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Sample records for reveal essential links

  1. Linking Essential Tremor to the Cerebellum: Neurochemical Evidence.

    Science.gov (United States)

    Marin-Lahoz, Juan; Gironell, Alexandre

    2016-06-01

    The pathophysiology and the exact anatomy of essential tremor (ET) is not well known. One of the pillars that support the cerebellum as the main anatomical locus in ET is neurochemistry. This review examines the link between neurochemical abnormalities found in ET and cerebellum. The review is based on published data about neurochemical abnormalities described in ET both in human and in animal studies. We try to link those findings with cerebellum. γ-aminobutyric acid (GABA) is the main neurotransmitter involved in the pathophysiology of ET. There are several studies about GABA that clearly points to a main role of the cerebellum. There are few data about other neurochemical abnormalities in ET. These include studies with noradrenaline, glutamate, adenosine, proteins, and T-type calcium channels. One single study reveals high levels of noradrenaline in the cerebellar cortex. Another study about serotonin neurotransmitter results negative for cerebellum involvement. Finally, studies on T-type calcium channels yield positive results linking the rhythmicity of ET and cerebellum. Neurochemistry supports the cerebellum as the main anatomical locus in ET. The main neurotransmitter involved is GABA, and the GABA hypothesis remains the most robust pathophysiological theory of ET to date. However, this hypothesis does not rule out other mechanisms and may be seen as the main scaffold to support findings in other systems. We clearly need to perform more studies about neurochemistry in ET to better understand the relations among the diverse systems implied in ET. This is mandatory to develop more effective pharmacological therapies.

  2. A forward genetic screen reveals essential and non-essential RNAi factors in Paramecium tetraurelia

    Science.gov (United States)

    Marker, Simone; Carradec, Quentin; Tanty, Véronique; Arnaiz, Olivier; Meyer, Eric

    2014-01-01

    In most eukaryotes, small RNA-mediated gene silencing pathways form complex interacting networks. In the ciliate Paramecium tetraurelia, at least two RNA interference (RNAi) mechanisms coexist, involving distinct but overlapping sets of protein factors and producing different types of short interfering RNAs (siRNAs). One is specifically triggered by high-copy transgenes, and the other by feeding cells with double-stranded RNA (dsRNA)-producing bacteria. In this study, we designed a forward genetic screen for mutants deficient in dsRNA-induced silencing, and a powerful method to identify the relevant mutations by whole-genome sequencing. We present a set of 47 mutant alleles for five genes, revealing two previously unknown RNAi factors: a novel Paramecium-specific protein (Pds1) and a Cid1-like nucleotidyl transferase. Analyses of allelic diversity distinguish non-essential and essential genes and suggest that the screen is saturated for non-essential, single-copy genes. We show that non-essential genes are specifically involved in dsRNA-induced RNAi while essential ones are also involved in transgene-induced RNAi. One of the latter, the RNA-dependent RNA polymerase RDR2, is further shown to be required for all known types of siRNAs, as well as for sexual reproduction. These results open the way for the dissection of the genetic complexity, interconnection, mechanisms and natural functions of RNAi pathways in P. tetraurelia. PMID:24860163

  3. Linking Essential Tremor to the Cerebellum: Clinical Evidence.

    Science.gov (United States)

    Benito-León, Julián; Labiano-Fontcuberta, Andrés

    2016-06-01

    Essential tremor (ET) might be a family of diseases unified by the presence of kinetic tremor, but also showing etiological, pathological, and clinical heterogeneity. In this review, we will describe the most significant clinical evidence, which suggests that ET is linked to the cerebellum. Data for this review were identified by searching PUBMED (January 1966 to May 2015) crossing the terms "essential tremor" (ET) and "cerebellum," which yielded 201 entries, 11 of which included the term "cerebellum" in the article title. This was supplemented by articles in the author's files that pertained to this topic. The wide spectrum of clinical features of ET that suggest that it originates as a cerebellar or cerebellar outflow problem include the presence of intentional tremor, gait and balance abnormalities, subtle features of dysarthria, and oculomotor abnormalities, as well as deficits in eye-hand coordination, motor learning deficits, incoordination during spiral drawing task, abnormalities in motor timing and visual reaction time, impairment of social abilities, improvement in tremor after cerebellar stroke, efficacy of deep brain stimulation (which blocks cerebellar outflow), and cognitive dysfunction. It is unlikely, however, that cerebellar dysfunction, per se, fully explains ET-associated dementia, because the cognitive deficits that have been described in patients with cerebellar lesions are generally mild. Overall, a variety of clinical findings suggest that in at least a sizable proportion of patients with ET, there is an underlying abnormality of the cerebellum and/or its pathways.

