the early asthmatic response (EAR, which is characterized by acute airway obstruction beginning within a few minutes. The EAR is the earliest indicator of the pathological progression of allergic asthma. Because the molecular mechanism underlying the EAR is not fully defined, this study will contribute to a better understanding of asthma. Methods In order to gain insight into the molecular basis of the EAR, we examined changes in protein expression patterns in the lung tissue of asthmatic rats during the EAR using 2-DE/MS-based proteomic techniques. Bioinformatic analysis of the proteomic data was then performed using PPI Spider and KEGG Spider to investigate the underlying molecular mechanism. Results In total, 44 differentially expressed protein spots were detected in the 2-DE gels. Of these 44 protein spots, 42 corresponded to 36 unique proteins successfully identified using mass spectrometry. During subsequent bioinformatic analysis, the gene ontology classification, the protein-protein interaction networking and the biological pathway exploration demonstrated that the identified proteins were mainly involved in glycolysis, calcium binding and mitochondrial activity. Using western blot and semi-quantitative RT-PCR, we confirmed the changes in expression of five selected proteins, which further supports our proteomic and bioinformatic analyses. Conclusions Our results reveal that the allergen-induced EAR in asthmatic rats is associated with glycolysis, calcium binding and mitochondrial activity, which could establish a functional network in which calcium binding may play a central role in promoting the progression of asthma.

  8. Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics.

    Science.gov (United States)

    Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

    2016-11-01

    Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae-Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  9. Segment polarity gene expression in a myriapod reveals conserved and diverged aspects of early head patterning in arthropods.

    Science.gov (United States)

    Janssen, Ralf

    2012-09-01

    Arthropods show two kinds of developmental mode. In the so-called long germ developmental mode (as exemplified by the fly Drosophila), all segments are formed almost simultaneously from a preexisting field of cells. In contrast, in the so-called short germ developmental mode (as exemplified by the vast majority of arthropods), only the anterior segments are patterned similarly as in Drosophila, and posterior segments are added in a single or double segmental periodicity from a posterior segment addition zone (SAZ). The addition of segments from the SAZ is controlled by dynamic waves of gene activity. Recent studies on a spider have revealed that a similar dynamic process, involving expression of the segment polarity gene (SPG) hedgehog (hh), is involved in the formation of the anterior head segments. The present study shows that in the myriapod Glomeris marginata the early expression of hh is also in a broad anterior domain, but this domain corresponds only to the ocular and antennal segment. It does not, like in spiders, represent expression in the posterior adjacent segment. In contrast, the anterior hh pattern is conserved in Glomeris and insects. All investigated myriapod SPGs and associated factors are expressed with delay in the premandibular (tritocerebral) segment. This delay is exclusively found in insects and myriapods, but not in chelicerates, crustaceans and onychophorans. Therefore, it may represent a synapomorphy uniting insects and myriapods (Atelocerata hypothesis), contradicting the leading opinion that suggests a sister relationship of crustaceans and insects (Pancrustacea hypothesis). In Glomeris embryos, the SPG engrailed is first expressed in the mandibular segment. This feature is conserved in representatives of all arthropod classes suggesting that the mandibular segment may have a special function in anterior patterning.

  10. Cellular metabolism

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Walters, R.A.

    1977-01-01

    Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

  11. Characteristics of juvenile survivors reveal spatio-temporal differences in early life stage survival of Baltic cod

    DEFF Research Database (Denmark)

    Huwer, Bastian; Hinrichsen, H.H.; Böttcher, U.

    2014-01-01

    with previous modeling studies on the survival chances of early-stage larvae and with general spatio-temporal patterns of larval prey availability suggests that differences in survival are related to food availability during the early larval stage. Results are discussed in relation to the recruitment process...

  12. Epigenetics and Cellular Metabolism

    Directory of Open Access Journals (Sweden)

    Wenyi Xu

    2016-01-01

    Full Text Available Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc. is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  13. Pre-transplant donor-specific T-cell alloreactivity is strongly associated with early acute cellular rejection in kidney transplant recipients not receiving T-cell depleting induction therapy.

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    Elena Crespo

    Full Text Available Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90, to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67. We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction

  14. Proteomic responses reveal the differential effects induced by cadmium in mussels Mytilus galloprovincialis at early life stages.

    Science.gov (United States)

    Xu, Lanlan; Peng, Xiao; Yu, Deliang; Ji, Chenglong; Zhao, Jianmin; Wu, Huifeng

    2016-08-01

    Cadmium (Cd) has become an important metal contaminant and posed severe risk on the organisms in the coastal environments of the Bohai Sea. Marine mussel Mytilus galloprovincialis is widely distributed along the Bohai coast and consumed as seafood by local residents. Evidences indicate that the early stages of marine organisms are more sensitive to metal contaminants. In this study, we applied two-dimensional electrophoresis-based proteomics to characterize the biological effects of Cd (50 μg L(-1)) in the early life stages (D-shape larval and juvenile) of mussels. The different proteomic responses demonstrated the differential responsive mechanisms to Cd exposure in these two early life stages of mussels. In details, results indicated that Cd mainly induced immune and oxidative stresses in both D-shape larval and juvenile mussels via different pathways. In addition, the significant up-regulation of triosephosphate isomerase and metallothionein confirmed the enhanced energy demand and mobilized detoxification mechanism in D-shape larval mussels exposed to Cd. In juvenile mussels, Cd exposure also induced clear apoptosis. Overall, this work suggests that Cd is a potential immune toxicant to mussel M. galloprovincialis at early life stages. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis

    OpenAIRE

    Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

    2014-01-01

    Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P

  16. 7T T-2*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease

    NARCIS (Netherlands)

    van Rooden, S.; Doan, N.T.; Versluis, M.J.; Goos, J.D.C.; Webb, A.G.; Oleksik, A.M.; van der Flier, W.M.; Scheltens, P.; Barkhof, F.; Weverlinge-Rynsburger, A.W.E.; Blauw, G. J.; Reiber, J.H.C.; van Buchem, M.A.; Milles, J.; van der Grond, J.

    2015-01-01

    The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T

  17. Comparative Analysis of WUSCHEL-Related Homeobox Genes Revealed Their Parent-of-Origin and Cell Type-Specific Expression Pattern During Early Embryogenesis in Tobacco

    Directory of Open Access Journals (Sweden)

    Xuemei Zhou

    2018-03-01

    Full Text Available WUSCHEL-related homeobox (WOX gene is a plant-specific clade of homeobox transcription factors. Increasing evidences reveal that WOXs play critical roles in early embryogenesis, which involves zygote development, initiation of zygote division, and apical or basal cell lineage establishment. However, how WOXs regulate these developmental events remains largely unknown, and even detailed expression pattern in gametes and early proembryos is not yet available. Here, 13 WOX family genes were identified in Nicotiana tabacum genome. Comparative analysis of 13 WOX family genes with their homologs in Arabidopsis thaliana reveals relatively conserved expression pattern of WUS and WOX5 in shoot/root apical meristem. Whereas variations were also found, e.g., lacking homolog of WOX8 (a marker for suspensor cell in tobacco genome and the expression of WOX2/WOX9 in both apical cell and basal cell. Transient transcriptional activity analysis revealed that WOXs in WUS clade have repressive activities for their target's transcription, whereas WOXs in ancient and intermediate clade have activation activities, giving a molecular basis for the phylogenetic classification of tobacco WOXs into three major clades. Expression pattern analysis revealed that some WOXs (e.g., WOX 13a expressed in both male and female gametes and some WOXs (e.g., WOX 11 and WOX 13b displayed the characteristics of parent-of-origin genes. Interestingly, some WOXs (e.g., WOX2 and WOX9, which are essential for early embryo patterning, were de novo transcribed in zygote, indicating relevant mechanism for embryo pattern formation is only established in zygote right after fertilization and not carried in by gametes. We also found that most WOXs displayed a stage-specific and cell type-specific expression pattern. Taken together, this work provides a detailed landscape of WOXs in tobacco during fertilization and early embryogenesis, which will facilitate the understanding of their specific roles

  18. Metabolomics and transcriptomics reveal the toxicity of difenoconazole to the early life stages of zebrafish (Danio rerio).

    Science.gov (United States)

    Teng, Miaomiao; Zhu, Wentao; Wang, Dezhen; Qi, Suzhen; Wang, Yao; Yan, Jin; Dong, Kai; Zheng, Mingqi; Wang, Chengju

    2018-01-01

    Difenoconazole is widely used to inhibit the growth of fungi, but its residue in the water environment may threaten ecosystem and human health. Here, 1 H nuclear magnetic resonance (NMR) and LC-MS/MS based metabolomics and transcriptomics approaches were used to assess the response of zebrafish to difenoconazole exposure. Early life stages of zebrafish were exposed to difenoconazole at environmentally relevant concentrations for 168h. Their comparison with the control group suggested an adverse development and disturbance of steroid hormones and VTG. KEGG pathway analysis identified five biological processes on the basis of differentially expressed genes (DEGs), as well as altered metabolites and amino acids in zebrafish following difenoconazole exposure. These affected processes included energy metabolism, amino acids metabolism, lipid metabolism, nucleotide metabolism, and an immune-related pathway. Collectively, these results bring us closer to an incremental understanding of the toxic effects of difenoconazole on zebrafish in its early development, and lend support to the continued use of the early life stages of zebrafish as a classical model to evaluate underlying environmental risks of xenobiotics in aquatic organisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Tikal, Guatemala, and Emergent Maya Civilization: Excavations reveal evidence of early complex-living at a prime Maya Indian site.

    Science.gov (United States)

    Coe, W R

    1965-03-19

    It would be extravagant to claim that these pages have outlined meaningfully the early evolution of Tikal. Data have been provided largely for one excavation locus at a site which, for all its importance, merely has symptomatic value. We cannot claim to have, at present, sufficient material to document satisfyingly the conditions and products of community-wide living at any point in these early times. Present knowledge of Eb and Tzec ceramics and of all the usual archeological correlates (architecture and so on) is disturbingly incomplete. While we do have a good many data on residence throughout much of Preclassic time, considerably more information is needed before a solid evaluation of Preclassic Tikal society can be achieved. One can only hope that pending excavation programs will provide it. Yet, experience shows that probably only a tiny percentage of early cultural remains, regardless of their grandeur and importance at the time, would have survived the constant quest for construction fills to satisfy a seemingly interminable need to build and revamp.

  20. A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging.

    Science.gov (United States)

    Baroncelli, Laura; Molinaro, Angelo; Cacciante, Francesco; Alessandrì, Maria Grazia; Napoli, Debora; Putignano, Elena; Tola, Jonida; Leuzzi, Vincenzo; Cioni, Giovanni; Pizzorusso, Tommaso

    2016-10-01

    Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and autistic-like behavioural disturbances, language and speech impairment. Since no data are available about the neural and molecular underpinnings of this disease, we performed a longitudinal analysis of behavioural and pathological alterations associated with CrT deficiency in a CCDS1 mouse model. We found precocious cognitive and autistic-like defects, mimicking the early key features of human CCDS1. Moreover, mutant mice displayed a progressive impairment of short and long-term declarative memory denoting an early brain aging. Pathological examination showed a prominent loss of GABAergic synapses, marked activation of microglia, reduction of hippocampal neurogenesis and the accumulation of autofluorescent lipofuscin. Our data suggest that brain Cr depletion causes both early intellectual disability and late progressive cognitive decline, and identify novel targets to design intervention strategies aimed at overcoming brain CCDS1 alterations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Small RNA Sequencing Reveals Differential miRNA Expression in the Early Development of Broccoli (Brassica oleracea var. italica) Pollen.

    Science.gov (United States)

    Li, Hui; Wang, Yu; Wu, Mei; Li, Lihong; Jin, Chuan; Zhang, Qingli; Chen, Chengbin; Song, Wenqin; Wang, Chunguo

    2017-01-01

    Pollen development is an important and complex biological process in the sexual reproduction of flowering plants. Although the cytological characteristics of pollen development are well defined, the regulation of its early stages remains largely unknown. In the present study, miRNAs were explored in the early development of broccoli ( Brassica oleracea var. italica ) pollen. A total of 333 known miRNAs that originated from 235 miRNA families were detected. Fifty-five novel miRNA candidates were identified. Sixty of the 333 known miRNAs and 49 of the 55 predicted novel miRNAs exhibited significantly differential expression profiling in the three distinct developmental stages of broccoli pollen. Among these differentially expressed miRNAs, miRNAs that would be involved in the developmental phase transition from uninucleate microspores to binucleate pollen grains or from binucleate to trinucleate pollen grains were identified. miRNAs that showed significantly enriched expression in a specific early stage of broccoli pollen development were also observed. In addition, 552 targets for 127 known miRNAs and 69 targets for 40 predicted novel miRNAs were bioinformatically identified. Functional annotation and GO (Gene Ontology) analysis indicated that the putative miRNA targets showed significant enrichment in GO terms that were related to plant organ formation and morphogenesis. Some of enriched GO terms were detected for the targets directly involved in plant male reproduction development. These findings provided new insights into the functions of miRNA-mediated regulatory networks in broccoli pollen development.

  2. New early Eocene vertebrate assemblage from western India reveals a mixed fauna of European and Gondwana affinities

    Directory of Open Access Journals (Sweden)

    Thierry Smith

    2016-11-01

    Full Text Available The Ypresian Cambay Shale Formation at Vastan and Mangrol lignite mines in Gujarat, western India, has yielded a rich vertebrate fauna with numerous taxa of European affinities. Here we report a new, approximately contemporary vertebrate assemblage from two fossiliferous layers in the nearby mine of Tadkeshwar. These layers have yielded a similar mammal fauna with the co-occurrence of the perissodactyl-like cambaytheriid Cambaytherium thewissi, the adapoid primates Marcgodinotius indicus and cf. Asiadapis cambayensis, and the hyaenodontid Indohyaenodon raoi. The presence of these species in both Vastan and Tadkeshwar mines and at different levels suggests that the deposits between the two major lignite seams represent a single land mammal age. Apart from the aforementioned species there is a new, smaller species of Cambaytherium, and a new genus and species of esthonychid tillodont. This fauna also contains the first large early Eocene vertebrates from India, including an unidentified Coryphodon-like pantodont, a dyrosaurid crocodyliform and a new giant madtsoiid snake. Among the Tadkeshwar vertebrates several taxa are of Gondwana affinities, such as Pelomedusoides turtles, dyrosaurids, and large madtsoiids, attesting that the early Eocene was a crucial period in India during which Laurasian taxa of European affinities co-existed with relict taxa from Gondwana before the India-Asia collision. Our results suggest that terrestrial faunas could have dispersed to or from Europe during episodes of contact between the Indian subcontinent and different island blocks along the northern margin of the Neotethys, such as the Kohistan–Ladakh island-arc system. Gondwana taxa might represent remnants of ghost lineages shared with Madagascar, which reached the Indian subcontinent during the late Cretaceous; alternatively they might have come from North Africa and passed along the southern margin of the Neotethys to reach the Indian subcontinent. These

  3. Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever

    Science.gov (United States)

    Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R.

    2016-01-01

    Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (1.5) in the serum, among which are two products of tryptophan metabolism–serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved the prognosis performance (AUC = 0.92, sensitivity = 77.8%, specificity = 95.8%), suggesting this duplex panel as accurate metrics for the early prognosis of DHF. PMID:27055163

  4. Ancient DNA from South-East Europe Reveals Different Events during Early and Middle Neolithic Influencing the European Genetic Heritage.

    Science.gov (United States)

    Hervella, Montserrat; Rotea, Mihai; Izagirre, Neskuts; Constantinescu, Mihai; Alonso, Santos; Ioana, Mihai; Lazăr, Cătălin; Ridiche, Florin; Soficaru, Andrei Dorian; Netea, Mihai G; de-la-Rua, Concepcion

    2015-01-01

    The importance of the process of Neolithization for the genetic make-up of European populations has been hotly debated, with shifting hypotheses from a demic diffusion (DD) to a cultural diffusion (CD) model. In this regard, ancient DNA data from the Balkan Peninsula, which is an important source of information to assess the process of Neolithization in Europe, is however missing. In the present study we show genetic information on ancient populations of the South-East of Europe. We assessed mtDNA from ten sites from the current territory of Romania, spanning a time-period from the Early Neolithic to the Late Bronze Age. mtDNA data from Early Neolithic farmers of the Starčevo Criş culture in Romania (Cârcea, Gura Baciului and Negrileşti sites), confirm their genetic relationship with those of the LBK culture (Linienbandkeramik Kultur) in Central Europe, and they show little genetic continuity with modern European populations. On the other hand, populations of the Middle-Late Neolithic (Boian, Zau and Gumelniţa cultures), supposedly a second wave of Neolithic migration from Anatolia, had a much stronger effect on the genetic heritage of the European populations. In contrast, we find a smaller contribution of Late Bronze Age migrations to the genetic composition of Europeans. Based on these findings, we propose that permeation of mtDNA lineages from a second wave of Middle-Late Neolithic migration from North-West Anatolia into the Balkan Peninsula and Central Europe represent an important contribution to the genetic shift between Early and Late Neolithic populations in Europe, and consequently to the genetic make-up of modern European populations.

  5. Cellular dosimetry

    International Nuclear Information System (INIS)

    Humm, J.L.; Chin, L.M.

    1989-01-01

    Radiation dose is a useful predictive parameter for describing radiation toxicity in conventional radiotherapy. Traditionally, in vitro radiation biology dose-effect relations are expressed in the form of cell survival curves, a semilog plot of cell survival versus dose. However, the characteristic linear or linear quadratic survival curve shape, for high- and low-LET radiations respectively, is only strictly valid when the radiation dose is uniform across the entire target population. With an external beam of 60 Co gamma rays or x-rays, a uniform field may be readily achievable. When radionuclides are incorporated into a cell milieu, several new problems emerge which can result in a departure from uniformity in energy deposition throughout a cell population. This nonuniformity can have very important consequences for the shape of the survival curve. Cases in which perturbations of source uniformity may arise include: 1. Elemental sources may equilibrate in the cell medium with partition coefficients between the extracellular, cytosol, and nuclear compartments. The effect of preferential cell internalization or binding to cell membrane of some radionuclides can increase or decrease the slope of the survival curve. 2. Radionuclides bound to antibodies, hormones, metabolite precursors, etc., may result in a source localization pattern characteristic of the carrier agent, i.e., the sources may bind to cell surface receptors or antigens, be internalized, bind to secreted antigen concentrated around a fraction of the cell population, or become directly incorporated into the cell DNA. We propose to relate the distribution of energy deposition in cell nuclei to biological correlates of cellular inactivation. The probability of each cell's survival is weighted by its individual radiation burden, and the summation of these probabilities for the cell population can be used to predict the number or fraction of cell survivors

  6. Historical DNA reveals the demographic history of Atlantic cod (Gadus morhua) in medieval and early modern Iceland.

    Science.gov (United States)

    Ólafsdóttir, Guðbjörg Ásta; Westfall, Kristen M; Edvardsson, Ragnar; Pálsson, Snæbjörn

    2014-02-22

    Atlantic cod (Gadus morhua) vertebrae from archaeological sites were used to study the history of the Icelandic Atlantic cod population in the time period of 1500-1990. Specifically, we used coalescence modelling to estimate population size and fluctuations from the sequence diversity at the cytochrome b (cytb) and Pantophysin I (PanI) loci. The models are consistent with an expanding population during the warm medieval period, large historical effective population size (NE), a marked bottleneck event at 1400-1500 and a decrease in NE in early modern times. The model results are corroborated by the reduction of haplotype and nucleotide variation over time and pairwise population distance as a significant portion of nucleotide variation partitioned across the 1550 time mark. The mean age of the historical fished stock is high in medieval times with a truncation in age in early modern times. The population size crash coincides with a period of known cooling in the North Atlantic, and we conclude that the collapse may be related to climate or climate-induced ecosystem change.

  7. Effects of Repeated Concussions and Sex on Early Processing of Emotional Facial Expressions as Revealed by Electrophysiology.

    Science.gov (United States)

    Carrier-Toutant, Frédérike; Guay, Samuel; Beaulieu, Christelle; Léveillé, Édith; Turcotte-Giroux, Alexandre; Papineau, Samaël D; Brisson, Benoit; D'Hondt, Fabien; De Beaumont, Louis

    2018-05-06

    Concussions affect the processing of emotional stimuli. This study aimed to investigate how sex interacts with concussion effects on early event-related brain potentials (ERP) measures (P1, N1) of emotional facial expressions (EFE) processing in asymptomatic, multi-concussion athletes during an EFE identification task. Forty control athletes (20 females and 20 males) and 43 multi-concussed athletes (22 females and 21 males), recruited more than 3 months after their last concussion, were tested. Participants completed the Beck Depression Inventory II, the Beck Anxiety Inventory, the Post-Concussion Symptom Scale, and an Emotional Facial Expression Identification Task. Pictures of male and female faces expressing neutral, angry, and happy emotions were randomly presented and the emotion depicted had to be identified as fast as possible during EEG acquisition. Relative to controls, concussed athletes of both sex exhibited a significant suppression of P1 amplitude recorded from the dominant right hemisphere while performing the emotional face expression identification task. The present study also highlighted a sex-specific suppression of the N1 component amplitude after concussion which affected male athletes. These findings suggest that repeated concussions alter the typical pattern of right-hemisphere response dominance to EFE in early stages of EFE processing and that the neurophysiological mechanisms underlying the processing of emotional stimuli are distinctively affected across sex. (JINS, 2018, 24, 1-11).

  8. New Genetic Insights into Pearl Millet Diversity As Revealed by Characterization of Early- and Late-Flowering Landraces from Senegal

    Directory of Open Access Journals (Sweden)

    Oumar Diack

    2017-05-01

    Full Text Available Pearl millet (Pennisetum glaucum (L. R. Br. is a staple food and a drought-tolerant cereal well adapted to Sub-Saharan Africa agro-ecosystems. An important diversity of pearl millet landraces has been widely conserved by farmers and therefore could help copping with climate changes and contribute to future food security. Hence, characterizing its genetic diversity and population structure can contribute to better assist breeding programs for a sustainable agricultural productivity enhancement. Toward this goal, a comprehensive panel of 404 accessions were used that correspond to 12 improved varieties, 306 early flowering and 86 late-flowering cultivated landraces from Senegal. Twelve highly polymorphic SSR markers were used to study diversity and population structure. Two genes, PgMADS11 and PgPHYC, were genotyped to assess their association to flowering phenotypic difference in landraces. Results indicate a large diversity and untapped potential of Senegalese pearl millet germplasm as well as a genetic differentiation between early- and late-flowering landraces. Further, a fine-scale genetic difference of PgPHYC and PgMADS11 (SNP and indel, respectively and co-variation of their alleles with flowering time were found among landraces. These findings highlight new genetic insights of pearl millet useful to define heterotic populations for breeding, genomic association panel, or crosses for trait-specific mapping.

  9. Combined chromatin and expression analysis reveals specific regulatory mechanisms within cytokine genes in the macrophage early immune response.

    Directory of Open Access Journals (Sweden)

    Maria Jesus Iglesias

    Full Text Available Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS.To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches--gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII, which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of up-regulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF, was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines, was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40% was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at

  10. Studies of Physcomitrella patens reveal that ethylene-mediated submergence responses arose relatively early in land-plant evolution

    KAUST Repository

    Yasumura, Yuki

    2012-10-18

    Colonization of the land by multicellular green plants was a fundamental step in the evolution of life on earth. Land plants evolved from fresh-water aquatic algae, and the transition to a terrestrial environment required the acquisition of developmental plasticity appropriate to the conditions of water availability, ranging from drought to flood. Here we show that extant bryophytes exhibit submergence-induced developmental plasticity, suggesting that submergence responses evolved relatively early in the evolution of land plants. We also show that a major component of the bryophyte submergence response is controlled by the phytohormone ethylene, using a perception mechanism that has subsequently been conserved throughout the evolution of land plants. Thus a plant environmental response mechanism with major ecological and agricultural importance probably had its origins in the very earliest stages of the colonization of the land. © 2012 Blackwell Publishing Ltd.

  11. Automated analysis of connected speech reveals early biomarkers of Parkinson's disease in patients with rapid eye movement sleep behaviour disorder.

    Science.gov (United States)

    Hlavnička, Jan; Čmejla, Roman; Tykalová, Tereza; Šonka, Karel; Růžička, Evžen; Rusz, Jan

    2017-02-02

    For generations, the evaluation of speech abnormalities in neurodegenerative disorders such as Parkinson's disease (PD) has been limited to perceptual tests or user-controlled laboratory analysis based upon rather small samples of human vocalizations. Our study introduces a fully automated method that yields significant features related to respiratory deficits, dysphonia, imprecise articulation and dysrhythmia from acoustic microphone data of natural connected speech for predicting early and distinctive patterns of neurodegeneration. We compared speech recordings of 50 subjects with rapid eye movement sleep behaviour disorder (RBD), 30 newly diagnosed, untreated PD patients and 50 healthy controls, and showed that subliminal parkinsonian speech deficits can be reliably captured even in RBD patients, which are at high risk of developing PD or other synucleinopathies. Thus, automated vocal analysis should soon be able to contribute to screening and diagnostic procedures for prodromal parkinsonian neurodegeneration in natural environments.

  12. Weighted gene co-expression network analysis reveals potential genes involved in early metamorphosis process in sea cucumber Apostichopus japonicus.

    Science.gov (United States)

    Li, Yongxin; Kikuchi, Mani; Li, Xueyan; Gao, Qionghua; Xiong, Zijun; Ren, Yandong; Zhao, Ruoping; Mao, Bingyu; Kondo, Mariko; Irie, Naoki; Wang, Wen

    2018-01-01

    Sea cucumbers, one main class of Echinoderms, have a very fast and drastic metamorphosis process during their development. However, the molecular basis under this process remains largely unknown. Here we systematically examined the gene expression profiles of Japanese common sea cucumber (Apostichopus japonicus) for the first time by RNA sequencing across 16 developmental time points from fertilized egg to juvenile stage. Based on the weighted gene co-expression network analysis (WGCNA), we identified 21 modules. Among them, MEdarkmagenta was highly expressed and correlated with the early metamorphosis process from late auricularia to doliolaria larva. Furthermore, gene enrichment and differentially expressed gene analysis identified several genes in the module that may play key roles in the metamorphosis process. Our results not only provide a molecular basis for experimentally studying the development and morphological complexity of sea cucumber, but also lay a foundation for improving its emergence rate. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Differential gene expression profile reveals deregulation of pregnancy specific β1 glycoprotein 9 early during colorectal carcinogenesis

    Directory of Open Access Journals (Sweden)

    Gallinger Steven

    2005-06-01

    Full Text Available Abstract Background APC (Adenomatous polyposis coli plays an important role in the pathogenesis of both familial and sporadic colorectal cancer. Patients carrying germline APC mutations develop multiple colonic adenomas at younger age and higher frequency than non-carrier cases which indicates that silencing of one APC allele may be sufficient to initiate the transformation process. Methods To elucidate the biological dysregulation underlying adenoma formation we examined global gene expression profiles of adenomas and corresponding normal mucosa from an FAP patient. Differential expression of the most significant gene identified in this study was further validated by mRNA in situ hybridization, reverse transcriptase PCR and Northern blotting in different sets of adenomas, tumours and cancer cell lines. Results Eighty four genes were differentially expressed between all adenomas and corresponding normal mucosa, while only seven genes showed differential expression within the adenomas. The first group included pregnancy specific β-1 glycoprotein 9 (PSG9 (p PSG9 is a member of the carcinoembryonic antigen (CEA/PSG family and is produced at high levels during pregnancy, mainly by syncytiotrophoblasts. Further analysis of sporadic and familial colorectal cancer confirmed that PSG9 is ectopically upregulated in vivo by cancer cells. In total, deregulation of PSG9 mRNA was detected in 78% (14/18 of FAP adenomas and 75% (45/60 of sporadic colorectal cancer cases tested. Conclusion Detection of PSG9 expression in adenomas, and at higher levels in FAP cases, indicates that germline APC mutations and defects in Wnt signalling modulate PSG9 expression. Since PSG9 is not found in the non-pregnant adult except in association with cancer, and it appears to be an early molecular event associated with colorectal cancer monitoring of its expression may be useful as a biomarker for the early detection of this disease.

  14. An alternative model for the early peopling of southern South America revealed by analyses of three mitochondrial DNA haplogroups.

    Science.gov (United States)

    de Saint Pierre, Michelle; Bravi, Claudio M; Motti, Josefina M B; Fuku, Noriyuki; Tanaka, Masashi; Llop, Elena; Bonatto, Sandro L; Moraga, Mauricio

    2012-01-01

    After several years of research, there is now a consensus that America was populated from Asia through Beringia, probably at the end of the Pleistocene. But many details such as the timing, route(s), and origin of the first settlers remain uncertain. In the last decade genetic evidence has taken on a major role in elucidating the peopling of the Americas. To study the early peopling of South America, we sequenced the control region of mitochondrial DNA from 300 individuals belonging to indigenous populations of Chile and Argentina, and also obtained seven complete mitochondrial DNA sequences. We identified two novel mtDNA monophyletic clades, preliminarily designated B2l and C1b13, which together with the recently described D1g sub-haplogroup have locally high frequencies and are basically restricted to populations from the extreme south of South America. The estimated ages of D1g and B2l, about ~15,000 years BP, together with their similar population dynamics and the high haplotype diversity shown by the networks, suggests that they probably appeared soon after the arrival of the first settlers and agrees with the dating of the earliest archaeological sites in South America (Monte Verde, Chile, 14,500 BP). One further sub-haplogroup, D4h3a5, appears to be restricted to Fuegian-Patagonian populations and reinforces our hypothesis of the continuity of the current Patagonian populations with the initial founders. Our results indicate that the extant native populations inhabiting South Chile and Argentina are a group which had a common origin, and suggest a population break between the extreme south of South America and the more northern part of the continent. Thus the early colonization process was not just an expansion from north to south, but also included movements across the Andes.

  15. Multisensory representation of frequency across audition and touch: high density electrical mapping reveals early sensory-perceptual coupling.

    Science.gov (United States)

    Butler, John S; Foxe, John J; Fiebelkorn, Ian C; Mercier, Manuel R; Molholm, Sophie

    2012-10-31

    The frequency of environmental vibrations is sampled by two of the major sensory systems, audition and touch, notwithstanding that these signals are transduced through very different physical media and entirely separate sensory epithelia. Psychophysical studies have shown that manipulating frequency in audition or touch can have a significant cross-sensory impact on perceived frequency in the other sensory system, pointing to intimate links between these senses during computation of frequency. In this regard, the frequency of a vibratory event can be thought of as a multisensory perceptual construct. In turn, electrophysiological studies point to temporally early multisensory interactions that occur in hierarchically early sensory regions where convergent inputs from the auditory and somatosensory systems are to be found. A key question pertains to the level of processing at which the multisensory integration of featural information, such as frequency, occurs. Do the sensory systems calculate frequency independently before this information is combined, or is this feature calculated in an integrated fashion during preattentive sensory processing? The well characterized mismatch negativity, an electrophysiological response that indexes preattentive detection of a change within the context of a regular pattern of stimulation, served as our dependent measure. High-density electrophysiological recordings were made in humans while they were presented with separate blocks of somatosensory, auditory, and audio-somatosensory "standards" and "deviants," where the deviant differed in frequency. Multisensory effects were identified beginning at ∼200 ms, with the multisensory mismatch negativity (MMN) significantly different from the sum of the unisensory MMNs. This provides compelling evidence for preattentive coupling between the somatosensory and auditory channels in the cortical representation of frequency.

  16. Behavioral characterization of A53T mice reveals early and late stage deficits related to Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Katrina L Paumier

    Full Text Available Parkinson's disease (PD pathology is characterized by the formation of intra-neuronal inclusions called Lewy bodies, which are comprised of alpha-synuclein (α-syn. Duplication, triplication or genetic mutations in α-syn (A53T, A30P and E46K are linked to autosomal dominant PD; thus implicating its role in the pathogenesis of PD. In both PD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of protein aggregates (i.e., α-syn and neurodegeneration. Characterization of the timing and nature of symptomatic dysfunction is important for understanding the impact of α-syn on disease progression. Furthermore, this knowledge is essential for identifying pathways and molecular targets for therapeutic intervention. To this end, we examined various functional and morphological endpoints in the transgenic mouse model expressing the human A53T α-syn variant directed by the mouse prion promoter at specific ages relating to disease progression (2, 6 and 12 months of age. Our findings indicate A53T mice develop fine, sensorimotor, and synaptic deficits before the onset of age-related gross motor and cognitive dysfunction. Results from open field and rotarod tests show A53T mice develop age-dependent changes in locomotor activity and reduced anxiety-like behavior. Additionally, digigait analysis shows these mice develop an abnormal gait by 12 months of age. A53T mice also exhibit spatial memory deficits at 6 and 12 months, as demonstrated by Y-maze performance. In contrast to gross motor and cognitive changes, A53T mice display significant impairments in fine- and sensorimotor tasks such as grooming, nest building and acoustic startle as early as 1-2 months of age. These mice also show significant abnormalities in basal synaptic transmission, paired-pulse facilitation and long-term depression (LTD. Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic

  17. Behavioral Characterization of A53T Mice Reveals Early and Late Stage Deficits Related to Parkinson’s Disease

    Science.gov (United States)

    Paumier, Katrina L.; Sukoff Rizzo, Stacey J.; Berger, Zdenek; Chen, Yi; Gonzales, Cathleen; Kaftan, Edward; Li, Li; Lotarski, Susan; Monaghan, Michael; Shen, Wei; Stolyar, Polina; Vasilyev, Dmytro; Zaleska, Margaret; D. Hirst, Warren; Dunlop, John

    2013-01-01

    Parkinson's disease (PD) pathology is characterized by the formation of intra-neuronal inclusions called Lewy bodies, which are comprised of alpha-synuclein (α-syn). Duplication, triplication or genetic mutations in α-syn (A53T, A30P and E46K) are linked to autosomal dominant PD; thus implicating its role in the pathogenesis of PD. In both PD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of protein aggregates (i.e., α-syn) and neurodegeneration. Characterization of the timing and nature of symptomatic dysfunction is important for understanding the impact of α-syn on disease progression. Furthermore, this knowledge is essential for identifying pathways and molecular targets for therapeutic intervention. To this end, we examined various functional and morphological endpoints in the transgenic mouse model expressing the human A53T α-syn variant directed by the mouse prion promoter at specific ages relating to disease progression (2, 6 and 12 months of age). Our findings indicate A53T mice develop fine, sensorimotor, and synaptic deficits before the onset of age-related gross motor and cognitive dysfunction. Results from open field and rotarod tests show A53T mice develop age-dependent changes in locomotor activity and reduced anxiety-like behavior. Additionally, digigait analysis shows these mice develop an abnormal gait by 12 months of age. A53T mice also exhibit spatial memory deficits at 6 and 12 months, as demonstrated by Y-maze performance. In contrast to gross motor and cognitive changes, A53T mice display significant impairments in fine- and sensorimotor tasks such as grooming, nest building and acoustic startle as early as 1–2 months of age. These mice also show significant abnormalities in basal synaptic transmission, paired-pulse facilitation and long-term depression (LTD). Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic impairments

  18. Quantitative N-linked Glycoproteomics of Myocardial Ischemia and Reperfusion Injury Reveals Early Remodeling in the Extracellular Environment

    DEFF Research Database (Denmark)

    Parker, Benjamin L; Palmisano, Giuseppe; Edwards, Alistair V G

    2011-01-01

    , while dimethyl labeling confirmed 46 of these and revealed an additional 62 significant changes. These were mainly from predicted extracellular matrix and basement membrane proteins that are implicated in cardiac remodeling. Analysis of N-glycans released from myocardial proteins suggest...... that the observed changes were not due to significant alterations in N-glycan structures. Altered proteins included the collagen-laminin-integrin complexes and collagen assembly enzymes, cadherins, mast cell proteases, proliferation-associated secreted protein acidic and rich in cysteine, and microfibril......Extracellular and cell surface proteins are generally modified with N-linked glycans and glycopeptide enrichment is an attractive tool to analyze these proteins. The role of N-linked glycoproteins in cardiovascular disease, particularly ischemia and reperfusion injury, is poorly understood...

  19. Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1delTTAG/+ Mice.

    Science.gov (United States)

    Chao de la Barca, Juan Manuel; Simard, Gilles; Sarzi, Emmanuelle; Chaumette, Tanguy; Rousseau, Guillaume; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Ferré, Marc; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Gueguen, Naïg; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Amati-Bonneau, Patrizia; Procaccio, Vincent; Hamel, Christian; Lenaers, Guy; Reynier, Pascal; Prunier-Mirebeau, Delphine

    2017-02-01

    Dominant optic atrophy (MIM No. 165500) is a blinding condition related to mutations in OPA1, a gene encoding a large GTPase involved in mitochondrial inner membrane dynamics. Although several mouse models mimicking the disease have been developed, the pathophysiological mechanisms responsible for retinal ganglion cell degeneration remain poorly understood. Using a targeted metabolomic approach, we measured the concentrations of 188 metabolites in nine tissues, that is, brain, three types of skeletal muscle, heart, liver, retina, optic nerve, and plasma in symptomatic 11-month-old Opa1delTTAG/+ mice. Significant metabolic signatures were found only in the optic nerve and plasma of female mice. The optic nerve signature was characterized by altered concentrations of phospholipids, amino acids, acylcarnitines, and carnosine, whereas the plasma signature showed decreased concentrations of amino acids and sarcosine associated with increased concentrations of several phospholipids. In contrast, the investigation of 3-month-old presymptomatic Opa1delTTAG/+ mice showed no specific plasma signature but revealed a significant optic nerve signature in both sexes, although with a sex effect. The Opa1delTTAG/+ versus wild-type optic nerve signature was characterized by the decreased concentrations of 10 sphingomyelins and 10 lysophosphatidylcholines, suggestive of myelin sheath alteration, and by alteration in the concentrations of metabolites involved in neuroprotection, such as dimethylarginine, carnitine, spermine, spermidine, carnosine, and glutamate, suggesting a concomitant axonal metabolic dysfunction. Our comprehensive metabolomic investigations revealed in symptomatic as well as in presymptomatic Opa1delTTAG/+ mice, a specific sensitiveness of the optic nerve to Opa1 insufficiency, opening new routes for protective therapeutic strategies.

  20. Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression

    International Nuclear Information System (INIS)

    Liu, Chih-Wei; Bramer, Lisa; Computational Modeling); Webb-Robertson, Bobbie-Jo; Computational Modeling); Waugh, Kathleen; Rewers, Marian J.; Zhang, Qibin; Biochemistry)

    2017-01-01

    We report that blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n = 11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n = 10). To our knowledge, the current study represents the largest (> 2000 proteins measured) longitudinal expression profiles of human plasma proteome in T1D research. By applying statistical trend analysis on the temporal expression patterns between T1D and controls, and Benjamini-Hochberg procedure for multiple-testing correction, 13 protein groups were regarded as having statistically significant differences during the entire follow-up period. Moreover, 16 protein groups, which play pivotal roles in response to oxidative stress, have consistently abnormal expression trend before seroconversion to islet autoimmunity. Importantly, the expression trends of two key reactive oxygen species-decomposing enzymes, Catalase and Superoxide dismutase were verified independently by ELISA.

  1. 7T T₂*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease.

    Science.gov (United States)

    van Rooden, Sanneke; Doan, Nhat Trung; Versluis, Maarten J; Goos, Jeroen D C; Webb, Andrew G; Oleksik, Ania M; van der Flier, Wiesje M; Scheltens, Philip; Barkhof, Frederik; Weverling-Rynsburger, Annelies W E; Blauw, Gerard Jan; Reiber, Johan H C; van Buchem, Mark A; Milles, Julien; van der Grond, Jeroen

    2015-01-01

    The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T2(∗)-weighted scans were acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and regional mean phase contrasts were computed. An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p < 0.05). Regional mean phase contrast in EOAD patients was higher than in LOAD patients in the superior medial and middle frontal gyrus, anterior and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal gyrus, and precuneus (p ≤ 0.042). These data suggest that EOAD patients have an increased iron accumulation, possibly related to an increased amyloid deposition, in specific cortical regions as compared with LOAD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage.

    Science.gov (United States)

    Tulpule, Asmin; Lensch, M William; Miller, Justine D; Austin, Karyn; D'Andrea, Alan; Schlaeger, Thorsten M; Shimamura, Akiko; Daley, George Q

    2010-04-29

    Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease.

  3. Early stages of functional diversification in the Rab GTPase gene family revealed by genomic and localization studies in Paramecium species.

    Science.gov (United States)

    Bright, Lydia J; Gout, Jean-Francois; Lynch, Michael

    2017-04-15

    New gene functions arise within existing gene families as a result of gene duplication and subsequent diversification. To gain insight into the steps that led to the functional diversification of paralogues, we tracked duplicate retention patterns, expression-level divergence, and subcellular markers of functional diversification in the Rab GTPase gene family in three Paramecium aurelia species. After whole-genome duplication, Rab GTPase duplicates are more highly retained than other genes in the genome but appear to be diverging more rapidly in expression levels, consistent with early steps in functional diversification. However, by localizing specific Rab proteins in Paramecium cells, we found that paralogues from the two most recent whole-genome duplications had virtually identical localization patterns, and that less closely related paralogues showed evidence of both conservation and diversification. The functionally conserved paralogues appear to target to compartments associated with both endocytic and phagocytic recycling functions, confirming evolutionary and functional links between the two pathways in a divergent eukaryotic lineage. Because the functionally diversifying paralogues are still closely related to and derived from a clade of functionally conserved Rab11 genes, we were able to pinpoint three specific amino acid residues that may be driving the change in the localization and thus the function in these proteins. © 2017 Bright et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  4. Whole transcriptome profiling of maize during early somatic embryogenesis reveals altered expression of stress factors and embryogenesis-related genes.

    Directory of Open Access Journals (Sweden)

    Stella A G D Salvo

    Full Text Available Embryogenic tissue culture systems are utilized in propagation and genetic engineering of crop plants, but applications are limited by genotype-dependent culture response. To date, few genes necessary for embryogenic callus formation have been identified or characterized. The goal of this research was to enhance our understanding of gene expression during maize embryogenic tissue culture initiation. In this study, we highlight the expression of candidate genes that have been previously regarded in the literature as having important roles in somatic embryogenesis. We utilized RNA based sequencing (RNA-seq to characterize the transcriptome of immature embryo explants of the highly embryogenic and regenerable maize genotype A188 at 0, 24, 36, 48, and 72 hours after placement of explants on tissue culture initiation medium. Genes annotated as functioning in stress response, such as glutathione-S-transferases and germin-like proteins, and genes involved with hormone transport, such as PINFORMED, increased in expression over 8-fold in the study. Maize genes with high sequence similarity to genes previously described in the initiation of embryogenic cultures, such as transcription factors BABY BOOM, LEAFY COTYLEDON, and AGAMOUS, and important receptor-like kinases such as SOMATIC EMBRYOGENESIS RECEPTOR LIKE KINASES and CLAVATA, were also expressed in this time course study. By combining results from whole genome transcriptome analysis with an in depth review of key genes that play a role in the onset of embryogenesis, we propose a model of coordinated expression of somatic embryogenesis-related genes, providing an improved understanding of genomic factors involved in the early steps of embryogenic culture initiation in maize and other plant species.