  4. Linking Essential Tremor to the Cerebellum: Neuropathological Evidence.

    Science.gov (United States)

    Louis, Elan D

    2016-06-01

    A fundamental question about essential tremor (ET) is whether its associated pathological changes and disease mechanisms are linkable to a specific brain region. To that end, recent tissue-based studies have made significant strides in elucidating changes in the ET brain. Emerging from these studies is increasing neuropathological evidence linking ET to the cerebellum. These studies have systematically identified a broad range of structural, degenerative changes in the ET cerebellum, spanning across all Purkinje cell compartments. These include the dendritic compartment (where there is an increase in number of Purkinje cell dendritic swellings, a pruning of the dendritic arbor, and a reduction in spine density), the cell body (where, aside from reductions in Purkinje cell linear density in some studies, there is an increase in the number of heterotopic Purkinje cell soma), and the axonal compartment (where a plethora of changes in axonal morphology have been observed, including an increase in the number of thickened axonal profiles, torpedoes, axonal recurrent collaterals, axonal branching, and terminal axonal sprouting). Additional changes, possibly due to secondary remodeling, have been observed in neighboring neuronal populations. These include a hypertrophy of basket cell axonal processes and changes in the distribution of climbing fiber-Purkinje cell synapses. These changes all distinguish ET from normal control brains. Initial studies further indicate that the profile (i.e., constellation) of these changes may separate ET from other diseases of the cerebellum, thereby serving as a disease signature. With the discovery of these changes, a new model of ET has arisen, which posits that it may be a neurodegenerative disorder centered in the cerebellar cortex. These newly emerging neuropathological studies pave the way for anatomically focused, hypothesis-driven, molecular mechanistic studies of disease pathogenesis.

  5. Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor.

    Science.gov (United States)

    Buijink, A W G; Broersma, M; van der Stouwe, A M M; van Wingen, G A; Groot, P F C; Speelman, J D; Maurits, N M; van Rootselaar, A F

    2015-04-01

    Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar output in essential tremor during rhythmic finger tapping employing functional MRI. Thirty-one propranolol-sensitive essential tremor patients with upper limb tremor and 29 healthy controls were measured. T2*-weighted EPI sequences were acquired. The task consisted of alternating rest and finger tapping blocks. A whole-brain and region-of-interest analysis was performed, the latter focusing on the cerebellar cortex, dentate nucleus and inferior olive nucleus. Activations were also related to tremor severity. In patients, dentate activation correlated positively with tremor severity as measured by the tremor rating scale part A. Patients had reduced activation in widespread cerebellar cortical regions, and additionally in the inferior olive nucleus, and parietal and frontal cortex, compared to controls. The increase in dentate activation with tremor severity supports involvement of the dentate nucleus in essential tremor. Cortical and cerebellar changes during a motor timing task in essential tremor might point to widespread changes in cerebellar output in essential tremor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Money Is Essential: Ownership Intuitions Are Linked to Physical Currency

    Science.gov (United States)

    Uhlmann, Eric Luis; Zhu, Luke

    2013-01-01

    Due to basic processes of psychological essentialism and contagion, one particular token of monetary currency is not always interchangeable with another piece of currency of equal economic value. When money loses its physical form it is perceived as "not quite the same" money (i.e., to have partly lost the original essence that distinguished it…

  7. Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor

    NARCIS (Netherlands)

    Buijink, A. W. G.; Broersma, M.; van der Stouwe, A. M. M.; van Wingen, G. A.; Groot, P. F. C.; Speelman, J. D.; Maurits, N. M.; van Rootselaar, A. F.

    Introduction: Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of

  8. Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor

    NARCIS (Netherlands)

    Buijink, A. W. G.; Broersma, M.; van der Stouwe, A. M. M.; van Wingen, G. A.; Groot, P. F. C.; Speelman, J. D.; Maurits, N. M.; van Rootselaar, A. F.

    2015-01-01

    Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar

  9. Linking the Observation of Essential Variables to Societal Benefits

    Science.gov (United States)

    Sylak-Glassman, E.