  5. Asynchrony of the early maturation of white matter bundles in healthy infants: Quantitative landmarks revealed noninvasively by diffusion tensor imaging

    International Nuclear Information System (INIS)

    Dubois, J.; Perrin, M.; Mangin, J.F.; Cointepas, Y.; Duchesnay, E.; Le Bihan, D.; Hertz-Pannier, L.; Dehaene-Lambertz, G.; Dubois, J.; Dehaene-Lambertz, G.; Perrin, M.; Mangin, J.F.; Cointepas, Y.; Duchesnay, E.; Le Bihan, D.; Hertz-Pannier, L.

    2008-01-01

    Normal cognitive development in infants follows a well-known temporal sequence, which is assumed to be correlated with the structural maturation of underlying functional networks. Postmortem studies and, more recently, structural MR imaging studies have described qualitatively the heterogeneous spatio-temporal progression of white matter myelination. However, in vivo quantification of the maturation phases of fiber bundles is still lacking. We used noninvasive diffusion tensor MR imaging and tractography in twenty-three 1-4-month-old healthy infants to quantify the early maturation of the main cerebral fascicles. A specific maturation model, based on the respective roles of different maturational processes on the diffusion phenomena, was designed to highlight asynchronous maturation across bundles by evaluating the time-course of mean diffusivity and anisotropy changes over the considered developmental period. Using an original approach, a progression of maturation in four relative stages was determined in each tract by estimating the maturation state and speed, from the diffusion indices over the infants group compared with an adults group on one hand, and in each tract compared with the average over bundles on the other hand. Results were coherent with, and extended previous findings in 8 of 11 bundles, showing the anterior limb of the internal capsule and cingulum as the most immature, followed by the optic radiations, arcuate and inferior longitudinal fascicles, then the spino-thalamic tract and fornix, and finally the cortico-spinal tract as the most mature bundle. Thus, this approach provides new quantitative landmarks for further noninvasive research on brain-behavior relationships during normal and abnormal development. (authors)

  6. Contrasting Networks for Recognition Memory and Recency Memory Revealed by Immediate-Early Gene Imaging in the Rat

    Science.gov (United States)

    2014-01-01

    The expression of the immediate-early gene c-fos was used to compare networks of activity associated with recency memory (temporal order memory) and recognition memory. In Experiment 1, rats were first familiarized with sets of objects and then given pairs of different, familiar objects to explore. For the recency test group, each object in a pair was separated by 110 min in the time between their previous presentations. For the recency control test, each object in a pair was separated by less than a 1 min between their prior presentations. Temporal discrimination of the objects correlated with c-fos activity in the recency test group in several sites, including area Te2, the perirhinal cortex, lateral entorhinal cortex, as well as the dentate gyrus, hippocampal fields CA3 and CA1. For both the test and control conditions, network models were derived using structural equation modeling. The recency test model emphasized serial connections from the perirhinal cortex to lateral entorhinal cortex and then to the CA1 subfield. The recency control condition involved more parallel pathways, but again highlighted CA1 within the hippocampus. Both models contrasted with those derived from tests of object recognition (Experiment 2), because stimulus novelty was associated with pathways from the perirhinal cortex to lateral entorhinal cortex that then involved both the dentate gyrus (and CA3) and CA1 in parallel. The present findings implicate CA1 for the processing of familiar stimuli, including recency discriminations, while the dentate gyrus and CA3 pathways are recruited when the perirhinal cortex signals novel stimuli. PMID:24933661

  7. Cellular and ionic mechanisms underlying the effects of cilostazol, milrinone, and isoproterenol to suppress arrhythmogenesis in an experimental model of early repolarization syndrome.

    Science.gov (United States)

    Patocskai, Bence; Barajas-Martinez, Hector; Hu, Dan; Gurabi, Zsolt; Koncz, István; Antzelevitch, Charles

    2016-06-01

    Early repolarization syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and ventricular fibrillation, leading to sudden cardiac death. The present study tests the hypothesis that the transient outward potassium current (Ito)-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS. Transmembrane action potentials (APs) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left ventricular (LV) wedge preparations, together with a transmural pseudo-electrocardiogram. The Ito agonist NS5806 (7-15 μM) and L-type calcium current (ICa) blocker verapamil (2-3 μM) were used to induce an early repolarization pattern and PVT. After stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase 2 reentry and PVT. Arrhythmic activity was suppressed in 7 of 8 preparations by cilostazol (10 μM), 6 of 7 by milrinone (2.5 μM), and 7 of 8 by isoproterenol (0.1-1 μM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 μM) and milrinone (2.5 μM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa. Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current during the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying the development of phase 2 reentry and ventricular tachycardia/ventricular fibrillation. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  8. Early Response Roles for Prolactin Cortisol and Circulating and Cellular Levels of Heat Shock Proteins 72 and 90α in Severe Sepsis and SIRS

    Directory of Open Access Journals (Sweden)

    K. Vardas

    2014-01-01

    Full Text Available Objective. To evaluate the early heat shock protein (HSP and hormonal stress response of intensive care unit (ICU patients with severe sepsis/septic shock (SS or systemic inflammatory response syndrome (SIRS compared to healthy subjects (H. Methods. Patients with early (first 48 hrs SS (n=29 or SIRS (n=29 admitted to a university ICU and 16 H were enrolled in the study. Serum prolactin, cortisol, and plasma ACTH were determined using immunoassay analyzers. ELISA was used to evaluate extracellular HSPs (eHSP90α, eHSP72 and interleukins. Mean fluorescence intensity (MFI values for intracellular HSPs (iHSP72, iHSP90α were measured using 4-colour flow-cytometry. Results. Prolactin, cortisol, and eHSP90α levels were significantly increased in SS patients compared to SIRS and H (P<0.003. ACTH and eHSP72 were significantly higher in SS and SIRS compared to H (P<0.005. SS monocytes expressed lower iHSP72 MFI levels compared to H (P=0.03. Prolactin was related with SAPS III and APACHE II scores and cortisol with eHSP90α, IL-6, and lactate (P<0.05. In SS and SIRS eHSP90α was related with eHSP72, IL-6, and IL-10. Conclusion. Prolactin, apart from cortisol, may have a role in the acute stress response in severe sepsis. In this early-onset inflammatory process, cortisol relates to eHSP90α, monocytes suppress iHSP72, and plasma eHSP72 increases.

  9. Deep RNA sequencing reveals hidden features and dynamics of early gene transcription in Paramecium bursaria chlorella virus 1.

    Directory of Open Access Journals (Sweden)

    Guillaume Blanc

    Full Text Available Paramecium bursaria chlorella virus 1 (PBCV-1 is the prototype of the genus Chlorovirus (family Phycodnaviridae that infects the unicellular, eukaryotic green alga Chlorella variabilis NC64A. The 331-kb PBCV-1 genome contains 416 major open reading frames. A mRNA-seq approach was used to analyze PBCV-1 transcriptomes at 6 progressive times during the first hour of infection. The alignment of 17 million reads to the PBCV-1 genome allowed the construction of single-base transcriptome maps. Significant transcription was detected for a subset of 50 viral genes as soon as 7 min after infection. By 20 min post infection (p.i., transcripts were detected for most PBCV-1 genes and transcript levels continued to increase globally up to 60 min p.i., at which time 41% or the poly (A+-containing RNAs in the infected cells mapped to the PBCV-1 genome. For some viral genes, the number of transcripts in the latter time points (20 to 60 min p.i. was much higher than that of the most highly expressed host genes. RNA-seq data revealed putative polyadenylation signal sequences in PBCV-1 genes that were identical to the polyadenylation signal AAUAAA of green algae. Several transcripts have an RNA fragment excised. However, the frequency of excision and the resulting putative shortened protein products suggest that most of these excision events have no functional role but are probably the result of the activity of misled splicesomes.

  10. Environmental proteomics reveals early microbial community responses to biostimulation at a uranium- and nitrate-contaminated site

    Energy Technology Data Exchange (ETDEWEB)

    Chourey, Karuna [ORNL; Nissen, Silke [ORNL; Vishnivetskaya, T. [University of Tennessee, Knoxville (UTK); Shah, Manesh B [ORNL; Pffifner, Susan [University of Tennessee, Knoxville (UTK); Hettich, Robert {Bob} L [ORNL; Loeffler, Frank E [ORNL

    2013-01-01

    High performance mass spectrometry instrumentation coupled with improved protein extraction techniques enable metaproteomics to identify active members of soil and groundwater microbial communities. Metaproteomics workflows were applied to study the initial responses (i.e., 4 days post treatment) of the indigenous aquifer microbiota to biostimulation with emulsified vegetable oil (EVO) at a uranium-contaminated site. Members of the Betaproteobacteria (i.e., Dechloromonas, Ralstonia, Rhodoferax, Polaromonas, Delftia, Chromobacterium) and Firmicutes dominated the biostimulated aquifer community. Proteome characterization revealed distinct differences in protein expression between the microbial biomass collected from groundwater influenced by biostimulation and groundwater collected up-gradient of the EVO injection points. In particular, proteins involved in ammonium assimilation, EVO degradation, and polyhydroxybutyrate (PHB) granule formation were prominent following biostimulation. Interestingly, the atypical NosZ of a Dechloromonas sp. was highly expressed suggesting active nitrous oxide (N2O) respiration. c-type cytochromes were barely detected, as was citrate synthase, a biomarker for hexavalent uranium reduction activity, suggesting that metal reduction has not commenced 4 days post EVO delivery. Environmental metaproteomics identified microbial community responses to biostimulation and elucidated active pathways demonstrating the value of this technique for complementing nucleic acid-based approaches.

  11. Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.

    Directory of Open Access Journals (Sweden)

    Dogus Murat Altintas

    Full Text Available BACKGROUND: Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa among androgen-regulated genes (ARG and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely give rise to cancer. METHODS: ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1. RESULTS AND DISCUSSION: By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91 and DLX1 (0.94. CONCLUSIONS: We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could

  12. Exome sequencing analysis reveals variants in primary immunodeficiency genes in patients with very early onset inflammatory bowel disease.

    Science.gov (United States)

    Kelsen, Judith R; Dawany, Noor; Moran, Christopher J; Petersen, Britt-Sabina; Sarmady, Mahdi; Sasson, Ariella; Pauly-Hubbard, Helen; Martinez, Alejandro; Maurer, Kelly; Soong, Joanne; Rappaport, Eric; Franke, Andre; Keller, Andreas; Winter, Harland S; Mamula, Petar; Piccoli, David; Artis, David; Sonnenberg, Gregory F; Daly, Mark; Sullivan, Kathleen E; Baldassano, Robert N; Devoto, Marcella

    2015-11-01

    Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed at 5 years of age or younger, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development. Patients with VEO-IBD and parents (when available) were recruited from the Children's Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (age, 3 wk to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by postprocessing and variant calling. After functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency less than 0.1%, and scaled combined annotation-dependent depletion scores of 10 or less. We focused on genes associated with primary immunodeficiencies and related pathways. An additional 210 exome samples from patients with pediatric IBD (n = 45) or adult-onset Crohn's disease (n = 20) and healthy individuals (controls, n = 145) were obtained from the University of Kiel, Germany, and used as control groups. Four hundred genes and regions associated with primary immunodeficiency, covering approximately 6500 coding exons totaling more than 1 Mbp of coding sequence, were selected from the whole-exome data. Our analysis showed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19. In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the

  13. Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis.

    Directory of Open Access Journals (Sweden)

    Britta Stadelmann

    2016-03-01

    Full Text Available The metacestode (larval stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE, a very severe and in many cases incurable disease. To date, benzimidazoles such as albendazole and mebendazole are the only approved chemotherapeutical treatment options. Benzimidazoles inhibit metacestode proliferation, but do not act parasiticidal. Thus, benzimidazoles have to be taken a lifelong, can cause adverse side effects such as hepatotoxicity, and are ineffective in some patients. We here describe a newly developed screening cascade for the evaluation of the in vitro efficacy of new compounds that includes assessment of parasiticidal activity. The Malaria Box from Medicines for Malaria Venture (MMV, comprised of 400 commercially available chemicals that show in vitro activity against Plasmodium falciparum, was repurposed. Primary screening was carried out at 10 μM by employing the previously described PGI assay, and resulted in the identification of 24 compounds that caused physical damage in metacestodes. Seven out of these 24 drugs were also active at 1 μM. Dose-response assays revealed that only 2 compounds, namely MMV665807 and MMV665794, exhibited an EC50 value below 5 μM. Assessments using human foreskin fibroblasts and Reuber rat hepatoma cells showed that the salicylanilide MMV665807 was less toxic for these two mammalian cell lines than for metacestodes. The parasiticidal activity of MMV665807 was then confirmed using isolated germinal layer cell cultures as well as metacestode vesicles by employing viability assays, and its effect on metacestodes was morphologically evaluated by electron microscopy. However, both oral and intraperitoneal application of MMV665807 to mice experimentally infected with E. multilocularis metacestodes did not result in any reduction of the parasite load.

  14. Cellular Angiofibroma of the Nasopharynx.

    Science.gov (United States)

    Erdur, Zülküf Burak; Yener, Haydar Murat; Yilmaz, Mehmet; Karaaltin, Ayşegül Batioğlu; Inan, Hakki Caner; Alaskarov, Elvin; Gozen, Emine Deniz

    2017-11-01

    Angiofibroma is a common tumor of the nasopharynx region but cellular type is extremely rare in head and neck. A 13-year-old boy presented with frequent epistaxis and nasal obstruction persisting for 6 months. According to the clinical symptoms and imaging studies juvenile angiofibroma was suspected. Following angiographic embolization total excision of the lesion by midfacial degloving approach was performed. Histological examination revealed that the tumor consisted of staghorn blood vessels and irregular fibrous stroma. Stellate fibroblasts with small pyknotic to large vesicular nuclei were seen in a highly cellular stroma. These findings identified cellular angiofibroma mimicking juvenile angiofibroma. This article is about a very rare patient of cellular angiofibroma of nasopharynx.

  15. RNA-Seq reveals the dynamic and diverse features of digestive enzymes during early development of Pacific white shrimp Litopenaeus vannamei.

    Science.gov (United States)

    Wei, Jiankai; Zhang, Xiaojun; Yu, Yang; Li, Fuhua; Xiang, Jianhai

    2014-09-01

    The Pacific white shrimp (Litopenaeus vannamei), with high commercial value, has a typical metamorphosis pattern by going through embryo, nauplius, zoea, mysis and postlarvae during early development. Its diets change continually in this period, and a high mortality of larvae also occurs in this period. Since there is a close relationship between diets and digestive enzymes, a comprehensive investigation about the types and expression patterns of all digestive enzyme genes during early development of L. vannamei is of considerable significance for shrimp diets and larvae culture. Using RNA-Seq data, the types and expression characteristics of the digestive enzyme genes were analyzed during five different development stages (embryo, nauplius, zoea, mysis and postlarvae) in L. vannamei. Among the obtained 66,815 unigenes, 296 were annotated as 16 different digestive enzymes including five types of carbohydrase, seven types of peptidase and four types of lipase. Such a diverse suite of enzymes illustrated the capacity of L. vannamei to exploit varied diets to fit their nutritional requirements. The analysis of their dynamic expression patterns during development also indicated the importance of transcriptional regulation to adapt to the diet transition. Our study revealed the diverse and dynamic features of digestive enzymes during early development of L. vannamei. These results would provide support to better understand the physiological changes during diet transition. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Cellular and Ionic Mechanisms Underlying Effects of Cilostazol, Milrinone and Isoproterenol to Suppress Arrhythmogenesis in an Experimental Model of Early Repolarization Syndrome

    Science.gov (United States)

    Patocskai, Bence; Barajas-Martinez, Hector; Hu, Dan; Gurabi, Zsolt; Koncz, István; Antzelevitch, Charles

    2016-01-01

    Background Early Repolarization Syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and fibrillation (VF), leading to sudden cardiac death. Objective The present study tests the hypothesis that the Ito-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS. Methods Transmembrane action potentials (AP) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left-ventricular (LV) wedge preparations, together with a transmural pseudo-ECG. The Ito-agonist NS5806 (7–15 μM) and ICa-blocker verapamil (2–3 uM) were used to induce an ER pattern and PVT. Results Following stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase-2-reentry (P2R) and PVT. Arrhythmic activity was suppressed in 7/8 preparations by cilostazol (10 μM), 6/7 by milrinone (2.5 μM) and 7/8 by isoproterenol (0.1–1μM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 μM) and milrinone (2.5 μM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa. Conclusions Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current in the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying development of P2R and VT/VF. PMID:26820510

  17. Cellular Automata and the Humanities.

    Science.gov (United States)

    Gallo, Ernest

    1994-01-01

    The use of cellular automata to analyze several pre-Socratic hypotheses about the evolution of the physical world is discussed. These hypotheses combine characteristics of both rigorous and metaphoric language. Since the computer demands explicit instructions for each step in the evolution of the automaton, such models can reveal conceptual…

  18. Lobular and cellular patterns of early hepatic glycogen deposition in the rat as observed by light and electron microscopic radioautography after injection of 3H-galactose

    International Nuclear Information System (INIS)

    Michaels, J.E.; Hung, J.T.; Garfield, S.A.; Cardell, R.R. Jr.

    1984-01-01

    Very low hepatic glycogen levels are achieved by overnight fasting of adrenalectomized (ADX) rats. Subsequent injection of dexamethasone (DEX), a synthetic glucocorticoid, stimulates marked increases in glycogen synthesis. Using this system and injecting 3 H-galactose as a glycogen precursor 1 hr prior to sacrifice, the intralobular and intracellular patterns of labeled glycogen deposition were studied by light (LM) and electron (EM) microscopic radioautography. LM radioautography revealed that 1 hr after DEX treatment, labeling patterns for both periportal and centrilobular hepatocytes resembled those in rats with no DEX treatment: 18% of the hepatocytes were unlabeled, and 82% showed light labeling. Two hours after treatment with DEX, 14% of the hepatocytes remained unlabeled, and 78% were lightly labeled; however, 8% of the cells, located randomly throughout the lobule, were intensely labeled. An increased number of heavily labeled cells (26%) appeared 3 hr after DEX treatment; and by 5 hr 91% of the hepatocytes were intensely labeled. Label over the periportal cells at this time was aggregated, whereas centrilobular cells displayed dispersed label. EM radioautographs showed that 2 to 3 hr after DEX injection initial labeling of hepatocytes, regardless of their intralobular location, occurred over foci of smooth endoplasmic reticulum (SER) and small electron-dense particles of presumptive glycogen, and in areas of SER and distinct glycogen particles. After 5 hrs of treatment with DEX, the intracellular distribution of label reflected the glycogen patterns characteristic of periportal or centrilobular regions

  19. Switch of Sensitivity Dynamics Revealed with DyGloSA Toolbox for Dynamical Global Sensitivity Analysis as an Early Warning for System's Critical Transition

    Science.gov (United States)

    Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

    2013-01-01

    Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA – a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits. PMID:24367574

  20. Switch of sensitivity dynamics revealed with DyGloSA toolbox for dynamical global sensitivity analysis as an early warning for system's critical transition.

    Science.gov (United States)

    Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

    2013-01-01

    Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA - a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits.

  1. Successful in vitro expansion and differentiation of cord blood derived CD34+ cells into early endothelial progenitor cells reveals highly differential gene expression.

    Directory of Open Access Journals (Sweden)

    Ingo Ahrens

    Full Text Available Endothelial progenitor cells (EPCs can be purified from peripheral blood, bone marrow or cord blood and are typically defined by a limited number of cell surface markers and a few functional tests. A detailed in vitro characterization is often restricted by the low cell numbers of circulating EPCs. Therefore in vitro culturing and expansion methods are applied, which allow at least distinguishing two different types of EPCs, early and late EPCs. Herein, we describe an in vitro culture technique with the aim to generate high numbers of phenotypically, functionally and genetically defined early EPCs from human cord blood. Characterization of EPCs was done by flow cytometry, immunofluorescence microscopy, colony forming unit (CFU assay and endothelial tube formation assay. There was an average 48-fold increase in EPC numbers. EPCs expressed VEGFR-2, CD144, CD18, and CD61, and were positive for acetylated LDL uptake and ulex lectin binding. The cells stimulated endothelial tube formation only in co-cultures with mature endothelial cells and formed CFUs. Microarray analysis revealed highly up-regulated genes, including LL-37 (CAMP, PDK4, and alpha-2-macroglobulin. In addition, genes known to be associated with cardioprotective (GDF15 or pro-angiogenic (galectin-3 properties were also significantly up-regulated after a 72 h differentiation period on fibronectin. We present a novel method that allows to generate high numbers of phenotypically, functionally and genetically characterized early EPCs. Furthermore, we identified several genes newly linked to EPC differentiation, among them LL-37 (CAMP was the most up-regulated gene.

  2. Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice

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    Grau Georges E

    2007-12-01

    Full Text Available Abstract Background Microarray analyses allow the identification and assessment of molecular signatures in whole tissues undergoing pathological processes. To better understand cerebral malaria pathogenesis, we investigated intra-cerebral gene-expression profiles in well-defined genetically cerebral malaria-resistant (CM-R and CM-susceptible (CM-S mice, upon infection by Plasmodium berghei ANKA (PbA. We investigated mouse transcriptional responses at early and late stages of infection by use of cDNA microarrays. Results Through a rigorous statistical approach with multiple testing corrections, we showed that PbA significantly altered brain gene expression in CM-R (BALB/c, and in CM-S (CBA/J and C57BL/6 mice, and that 327 genes discriminated between early and late infection stages, between mouse strains, and between CM-R and CM-S mice. We further identified 104, 56, 84 genes with significant differential expression between CM-R and CM-S mice on days 2, 5, and 7 respectively. The analysis of their functional annotation indicates that genes involved in metabolic energy pathways, the inflammatory response, and the neuroprotection/neurotoxicity balance play a major role in cerebral malaria pathogenesis. In addition, our data suggest that cerebral malaria and Alzheimer's disease may share some common mechanisms of pathogenesis, as illustrated by the accumulation of β-amyloid proteins in brains of CM-S mice, but not of CM-R mice. Conclusion Our microarray analysis highlighted marked changes in several molecular pathways in CM-S compared to CM-R mice, particularly at early stages of infection. This study revealed some promising areas for exploration that may both provide new insight into the knowledge of CM pathogenesis and the development of novel therapeutic strategies.

  3. The origin of snakes: revealing the ecology, behavior, and evolutionary history of early snakes using genomics, phenomics, and the fossil record.

    Science.gov (United States)

    Hsiang, Allison Y; Field, Daniel J; Webster, Timothy H; Behlke, Adam D B; Davis, Matthew B; Racicot, Rachel A; Gauthier, Jacques A

    2015-05-20

    The highly derived morphology and astounding diversity of snakes has long inspired debate regarding the ecological and evolutionary origin of both the snake total-group (Pan-Serpentes) and crown snakes (Serpentes). Although speculation abounds on the ecology, behavior, and provenance of the earliest snakes, a rigorous, clade-wide analysis of snake origins has yet to be attempted, in part due to a dearth of adequate paleontological data on early stem snakes. Here, we present the first comprehensive analytical reconstruction of the ancestor of crown snakes and the ancestor of the snake total-group, as inferred using multiple methods of ancestral state reconstruction. We use a combined-data approach that includes new information from the fossil record on extinct crown snakes, new data on the anatomy of the stem snakes Najash rionegrina, Dinilysia patagonica, and Coniophis precedens, and a deeper understanding of the distribution of phenotypic apomorphies among the major clades of fossil and Recent snakes. Additionally, we infer time-calibrated phylogenies using both new 'tip-dating' and traditional node-based approaches, providing new insights on temporal patterns in the early evolutionary history of snakes. Comprehensive ancestral state reconstructions reveal that both the ancestor of crown snakes and the ancestor of total-group snakes were nocturnal, widely foraging, non-constricting stealth hunters. They likely consumed soft-bodied vertebrate and invertebrate prey that was subequal to head size, and occupied terrestrial settings in warm, well-watered, and well-vegetated environments. The snake total-group - approximated by the Coniophis node - is inferred to have originated on land during the middle Early Cretaceous (~128.5 Ma), with the crown-group following about 20 million years later, during the Albian stage. Our inferred divergence dates provide strong evidence for a major radiation of henophidian snake diversity in the wake of the Cretaceous-Paleogene (K

  4. Transcriptome analyses of rhesus monkey preimplantation embryos reveal a reduced capacity for DNA double-strand break repair in primate oocytes and early embryos

    Science.gov (United States)

    Wang, Xinyi; Liu, Denghui; He, Dajian; Suo, Shengbao; Xia, Xian; He, Xiechao; Han, Jing-Dong J.; Zheng, Ping

    2017-01-01

    Preimplantation embryogenesis encompasses several critical events including genome reprogramming, zygotic genome activation (ZGA), and cell-fate commitment. The molecular basis of these processes remains obscure in primates in which there is a high rate of embryo wastage. Thus, understanding the factors involved in genome reprogramming and ZGA might help reproductive success during this susceptible period of early development and generate induced pluripotent stem cells with greater efficiency. Moreover, explaining the molecular basis responsible for embryo wastage in primates will greatly expand our knowledge of species evolution. By using RNA-seq in single and pooled oocytes and embryos, we defined the transcriptome throughout preimplantation development in rhesus monkey. In comparison to archival human and mouse data, we found that the transcriptome dynamics of monkey oocytes and embryos were very similar to those of human but very different from those of mouse. We identified several classes of maternal and zygotic genes, whose expression peaks were highly correlated with the time frames of genome reprogramming, ZGA, and cell-fate commitment, respectively. Importantly, comparison of the ZGA-related network modules among the three species revealed less robust surveillance of genomic instability in primate oocytes and embryos than in rodents, particularly in the pathways of DNA damage signaling and homology-directed DNA double-strand break repair. This study highlights the utility of monkey models to better understand the molecular basis for genome reprogramming, ZGA, and genomic stability surveillance in human early embryogenesis and may provide insights for improved homologous recombination-mediated gene editing in monkey. PMID:28223401

  5. An early function of the adenoviral E1B 55 kDa protein is required for the nuclear relocalization of the cellular p53 protein in adenovirus-infected normal human cells

    International Nuclear Information System (INIS)

    Cardoso, F.M.; Kato, Sayuri E.M.; Huang Wenying; Flint, S. Jane; Gonzalez, Ramon A.

    2008-01-01

    It is well established that the human subgroup C adenovirus type 5 (Ad5) E1B 55 kDa protein can regulate the activity and concentration of the cellular tumor suppressor, p53. However, the contribution(s) of these functions of the E1B protein to viral reproduction remains unclear. To investigate this issue, we examined properties of p53 in normal human cells infected by E1B mutant viruses that display defective entry into the late phase or viral late mRNA export. The steady-state concentrations of p53 were significantly higher in cells infected by the E1B 55 kDa null mutant Hr6 or three mutants carrying small insertions in the E1B 55 kDa protein coding sequence than in Ad5-infected cells. Nevertheless, none of the mutants induced apoptosis in infected cells. Rather, the localization of p53 to E1B containing nuclear sites observed during infection by Ad5 was prevented by mutations that impair interaction of the E1B protein with p53 and/or with the E4 Orf6 protein. These results indicate that the E1B protein fulfills an early function that correlates efficient entry into the late phase with the localization of E1B and p53 in the nucleus of Ad5-infected normal human cells

  6. Genome-resolved metaproteomic characterization of preterm infant gut microbiota development reveals species-specific metabolic shifts and variabilities during early life.

    Science.gov (United States)

    Xiong, Weili; Brown, Christopher T; Morowitz, Michael J; Banfield, Jillian F; Hettich, Robert L

    2017-07-10

    ) utilization and short-chain fatty acid production. Overall, this study reports species-specific proteome profiles and metabolic functions of human gut microbiota during early colonization. In particular, our work contributes to reveal microbiota-associated shifts and variations in the metabolism of three major nutrient sources and short-chain fatty acid during colonization of preterm infant gut.

  7. Spontaneous Recovery from Unresponsive Wakefulness Syndrome to a Minimally Conscious State: Early Structural Changes Revealed by 7-T Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Xufei Tan

    2018-01-01

    Full Text Available BackgroundDetermining the early changes of brain structure that occur from vegetative state/unresponsive wakefulness syndrome (VS/UWS to a minimally conscious state (MCS is important for developing our understanding of the processes underlying disorders of consciousness (DOC, particularly during spontaneous recovery from severe brain damage.ObjectiveThis study used a multi-modal neuroimaging approach to investigate early structural changes during spontaneous recovery from VS/UWS to MCS.MethodsThe Coma Recovery Scale-Revised (CRS-R score, 24-h electroencephalography (EEG, and ultra-high field 7-T magnetic resonance imaging were used to investigate a male patient with severe brain injury when he was in VS/UWS compared to MCS. Using white matter connectometry analysis, fibers in MCS were compared with the same fibers in VS/UWS. Whole-brain analysis was used to compare all fibers showing a 10% increase in density with each other as a population.ResultsBased on connectometry analysis, the number of fibers with increased density, and the magnitude of increase in MCS compared to VS/UWS, was greatest in the area of the temporoparietal junction (TPJ, and was mostly located in the right hemisphere. These results are in accordance with the active areas observed on 24-h EEG recordings. Moreover, analysis of different fibers across the brain, showing at least a 10% increase in density, revealed that altered white matter connections with higher discriminative weights were located within or across visual-related areas, including the cuneus_R, calcarine_R, occipital_sup_R, and occipital_mid_R. Furthermore, the temporal_mid_R, which is related to the auditory cortex, showed the highest increase in connectivity to other areas. This was consistent with improvements in the visual and auditory components of the CRS-R, which were greater than other improvements.ConclusionThese results provide evidence to support the important roles for the TPJ and the visual and

  8. Proteomic analysis of stipe explants reveals differentially expressed proteins involved in early direct somatic embryogenesis of the tree fern Cyathea delgadii Sternb.

    Science.gov (United States)

    Domżalska, Lucyna; Kędracka-Krok, Sylwia; Jankowska, Urszula; Grzyb, Małgorzata; Sobczak, Mirosław; Rybczyński, Jan J; Mikuła, Anna

    2017-05-01

    Using cyto-morphological analysis of somatic embryogenesis (SE) in the tree fern Cyathea delgadii as a guide, we performed a comparative proteomic analysis in stipe explants undergoing direct SE. Plant material was cultured on hormone-free medium supplemented with 2% sucrose. Phenol extracted proteins were separated using two-dimensional gel electrophoresis (2-DE) and mass spectrometry was performed for protein identification. A total number of 114 differentially regulated proteins was identified during early SE, i.e. when the first cell divisions started and several-cell pro-embryos were formed. Proteins were assigned to seven functional categories: carbohydrate metabolism, protein metabolism, cell organization, defense and stress responses, amino acid metabolism, purine metabolism, and fatty acid metabolism. Carbohydrate and protein metabolism were found to be the most sensitive SE functions with the greatest number of alterations in the intensity of spots in gel. Differences, especially in non-enzymatic and structural protein abundance, are indicative for cell organization, including cytoskeleton rearrangement and changes in cell wall components. The highest induced changes concern those enzymes related to fatty acid metabolism. Global analysis of the proteome reveals several proteins that can represent markers for the first 16days of SE induction and expression in fern. The findings of this research improve the understanding of molecular processes involved in direct SE in C. delgadii. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Paleoarchean bedrock lithologies across the Makhonjwa Mountains of South Africa and Swaziland linked to geochemical, magnetic and tectonic data reveal early plate tectonic genes flanking subduction margins

    Directory of Open Access Journals (Sweden)

    Maarten de Wit

    2018-05-01

    Full Text Available The Makhonjwa Mountains, traditionally referred to as the Barberton Greenstone Belt, retain an iconic Paleoarchean archive against which numerical models of early earth geodynamics can be tested. We present new geologic and structural maps, geochemical plots, geo- and thermo-chronology, and geophysical data from seven silicic, mafic to ultramafic complexes separated by major shear systems across the southern Makhonjwa Mountains. All reveal signs of modern oceanic back-arc crust and subduction-related processes. We compare the rates of processes determined from this data and balance these against plate tectonic and plume related models. Robust rates of both horizontal and vertical tectonic processes derived from the Makhonjwa Mountain complexes are similar, well within an order of magnitude, to those encountered across modern oceanic and orogenic terrains flanking Western Pacific-like subduction zones. We conclude that plate tectonics and linked plate-boundary processes were well established by 3.2–3.6 Ga. Our work provides new constraints for modellers with rates of a ‘basket’ of processes against which to test Paleoarchean geodynamic models over a time period close to the length of the Phanerozoic. Keywords: Paleoarchean, Barberton Greenstone Belt, Onverwacht Suite, Geologic bedrock and structural maps, Geochemistry and geophysics, Plate tectonics

  10. Infection and cellular defense dynamics in a novel 17β-estradiol murine model of chronic human group B streptococcus genital tract colonization reveal a role for hemolysin in persistence and neutrophil accumulation.

    Science.gov (United States)

    Carey, Alison J; Tan, Chee Keong; Mirza, Shaper; Irving-Rodgers, Helen; Webb, Richard I; Lam, Alfred; Ulett, Glen C

    2014-02-15

    Genital tract carriage of group B streptococcus (GBS) is prevalent among adult women; however, the dynamics of chronic GBS genital tract carriage, including how GBS persists in this immunologically active host niche long term, are not well defined. To our knowledge, in this study, we report the first animal model of chronic GBS genital tract colonization using female mice synchronized into estrus by delivery of 17β-estradiol prior to intravaginal challenge with wild-type GBS 874391. Cervicovaginal swabs, which were used to measure bacterial persistence, showed that GBS colonized the vaginal mucosa of mice at high numbers (10(6)-10(7) CFU/swab) for at least 90 d. Cellular and histological analyses showed that chronic GBS colonization of the murine genital tract caused significant lymphocyte and PMN cell infiltrates, which were localized to the vaginal mucosal surface. Long-term colonization was independent of regular hormone cycling. Immunological analyses of 23 soluble proteins related to chemotaxis and inflammation showed that the host response to GBS in the genital tract comprised markers of innate immune activation including cytokines such as GM-CSF and TNF-α. A nonhemolytic isogenic mutant of GBS 874391, Δcyle9, was impaired for colonization and was associated with amplified local PMN responses. Induction of DNA neutrophil extracellular traps, which was observed in GBS-infected human PMNs in vitro in a hemolysin-dependent manner, appeared to be part of this response. Overall, this study defines key infection dynamics in a novel murine model of chronic GBS genital tract colonization and establishes previously unknown cellular and soluble defense responses to GBS in the female genital tract.

  11. Analysis of a vinculin homolog in a sponge (phylum Porifera) reveals that vertebrate-like cell adhesions emerged early in animal evolution.

    Science.gov (United States)

    Miller, Phillip W; Pokutta, Sabine; Mitchell, Jennyfer M; Chodaparambil, Jayanth V; Clarke, D Nathaniel; Nelson, William; Weis, William I; Nichols, Scott A

    2018-06-07

    The evolution of cell adhesion mechanisms in animals facilitated the assembly of organized multicellular tissues. Studies in traditional animal models have revealed two predominant adhesion structures, the adherens junction (AJ) and focal adhesions (FAs), which are involved in the attachment of neighboring cells to each other and to the secreted extracellular matrix (ECM), respectively. The AJ (containing cadherins and catenins) and FAs (comprising integrins, talin, and paxillin) differ in protein composition, but both junctions contain the actin-binding protein vinculin. The near ubiquity of these structures in animals suggests that AJ and FAs evolved early, possibly coincident with multicellularity. However, a challenge to this perspective is that previous studies of sponges-a divergent animal lineage-indicate that their tissues are organized primarily by an alternative, sponge-specific cell adhesion mechanism called "aggregation factor." In this study, we examined the structure, biochemical properties, and tissue localization of a vinculin ortholog in the sponge Oscarella pearsei ( Op ). Our results indicate that Op vinculin localizes to both cell-cell and cell-ECM contacts and has biochemical and structural properties similar to those of vertebrate vinculin. We propose that Op vinculin played a role in cell adhesion and tissue organization in the last common ancestor of sponges and other animals. These findings provide compelling evidence that sponge tissues are indeed organized like epithelia in other animals and support the notion that AJ- and FA-like structures extend to the earliest periods of animal evolution. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL).

    Science.gov (United States)

    Preston, Ioana R; Roberts, Kari E; Miller, Dave P; Sen, Ginny P; Selej, Mona; Benton, Wade W; Hill, Nicholas S; Farber, Harrison W

    2015-12-22

    Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. © 2015 The Authors.

  13. Mass Cytometry Analysis Reveals the Landscape and Dynamics of CD32a+ CD4+ T Cells From Early HIV Infection to Effective cART.

    Science.gov (United States)

    Coindre, Sixtine; Tchitchek, Nicolas; Alaoui, Lamine; Vaslin, Bruno; Bourgeois, Christine; Goujard, Cecile; Avettand-Fenoel, Veronique; Lecuroux, Camille; Bruhns, Pierre; Le Grand, Roger; Beignon, Anne-Sophie; Lambotte, Olivier; Favier, Benoit

    2018-01-01

    CD32a has been proposed as a specific marker of latently HIV-infected CD4 + T cells. However, CD32a was recently found to be expressed on CD4 + T cells of healthy donors, leading to controversy on the relevance of this marker in HIV persistence. Here, we used mass cytometry to characterize the landscape and variation in the abundance of CD32a + CD4 + T cells during HIV infection. To this end, we analyzed CD32a + CD4 + T cells in primary HIV infection before and after effective combination antiretroviral therapy (cART) and in healthy donors. We found that CD32a + CD4 + T cells include heterogeneous subsets that are differentially affected by HIV infection. Our analysis revealed that naive ( N ), central memory ( CM ), and effector/memory ( Eff/Mem ) CD32a + CD4 + T-cell clusters that co-express LILRA2- and CD64-activating receptors were more abundant in primary HIV infection and cART stages. Conversely, LILRA2 - CD32a + CD4 + T-cell clusters of either the T N , T CM , or T Eff/Mem phenotype were more abundant in healthy individuals. Finally, an activated CD32a + CD4 + T Eff/Mem cell cluster co-expressing LILRA2, CD57, and NKG2C was more abundant in all HIV stages, particularly during primary HIV infection. Overall, our data show that multiple abundance modifications of CD32a + CD4 + T-cell subsets occur in the early phase of HIV infection, and some of which are conserved after effective cART. Our study brings a better comprehension of the relationship between CD32a expression and CD4 + T cells during HIV infection.

  14. Mass Cytometry Analysis Reveals the Landscape and Dynamics of CD32a+ CD4+ T Cells From Early HIV Infection to Effective cART

    Directory of Open Access Journals (Sweden)

    Sixtine Coindre

    2018-06-01

    Full Text Available CD32a has been proposed as a specific marker of latently HIV-infected CD4+ T cells. However, CD32a was recently found to be expressed on CD4+ T cells of healthy donors, leading to controversy on the relevance of this marker in HIV persistence. Here, we used mass cytometry to characterize the landscape and variation in the abundance of CD32a+ CD4+ T cells during HIV infection. To this end, we analyzed CD32a+ CD4+ T cells in primary HIV infection before and after effective combination antiretroviral therapy (cART and in healthy donors. We found that CD32a+ CD4+ T cells include heterogeneous subsets that are differentially affected by HIV infection. Our analysis revealed that naive (N, central memory (CM, and effector/memory (Eff/Mem CD32a+ CD4+ T-cell clusters that co-express LILRA2- and CD64-activating receptors were more abundant in primary HIV infection and cART stages. Conversely, LILRA2− CD32a+ CD4+ T-cell clusters of either the TN, TCM, or TEff/Mem phenotype were more abundant in healthy individuals. Finally, an activated CD32a+ CD4+ TEff/Mem cell cluster co-expressing LILRA2, CD57, and NKG2C was more abundant in all HIV stages, particularly during primary HIV infection. Overall, our data show that multiple abundance modifications of CD32a+ CD4+ T-cell subsets occur in the early phase of HIV infection, and some of which are conserved after effective cART. Our study brings a better comprehension of the relationship between CD32a expression and CD4+ T cells during HIV infection.

  15. Wireless Cellular Mobile Communications

    OpenAIRE

    Zalud, V.

    2002-01-01

    In this article is briefly reviewed the history of wireless cellular mobile communications, examined the progress in current second generation (2G) cellular standards and discussed their migration to the third generation (3G). The European 2G cellular standard GSM and its evolution phases GPRS and EDGE are described somewhat in detail. The third generation standard UMTS taking up on GSM/GPRS core network and equipped with a new advanced access network on the basis of code division multiple ac...

  16. Biomechanics of cellular solids.

    Science.gov (United States)

    Gibson, Lorna J

    2005-03-01

    Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

  17. Linearizable cellular automata

    International Nuclear Information System (INIS)

    Nobe, Atsushi; Yura, Fumitaka

    2007-01-01

    The initial value problem for a class of reversible elementary cellular automata with periodic boundaries is reduced to an initial-boundary value problem for a class of linear systems on a finite commutative ring Z 2 . Moreover, a family of such linearizable cellular automata is given

  18. The complete chloroplast DNA sequence of the green alga Oltmannsiellopsis viridis reveals a distinctive quadripartite architecture in the chloroplast genome of early diverging ulvophytes

    Directory of Open Access Journals (Sweden)

    Lemieux Claude

    2006-02-01

    Full Text Available Abstract Background The phylum Chlorophyta contains the majority of the green algae and is divided into four classes. The basal position of the Prasinophyceae has been well documented, but the divergence order of the Ulvophyceae, Trebouxiophyceae and Chlorophyceae is currently debated. The four complete chloroplast DNA (cpDNA sequences presently available for representatives of these classes have revealed extensive variability in overall structure, gene content, intron composition and gene order. The chloroplast genome of Pseudendoclonium (Ulvophyceae, in particular, is characterized by an atypical quadripartite architecture that deviates from the ancestral type by a large inverted repeat (IR featuring an inverted rRNA operon and a small single-copy (SSC region containing 14 genes normally found in the large single-copy (LSC region. To gain insights into the nature of the events that led to the reorganization of the chloroplast genome in the Ulvophyceae, we have determined the complete cpDNA sequence of Oltmannsiellopsis viridis, a representative of a distinct, early diverging lineage. Results The 151,933 bp IR-containing genome of Oltmannsiellopsis differs considerably from Pseudendoclonium and other chlorophyte cpDNAs in intron content and gene order, but shares close similarities with its ulvophyte homologue at the levels of quadripartite architecture, gene content and gene density. Oltmannsiellopsis cpDNA encodes 105 genes, contains five group I introns, and features many short dispersed repeats. As in Pseudendoclonium cpDNA, the rRNA genes in the IR are transcribed toward the single copy region featuring the genes typically found in the ancestral LSC region, and the opposite single copy region harbours genes characteristic of both the ancestral SSC and LSC regions. The 52 genes that were transferred from the ancestral LSC to SSC region include 12 of those observed in Pseudendoclonium cpDNA. Surprisingly, the overall gene organization of

  19. DNA methylation profiling of sorted cells from myelofibrosis patients reveals aberrant epigenetic regulation of immune pathways and identifies early MPN driver genes

    DEFF Research Database (Denmark)

    Nielsen, Helene Myrtue; Andersen, Christen Lykkegaard; Kristensen, Lasse Sommer

    2015-01-01

    Background: Primary myelofibrosis (PMF) belongs to the heterogeneous group of chronic myeloproliferative neoplasms (MPN) together with essential thrombocytosis (ET) and polycythemia vera (PV). It has been suggested that these neoplasms represent a biological continuum from early cancer stage (ET...