    2017-12-01

    Different scientific communities have established sets of commonly agreed upon essential variables to help coordinate data collection in a variety of Earth observation areas. As an example, the World Meteorological Organization Global Climate Observing System has identified 50 Essential Climate Variables (ECVs), such as sea-surface temperature and carbon dioxide, which are required to monitoring the climate and detect and attribute climate change. In addition to supporting climate science, measuring these ECVs deliver many types of societal benefits, ranging from disaster mitigation to agricultural productivity to human health. While communicating the value in maintaining and improving observational records for these variables has been a challenge, quantifying how the measurement of these ECVs results in the delivery of many different societal benefits may help support their continued measurement. The 2016 National Earth Observation Assessment (EOA 2016) quantified the impact of individual Earth observation systems, sensors, networks, and surveys (or Earth observation systems, for short) on the achievement of 217 Federal objectives in 13 societal benefit areas (SBAs). This study will demonstrate the use of the EOA 2016 dataset to show the different Federal objectives and SBAs that are impacted by the Earth observation systems used to measure ECVs. Describing how the measurements from these Earth observation systems are used not only to maintain the climate record but also to meet additional Federal objectives may help articulate the continued measurement of the ECVs. This study will act as a pilot for the use of the EOA 2016 dataset to map between the measurements required to observe additional sets of variables, such as the Essential Ocean Variables and Essential Biodiversity Variables, and the ability to achieve a variety of societal benefits.

  10. Uncovering the essential links in online commercial networks

    Science.gov (United States)

    Zeng, Wei; Fang, Meiling; Shao, Junming; Shang, Mingsheng

    2016-09-01

    Recommender systems are designed to effectively support individuals' decision-making process on various web sites. It can be naturally represented by a user-object bipartite network, where a link indicates that a user has collected an object. Recently, research on the information backbone has attracted researchers' interests, which is a sub-network with fewer nodes and links but carrying most of the relevant information. With the backbone, a system can generate satisfactory recommenda- tions while saving much computing resource. In this paper, we propose an enhanced topology-aware method to extract the information backbone in the bipartite network mainly based on the information of neighboring users and objects. Our backbone extraction method enables the recommender systems achieve more than 90% of the accuracy of the top-L recommendation, however, consuming only 20% links. The experimental results show that our method outperforms the alternative backbone extraction methods. Moreover, the structure of the information backbone is studied in detail. Finally, we highlight that the information backbone is one of the most important properties of the bipartite network, with which one can significantly improve the efficiency of the recommender system.

  11. Linking Essential Tremor to the Cerebellum: Physiological Evidence.

    Science.gov (United States)

    Filip, Pavel; Lungu, Ovidiu V; Manto, Mario-Ubaldo; Bareš, Martin

    2016-12-01

    Essential tremor (ET), clinically characterized by postural and kinetic tremors, predominantly in the upper extremities, originates from pathological activity in the dynamic oscillatory network comprising the majority of nodes in the central motor network. Evidence indicates dysfunction in the thalamus, the olivocerebellar loops, and intermittent cortical engagement. Pathology of the cerebellum, a structure with architecture intrinsically predisposed to oscillatory activity, has also been implicated in ET as shown by clinical, neuroimaging, and pathological studies. Despite electrophysiological studies assessing cerebellar impairment in ET being scarce, their impact is tangible, as summarized in this review. The electromyography-magnetoencephalography combination provided the first direct evidence of pathological alteration in cortico-subcortical communication, with a significant emphasis on the cerebellum. Furthermore, complex electromyography studies showed disruptions in the timing of agonist and antagonist muscle activation, a process generally attributed to the cerebellum. Evidence pointing to cerebellar engagement in ET has also been found in electrooculography measurements, cerebellar repetitive transcranial magnetic stimulation studies, and, indirectly, in complex analyses of the activity of the ventral intermediate thalamic nucleus (an area primarily receiving inputs from the cerebellum), which is also used in the advanced treatment of ET. In summary, further progress in therapy will require comprehensive electrophysiological and physiological analyses to elucidate the precise mechanisms leading to disease symptoms. The cerebellum, as a major node of this dynamic oscillatory network, requires further study to aid this endeavor.