  20. Heterogeneous cellular networks

    CERN Document Server

    Hu, Rose Qingyang

    2013-01-01

    A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

  1. Cellular decomposition in vikalloys

    International Nuclear Information System (INIS)

    Belyatskaya, I.S.; Vintajkin, E.Z.; Georgieva, I.Ya.; Golikov, V.A.; Udovenko, V.A.

    1981-01-01

    Austenite decomposition in Fe-Co-V and Fe-Co-V-Ni alloys at 475-600 deg C is investigated. The cellular decomposition in ternary alloys results in the formation of bcc (ordered) and fcc structures, and in quaternary alloys - bcc (ordered) and 12R structures. The cellular 12R structure results from the emergence of stacking faults in the fcc lattice with irregular spacing in four layers. The cellular decomposition results in a high-dispersion structure and magnetic properties approaching the level of well-known vikalloys [ru

  2. Cellular Reflectarray Antenna

    Science.gov (United States)

    Romanofsky, Robert R.

    2010-01-01

    The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

  3. The ATLAS3D project - IX. The merger origin of a fast- and a slow-rotating early-type galaxy revealed with deep optical imaging: first results

    Science.gov (United States)

    Duc, Pierre-Alain; Cuillandre, Jean-Charles; Serra, Paolo; Michel-Dansac, Leo; Ferriere, Etienne; Alatalo, Katherine; Blitz, Leo; Bois, Maxime; Bournaud, Frédéric; Bureau, Martin; Cappellari, Michele; Davies, Roger L.; Davis, Timothy A.; de Zeeuw, P. T.; Emsellem, Eric; Khochfar, Sadegh; Krajnović, Davor; Kuntschner, Harald; Lablanche, Pierre-Yves; McDermid, Richard M.; Morganti, Raffaella; Naab, Thorsten; Oosterloo, Tom; Sarzi, Marc; Scott, Nicholas; Weijmans, Anne-Marie; Young, Lisa M.

    2011-10-01

    The mass assembly of galaxies leaves imprints in their outskirts, such as shells and tidal tails. The frequency and properties of such fine structures depend on the main acting mechanisms - secular evolution, minor or major mergers - and on the age of the last substantial accretion event. We use this to constrain the mass assembly history of two apparently relaxed nearby early-type galaxies (ETGs) selected from the ATLAS3D sample, NGC 680 and 5557. Our ultra-deep optical images obtained with MegaCam on the Canada-France-Hawaii Telescope reach 29 mag arcsec-2 in the g band. They reveal very low surface brightness (LSB) filamentary structures around these ellipticals. Among them, a gigantic 160 kpc long, narrow, tail east of NGC 5557 hosts three gas-rich star-forming objects, previously detected in H I with the Westerbork Synthesis Radio Telescope and in UV with GALEX. NGC 680 exhibits two major diffuse plumes apparently connected to extended H I tails, as well as a series of arcs and shells. Comparing the outer stellar and gaseous morphology of the two ellipticals with that predicted from models of colliding galaxies, we argue that the LSB features are tidal debris and that each of these two ETGs was assembled during a relatively recent, major wet merger, which most likely occurred after the redshift z ≃ 0.5 epoch. Had these mergers been older, the tidal features should have already fallen back or be destroyed by more recent accretion events. However, the absence of molecular gas and of a prominent young stellar population in the core region of the galaxies indicates that the merger is at least 1-2 Gyr old: the memory of any merger-triggered nuclear starburst has indeed been lost. The star-forming objects found towards the collisional debris of NGC 5557 are then likely tidal dwarf galaxies. Such recycled galaxies here appear to be long-lived and continue to form stars while any star formation activity has stopped in their parent galaxy. The inner kinematics of NGC

  4. Magnetohydrodynamics cellular automata

    International Nuclear Information System (INIS)

    Hatori, Tadatsugu.

    1990-02-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

  5. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  6. Magnetohydrodynamic cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Hatori, Tadatsugu [National Inst. for Fusion Science, Nagoya (Japan)

    1990-03-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author).

  7. Magnetohydrodynamic cellular automata

    International Nuclear Information System (INIS)

    Hatori, Tadatsugu

    1990-01-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

  8. Cellular MR Imaging

    Directory of Open Access Journals (Sweden)

    Michel Modo

    2005-07-01

    Full Text Available Cellular MR imaging is a young field that aims to visualize targeted cells in living organisms. In order to provide a different signal intensity of the targeted cell, they are either labeled with MR contrast agents in vivo or prelabeled in vitro. Either (ultrasmall superparamagnetic iron oxide [(USPIO] particles or (polymeric paramagnetic chelates can be used for this purpose. For in vivo cellular labeling, Gd3+- and Mn2+- chelates have mainly been used for targeted hepatobiliary imaging, and (USPIO-based cellular imaging has been focused on imaging of macrophage activity. Several of these magneto-pharmaceuticals have been FDA-approved or are in late-phase clinical trials. As for prelabeling of cells in vitro, a challenge has been to induce a sufficient uptake of contrast agents into nonphagocytic cells, without affecting normal cellular function. It appears that this issue has now largely been resolved, leading to an active research on monitoring the cellular biodistribution in vivo following transplantation or transfusion of these cells, including cell migration and trafficking. New applications of cellular MR imaging will be directed, for instance, towards our understanding of hematopoietic (immune cell trafficking and of novel guided (stem cell-based therapies aimed to be translated to the clinic in the future.

  9. Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures

    Science.gov (United States)

    Moreira-Filho, Carlos Alberto; Bando, Silvia Yumi; Bertonha, Fernanda Bernardi; Iamashita, Priscila; Silva, Filipi Nascimento; Costa, Luciano da Fontoura; Silva, Alexandre Valotta; Castro, Luiz Henrique Martins; Wen, Hung-Tzu

    2015-01-01

    Age at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system’s constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to

  10. Gene expression profiling reveals different molecular patterns in G-protein coupled receptor signaling pathways between early- and late-onset preeclampsia.

    Science.gov (United States)

    Liang, Mengmeng; Niu, Jianmin; Zhang, Liang; Deng, Hua; Ma, Jian; Zhou, Weiping; Duan, Dongmei; Zhou, Yuheng; Xu, Huikun; Chen, Longding

    2016-04-01

    Early-onset preeclampsia and late-onset preeclampsia have been regarded as two different phenotypes with heterogeneous manifestations; To gain insights into the pathogenesis of the two traits, we analyzed the gene expression profiles in preeclamptic placentas. A whole genome-wide microarray was used to determine the gene expression profiles in placental tissues from patients with early-onset (n = 7; 36 weeks) preeclampsia and their controls who delivered preterm (n = 5; 36 weeks). Genes were termed differentially expressed if they showed a fold-change ≥ 2 and q-value preeclampsia (177 genes were up-regulated and 450 were down-regulated). Gene ontology analysis identified significant alterations in several biological processes; the top two were immune response and cell surface receptor linked signal transduction. Among the cell surface receptor linked signal transduction-related, differentially expressed genes, those involved in the G-protein coupled receptor protein signaling pathway were significantly enriched. G-protein coupled receptor signaling pathway related genes, such as GPR124 and MRGPRF, were both found to be down-regulated in early-onset preeclampsia. The results were consistent with those of western blotting that the abundance of GPR124 was lower in early-onset compared with late-onset preeclampsia. The different gene expression profiles reflect the different levels of transcription regulation between the two conditions and supported the hypothesis that they are separate disease entities. Moreover, the G-protein coupled receptor signaling pathway related genes may contribute to the mechanism underlying early- and late-onset preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Synchrony of plant cellular circadian clocks with heterogeneous properties under light/dark cycles.

    Science.gov (United States)

    Okada, Masaaki; Muranaka, Tomoaki; Ito, Shogo; Oyama, Tokitaka

    2017-03-22

    Individual cells in a plant can work independently as circadian clocks, and their properties are the basis of various circadian phenomena. The behaviour of individual cellular clocks in Lemna gibba was orderly under 24-h light/dark cycles despite their heterogeneous free-running periods (FRPs). Here, we reveal the entrainment habits of heterogeneous cellular clocks using non-24-h light/dark cycles (T-cycles). The cellular rhythms of AtCCA1::LUC under T = 16 h cycles showed heterogeneous entrainment that was associated with their heterogeneous FRPs. Under T = 12 h cycles, most cells showed rhythms having ~24-h periods. This suggested that the lower limit of entrainment to the light/dark cycles of heterogeneous cellular circadian clocks is set to a period longer than 12 h, which enables them to be synchronous under ~24-h daily cycles without being perturbed by short light/dark cycles. The entrainment habits of individual cellular clocks are likely to be the basis of the circadian behaviour of plant under the natural day-night cycle with noisy environmental fluctuations. We further suggest that modifications of EARLY FLOWERING3 (ELF3) in individual cells deviate the entrainability to shorter T-cycles possibly by altering both the FRPs and light responsiveness.

  12. Cellularized Cellular Solids via Freeze-Casting.

    Science.gov (United States)

    Christoph, Sarah; Kwiatoszynski, Julien; Coradin, Thibaud; Fernandes, Francisco M

    2016-02-01

    The elaboration of metabolically active cell-containing materials is a decisive step toward the successful application of cell based technologies. The present work unveils a new process allowing to simultaneously encapsulate living cells and shaping cell-containing materials into solid-state macroporous foams with precisely controlled morphology. Our strategy is based on freeze casting, an ice templating materials processing technique that has recently emerged for the structuration of colloids into macroporous materials. Our results indicate that it is possible to combine the precise structuration of the materials with cellular metabolic activity for the model organism Saccharomyces cerevisiae. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Wireless Cellular Mobile Communications

    Directory of Open Access Journals (Sweden)

    V. Zalud

    2002-12-01

    Full Text Available In this article is briefly reviewed the history of wireless cellularmobile communications, examined the progress in current secondgeneration (2G cellular standards and discussed their migration to thethird generation (3G. The European 2G cellular standard GSM and itsevolution phases GPRS and EDGE are described somewhat in detail. Thethird generation standard UMTS taking up on GSM/GPRS core network andequipped with a new advanced access network on the basis of codedivision multiple access (CDMA is investigated too. A sketch of theperspective of mobile communication beyond 3G concludes this article.

  14. Early transcriptome analyses of Z-3-Hexenol-treated zea mays revealed distinct transcriptional networks and anti-herbivore defense potential of green leaf volatiles.

    Directory of Open Access Journals (Sweden)

    Jurgen Engelberth

    Full Text Available Green leaf volatiles (GLV, which are rapidly emitted by plants in response to insect herbivore damage, are now established as volatile defense signals. Receiving plants utilize these molecules to prime their defenses and respond faster and stronger when actually attacked. To further characterize the biological activity of these compounds we performed a microarray analysis of global gene expression. The focus of this project was to identify early transcriptional events elicited by Z-3-hexenol (Z-3-HOL as our model GLV in maize (Zea mays seedlings. The microarray results confirmed previous studies on Z-3-HOL -induced gene expression but also provided novel information about the complexity of Z-3-HOL -induced transcriptional networks. Besides identifying a distinct set of genes involved in direct and indirect defenses we also found significant expression of genes involved in transcriptional regulation, Ca(2+-and lipid-related signaling, and cell wall reinforcement. By comparing these results with those obtained by treatment of maize seedlings with insect elicitors we found a high degree of correlation between the two expression profiles at this early time point, in particular for those genes related to defense. We further analyzed defense gene expression induced by other volatile defense signals and found Z-3-HOL to be significantly more active than methyl jasmonate, methyl salicylate, and ethylene. The data presented herein provides important information on early genetic networks that are activated by Z-3-HOL and demonstrates the effectiveness of this compound in the regulation of typical plant defenses against insect herbivores in maize.

  15. Magnetic fabrics of arc plutons reveal a significant Late Jurassic to Early Cretaceous change in the relative plate motions of the Pacific Ocean basin and North America

    Czech Academy of Sciences Publication Activity Database

    Žák, J.; Verner, K.; Tomek, Filip; Johnson, K.; Schwartz, J. J.

    2017-01-01

    Roč. 13, č. 1 (2017), s. 11-21 ISSN 1553-040X Grant - others:AV ČR(CZ) MSM100131601 Program:Program na podporu mezinárodní spolupráce začínajících výzkumných pracovníků Institutional support: RVO:67985831 Keywords : PB geochronology * Late Jurassic/Early Cretaceous * Blue Mountains province Subject RIV: DB - Geology ; Mineralogy OBOR OECD: Geology Impact factor: 2.304, year: 2016

  16. Radiolabelled cellular blood elements

    International Nuclear Information System (INIS)

    Sinzinger, H.

    1990-01-01

    This book reports on radiolabelled cellular blood elements, covering new advances made during the past several years, in particular the use of Tc-99 as a tracer for blood elements. Coverage extends to several radiolabelled monoclonal antibodies that are specific for blood components and may label blood elements in vivo

  17. Building synthetic cellular organization

    OpenAIRE

    Polka, Jessica K.; Silver, Pamela A.

    2013-01-01

    The elaborate spatial organization of cells enhances, restricts, and regulates protein–protein interactions. However, the biological significance of this organization has been difficult to study without ways of directly perturbing it. We highlight synthetic biology tools for engineering novel cellular organization, describing how they have been, and can be, used to advance cell biology.

  18. The New Cellular Immunology

    Science.gov (United States)

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  19. Electromagnetic cellular interactions.

    Science.gov (United States)

    Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

    2011-05-01

    Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Genetic Dominance & Cellular Processes

    Science.gov (United States)

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  1. High performance mass spectrometry based proteomics reveals enzyme and signaling pathway regulation in neutrophils during the early stage of surgical trauma

    DEFF Research Database (Denmark)

    Arshid, Samina; Tahir, Muhammad; Fontes, Belchor

    2017-01-01

    and surgical trauma rats in this study. Extracted proteins were analyzed using nano liquid chromatography coupled to tandem mass spectrometry. A total of 2924 rat neutrophil proteins were identified in our analysis, of which 393 were found differentially regulated between control and trauma groups. By using...... functional pathways analysis of the 190 proteins up-regulated in surgical trauma we found proteins related to transcription initiation and protein biosynthesis. On the other hand, among the 203 proteins down-regulated in surgical trauma we found enrichment for proteins of the immune response, proteasome...... degradation and actin cytoskeleton. Overall, enzyme prediction analysis revealed that regulated enzymes are directly involved in neutrophil apoptosis, directional migration and chemotaxis. Our observations were then confirmed by in silico protein-protein interaction analysis. Collectively, our results reveal...

  2. Diffusion tractography and graph theory analysis reveal the disrupted rich-club organization of white matter structural networks in early Tourette Syndrome children

    Science.gov (United States)

    Wen, Hongwei; Liu, Yue; Wang, Shengpei; Zhang, Jishui; Peng, Yun; He, Huiguang

    2017-03-01

    Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder. At present, the topological disruptions of the whole brain white matter (WM) structural networks remain poorly understood in TS children. Considering the unique position of the topologically central role of densely interconnected brain hubs, namely the rich club regions, therefore, we aimed to investigate whether the rich club regions and their related connections would be particularly vulnerable in early TS children. In our study, we used diffusion tractography and graph theoretical analyses to explore the rich club structures in 44 TS children and 48 healthy children. The structural networks of TS children exhibited significantly increased normalized rich club coefficient, suggesting that TS is characterized by increased structural integrity of this centrally embedded rich club backbone, potentially resulting in increased global communication capacity. In addition, TS children showed a reorganization of rich club regions, as well as significantly increased density and decreased number in feeder connections. Furthermore, the increased rich club coefficients and feeder connections density of TS children were significantly positively correlated to tic severity, indicating that TS may be characterized by a selective alteration of the structural connectivity of the rich club regions, tending to have higher bridging with non-rich club regions, which may increase the integration among tic-related brain circuits with more excitability but less inhibition for information exchanges between highly centered brain regions and peripheral areas. In all, our results suggest the disrupted rich club organization in early TS children and provide structural insights into the brain networks.

  3. Retroperitoneal Cellular Angiofibroma: A Rare Gynecological Entity

    Directory of Open Access Journals (Sweden)

    Ana Brandão

    2017-12-01

    Full Text Available Cellular angiofibroma is a mesenchymal tumor, described in 1997, without gender preference, that usually appears at age 40. The vulvovaginal area is the most common site in women, mimicking vulvar benign tumors, like Bartholin gland cyst. However, there are a few described cases of a deep or extra-pelvic angiofibroma. Excision is the treatment of choice and the recurrence rate appears to be low. We present the case of a woman with a heterogeneous tumor in the right adnexial region. At the surgery, a retroperitoneal tumor was excised and the histopathological tissue analysis revealed a cellular angiofibroma.

  4. Chaotic behavior in the disorder cellular automata

    International Nuclear Information System (INIS)

    Ko, J.-Y.; Hung, Y.-C.; Ho, M.-C.; Jiang, I-M.

    2008-01-01

    Disordered cellular automata (DCA) represent an intermediate class between elementary cellular automata and the Kauffman network. Recently, Rule 126 of DCA has been explicated: the system can be accurately described by a discrete probability function. However, a means of extending to other rules has not been developed. In this investigation, a density map of the dynamical behavior of DCA is formulated based on Rule 22 and other totalistic rules. The numerical results reveal excellent agreement between the model and original automata. Furthermore, the inhomogeneous situation is also discussed

  5. Examination of two lowland rice cultivars reveals that gibberellin-dependent early response to submergence is not necessarily mediated by ethylene.

    Science.gov (United States)

    Dubois, Vincent; Moritz, Thomas; García-Martínez, José L

    2011-01-01

    Using two lowland rice (Oryza sativa L.) cultivars we found that in both cases submerged-induced elongation early after germination depends on gibberellins (GAs). Submergence increases the content of the active GA 1 by enhancing the expression of GA biosynthesis genes, thus facilitating the seedlings to escape from the water and preventing asphyxiation. However, the two cultivars differ in their response to ethylene. The cultivar Senia (short), by contrast to cultivar Bomba (tall), does not elongate after ethylene application, and submerged-induced elongation is not negated by an inhibitor of ethylene perception. Also, while ethylene emanation in Senia is not altered by submergence, Bomba seedlings emanate more ethylene upon de-submergence, associated with enhanced expression of the ethylene biosynthesis gene OsACS5. The cultivar Senia thus allows the possibility of clarifying the role of ethylene and other factors as triggers of GA biosynthesis enhancement in rice seedlings under submergence.

  6. Transmission of clonal hepatitis C virus genomes reveals the dominant but transitory role of CD8¿ T cells in early viral evolution

    DEFF Research Database (Denmark)

    Callendret, Benoît; Bukh, Jens; Eccleston, Heather B

    2011-01-01

    occurred slowly over several years of chronic infection. Together these observations indicate that during acute hepatitis C, virus evolution was driven primarily by positive selection pressure exerted by CD8(+) T cells. This influence of immune pressure on viral evolution appears to subside as chronic......The RNA genome of the hepatitis C virus (HCV) diversifies rapidly during the acute phase of infection, but the selective forces that drive this process remain poorly defined. Here we examined whether Darwinian selection pressure imposed by CD8(+) T cells is a dominant force driving early amino acid...... replacement in HCV viral populations. This question was addressed in two chimpanzees followed for 8 to 10 years after infection with a well-defined inoculum composed of a clonal genotype 1a (isolate H77C) HCV genome. Detailed characterization of CD8(+) T cell responses combined with sequencing of recovered...

  7. De novo analysis of Wolfiporia cocos transcriptome to reveal the differentially expressed carbohydrate-active enzymes (CAZymes genes during the early stage of sclerotial growth

    Directory of Open Access Journals (Sweden)

    Shaopeng eZhang

    2016-02-01

    Full Text Available The sclerotium of Wolfiporia cocos has been used as an edible mushroom and/or a traditional herbal medicine for centuries. W. cocos sclerotial formation is dependent on parasitism of the wood of Pinus species. Currently, the sclerotial development mechanisms of W. cocos remain largely unknown and the lack of pine resources limit the commercial production. The CAZymes (carbohydrate-active enzymes play important roles in degradation of the plant cell wall to provide carbohydrates for fungal growth, development and reproduction. In this study, the transcript profiles from W. cocos mycelium and two-months-old sclerotium, the early stage of sclerotial growth, were specially analyzed using de novo sequencing technology. A total of 142,428,180 high-quality reads of mycelium and 70,594,319 high-quality reads of two-months-old sclerotium were obtained. Additionally, differentially expressed genes from the W. cocos mycelium and two-months-old sclerotium stages were analyzed, resulting in identification of 69 CAZymes genes which were significantly up-regulated during the early stage of sclerotial growth compared to that of in mycelium stage, and more than half of them belonged to glycosyl hydrolases (GHs family, indicating the importance of W. cocos GHs family for degrading the pine woods. And qRT-PCR was further used to confirm the expression pattern of these up-regulated CAZymes genes. Our results will provide comprehensive CAZymes genes expression information during W. cocos sclerotial growth at the transcriptional level and will lay a foundation for functional genes studies in this fungus. In addition, our study will also facilitate the efficient use of limited pine resources, which is significant for promoting steady development of Chinese W. cocos industry.

  8. Eye Tracking Reveals Abnormal Visual Preference for Geometric Images as an Early Biomarker of an Autism Spectrum Disorder Subtype Associated With Increased Symptom Severity.

    Science.gov (United States)

    Pierce, Karen; Marinero, Steven; Hazin, Roxana; McKenna, Benjamin; Barnes, Cynthia Carter; Malige, Ajith

    2016-04-15

    Clinically and biologically, autism spectrum disorder (ASD) is heterogeneous. Unusual patterns of visual preference as indexed by eye tracking are hallmarks; however, whether they can be used to define an early biomarker of ASD as a whole or leveraged to define a subtype is unclear. To begin to examine this issue, large cohorts are required. A sample of 334 toddlers from six distinct groups (115 toddlers with ASD, 20 toddlers with ASD features, 57 toddlers with developmental delay, 53 toddlers with other conditions [e.g., premature birth, prenatal drug exposure], 64 toddlers with typical development, and 25 unaffected toddlers with siblings with ASD) was studied. Toddlers watched a movie containing geometric and social images. Fixation duration and number of saccades within each area of interest and validation statistics for this independent sample were computed. Next, to maximize power, data from our previous study (n = 110) were added for a total of 444 subjects. A subset of toddlers repeated the eye-tracking procedure. As in the original study, a subset of toddlers with ASD fixated on geometric images >69% of the time. Using this cutoff, sensitivity for ASD was 21%, specificity was 98%, and positive predictive value was 86%. Toddlers with ASD who strongly preferred geometric images had 1) worse cognitive, language, and social skills relative to toddlers with ASD who strongly preferred social images and 2) fewer saccades when viewing geometric images. Unaffected siblings of ASD probands did not show evidence of heightened preference for geometric images. Test-retest reliability was good. Examination of age effects suggested that this test may not be appropriate with children >4 years old. Enhanced visual preference for geometric repetition may be an early developmental biomarker of an ASD subtype with more severe symptoms. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Eye-tracking Reveals Abnormal Visual Preference for Geometric Images as an Early Biomarker of an ASD Subtype Associated with Increased Symptom Severity

    Science.gov (United States)

    Pierce, Karen; Marinero, Steven; Hazin, Roxana; McKenna, Benjamin; Barnes, Cynthia Carter; Malige, Ajith

    2015-01-01

    Background Clinically and biologically, ASD is heterogeneous. Unusual patterns of visual preference as indexed by eye-tracking are hallmarks, yet whether they can be used to define an early biomarker of ASD as a whole, or leveraged to define a subtype is unclear. To begin to examine this issue, large cohorts are required. Methods A sample of 334 toddlers from 6 distinct groups (115 ASD, 20 ASD-Features, 57 DD, 53 Other, 64 TD, and 25 Typ SIB) participated. Toddlers watched a movie containing both geometric and social images. Fixation duration and number of saccades within each AOI and validation statistics for this independent sample computed. Next, to maximize power, data from our previous study (N=110) was added totaling 444 subjects. A subset of toddlers repeated the eye-tracking procedure. Results As in the original study, a subset of toddlers with ASD fixated on geometric images greater than 69%. Using this cutoff, sensitivity for ASD was 21%, specificity 98%, and PPV 86%. Toddlers with ASD who strongly preferred geometric images had (a) worse cognitive, language, and social skills relative to toddlers with ASD who strongly preferred social images and (b) fewer saccades when viewing geometric images. Unaffected siblings of ASD probands did not show evidence of heightened preference for geometric images. Test-retest reliability was good. Examination of age effects suggest that this test may not be appropriate with children > 4 years. Conclusions Enhanced visual preference for geometric repetition may be an early developmental biomarker of an ASD subtype with more severe symptoms. PMID:25981170

  10. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  11. Nested cellular automata

    International Nuclear Information System (INIS)

    Quasthoff, U.

    1985-07-01

    Cellular automata by definition consist of a finite or infinite number of cells, say of unit length, with each cell having the same transition function. These cells are usually considered as the smallest elements and so the space filled with these cells becomes discrete. Nevertheless, large pictures created by such cellular automata look very fractal. So we try to replace each cell by a couple of smaller cells, which have the same transition functions as the large ones. There are automata where this replacement does not destroy the macroscopic structure. In these cases this nesting process can be iterated. The paper contains large classes of automata with the above properties. In the case of one dimensional automata with two states and next neighbour interaction and a nesting function of the same type a complete classification is given. (author)

  12. Predictability in cellular automata.

    Science.gov (United States)

    Agapie, Alexandru; Andreica, Anca; Chira, Camelia; Giuclea, Marius

    2014-01-01

    Modelled as finite homogeneous Markov chains, probabilistic cellular automata with local transition probabilities in (0, 1) always posses a stationary distribution. This result alone is not very helpful when it comes to predicting the final configuration; one needs also a formula connecting the probabilities in the stationary distribution to some intrinsic feature of the lattice configuration. Previous results on the asynchronous cellular automata have showed that such feature really exists. It is the number of zero-one borders within the automaton's binary configuration. An exponential formula in the number of zero-one borders has been proved for the 1-D, 2-D and 3-D asynchronous automata with neighborhood three, five and seven, respectively. We perform computer experiments on a synchronous cellular automaton to check whether the empirical distribution obeys also that theoretical formula. The numerical results indicate a perfect fit for neighbourhood three and five, which opens the way for a rigorous proof of the formula in this new, synchronous case.

  13. Probabilistic cellular automata.

    Science.gov (United States)

    Agapie, Alexandru; Andreica, Anca; Giuclea, Marius

    2014-09-01

    Cellular automata are binary lattices used for modeling complex dynamical systems. The automaton evolves iteratively from one configuration to another, using some local transition rule based on the number of ones in the neighborhood of each cell. With respect to the number of cells allowed to change per iteration, we speak of either synchronous or asynchronous automata. If randomness is involved to some degree in the transition rule, we speak of probabilistic automata, otherwise they are called deterministic. With either type of cellular automaton we are dealing with, the main theoretical challenge stays the same: starting from an arbitrary initial configuration, predict (with highest accuracy) the end configuration. If the automaton is deterministic, the outcome simplifies to one of two configurations, all zeros or all ones. If the automaton is probabilistic, the whole process is modeled by a finite homogeneous Markov chain, and the outcome is the corresponding stationary distribution. Based on our previous results for the asynchronous case-connecting the probability of a configuration in the stationary distribution to its number of zero-one borders-the article offers both numerical and theoretical insight into the long-term behavior of synchronous cellular automata.

  14. Wavefront cellular learning automata.

    Science.gov (United States)

    Moradabadi, Behnaz; Meybodi, Mohammad Reza

    2018-02-01

    This paper proposes a new cellular learning automaton, called a wavefront cellular learning automaton (WCLA). The proposed WCLA has a set of learning automata mapped to a connected structure and uses this structure to propagate the state changes of the learning automata over the structure using waves. In the WCLA, after one learning automaton chooses its action, if this chosen action is different from the previous action, it can send a wave to its neighbors and activate them. Each neighbor receiving the wave is activated and must choose a new action. This structure for the WCLA is necessary in many dynamic areas such as social networks, computer networks, grid computing, and web mining. In this paper, we introduce the WCLA framework as an optimization tool with diffusion capability, study its behavior over time using ordinary differential equation solutions, and present its accuracy using expediency analysis. To show the superiority of the proposed WCLA, we compare the proposed method with some other types of cellular learning automata using two benchmark problems.

  15. Algorithm for cellular reprogramming.

    Science.gov (United States)

    Ronquist, Scott; Patterson, Geoff; Muir, Lindsey A; Lindsly, Stephen; Chen, Haiming; Brown, Markus; Wicha, Max S; Bloch, Anthony; Brockett, Roger; Rajapakse, Indika

    2017-11-07

    The day we understand the time evolution of subcellular events at a level of detail comparable to physical systems governed by Newton's laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology. With data-guided frameworks we can develop better predictions about, and methods for, control over specific biological processes and system-wide cell behavior. Here we describe an approach for optimizing the use of transcription factors (TFs) in cellular reprogramming, based on a device commonly used in optimal control. We construct an approximate model for the natural evolution of a cell-cycle-synchronized population of human fibroblasts, based on data obtained by sampling the expression of 22,083 genes at several time points during the cell cycle. To arrive at a model of moderate complexity, we cluster gene expression based on division of the genome into topologically associating domains (TADs) and then model the dynamics of TAD expression levels. Based on this dynamical model and additional data, such as known TF binding sites and activity, we develop a methodology for identifying the top TF candidates for a specific cellular reprogramming task. Our data-guided methodology identifies a number of TFs previously validated for reprogramming and/or natural differentiation and predicts some potentially useful combinations of TFs. Our findings highlight the immense potential of dynamical models, mathematics, and data-guided methodologies for improving strategies for control over biological processes. Copyright © 2017 the Author(s). Published by PNAS.

  16. Wavefront cellular learning automata

    Science.gov (United States)

    Moradabadi, Behnaz; Meybodi, Mohammad Reza

    2018-02-01

    This paper proposes a new cellular learning automaton, called a wavefront cellular learning automaton (WCLA). The proposed WCLA has a set of learning automata mapped to a connected structure and uses this structure to propagate the state changes of the learning automata over the structure using waves. In the WCLA, after one learning automaton chooses its action, if this chosen action is different from the previous action, it can send a wave to its neighbors and activate them. Each neighbor receiving the wave is activated and must choose a new action. This structure for the WCLA is necessary in many dynamic areas such as social networks, computer networks, grid computing, and web mining. In this paper, we introduce the WCLA framework as an optimization tool with diffusion capability, study its behavior over time using ordinary differential equation solutions, and present its accuracy using expediency analysis. To show the superiority of the proposed WCLA, we compare the proposed method with some other types of cellular learning automata using two benchmark problems.

  17. Unbiased cell quantification reveals a continued increase in the number of neocortical neurones during early post-natal development in mice

    DEFF Research Database (Denmark)

    Lyck, Lise; Krøigård, Thomas; Finsen, Bente

    2007-01-01

    The post-natal growth spurt of the mammalian neocortex has been attributed to maturation of dendritic arborizations, growth and myelination of axons, and addition of glia. It is unclear whether this growth may also involve recruitment of additional neurones. Using stereological methods, we analysed...... the number of neurones and glia in the neocortex during post-natal development in two separate strains of mice. Cell counting by the optical fractionator revealed that the number of neurones increased 80-100% from the time of birth to post-natal day (P)16, followed by a reduction by approximately 25...... was delayed until P16. The number of glia reached its maximum at P16, whereas the number of oligodendroglia, identified using a transgenic marker, increased until P55, the latest time of observation. Neurones continued to accumulate in the developing neocortex during the first 2 weeks of post...

  18. Detection of histone acetylation levels in the dorsal hippocampus reveals early tagging on specific residues of H2B and H4 histones in response to learning.

    Directory of Open Access Journals (Sweden)

    Olivier Bousiges

    Full Text Available The recent literature provides evidence that epigenetic mechanisms such as DNA methylation and histone modification are crucial to gene transcription linked to synaptic plasticity in the mammalian brain--notably in the hippocampus--and memory formation. We measured global histone acetylation levels in the rat hippocampus at an early stage of spatial or fear memory formation. We found that H3, H4 and H2B underwent differential acetylation at specific sites depending on whether rats had been exposed to the context of a task without having to learn or had to learn about a place or fear therein: H3K9K14 acetylation was mostly responsive to any experimental conditions compared to naive animals, whereas H2B N-terminus and H4K12 acetylations were mostly associated with memory for either spatial or fear learning. Altogether, these data suggest that behavior/experience-dependent changes differently regulate specific acetylation modifications of histones in the hippocampus, depending on whether a memory trace is established or not: tagging of H3K9K14 could be associated with perception/processing of testing-related manipulations and context, thereby enhancing chromatin accessibility, while tagging of H2B N-terminus tail and H4K12 could be more closely associated with the formation of memories requiring an engagement of the hippocampus.

  19. Fetal and early post-natal mineralization of the tympanic bulla in fin whales may reveal a Hitherto undiscovered evolutionary trait.

    Directory of Open Access Journals (Sweden)

    Bruno Cozzi

    Full Text Available The evolution of the cetacean skeleton followed a path that differentiated this group from other terrestrial mammals about 50 million years ago [1], and debate is still going on about the relationships between Cetacea and Artiodactyla [2], [3], [4]. Some skeletal traits of the basilosaurids (the more advanced forms of Archaeocetes, such as the expansion of the peribullary air sinuses, dental modification and vertebral size uniformity [5] are maintained and further emphasized also in contemporary odontocetes and mysticetes. Using Dual-Energy X-Ray Absorptiometry here we report that the deposition of bone mineral in fetal and newborn specimens of the fin whale Balaenoptera physalus is remarkably higher in the bulla tympanica than in the adjacent basal skull or in the rest of the skeleton. Ossification of the tympanic bulla in fetal Artiodactyla (bovine, hippopotamus is minimal, becomes sensible after birth and then progresses during growth, contrarily to the precocious mineralization that we observed in fin whales. Given the importance of the ear bones for the precise identification of phylogenetic relationship in therian evolution [6], this feature may indicate a specific evolutionary trait of fin whales and possibly other cetacean species or families. Early mineralization of the tympanic bulla allows immediate sound conduction in the aquatic medium and consequently holds potential importance for mother-calf relationship and postnatal survival.

  20. Proteomics Analysis Reveals Abnormal Electron Transport and Excessive Oxidative Stress Cause Mitochondrial Dysfunction in Placental Tissues of Early-Onset Preeclampsia.

    Science.gov (United States)

    Xu, Zhongwei; Jin, Xiaohan; Cai, Wei; Zhou, Maobin; Shao, Ping; Yang, Zhen; Fu, Rong; Cao, Jin; Liu, Yan; Yu, Fang; Fan, Rong; Zhang, Yan; Zou, Shuang; Zhou, Xin; Yang, Ning; Chen, Xu; Li, Yuming

    2018-04-20

    Early-onset preeclampsia (EOS-PE) refers to preeclampsia that occurred before 34 gestation weeks. This study was conducted to explore the relationship between mitochondrial dysfunction and the pathogenesis of EOS-PE using proteomic strategy. To identify altering expressed mitochondrial proteins between severe EOS-PE and healthy pregnancies, enrichment of mitochondria coupled with iTRAQ-based quantitative proteomic method was performed. IHC and western blot were performed to detect the alteration of changing expression proteins, and confirmed the accuracy of proteomic results. We totally quantified 1372 proteins and screened 132 altering expressed mitochondrial proteins, including 86 down-regulated expression proteins and 46 up-regulated expression proteins (pelectron transport chain and oxidative phosphorylation. Especially, mitochondrial related molecules, PRDX2, PARK7, BNIP3, BCL2, PDHA1, SUCLG1, ACADM and NDUFV1, were involved in energy production process in the matrix and membrane of mitochondria. Our results showed that abnormal electron transport, excessive oxidative stress and mitochondrion disassembly might be the main cause of mitochondrial dysfunction, and was related to the pathogenesis of EOS-PE. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. THE LOCATION OF NON-THERMAL VELOCITY IN THE EARLY PHASES OF LARGE FLARES—REVEALING PRE-ERUPTION FLUX ROPES

    International Nuclear Information System (INIS)

    Harra, Louise K.; Matthews, Sarah; Culhane, J. L.; Cheung, Mark C. M.; Kontar, Eduard P.; Hara, Hirohisa

    2013-01-01

    Non-thermal velocity measurements of the solar atmosphere, particularly from UV and X-ray emission lines have demonstrated over the decades that this parameter is important in understanding the triggering of solar flares. Enhancements have often been observed before intensity enhancements are seen. However, until the launch of Hinode, it has been difficult to determine the spatial location of the enhancements to better understand the source region. The Hinode EUV Imaging Spectrometer has the spectral and spatial resolution to allow us to probe the early stages of flares in detail. We analyze four events, all of which are GOES M- or X-classification flares, and all are located toward the limb for ease of flare geometry interpretation. Three of the flares were eruptive and one was confined. In all events, pre-flare enhancement in non-thermal velocity at the base of the active region and its surroundings has been found. These enhancements seem to be consistent with the footpoints of the dimming regions, and hence may be highlighting the activation of a coronal flux rope for the three eruptive events. In addition, pre-flare enhancements in non-thermal velocity were found above the looptops for the three eruptive events

  2. Molecular characterization of WFS1 in an Iranian family with Wolfram syndrome reveals a novel frameshift mutation associated with early symptoms.

    Science.gov (United States)

    Sobhani, Maryam; Tabatabaiefar, Mohammad Amin; Rajab, Asadollah; Kajbafzadeh, Abdol-Mohammad; Noori-Daloii, Mohammad Reza

    2013-10-10

    Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder that represents a likely source of childhood diabetes especially among countries in the consanguinity belt. The main responsible gene is WFS1 for which over one hundred mutations have been reported from different ethnic groups. The aim of this study was to identify the molecular etiology of WS and to perform a possible genotype-phenotype correlation in Iranian kindred. An Iranian family with two patients was clinically studied and WS was suspected. Genetic linkage analysis via 5 STR markers was carried out. For identification of mutations, DNA sequencing of WFS1 including all the exons, exon-intron boundaries and the promoter was performed. Linkage analysis indicated linkage to the WFS1 region. After DNA sequencing of WFS1, one novel pathogenic mutation, which causes frameshift alteration c.2177_2178insTCTTC (or c.2173_2177dupTCTTC) in exon eight, was found. The genotype-phenotype correlation analysis suggests that the presence of the homozygous mutation may be associated with early onset of disease symptoms. This study stresses the necessity of considering the molecular analysis of WFS1 in childhood diabetes with some symptoms of WS. © 2013 Elsevier B.V. All rights reserved.

  3. Environment Aware Cellular Networks

    KAUST Repository

    Ghazzai, Hakim

    2015-02-01

    The unprecedented rise of mobile user demand over the years have led to an enormous growth of the energy consumption of wireless networks as well as the greenhouse gas emissions which are estimated currently to be around 70 million tons per year. This significant growth of energy consumption impels network companies to pay huge bills which represent around half of their operating expenditures. Therefore, many service providers, including mobile operators, are looking for new and modern green solutions to help reduce their expenses as well as the level of their CO2 emissions. Base stations are the most power greedy element in cellular networks: they drain around 80% of the total network energy consumption even during low traffic periods. Thus, there is a growing need to develop more energy-efficient techniques to enhance the green performance of future 4G/5G cellular networks. Due to the problem of traffic load fluctuations in cellular networks during different periods of the day and between different areas (shopping or business districts and residential areas), the base station sleeping strategy has been one of the main popular research topics in green communications. In this presentation, we present several practical green techniques that provide significant gains for mobile operators. Indeed, combined with the base station sleeping strategy, these techniques achieve not only a minimization of the fossil fuel consumption but also an enhancement of mobile operator profits. We start with an optimized cell planning method that considers varying spatial and temporal user densities. We then use the optimal transport theory in order to define the cell boundaries such that the network total transmit power is reduced. Afterwards, we exploit the features of the modern electrical grid, the smart grid, as a new tool of power management for cellular networks and we optimize the energy procurement from multiple energy retailers characterized by different prices and pollutant

  4. Integrative testis transcriptome analysis reveals differentially expressed miRNAs and their mRNA targets during early puberty in Atlantic salmon.