  12. Linking Essential Tremor to the Cerebellum-Neuroimaging Evidence.

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    Cerasa, Antonio; Quattrone, Aldo

    2016-06-01

    Essential tremor (ET) is the most common pathological tremor disorder in the world, and post-mortem evidence has shown that the cerebellum is the most consistent area of pathology in ET. In the last few years, advanced neuroimaging has tried to confirm this evidence. The aim of the present review is to discuss to what extent the evidence provided by this field of study may be generalised. We performed a systematic literature search combining the terms ET with the following keywords: MRI, VBM, MRS, DTI, fMRI, PET and SPECT. We summarised and discussed each study and placed the results in the context of existing knowledge regarding the cerebellar involvement in ET. A total of 51 neuroimaging studies met our search criteria, roughly divided into 19 structural and 32 functional studies. Despite clinical and methodological differences, both functional and structural imaging studies showed similar findings but without defining a clear topography of neurodegeneration. Indeed, the vast majority of studies found functional and structural abnormalities in several parts of the anterior and posterior cerebellar lobules, but it remains to be established to what degree these neural changes contribute to clinical symptoms of ET. Currently, advanced neuroimaging has confirmed the involvement of the cerebellum in pathophysiological processes of ET, although a high variability in results persists. For this reason, the translation of this knowledge into daily clinical practice is again partially limited, although new advanced multivariate neuroimaging approaches (machine-learning) are proving interesting changes of perspective.

  13. Linking Essential Tremor to the Cerebellum-Animal Model Evidence.

    Science.gov (United States)

    Handforth, Adrian

    2016-06-01

    In this review, we hope to stimulate interest in animal models as opportunities to understand tremor mechanisms within the cerebellar system. We begin by considering the harmaline model of essential tremor (ET), which has ET-like anatomy and pharmacology. Harmaline induces the inferior olive (IO) to burst fire rhythmically, recruiting rhythmic activity in Purkinje cells (PCs) and deep cerebellar nuclei (DCN). This model has fostered the IO hypothesis of ET, which postulates that factors that promote excess IO, and hence PC complex spike synchrony, also promote tremor. In contrast, the PC hypothesis postulates that partial PC cell loss underlies tremor of ET. We describe models in which chronic partial PC loss is associated with tremor, such as the Weaver mouse, and others with PC loss that do not show tremor, such as the Purkinje cell degeneration mouse. We postulate that partial PC loss with tremor is associated with terminal axonal sprouting. We then discuss tremor that occurs with large lesions of the cerebellum in primates. This tremor has variable frequency and is an ataxic tremor not related to ET. Another tremor type that is not likely related to ET is tremor in mice with mutations that cause prolonged synaptic GABA action. This tremor is probably due to mistiming within cerebellar circuitry. In the final section, we catalog tremor models involving neurotransmitter and ion channel perturbations. Some appear to be related to the IO hypothesis of ET, while in others tremor may be ataxic or due to mistiming. In summary, we offer a tentative framework for classifying animal action tremor, such that various models may be considered potentially relevant to ET, subscribing to IO or PC hypotheses, or not likely relevant, as with mistiming or ataxic tremor. Considerable further research is needed to elucidate the mechanisms of tremor in animal models.

  14. With neutrino masses revealed, proton decay is the missing link

    International Nuclear Information System (INIS)

    Pati, J.C.

    1999-01-01

    By way of paying tribute to Abdus Salam, I recall the ideas of higher unification that he and I initiated. I discuss the current status of those ideas in the light of recent developments, including those of: (a) gauge coupling unification, (b) discovery of neutrino-oscillation at SuperKamiokande, and (c) ongoing searches for proton decay. It is noted that the mass of ν τ (∼ 1/20 eV), suggested by the SuperK result, provides clear support for the route to higher unification based on the ideas of (i) SU(4)-color, (ii) left-right symmetry and (iii) supersymmetry. The change in perspective, pertaining to both gauge coupling unification and proton decay, brought forth by supersymmetry and superstrings, is noted. And, the beneficial roles of string-symmetries in addressing certain naturalness problems of supersymmetry, including that of rapid proton decay, are emphasized. Further, it is noted that with neutrino masses and coupling unification revealed, proton decay is the missing link. Following recent joint work with K. Babu and F. Wilczek, based on supersymmetric unification, it is remarked that the SuperKamiokande result on neutrino oscillation in fact enhances the expected rate of proton decay compared to prior estimates. Thus, assuming supersymmetric unification, one expects that the discovery of proton decay should not be far behind. (author)

  15. Integrative modelling reveals mechanisms linking productivity and plant species richness.

    Science.gov (United States)

    Grace, James B; Anderson, T Michael; Seabloom, Eric W; Borer, Elizabeth T; Adler, Peter B; Harpole, W Stanley; Hautier, Yann; Hillebrand, Helmut; Lind, Eric M; Pärtel, Meelis; Bakker, Jonathan D; Buckley, Yvonne M; Crawley, Michael J; Damschen, Ellen I; Davies, Kendi F; Fay, Philip A; Firn, Jennifer; Gruner, Daniel S; Hector, Andy; Knops, Johannes M H; MacDougall, Andrew S; Melbourne, Brett A; Morgan, John W; Orrock, John L; Prober, Suzanne M; Smith, Melinda D

    2016-01-21

    How ecosystem productivity and species richness are interrelated is one of the most debated subjects in the history of ecology. Decades of intensive study have yet to discern the actual mechanisms behind observed global patterns. Here, by integrating the predictions from multiple theories into a single model and using data from 1,126 grassland plots spanning five continents, we detect the clear signals of numerous underlying mechanisms linking productivity and richness. We find that an integrative model has substantially higher explanatory power than traditional bivariate analyses. In addition, the specific results unveil several surprising findings that conflict with classical models. These include the isolation of a strong and consistent enhancement of productivity by richness, an effect in striking contrast with superficial data patterns. Also revealed is a consistent importance of competition across the full range of productivity values, in direct conflict with some (but not all) proposed models. The promotion of local richness by macroecological gradients in climatic favourability, generally seen as a competing hypothesis, is also found to be important in our analysis. The results demonstrate that an integrative modelling approach leads to a major advance in our ability to discern the underlying processes operating in ecological systems.

  16. Concurrent growth rate and transcript analyses reveal essential gene stringency in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Shan Goh

    Full Text Available BACKGROUND: Genes essential for bacterial growth are of particular scientific interest. Many putative essential genes have been identified or predicted in several species, however, little is known about gene expression requirement stringency, which may be an important aspect of bacterial physiology and likely a determining factor in drug target development. METHODOLOGY/PRINCIPAL FINDINGS: Working from the premise that essential genes differ in absolute requirement for growth, we describe silencing of putative essential genes in E. coli to obtain a titration of declining growth rates and transcript levels by using antisense peptide nucleic acids (PNA and expressed antisense RNA. The relationship between mRNA decline and growth rate decline reflects the degree of essentiality, or stringency, of an essential gene, which is here defined by the minimum transcript level for a 50% reduction in growth rate (MTL(50. When applied to four growth essential genes, both RNA silencing methods resulted in MTL(50 values that reveal acpP as the most stringently required of the four genes examined, with ftsZ the next most stringently required. The established antibacterial targets murA and fabI were less stringently required. CONCLUSIONS: RNA silencing can reveal stringent requirements for gene expression with respect to growth. This method may be used to validate existing essential genes and to quantify drug target requirement.

  17. A synthetic system links FeFe-hydrogenases to essential E. coli sulfur metabolism

    Directory of Open Access Journals (Sweden)

    Grandl Gerald

    2011-05-01

    Full Text Available Abstract Background FeFe-hydrogenases are the most active class of H2-producing enzymes known in nature and may have important applications in clean H2 energy production. Many potential uses are currently complicated by a crucial weakness: the active sites of all known FeFe-hydrogenases are irreversibly inactivated by O2. Results We have developed a synthetic metabolic pathway in E. coli that links FeFe-hydrogenase activity to the production of the essential amino acid cysteine. Our design includes a complementary host strain whose endogenous redox pool is insulated from the synthetic metabolic pathway. Host viability on a selective medium requires hydrogenase expression, and moderate O2 levels eliminate growth. This pathway forms the basis for a genetic selection for O2 tolerance. Genetically selected hydrogenases did not show improved stability in O2 and in many cases had lost H2 production activity. The isolated mutations cluster significantly on charged surface residues, suggesting the evolution of binding surfaces that may accelerate hydrogenase electron transfer. Conclusions Rational design can optimize a fully heterologous three-component pathway to provide an essential metabolic flux while remaining insulated from the endogenous redox pool. We have developed a number of convenient in vivo assays to aid in the engineering of synthetic H2 metabolism. Our results also indicate a H2-independent redox activity in three different FeFe-hydrogenases, with implications for the future directed evolution of H2-activating catalysts.