    Science.gov (United States)

    Skaftnesmo, K O; Edvardsen, R B; Furmanek, T; Crespo, D; Andersson, E; Kleppe, L; Taranger, G L; Bogerd, J; Schulz, R W; Wargelius, A

    2017-10-18

    Our understanding of the molecular mechanisms implementing pubertal maturation of the testis in vertebrates is incomplete. This topic is relevant in Atlantic salmon aquaculture, since precocious male puberty negatively impacts animal welfare and growth. We hypothesize that certain miRNAs modulate mRNAs relevant for the initiation of puberty. To explore which miRNAs regulate mRNAs during initiation of puberty in salmon, we performed an integrated transcriptome analysis (miRNA and mRNA-seq) of salmon testis at three stages of development: an immature, long-term quiescent stage, a prepubertal stage just before, and a pubertal stage just after the onset of single cell proliferation activity in the testis. Differentially expressed miRNAs clustered into 5 distinct expression profiles related to the immature, prepubertal and pubertal salmon testis. Potential mRNA targets of these miRNAs were predicted with miRmap and filtered for mRNAs displaying negatively correlated expression patterns. In summary, this analysis revealed miRNAs previously known to be regulated in immature vertebrate testis (miR-101, miR-137, miR-92b, miR-18a, miR-20a), but also miRNAs first reported here as regulated in the testis (miR-new289, miR-30c, miR-724, miR-26b, miR-new271, miR-217, miR-216a, miR-135a, miR-new194 and the novel predicted n268). By KEGG enrichment analysis, progesterone signaling and cell cycle pathway genes were found regulated by these differentially expressed miRNAs. During the transition into puberty we found differential expression of miRNAs previously associated (let7a/b/c), or newly associated (miR-15c, miR-2184, miR-145 and the novel predicted n7a and b) with this stage. KEGG enrichment analysis revealed that mRNAs of the Wnt, Hedgehog and Apelin signaling pathways were potential regulated targets during the transition into puberty. Likewise, several regulated miRNAs in the pubertal stage had earlier been associated (miR-20a, miR-25, miR-181a, miR-202, let7c/d/a, miR-125b

  5. High-Throughput Genetic Screen Reveals that Early Attachment and Biofilm Formation Are Necessary for Full Pyoverdine Production by Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Donghoon Kang

    2017-09-01

    Full Text Available Pseudomonas aeruginosa is a re-emerging, multidrug-resistant, opportunistic pathogen that threatens the lives of immunocompromised patients, patients with cystic fibrosis, and those in critical care units. One of the most important virulence factors in this pathogen is the siderophore pyoverdine. Pyoverdine serves several critical roles during infection. Due to its extremely high affinity for ferric iron, pyoverdine gives the pathogen a significant advantage over the host in their competition for iron. In addition, pyoverdine can regulate the production of multiple bacterial virulence factors and perturb host mitochondrial homeostasis. Inhibition of pyoverdine biosynthesis decreases P. aeruginosa pathogenicity in multiple host models. To better understand the regulation of pyoverdine production, we developed a high-throughput genetic screen that uses the innate fluorescence of pyoverdine to identify genes necessary for its biosynthesis. A substantial number of hits showing severe impairment of pyoverdine production were in genes responsible for early attachment and biofilm formation. In addition to genetic disruption of biofilm, both physical and chemical perturbations also attenuated pyoverdine production. This regulatory relationship between pyoverdine and biofilm is particularly significant in the context of P. aeruginosa multidrug resistance, where the formation of biofilm is a key mechanism preventing access to antimicrobials and the immune system. Furthermore, we demonstrate that the biofilm inhibitor 2-amino-5,6-dimethylbenzimidazole effectively attenuates pyoverdine production and rescues Caenorhabditis elegans from P. aeruginosa-mediated pathogenesis. Our findings suggest that targeting biofilm formation in P. aeruginosa infections may have multiple therapeutic benefits and that employing an unbiased, systems biology-based approach may be useful for understanding the regulation of specific virulence factors and identifying novel anti

  6. Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord-specific markers during early human intervertebral disc development.

    Science.gov (United States)

    Rodrigues-Pinto, Ricardo; Berry, Andrew; Piper-Hanley, Karen; Hanley, Neil; Richardson, Stephen M; Hoyland, Judith A

    2016-08-01

    In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte-like cells. Although animal studies indicate that notochord-derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5-18 weeks post-conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E-cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co-expressed by sclerotomal cells. CD90, Tie2, and E-cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord-specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327-1340, 2016. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc.

  7. Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord‐specific markers during early human intervertebral disc development

    Science.gov (United States)

    Rodrigues‐Pinto, Ricardo; Berry, Andrew; Piper‐Hanley, Karen; Hanley, Neil; Richardson, Stephen M.

    2016-01-01

    ABSTRACT In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte‐like cells. Although animal studies indicate that notochord‐derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5–18 weeks post‐conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E‐cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co‐expressed by sclerotomal cells. CD90, Tie2, and E‐cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord‐specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327–1340, 2016. PMID:26910849

  8. Unsupervised Analysis of Array Comparative Genomic Hybridization Data from Early-Onset Colorectal Cancer Reveals Equivalence with Molecular Classification and Phenotypes

    Directory of Open Access Journals (Sweden)

    María Arriba

    2017-01-01

    Full Text Available AIM: To investigate whether chromosomal instability (CIN is associated with tumor phenotypes and/or with global genomic status based on MSI (microsatellite instability and CIMP (CpG island methylator phenotype in early-onset colorectal cancer (EOCRC. METHODS: Taking as a starting point our previous work in which tumors from 60 EOCRC cases (≤45 years at the time of diagnosis were analyzed by array comparative genomic hybridization (aCGH, in the present study we performed an unsupervised hierarchical clustering analysis of those aCGH data in order to unveil possible associations between the CIN profile and the clinical features of the tumors. In addition, we evaluated the MSI and the CIMP statuses of the samples with the aim of investigating a possible relationship between copy number alterations (CNAs and the MSI/CIMP condition in EOCRC. RESULTS: Based on the similarity of the CNAs detected, the unsupervised analysis stratified samples into two main clusters (A, B and four secondary clusters (A1, A2, B3, B4. The different subgroups showed a certain correspondence with the molecular classification of colorectal cancer (CRC, which enabled us to outline an algorithm to categorize tumors according to their CIMP status. Interestingly, each subcluster showed some distinctive clinicopathological features. But more interestingly, the CIN of each subcluster mainly affected particular chromosomes, allowing us to define chromosomal regions more specifically affected depending on the CIMP/MSI status of the samples. CONCLUSIONS: Our findings may provide a basis for a new form of classifying EOCRC according to the genomic status of the tumors.

  9. Dual pulse-chase microscopy reveals early divergence in the biosynthetic trafficking of the Na,K-ATPase and E-cadherin

    Science.gov (United States)

    Farr, Glen A.; Hull, Michael; Stoops, Emily H.; Bateson, Rosalie; Caplan, Michael J.

    2015-01-01

    Recent evidence indicates that newly synthesized membrane proteins that share the same distributions in the plasma membranes of polarized epithelial cells can pursue a variety of distinct trafficking routes as they travel from the Golgi complex to their common destination at the cell surface. In most polarized epithelial cells, both the Na,K-ATPase and E-cadherin are localized to the basolateral domains of the plasma membrane. To examine the itineraries pursued by newly synthesized Na,K-ATPase and E-cadherin in polarized MDCK epithelial cells, we used the SNAP and CLIP labeling systems to fluorescently tag temporally defined cohorts of these proteins and observe their behaviors simultaneously as they traverse the secretory pathway. These experiments reveal that E-cadherin is delivered to the cell surface substantially faster than is the Na,K-ATPase. Furthermore, the surface delivery of newly synthesized E-cadherin to the plasma membrane was not prevented by the 19°C temperature block that inhibits the trafficking of most proteins, including the Na,K-ATPase, out of the trans-Golgi network. Consistent with these distinct behaviors, populations of newly synthesized E-cadherin and Na,K-ATPase become separated from one another within the trans-Golgi network, suggesting that they are sorted into different carrier vesicles that mediate their post-Golgi trafficking. PMID:26424804

  10. Characterizing heterogeneous cellular responses to perturbations.

    Science.gov (United States)

    Slack, Michael D; Martinez, Elisabeth D; Wu, Lani F; Altschuler, Steven J

    2008-12-09

    Cellular populations have been widely observed to respond heterogeneously to perturbation. However, interpreting the observed heterogeneity is an extremely challenging problem because of the complexity of possible cellular phenotypes, the large dimension of potential perturbations, and the lack of methods for separating meaningful biological information from noise. Here, we develop an image-based approach to characterize cellular phenotypes based on patterns of signaling marker colocalization. Heterogeneous cellular populations are characterized as mixtures of phenotypically distinct subpopulations, and responses to perturbations are summarized succinctly as probabilistic redistributions of these mixtures. We apply our method to characterize the heterogeneous responses of cancer cells to a panel of drugs. We find that cells treated with drugs of (dis-)similar mechanism exhibit (dis-)similar patterns of heterogeneity. Despite the observed phenotypic diversity of cells observed within our data, low-complexity models of heterogeneity were sufficient to distinguish most classes of drug mechanism. Our approach offers a computational framework for assessing the complexity of cellular heterogeneity, investigating the degree to which perturbations induce redistributions of a limited, but nontrivial, repertoire of underlying states and revealing functional significance contained within distinct patterns of heterogeneous responses.

  11. Cosserat modeling of cellular solids

    NARCIS (Netherlands)

    Onck, P.R.

    Cellular solids inherit their macroscopic mechanical properties directly from the cellular microstructure. However, the characteristic material length scale is often not small compared to macroscopic dimensions, which limits the applicability of classical continuum-type constitutive models. Cosserat

  12. Evaluation of Structural Cellular Glass

    Science.gov (United States)

    Adams, M. A.; Zwissler, J. G.

    1984-01-01

    Preliminary design information presented. First report discusses state of structural-cellular-glass programs as of June 1979. Second report gives further details of program to develop improved cellular glasses and to characterize properties of glasses and commercially available materials.

  13. An agent-based model of cellular dynamics and circadian variability in human endotoxemia.

    Directory of Open Access Journals (Sweden)

    Tung T Nguyen

    Full Text Available As cellular variability and circadian rhythmicity play critical roles in immune and inflammatory responses, we present in this study an agent-based model of human endotoxemia to examine the interplay between circadian controls, cellular variability and stochastic dynamics of inflammatory cytokines. The model is qualitatively validated by its ability to reproduce circadian dynamics of inflammatory mediators and critical inflammatory responses after endotoxin administration in vivo. Novel computational concepts are proposed to characterize the cellular variability and synchronization of inflammatory cytokines in a population of heterogeneous leukocytes. Our results suggest that there is a decrease in cell-to-cell variability of inflammatory cytokines while their synchronization is increased after endotoxin challenge. Model parameters that are responsible for IκB production stimulated by NFκB activation and for the production of anti-inflammatory cytokines have large impacts on system behaviors. Additionally, examining time-dependent systemic responses revealed that the system is least vulnerable to endotoxin in the early morning and most vulnerable around midnight. Although much remains to be explored, proposed computational concepts and the model we have pioneered will provide important insights for future investigations and extensions, especially for single-cell studies to discover how cellular variability contributes to clinical implications.

  14. Cellular communication through light.

    Directory of Open Access Journals (Sweden)

    Daniel Fels

    Full Text Available Information transfer is a fundamental of life. A few studies have reported that cells use photons (from an endogenous source as information carriers. This study finds that cells can have an influence on other cells even when separated with a glass barrier, thereby disabling molecule diffusion through the cell-containing medium. As there is still very little known about the potential of photons for intercellular communication this study is designed to test for non-molecule-based triggering of two fundamental properties of life: cell division and energy uptake. The study was performed with a cellular organism, the ciliate Paramecium caudatum. Mutual exposure of cell populations occurred under conditions of darkness and separation with cuvettes (vials allowing photon but not molecule transfer. The cell populations were separated either with glass allowing photon transmission from 340 nm to longer waves, or quartz being transmittable from 150 nm, i.e. from UV-light to longer waves. Even through glass, the cells affected cell division and energy uptake in neighboring cell populations. Depending on the cuvette material and the number of cells involved, these effects were positive or negative. Also, while paired populations with lower growth rates grew uncorrelated, growth of the better growing populations was correlated. As there were significant differences when separating the populations with glass or quartz, it is suggested that the cell populations use two (or more frequencies for cellular information transfer, which influences at least energy uptake, cell division rate and growth correlation. Altogether the study strongly supports a cellular communication system, which is different from a molecule-receptor-based system and hints that photon-triggering is a fine tuning principle in cell chemistry.

  15. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  16. Cellular mechanics and motility

    Science.gov (United States)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

  17. A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

    Science.gov (United States)

    Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

    2016-03-01

    Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

  18. Cellular image classification

    CERN Document Server

    Xu, Xiang; Lin, Feng

    2017-01-01

    This book introduces new techniques for cellular image feature extraction, pattern recognition and classification. The authors use the antinuclear antibodies (ANAs) in patient serum as the subjects and the Indirect Immunofluorescence (IIF) technique as the imaging protocol to illustrate the applications of the described methods. Throughout the book, the authors provide evaluations for the proposed methods on two publicly available human epithelial (HEp-2) cell datasets: ICPR2012 dataset from the ICPR'12 HEp-2 cell classification contest and ICIP2013 training dataset from the ICIP'13 Competition on cells classification by fluorescent image analysis. First, the reading of imaging results is significantly influenced by one’s qualification and reading systems, causing high intra- and inter-laboratory variance. The authors present a low-order LP21 fiber mode for optical single cell manipulation and imaging staining patterns of HEp-2 cells. A focused four-lobed mode distribution is stable and effective in optical...

  19. Modeling and cellular studies

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    Testing the applicability of mathematical models with carefully designed experiments is a powerful tool in the investigations of the effects of ionizing radiation on cells. The modeling and cellular studies complement each other, for modeling provides guidance for designing critical experiments which must provide definitive results, while the experiments themselves provide new input to the model. Based on previous experimental results the model for the accumulation of damage in Chlamydomonas reinhardi has been extended to include various multiple two-event combinations. Split dose survival experiments have shown that models tested to date predict most but not all the observed behavior. Stationary-phase mammalian cells, required for tests of other aspects of the model, have been shown to be at different points in the cell cycle depending on how they were forced to stop proliferating. These cultures also demonstrate different capacities for repair of sublethal radiation damage

  20. Cellular Antiviral Factors that Target Particle Infectivity of HIV-1.

    Science.gov (United States)

    Goffinet, Christine

    2016-01-01

    In the past decade, the identification and characterization of antiviral genes with the ability to interfere with virus replication has established cell-intrinsic innate immunity as a third line of antiviral defense in addition to adaptive and classical innate immunity. Understanding how cellular factors have evolved to inhibit HIV-1 reveals particularly vulnerable points of the viral replication cycle. Many, but not all, antiviral proteins share type I interferon-upregulated expression and sensitivity to viral counteraction or evasion measures. Whereas well-established restriction factors interfere with early post-entry steps and release of HIV-1, recent research has revealed a diverse set of proteins that reduce the infectious quality of released particles using individual, to date poorly understood modes of action. These include induction of paucity of mature glycoproteins in nascent virions or self-incorporation into the virus particle, resulting in poor infectiousness of the virion and impaired spread of the infection. A better understanding of these newly discovered antiviral factors may open new avenues towards the design of drugs that repress the spread of viruses whose genomes have already integrated.

  1. [Incontinentia pigmenti with defect in cellular immunity].

    Science.gov (United States)

    Zamora-Chávez, Antonio; Escobar-Sánchez, Argelia; Sadowinski-Pine, Stanislaw; Saucedo-Ramírez, Omar Josué; Delgado-Barrera, Palmira; Enríquez-Quiñones, Claudia G

    Incontinentia pigmenti is a rare, X-linked genetic disease and affects all ectoderm-derived tissues such as skin, appendages, eyes, teeth and central nervous system as well as disorders of varying degree of cellular immunity characterized by decreasing melanin in the epidermis and increase in the dermis. When the condition occurs in males, it is lethal. We present the case of a 2-month-old infant with severe incontinentia pigmenti confirmed by histological examination of skin biopsy. The condition evolved with severe neurological disorders and seizures along with severe cellular immune deficiency, which affected the development of severe infections and caused the death of the patient. The importance of early clinical diagnosis is highlighted along with the importance of multidisciplinary management of neurological disorders and infectious complications. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  2. Statistical mechanics of cellular automata

    International Nuclear Information System (INIS)

    Wolfram, S.

    1983-01-01

    Cellular automata are used as simple mathematical models to investigate self-organization in statistical mechanics. A detailed analysis is given of ''elementary'' cellular automata consisting of a sequence of sites with values 0 or 1 on a line, with each site evolving deterministically in discrete time steps according to p definite rules involving the values of its nearest neighbors. With simple initial configurations, the cellular automata either tend to homogeneous states, or generate self-similar patterns with fractal dimensions approx. =1.59 or approx. =1.69. With ''random'' initial configurations, the irreversible character of the cellular automaton evolution leads to several self-organization phenomena. Statistical properties of the structures generated are found to lie in two universality classes, independent of the details of the initial state or the cellular automaton rules. More complicated cellular automata are briefly considered, and connections with dynamical systems theory and the formal theory of computation are discussed

  3. The Subduction of an Exhumed and Serpentinized Magma-Poor Basement Beneath the Northern Lesser Antilles Reveals the Early Tectonic Fabric at Slow-Spreading Mid-Oceanic Ridges

    Science.gov (United States)

    Marcaillou, B.; Klingelhoefer, F.; Laurencin, M.; Biari, Y.; Graindorge, D.; Jean-Frederic, L.; Laigle, M.; Lallemand, S.

    2017-12-01

    Multichannel and wide-angle seismic data as well as heat-flow measurements (ANTITHESIS cruise, 2016) reveal a 200x200km patch of magma-poor oceanic basement in the trench and beneath the outer fore-arc offshore of Antigua to Saint Martin in the Northern Lesser Antilles. These data highlight an oceanic basement with the following features: 1/ Absence of any reflection at typical Moho depth and layer2/layer3 limit depths. 2/ High Velocity Vp at the top (>5.5 km/s), low velocity gradient with depth (serpentinized at the slow-spreading mid-Atlantic Ridge 80 Myr ago, is currently subducting beneath the Northern Lesser Antilles. During the exhumation, early extension triggers penetrative shear zones sub-parallel to the ridge and to the transform fault. Eventually, this early extension generates sliding along the so-called detachment fault, while the other proto-detachment abort. Approaching the trench, the plate bending reactivates these weak zones in normal faults and fluid pathways promoting deep serpentinisation and localizing tectonic deformation at the plate interface. These subducting fluid-rich mechanically weak mantle rocks rise questions about their relation to the faster slab deepening, the lower seismic activity and the pervasive tectonic partitioning in this margin segment.

  4. Analysis of the asymmetrically expressed Ablim1 locus reveals existence of a lateral plate Nodal-independent left sided signal and an early, left-right independent role for nodal flow

    Directory of Open Access Journals (Sweden)

    Hilton Helen

    2010-05-01

    Full Text Available Abstract Background Vertebrates show clear asymmetry in left-right (L-R patterning of their organs and associated vasculature. During mammalian development a cilia driven leftwards flow of liquid leads to the left-sided expression of Nodal, which in turn activates asymmetric expression of the transcription factor Pitx2. While Pitx2 asymmetry drives many aspects of asymmetric morphogenesis, it is clear from published data that additional asymmetrically expressed loci must exist. Results A L-R expression screen identified the cytoskeletally-associated gene, actin binding lim protein 1 (Ablim1, as asymmetrically expressed in both the node and left lateral plate mesoderm (LPM. LPM expression closely mirrors that of Nodal. Significantly, Ablim1 LPM asymmetry was detected in the absence of detectable Nodal. In the node, Ablim1 was initially expressed symmetrically across the entire structure, resolving to give a peri-nodal ring at the headfold stage in a flow and Pkd2-dependent manner. The peri-nodal ring of Ablim1 expression became asymmetric by the mid-headfold stage, showing stronger right than left-sided expression. Node asymmetry became more apparent as development proceeded; expression retreated in an anticlockwise direction, disappearing first from the left anterior node. Indeed, at early somite stages Ablim1 shows a unique asymmetric expression pattern, in the left lateral plate and to the right side of the node. Conclusion Left LPM Ablim1 is expressed in the absence of detectable LPM Nodal, clearly revealing existence of a Pitx2 and Nodal-independent left-sided signal in mammals. At the node, a previously unrecognised action of early nodal flow and Pkd2 activity, within the pit of the node, influences gene expression in a symmetric manner. Subsequent Ablim1 expression in the peri-nodal ring reveals a very early indication of L-R asymmetry. Ablim1 expression analysis at the node acts as an indicator of nodal flow. Together these results make

  5. 47 CFR 22.909 - Cellular markets.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets...

  6. Uncovering the footprints of malicious traffic in cellular data networks

    OpenAIRE

    Raghuramu, A; Zang, H; Chuah, CN

    2015-01-01

    © Springer International Publishing Switzerland 2015. In this paper, we present a comprehensive characterization of malicious traffic generated by mobile devices using Deep Packet Inspection (DPI) records and security event logs from a large US based cellular provider network. Our analysis reveals that 0.17% of mobile devices in the cellular network are affected by security threats. This proportion, while small, is orders of magnitude higher than the last reported (in 2013) infection rate of ...

  7. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  8. MSAT and cellular hybrid networking

    Science.gov (United States)

    Baranowsky, Patrick W., II

    Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

  9. Cellular automata analysis and applications

    CERN Document Server

    Hadeler, Karl-Peter

    2017-01-01

    This book focuses on a coherent representation of the main approaches to analyze the dynamics of cellular automata. Cellular automata are an inevitable tool in mathematical modeling. In contrast to classical modeling approaches as partial differential equations, cellular automata are straightforward to simulate but hard to analyze. In this book we present a review of approaches and theories that allow the reader to understand the behavior of cellular automata beyond simulations. The first part consists of an introduction of cellular automata on Cayley graphs, and their characterization via the fundamental Cutis-Hedlund-Lyndon theorems in the context of different topological concepts (Cantor, Besicovitch and Weyl topology). The second part focuses on classification results: What classification follows from topological concepts (Hurley classification), Lyapunov stability (Gilman classification), and the theory of formal languages and grammars (Kůrka classification). These classifications suggest to cluster cel...

  10. MIMO Communication for Cellular Networks

    CERN Document Server

    Huang, Howard; Venkatesan, Sivarama

    2012-01-01

    As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

  11. Programmable cellular arrays. Faults testing and correcting in cellular arrays

    International Nuclear Information System (INIS)

    Cercel, L.

    1978-03-01

    A review of some recent researches about programmable cellular arrays in computing and digital processing of information systems is presented, and includes both combinational and sequential arrays, with full arbitrary behaviour, or which can realize better implementations of specialized blocks as: arithmetic units, counters, comparators, control systems, memory blocks, etc. Also, the paper presents applications of cellular arrays in microprogramming, in implementing of a specialized computer for matrix operations, in modeling of universal computing systems. The last section deals with problems of fault testing and correcting in cellular arrays. (author)

  12. Dopaminergic enhancement of cellular adhesion in bone marrow derived mesenchymal stem cells (MSCs).

    Science.gov (United States)

    Chen, Si; Bai, Bing; Lee, Dong Joon; Diachina, Shannon; Li, Yina; Wong, Sing Wai; Wang, Zhengyan; Tseng, Henry C; Ko, Ching-Chang

    2017-08-01

    Dopamine (DA) is a well-known neurotransmitter and critical element in the mussel adhesive protein that has gained increasing attention for its role in cellular growth enhancement in biomaterials, including cellular adhesion improvement. As the mechanism underlying this remains unclear, the objective of this study was to explore the effects of DA on the adhesion properties of bone marrow derived rat mesenchymal stem cells (rMSCs) using an hydroxyapatite gelatin nanocomposite biomaterial and to test whether the effects are mediated through various endogenously expressed DA receptors. Primary rMSCs were pretreated with D1-like antagonist, D2-like antagonist, or a combination of these antagonists followed by treatment with 50 μM DA and cellular adhesion quantification at 0.5, 1, 2 and 4 hours post DA addition. DA was found to increase rMSC adhesion and spreading at the 0.5 hour time-point and the dopaminergic effect on cell adhesion was partially blocked by DA antagonists. In addition, the D1-like and D2-like antagonists appeared to have a similar effect on rMSCs. Immunofluorescent staining indicated that the rMSC spreading area was significantly increased in the DA treated group versus the control group. Treatment of the D1-like DA antagonists with DA revealed that the actin filaments of rMSCs could not connect the membrane with the nucleus. In summary, DA was found to enhance early rMSC adhesion partially via DA receptor activation.

  13. Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) analysis.

    Science.gov (United States)

    Benza, Raymond L; Miller, Dave P; Foreman, Aimee J; Frost, Adaani E; Badesch, David B; Benton, Wade W; McGoon, Michael D

    2015-03-01

    Data from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) were used previously to develop a risk score calculator to predict 1-year survival. We evaluated prognostic implications of changes in the risk score and individual risk-score parameters over 12 months. Patients were grouped by decreased, unchanged, or increased risk score from enrollment to 12 months. Kaplan-Meier estimates of subsequent 1-year survival were made based on change in the risk score during the initial 12 months of follow-up. Cox regression was used for multivariable analysis. Of 2,529 patients in the analysis cohort, the risk score was decreased in 800, unchanged in 959, and increased in 770 at 12 months post-enrollment. Six parameters (functional class, systolic blood pressure, heart rate, 6-minute walk distance, brain natriuretic peptide levels, and pericardial effusion) each changed sufficiently over time to improve or worsen risk scores in ≥5% of patients. One-year survival estimates in the subsequent year were 93.7%, 90.3%, and 84.6% in patients with a decreased, unchanged, and increased risk score at 12 months, respectively. Change in risk score significantly predicted future survival, adjusting for risk at enrollment. Considering follow-up risk concurrently with risk at enrollment, follow-up risk was a much stronger predictor, although risk at enrollment maintained a significant effect on future survival. Changes in REVEAL risk scores occur in most patients with pulmonary arterial hypertension over a 12-month period and are predictive of survival. Thus, serial risk score assessments can identify changes in disease trajectory that may warrant treatment modifications. Copyright © 2015 International Society for Heart and Lung Transplantation. All rights reserved.

  14. Top-down cellular pyramids

    Energy Technology Data Exchange (ETDEWEB)

    Wu, A Y; Rosenfeld, A

    1983-10-01

    A cellular pyramid is an exponentially tapering stack of arrays of processors (cells), where each cell is connected to its neighbors (siblings) on its own level, to a parent on the level above, and to its children on the level below. It is shown that in some situations, if information flows top-down only, from fathers to sons, then a cellular pyramid may be no faster than a one-level cellular array; but it may be possible to use simpler cells in the pyramid case. 23 references.

  15. Cellular senescence and organismal aging.

    Science.gov (United States)

    Jeyapalan, Jessie C; Sedivy, John M

    2008-01-01

    Cellular senescence, first observed and defined using in vitro cell culture studies, is an irreversible cell cycle arrest which can be triggered by a variety of factors. Emerging evidence suggests that cellular senescence acts as an in vivo tumor suppression mechanism by limiting aberrant proliferation. It has also been postulated that cellular senescence can occur independently of cancer and contribute to the physiological processes of normal organismal aging. Recent data have demonstrated the in vivo accumulation of senescent cells with advancing age. Some characteristics of senescent cells, such as the ability to modify their extracellular environment, could play a role in aging and age-related pathology. In this review, we examine current evidence that links cellular senescence and organismal aging.

  16. Origami interleaved tube cellular materials

    International Nuclear Information System (INIS)

    Cheung, Kenneth C; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

    2014-01-01

    A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis. (paper)

  17. Origami interleaved tube cellular materials

    Science.gov (United States)

    Cheung, Kenneth C.; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

    2014-09-01

    A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis.

  18. Cellular Adhesion Promotes Prostate Cancer Cells Escape from Dormancy.

    Science.gov (United States)

    Ruppender, Nazanin; Larson, Sandy; Lakely, Bryce; Kollath, Lori; Brown, Lisha; Coleman, Ilsa; Coleman, Roger; Nguyen, Holly; Nelson, Peter S; Corey, Eva; Snyder, Linda A; Vessella, Robert L; Morrissey, Colm; Lam, Hung-Ming

    2015-01-01

    Dissemination of prostate cancer (PCa) cells to the bone marrow is an early event in the disease process. In some patients, disseminated tumor cells (DTC) proliferate to form active metastases after a prolonged period of undetectable disease known as tumor dormancy. Identifying mechanisms of PCa dormancy and reactivation remain a challenge partly due to the lack of in vitro models. Here, we characterized in vitro PCa dormancy-reactivation by inducing cells from three patient-derived xenograft (PDX) lines to proliferate through tumor cell contact with each other and with bone marrow stroma. Proliferating PCa cells demonstrated tumor cell-cell contact and integrin clustering by immunofluorescence. Global gene expression analyses on proliferating cells cultured on bone marrow stroma revealed a downregulation of TGFB2 in all of the three proliferating PCa PDX lines when compared to their non-proliferating counterparts. Furthermore, constitutive activation of myosin light chain kinase (MLCK), a downstream effector of integrin-beta1 and TGF-beta2, in non-proliferating cells promoted cell proliferation. This cell proliferation was associated with an upregulation of CDK6 and a downregulation of E2F4. Taken together, our data provide the first clinically relevant in vitro model to support cellular adhesion and downregulation of TGFB2 as a potential mechanism by which PCa cells may escape from dormancy. Targeting the TGF-beta2-associated mechanism could provide novel opportunities to prevent lethal PCa metastasis.

  19. Revealing Rembrandt

    Directory of Open Access Journals (Sweden)

    Andrew J Parker

    2014-04-01

    Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

  20. Cellular registration without behavioral recall of olfactory sensory input under general anesthesia.

    Science.gov (United States)

    Samuelsson, Andrew R; Brandon, Nicole R; Tang, Pei; Xu, Yan

    2014-04-01

    Previous studies suggest that sensory information is "received" but not "perceived" under general anesthesia. Whether and to what extent the brain continues to process sensory inputs in a drug-induced unconscious state remain unclear. One hundred seven rats were randomly assigned to 12 different anesthesia and odor exposure paradigms. The immunoreactivities of the immediate early gene products c-Fos and Egr1 as neural activity markers were combined with behavioral tests to assess the integrity and relationship of cellular and behavioral responsiveness to olfactory stimuli under a surgical plane of ketamine-xylazine general anesthesia. The olfactory sensory processing centers could distinguish the presence or absence of experimental odorants even when animals were fully anesthetized. In the anesthetized state, the c-Fos immunoreactivity in the higher olfactory cortices revealed a difference between novel and familiar odorants similar to that seen in the awake state, suggesting that the anesthetized brain functions beyond simply receiving external stimulation. Reexposing animals to odorants previously experienced only under anesthesia resulted in c-Fos immunoreactivity, which was similar to that elicited by familiar odorants, indicating that previous registration had occurred in the anesthetized brain. Despite the "cellular memory," however, odor discrimination and forced-choice odor-recognition tests showed absence of behavioral recall of the registered sensations, except for a longer latency in odor recognition tests. Histologically distinguishable registration of sensory processing continues to occur at the cellular level under ketamine-xylazine general anesthesia despite the absence of behavioral recognition, consistent with the notion that general anesthesia causes disintegration of information processing without completely blocking cellular communications.

  1. Influence of postoperative enteral nutrition on cellular immunity. A random double-blinded placebo controlled clinical trial

    DEFF Research Database (Denmark)

    Beier-Holgersen, R; Brandstrup, B

    2012-01-01

    The aim of this study was to discover if the cellular immunological response is different in patients receiving early postoperative enteral nutrition compared to patients who only receive "water".......The aim of this study was to discover if the cellular immunological response is different in patients receiving early postoperative enteral nutrition compared to patients who only receive "water"....

  2. Genomic Analysis of Uterine Lavage Fluid Detects Early Endometrial Cancers and Reveals a Prevalent Landscape of Driver Mutations in Women without Histopathologic Evidence of Cancer: A Prospective Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Navya Nair

    2016-12-01

    Full Text Available Endometrial cancer is the most common gynecologic malignancy, and its incidence and associated mortality are increasing. Despite the immediate need to detect these cancers at an earlier stage, there is no effective screening methodology or protocol for endometrial cancer. The comprehensive, genomics-based analysis of endometrial cancer by The Cancer Genome Atlas (TCGA revealed many of the molecular defects that define this cancer. Based on these cancer genome results, and in a prospective study, we hypothesized that the use of ultra-deep, targeted gene sequencing could detect somatic mutations in uterine lavage fluid obtained from women undergoing hysteroscopy as a means of molecular screening and diagnosis.Uterine lavage and paired blood samples were collected and analyzed from 107 consecutive patients who were undergoing hysteroscopy and curettage for diagnostic evaluation from this single-institution study. The lavage fluid was separated into cellular and acellular fractions by centrifugation. Cellular and cell-free DNA (cfDNA were isolated from each lavage. Two targeted next-generation sequencing (NGS gene panels, one composed of 56 genes and the other of 12 genes, were used for ultra-deep sequencing. To rule out potential NGS-based errors, orthogonal mutation validation was performed using digital PCR and Sanger sequencing. Seven patients were diagnosed with endometrial cancer based on classic histopathologic analysis. Six of these patients had stage IA cancer, and one of these cancers was only detectable as a microscopic focus within a polyp. All seven patients were found to have significant cancer-associated gene mutations in both cell pellet and cfDNA fractions. In the four patients in whom adequate tumor sample was available, all tumor mutations above a specific allele fraction were present in the uterine lavage DNA samples. Mutations originally only detected in lavage fluid fractions were later confirmed to be present in tumor but at

  3. Cellular-based preemption system

    Science.gov (United States)

    Bachelder, Aaron D. (Inventor)

    2011-01-01

    A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

  4. Novel Materials for Cellular Nanosensors

    DEFF Research Database (Denmark)

    Sasso, Luigi

    The monitoring of cellular behavior is useful for the advancement of biomedical diagnostics, drug development and the understanding of a cell as the main unit of the human body. Micro- and nanotechnology allow for the creation of functional devices that enhance the study of cellular dynamics...... modifications for electrochemical nanosensors for the detection of analytes released from cells. Two type of materials were investigated, each pertaining to the two different aspects of such devices: peptide nanostructures were studied for the creation of cellular sensing substrates that mimic in vivo surfaces...... and that offer advantages of functionalization, and conducting polymers were used as electrochemical sensor surface modifications for increasing the sensitivity towards relevant analytes, with focus on the detection of dopamine released from cells via exocytosis. Vertical peptide nanowires were synthesized from...

  5. Scintigraphic demonstration of a metastasizing hepato-cellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Heintz, P; Gratz, K F; Schwarzrock, R; Schober, O; Neuhaus, P; Creutzig, H

    1986-01-01

    Adenomas and hepato cellular carcinomas cannot be differentiated by nuclear medicine: both exhibit masked radiodrug trapping at reduced perfusion. Two patients revealed specific accumulation in extrahepatic foci unknown before; hence, the diagnosis of a metastasizing hepatocellular carcinoma had to be verified. One case is demonstrated in full detail. (orig./SHA).

  6. Global properties of cellular automata

    International Nuclear Information System (INIS)

    Jen, E.

    1986-01-01

    Cellular automata are discrete mathematical systems that generate diverse, often complicated, behavior using simple deterministic rules. Analysis of the local structure of these rules makes possible a description of the global properties of the associated automata. A class of cellular automata that generate infinitely many aperoidic temporal sequences is defined,a s is the set of rules for which inverses exist. Necessary and sufficient conditions are derived characterizing the classes of ''nearest-neighbor'' rules for which arbitrary finite initial conditions (i) evolve to a homogeneous state; (ii) generate at least one constant temporal sequence

  7. Cellular structures with interconnected microchannels

    Science.gov (United States)

    Shaefer, Robert Shahram; Ghoniem, Nasr M.; Williams, Brian

    2018-01-30

    A method for fabricating a cellular tritium breeder component includes obtaining a reticulated carbon foam skeleton comprising a network of interconnected ligaments. The foam skeleton is then melt-infiltrated with a tritium breeder material, for example, lithium zirconate or lithium titanate. The foam skeleton is then removed to define a cellular breeder component having a network of interconnected tritium purge channels. In an embodiment the ligaments of the foam skeleton are enlarged by adding carbon using chemical vapor infiltration (CVI) prior to melt-infiltration. In an embodiment the foam skeleton is coated with a refractory material, for example, tungsten, prior to melt infiltration.

  8. Probabilistic cellular automata: Some statistical mechanical considerations

    International Nuclear Information System (INIS)

    Lebowitz, J.L.; Maes, C.; Speer, E.R.

    1990-01-01

    Spin systems evolving in continuous or discrete time under the action of stochastic dynamics are used to model phenomena as diverse as the structure of alloys and the functioning of neural networks. While in some cases the dynamics are secondary, designed to produce a specific stationary measure whose properties one is interested in studying, there are other cases in which the only available information is the dynamical rule. Prime examples of the former are computer simulations, via Glauber dynamics, of equilibrium Gibbs measures with a specified interaction potential. Examples of the latter include various types of majority rule dynamics used as models for pattern recognition and for error-tolerant computations. The present note discusses ways in which techniques found useful in equilibrium statistical mechanics can be applied to a particular class of models of the latter types. These are cellular automata with noise: systems in which the spins are updated stochastically at integer times, simultaneously at all sites of some regular lattice. These models were first investigated in detail in the Soviet literature of the late sixties and early seventies. They are now generally referred to as Stochastic or Probabilistic Cellular Automata (PCA), and may be considered to include deterministic automata (CA) as special limits. 16 refs., 3 figs

  9. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN...

  10. Repaglinide at a cellular level

    DEFF Research Database (Denmark)

    Krogsgaard Thomsen, M; Bokvist, K; Høy, M

    2002-01-01

    To investigate the hormonal and cellular selectivity of the prandial glucose regulators, we have undertaken a series of experiments, in which we characterised the effects of repaglinide and nateglinide on ATP-sensitive potassium ion (KATP) channel activity, membrane potential and exocytosis in ra...

  11. Cellular automaton for surface reactions

    Energy Technology Data Exchange (ETDEWEB)

    Pechatnikov, E L [AN SSSR, Chernogolovka (Russian Federation). Otdelenie Inst. Khimicheskoj Fiziki; Frankowicz, A; Danielak, R [Uniwersytet Jagiellonski, Cracow (Poland)

    1994-06-01

    A new algorithm which overcomes some specific difficulties arising in modeling of heterogeneous catalytic processes by cellular automata (CA) technique is proposed. The algorithm was tested with scheme introduced by Ziff, Gulari and Barshad and showed a good agreement with their results. The problem of the physical adequacy and interpretation of the algorithm was discussed. (author). 10 refs, 4 figs.

  12. Cellular buckling in long structures

    NARCIS (Netherlands)

    Hunt, G.W.; Peletier, M.A.; Champneys, A.R.; Woods, P.D.; Wadee, M.A.; Budd, C.J.; Lord, G.J.

    2000-01-01

    A long structural system with an unstable (subcritical)post-buckling response that subsequently restabilizes typically deformsin a cellular manner, with localized buckles first forming and thenlocking up in sequence. As buckling continues over a growing number ofcells, the response can be described

  13. Characterization of early autophagy signaling by quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Rigbolt, Kristoffer Tg; Zarei, Mostafa; Sprenger, Adrian

    2014-01-01

    . To elucidate the regulation of early signaling events upon autophagy induction, we applied quantitative phosphoproteomics characterizing the temporal phosphorylation dynamics after starvation and rapamycin treatment. We obtained a comprehensive atlas of phosphorylation kinetics within the first 30 min upon...... revealing regulated phosphorylation sites on proteins involved in a wide range of cellular processes and an impact of the treatments on the kinome. To approach the potential function of the identified phosphorylation sites we performed a screen for MAP1LC3-interacting proteins and identified a group...... induction of autophagy with both treatments affecting widely different cellular processes. The identification of dynamic phosphorylation already after 2 min demonstrates that the earliest events in autophagy signaling occur rapidly after induction. The data was subjected to extensive bioinformatics analysis...

  14. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    Directory of Open Access Journals (Sweden)

    O.Popescu

    1999-01-01

    Full Text Available Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of isolated and purified glyconectins revealed the presence of specific carbohydrate structures, acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight containing fucose, glucuronic or galacturonic acids, and sulfate groups, originally found in sponges and sea urchin embryos, may represent a new class of carbohydrate carcino-embryonal antigens in mice and humans. Such interactions between biological macromolecules are usually investigated by kinetic binding studies, calorimetric methods, X-ray diffraction, nuclear magnetic resonance, and other spectroscopic analyses. However, these methods do not supply a direct estimation of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Recently, we have introduced atomic force microscopy to quantify the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion proteoglycans is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. As a model, we selected the glyconectin 1, a cell adhesion proteoglycan isolated from the marine sponge Microciona prolifera. This glyconectin mediates in vivo cell recognition and aggregation via homophilic, species-specific, polyvalent, and calcium ion-dependent carbohydrate-carbohydrate interactions. Under physiological conditions, an adhesive force of up to 400 piconewtons

  15. Nonsynchronous updating in the multiverse of cellular automata

    Science.gov (United States)

    Reia, Sandro M.; Kinouchi, Osame

    2015-04-01

    In this paper we study updating effects on cellular automata rule space. We consider a subset of 6144 order-3 automata from the space of 262144 bidimensional outer-totalistic rules. We compare synchronous to asynchronous and sequential updatings. Focusing on two automata, we discuss how update changes destroy typical structures of these rules. Besides, we show that the first-order phase transition in the multiverse of synchronous cellular automata, revealed with the use of a recently introduced control parameter, seems to be robust not only to changes in update schema but also to different initial densities.

  16. Nonsynchronous updating in the multiverse of cellular automata.

    Science.gov (United States)

    Reia, Sandro M; Kinouchi, Osame

    2015-04-01

    In this paper we study updating effects on cellular automata rule space. We consider a subset of 6144 order-3 automata from the space of 262144 bidimensional outer-totalistic rules. We compare synchronous to asynchronous and sequential updatings. Focusing on two automata, we discuss how update changes destroy typical structures of these rules. Besides, we show that the first-order phase transition in the multiverse of synchronous cellular automata, revealed with the use of a recently introduced control parameter, seems to be robust not only to changes in update schema but also to different initial densities.

  17. Universal map for cellular automata

    International Nuclear Information System (INIS)

    García-Morales, V.

    2012-01-01

    A universal map is derived for all deterministic 1D cellular automata (CAs) containing no freely adjustable parameters and valid for any alphabet size and any neighborhood range (including non-symmetrical neighborhoods). The map can be extended to an arbitrary number of dimensions and topologies and to arbitrary order in time. Specific CA maps for the famous Conway's Game of Life and Wolfram's 256 elementary CAs are given. An induction method for CAs, based in the universal map, allows mathematical expressions for the orbits of a wide variety of elementary CAs to be systematically derived. -- Highlights: ► A universal map is derived for all deterministic 1D cellular automata (CA). ► The map is generalized to 2D for Von Neumann, Moore and hexagonal neighborhoods. ► A map for all Wolfram's 256 elementary CAs is derived. ► A map for Conway's “Game of Life” is obtained.

  18. Simulating physics with cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Vichniac, G Y

    1984-01-01

    Cellular automata are dynamical systems where space, time, and variables are discrete. They are shown on two-dimensional examples to be capable of non-numerical simulations of physics. They are useful for faithful parallel processing of lattice models. At another level, they exhibit behaviours and illustrate concepts that are unmistakably physical, such as non-ergodicity and order parameters, frustration, relaxation to chaos through period doublings, a conspicuous arrow of time in reversible microscopic dynamics, causality and light-cone, and non-separability. In general, they constitute exactly computable models for complex phenomena and large-scale correlations that result from very simple short-range interactions. The author studies their space, time, and intrinsic symmetries and the corresponding conservation laws, with an emphasis on the conservation of information obeyed by reversible cellular automata. 60 references.

  19. Cellular Adhesion and Adhesion Molecules

    OpenAIRE

    SELLER, Zerrin

    2014-01-01

    In recent years, cell adhesion and cell adhesion molecules have been shown to be important for many normal biological processes, including embryonic cell migration, immune system functions and wound healing. It has also been shown that they contribute to the pathogenesis of a large number of common human disorders, such as rheumatoid arthritis and tumor cell metastasis in cancer. In this review, the basic mechanisms of cellular adhesion and the structural and functional features of adhes...

  20. Cellular automata with voting rule

    International Nuclear Information System (INIS)

    Makowiec, D.

    1996-01-01

    The chosen local interaction - the voting (majority) rule applied to the square lattice is known to cause the non ergodic cellular automata behaviour. Presented computer simulation results verify two cases of non ergodicity. The first one is implicated by the noise introduced to the local interactions and the second one follows properties of the initial lattice configuration selected at random. For the simplified voting rule - non symmetric voting, the critical behaviour has been explained rigorously. (author)

  1. Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model

    Science.gov (United States)

    Limmer, Stefanie; Haller, Samantha; Drenkard, Eliana; Lee, Janice; Yu, Shen; Kocks, Christine; Ausubel, Frederick M.; Ferrandon, Dominique

    2011-01-01

    An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host–pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated. PMID:21987808

  2. Cellular communications a comprehensive and practical guide

    CERN Document Server

    Tripathi, Nishith

    2014-01-01

    Even as newer cellular technologies and standards emerge, many of the fundamental principles and the components of the cellular network remain the same. Presenting a simple yet comprehensive view of cellular communications technologies, Cellular Communications provides an end-to-end perspective of cellular operations, ranging from physical layer details to call set-up and from the radio network to the core network. This self-contained source forpractitioners and students represents a comprehensive survey of the fundamentals of cellular communications and the landscape of commercially deployed

  3. The cellular approach to band structure calculations

    International Nuclear Information System (INIS)

    Verwoerd, W.S.

    1982-01-01

    A short introduction to the cellular approach in band structure calculations is given. The linear cellular approach and its potantial applicability in surface structure calculations is given some consideration in particular

  4. [Cellular subcutaneous tissue. Anatomic observations].

    Science.gov (United States)

    Marquart-Elbaz, C; Varnaison, E; Sick, H; Grosshans, E; Cribier, B

    2001-11-01

    We showed in a companion paper that the definition of the French "subcutaneous cellular tissue" considerably varied from the 18th to the end of the 20th centuries and has not yet reached a consensus. To address the anatomic reality of this "subcutaneous cellular tissue", we investigated the anatomic structures underlying the fat tissue in normal human skin. Sixty specimens were excised from the surface to the deep structures (bone, muscle, cartilage) on different body sites of 3 cadavers from the Institut d'Anatomie Normale de Strasbourg. Samples were paraffin-embedded, stained and analysed with a binocular microscope taking x 1 photographs. Specimens were also excised and fixed after subcutaneous injection of Indian ink, after mechanic tissue splitting and after performing artificial skin folds. The aspects of the deep parts of the skin greatly varied according to their anatomic localisation. Below the adipose tissue, we often found a lamellar fibrous layer which extended from the interlobular septa and contained horizontally distributed fat cells. No specific tissue below the hypodermis was observed. Artificial skin folds concerned either exclusively the dermis, when they were superficial or included the hypodermis, but no specific structure was apparent in the center of the fold. India ink diffused to the adipose tissue, mainly along the septa, but did not localise in a specific subcutaneous compartment. This study shows that the histologic aspects of the deep part of the skin depend mainly on the anatomic localisation. Skin is composed of epidermis, dermis and hypodermis and thus the hypodermis can not be considered as being "subcutaneous". A difficult to individualise, fibrous lamellar structure in continuity with the interlobular septa is often found under the fat lobules. This structure is a cleavage line, as is always the case with loose connective tissues, but belongs to the hypodermis (i.e. fat tissue). No specific tissue nor any virtual space was

  5. Zeno's paradox in quantum cellular automata

    International Nuclear Information System (INIS)

    Groessing, G.; Zeilinger, A.

    1991-01-01

    The effect of Zeno's paradox in quantum theory is demonstrated with the aid of quantum mechanical cellular automata. It is shown that the degree of non-unitarity of the cellular automaton evolution and the frequency of consecutive measurements of cellular automaton states are operationally indistinguishable. (orig.)

  6. Zeno's paradox in quantum cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Groessing, G [Atominst. der Oesterreichischen Universitaeten, Vienna (Austria); Zeilinger, A [Inst. fuer Experimentalphysik, Univ. Innsbruck (Austria)

    1991-07-01

    The effect of Zeno's paradox in quantum theory is demonstrated with the aid of quantum mechanical cellular automata. It is shown that the degree of non-unitarity of the cellular automaton evolution and the frequency of consecutive measurements of cellular automaton states are operationally indistinguishable. (orig.).

  7. Game of Life Cellular Automata

    CERN Document Server

    Adamatzky, Andrew

    2010-01-01

    In the late 1960s, British mathematician John Conway invented a virtual mathematical machine that operates on a two-dimensional array of square cell. Each cell takes two states, live and dead. The cells' states are updated simultaneously and in discrete time. A dead cell comes to life if it has exactly three live neighbours. A live cell remains alive if two or three of its neighbours are alive, otherwise the cell dies. Conway's Game of Life became the most programmed solitary game and the most known cellular automaton. The book brings together results of forty years of study into computational

  8. 'Biomoleculas': cellular metabolism didactic software

    International Nuclear Information System (INIS)

    Menghi, M L; Novella, L P; Siebenlist, M R

    2007-01-01

    'Biomoleculas' is a software that deals with topics such as the digestion, cellular metabolism and excretion of nutrients. It is a pleasant, simple and didactic guide, made by and for students. In this program, each biomolecule (carbohydrates, lipids and proteins) is accompanied until its degradation and assimilation by crossing and interrelating the different metabolic channels to finally show the destination of the different metabolites formed and the way in which these are excreted. It is used at present as a teaching-learning process tool by the chair of Physiology and Biophysics at the Facultad de Ingenieria - Universidad Nacional de Entre Rios

  9. Symmetry analysis of cellular automata

    International Nuclear Information System (INIS)

    García-Morales, V.

    2013-01-01

    By means of B-calculus [V. García-Morales, Phys. Lett. A 376 (2012) 2645] a universal map for deterministic cellular automata (CAs) has been derived. The latter is shown here to be invariant upon certain transformations (global complementation, reflection and shift). When constructing CA rules in terms of rules of lower range a new symmetry, “invariance under construction” is uncovered. Modular arithmetic is also reformulated within B-calculus and a new symmetry of certain totalistic CA rules, which calculate the Pascal simplices modulo an integer number p, is then also uncovered.

  10. On two integrable cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Bobenko, A [Technische Univ. Berlin (Germany). Fachbereich Mathematik; Bordemann, M [Freiburg Univ. (Germany). Fachbereich Physik; Gunn, C [Technische Univ. Berlin (Germany). Fachbereich Mathematik; Pinkall, U [Technische Univ. Berlin (Germany). Fachbereich Mathematik

    1993-11-01

    We describe two simple cellular automata (CA) models which exhibit the essential attributes of soliton systems. The first one is an invertible, 2-state, 1-dimensional CA or, in other words, a nonlinear Z[sub 2]-valued dynamical system with discrete space and time. Against a vacuum state of 0, the system exhibits light cone particles in both spatial directions, which interact in a soliton-like fashion. A complete solution of this system is obtained. We also consider another CA, which is described by the Hirota equation over a finite field, and present a Lax representation for it. (orig.)

  11. Cellular automata a parallel model

    CERN Document Server

    Mazoyer, J

    1999-01-01

    Cellular automata can be viewed both as computational models and modelling systems of real processes. This volume emphasises the first aspect. In articles written by leading researchers, sophisticated massive parallel algorithms (firing squad, life, Fischer's primes recognition) are treated. Their computational power and the specific complexity classes they determine are surveyed, while some recent results in relation to chaos from a new dynamic systems point of view are also presented. Audience: This book will be of interest to specialists of theoretical computer science and the parallelism challenge.

  12. Time scale of diffusion in molecular and cellular biology

    International Nuclear Information System (INIS)

    Holcman, D; Schuss, Z

    2014-01-01

    Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function. (topical review)

  13. Time scale of diffusion in molecular and cellular biology

    Science.gov (United States)

    Holcman, D.; Schuss, Z.

    2014-05-01

    Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function.

  14. Melanoma screening with cellular phones.

    Directory of Open Access Journals (Sweden)

    Cesare Massone

    Full Text Available BACKGROUND: Mobile teledermatology has recently been shown to be suitable for teledermatology despite limitations in image definition in preliminary studies. The unique aspect of mobile teledermatology is that this system represents a filtering or triage system, allowing a sensitive approach for the management of patients with emergent skin diseases. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated the feasibility of teleconsultation using a new generation of cellular phones in pigmented skin lesions. 18 patients were selected consecutively in the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, Graz (Austria. Clinical and dermoscopic images were acquired using a Sony Ericsson with a built-in two-megapixel camera. Two teleconsultants reviewed the images on a specific web application (http://www.dermahandy.net/default.asp where images had been uploaded in JPEG format. Compared to the face-to-face diagnoses, the two teleconsultants obtained a score of correct telediagnoses of 89% and of 91.5% reporting the clinical and dermoscopic images, respectively. CONCLUSIONS/SIGNIFICANCE: The present work is the first study performing mobile teledermoscopy using cellular phones. Mobile teledermatology has the potential to become an easy applicable tool for everyone and a new approach for enhanced self-monitoring for skin cancer screening in the spirit of the eHealth program of the European Commission Information for Society and Media.

  15. Cellular Therapies Clinical Research Roadmap: lessons learned on how to move a cellular therapy into a clinical trial.

    Science.gov (United States)

    Ouseph, Stacy; Tappitake, Darah; Armant, Myriam; Wesselschmidt, Robin; Derecho, Ivy; Draxler, Rebecca; Wood, Deborah; Centanni, John M

    2015-04-01

    A clinical research roadmap has been developed as a resource for researchers to identify critical areas and potential pitfalls when transitioning a cellular therapy product from the research laboratory, by means of an Investigational New Drug (IND) application, into early-phase clinical trials. The roadmap describes four key areas: basic and preclinical research, resource development, translational research and Good Manufacturing Practice (GMP) and IND assembly and submission. Basic and preclinical research identifies a new therapeutic concept and demonstrates its potential value with the use of a model of the relevant disease. During resource development, the appropriate specialists and the required expertise to bring this product into the clinic are identified (eg, researchers, regulatory specialists, GMP manufacturing staff, clinicians and clinical trials staff, etc). Additionally, the funds required to achieve this goal (or a plan to procure them) are identified. In the next phase, the plan to translate the research product into a clinical-grade therapeutic is developed. Finally regulatory approval to start the trial must be obtained. In the United States, this is done by filing an IND application with the Food and Drug Administration. The National Heart, Lung and Blood Institute-funded Production Assistance for Cellular Therapies program has facilitated the transition of a variety of cellular therapy products from the laboratory into Phase1/2 trials. The five Production Assistance for Cellular Therapies facilities have assisted investigators by performing translational studies and GMP manufacturing to ensure that cellular products met release specifications and were manufactured safely, reproducibly and at the appropriate scale. The roadmap resulting from this experience is the focus of this article. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  16. Winding through the WNT pathway during cellular development and demise.

    Science.gov (United States)

    Li, F; Chong, Z Z; Maiese, K

    2006-01-01

    In slightly over a period of twenty years, our comprehension of the cellular and molecular mechanisms that govern the Wnt signaling pathway continue to unfold. The Wnt proteins were initially implicated in viral carcinogenesis experiments associated with mammary tumors, but since this period investigations focusing on the Wnt pathways and their transmembrane receptors termed Frizzled have been advanced to demonstrate the critical nature of Wnt for the development of a variety of cell populations as well as the potential of the Wnt pathway to avert apoptotic injury. In particular, Wnt signaling plays a significant role in both the cardiovascular and nervous systems during embryonic cell patterning, proliferation, differentiation, and orientation. Furthermore, modulation of Wnt signaling under specific cellular influences can either promote or prevent the early and late stages of apoptotic cellular injury in neurons, endothelial cells, vascular smooth muscle cells, and cardiomyocytes. A number of downstream signal transduction pathways can mediate the biological response of the Wnt proteins that include Dishevelled, beta-catenin, intracellular calcium, protein kinase C, Akt, and glycogen synthase kinase-3beta. Interestingly, these cellular cascades of the Wnt-Frizzled pathways can participate in several neurodegenerative, vascular, and cardiac disorders and may be closely integrated with the function of trophic factors. Identification of the critical elements that modulate the Wnt-Frizzled signaling pathway should continue to unlock the potential of Wnt pathway for the development of new therapeutic options against neurodegenerative and vascular diseases.

  17. Molecular and cellular mechanisms of aortic stenosis.

    Science.gov (United States)

    Yetkin, Ertan; Waltenberger, Johannes

    2009-06-12

    Calcific aortic stenosis is the most common cause of aortic valve replacement in developed countries, and this condition increases in prevalence with advancing age. The fibrotic thickening and calcification are common eventual endpoint in both non-rheumatic calcific and rheumatic aortic stenoses. New observations in human aortic valves support the hypothesis that degenerative valvular aortic stenosis is the result of active bone formation in the aortic valve, which may be mediated through a process of osteoblast-like differentiation in these tissues. Additionally histopathologic evidence suggests that early lesions in aortic valves are not just a disease process secondary to aging, but an active cellular process that follows the classical "response to injury hypothesis" similar to the situation in atherosclerosis. Although there are similarities with the risk factor and as well as with the process of atherogenesis, not all the patients with coronary artery disease or atherosclerosis have calcific aortic stenosis. This review mainly focuses on the potential vascular and molecular mechanisms involved in the pathogenesis of aortic valve stenosis. Namely extracellular matrix remodeling, angiogenesis, inflammation, and eventually osteoblast-like differentiation resulting in bone formation have been shown to play a role in the pathogenesis of calcific aortic stenosis. Several mediators related to underlying mechanisms, including growth factors especially transforming growth factor-beta1 and vascular endothelial growth factors, angiogenesis, cathepsin enzymes, adhesion molecules, bone regulatory proteins and matrix metalloproteinases have been demonstrated, however the target to be attacked is not defined yet.

  18. Metabonomics reveals metabolite changes in biliary atresia infants.

    Science.gov (United States)

    Zhou, Kejun; Xie, Guoxiang; Wang, Jun; Zhao, Aihua; Liu, Jiajian; Su, Mingming; Ni, Yan; Zhou, Ying; Pan, Weihua; Che, Yanran; Zhang, Ting; Xiao, Yongtao; Wang, Yang; Wen, Jie; Jia, Wei; Cai, Wei

    2015-06-05

    Biliary atresia (BA) is a rare neonatal cholestatic disorder caused by obstruction of extra- and intra-hepatic bile ducts. If untreated, progressive liver cirrhosis will lead to death within 2 years. Early diagnosis and operation improve the outcome significantly. Infants with neonatal hepatitis syndrome (NHS) present similar symptoms, confounding the early diagnosis of BA. The lack of noninvasive diagnostic methods to differentiate BA from NHS greatly delays the surgery of BA infants, thus deteriorating the outcome. Here we performed a metabolomics study in plasma of BA, NHS, and healthy infants using gas chromatography-time-of-flight mass spectrometry. Scores plots of orthogonal partial least-squares discriminant analysis clearly separated BA from NHS and healthy infants. Eighteen metabolites were found to be differentially expressed between BA and NHS, among which seven (l-glutamic acid, l-ornithine, l-isoleucine, l-lysine, l-valine, l-tryptophan, and l-serine) were amino acids. The altered amino acids were quantitatively verified using ultraperformance liquid chromatography-tandem mass spectrometry. Ingenuity pathway analysis revealed the network of "Cellular Function and Maintenance, Hepatic System Development and Function, Neurological Disease" was altered most significantly. This study suggests that plasma metabolic profiling has great potential in differentiating BA from NHS, and amino acid metabolism is significantly different between the two diseases.

  19. 47 CFR 22.970 - Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone...

    Science.gov (United States)

    2010-10-01

    ...-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. 22.970 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.970 Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. (a) Definition...

  20. Cellularized Bilayer Pullulan-Gelatin Hydrogel for Skin Regeneration.

    Science.gov (United States)

    Nicholas, Mathew N; Jeschke, Marc G; Amini-Nik, Saeid

    2016-05-01

    Skin substitutes significantly reduce the morbidity and mortality of patients with burn injuries and chronic wounds. However, current skin substitutes have disadvantages related to high costs and inadequate skin regeneration due to highly inflammatory wounds. Thus, new skin substitutes are needed. By combining two polymers, pullulan, an inexpensive polysaccharide with antioxidant properties, and gelatin, a derivative of collagen with high water absorbency, we created a novel inexpensive hydrogel-named PG-1 for "pullulan-gelatin first generation hydrogel"-suitable for skin substitutes. After incorporating human fibroblasts and keratinocytes onto PG-1 using centrifugation over 5 days, we created a cellularized bilayer skin substitute. Cellularized PG-1 was compared to acellular PG-1 and no hydrogel (control) in vivo in a mouse excisional skin biopsy model using newly developed dome inserts to house the skin substitutes and prevent mouse skin contraction during wound healing. PG-1 had an average pore size of 61.69 μm with an ideal elastic modulus, swelling behavior, and biodegradability for use as a hydrogel for skin substitutes. Excellent skin cell viability, proliferation, differentiation, and morphology were visualized through live/dead assays, 5-bromo-2'-deoxyuridine proliferation assays, and confocal microscopy. Trichrome and immunohistochemical staining of excisional wounds treated with the cellularized skin substitute revealed thicker newly formed skin with a higher proportion of actively proliferating cells and incorporation of human cells compared to acellular PG-1 or control. Excisional wounds treated with acellular or cellularized hydrogels showed significantly less macrophage infiltration and increased angiogenesis 14 days post skin biopsy compared to control. These results show that PG-1 has ideal mechanical characteristics and allows ideal cellular characteristics. In vivo evidence suggests that cellularized PG-1 promotes skin regeneration and may

  1. Molecular, cellular, and tissue engineering

    CERN Document Server

    Bronzino, Joseph D

    2015-01-01

    Known as the bible of biomedical engineering, The Biomedical Engineering Handbook, Fourth Edition, sets the standard against which all other references of this nature are measured. As such, it has served as a major resource for both skilled professionals and novices to biomedical engineering. Molecular, Cellular, and Tissue Engineering, the fourth volume of the handbook, presents material from respected scientists with diverse backgrounds in molecular biology, transport phenomena, physiological modeling, tissue engineering, stem cells, drug delivery systems, artificial organs, and personalized medicine. More than three dozen specific topics are examined, including DNA vaccines, biomimetic systems, cardiovascular dynamics, biomaterial scaffolds, cell mechanobiology, synthetic biomaterials, pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, nanobiomaterials for tissue engineering, biomedical imaging of engineered tissues, gene therapy, noninvasive targeted protein and peptide drug deliver...

  2. Pressure-actuated cellular structures

    International Nuclear Information System (INIS)

    Pagitz, M; Hol, J M A M; Lamacchia, E

    2012-01-01

    Shape changing structures will play an important role in future engineering designs since rigid structures are usually only optimal for a small range of service conditions. Hence, a concept for reliable and energy-efficient morphing structures that possess a large strength to self-weight ratio would be widely applicable. We propose a novel concept for morphing structures that is inspired by the nastic movement of plants. The idea is to connect prismatic cells with tailored pentagonal and/or hexagonal cross sections such that the resulting cellular structure morphs into given target shapes for certain cell pressures. An efficient algorithm for computing equilibrium shapes as well as cross-sectional geometries is presented. The potential of this novel concept is demonstrated by several examples that range from a flagellum like propulsion device to a morphing aircraft wing.

  3. Cellular automata in cytoskeletal lattices

    Energy Technology Data Exchange (ETDEWEB)

    Smith, S A; Watt, R C; Hameroff, S R

    1984-01-01

    Cellular automata (CA) activities could mediate biological regulation and information processing via nonlinear electrodynamic effects in cytoskeletal lattice arrays. Frohlich coherent oscillations and other nonlinear mechanisms may effect discrete 10/sup -10/ to 10/sup -11/ s interval events which result in dynamic patterns in biolattices such as cylindrical protein polymers: microtubules (MT). Structural geometry and electrostatic forces of MT subunit dipole oscillations suggest neighbor rules among the hexagonally packed protein subunits. Computer simulations using these suggested rules and MT structural geometry demonstrate CA activities including dynamical and stable self-organizing patterns, oscillators, and traveling gliders. CA activities in MT and other cytoskeletal lattices may have important biological regulatory functions. 23 references, 6 figures, 1 table.

  4. Sensing Phosphatidylserine in Cellular Membranes

    Directory of Open Access Journals (Sweden)

    Jason G. Kay

    2011-01-01

    Full Text Available Phosphatidylserine, a phospholipid with a negatively charged head-group, is an important constituent of eukaryotic cellular membranes. On the plasma membrane, rather than being evenly distributed, phosphatidylserine is found preferentially in the inner leaflet. Disruption of this asymmetry, leading to the appearance of phosphatidylserine on the surface of the cell, is known to play a central role in both apoptosis and blood clotting. Despite its importance, comparatively little is known about phosphatidylserine in cells: its precise subcellular localization, transmembrane topology and intracellular dynamics are poorly characterized. The recent development of new, genetically-encoded probes able to detect phosphatidylserine within live cells, however, is leading to a more in-depth understanding of the biology of this phospholipid. This review aims to give an overview of the current methods for phosphatidylserine detection within cells, and some of the recent realizations derived from their use.

  5. Pricing Patterns of Cellular Phones and Phonecalls: A Segment-Level Analysis

    OpenAIRE

    Dipak C. Jain; Eitan Muller; Naufel J. Vilcassim

    1999-01-01

    One expectation of the U.S. Federal Communications Commission (FCC) in the early stages of the cellular communications industry was that the presence of two licensees in each market would ensure competition, and thereby result in declining prices over time for both cellular phones (handsets) and phonecalls. However, industry observers have noted recently that although the price of handsets has declined over time, the price of the phonecalls has not. We investigate this interesting pricing iss...

  6. In vitro kinetic studies on the mechanism of oxygen-dependent cellular uptake of copper radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Holland, Jason P; Bell, Stephen G; Wong, Luet-Lok; Dilworth, Jonathan R [Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA (United Kingdom); Giansiracusa, Jeffrey H [Department of Mathematics, Mathematical Institute, University of Oxford, 24-29 St Giles' , Oxford, OX1 3LB (United Kingdom)], E-mail: hollanj3@mskcc.org, E-mail: jasonpholland@gmail.com

    2009-04-07

    The development of hypoxia-selective radiopharmaceuticals for use as therapeutic and/or imaging agents is of vital importance for both early identification and treatment of cancer and in the design of new drugs. Radiotracers based on copper for use in positron emission tomography have received great attention due to the successful application of copper(II) bis(thiosemicarbazonato) complexes, such as [{sup 60/62/64}Cu(II)ATSM] and [{sup 60/62/64}Cu(II)PTSM], as markers for tumour hypoxia and blood perfusion, respectively. Recent work has led to the proposal of a revised mechanism of hypoxia-selective cellular uptake and retention of [Cu(II)ATSM]. The work presented here describes non-steady-state kinetic simulations in which the reported pO{sub 2}-dependent in vitro cellular uptake and retention of [{sup 64}Cu(II)ATSM] in EMT6 murine carcinoma cells has been modelled by using the revised mechanistic scheme. Non-steady-state (NSS) kinetic analysis reveals that the model is in very good agreement with the reported experimental data with a root-mean-squared error of less than 6% between the simulated and experimental cellular uptake profiles. Estimated rate constants are derived for the cellular uptake and washout (k{sub 1} = 9.8 {+-} 0.59 x 10{sup -4} s{sup -1} and k{sub 2} = 2.9 {+-} 0.17 x 10{sup -3} s{sup -1}), intracellular reduction (k{sub 3} = 5.2 {+-} 0.31 x 10{sup -2} s{sup -1}), reoxidation (k{sub 4} = 2.2 {+-} 0.13 mol{sup -1} dm{sup 3} s{sup -1}) and proton-mediated ligand dissociation (k{sub 5} = 9.0 {+-} 0.54 x 10{sup -5} s{sup -1}). Previous mechanisms focused on the reduction and reoxidation steps. However, the data suggest that the origins of hypoxia-selective retention may reside with the stability of the copper(I) anion with respect to protonation and ligand dissociation. In vitro kinetic studies using the nicotimamide adenine dinucleotide (NADH)-dependent ferredoxin reductase enzyme PuR isolated from the bacterium Rhodopseudomonas palustris have

  7. Respiratory syncytial virus increases lung cellular bioenergetics in neonatal C57BL/6 mice

    International Nuclear Information System (INIS)

    Alsuwaidi, Ahmed R.; Albawardi, Alia; Almarzooqi, Saeeda; Benedict, Sheela; Othman, Aws R.; Hartwig, Stacey M.; Varga, Steven M.; Souid, Abdul-Kader

    2014-01-01

    We have previously reported that lung cellular bioenergetics (cellular respiration and ATP) increased in 4–10 week-old BALB/c mice infected with respiratory syncytial virus (RSV). This study examined the kinetics and changes in cellular bioenergetics in ≤2-week-old C57BL/6 mice following RSV infection. Mice (5–14 days old) were inoculated intranasally with RSV and the lungs were examined on days 1–10 post-infection. Histopathology and electron microscopy revealed preserved pneumocyte architectures and organelles. Increased lung cellular bioenergetics was noted from days 1–10 post-infection. Cellular GSH remained unchanged. These results indicate that the increased lung cellular respiration (measured by mitochondrial O 2 consumption) and ATP following RSV infection is independent of either age or genetic background of the host. - Highlights: • RSV infection increases lung cellular respiration and ATP in neonatal C57BL/6 mice. • Increased lung cellular bioenergetics is a biomarker of RSV infection. • Lung cellular glutathione remains unchanged in RSV infection

  8. Respiratory syncytial virus increases lung cellular bioenergetics in neonatal C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Alsuwaidi, Ahmed R., E-mail: alsuwaidia@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Albawardi, Alia, E-mail: alia.albawardi@uaeu.ac.ae [Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Almarzooqi, Saeeda, E-mail: saeeda.almarzooqi@uaeu.ac.ae [Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Benedict, Sheela, E-mail: sheela.benedict@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Othman, Aws R., E-mail: aws.rashad@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Hartwig, Stacey M., E-mail: stacey-hartwig@uiowa.edu [Department of Microbiology, Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 (United States); Varga, Steven M., E-mail: steven-varga@uiowa.edu [Department of Microbiology, Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 (United States); Souid, Abdul-Kader, E-mail: asouid@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates)

    2014-04-15

    We have previously reported that lung cellular bioenergetics (cellular respiration and ATP) increased in 4–10 week-old BALB/c mice infected with respiratory syncytial virus (RSV). This study examined the kinetics and changes in cellular bioenergetics in ≤2-week-old C57BL/6 mice following RSV infection. Mice (5–14 days old) were inoculated intranasally with RSV and the lungs were examined on days 1–10 post-infection. Histopathology and electron microscopy revealed preserved pneumocyte architectures and organelles. Increased lung cellular bioenergetics was noted from days 1–10 post-infection. Cellular GSH remained unchanged. These results indicate that the increased lung cellular respiration (measured by mitochondrial O{sub 2} consumption) and ATP following RSV infection is independent of either age or genetic background of the host. - Highlights: • RSV infection increases lung cellular respiration and ATP in neonatal C57BL/6 mice. • Increased lung cellular bioenergetics is a biomarker of RSV infection. • Lung cellular glutathione remains unchanged in RSV infection.

  9. Quantitative proteomic analysis of HIV-1 infected CD4+ T cells reveals an early host response in important biological pathways: Protein synthesis, cell proliferation, and T-cell activation

    Energy Technology Data Exchange (ETDEWEB)

    Navare, Arti T.; Sova, Pavel; Purdy, David E.; Weiss, Jeffrey M. [Department of Microbiology, University of Washington, Seattle, WA (United States); Wolf-Yadlin, Alejandro [Department of Genome Sciences, University of Washington, Seattle, WA (United States); Korth, Marcus J.; Chang, Stewart T.; Proll, Sean C. [Department of Microbiology, University of Washington, Seattle, WA (United States); Jahan, Tahmina A. [Proteomics Resource, UW Medicine at South Lake Union, Seattle, WA (United States); Krasnoselsky, Alexei L.; Palermo, Robert E. [Department of Microbiology, University of Washington, Seattle, WA (United States); Katze, Michael G., E-mail: honey@uw.edu [Department of Microbiology, University of Washington, Seattle, WA (United States); Washington National Primate Research Center, University of Washington, Seattle, WA (United States)

    2012-07-20

    Human immunodeficiency virus (HIV-1) depends upon host-encoded proteins to facilitate its replication while at the same time inhibiting critical components of innate and/or intrinsic immune response pathways. To characterize the host cell response on protein levels in CD4+ lymphoblastoid SUP-T1 cells after infection with HIV-1 strain LAI, we used mass spectrometry (MS)-based global quantitation with iTRAQ (isobaric tag for relative and absolute quantification). We found 266, 60 and 22 proteins differentially expressed (DE) (P-value{<=}0.05) at 4, 8, and 20 hours post-infection (hpi), respectively, compared to time-matched mock-infected samples. The majority of changes in protein abundance occurred at an early stage of infection well before the de novo production of viral proteins. Functional analyses of these DE proteins showed enrichment in several biological pathways including protein synthesis, cell proliferation, and T-cell activation. Importantly, these early changes before the time of robust viral production have not been described before.

  10. A radiation measurement study on cellular phone

    International Nuclear Information System (INIS)

    Mohd Yusof Mohd Ali; Rozaimah Abd Rahim; Roha Tukimin; Khairol Nizam Mohamed; Mohd Amirul Nizam Mohamad Thari; Ahmad Fadzli Ahmad Sanusi

    2007-01-01

    This paper will explain the radiation level produced by various selected cellular phone from various models and brands available in the market. The result obtained from this study will also recommend whether a cellular phone is safe for public usage or it might cause any effect on public health. Finally, a database of radiation measurement level produced by selected various cellular phone will also be developed and exhibited in this paper. (Author)

  11. Outer-totalistic cellular automata on graphs

    International Nuclear Information System (INIS)

    Marr, Carsten; Huett, Marc-Thorsten

    2009-01-01

    We present an intuitive formalism for implementing cellular automata on arbitrary topologies. By that means, we identify a symmetry operation in the class of elementary cellular automata. Moreover, we determine the subset of topologically sensitive elementary cellular automata and find that the overall number of complex patterns decreases under increasing neighborhood size in regular graphs. As exemplary applications, we apply the formalism to complex networks and compare the potential of scale-free graphs and metabolic networks to generate complex dynamics

  12. Radiation, nitric oxide and cellular death

    International Nuclear Information System (INIS)

    Dubner, D.; Perez, M.R. Del; Michelin, S.C.; Gisone, P.A.

    1997-01-01

    The mechanisms of radiation induced cellular death constitute an objective of research ever since the first biological effects of radiation were first observed. The explosion of information produced in the last 20 years calls for a careful analysis due to the apparent contradictory data related to the cellular system studied and the range of doses used. This review focuses on the role of the active oxygen species, in particular the nitric oxides, in its relevance as potential mediator of radiation induced cellular death

  13. Cellular Targets of Dietary Polyphenol Resveratrol

    National Research Council Canada - National Science Library

    Wu, Joseph M

    2006-01-01

    To test the hypothesis that resveratrol, a grape derived polyphenol, exerts its chemopreventive properties against prostate cancer by interacting with specific cellular targets, denoted resveratrol targeting proteins (RTPs...

  14. The cellular memory disc of reprogrammed cells.

    Science.gov (United States)

    Anjamrooz, Seyed Hadi

    2013-04-01

    The crucial facts underlying the low efficiency of cellular reprogramming are poorly understood. Cellular reprogramming occurs in nuclear transfer, induced pluripotent stem cell (iPSC) formation, cell fusion, and lineage-switching experiments. Despite these advances, there are three fundamental problems to be addressed: (1) the majority of cells cannot be reprogrammed, (2) the efficiency of reprogramming cells is usually low, and (3) the reprogrammed cells developed from a patient's own cells activate immune responses. These shortcomings present major obstacles for using reprogramming approaches in customised cell therapy. In this Perspective, the author synthesises past and present observations in the field of cellular reprogramming to propose a theoretical picture of the cellular memory disc. The current hypothesis is that all cells undergo an endogenous and exogenous holographic memorisation such that parts of the cellular memory dramatically decrease the efficiency of reprogramming cells, act like a barrier against reprogramming in the majority of cells, and activate immune responses. Accordingly, the focus of this review is mainly to describe the cellular memory disc (CMD). Based on the present theory, cellular memory includes three parts: a reprogramming-resistance memory (RRM), a switch-promoting memory (SPM) and a culture-induced memory (CIM). The cellular memory arises genetically, epigenetically and non-genetically and affects cellular behaviours. [corrected].

  15. p16(INK4a suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Li

    2011-02-01

    Full Text Available Although caloric restriction (CR has been shown to increase lifespan in various animal models, the mechanisms underlying this phenomenon have not yet been revealed. We developed an in vitro system to mimic CR by reducing glucose concentration in cell growth medium which excludes metabolic factors and allows assessment of the effects of CR at the cellular and molecular level. We monitored cellular proliferation of normal WI-38, IMR-90 and MRC-5 human lung fibroblasts and found that glucose restriction (GR can inhibit cellular senescence and significantly extend cellular lifespan compared with cells receiving normal glucose (NG in the culture medium. Moreover, GR decreased expression of p16(INK4a (p16, a well-known senescence-related gene, in all of the tested cell lines. Over-expressed p16 resulted in early replicative senescence in glucose-restricted cells suggesting a crucial role of p16 regulation in GR-induced cellular lifespan extension. The decreased expression of p16 was partly due to GR-induced chromatin remodeling through effects on histone acetylation and methylation of the p16 promoter. GR resulted in an increased expression of SIRT1, a NAD-dependent histone deacetylase, which has positive correlation with CR-induced longevity. The elevated SIRT1 was accompanied by enhanced activation of the Akt/p70S6K1 signaling pathway in response to GR. Furthermore, knockdown of SIRT1 abolished GR-induced p16 repression as well as Akt/p70S6K1 activation implying that SIRT1 may affect p16 repression through direct deacetylation effects and indirect regulation of Akt/p70S6K1 signaling. Collectively, these results provide new insights into interactions between epigenetic and genetic mechanisms on CR-induced longevity that may contribute to anti-aging approaches and also provide a general molecular model for studying CR in vitro in mammalian systems.

  16. Infiltrating giant cellular blue naevus.

    Science.gov (United States)

    Bittencourt, A L; Monteiro, D A; De Pretto, O J

    2007-01-01

    Cellular blue naevi (CBN) measure 1-2 cm in diameter and affect the dermis, occasionally extending into the subcutaneous fat. The case of a 14-year-old boy with a giant CBN (GCBN) involving the right half of the face, the jugal mucosa and the lower eyelid with a tumour that had infiltrated the bone and the maxillary and ethmoidal sinuses is reported. Biopsies were taken from the skin, jugal mucosa and maxillary sinus. The following markers were used in the immunohistochemical evaluation: CD34, CD56, HMB-45, anti-S100, A-103, Melan A and MIB-1. The biopsy specimens showed a biphasic pattern affecting the lower dermis, subcutaneous fat, skeletal muscle, bone, jugal mucosa and maxillary sinus, but there was no histological evidence of malignancy. The tumour cells were CD34-, CD56-, HMB45+, anti-S100+ and A-103+. Melan A was focally expressed. No positive MIB-1 cells were identified. The present case shows that GCBN may infiltrate deeply, with no evidence of malignancy.

  17. Diselenolane-mediated cellular uptake.

    Science.gov (United States)

    Chuard, Nicolas; Poblador-Bahamonde, Amalia I; Zong, Lili; Bartolami, Eline; Hildebrandt, Jana; Weigand, Wolfgang; Sakai, Naomi; Matile, Stefan

    2018-02-21

    The emerging power of thiol-mediated uptake with strained disulfides called for a move from sulfur to selenium. We report that according to results with fluorescent model substrates, cellular uptake with 1,2-diselenolanes exceeds uptake with 1,2-dithiolanes and epidithiodiketopiperazines with regard to efficiency as well as intracellular localization. The diselenide analog of lipoic acid performs best. This 1,2-diselenolane delivers fluorophores efficiently to the cytosol of HeLa Kyoto cells, without detectable endosomal capture as with 1,2-dithiolanes or dominant escape into the nucleus as with epidithiodiketopiperazines. Diselenolane-mediated cytosolic delivery is non-toxic (MTT assay), sensitive to temperature but insensitive to inhibitors of endocytosis (chlorpromazine, methyl-β-cyclodextrin, wortmannin, cytochalasin B) and conventional thiol-mediated uptake (Ellman's reagent), and to serum. Selenophilicity, the extreme CSeSeC dihedral angle of 0° and the high but different acidity of primary and secondary selenols might all contribute to uptake. Thiol-exchange affinity chromatography is introduced as operational mimic of thiol-mediated uptake that provides, in combination with rate enhancement of DTT oxidation, direct experimental evidence for existence and nature of the involved selenosulfides.

  18. Cellular Senescence: A Translational Perspective

    Directory of Open Access Journals (Sweden)

    James L. Kirkland

    2017-07-01

    Full Text Available Cellular senescence entails essentially irreversible replicative arrest, apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue-destructive senescence-associated secretory phenotype (SASP. Senescent cells accumulate in various tissues with aging and at sites of pathogenesis in many chronic diseases and conditions. The SASP can contribute to senescence-related inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes, chronic diseases, geriatric syndromes, and loss of resilience. Delaying senescent cell accumulation or reducing senescent cell burden is associated with delay, prevention, or alleviation of multiple senescence-associated conditions. We used a hypothesis-driven approach to discover pro-survival Senescent Cell Anti-apoptotic Pathways (SCAPs and, based on these SCAPs, the first senolytic agents, drugs that cause senescent cells to become susceptible to their own pro-apoptotic microenvironment. Several senolytic agents, which appear to alleviate multiple senescence-related phenotypes in pre-clinical models, are beginning the process of being translated into clinical interventions that could be transformative.

  19. Re: Epigenetics of Cellular Reprogramming

    Directory of Open Access Journals (Sweden)

    Fehmi Narter

    2016-12-01

    Full Text Available EDITORIAL COMMENT Cells have some specific molecular and physiological properties that act their functional process. However, many cells have an ability of efficient transition from one type to another. This ability is named plasticity. This process occurs due to epigenetic reprogramming that involves changes in transcription and chromatin structure. Some changes during reprogramming that have been identified in recent years as genomic demethylation (both histone and DNA, histone acetylation and loss of heterochromatin during the development of many diseases such as infertility and cancer progression. In this review, the authors focused on the latest work addressing the mechanisms surrounding the epigenetic regulation of various types of reprogramming, including somatic cell nuclear transfer, cell fusion and transcription factor- and microRNA-induced pluripotency. There are many responsible factors such as genes, cytokines, proteins, co-factors (i.e. vitamin C in this local area network. The exact mechanisms by which these changes are achieved and the detailed interplay between the players responsible, however, remain relatively unclear. In the treatment of diseases, such as infertility, urooncology, reconstructive urology, etc., epigenetic changes and cellular reprogramming will be crucial in the near future. Central to achieving that goal is a more thorough understanding of the epigenetic state of fully reprogrammed cells. By the progress of researches on this topic, new treatment modalities will be identified for these diseases.

  20. Efficiency of cellular information processing

    International Nuclear Information System (INIS)

    Barato, Andre C; Hartich, David; Seifert, Udo

    2014-01-01

    We show that a rate of conditional Shannon entropy reduction, characterizing the learning of an internal process about an external process, is bounded by the thermodynamic entropy production. This approach allows for the definition of an informational efficiency that can be used to study cellular information processing. We analyze three models of increasing complexity inspired by the Escherichia coli sensory network, where the external process is an external ligand concentration jumping between two values. We start with a simple model for which ATP must be consumed so that a protein inside the cell can learn about the external concentration. With a second model for a single receptor we show that the rate at which the receptor learns about the external environment can be nonzero even without any dissipation inside the cell since chemical work done by the external process compensates for this learning rate. The third model is more complete, also containing adaptation. For this model we show inter alia that a bacterium in an environment that changes at a very slow time-scale is quite inefficient, dissipating much more than it learns. Using the concept of a coarse-grained learning rate, we show for the model with adaptation that while the activity learns about the external signal the option of changing the methylation level increases the concentration range for which the learning rate is substantial. (paper)

  1. Simulation Modeling by Classification of Problems: A Case of Cellular Manufacturing

    International Nuclear Information System (INIS)

    Afiqah, K N; Mahayuddin, Z R

    2016-01-01

    Cellular manufacturing provides good solution approach to manufacturing area by applying Group Technology concept. The evolution of cellular manufacturing can enhance performance of the cell and to increase the quality of the product manufactured but it triggers other problem. Generally, this paper highlights factors and problems which emerge commonly in cellular manufacturing. The aim of the research is to develop a thorough understanding of common problems in cellular manufacturing. A part from that, in order to find a solution to the problems exist using simulation technique, this classification framework is very useful to be adapted during model building. Biology evolution tool was used in the research in order to classify the problems emerge. The result reveals 22 problems and 25 factors using cladistic technique. In this research, the expected result is the cladogram established based on the problems in cellular manufacturing gathered. (paper)

  2. Cellular Angiofibroma of the Prostate: A Rare Tumor in an Unusual Location

    Directory of Open Access Journals (Sweden)

    Inez Wyn

    2014-01-01

    Full Text Available We report the unusual occurrence of a cellular angiofibroma in prostatic tissue. In this case, a 84-year-old man presented in the emergency room with urinary retention. Ultrasound revealed an enlarged prostate, which was suggestive for benign prostatic hyperplasia. The patient was treated with a Millin retropubic prostatectomy. Macroscopically the prostate contained multiple circumscribed nodules. Microscopic examination of the tumor showed the appearance of cellular angiofibroma, consisting of bland spindle cells and prominent, hyalinized vessels. The diagnosis was supported by FISH, which revealed monoallelic loss of RB1/13q14 region, as seen in spindle cell lipoma, (extra- mammary myofibroblastoma, and cellular angiofibroma. Cellular angiofibromas are rare, benign soft tissue tumours and were never reported in the prostatic gland.