  18. Essential role of integrin-linked kinase in regulation of phagocytosis in keratinocytes.

    Science.gov (United States)

    Sayedyahossein, Samar; Nini, Lylia; Irvine, Timothy S; Dagnino, Lina

    2012-10-01

    Phagocytic melanosome uptake by epidermal keratinocytes is a central protective mechanism against damage induced by ultraviolet radiation. Phagocytosis requires formation of pseudopodia via actin cytoskeleton rearrangements. Integrin-linked kinase (ILK) is an important modulator of actin cytoskeletal dynamics. We have examined the role of ILK in regulation of phagocytosis, using epidermal keratinocytes isolated from mice with epidermis-restricted Ilk gene inactivation. ILK-deficient cells exhibited severely impaired capacity to engulf fluorescent microspheres in response to stimulation of the keratinocyte growth factor (KGF) receptor or the protease-activated receptor-2. KGF induced ERK phosphorylation in ILK-expressing and ILK-deficient cells, suggesting that ILK is not essential for KGF receptor signaling. In contrast, KGF promoted activation of Rac1 and formation of pseudopodia in ILK-expressing, but not in ILK-deficient cells. Rac1-deficient keratinocytes also showed substantially impaired phagocytic ability, underlining the importance of ILK-dependent Rac1 function for particle engulfment. Finally, cross-modulation of KGF receptors by integrins may be another important element, as integrin β1-deficient keratinocytes also fail to show significant phagocytosis in response to KGF. Thus, we have identified a novel signaling pathway essential for phagocytosis in keratinocytes, which involves ILK-dependent activation of Rac1 in response to KGF, resulting in the formation of pseudopodia and particle uptake.

  19. Host behaviour–parasite feedback: an essential link between animal behaviour and disease ecology

    Science.gov (United States)

    Archie, Elizabeth A.; Craft, Meggan E.; Hawley, Dana M.; Martin, Lynn B.; Moore, Janice; White, Lauren

    2016-01-01

    Animal behaviour and the ecology and evolution of parasites are inextricably linked. For this reason, animal behaviourists and disease ecologists have been interested in the intersection of their respective fields for decades. Despite this interest, most research at the behaviour–disease interface focuses either on how host behaviour affects parasites or how parasites affect behaviour, with little overlap between the two. Yet, the majority of interactions between hosts and parasites are probably reciprocal, such that host behaviour feeds back on parasites and vice versa. Explicitly considering these feedbacks is essential for understanding the complex connections between animal behaviour and parasite ecology and evolution. To illustrate this point, we discuss how host behaviour–parasite feedbacks might operate and explore the consequences of feedback for studies of animal behaviour and parasites. For example, ignoring the feedback of host social structure on parasite dynamics can limit the accuracy of predictions about parasite spread. Likewise, considering feedback in studies of parasites and animal personalities may provide unique insight about the maintenance of variation in personality types. Finally, applying the feedback concept to links between host behaviour and beneficial, rather than pathogenic, microbes may shed new light on transitions between mutualism and parasitism. More generally, accounting for host behaviour–parasite feedbacks can help identify critical gaps in our understanding of how key host behaviours and parasite traits evolve and are maintained. PMID:27053751

  20. Host behaviour-parasite feedback: an essential link between animal behaviour and disease ecology.

    Science.gov (United States)

    Ezenwa, Vanessa O; Archie, Elizabeth A; Craft, Meggan E; Hawley, Dana M; Martin, Lynn B; Moore, Janice; White, Lauren

    2016-04-13

    Animal behaviour and the ecology and evolution of parasites are inextricably linked. For this reason, animal behaviourists and disease ecologists have been interested in the intersection of their respective fields for decades. Despite this interest, most research at the behaviour-disease interface focuses either on how host behaviour affects parasites or how parasites affect behaviour, with little overlap between the two. Yet, the majority of interactions between hosts and parasites are probably reciprocal, such that host behaviour feeds back on parasites and vice versa. Explicitly considering these feedbacks is essential for understanding the complex connections between animal behaviour and parasite ecology and evolution. To illustrate this point, we discuss how host behaviour-parasite feedbacks might operate and explore the consequences of feedback for studies of animal behaviour and parasites. For example, ignoring the feedback of host social structure on parasite dynamics can limit the accuracy of predictions about parasite spread. Likewise, considering feedback in studies of parasites and animal personalities may provide unique insight about the maintenance of variation in personality types. Finally, applying the feedback concept to links between host behaviour and beneficial, rather than pathogenic, microbes may shed new light on transitions between mutualism and parasitism. More generally, accounting for host behaviour-parasite feedbacks can help identify critical gaps in our understanding of how key host behaviours and parasite traits evolve and are maintained. © 2016 The Author(s).