  3. Location and cellular stages of NK cell development

    Science.gov (United States)

    Yu, Jianhua; Freud, Aharon G.; Caligiuri, Michael A

    2013-01-01

    The identification of distinct tissue-specific natural killer (NK) cell populations that apparently mature from local precursor populations has brought new insight into the diversity and developmental regulation of this important lymphoid subset. NK cells provide a necessary link between the early (innate) and late (adaptive) immune responses to infection. Gaining a better understanding of the processes that govern NK cell development should allow us to better harness NK cell functions in multiple clinical settings as well as to gain further insight into how these cells undergo malignant transformation. In this review, we summarize recent advances in understanding sites and cellular stages of NK cell development in humans and mice. PMID:24055329

  4. Molecular and cellular heterogeneity: the hallmark of glioblastoma.

    Science.gov (United States)

    Aum, Diane J; Kim, David H; Beaumont, Thomas L; Leuthardt, Eric C; Dunn, Gavin P; Kim, Albert H

    2014-12-01

    There has been increasing awareness that glioblastoma, which may seem histopathologically similar across many tumors, actually represents a group of molecularly distinct tumors. Emerging evidence suggests that cells even within the same tumor exhibit wide-ranging molecular diversity. Parallel to the discoveries of molecular heterogeneity among tumors and their individual cells, intense investigation of the cellular biology of glioblastoma has revealed that not all cancer cells within a given tumor behave the same. The identification of a subpopulation of brain tumor cells termed "glioblastoma cancer stem cells" or "tumor-initiating cells" has implications for the management of glioblastoma. This focused review will therefore summarize emerging concepts on the molecular and cellular heterogeneity of glioblastoma and emphasize that we should begin to consider each individual glioblastoma to be an ensemble of molecularly distinct subclones that reflect a spectrum of dynamic cell states.

  5. A nucleator arms race: cellular control of actin assembly.

    Science.gov (United States)

    Campellone, Kenneth G; Welch, Matthew D

    2010-04-01

    For over a decade, the actin-related protein 2/3 (ARP2/3) complex, a handful of nucleation-promoting factors and formins were the only molecules known to directly nucleate actin filament formation de novo. However, the past several years have seen a surge in the discovery of mammalian proteins with roles in actin nucleation and dynamics. Newly recognized nucleation-promoting factors, such as WASP and SCAR homologue (WASH), WASP homologue associated with actin, membranes and microtubules (WHAMM), and junction-mediating regulatory protein (JMY), stimulate ARP2/3 activity at distinct cellular locations. Formin nucleators with additional biochemical and cellular activities have also been uncovered. Finally, the Spire, cordon-bleu and leiomodin nucleators have revealed new ways of overcoming the kinetic barriers to actin polymerization.

  6. Multi-cellular logistics of collective cell migration.

    Directory of Open Access Journals (Sweden)

    Masataka Yamao

    Full Text Available During development, the formation of biological networks (such as organs and neuronal networks is controlled by multicellular transportation phenomena based on cell migration. In multi-cellular systems, cellular locomotion is restricted by physical interactions with other cells in a crowded space, similar to passengers pushing others out of their way on a packed train. The motion of individual cells is intrinsically stochastic and may be viewed as a type of random walk. However, this walk takes place in a noisy environment because the cell interacts with its randomly moving neighbors. Despite this randomness and complexity, development is highly orchestrated and precisely regulated, following genetic (and even epigenetic blueprints. Although individual cell migration has long been studied, the manner in which stochasticity affects multi-cellular transportation within the precisely controlled process of development remains largely unknown. To explore the general principles underlying multicellular migration, we focus on the migration of neural crest cells, which migrate collectively and form streams. We introduce a mechanical model of multi-cellular migration. Simulations based on the model show that the migration mode depends on the relative strengths of the noise from migratory and non-migratory cells. Strong noise from migratory cells and weak noise from surrounding cells causes "collective migration," whereas strong noise from non-migratory cells causes "dispersive migration." Moreover, our theoretical analyses reveal that migratory cells attract each other over long distances, even without direct mechanical contacts. This effective interaction depends on the stochasticity of the migratory and non-migratory cells. On the basis of these findings, we propose that stochastic behavior at the single-cell level works effectively and precisely to achieve collective migration in multi-cellular systems.

  7. Network signatures of cellular immortalization in human lymphoblastoid cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Sung-Mi; Jung, So-Young; Nam, Hye-Young; Kim, Hye-Ryun; Lee, Mee-Hee; Kim, Jun-Woo; Han, Bok-Ghee [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Osong 363-951 (Korea, Republic of); Jeon, Jae-Pil, E-mail: jaepiljeon@hanmail.net [Division of Brain Diseases, Center for Biomedical Science, Korea National Institute of Health, Osong 363-951 (Korea, Republic of)

    2013-11-15

    Highlights: •We identified network signatures of LCL immortalization from transcriptomic profiles. •More than 41% of DEGs are possibly regulated by miRNAs in LCLs. •MicroRNA target genes in LCLs are involved in apoptosis and immune-related functions. •This approach is useful to find functional miRNA targets in specific cell conditions. -- Abstract: Human lymphoblastoid cell line (LCL) has been used as an in vitro cell model in genetic and pharmacogenomic studies, as well as a good model for studying gene expression regulatory machinery using integrated genomic analyses. In this study, we aimed to identify biological networks of LCL immortalization from transcriptomic profiles of microRNAs and their target genes in LCLs. We first selected differentially expressed genes (DEGs) and microRNAs (DEmiRs) between early passage LCLs (eLCLs) and terminally differentiated late passage LCLs (tLCLs). The in silico and correlation analysis of these DEGs and DEmiRs revealed that 1098 DEG–DEmiR pairs were found to be positively (n = 591 pairs) or negatively (n = 507 pairs) correlated with each other. More than 41% of DEGs are possibly regulated by miRNAs in LCL immortalizations. The target DEGs of DEmiRs were enriched for cellular functions associated with apoptosis, immune response, cell death, JAK–STAT cascade and lymphocyte activation while non-miRNA target DEGs were over-represented for basic cell metabolisms. The target DEGs correlated negatively with miR-548a-3p and miR-219-5p were significantly associated with protein kinase cascade, and the lymphocyte proliferation and apoptosis, respectively. In addition, the miR-106a and miR-424 clusters located in the X chromosome were enriched in DEmiR–mRNA pairs for LCL immortalization. In this study, the integrated transcriptomic analysis of LCLs could identify functional networks of biologically active microRNAs and their target genes involved in LCL immortalization.

  8. Pulsed feedback defers cellular differentiation.

    Directory of Open Access Journals (Sweden)

    Joe H Levine

    2012-01-01

    Full Text Available Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable "polyphasic" positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a "timer" that operates over timescales much longer than a cell cycle.

  9. Quartz exposure, retention, and early silicosis in sheep.

    Science.gov (United States)

    Bégin, R; Dufresne, A; Cantin, A; Possmayer, F; Sébastien, P; Fabi, D; Bilodeau, G; Martel, M; Bisson, D; Pietrowski, B

    1989-05-01

    The purposes of this study were (1) to investigate the chronology of events in cellular and biochemical changes thought to be important in the development of silicosis, (2) to relate these to changes in lung function and radiograph, and (3) to evaluate the relation of quartz exposure and retention to individual response leading to early silicosis. Thirty-six sheep were exposed by repeated intratracheal infusion at 10-day intervals to 100 mg Minusil-5 in 100 ml saline (Si group), and 10 sheep were exposed at the same intervals to 100 ml saline (control). All sheep were investigated at 3-month intervals by chest radiograph, lung function, and lung lavage. At month 9, chest radiograph score of parenchymal opacities was significantly increased at 2.8 +/- 0.6 versus 0.4 +/- 0.4 in the Si group (p less than .05), establishing early radiologic silicosis. Lung function was significantly altered with reduction in lung compliance, vital capacity, and diffusion capacity (p less than .05). Lung lavage cellularity revealed significant increase in total cells (X 2.5), macrophages (X3), and neutrophils (X3). Albumin in BAL remained at the control level. Fibronectin production was significantly increased, as was the fibroblast growth activity, without significant change in procollagen 3 at this early stage of disease. Total phospholipids were significantly elevated in the Si-exposed sheep, and the profile demonstrated an increase in all the phospholipid components. Spontaneous release of hydrogen peroxide by alveolar cells was not increased, but in the presence of phorbol myristate acetate (PMA) higher levels of peroxide were found in the quartz-exposed sheep (p less than .05). The cellular and biochemical alterations of lung lavage preceded other changes. At month 12, there were good correlations (r greater than .49, p less than .001) between parameters evaluating related phenomena but poor correlations between measurements evaluating different aspects of the disorder. To

  10. Radioactive particles revealed by electron microscopy. Chemical and physical properties of radioactive particles in aerosol samples emitted during the early stage of Fukushima Dai-ichi Nuclear Power Plant accident

    International Nuclear Information System (INIS)

    Adachi, Kouji

    2015-01-01

    Water-insoluble radioactive materials emitted during an early stage of the Fukushima Dai-ichi Nuclear Power Plant accident in 2011 were identified, and their chemical and physical properties were characterized as particulate matters. In this report, studies on radioactive particles collected from filter samples in Tsukuba on March 14–15, 2011 are summarized. Their compositions, chemical states, sizes, shapes, crystallinity, and hygroscopicity were analyzed using microscopic analyses such as electron microscopy and synchrotron with a micro-beam. The results indicate that they include Cs, Fe, and Zn as well as elements from fission products and are water insoluble, spherical-glassy particles with ca. 2 micrometer in size. Understanding of their detailed properties is significant to improve the numerical models during the accident and to understand their occurrences in soil as well as the accident itself. In addition to the water-insoluble radioactive materials, water-soluble radioactive materials, which were likely emitted in different events during the accident, should be investigated to have comprehensive understanding of the accident and its environmental effects. More samples from various environments such as soil will be needed, and more detailed chemical and physical analyses will help to understand their formation process, influences on human health, and long term decrements in ambient conditions. (author)

  11. Early transcriptomic changes induced by magnesium deficiency in Arabidopsis thaliana reveal the alteration of circadian clock gene expression in roots and the triggering of abscisic acid-responsive genes.

    Science.gov (United States)

    Hermans, Christian; Vuylsteke, Marnik; Coppens, Frederik; Craciun, Adrian; Inzé, Dirk; Verbruggen, Nathalie

    2010-07-01

    *Plant growth and development ultimately depend on environmental variables such as the availability of essential minerals. Unravelling how nutrients affect gene expression will help to understand how they regulate plant growth. *This study reports the early transcriptomic response to magnesium (Mg) deprivation in Arabidopsis. Whole-genome transcriptome was studied in the roots and young mature leaves 4, 8 and 28 h after the removal of Mg from the nutrient solution. *The highest number of regulated genes was first observed in the roots. Contrary to other mineral deficiencies, Mg depletion did not induce a higher expression of annotated genes in Mg uptake. Remarkable responses include the perturbation of the central oscillator of the circadian clock in roots and the triggering of abscisic acid (ABA) signalling, with half of the up-regulated Mg genes in leaves being ABA-responsive. However, no change in ABA content was observed. *The specificity of the response of some Mg-regulated genes was challenged by studying their expression after other mineral deficiencies and environmental stresses. The possibility to develop markers for Mg incipient deficiency is discussed here.

  12. Three-Dimensional Spatiotemporal Modeling of Colon Cancer Organoids Reveals that Multimodal Control of Stem Cell Self-Renewal is a Critical Determinant of Size and Shape in Early Stages of Tumor Growth.

    Science.gov (United States)

    Yan, Huaming; Konstorum, Anna; Lowengrub, John S

    2018-05-01

    We develop a three-dimensional multispecies mathematical model to simulate the growth of colon cancer organoids containing stem, progenitor and terminally differentiated cells, as a model of early (prevascular) tumor growth. Stem cells (SCs) secrete short-range self-renewal promoters (e.g., Wnt) and their long-range inhibitors (e.g., Dkk) and proliferate slowly. Committed progenitor (CP) cells proliferate more rapidly and differentiate to produce post-mitotic terminally differentiated cells that release differentiation promoters, forming negative feedback loops on SC and CP self-renewal. We demonstrate that SCs play a central role in normal and cancer colon organoids. Spatial patterning of the SC self-renewal promoter gives rise to SC clusters, which mimic stem cell niches, around the organoid surface, and drive the development of invasive fingers. We also study the effects of externally applied signaling factors. Applying bone morphogenic proteins, which inhibit SC and CP self-renewal, reduces invasiveness and organoid size. Applying hepatocyte growth factor, which enhances SC self-renewal, produces larger sizes and enhances finger development at low concentrations but suppresses fingers at high concentrations. These results are consistent with recent experiments on colon organoids. Because many cancers are hierarchically organized and are subject to feedback regulation similar to that in normal tissues, our results suggest that in cancer, control of cancer stem cell self-renewal should influence the size and shape in similar ways, thereby opening the door to novel therapies.

  13. Cellular phone use while driving at night.

    Science.gov (United States)

    Vivoda, Jonathon M; Eby, David W; St Louis, Renée M; Kostyniuk, Lidia P

    2008-03-01

    Use of a cellular phone has been shown to negatively affect one's attention to the driving task, leading to an increase in crash risk. At any given daylight hour, about 6% of US drivers are actively talking on a hand-held cell phone. However, previous surveys have focused only on cell phone use during the day. Driving at night has been shown to be a riskier activity than driving during the day. The purpose of the current study was to assess the rate of hand-held cellular phone use while driving at night, using specialized night vision equipment. In 2006, two statewide direct observation survey waves of nighttime cellular phone use were conducted in Indiana utilizing specialized night vision equipment. Combined results of driver hand-held cellular phone use from both waves are presented in this manuscript. The rates of nighttime cell phone use were similar to results found in previous daytime studies. The overall rate of nighttime hand-held cellular phone use was 5.8 +/- 0.6%. Cellular phone use was highest for females and for younger drivers. In fact, the highest rate observed during the study (of 11.9%) was for 16-to 29-year-old females. The high level of cellular phone use found within the young age group, coupled with the increased crash risk associated with cellular phone use, nighttime driving, and for young drivers in general, suggests that this issue may become an important transportation-related concern.

  14. On Elementary and Algebraic Cellular Automata

    Science.gov (United States)

    Gulak, Yuriy

    In this paper we study elementary cellular automata from an algebraic viewpoint. The goal is to relate the emergent complex behavior observed in such systems with the properties of corresponding algebraic structures. We introduce algebraic cellular automata as a natural generalization of elementary ones and discuss their applications as generic models of complex systems.

  15. Cellular Factors Shape 3D Genome Landscape

    Science.gov (United States)

    Researchers, using novel large-scale imaging technology, have mapped the spatial location of individual genes in the nucleus of human cells and identified 50 cellular factors required for the proper 3D positioning of genes. These spatial locations play important roles in gene expression, DNA repair, genome stability, and other cellular activities.

  16. Cellular chain formation in Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk; Klemm, Per

    2009-01-01

    ; type I fimbriae expression significantly reduced cellular chain formation, presumably by steric hindrance. Cellular chain formation did not appear to be specific to E coli K-12. Although many urinary tract infection (UTI) isolates were found to form rather homogeneous, flat biofilms, three isolates...

  17. Tectonic/climatic control on sediment provenance in the Cape Roberts Project core record (southern Victoria Land, Antarctica): A pulsing late Oligocene/early Miocene signal from south revealed by detrital thermochronology

    Science.gov (United States)

    Olivetti, V.; Balestrieri, M. L.; Rossetti, F.; Talarico, F. M.

    2012-04-01

    The Mesozoic-Cenozoic West Antarctic Rift System (WARS) is one of the largest intracontinental rift on Earth. The Transantarctic Mountains (TAM) form its western shoulder, marking the boundary between the East and West Antarctica. The rifting evolution is commonly considered polyphase and involves an Early Cretaceous phase linked to the Gondwana break-up followed by a major Cenozoic one, starting at c. 50-40 Ma. This Cenozoic episode corresponds to the major uplift/denudation phase of the TAM, which occurred concurrently with transition from orthogonal to oblique rifting. The Cenozoic rift reorganization occurred concurrently with a major change in the global climate system and a global reorganization of plate motions. This area thus provide an outstanding natural laboratory for studying a range of geological problems that involve feedback relationships between tectonics and climate. A key to address the tectonic/climate feedback relations is to look on apparent synchronicity in erosion signal between different segments, and to compare these with well-dated regional and global climatic events. However, due to the paucity of Cenozoic rock sequences exposed along the TAM front, a few information is available about the neotectonics of the rift and rift-flank uplift system. The direct physical record of the tectonic/climate history of the WARS recovered by core drillings along the western margin of the Ross sea (DSDP, CIROS, Cape Roberts and ANDRILL projects) provides an invaluable tool to address this issue. Twenty-three samples distributed throughout the entire composite drill-cored stratigraphic succession of Cape Roberts were analyzed. Age probability plots of eighteen detrital samples with depositional ages between 34 Ma and the Pliocene were decomposed into statistically significant age populations or peaks using binomial peak-fitting. Moreover, three granitic pebbles, one dolerite clast and one sample of Beacon sandstones have been dated. From detrital samples

  18. What the voice reveals

    NARCIS (Netherlands)

    Ko, Sei Jin

    2007-01-01

    Given that the voice is our main form of communication, we know surprisingly little about how it impacts judgment and behavior. Furthermore, the modern advancement in telecommunication systems, such as cellular phones, has meant that a large proportion of our everyday interactions are conducted

  19. Enhanced Medial Collateral Ligament Healing using Mesenchymal Stem Cells: Dosage Effects on Cellular Response and Cytokine Profile

    Science.gov (United States)

    Saether, Erin E.; Chamberlain, Connie S.; Leiferman, Ellen M.; Kondratko-Mittnacht, Jaclyn R.; Li, Wan Ju; Brickson, Stacey L.; Vanderby, Ray

    2013-01-01

    Mesenchymal stem cells (MSCs) have potential therapeutic applications for musculoskeletal injuries due to their ability to differentiate into several tissue cell types and modulate immune and inflammatory responses. These immune-modulatory properties were examined in vivo during early stage rat medial collateral ligament healing. Two different cell doses (low dose 1×106 or high dose 4×106 MSCs) were administered at the time of injury and compared with normal ligament healing at days 5 and 14 post-injury. At both times, the high dose MSC group demonstrated a significant decrease in M2 macrophages compared to controls. At day 14, fewer M1 macrophages were detected in the low dose group compared to the high dose group. These results, along with significant changes in procollagen I, proliferating cells, and endothelialization suggest that MSCs can alter the cellular response during healing in a dose-dependent manner. The higher dose ligaments also had increased expression of several pro-inflammatory cytokines at day 5 (IL-1β, IFNγ, IL-2) and increased expression of IL-12 at day 14. Mechanical testing at day 14 revealed increased failure strength and stiffness in low dose ligaments compared to controls. Based on these improved mechanical properties, MSCs enhanced functional healing when applied at a lower dose. Different doses of MSCs uniquely affected the cellular response and cytokine expression in healing ligaments. Interestingly, the lower dose of cells proved to be most effective in improving functional properties. PMID:24174129

  20. Drosophila embryos as model to assess cellular and developmental toxicity of multi-walled carbon nanotubes (MWCNT in living organisms.

    Directory of Open Access Journals (Sweden)

    Boyin Liu

    Full Text Available Different toxicity tests for carbon nanotubes (CNT have been developed to assess their impact on human health and on aquatic and terrestrial animal and plant life. We present a new model, the fruit fly Drosophila embryo offering the opportunity for rapid, inexpensive and detailed analysis of CNTs toxicity during embryonic development. We show that injected DiI labelled multi-walled carbon nanotubes (MWCNTs become incorporated into cells in early Drosophila embryos, allowing the study of the consequences of cellular uptake of CNTs on cell communication, tissue and organ formation in living embryos. Fluorescently labelled subcellular structures showed that MWCNTs remained cytoplasmic and were excluded from the nucleus. Analysis of developing ectodermal and neural stem cells in MWCNTs injected embryos revealed normal division patterns and differentiation capacity. However, an increase in cell death of ectodermal but not of neural stem cells was observed, indicating stem cell-specific vulnerability to MWCNT exposure. The ease of CNT embryo injections, the possibility of detailed morphological and genomic analysis and the low costs make Drosophila embryos a system of choice to assess potential developmental and cellular effects of CNTs and test their use in future CNT based new therapies including drug delivery.

  1. High Content Screening: Understanding Cellular Pathway

    International Nuclear Information System (INIS)

    Mohamed Zaffar Ali Mohamed Amiroudine; Daryl Jesus Arapoc; Zainah Adam; Shafii Khamis

    2015-01-01

    High content screening (HCS) is the convergence between cell-based assays, high-resolution fluorescence imaging, phase-contrast imaging of fixed- or live-cell assays, tissues and small organisms. It has been widely adopted in the pharmaceutical and biotech industries for target identification and validation and as secondary screens to reveal potential toxicities or to elucidate a drugs mechanism of action. By using the ImageXpress® Micro XLS System HCS, the complex network of key players controlling proliferation and apoptosis can be reduced to several sentinel markers for analysis. Cell proliferation and apoptosis are two key areas in cell biology and drug discovery research. Understanding the signaling pathways in cell proliferation and apoptosis is important for new therapeutic discovery because the imbalance between these two events is predominant in the progression of many human diseases, including cancer. The DNA binding dye DAPI is used to determine the nuclear size and nuclear morphology as well as cell cycle phases by DNA content. Images together with MetaXpress® analysis results provide a convenient and easy to use solution to high volume image management. In particular, HCS platform is beginning to have an important impact on early drug discovery, basic research in systems cell biology, and is expected to play a role in personalized medicine or revealing off-target drug effects. (author)

  2. Expression profiling of migrated and invaded breast cancer cells predicts early metastatic relapse and reveals Krüppel-like factor 9 as a potential suppressor of invasive growth in breast cancer

    Science.gov (United States)

    Limame, Ridha; de Beeck, Ken Op; Van Laere, Steven; Croes, Lieselot; De Wilde, Annemieke; Dirix, Luc; Van Camp, Guy; Peeters, Marc; De Wever, Olivier; Lardon, Filip; Pauwels, Patrick

    2014-01-01

    Cell motility and invasion initiate metastasis. However, only a subpopulation of cancer cells within a tumor will ultimately become invasive. Due to this stochastic and transient nature, in an experimental setting, migrating and invading cells need to be isolated from the general population in order to study the gene expression profiles linked to these processes. This report describes microarray analysis on RNA derived from migrated or invaded subpopulations of triple negative breast cancer cells in a Transwell set-up, at two different time points during motility and invasion, pre-determined as “early” and “late” in real-time kinetic assessments. Invasion- and migration-related gene expression signatures were generated through comparison with non-invasive cells, remaining at the upper side of the Transwell membranes. Late-phase signatures of both invasion and migration indicated poor prognosis in a series of breast cancer data sets. Furthermore, evaluation of the genes constituting the prognostic invasion-related gene signature revealed Krüppel-like factor 9 (KLF9) as a putative suppressor of invasive growth in breast cancer. Next to loss in invasive vs non-invasive cell lines, KLF9 also showed significantly lower expression levels in the “early” invasive cell population, in several public expression data sets and in clinical breast cancer samples when compared to normal tissue. Overexpression of EGFP-KLF9 fusion protein significantly altered morphology and blocked invasion and growth of MDA-MB-231 cells in vitro. In addition, KLF9 expression correlated inversely with mitotic activity in clinical samples, indicating anti-proliferative effects. PMID:25593984

  3. Estimating cellular network performance during hurricanes

    International Nuclear Information System (INIS)

    Booker, Graham; Torres, Jacob; Guikema, Seth; Sprintson, Alex; Brumbelow, Kelly

    2010-01-01

    Cellular networks serve a critical role during and immediately after a hurricane, allowing citizens to contact emergency services when land-line communication is lost and serving as a backup communication channel for emergency responders. However, due to their ubiquitous deployment and limited design for extreme loading events, basic network elements, such as cellular towers and antennas are prone to failures during adverse weather conditions such as hurricanes. Accordingly, a systematic and computationally feasible approach is required for assessing and improving the reliability of cellular networks during hurricanes. In this paper we develop a new multi-disciplinary approach to efficiently and accurately assess cellular network reliability during hurricanes. We show how the performance of a cellular network during and immediately after future hurricanes can be estimated based on a combination of hurricane wind field models, structural reliability analysis, Monte Carlo simulation, and cellular network models and simulation tools. We then demonstrate the use of this approach for assessing the improvement in system reliability that can be achieved with discrete topological changes in the system. Our results suggest that adding redundancy, particularly through a mesh topology or through the addition of an optical fiber ring around the perimeter of the system can be an effective way to significantly increase the reliability of some cellular systems during hurricanes.

  4. Isogenic Cellular Systems Model the Impact of Genetic Risk Variants in the Pathogenesis of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Mark A. Wallet

    2017-10-01

    Full Text Available At least 57 independent loci within the human genome confer varying degrees of risk for the development of type 1 diabetes (T1D. The majority of these variants are thought to contribute to overall genetic risk by modulating host innate and adaptive immune responses, ultimately resulting in a loss of immunological tolerance to β cell antigens. Early efforts to link specific risk variants with functional alterations in host immune responses have employed animal models or genotype-selected individuals from clinical bioresource banks. While some notable genotype:phenotype associations have been described, there remains an urgent need to accelerate the discovery of causal variants and elucidate the molecular mechanisms by which susceptible alleles alter immune functions. One significant limitation has been the inability to study human T1D risk loci on an isogenic background. The advent of induced pluripotent stem cells (iPSCs and genome-editing technologies have made it possible to address a number of these outstanding questions. Specifically, the ability to drive multiple cell fates from iPSC under isogenic conditions now facilitates the analysis of causal variants in multiple cellular lineages. Bioinformatic analyses have revealed that T1D risk genes cluster within a limited number of immune signaling pathways, yet the relevant immune cell subsets and cellular activation states in which candidate risk genes impact cellular activities remain largely unknown. In this review, we summarize the functional impact of several candidate risk variants on host immunity in T1D and present an isogenic disease-in-a-dish model system for interrogating risk variants, with the goal of expediting precision therapeutics in T1D.

  5. The induction and regulation of radiogenic transformation in vitro: Cellular and molecular mechanisms

    International Nuclear Information System (INIS)

    Borek, C.

    1987-01-01

    Rodent and human cells in culture, transformed in vitro by ionizing radiation, ultraviolet light, or chemicals into malignant cells afford us the opportunity to probe into early and late events in the neoplastic process at a cellular and molecular level. Transformation can be regarded as an abnormal expression of cellular genes. The initiating agents disrupt the integrity of the genetic apparatus altering DNA in ways that result in the activation of cellular transforming genes (oncogenes) during some stage of the neoplastic process. Events associated with initiation and promotion may overlap to some degree, but in order for them to occur, cellular permissive conditions must prevail. Permissive factors include thyroid and steroid hormones, specific states of differentiation, certain stages in the cell cycle, specific genetic impairment, and inadequate antioxidants. Genetically susceptible cells require physiological states conducive to transformation. These may differ with age, tissue, and species and in part may be responsible for the observed lower sensitivity of human cells to transformation

  6. In vivo cellular imaging with microscopes enabled by MEMS scanners

    Science.gov (United States)

    Ra, Hyejun

    High-resolution optical imaging plays an important role in medical diagnosis and biomedical research. Confocal microscopy is a widely used imaging method for obtaining cellular and sub-cellular images of biological tissue in reflectance and fluorescence modes. Its characteristic optical sectioning capability also enables three-dimensional (3-D) image reconstruction. However, its use has mostly been limited to excised tissues due to the requirement of high numerical aperture (NA) lenses for cellular resolution. Microscope miniaturization can enable in vivo imaging to make possible early cancer diagnosis and biological studies in the innate environment. In this dissertation, microscope miniaturization for in vivo cellular imaging is presented. The dual-axes confocal (DAC) architecture overcomes limitations of the conventional single-axis confocal (SAC) architecture to allow for miniaturization with high resolution. A microelectromechanical systems (MEMS) scanner is the central imaging component that is key in miniaturization of the DAC architecture. The design, fabrication, and characterization of the two-dimensional (2-D) MEMS scanner are presented. The gimbaled MEMS scanner is fabricated on a double silicon-on-insulator (SOI) wafer and is actuated by self-aligned vertical electrostatic combdrives. The imaging performance of the MEMS scanner in a DAC configuration is shown in a breadboard microscope setup, where reflectance and fluorescence imaging is demonstrated. Then, the MEMS scanner is integrated into a miniature DAC microscope. The whole imaging system is integrated into a portable unit for research in small animal models of human biology and disease. In vivo 3-D imaging is demonstrated on mouse skin models showing gene transfer and siRNA silencing. The siRNA silencing process is sequentially imaged in one mouse over time.

  7. Dynamics and mechanisms of quantum dot nanoparticle cellular uptake

    Directory of Open Access Journals (Sweden)

    Telford William G

    2010-06-01

    Full Text Available Abstract Background The rapid growth of the nanotechnology industry and the wide application of various nanomaterials have raised concerns over their impact on the environment and human health. Yet little is known about the mechanism of cellular uptake and cytotoxicity of nanoparticles. An array of nanomaterials has recently been introduced into cancer research promising for remarkable improvements in diagnosis and treatment of the disease. Among them, quantum dots (QDs distinguish themselves in offering many intrinsic photophysical properties that are desirable for targeted imaging and drug delivery. Results We explored the kinetics and mechanism of cellular uptake of QDs with different surface coatings in two human mammary cells. Using fluorescence microscopy and laser scanning cytometry (LSC, we found that both MCF-7 and MCF-10A cells internalized large amount of QD655-COOH, but the percentage of endocytosing cells is slightly higher in MCF-7 cell line than in MCF-10A cell line. Live cell fluorescent imaging showed that QD cellular uptake increases with time over 40 h of incubation. Staining cells with dyes specific to various intracellular organelles indicated that QDs were localized in lysosomes. Transmission electron microscopy (TEM images suggested a potential pathway for QD cellular uptake mechanism involving three major stages: endocytosis, sequestration in early endosomes, and translocation to later endosomes or lysosomes. No cytotoxicity was observed in cells incubated with 0.8 nM of QDs for a period of 72 h. Conclusions The findings presented here provide information on the mechanism of QD endocytosis that could be exploited to reduce non-specific targeting, thereby improving specific targeting of QDs in cancer diagnosis and treatment applications. These findings are also important in understanding the cytotoxicity of nanomaterials and in emphasizing the importance of strict environmental control of nanoparticles.

  8. Imaging in cellular and tissue engineering

    CERN Document Server

    Yu, Hanry

    2013-01-01

    Details on specific imaging modalities for different cellular and tissue engineering applications are scattered throughout articles and chapters in the literature. Gathering this information into a single reference, Imaging in Cellular and Tissue Engineering presents both the fundamentals and state of the art in imaging methods, approaches, and applications in regenerative medicine. The book underscores the broadening scope of imaging applications in cellular and tissue engineering. It covers a wide range of optical and biological applications, including the repair or replacement of whole tiss

  9. Advanced 3D Printers for Cellular Solids

    Science.gov (United States)

    2016-06-30

    06-2016 1-Aug-2014 31-Dec-2015 Final Report: Advanced 3D printers for Cellular Solids The views, opinions and/or findings contained in this report are...2211 3d printing, cellular solids REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 10. SPONSOR/MONITOR’S ACRONYM(S) ARO 8...Papers published in non peer-reviewed journals: Final Report: Advanced 3D printers for Cellular Solids Report Title Final Report for DURIP grant W911NF

  10. Cellularity of certain quantum endomorphism algebras

    DEFF Research Database (Denmark)

    Andersen, Henning Haahr; Lehrer, G. I.; Zhang, R.

    Let $\\tA=\\Z[q^{\\pm \\frac{1}{2}}][([d]!)\\inv]$ and let $\\Delta_{\\tA}(d)$ be an integral form of the Weyl module of highest weight $d \\in \\N$ of the quantised enveloping algebra $\\U_{\\tA}$ of $\\fsl_2$. We exhibit for all positive integers $r$ an explicit cellular structure for $\\End...... of endomorphism algebras, and another which relates the multiplicities of indecomposable summands to the dimensions of simple modules for an endomorphism algebra. Our cellularity result then allows us to prove that knowledge of the dimensions of the simple modules of the specialised cellular algebra above...

  11. Somatic mutations, allele loss, and DNA methylation of the Cub and Sushi Multiple Domains 1 (CSMD1 gene reveals association with early age of diagnosis in colorectal cancer patients.

    Directory of Open Access Journals (Sweden)

    Austin Y Shull

    Full Text Available The Cub and Sushi Multiple Domains 1 (CSMD1 gene, located on the short arm of chromosome 8, codes for a type I transmembrane protein whose function is currently unknown. CSMD1 expression is frequently lost in many epithelial cancers. Our goal was to characterize the relationships between CSMD1 somatic mutations, allele imbalance, DNA methylation, and the clinical characteristics in colorectal cancer patients.We sequenced the CSMD1 coding regions in 54 colorectal tumors using the 454FLX pyrosequencing platform to interrogate 72 amplicons covering the entire coding sequence. We used heterozygous SNP allele ratios at multiple CSMD1 loci to determine allelic balance and infer loss of heterozygosity. Finally, we performed methylation-specific PCR on 76 colorectal tumors to determine DNA methylation status for CSMD1 and known methylation targets ALX4, RUNX3, NEUROG1, and CDKN2A.Using 454FLX sequencing and confirming with Sanger sequencing, 16 CSMD1 somatic mutations were identified in 6 of the 54 colorectal tumors (11%. The nonsynonymous to synonymous mutation ratio of the 16 somatic mutations was 15:1, a ratio significantly higher than the expected 2:1 ratio (p = 0.014. This ratio indicates a presence of positive selection for mutations in the CSMD1 protein sequence. CSMD1 allelic imbalance was present in 19 of 37 informative cases (56%. Patients with allelic imbalance and CSMD1 mutations were significantly younger (average age, 41 years than those without somatic mutations (average age, 68 years. The majority of tumors were methylated at one or more CpG loci within the CSMD1 coding sequence, and CSMD1 methylation significantly correlated with two known methylation targets ALX4 and RUNX3. C:G>T:A substitutions were significantly overrepresented (47%, suggesting extensive cytosine methylation predisposing to somatic mutations.Deep amplicon sequencing and methylation-specific PCR reveal that CSMD1 alterations can correlate with earlier clinical

  12. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    NARCIS (Netherlands)

    Rooijers, K.; Loayza-Puch, F.; Nijtmans, L.G.J.; Agami, R.

    2013-01-01

    Mitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson's disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial mutations

  13. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    NARCIS (Netherlands)

    K. Rooijers (Koos); F. Loayza-Puch (Fabricio); L.G.J. Nijtmans (Leo); R. Agami (Reuven)

    2013-01-01

    textabstractMitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson's disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial

  14. Early life adversity and telomere length: a meta-analysis.

    Science.gov (United States)

    Ridout, K K; Levandowski, M; Ridout, S J; Gantz, L; Goonan, K; Palermo, D; Price, L H; Tyrka, A R

    2018-04-01

    Early adversity, in the form of abuse, neglect, socioeconomic status and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regard to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO and Web of Science identified 2462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data were extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N=30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen's d effect size=-0.35; 95% CI, -0.46 to -0.24; P<0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (P<0.0001 and P=0.0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control vs longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.

  15. Bistable switches control memory and plasticity in cellular differentiation

    Science.gov (United States)

    Wang, Lei; Walker, Brandon L.; Iannaccone, Stephen; Bhatt, Devang; Kennedy, Patrick J.; Tse, William T.

    2009-01-01

    Development of stem and progenitor cells into specialized tissues in multicellular organisms involves a series of cell fate decisions. Cellular differentiation in higher organisms is generally considered irreversible, and the idea of developmental plasticity in postnatal tissues is controversial. Here, we show that inhibition of mitogen-activated protein kinase (MAPK) in a human bone marrow stromal cell-derived myogenic subclone suppresses their myogenic ability and converts them into satellite cell-like precursors that respond to osteogenic stimulation. Clonal analysis of the induced osteogenic response reveals ultrasensitivity and an “all-or-none” behavior, hallmarks of a bistable switch mechanism with stochastic noise. The response demonstrates cellular memory, which is contingent on the accumulation of an intracellular factor and can be erased by factor dilution through cell divisions or inhibition of protein synthesis. The effect of MAPK inhibition also exhibits memory and appears to be controlled by another bistable switch further upstream that determines cell fate. Once the memory associated with osteogenic differentiation is erased, the cells regain their myogenic ability. These results support a model of cell fate decision in which a network of bistable switches controls inducible production of lineage-specific differentiation factors. A competitive balance between these factors determines cell fate. Our work underscores the dynamic nature of cellular differentiation and explains mechanistically the dual properties of stability and plasticity associated with the process. PMID:19366677

  16. Increased cellular uptake of peptide-modified PEGylated gold nanoparticles.

    Science.gov (United States)

    He, Bo; Yang, Dan; Qin, Mengmeng; Zhang, Yuan; He, Bing; Dai, Wenbing; Wang, Xueqing; Zhang, Qiang; Zhang, Hua; Yin, Changcheng

    2017-12-09

    Gold nanoparticles are promising drug delivery vehicles for nucleic acids, small molecules, and proteins, allowing various modifications on the particle surface. However, the instability and low bioavailability of gold nanoparticles compromise their clinical application. Here, we functionalized gold nanoparticles with CPP fragments (CALNNPFVYLI, CALRRRRRRRR) through sulfhydryl PEG to increase their stability and bioavailability. The resulting gold nanoparticles were characterized with transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-visible spectrometry and X-ray photoelectron spectroscopy (XPS), and the stability in biological solutions was evaluated. Comparing to PEGylated gold nanoparticles, CPP (CALNNPFVYLI, CALRRRRRRRR)-modified gold nanoparticles showed 46 folds increase in cellular uptake in A549 and B16 cell lines, as evidenced by the inductively coupled plasma atomic emission spectroscopy (ICP-AES). The interactions between gold nanoparticles and liposomes indicated CPP-modified gold nanoparticles bind to cell membrane more effectively than PEGylated gold nanoparticles. Surface plasmon resonance (SPR) was used to measure interactions between nanoparticles and the membrane. TEM and uptake inhibitor experiments indicated that the cellular entry of gold nanoparticles was mediated by clathrin and macropinocytosis. Other energy independent endocytosis pathways were also identified. Our work revealed a new strategy to modify gold nanoparticles with CPP and illustrated the cellular uptake pathway of CPP-modified gold nanoparticles. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. 47 CFR 22.901 - Cellular service requirements and limitations.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular service requirements and limitations... SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.901 Cellular service requirements and limitations. The licensee of each cellular system is responsible for ensuring that its cellular system...

  18. Quantitative Analysis of MicroRNAs in Vaccinia virus Infection Reveals Diversity in Their Susceptibility to Modification and Suppression.

    Directory of Open Access Journals (Sweden)

    Amy H Buck

    Full Text Available Vaccinia virus (VACV is a large cytoplasmic DNA virus that causes dramatic alterations to many cellular pathways including microRNA biogenesis. The virus encodes a poly(A polymerase which was previously shown to add poly(A tails to the 3' end of cellular miRNAs, resulting in their degradation by 24 hours post infection (hpi. Here we used small RNA sequencing to quantify the impact of VACV infection on cellular miRNAs in human cells at both early (6 h and late (24 h times post infection. A detailed quantitative analysis of individual miRNAs revealed marked diversity in the extent of their modification and relative change in abundance during infection. Some miRNAs became highly modified (e.g. miR-29a-3p, miR-27b-3p whereas others appeared resistant (e.g. miR-16-5p. Furthermore, miRNAs that were highly tailed at 6 hpi were not necessarily among the most reduced at 24 hpi. These results suggest that intrinsic features of human cellular miRNAs cause them to be differentially polyadenylated and altered in abundance during VACV infection. We also demonstrate that intermediate and late VACV gene expression are required for optimal repression of some miRNAs including miR-27-3p. Overall this work reveals complex and varied consequences of VACV infection on host miRNAs and identifies miRNAs which are largely resistant to VACV-induced polyadenylation and are therefore present at functional levels during the initial stages of infection and replication.

  19. Green Virtualization for Multiple Collaborative Cellular Operators

    KAUST Repository

    Farooq, Muhammad Junaid; Ghazzai, Hakim; Yaacoub, Elias; Kadri, Abdullah; Alouini, Mohamed-Slim

    2017-01-01

    This paper proposes and investigates a green virtualization framework for infrastructure sharing among multiple cellular operators whose networks are powered by a combination of conventional and renewable sources of energy. Under the proposed

  20. Corrosion of Cellular Metals in Marine Environments

    National Research Council Canada - National Science Library

    Scully, John R

    2006-01-01

    .... The basis for this work is an interdisciplinary approach that aims to understand: (a) the electrochemical, chemical, and metallurgical conditions that corrode cellular metals in marine environments when fabricated by brazing processes, (b...

  1. A cryptosystem based on elementary cellular automata

    Science.gov (United States)

    Abdo, A. A.; Lian, Shiguo; Ismail, I. A.; Amin, M.; Diab, H.

    2013-01-01

    Based on elementary cellular automata, a new image encryption algorithm is proposed in this paper. In this algorithm, a special kind of periodic boundary cellular automata with unity attractors is used. From the viewpoint of security, the number of cellular automata attractor states are changed with respect to the encrypted image, and different key streams are used to encrypt different plain images. The cellular neural network with chaotic properties is used as the generator of a pseudo-random key stream. Theoretical analysis and experimental results have both confirmed that the proposed algorithm possesses high security level and good performances against differential and statistical attacks. The comparison with other existing schemes is given, which shows the superiority of the proposal scheme.

  2. Mapping crime scenes and cellular telephone usage

    CSIR Research Space (South Africa)

    Schmitz, Peter MU

    2000-12-01

    Full Text Available This paper describes a method that uses a desktop geographical information system (GIS) to plot cellular telephone conversations made when crimes are committed, such as hijackings, hostage taking, kidnapping, rape and murder. The maps produced...

  3. Recent development of cellular manufacturing systems

    Indian Academy of Sciences (India)

    be manufactured in a cell, and the machines, which will comprise that cell, can be ... approaches for the CF problem which is referred to as Production Flow Analysis (PFA). ... programming model of cellular manufacturing system design which ...

  4. Cellular strategies to cope with protein aggregation

    NARCIS (Netherlands)

    Scior, Annika; Juenemann, Katrin; Kirstein, Janine

    2016-01-01

    Nature has evolved several mechanisms to detoxify intracellular protein aggregates that arise upon proteotoxic challenges. These include the controlled deposition of misfolded proteins at distinct cellular sites, the protein disaggregation and refolding by molecular chaperones and/or degradation of

  5. Cellular Reprogramming–Turning the Clock Back

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 6. Cellular Reprogramming - Turning the Clock Back - Nobel Prize in Physiology or Medicine, 2012. Deepa Subramanyam. General Article Volume 18 Issue 6 June 2013 pp 514-521 ...

  6. Dynamic cellular manufacturing system design considering ...

    Indian Academy of Sciences (India)

    Kamal Deep

    cellular manufacturing system in a company is division of ... designed to be assembled from a small number of stan- ..... contingency part process route in addition to the alternate .... istic industrial manufacturing vision considering multiple.

  7. Probing Cellular Dynamics with Mesoscopic Simulations

    DEFF Research Database (Denmark)

    Shillcock, Julian C.

    2010-01-01

    Cellular processes span a huge range of length and time scales from the molecular to the near-macroscopic. Understanding how effects on one scale influence, and are themselves influenced by, those on lower and higher scales is a critical issue for the construction of models in Systems Biology....... Advances in computing hardware and software now allow explicit simulation of some aspects of cellular dynamics close to the molecular scale. Vesicle fusion is one example of such a process. Experiments, however, typically probe cellular behavior from the molecular scale up to microns. Standard particle...... soon be coupled to Mass Action models allowing the parameters in such models to be continuously tuned according to the finer resolution simulation. This will help realize the goal of a computational cellular simulation that is able to capture the dynamics of membrane-associated processes...

  8. Cellular telephone use and cancer risk

    DEFF Research Database (Denmark)

    Schüz, Joachim; Jacobsen, Rune; Olsen, Jørgen H.

    2006-01-01

    BACKGROUND: The widespread use of cellular telephones has heightened concerns about possible adverse health effects. The objective of this study was to investigate cancer risk among Danish cellular telephone users who were followed for up to 21 years. METHODS: This study is an extended follow......-up of a large nationwide cohort of 420,095 persons whose first cellular telephone subscription was between 1982 and 1995 and who were followed through 2002 for cancer incidence. Standardized incidence ratios (SIRs) were calculated by dividing the number of observed cancer cases in the cohort by the number...... expected in the Danish population. RESULTS: A total of 14,249 cancers were observed (SIR = 0.95; 95% confidence interval [CI] = 0.93 to 0.97) for men and women combined. Cellular telephone use was not associated with increased risk for brain tumors (SIR = 0.97), acoustic neuromas (SIR = 0.73), salivary...

  9. Cellular and molecular etiology of hepatocyte injury in a murine model of environmentally induced liver abnormality

    Directory of Open Access Journals (Sweden)

    M.A. Al-Griw

    2016-09-01

    Full Text Available Exposures to a wide variety of environmental substances are negatively associated with many biological cell systems both in humans and rodents. Trichloroethane (TCE, a ubiquitous environmental toxicant, is used in large quantities as a dissolvent, metal degreaser, chemical intermediate, and component of consumer products. This increases the likelihood of human exposure to these compounds through dermal, inhalation and oral routes. The present in vivo study was aimed to investigate the possible cellular and molecular etiology of liver abnormality induced by early exposure to TCE using a murine model. The results showed a significant increase in liver weight. Histopathological examination revealed a TCE-induced hepatotoxicity which appeared as heavily congested central vein and blood sinusoids as well as leukocytic infiltration. Mitotic figures and apoptotic changes such as chromatin condensation and nuclear fragments were also identified. Cell death analysis demonstrates hepatocellular apoptosis was evident in the treated mice compared to control. TCE was also found to induce oxidative stress as indicated by an increase in the levels of lipid peroxidation, an oxidative stress marker. There was also a significant decrease in the DNA content of the hepatocytes of the treated groups compared to control. Agarose gel electrophoresis also provided further biochemical evidence of apoptosis by showing internucleosomal DNA fragmentation in the liver cells, indicating oxidative stress as the cause of DNA damage. These results suggest the need for a complete risk assessment of any new chemical prior to its arrival into the consumer market.

  10. Oxysterols and Their Cellular Effectors

    Directory of Open Access Journals (Sweden)

    Eija Nissilä

    2012-02-01

    Full Text Available Oxysterols are oxidized 27-carbon cholesterol derivatives or by-products of cholesterol biosynthesis, with a spectrum of biologic activities. Several oxysterols have cytotoxic and pro-apoptotic activities, the ability to interfere with the lateral domain organization, and packing of membrane lipids. These properties may account for their suggested roles in the pathology of diseases such as atherosclerosis, age-onset macular degeneration and Alzheimer’s disease. Oxysterols also have the capacity to induce inflammatory responses and play roles in cell differentiation processes. The functions of oxysterols as intermediates in the synthesis of bile acids and steroid hormones, and as readily transportable forms of sterol, are well established. Furthermore, their actions as endogenous regulators of gene expression in lipid metabolism via liver X receptors and the Insig (insulin-induced gene proteins have been investigated in detail. The cytoplasmic oxysterol-binding protein (OSBP homologues form a group of oxysterol/cholesterol sensors that has recently attracted a lot of attention. However, their mode of action is, as yet, poorly understood. Retinoic acid receptor-related orphan receptors (ROR α and γ, and Epstein-Barr virus induced gene 2 (EBI2 have been identified as novel oxysterol receptors, revealing new physiologic oxysterol effector mechanisms in development, metabolism, and immunity, and evoking enhanced interest in these compounds in the field of biomedicine.

  11. Cellular Phone Users- Willingness to Shop Online

    OpenAIRE

    Norazah Mohd Suki; Norbayah Mohd Suki

    2009-01-01

    This study aims to identify cellular phone users- shopping motivating factors towards online shopping. 100 university students located in Klang Valley, Malaysia were involved as the respondents. They were required to complete a set of questionnaire and had to own a cellular phone in order to be selected as sample in this study. Three from five proposed hypotheses were supported: purchasing information, shopping utilities and service quality. As a result, marketers and retailers should concent...

  12. Modeling of coupled differential equations for cellular chemical signaling pathways: Implications for assay protocols utilized in cellular engineering.

    Science.gov (United States)

    O'Clock, George D

    2016-08-01

    Cellular engineering involves modification and control of cell properties, and requires an understanding of fundamentals and mechanisms of action for cellular derived product development. One of the keys to success in cellular engineering involves the quality and validity of results obtained from cell chemical signaling pathway assays. The accuracy of the assay data cannot be verified or assured if the effect of positive feedback, nonlinearities, and interrelationships between cell chemical signaling pathway elements are not understood, modeled, and simulated. Nonlinearities and positive feedback in the cell chemical signaling pathway can produce significant aberrations in assay data collection. Simulating the pathway can reveal potential instability problems that will affect assay results. A simulation, using an electrical analog for the coupled differential equations representing each segment of the pathway, provides an excellent tool for assay validation purposes. With this approach, voltages represent pathway enzyme concentrations and operational amplifier feedback resistance and input resistance values determine pathway gain and rate constants. The understanding provided by pathway modeling and simulation is strategically important in order to establish experimental controls for assay protocol structure, time frames specified between assays, and assay concentration variation limits; to ensure accuracy and reproducibility of results.

  13. Postnatal odorant exposure induces peripheral olfactory plasticity at the cellular level.

    Science.gov (United States)

    Cadiou, Hervé; Aoudé, Imad; Tazir, Bassim; Molinas, Adrien; Fenech, Claire; Meunier, Nicolas; Grosmaitre, Xavier

    2014-04-02

    Mammalian olfactory sensory neurons (OSNs) form the primary elements of the olfactory system. Inserted in the olfactory mucosa lining of the nasal cavity, they are exposed to the environment and their lifespan is brief. Several reports say that OSNs are regularly regenerated during the entire life and that odorant environment affects the olfactory epithelium. However, little is known about the impact of the odorant environment on OSNs at the cellular level and more precisely in the context of early postnatal olfactory exposure. Here we exposed MOR23-green fluorescent protein (GFP) and M71-GFP mice to lyral or acetophenone, ligands for MOR23 or M71, respectively. Daily postnatal exposure to lyral induces plasticity in the population of OSNs expressing MOR23. Their density decreases after odorant exposure, whereas the amount of MOR23 mRNA and protein remain stable in the whole epithelium. Meanwhile, quantitative PCR indicates that each MOR23 neuron has higher levels of olfactory receptor transcripts and also expresses more CNGA2 and phosphodiesterase 1C, fundamental olfactory transduction pathway proteins. Transcript levels return to baseline after 4 weeks recovery. Patch-clamp recordings reveal that exposed MOR23 neurons respond to lyral with higher sensitivity and broader dynamic range while the responses' kinetics were faster. These effects are specific to the odorant-receptor pair lyral-MOR23: there was no effect of acetophenone on MOR23 neurons and no effect of acetophenone and lyral on the M71 population. Together, our results clearly demonstrate that OSNs undergo specific anatomical, molecular, and functional adaptation when chronically exposed to odorants in the early stage of life.

  14. Cellular injury evidenced by impedance technology and infrared microspectroscopy

    Science.gov (United States)

    le Roux, K.; Prinsloo, L. C.; Meyer, D.

    2015-03-01

    Fourier Transform Infrared (FTIR) spectroscopy is finding increasing biological application, for example in the analysis of diseased tissues and cells, cell cycle studies and investigating the mechanisms of action of anticancer drugs. Cancer treatment studies routinely define the types of cell-drug responses as either total cell destruction by the drug (all cells die), moderate damage (cell deterioration where some cells survive) or reversible cell cycle arrest (cytostasis). In this study the loss of viability and related chemical stress experienced by cells treated with the medicinal plant, Plectranthus ciliatus, was investigated using real time cell electronic sensing (RT-CES) technology and FTIR microspectroscopy. The use of plants as medicines is well established and ethnobotany has proven that crude extracts can serve as treatments against various ailments. The aim of this study was to determine whether FTIR microspectroscopy would successfully distinguish between different types of cellular injury induced by a potentially anticancerous plant extract. Cervical adenocarcinoma (HeLa) cells were treated with a crude extract of Pciliatus and cells monitored using RT-CES to characterize the type of cellular responses induced. Cell populations were then investigated using FTIR microspectroscopy and statistically analysed using One-way Analysis of Variance (ANOVA) and Principal Component Analysis (PCA). The plant extract and a cancer drug control (actinomycin D) induced concentration dependent cellular responses ranging from nontoxic, cytostatic or cytotoxic. Thirteen spectral peaks (915 cm-1, 933 cm-1, 989 cm-1, 1192 cm-1, 1369 cm-1, 1437 cm-1, 1450 cm-1, 1546 cm-1, 1634 cm-1, 1679 cm-1 1772 cm-1, 2874 cm-1 and 2962 cm-1) associated with cytotoxicity were significantly (p value < 0.05, one way ANOVA, Tukey test, Bonferroni) altered, while two of the bands were also indicative of early stress related responses. In PCA, poor separation between nontoxic and cytostatic

  15. The zebrafish miR-462/miR-731 cluster is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations.

    Science.gov (United States)

    Huang, Chun-Xiao; Chen, Nan; Wu, Xin-Jie; Huang, Cui-Hong; He, Yan; Tang, Rong; Wang, Wei-Min; Wang, Huan-Ling

    2015-12-01

    Hypoxia, a unique and essential environmental stress, evokes highly coordinated cellular responses, and hypoxia-inducible factor (HIF) 1 in the hypoxia signaling pathway, an evolutionarily conserved cellular signaling pathway, acts as a master regulator of the transcriptional response to hypoxic stress. MicroRNAs (miRNAs), a major class of posttranscriptional gene expression regulators, also play pivotal roles in orchestrating hypoxia-mediated cellular adaptations. Here, global miRNA expression profiling and quantitative real-time PCR indicated that the up-regulation of the miR-462/miR-731 cluster in zebrafish larvae is induced by hypoxia. It was further validated that miR-462 and miR-731 are up-regulated in a Hif-1α-mediated manner under hypoxia and specifically target ddx5 and ppm1da, respectively. Overexpression of miR-462 and miR-731 represses cell proliferation through blocking cell cycle progress of DNA replication, and induces apoptosis. In situ detection revealed that the miR-462/miR-731 cluster is highly expressed in a consistent and ubiquitous manner throughout the early developmental stages. Additionally, the transcripts become restricted to the notochord, pharyngeal arch, liver, and gut regions from postfertilization d 3 to 5. These data highlight a previously unidentified role of the miR-462/miR-731 cluster as a crucial signaling mediator for hypoxia-mediated cellular adaptations and provide some insights into the potential function of the cluster during embryonic development. © FASEB.

  16. Cellular pH measurements in Emiliania huxleyi reveal pronounced membrane proton permeability.

    Science.gov (United States)

    Suffrian, K; Schulz, K G; Gutowska, M A; Riebesell, U; Bleich, M

    2011-05-01

    • To understand the influence of changing surface ocean pH and carbonate chemistry on the coccolithophore Emiliania huxleyi, it is necessary to characterize mechanisms involved in pH homeostasis and ion transport. • Here, we measured effects of changes in seawater carbonate chemistry on the fluorescence emission ratio of BCECF (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein) as a measure of intracellular pH (pH(i)). Out of equilibrium solutions were used to differentiate between membrane permeation pathways for H(+), CO(2) and HCO(3)(-). • Changes in fluorescence ratio were calibrated in single cells, resulting in a ratio change of 0.78 per pH(i) unit. pH(i) acutely followed the pH of seawater (pH(e)) in a linear fashion between pH(e) values of 6.5 and 9 with a slope of 0.44 per pH(e) unit. pH(i) was nearly insensitive to changes in seawater CO(2) at constant pH(e) and HCO(3)(-). An increase in extracellular HCO(3)(-) resulted in a slight intracellular acidification. In the presence of DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid), a broad-spectrum inhibitor of anion exchangers, E. huxleyi acidified irreversibly. DIDS slightly reduced the effect of pH(e) on pH(i). • The data for the first time show the occurrence of a proton permeation pathway in E. huxleyi plasma membrane. pH(i) homeostasis involves a DIDS-sensitive mechanism. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

  17. A glimpse at mRNA dynamics reveals cellular domains and rapid trafficking through granules

    NARCIS (Netherlands)

    Gemert, Alice Myriam Christi van

    2011-01-01

    mRNA transport and targeting are essential to gene expression regulation. Specific mRNA sequences can bind several proteins and together form RiboNucleoProtein particles (RNP). The various proteins within the RNP determine mRNA fate: translation, transport or decay. RNP composition varies with

  18. Perilipin Expression Reveals Adipogenic Potential of hADSCs inside Superporous Polymeric Cellular Delivery Systems

    Directory of Open Access Journals (Sweden)

    Sorina Dinescu

    2014-01-01

    Full Text Available Recent progress in tissue engineering and regenerative medicine envisages the use of cell-scaffold bioconstructs to best mimic the natural in vivo microenvironment. Our aim was not only to develop novel 3D porous scaffolds for regenerative applications by the association of gelatin (G, alginate (A, and polyacrylamide (PAA major assets but also to evaluate their in vitro potential to support human adipose-derived stem cells (hADSCs adipogenesis. G-A-PAA biomatrix investigated in this work is an interesting substrate combining the advantages of the three individual constituents, namely, biodegradability of G, hydrophilicity of A and PAA, superior elasticity at compression with respect to the G-A and PAA controls, and the capacity to generate porous scaffolds. hADSCs inside these novel interpenetrating polymer networks (IPNs were able to populate the entire scaffold structure and to display their characteristic spindle-like shape as a consequence of a good interaction with G component of the matrices. Additionally, hADSCs proved to display the capacity to differentiate towards mature adipocytes, to accumulate lipids inside their cytoplasm, and to express perilipin late adipogenic marker inside novel IPNs described in this study. On long term, this newly designed biomatrix aims to represent a stem cell delivery system product dedicated for modern regenerative strategies.

  19. Model-based traction force microscopy reveals differential tension in cellular actin bundles.

    Science.gov (United States)

    Soiné, Jérôme R D; Brand, Christoph A; Stricker, Jonathan; Oakes, Patrick W; Gardel, Margaret L; Schwarz, Ulrich S

    2015-03-01

    Adherent cells use forces at the cell-substrate interface to sense and respond to the physical properties of their environment. These cell forces can be measured with traction force microscopy which inverts the equations of elasticity theory to calculate them from the deformations of soft polymer substrates. We introduce a new type of traction force microscopy that in contrast to traditional methods uses additional image data for cytoskeleton and adhesion structures and a biophysical model to improve the robustness of the inverse procedure and abolishes the need for regularization. We use this method to demonstrate that ventral stress fibers of U2OS-cells are typically under higher mechanical tension than dorsal stress fibers or transverse arcs.

  20. Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Steve

    2015-08-28

    Silymarin (SM), a natural product, is touted as a liver protectant and preventer of both chronic inflammation and diseases. To define how SM elicits these effects at a systems level, we performed transcriptional profiling, metabolomics, and signaling studies in human liver and T cell lines. Multiple pathways associated with cellular stress and metabolism were modulated by SM treatment within 0.5 to four hours: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed suppression of glycolytic, TCA cycle, and amino acid metabolism by SM treatment. Antiinflammatory effects arose with prolonged (i.e. 24 hours) SM exposure, with suppression of multiple proinflammatory mRNAs and nuclear factor kappa B (NF-κB) and forkhead box O (FOXO) signaling. Studies with murine knock out cells revealed that SM inhibition of both mTOR and NF-κB was partially AMPK dependent, while SM inhibition of the mTOR pathway in part required DDIT4. Thus, SM activates stress and repair responses that culminate in an anti-inflammatory phenotype. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Therefore, natural products like SM may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

  1. Shape Memory Alloy-Based Periodic Cellular Structures, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This SBIR Phase I effort will develop and demonstrate an innovative shape memory alloy (SMA) periodic cellular structural technology. Periodic cellular structures...

  2. Investigation of cellular detonation structure formation via linear stability theory and 2D and 3D numerical simulations

    Science.gov (United States)

    Borisov, S. P.; Kudryavtsev, A. N.

    2017-10-01

    Linear and nonlinear stages of the instability of a plane detonation wave (DW) and the subsequent process of formation of cellular detonation structure are investigated. A simple model with one-step irreversible chemical reaction is used. The linear analysis is employed to predict the DW front structure at the early stages of its formation. An emerging eigenvalue problem is solved with a global method using a Chebyshev pseudospectral method and the LAPACK software library. A local iterative shooting procedure is used for eigenvalue refinement. Numerical simulations of a propagation of a DW in plane and rectangular channels are performed with a shock capturing WENO scheme of 5th order. A special method of a computational domain shift is implemented in order to maintain the DW in the domain. It is shown that the linear analysis gives certain predictions about the DW structure that are in agreement with the numerical simulations of early stages of DW propagation. However, at later stages, a merger of detonation cells occurs so that their number is approximately halved. Computations of DW propagation in a square channel reveal two different types of spatial structure of the DW front, "rectangular" and "diagonal" types. A spontaneous transition from the rectangular to diagonal type of structure is observed during propagation of the DW.

  3. Pathogen–host reorganization during Chlamydia invasion revealed by cryo-electron tomography

    Science.gov (United States)

    Nans, Andrea; Saibil, Helen R; Hayward, Richard D

    2014-01-01

    Invasion of host cells is a key early event during bacterial infection, but the underlying pathogen–host interactions are yet to be fully visualized in three-dimensional detail. We have captured snapshots of the early stages of bacterial-mediated endocytosis in situ by exploiting the small size of chlamydial elementary bodies (EBs) for whole-cell cryo-electron tomography. Chlamydiae are obligate intracellular bacteria that infect eukaryotic cells and cause sexually transmitted infections and trachoma, the leading cause of preventable blindness. We demonstrate that Chlamydia trachomatis LGV2 EBs are intrinsically polarized. One pole is characterized by a tubular inner membrane invagination, while the other exhibits asymmetric periplasmic expansion to accommodate an array of type III secretion systems (T3SSs). Strikingly, EBs orient with their T3SS-containing pole facing target cells, enabling the T3SSs to directly contact the cellular plasma membrane. This contact induces enveloping macropinosomes, actin-rich filopodia and phagocytic cups to zipper tightly around the internalizing bacteria. Once encapsulated into tight early vacuoles, EB polarity and the T3SSs are lost. Our findings reveal previously undescribed structural transitions in both pathogen and host during the initial steps of chlamydial invasion. PMID:24809274

  4. IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Takahashi, Yutaka, E-mail: takahash@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Cellular senescence plays an important role in tumorigenesis and aging process. Black-Right-Pointing-Pointer We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. Black-Right-Pointing-Pointer IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. Black-Right-Pointing-Pointer These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated {beta}-galactosidase (SA-{beta}-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, {gamma}H2AX, the increased levels of p53 and p21 proteins, and activated SA-{beta}-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-{beta}-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

  5. IGF-I enhances cellular senescence via the reactive oxygen species–p53 pathway

    International Nuclear Information System (INIS)

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro; Takahashi, Yutaka

    2012-01-01

    Highlights: ► Cellular senescence plays an important role in tumorigenesis and aging process. ► We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. ► IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. ► These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated β-galactosidase (SA-β-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, γH2AX, the increased levels of p53 and p21 proteins, and activated SA-β-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-β-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

  6. Early phonology revealed by international adoptees' birth language retention.

    Science.gov (United States)

    Choi, Jiyoun; Broersma, Mirjam; Cutler, Anne

    2017-07-11

    Until at least 6 mo of age, infants show good discrimination for familiar phonetic contrasts (i.e., those heard in the environmental language) and contrasts that are unfamiliar. Adult-like discrimination (significantly worse for nonnative than for native contrasts) appears only later, by 9-10 mo. This has been interpreted as indicating that infants have no knowledge of phonology until vocabulary development begins, after 6 mo of age. Recently, however, word recognition has been observed before age 6 mo, apparently decoupling the vocabulary and phonology acquisition processes. Here we show that phonological acquisition is also in progress before 6 mo of age. The evidence comes from retention of birth-language knowledge in international adoptees. In the largest ever such study, we recruited 29 adult Dutch speakers who had been adopted from Korea when young and had no conscious knowledge of Korean language at all. Half were adopted at age 3-5 mo (before native-specific discrimination develops) and half at 17 mo or older (after word learning has begun). In a short intensive training program, we observe that adoptees (compared with 29 matched controls) more rapidly learn tripartite Korean consonant distinctions without counterparts in their later-acquired Dutch, suggesting that the adoptees retained phonological knowledge about the Korean distinction. The advantage is equivalent for the younger-adopted and the older-adopted groups, and both groups not only acquire the tripartite distinction for the trained consonants but also generalize it to untrained consonants. Although infants younger than 6 mo can still discriminate unfamiliar phonetic distinctions, this finding indicates that native-language phonological knowledge is nonetheless being acquired at that age.

  7. Cellular automatons applied to gas dynamic problems

    Science.gov (United States)

    Long, Lyle N.; Coopersmith, Robert M.; Mclachlan, B. G.

    1987-01-01

    This paper compares the results of a relatively new computational fluid dynamics method, cellular automatons, with experimental data and analytical results. This technique has been shown to qualitatively predict fluidlike behavior; however, there have been few published comparisons with experiment or other theories. Comparisons are made for a one-dimensional supersonic piston problem, Stokes first problem, and the flow past a normal flat plate. These comparisons are used to assess the ability of the method to accurately model fluid dynamic behavior and to point out its limitations. Reasonable results were obtained for all three test cases, but the fundamental limitations of cellular automatons are numerous. It may be misleading, at this time, to say that cellular automatons are a computationally efficient technique. Other methods, based on continuum or kinetic theory, would also be very efficient if as little of the physics were included.

  8. Alleviate Cellular Congestion Through Opportunistic Trough Filling

    Directory of Open Access Journals (Sweden)

    Yichuan Wang

    2014-04-01

    Full Text Available The demand for cellular data service has been skyrocketing since the debut of data-intensive smart phones and touchpads. However, not all data are created equal. Many popular applications on mobile devices, such as email synchronization and social network updates, are delay tolerant. In addition, cellular load varies significantly in both large and small time scales. To alleviate network congestion and improve network performance, we present a set of opportunistic trough filling schemes that leverage the time-variation of network congestion and delay-tolerance of certain traffic in this paper. We consider average delay, deadline, and clearance time as the performance metrics. Simulation results show promising performance improvement over the standard schemes. The work shed lights on addressing the pressing issue of cellular overload.

  9. Cellular Signaling in Health and Disease

    CERN Document Server

    Beckerman, Martin

    2009-01-01

    In today’s world, three great classes of non-infectious diseases – the metabolic syndromes (such as type 2 diabetes and atherosclerosis), the cancers, and the neurodegenerative disorders – have risen to the fore. These diseases, all associated with increasing age of an individual, have proven to be remarkably complex and difficult to treat. This is because, in large measure, when the cellular signaling pathways responsible for maintaining homeostasis and health of the body become dysregulated, they generate equally stable disease states. As a result the body may respond positively to a drug, but only for a while and then revert back to the disease state. Cellular Signaling in Health and Disease summarizes our current understanding of these regulatory networks in the healthy and diseased states, showing which molecular components might be prime targets for drug interventions. This is accomplished by presenting models that explain in mechanistic, molecular detail how a particular part of the cellular sign...

  10. Passive Noise Filtering by Cellular Compartmentalization.

    Science.gov (United States)

    Stoeger, Thomas; Battich, Nico; Pelkmans, Lucas

    2016-03-10

    Chemical reactions contain an inherent element of randomness, which presents itself as noise that interferes with cellular processes and communication. Here we discuss the ability of the spatial partitioning of molecular systems to filter and, thus, remove noise, while preserving regulated and predictable differences between single living cells. In contrast to active noise filtering by network motifs, cellular compartmentalization is highly effective and easily scales to numerous systems without requiring a substantial usage of cellular energy. We will use passive noise filtering by the eukaryotic cell nucleus as an example of how this increases predictability of transcriptional output, with possible implications for the evolution of complex multicellularity. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Cellular-automata method for phase unwrapping

    International Nuclear Information System (INIS)

    Ghiglia, D.C.; Mastin, G.A.; Romero, L.A.

    1987-01-01

    Research into two-dimensional phase unwrapping has uncovered interesting and troublesome inconsistencies that cause path-dependent results. Cellular automata, which are simple, discrete mathematical systems, offered promise of computation in nondirectional, parallel manner. A cellular automaton was discovered that can unwrap consistent phase data in n dimensions in a path-independent manner and can automatically accommodate noise-induced (pointlike) inconsistencies and arbitrary boundary conditions (region partitioning). For data with regional (nonpointlike) inconsistencies, no phase-unwrapping algorithm will converge, including the cellular-automata approach. However, the automata method permits more simple visualization of the regional inconsistencies. Examples of its behavior on one- and two-dimensional data are presented

  12. Cyclic cellular automata in 3D

    International Nuclear Information System (INIS)

    Reiter, Clifford A.

    2011-01-01

    Highlights: → We explore the self-organization of cyclic cellular automata in 3D. → Von Neumann, Moore and two types of intermediate neighborhoods are investigated. → Random neighborhoods self organize through phases into complex nested structures. → Demons are seen to have many alternatives in 3D. - Abstract: Cyclic cellular automata in two dimensions have long been intriguing because they self organize into spirals and that behavior can be analyzed. The form for the patterns that develop is highly dependent upon the form of the neighborhood. We extend this work to three dimensional cyclic cellular automata and observe self organization dependent upon the neighborhood type. This includes neighborhood types intermediate between Von Neumann and Moore neighborhoods. We also observe that the patterns include nested shells with the appropriate forms but that the nesting is far more complex than the spirals that occur in two dimensions.

  13. VUV spectroscopy of water under cellular conditions

    International Nuclear Information System (INIS)

    Mota, R.; Parafita, R.; Maneira, M. J. P.; Mason, N. J.; Garcia, G.; Ribeiro, P. A.; Raposo, M.; Limao-Vieira, P.

    2006-01-01

    The understanding of radiation damage within cells, and thence mutagenesis, depends upon a detailed knowledge of the spectroscopy and dissociation dynamics of water. Results of a new study of the electronic state spectroscopy of water, using synchrotron radiation are reported. In order to gain some insight into how the spectroscopy and dissociation dynamics of water is influenced by its environment we also report photo-absorption spectra of water within thin films of poly(o-methoxyaniline) which have been suggested as a good mimic for biological membranes in the cellular environment. Comparison of these spectra with those of gaseous water and condensed amorphous water ice suggest that water in such films is similar to gaseous water and does not show the blue shift suggested in some cellular models. The lowest energy of OH production from dissociation of water in the cellular environment may therefore be around 6.7 eV (185 nm). (authors)

  14. Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake

    Science.gov (United States)

    CELLULAR STRESS RESPONSE TO ENGINEERED NANOPARTICLES: EFFECT OF SIZE, SURFACE COATING, AND CELLULAR UPTAKE RY Prasad 1, JK McGee2, MG Killius1 D Ackerman2, CF Blackman2 DM DeMarini2 , SO Simmons2 1 Student Services Contractor, US EPA, RTP, NC 2 US EPA, RTP, NC The num...

  15. A korarchaeal genome reveals insights into the evolution of the Archaea

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Iain J; Elkins, James G.; Podar, Mircea; Graham, David E.; Makarova, Kira S.; Wolf, Yuri; Randau, Lennart; Hedlund, Brian P.; Brochier-Armanet, Celine; Kunin, Victor; Anderson, Iain; Lapidus, Alla; Goltsman, Eugene; Barry, Kerrie; Koonin, Eugene V.; Hugenholtz, Phil; Kyrpides, Nikos; Wanner, Gerhard; Richardson, Paul; Keller, Martin; Stetter, Karl O.

    2008-06-05

    The candidate division Korarchaeota comprises a group of uncultivated microorganisms that, by their small subunit rRNA phylogeny, may have diverged early from the major archaeal phyla Crenarchaeota and Euryarchaeota. Here, we report the initial characterization of a member of the Korarchaeota with the proposed name,"Candidatus Korarchaeum cryptofilum," which exhibits an ultrathin filamentous morphology. To investigate possible ancestral relationships between deep-branching Korarchaeota and other phyla, we used whole-genome shotgun sequencing to construct a complete composite korarchaeal genome from enriched cells. The genome was assembled into a single contig 1.59 Mb in length with a G + C content of 49percent. Of the 1,617 predicted protein-coding genes, 1,382 (85percent) could be assigned to a revised set of archaeal Clusters of Orthologous Groups (COGs). The predicted gene functions suggest that the organism relies on a simple mode of peptide fermentation for carbon and energy and lacks the ability to synthesize de novo purines, CoA, and several other cofactors. Phylogenetic analyses based on conserved single genes and concatenated protein sequences positioned the korarchaeote as a deep archaeal lineage with an apparent affinity to the Crenarchaeota. However, the predicted gene content revealed that several conserved cellular systems, such as cell division, DNA replication, and tRNA maturation, resemble the counterparts in the Euryarchaeota. In light of the known composition of archaeal genomes, the Korarchaeota might have retained a set of cellular features that represents the ancestral archaeal form.

  16. A Korarchael Genome Reveals Insights into the Evolution of the Archaea

    Energy Technology Data Exchange (ETDEWEB)

    Lapidus, Alla; Elkins, James G.; Podar, Mircea; Graham, David E.; Makarova, Kira S.; Wolf, Yuri; Randau, Lennart; Hedlund, Brian P.; Brochier-Armanet, Celine; Kunin, Victor; Anderson, Iain; Lapidus, Alla; Goltsman, Eugene; Barry, Kerrie; Koonin, Eugene V.; Hugenholtz, Phil; Kyrpides, Nikos; Wanner, Gerhard; Richardson, Paul; Keller, Martin; Stetter, Karl O.

    2008-01-07

    The candidate division Korarchaeota comprises a group of uncultivated microorganisms that, by their small subunit rRNA phylogeny, may have diverged early from the major archaeal phyla Crenarchaeota and Euryarchaeota. Here, we report the initial characterization of a member of the Korarchaeota with the proposed name, ?Candidatus Korarchaeum cryptofilum,? which exhibits an ultrathin filamentous morphology. To investigate possible ancestral relationships between deep-branching Korarchaeota and other phyla, we used whole-genome shotgun sequencing to construct a complete composite korarchaeal genome from enriched cells. The genome was assembled into a single contig 1.59 Mb in length with a G + C content of 49percent. Of the 1,617 predicted protein-coding genes, 1,382 (85percent) could be assigned to a revised set of archaeal Clusters of Orthologous Groups (COGs). The predicted gene functions suggest that the organism relies on a simple mode of peptide fermentation for carbon and energy and lacks the ability to synthesize de novo purines, CoA, and several other cofactors. Phylogenetic analyses based on conserved single genes and concatenated protein sequences positioned the korarchaeote as a deep archaeal lineage with an apparent affinity to the Crenarchaeota. However, the predicted gene content revealed that several conserved cellular systems, such as cell division, DNA replication, and tRNA maturation, resemble the counterparts in the Euryarchaeota. In light of the known composition of archaeal genomes, the Korarchaeota might have retained a set of cellular features that represents the ancestral archaeal form.

  17. Chromatin structure and cellular radiosensitivity : A comparison of two human tumour cell lines

    NARCIS (Netherlands)

    Woudstra, EC; Roesink, JM; Rosemann, M; Brunsting, JF; Driessen, C; Orta, T; Konings, AWT; Peacock, JH; Kampinga, HH

    1996-01-01

    The role of variation in susceptibility to DNA damage induction was studied as a determinant for cellular radiosensitivity. Comparison of the radiosensitive HX142 and radioresistant RT112 cell lines previously revealed higher susceptibility to X-ray-induced DNA damage in the sensitive cell line

  18. Genomic stability during cellular reprogramming: Mission impossible?

    Energy Technology Data Exchange (ETDEWEB)

    Joest, Mathieu von; Búa Aguín, Sabela; Li, Han, E-mail: han.li@pasteur.fr

    2016-06-15

    The generation of induced pluripotent stem cells (iPSCs) from adult somatic cells is one of the most exciting discoveries in recent biomedical research. It holds tremendous potential in drug discovery and regenerative medicine. However, a series of reports highlighting genomic instability in iPSCs raises concerns about their clinical application. Although the mechanisms cause genomic instability during cellular reprogramming are largely unknown, several potential sources have been suggested. This review summarizes current knowledge on this active research field and discusses the latest efforts to alleviate the genomic insults during cellular reprogramming to generate iPSCs with enhanced quality and safety.

  19. Toxicology and cellular effect of manufactured nanomaterials

    Science.gov (United States)

    Chen, Fanqing

    2014-07-22

    The increasing use of nanotechnology in consumer products and medical applications underlies the importance of understanding its potential toxic effects to people and the environment. Herein are described methods and assays to predict and evaluate the cellular effects of nanomaterial exposure. Exposing cells to nanomaterials at cytotoxic doses induces cell cycle arrest and increases apoptosis/necrosis, activates genes involved in cellular transport, metabolism, cell cycle regulation, and stress response. Certain nanomaterials induce genes indicative of a strong immune and inflammatory response within skin fibroblasts. Furthermore, the described multiwall carbon nanoonions (MWCNOs) can be used as a therapeutic in the treatment of cancer due to its cytotoxicity.

  20. Capacity on wireless quantum cellular communication system

    Science.gov (United States)

    Zhou, Xiang-Zhen; Yu, Xu-Tao; Zhang, Zai-Chen

    2018-03-01

    Quantum technology is making excellent prospects in future communication networks. Entanglement generation and purification are two major components in quantum networks. Combining these two techniques with classical cellular mobile communication, we proposed a novel wireless quantum cellular(WQC) communication system which is possible to realize commercial mobile quantum communication. In this paper, the architecture and network topology of WQC communication system are discussed, the mathematical model of WQC system is extracted and the serving capacity, indicating the ability to serve customers, is defined and calculated under certain circumstances.

  1. External insulation with cellular plastic materials

    DEFF Research Database (Denmark)

    Sørensen, Lars Schiøtt; Nielsen, Anker

    2014-01-01

    External thermal insulation composite systems (ETICS) can be used as extra insulation of existing buildings. The system can be made of cellular plastic materials or mineral wool. There is a European Technical guideline, ETAG 004, that describe the tests that shall be conducted on such systems....... This paper gives a comparison of systems with mineral wool and cellular plastic, based on experience from practice and literature. It is important to look at the details in the system and at long time stability of the properties such as thermal insulation, moisture and fire. Investigation of fire properties...

  2. Algorithmic crystal chemistry: A cellular automata approach

    International Nuclear Information System (INIS)

    Krivovichev, S. V.

    2012-01-01

    Atomic-molecular mechanisms of crystal growth can be modeled based on crystallochemical information using cellular automata (a particular case of finite deterministic automata). In particular, the formation of heteropolyhedral layered complexes in uranyl selenates can be modeled applying a one-dimensional three-colored cellular automaton. The use of the theory of calculations (in particular, the theory of automata) in crystallography allows one to interpret crystal growth as a computational process (the realization of an algorithm or program with a finite number of steps).

  3. Cellular Automata Simulation for Wealth Distribution

    Science.gov (United States)

    Lo, Shih-Ching

    2009-08-01

    Wealth distribution of a country is a complicate system. A model, which is based on the Epstein & Axtell's "Sugars cape" model, is presented in Netlogo. The model considers the income, age, working opportunity and salary as control variables. There are still other variables should be considered while an artificial society is established. In this study, a more complicate cellular automata model for wealth distribution model is proposed. The effects of social welfare, tax, economical investment and inheritance are considered and simulated. According to the cellular automata simulation for wealth distribution, we will have a deep insight of financial policy of the government.

  4. Cellular consequences of sleep deprivation in the brain.

    Science.gov (United States)

    Cirelli, Chiara

    2006-10-01

    Several recent studies have used transcriptomics approaches to characterize the molecular correlates of sleep, waking, and sleep deprivation. This analysis may help in understanding the benefits that sleep brings to the brain at the cellular level. The studies are still limited in number and focus on a few brain regions, but some consistent findings are emerging. Sleep, spontaneous wakefulness, short-term, and long-term sleep deprivation are each associated with the upregulation of hundreds of genes in the cerebral cortex and other brain areas. In fruit flies as well as in mammals, three categories of genes are consistently upregulated during waking and short-term sleep deprivation relative to sleep. They include genes involved in energy metabolism, synaptic potentiation, and the response to cellular stress. In the rat cerebral cortex, transcriptional changes associated with prolonged sleep loss differ significantly from those observed during short-term sleep deprivation. However, it is too early to draw firm conclusions relative to the molecular consequences of sleep deprivation, and more extensive studies using DNA and protein arrays are needed in different species and in different brain regions.

  5. The Cellular Differential Evolution Based on Chaotic Local Search

    Directory of Open Access Journals (Sweden)

    Qingfeng Ding

    2015-01-01

    Full Text Available To avoid immature convergence and tune the selection pressure in the differential evolution (DE algorithm, a new differential evolution algorithm based on cellular automata and chaotic local search (CLS or ccDE is proposed. To balance the exploration and exploitation tradeoff of differential evolution, the interaction among individuals is limited in cellular neighbors instead of controlling parameters in the canonical DE. To improve the optimizing performance of DE, the CLS helps by exploring a large region to avoid immature convergence in the early evolutionary stage and exploiting a small region to refine the final solutions in the later evolutionary stage. What is more, to improve the convergence characteristics and maintain the population diversity, the binomial crossover operator in the canonical DE may be instead by the orthogonal crossover operator without crossover rate. The performance of ccDE is widely evaluated on a set of 14 bound constrained numerical optimization problems compared with the canonical DE and several DE variants. The simulation results show that ccDE has better performances in terms of convergence rate and solution accuracy than other optimizers.

  6. Early prenatal syphilis

    Directory of Open Access Journals (Sweden)

    Santosh Rathod

    2010-01-01

    Full Text Available Syphilis in pregnancy still remains a challenge despite the availability of adequate diagnostic tests for serological screening and penicillin therapy. We report a case of 2 month old female infant who presented with runny nose, papulosquamous lesions over both palms and soles and perianal erosions since 1 month after birth. Cutaneous examination revealed moist eroded areas in the perianal region and fine scaly lesions over palms and soles. Radiograph of both upper limbs and limbs revealed early periosteal changes in lower end of humerus and lower end of tibia. Diagnosis of early pre-natal syphilis was confirmed by Child′s Serum Rapid Plasma Reagin Antibody test [S.RPR] being positive with 1:64 dilution while that of mother was 1:8.

  7. Calcium movements and the cellular basis of gravitropism

    Science.gov (United States)

    Roux, S. J.; Biro, R. L.; Hale, C. C.

    An early gravity-transduction event in oat coleoptiles which precedes any noticeable bending is the accumulation of calcium on their prospective slower-growing side. Sub-cellular calcium localization studies indicate that the gravity-stimulated redistribution of calcium results in an increased concentration of calcium in the walls of responding cells. Since calcium can inhibit the extension growth of plant cell walls, this selective accumulation of calcium in walls may play a role in inducing the asymmetry of growth which characterizes gravitropism. The active transport of calcium from cells into walls is performed by a calcium-dependent ATPase localized in the plasma membrane. Evidence is presented in support of the hypothesis that this calcium pump is regulated by a feed-back mechanism which includes the participation of calmodulin.

  8. Cellular and Molecular Biological Approaches to Interpreting Ancient Biomarkers

    Science.gov (United States)

    Newman, Dianne K.; Neubauer, Cajetan; Ricci, Jessica N.; Wu, Chia-Hung; Pearson, Ann

    2016-06-01

    Our ability to read the molecular fossil record has advanced significantly in the past decade. Improvements in biomarker sampling and quantification methods, expansion of molecular sequence databases, and the application of genetic and cellular biological tools to problems in biomarker research have enabled much of this progress. By way of example, we review how attempts to understand the biological function of 2-methylhopanoids in modern bacteria have changed our interpretation of what their molecular fossils tell us about the early history of life. They were once thought to be biomarkers of cyanobacteria and hence the evolution of oxygenic photosynthesis, but we now believe that 2-methylhopanoid biosynthetic capacity originated in the Alphaproteobacteria, that 2-methylhopanoids are regulated in response to stress, and that hopanoid 2-methylation enhances membrane rigidity. We present a new interpretation of 2-methylhopanes that bridges the gap between studies of the functions of 2-methylhopanoids and their patterns of occurrence in the rock record.

  9. Early discontinuation

    DEFF Research Database (Denmark)

    Hansen, Dorte Gilså; Felde, Lina; Gichangi, Anthony

    2007-01-01

    prevalence and rate of early discontinuation of different drugs consisting of, in this study, lipid-lowering drugs, antihypertensive drugs, antidepressants, antidiabetics and drugs against osteoporosis. Material and methods This was a register study based on prescription data covering a 4-year period...... and consisting of 470,000 citizens. For each practice and group of drug, a 1-year prevalence for 2002 and the rate of early discontinuation among new users in 2002-2003 were estimated. Early discontinuation was defined as no prescriptions during the second half-year following the first prescription....... There was a positive association between the prevalence of prescribing for the specific drugs studied (antidepressants, antidiabetics, drugs against osteoporosis and lipid-lowering drugs) and early discontinuation (r = 0.29 -0.44), but not for anti-hypertensive drugs. The analysis of the association between prevalence...

  10. Early literacy

    DEFF Research Database (Denmark)

    Jensen, Anders Skriver

    2012-01-01

    This paper discusses findings from the Danish contribution to the EASE project, a European research project running from 2008 to 2010 on early literacy in relation to the transition from childcare to school. It explores a holistic, inclusive approach to early literacy that resists a narrow...... and schools. The paper also draws on Gee’s (2001, 2003, 2004, 2008) sociocultural approach to literacy, and Honneth’s (2003, 2006) concept of recognition. Emphasizing participation and recognition as key elements, it claims that stakeholders in early liter- acy must pay attention to how diverse early literacy...... opportunities empower children, especially when these opportunities are employed in a project-based learning environ- ment in which each child is able to contribute to the shared literacy events....

  11. Novel Approaches to Cellular Transplantation from the US Space Program

    Science.gov (United States)

    Pellis, Neal R.; Homick, Jerry L. (Technical Monitor)

    1999-01-01

    Research in the treatment of type I diabetes is entering a new era that takes advantage of our knowledge in an ever increasing variety of scientific disciplines. Some may originate from very diverse sources, one of which is the Space Program at National Aeronautics and Space Administration (NASA). The Space Program contributes to diabetes-related research in several treatment modalities. As an ongoing effort for medical monitoring of personnel involved in space exploration activities NASA and the extramural scientific community investigate strategies for noninvasive estimation of blood glucose levels. Part of the effort in the space protein crystal growth program is high-resolution structural analysis insulin as a means to better understand the interaction with its receptor and with host immune components and as a basis for rational design of a "better" insulin molecule. The Space Program is also developing laser technology for potential early cataract detection as well as a noninvasive analyses for addressing preclinical diabetic retinopathy. Finally, NASA developed an exciting cell culture system that affords some unique advantages in the propagation and maintenance of mammalian cells in vitro. The cell culture system was originally designed to maintain cell suspensions with a minimum of hydrodynamic and mechanical sheer while awaiting launch into microgravity. Currently the commercially available NASA bioreactor (Synthecon, Inc., Houston, TX) is used as a research tool in basic and applied cell biology. In recent years there is continued strong interest in cellular transplantation as treatment for type I diabetes. The advantages are the potential for successful long-term amelioration and a minimum risk for morbidity in the event of rejection of the transplanted cells. The pathway to successful application of this strategy is accompanied by several substantial hurdles: (1) isolation and propagation of a suitable uniform donor cell population; (2) management of

  12. 47 CFR 22.923 - Cellular system configuration.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular system configuration. 22.923 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.923 Cellular system configuration. Mobile stations... directly or through cellular repeaters. Auxiliary test stations may communicate with base or mobile...

  13. 47 CFR 22.905 - Channels for cellular service.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Channels for cellular service. 22.905 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.905 Channels for cellular service. The following frequency bands are allocated for assignment to service providers in the Cellular Radiotelephone Service. (a...

  14. Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus.

    Directory of Open Access Journals (Sweden)

    Fuqu Yu

    2007-03-01

    Full Text Available The herpesvirus life cycle has two distinct phases: latency and lytic replication. The balance between these two phases is critical for viral pathogenesis. It is believed that cellular signals regulate the switch from latency to lytic replication. To systematically evaluate the cellular signals regulating this reactivation process in Kaposi sarcoma-associated herpesvirus, the effects of 26,000 full-length cDNA expression constructs on viral reactivation were individually assessed in primary effusion lymphoma-derived cells that harbor the latent virus. A group of diverse cellular signaling proteins were identified and validated in their effect of inducing viral lytic gene expression from the latent viral genome. The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation. The same pathway also mediates spontaneous reactivation, which sets the first example to our knowledge of a specific cellular pathway being studied in the spontaneous reactivation process. Our study provides a functional genomic approach to systematically identify the cellular signals regulating the herpesvirus life cycle, thus facilitating better understanding of a fundamental issue in virology and identifying novel therapeutic targets.

  15. Generation and Comprehensive Analysis of an Influenza Virus Polymerase Cellular Interaction Network▿†§

    Science.gov (United States)

    Tafforeau, Lionel; Chantier, Thibault; Pradezynski, Fabrine; Pellet, Johann; Mangeot, Philippe E.; Vidalain, Pierre-Olivier; Andre, Patrice; Rabourdin-Combe, Chantal; Lotteau, Vincent

    2011-01-01

    The influenza virus transcribes and replicates its genome inside the nucleus of infected cells. Both activities are performed by the viral RNA-dependent RNA polymerase that is composed of the three subunits PA, PB1, and PB2, and recent studies have shown that it requires host cell factors to transcribe and replicate the viral genome. To identify these cellular partners, we generated a comprehensive physical interaction map between each polymerase subunit and the host cellular proteome. A total of 109 human interactors were identified by yeast two-hybrid screens, whereas 90 were retrieved by literature mining. We built the FluPol interactome network composed of the influenza virus polymerase (PA, PB1, and PB2) and the nucleoprotein NP and 234 human proteins that are connected through 279 viral-cellular protein interactions. Analysis of this interactome map revealed enriched cellular functions associated with the influenza virus polymerase, including host factors involved in RNA polymerase II-dependent transcription and mRNA processing. We confirmed that eight influenza virus polymerase-interacting proteins are required for virus replication and transcriptional activity of the viral polymerase. These are involved in cellular transcription (C14orf166, COPS5, MNAT1, NMI, and POLR2A), translation (EIF3S6IP), nuclear transport (NUP54), and DNA repair (FANCG). Conversely, we identified PRKRA, which acts as an inhibitor of the viral polymerase transcriptional activity and thus is required for the cellular antiviral response. PMID:21994455

  16. Generation and comprehensive analysis of an influenza virus polymerase cellular interaction network.

    Science.gov (United States)

    Tafforeau, Lionel; Chantier, Thibault; Pradezynski, Fabrine; Pellet, Johann; Mangeot, Philippe E; Vidalain, Pierre-Olivier; Andre, Patrice; Rabourdin-Combe, Chantal; Lotteau, Vincent

    2011-12-01

    The influenza virus transcribes and replicates its genome inside the nucleus of infected cells. Both activities are performed by the viral RNA-dependent RNA polymerase that is composed of the three subunits PA, PB1, and PB2, and recent studies have shown that it requires host cell factors to transcribe and replicate the viral genome. To identify these cellular partners, we generated a comprehensive physical interaction map between each polymerase subunit and the host cellular proteome. A total of 109 human interactors were identified by yeast two-hybrid screens, whereas 90 were retrieved by literature mining. We built the FluPol interactome network composed of the influenza virus polymerase (PA, PB1, and PB2) and the nucleoprotein NP and 234 human proteins that are connected through 279 viral-cellular protein interactions. Analysis of this interactome map revealed enriched cellular functions associated with the influenza virus polymerase, including host factors involved in RNA polymerase II-dependent transcription and mRNA processing. We confirmed that eight influenza virus polymerase-interacting proteins are required for virus replication and transcriptional activity of the viral polymerase. These are involved in cellular transcription (C14orf166, COPS5, MNAT1, NMI, and POLR2A), translation (EIF3S6IP), nuclear transport (NUP54), and DNA repair (FANCG). Conversely, we identified PRKRA, which acts as an inhibitor of the viral polymerase transcriptional activity and thus is required for the cellular antiviral response.

  17. A cellular automata model for ant trails

    Indian Academy of Sciences (India)

    In this study, the unidirectional ant traffic flow with U-turn in an ant trail was investigated using one-dimensional cellular automata model. It is known that ants communicate with each other by dropping a chemical, called pheromone, on the substrate. Apart from the studies in the literature, it was considered in the model that ...

  18. Adaptive downtilt for cellular base stations

    NARCIS (Netherlands)

    Mestrom, R.M.C.; Coenen, T.J.; Smolders, A.B.

    2012-01-01

    Efficiency, reconfigurability, and power consumption are paramount for future communication systems in applications such as cellular handsets, base stations and home networking systems. We present our work in the European PANAMA project which addresses the associated challenges. Our work focuses on

  19. Biochemical Factors Modulating Cellular Neurotoxicity of Methylmercury

    Directory of Open Access Journals (Sweden)

    Parvinder Kaur

    2011-01-01

    Full Text Available Methylmercury (MeHg, an environmental toxicant primarily found in fish and seafood, poses a dilemma to both consumers and regulatory authorities, given the nutritional benefits of fish consumption versus the possible adverse neurological damage. Several studies have shown that MeHg toxicity is influenced by a number of biochemical factors, such as glutathione (GSH, fatty acids, vitamins, and essential elements, but the cellular mechanisms underlying these complex interactions have not yet been fully elucidated. The objective of this paper is to outline the cellular response to dietary nutrients, as well as to describe the neurotoxic exposures to MeHg. In order to determine the cellular mechanism(s of toxicity, the effect of pretreatment with biochemical factors (e.g., N-acetyl cysteine, (NAC; diethyl maleate, (DEM; docosahexaenoic acid, (DHA; selenomethionine, SeM; Trolox and MeHg treatment on intercellular antioxidant status, MeHg content, and other endpoints was evaluated. This paper emphasizes that the protection against oxidative stress offered by these biochemical factors is among one of the major mechanisms responsible for conferring neuroprotection. It is therefore critical to ascertain the cellular mechanisms associated with various dietary nutrients as well as to determine the potential effects of neurotoxic exposures for accurately assessing the risks and benefits associated with fish consumption.

  20. Terminal addition in a cellular world.

    Science.gov (United States)

    Torday, J S; Miller, William B

    2018-07-01

    Recent advances in our understanding of evolutionary development permit a reframed appraisal of Terminal Addition as a continuous historical process of cellular-environmental complementarity. Within this frame of reference, evolutionary terminal additions can be identified as environmental induction of episodic adjustments to cell-cell signaling patterns that yield the cellular-molecular pathways that lead to differing developmental forms. Phenotypes derive, thereby, through cellular mutualistic/competitive niche constructions in reciprocating responsiveness to environmental stresses and epigenetic impacts. In such terms, Terminal Addition flows according to a logic of cellular needs confronting environmental challenges over space-time. A reconciliation of evolutionary development and Terminal Addition can be achieved through a combined focus on cell-cell signaling, molecular phylogenies and a broader understanding of epigenetic phenomena among eukaryotic organisms. When understood in this manner, Terminal Addition has an important role in evolutionary development, and chronic disease might be considered as a form of 'reverse evolution' of the self-same processes. Copyright © 2017. Published by Elsevier Ltd.

  1. Overview of cellular automaton models for corrosion

    International Nuclear Information System (INIS)

    Perez-Brokate, Cristian Felipe; De Lamare, Jacques; Dung di Caprio; Feron, Damien; Chausse, Annie

    2014-01-01

    A review of corrosion process modeling using cellular automata methods is presented. This relatively new and growing approach takes into account the stochastic nature of the phenomena and uses physico-chemical rules to make predictions at a mesoscopic scale. Milestone models are analyzed and perspectives are established. (authors)

  2. The cellular basis of organ ageing

    NARCIS (Netherlands)

    Knook, D.L.

    1978-01-01

    Ageing is associated with declines in the functional capacities of several organs. General causes for the decline can be divided into: 1. intrinsic cellular causes and 2. extracellular causes, e.g., changes in blood circulation and distribution. For the first group of causes, there is evidence for a

  3. Cellular automata machines as physics emulators

    International Nuclear Information System (INIS)

    Toffoli, T.

    1988-01-01

    Can one design a computer optimized to be a physics emulator rather than a software interpreter? Cellular automata are discrete dynamical systems whose behavior is completely specified in terms of a local relation, much as is the case for a large class of continuous dynamical systems defined by partial differential equations. 31 refs, 3 figs

  4. Cellular modeling of fault-tolerant multicomputers

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, G

    1987-01-01

    Work described was concerned with a novel method for investigation of fault tolerance in large regular networks of computers. Motivation was to provide a technique useful in rapid evaluation of highly reliable systems that exploit the low cost and ease of volume production of simple microcomputer components. First, a system model and simulator based upon cellular automata are developed. This model is characterized by its simplicity and ease of modification when adapting to new types of network. Second, in order to test and verify the predictive capabilities of the cellular system, a more-detailed simulation is performed based upon an existing computational model, that of the Transputer. An example application is used to exercise various systems designed using the cellular model. Using this simulator, experimental results are obtained both for existing well-understood configurations and for more novel types also developed here. In all cases it was found that the cellular model and simulator successfully predicted the ranking in reliability improvement of the systems studied.

  5. Fuzzy cellular automata models in immunology

    International Nuclear Information System (INIS)

    Ahmed, E.

    1996-01-01

    The self-nonself character of antigens is considered to be fuzzy. The Chowdhury et al. cellular automata model is generalized accordingly. New steady states are found. The first corresponds to a below-normal help and suppression and is proposed to be related to autoimmune diseases. The second corresponds to a below-normal B-cell level

  6. Gravitational Effects on Cellular Flame Structure

    Science.gov (United States)

    Dunsky, C. M.; Fernandez-Pello, A. C.

    1991-01-01

    An experimental investigation has been conducted of the effect of gravity on the structure of downwardly propagating, cellular premixed propane-oxygen-nitrogen flames anchored on a water-cooled porous-plug burner. The flame is subjected to microgravity conditions in the NASA Lewis 2.2-second drop tower, and flame characteristics are recorded on high-speed film. These are compared to flames at normal gravity conditions with the same equivalence ratio, dilution index, mixture flow rate, and ambient pressure. The results show that the cellular instability band, which is located in the rich mixture region, changes little under the absence of gravity. Lifted normal-gravity flames near the cellular/lifted limits, however, are observed to become cellular when gravity is reduced. Observations of a transient cell growth period following ignition point to heat loss as being an important mechanism in the overall flame stability, dominating the stabilizing effect of buoyancy for these downwardly-propagating burner-anchored flames. The pulsations that are observed in the plume and diffusion flame generated downstream of the premixed flame in the fuel rich cases disappear in microgravity, verifying that these fluctuations are gravity related.

  7. Cellular Automata Rules and Linear Numbers

    OpenAIRE

    Nayak, Birendra Kumar; Sahoo, Sudhakar; Biswal, Sagarika

    2012-01-01

    In this paper, linear Cellular Automta (CA) rules are recursively generated using a binary tree rooted at "0". Some mathematical results on linear as well as non-linear CA rules are derived. Integers associated with linear CA rules are defined as linear numbers and the properties of these linear numbers are studied.

  8. Cellular Restriction Factors of Feline Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Carsten Münk

    2011-10-01

    Full Text Available Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors or inhibit viral replication (restriction factors. Similar to Human immunodeficiency virus type 1 (HIV-1, the cat lentivirus Feline immunodeficiency virus (FIV is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating. Of particular importance are the cellular proteins APOBEC3, TRIM5α and tetherin/BST-2. In general, lentiviruses counteract or escape their species’ own variant of the restriction factor, but are targeted by the orthologous proteins of distantly related species. Most of the knowledge regarding lentiviral restriction factors has been obtained in the HIV-1 system; however, much less is known about their effects on other lentiviruses. We describe here the molecular mechanisms that explain how FIV maintains its replication in feline cells, but is largely prevented from cross-species infections by cellular restriction factors.

  9. Cellular Restriction Factors of Feline Immunodeficiency Virus

    Science.gov (United States)

    Zielonka, Jörg; Münk, Carsten

    2011-01-01

    Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating. Of particular importance are the cellular proteins APOBEC3, TRIM5α and tetherin/BST-2. In general, lentiviruses counteract or escape their species’ own variant of the restriction factor, but are targeted by the orthologous proteins of distantly related species. Most of the knowledge regarding lentiviral restriction factors has been obtained in the HIV-1 system; however, much less is known about their effects on other lentiviruses. We describe here the molecular mechanisms that explain how FIV maintains its replication in feline cells, but is largely prevented from cross-species infections by cellular restriction factors. PMID:22069525

  10. Cellular grafts in management of leucoderma

    Directory of Open Access Journals (Sweden)

    Mysore Venkataram

    2009-01-01

    Full Text Available Cellular grafting methods constitute important advances in the surgical management of leucoderma. Different methods such as noncultured epidermal suspensions, melanocyte cultures, and melanocyte-keratinocyte cultures have all been shown to be effective. This article reviews these methods.

  11. Power load balancing in cellular networks

    NARCIS (Netherlands)

    2010-01-01

    In one aspect, a system is provided. In one embodiment, the system includes a plurality of wireless base stations that are located in a contiguous spatial coverage region of a cellular communication system. Each wireless base station that is configured to generate a coverage pilot beam to enable

  12. Their function on angiogenesis and cellular signalling

    Indian Academy of Sciences (India)

    Copper, although known as a micronutrient, has a pivotal role in modulating the cellular metabolism. Many studieshave reported the role of copper in angiogenesis. Copper chaperones are intracellular proteins that mediate coppertrafficking to various cell organelles. However, the role and function of copper chaperones in ...

  13. Cellular biomarker responses of bagrid catfish, Chrysichthys ...

    African Journals Online (AJOL)

    An assessment of the pollution status of Agboyi creek, a water body associated with various anthropogenic activities was carried out in order to determine responses induced in Catfishes, Chrysichthys nigrodigitatus inhabiting it. Cellular biomarkers of stress including the antioxidative stress enzyme, catalase (CAT), lipid ...

  14. Designing cellular manufacturing system under risk conditions ...

    African Journals Online (AJOL)

    This paper develops a mathematical modeling to design a cellular manufacturing system. In addition some of the total or portion of the demand of the part types can be subcontracted.. In order to designing the optimal CMS, we needs to detrmined a plan to produce and subcontract parts at a minimum cost and to mitigate the ...

  15. Building mathematics cellular phone learning communities

    Directory of Open Access Journals (Sweden)

    Wajeeh M. Daher

    2011-04-01

    Full Text Available Researchers emphasize the importance of maintaining learning communities and environments. This article describes the building and nourishment of a learning community, one comprised of middle school students who learned mathematics out-of-class using the cellular phone. The building of the learning community was led by three third year pre-service teachers majoring in mathematics and computers. The pre-service teachers selected thirty 8th grade students to learn mathematics with the cellular phone and be part of a learning community experimenting with this learning. To analyze the building and development stages of the cellular phone learning community, two models of community building stages were used; first the team development model developed by Tuckman (1965, second the life cycle model of a virtual learning community developed by Garber (2004. The research findings indicate that a learning community which is centered on a new technology has five 'life' phases of development: Pre-birth, birth, formation, performing, and maturity. Further, the research finding indicate that the norms that were encouraged by the preservice teachers who initiated the cellular phone learning community resulted in a community which developed, nourished and matured to be similar to a community of experienced applied mathematicians who use mathematical formulae to study everyday phenomena.

  16. THE BASIC LAWS AND FEATURES OF CYTOKINE DYNAMICS IN PROCESS AND EARLY TERMS AFTER CARDIOPULMONARY BYPASS

    Directory of Open Access Journals (Sweden)

    S. I. Suskov

    2011-01-01

    Full Text Available The basic variants of cytokines reactions defining type of organ dysfunctions are revealed in the course of car- diopulmonary bypass and in the early postoperative period. Their character and expression, depends on gravity preoperative an immunodeficiency and initial degree of heart insufficiency. Diphasic dynamics of development of system inflammatory reaction is confirmed after cardiopulmonary bypass: increase of levels proinflammatory cytokines is in the first phase and anti-inflammatory cytokines with development immunodepression and cellular anergy in is the second phase. Also, key role IL-1Ra is revealed in restraint of hyperactivation of system inflam- matory reaction. Blood whey levels IL-6, IL-8, G-CSF, TNF-α and IL-1Ra should be defined to cardiopulmonary bypass, in 10–12 hours, 24 hours and 3 days after cardiopulmonary bypass and may be used as prognostic criteria of development of postoperative complications. 

  17. Predicting cellular growth from gene expression signatures.

    Directory of Open Access Journals (Sweden)

    Edoardo M Airoldi

    2009-01-01

    Full Text Available Maintaining balanced growth in a changing environment is a fundamental systems-level challenge for cellular physiology, particularly in microorganisms. While the complete set of regulatory and functional pathways supporting growth and cellular proliferation are not yet known, portions of them are well understood. In particular, cellular proliferation is governed by mechanisms that are highly conserved from unicellular to multicellular organisms, and the disruption of these processes in metazoans is a major factor in the development of cancer. In this paper, we develop statistical methodology to identify quantitative aspects of the regulatory mechanisms underlying cellular proliferation in Saccharomyces cerevisiae. We find that the expression levels of a small set of genes can be exploited to predict the instantaneous growth rate of any cellular culture with high accuracy. The predictions obtained in this fashion are robust to changing biological conditions, experimental methods, and technological platforms. The proposed model is also effective in predicting growth rates for the related yeast Saccharomyces bayanus and the highly diverged yeast Schizosaccharomyces pombe, suggesting that the underlying regulatory signature is conserved across a wide range of unicellular evolution. We investigate the biological significance of the gene expression signature that the predictions are based upon from multiple perspectives: by perturbing the regulatory network through the Ras/PKA pathway, observing strong upregulation of growth rate even in the absence of appropriate nutrients, and discovering putative transcription factor binding sites, observing enrichment in growth-correlated genes. More broadly, the proposed methodology enables biological insights about growth at an instantaneous time scale, inaccessible by direct experimental methods. Data and tools enabling others to apply our methods are available at http://function.princeton.edu/growthrate.

  18. Cellular glutathione prevents cytolethality of monomethylarsonic acid

    International Nuclear Information System (INIS)

    Sakurai, Teruaki; Kojima, Chikara; Ochiai, Masayuki; Ohta, Takami; Sakurai, Masumi H.; Waalkes, Michael P.; Fujiwara, Kitao

    2004-01-01

    Inorganic arsenicals are clearly toxicants and carcinogens in humans. In mammals, including humans, inorganic arsenic often undergoes methylation, forming compounds such as monomethylarsonic acid (MMAs V ) and dimethylarsinic acid (DMAs V ). However, much less information is available on the in vitro toxic potential or mechanisms of these methylated arsenicals, especially MMAs V . We studied the molecular mechanisms of in vitro cytolethality of MMAs V using a rat liver epithelial cell line (TRL 1215). MMAs V was not cytotoxic in TRL 1215 cells even at concentrations exceeding 10 mM, but it became weakly cytotoxic and induced both necrotic and apoptotic cell death when cellular reduced glutathione (GSH) was depleted with the glutathione synthase inhibitor, L-buthionine-[S,R]-sulfoximine (BSO), or the glutathione reductase inhibitor, carmustine. Similar results were observed in the other mammalian cells, such as human skin TIG-112 cells, chimpanzee skin CRT-1609 cells, and mouse metallothionein (MT) positive and MT negative embryonic cells. Ethacrynic acid (EA), an inhibitor of glutathione S-transferase (GST) that catalyses GSH-substrate conjugation, also enhanced the cytolethality of MMAs V , but aminooxyacetic acid (AOAA), an inhibitor of β-lyase that catalyses the final breakdown of GSH-substrate conjugates, had no effect. Both the cellular GSH levels and the cellular GST activity were increased by the exposure to MMAs V in TRL 1215 cells. On the other hand, the addition of exogenous extracellular GSH enhanced the cytolethality of MMAs V , although cellular GSH levels actually prevented the cytolethality of combined MMAs V and exogenous GSH. These findings indicate that human arsenic metabolite MMAs V is not a highly toxic compound in mammalian cells, and the level of cellular GSH is critical to its eventual toxic effects

  19. Cellular dosimetry in nuclear medicine imaging: training

    International Nuclear Information System (INIS)

    Gardin, I.; Faraggi, M.; Stievenart, J.L.; Le Guludec, D.; Bok, B.

    1998-01-01

    The radionuclides used in nuclear medicine imaging emit not only diagnostically useful photons, but also energy electron emissions, responsible for dose heterogeneity at the cellular level. The mean dose delivered to the cell nucleus by electron emissions of 99m Tc, 123 I, 111 In, 67 Ga, and 201 Tl, has been calculated, for the cell nucleus, a cytoplasmic and a cell membrane distribution of radioactivity. This model takes into account both the self-dose which results from the radionuclide located in the target cell, and the cross-dose, which comes from the surrounding cells. The results obtained by cellular dosimetry (D cel ) have been compared with those obtained with conventional dosimetry (D conv ), by assuming the same amount of radioactivity per cell. Cellular dosimetry shows, for a cytoplasmic and a cell membrane distributions of radioactivity, that the main contribution to the dose to the cell nucleus, comes from the surrounding cells. On the other hand, for a cell nucleus distribution of radioactivity, the self-dose is not negligible and may be the main contribution. The comparison between cellular and conventional dosimetry shows that D cel /D conv ratio ranges from 0.61 and O.89, in case of a cytoplasmic and a cell membrane distributions of radioactivity, depending on the radionuclide and cell dimensions. Thus, conventional dosimetry slightly overestimates the mean dose to the cell nucleus. On the other hand, D cel /D conv ranges from 1.1 to 75, in case of a cell nucleus distribution of radioactivity. Conventional dosimetry may strongly underestimates the absorbed dose to the nucleus, when radioactivity is located in the nucleus. The study indicates that in nuclear medicine imaging, cellular dosimetry may lead to a better understanding of biological effects of radiopharmaceuticals. (authors)

  20. Numerical Analysis of Characteristics of Cellular Counterflow Diffusion Flames near Radiative Extinction Limit

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Su Ryong [Seoul National University of Technology, Seoul (Korea, Republic of)

    2014-06-15

    Nonlinear characteristics of cellular counterflow diffusion flame near the radiative extinction limit at large Damköhler number are numerically investigated. Lewis number is assumed to be 0.5 and flame evolution is calculated by imposing an infinitesimal disturbance to a one-dimensional(1-D) steady state flame. The early stage of nonlinear development is very similar to that predicted in a linear stability analysis. The disturbance with the wavenumber of the fastest growing mode emerges and grows gradually. Eventual, an alternating pattern of reacting and quenching stripes is developed. The cellular flame temperature is higher than that of 1-D flame because of the gain of the total enthalpy. As the Damköhler number is further increased, the shape of the cell becomes circular to increase the surface area per unit reacting volume. The cellular flames do not extinguish but survive even above the 1-D steady state extinction condition.

  1. Induction of cellular transformation by irradiation from artificial light sources

    International Nuclear Information System (INIS)

    Withrow, T.J.

    1981-01-01

    Cellular transformation in vitro has been used to test for the carcinogenic potential of chemical and physical insults including light. This report discusses the measurement of transformation, and reviews studies done on the effects of exposure to artificial light on cellular transformation or on cellular transformation by a virus. To date, cool-white lamps have been found to cause cellular transformation, while germicidal lamps and sunlamps have been found to cause cellular transformation and to enhance virally produced transformation

  2. Evidence for an early innate immune response in the motor cortex of ALS.

    Science.gov (United States)

    Jara, Javier H; Genç, Barış; Stanford, Macdonell J; Pytel, Peter; Roos, Raymond P; Weintraub, Sandra; Mesulam, M Marsel; Bigio, Eileen H; Miller, Richard J; Özdinler, P Hande

    2017-06-26

    Recent evidence indicates the importance of innate immunity and neuroinflammation with microgliosis in amyotrophic lateral sclerosis (ALS) pathology. The MCP1 (monocyte chemoattractant protein-1) and CCR2 (CC chemokine receptor 2) signaling system has been strongly associated with the innate immune responses observed in ALS patients, but the motor cortex has not been studied in detail. After revealing the presence of MCP1 and CCR2 in the motor cortex of ALS patients, to elucidate, visualize, and define the timing, location and the extent of immune response in relation to upper motor neuron vulnerability and progressive degeneration in ALS, we developed MCP1-CCR2-hSOD1 G93A mice, an ALS reporter line, in which cells expressing MCP1 and CCR2 are genetically labeled by monomeric red fluorescent protein-1 and enhanced green fluorescent protein, respectively. In the motor cortex of MCP1-CCR2-hSOD1 G93A mice, unlike in the spinal cord, there was an early increase in the numbers of MCP1+ cells, which displayed microglial morphology and selectively expressed microglia markers. Even though fewer CCR2+ cells were present throughout the motor cortex, they were mainly infiltrating monocytes. Interestingly, MCP1+ cells were found in close proximity to the apical dendrites and cell bodies of corticospinal motor neurons (CSMN), further implicating the importance of their cellular interaction to neuronal pathology. Similar findings were observed in the motor cortex of ALS patients, where MCP1+ microglia were especially in close proximity to the degenerating apical dendrites of Betz cells. Our findings reveal that the intricate cellular interplay between immune cells and upper motor neurons observed in the motor cortex of ALS mice is indeed recapitulated in ALS patients. We generated and characterized a novel model system, to study the cellular and molecular basis of this close cellular interaction and how that relates to motor neuron vulnerability and progressive degeneration in

  3. Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements.

    Directory of Open Access Journals (Sweden)

    Olga V Viktorovskaya

    2016-08-01

    Full Text Available There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses replication.Seventy-nine novel RNA binding proteins for dengue virus (DENV were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated.The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps

  4. Cellular Mechanisms of Action of Drug Abuse on Olfactory Neurons

    Directory of Open Access Journals (Sweden)

    Thomas Heinbockel

    2015-12-01

    Full Text Available Cannabinoids (Δ9-tetrahydrocannabinol are the active ingredient of marijuana (cannabis which is the most commonly abused illicit drug in the USA. In addition to being known and used as recreational drugs, cannabinoids are produced endogenously by neurons in the brain (endocannabinoids and serve as important signaling molecules in the nervous system and the rest of the body. Cannabinoids have been implicated in bodily processes both in health and disease. Recent pharmacological and physiological experiments have described novel aspects of classic brain signaling mechanisms or revealed unknown mechanisms of cellular communication involving the endocannabinoid system. While several forms of signaling have been described for endocannabinoids, the most distinguishing feature of endocannabinoids is their ability to act as retrograde messengers in neural circuits. Neurons in the main olfactory bulb express high levels of cannabinoid receptors. Here, we describe the cellular mechanisms and function of this novel brain signaling system in regulating neural activity at synapses in olfactory circuits. Results from basic research have the potential to provide the groundwork for translating the neurobiology of drug abuse to the realm of the pharmacotherapeutic treatment of addiction, specifically marijuana substance use disorder.

  5. A dynamic cellular vertex model of growing epithelial tissues

    Science.gov (United States)

    Lin, Shao-Zhen; Li, Bo; Feng, Xi-Qiao

    2017-04-01

    Intercellular interactions play a significant role in a wide range of biological functions and processes at both the cellular and tissue scales, for example, embryogenesis, organogenesis, and cancer invasion. In this paper, a dynamic cellular vertex model is presented to study the morphomechanics of a growing epithelial monolayer. The regulating role of stresses in soft tissue growth is revealed. It is found that the cells originating from the same parent cell in the monolayer can orchestrate into clustering patterns as the tissue grows. Collective cell migration exhibits a feature of spatial correlation across multiple cells. Dynamic intercellular interactions can engender a variety of distinct tissue behaviors in a social context. Uniform cell proliferation may render high and heterogeneous residual compressive stresses, while stress-regulated proliferation can effectively release the stresses, reducing the stress heterogeneity in the tissue. The results highlight the critical role of mechanical factors in the growth and morphogenesis of epithelial tissues and help understand the development and invasion of epithelial tumors.

  6. A Fluid Model for Performance Analysis in Cellular Networks

    Directory of Open Access Journals (Sweden)

    Coupechoux Marceau

    2010-01-01

    Full Text Available We propose a new framework to study the performance of cellular networks using a fluid model and we derive from this model analytical formulas for interference, outage probability, and spatial outage probability. The key idea of the fluid model is to consider the discrete base station (BS entities as a continuum of transmitters that are spatially distributed in the network. This model allows us to obtain simple analytical expressions to reveal main characteristics of the network. In this paper, we focus on the downlink other-cell interference factor (OCIF, which is defined for a given user as the ratio of its outer cell received power to its inner cell received power. A closed-form formula of the OCIF is provided in this paper. From this formula, we are able to obtain the global outage probability as well as the spatial outage probability, which depends on the location of a mobile station (MS initiating a new call. Our analytical results are compared to Monte Carlo simulations performed in a traditional hexagonal network. Furthermore, we demonstrate an application of the outage probability related to cell breathing and densification of cellular networks.

  7. [Pain and emotional dysregulation: Cellular memory due to pain].

    Science.gov (United States)

    Narita, Minoru; Watanabe, Moe; Hamada, Yusuke; Tamura, Hideki; Ikegami, Daigo; Kuzumaki, Naoko; Igarashi, Katsuhide

    2015-08-01

    Genetic factors are involved in determinants for the risk of psychiatric disorders, and neurological and neurodegenerative diseases. Chronic pain stimuli and intense pain have effects at a cellular and/or gene expression level, and will eventually induce "cellular memory due to pain", which means that tissue damage, even if only transient, can elicit epigenetically abnormal transcription/translation and post-translational modification in related cells depending on the degree or kind of injury or associated conditions. Such cell memory/transformation due to pain can cause an abnormality in a fundamental intracellular response, such as a change in the three-dimensional structure of DNA, transcription, or translation. On the other hand, pain is a multidimensional experience with sensory-discriminative and motivational-affective components. Recent human brain imaging studies have examined differences in activity in the nucleus accumbens between controls and patients with chronic pain, and have revealed that the nucleus accumbens plays a role in predicting the value of a noxious stimulus and its offset, and in the consequent changes in the motivational state. In this review, we provide a very brief overview of a comprehensive understanding of chronic pain associated with emotional dysregulation due to transcriptional regulation, epigenetic modification and miRNA regulation.

  8. Cellular studies and interaction mechanisms of extremely low frequency fields

    Science.gov (United States)

    Liburdy, Robert P.

    1995-01-01

    Worldwide interest in the biological effects of ELF (extremely low frequency, level is to identify cellular responses to ELF fields, to develop a dose threshold for such interactions, and with such information to formulate and test appropriate interaction mechanisms. This review is selective and will discuss the most recent cellular studies directed at these goals which relate to power line, sinusoidal ELF fields. In these studies an interaction site at the cell membrane is by consensus a likely candidate, since changes in ion transport, ligand-receptor events such as antibody binding, and G protein activation have been reported. These changes strongly indicate that signal transduction (ST) can be influenced. Also, ELF fields are reported to influence enzyme activation, gene expression, protein synthesis, and cell proliferation, which are triggered by earlier ST events at the cell membrane. The concept of ELF fields altering early cell membrane events and thereby influencing intracellular cell function via the ST cascade is perhaps the most plausible biological framework currently being investigated for understanding ELF effects on cells. For example, the consequence of an increase due to ELF fields in mitogenesis, the final endpoint of the ST cascade, is an overall increase in the probability of mutagenesis and consequently cancer, according to the Ames epigenetic model of carcinogenesis. Consistent with this epigenetic mechanism and the ST pathway to carcinogenesis is recent evidence that ELF fields can alter breast cancer cell proliferation and can act as a copromoter in vitro. The most important dosimetric question being addressed currently is whether the electric (E) or the magnetic (B) field, or if combinations of static B and time-varying B fields represent an exposure metric for the cell. This question relates directly to understanding fundamental interaction mechanisms and to the development of a rationale for ELF dose threshold guidelines. The weight of

  9. The entomopathogenic fungus Nomuraea rileyi impairs cellular immunity of its host Helicoverpa armigera.

    Science.gov (United States)

    Zhong, Ke; Liu, Zhan-Chi; Wang, Jia-Lin; Liu, Xu-Sheng

    2017-09-01

    In this study, we investigated the effect of the entomopathogenic fungus Nomuraea rileyi on Helicoverpa armigera cellular immune responses. Nomuraea rileyi infection had no effect on total hemocyte count (THC), but impaired hemocyte-mediated phagocytosis, nodulation, and encapsulation responses. Nomuraea rileyi infection led to a significant reduction in hemocyte spreading. An in vitro assay revealed that plasma from N. rileyi infected H. armigera larvae suppressed the spreading ability of hemocytes from naïve larvae. We infer that N. rileyi suppresses the cellular immune response of its host, possibly by secreting exogenous, cytotoxic compounds into the host's hemolymph. © 2017 Wiley Periodicals, Inc.

  10. Drosophila melanogaster cellular repressor of E1A-stimulated genes is a lysosomal protein essential for fly development

    OpenAIRE

    Kowalewski-Nimmerfall, Elisabeth; Sch?hs, Philipp; Maresch, Daniel; Rendic, Dubravko; Kr?mer, Helmut; Mach, Lukas

    2014-01-01

    Mammalian cellular repressor of E1A-stimulated genes is a lysosomal glycoprotein implicated in cellular growth and differentiation. The genome of the fruit fly Drosophila melanogaster encodes a putative orthologue (dCREG), suggesting evolutionarily conserved physiological functions of this protein. In D. melanogaster S2 cells, dCREG was found to localize in lysosomes. Further studies revealed that intracellular dCREG is subject of proteolytic maturation. Processing and turnover could be subst...

  11. High-resolution sub-cellular imaging by correlative NanoSIMS and electron microscopy of amiodarone internalisation by lung macrophages as evidence for drug-induced phospholipidosis.

    Science.gov (United States)

    Jiang, Haibo; Passarelli, Melissa K; Munro, Peter M G; Kilburn, Matt R; West, Andrew; Dollery, Colin T; Gilmore, Ian S; Rakowska, Paulina D

    2017-01-26

    Correlative NanoSIMS and EM imaging of amiodarone-treated macrophages shows the internalisation of the drug at a sub-cellular level and reveals its accumulation within the lysosomes, providing direct evidence for amiodarone-induced phospholipidosis. Chemical fixation using tannic acid effectively seals cellular membranes aiding intracellular retention of diffusible drugs.

  12. Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases.

    Science.gov (United States)

    Ding, Suet Lee Shirley; Kumar, Suresh; Mok, Pooi Ling

    2017-07-28

    The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action.

  13. Pathloss Measurements and Modeling for UAVs Connected to Cellular Networks

    DEFF Research Database (Denmark)

    Amorim, Rafhael Medeiros de; Mogensen, Preben Elgaard; Sørensen, Troels Bundgaard

    2017-01-01

    . The measurements were conducted in an operating LTE network (850 MHz), using a commercial cell phone, placed inside the frame of the UAV. Trials were conducted for UAV flying at 5 different heights measured above ground level (20, 40, 60, 80 and 100m) and a pathloss regression line was obtained from results. Then......This paper assess field measurements, as part of the investigation of the suitability of cellular networks for providing connectivity to UAVs (unmanned aerial vehicles). Evaluation is done by means of field measurements obtained in a rural environment in Denmark with an airbone UAV......, downlink (DL) SINR levels obtained during flight measurements are also presented. An important result obtained from the measurents reveal that there is a height-related DL SINR degradation. Three main sources of uncertainty on the pathloss model that could be responsible for the SINR degradation are also...

  14. Cellular Dewetting: Opening of Macroapertures in Endothelial Cells

    Science.gov (United States)

    Gonzalez-Rodriguez, David; Maddugoda, Madhavi P.; Stefani, Caroline; Janel, Sebastien; Lafont, Frank; Cuvelier, Damien; Lemichez, Emmanuel; Brochard-Wyart, Françoise

    2012-05-01

    Pathogenic bacteria can cross from blood vessels to host tissues by opening transendothelial cell macroapertures (TEMs). To induce TEM opening, bacteria intoxicate endothelial cells with proteins that disrupt the contractile cytoskeletal network. Cell membrane tension is no longer resisted by contractile fibers, leading to the opening of TEMs. Here we model the opening of TEMs as a new form of dewetting. While liquid dewetting is irreversible, we show that cellular dewetting is transient. Our model predicts the minimum radius for hole nucleation, the maximum TEM size, and the dynamics of TEM opening, in good agreement with experimental data. The physical model is then coupled with biological experimental data to reveal that the protein missing in metastasis (MIM) controls the line tension at the rim of the TEM and opposes its opening.

  15. Modeling the mechanics of cancer: effect of changes in cellular and extra-cellular mechanical properties.

    Science.gov (United States)

    Katira, Parag; Bonnecaze, Roger T; Zaman, Muhammad H

    2013-01-01

    Malignant transformation, though primarily driven by genetic mutations in cells, is also accompanied by specific changes in cellular and extra-cellular mechanical properties such as stiffness and adhesivity. As the transformed cells grow into tumors, they interact with their surroundings via physical contacts and the application of forces. These forces can lead to changes in the mechanical regulation of cell fate based on the mechanical properties of the cells and their surrounding environment. A comprehensive understanding of cancer progression requires the study of how specific changes in mechanical properties influences collective cell behavior during tumor growth and metastasis. Here we review some key results from computational models describing the effect of changes in cellular and extra-cellular mechanical properties and identify mechanistic pathways for cancer progression that can be targeted for the prediction, treatment, and prevention of cancer.

  16. siRNA - Mediated LRP/LR knock-down reduces cellular viability of malignant melanoma cells through the activation of apoptotic caspases.

    Science.gov (United States)

    Rebelo, Thalia M; Vania, Leila; Ferreira, Eloise; Weiss, Stefan F T

    2018-07-01

    The 37 kDa/67 kDa laminin receptor (LRP/LR) is over-expressed in tumor cells and has been implicated in several tumourigenic processes such as metastasis and telomerase activation, however, more importantly the focus of the present study is on the maintenance of cellular viability and the evasion of apoptosis. The aim of the study was to investigate the role of LRP/LR on the cellular viability of early (A375) and late stage (A375SM) malignant melanoma cells. Flow cytometry and western blot analysis revealed that A375SM cells contain more cell-surface and total LRP/LR levels in comparison to the A375 cells, respectively. In order to determine the effect of LRP/LR on cell viability and apoptosis, LRP was down-regulated via siRNA technology. MTT assays revealed that LRP knock-down led to significant reductions in the viability of A375 and A375SM cells. Confocal microscopy indicated nuclear morphological changes suggestive of apoptotic induction in both cell lines and Annexin-V FITC/PI assays confirmed this observation. Additionally, caspase-3 activity assays revealed that apoptosis was induced in both cell lines after siRNA-mediated down-regulation of LRP. Caspase-8 and -9 activity assays suggested that post LRP knock-down; A375 cells undergo apoptosis solely via the extrinsic pathway, while A375SM cells undergo apoptosis via the intrinsic pathway. siRNAs mediated LRP knock-down might represent a powerful alternative therapeutic strategy for the treatment of malignant melanoma through the induction of apoptosis. Copyright © 2018. Published by Elsevier Inc.

  17. Early Math.

    Science.gov (United States)

    Van Nuys, Ute Elisabeth

    1986-01-01

    Presents reviews of the following mathematics software designed to teach young children counting, number recognition, visual discrimination, matching, addition, and subtraction skills; Stickybear Numbers, Learning with Leeper, Getting Ready to Read and Add, Counting Parade, Early Games for Young Children, Charlie Brown's 1,2,3's, Let's Go Fishing,…

  18. Designing beauty the art of cellular automata

    CERN Document Server

    Martínez, Genaro

    2016-01-01

    This fascinating, colourful book offers in-depth insights and first-hand working experiences in the production of art works, using simpl