  1. Remote sensing of Essential Biodiversity Variables: new measurements linking ecosystem structure, function and composition

    Science.gov (United States)

    Schimel, D.; Pavlick, R.; Stavros, E. N.; Townsend, P. A.; Ustin, S.; Thompson, D. R.

    2017-12-01

    Remote sensing can inform a wide variety of essential biodiversity variables, including measurements that define primary productivity, forest structure, biome distribution, plant communities, land use-land cover change and climate drivers of change. Emerging remote sensing technologies can add significantly to remote sensing of EBVs, providing new, large scale insights on plant and habitat diversity itself, as well as causes and consequences of biodiversity change. All current biodiversity assessments identify major data gaps, with insufficient coverage in critical regions, limited observations to monitor change over time, with very limited revisit of sample locations, as well as taxon-specific biased biases. Remote sensing cannot fill many of the gaps in global biodiversity observations, but spectroscopic measurements in terrestrial and marine environments can aid in assessing plant/phytoplankton functional diversity and efficiently reveal patterns in space, as well as changes over time, and, by making use of chlorophyll fluorescence, reveal associated patterns in photosynthesis. LIDAR and RADAR measurements quantify ecosystem structure, and can precisely define changes due to growth, disturbance and land use. Current satellite-based EBVs have taken advantage of the extraordinary time series from LANDSAT and MODIS, but new measurements more directly reveal ecosystem structure, function and composition. We will present results from pre-space airborne studies showing the synergistic ability of a suite of new remote observation techniques to quantify biodiversity and ecosystem function and show how it changes during major disturbance events.

  2. Metabolic multianalyte microphysiometry reveals extracellular acidosis is an essential mediator of neuronal preconditioning.

    Science.gov (United States)

    McKenzie, Jennifer R; Palubinsky, Amy M; Brown, Jacquelynn E; McLaughlin, Bethann; Cliffel, David E

    2012-07-18

    Metabolic adaptation to stress is a crucial yet poorly understood phenomenon, particularly in the central nervous system (CNS). The ability to identify essential metabolic events which predict neuronal fate in response to injury is critical to developing predictive markers of outcome, for interpreting CNS spectroscopic imaging, and for providing a richer understanding of the relevance of clinical indices of stress which are routinely collected. In this work, real-time multianalyte microphysiometry was used to dynamically assess multiple markers of aerobic and anaerobic respiration through simultaneous electrochemical measurement of extracellular glucose, lactate, oxygen, and acid. Pure neuronal cultures and mixed cultures of neurons and glia were compared following a 90 min exposure to aglycemia. This stress was cytotoxic to neurons yet resulted in no appreciable increase in cell death in age-matched mixed cultures. The metabolic profile of the cultures was similar in that aglycemia resulted in decreases in extracellular acidification and lactate release in both pure neurons and mixed cultures. However, oxygen consumption was only diminished in the neuron enriched cultures. The differences became more pronounced when cells were returned to glucose-containing media upon which extracellular acidification and oxygen consumption never returned to baseline in cells fated to die. Taken together, these data suggest that lactate release is not predictive of neuronal survival. Moreover, they reveal a previously unappreciated relationship of astrocytes in maintaining oxygen uptake and a correlation between metabolic recovery of neurons and extracellular acidification.

  3. The Inhibitory Effects of Curcuma longa L. Essential Oil and Curcumin on Aspergillus flavus Link Growth and Morphology

    Science.gov (United States)

    Mossini, Simone Aparecida Galerani; Ferreira, Francine Maery Dias; Arrotéia, Carla Cristina; da Costa, Christiane Luciana; Nakamura, Celso Vataru; Machinski Junior, Miguel

    2013-01-01

    The essential oil from Curcuma longa L. was analysed by GC/MS. The major components of the oil were ar-turmerone (33.2%), α-turmerone (23.5%) and β-turmerone (22.7%). The antifungal activities of the oil were studied with regard to Aspergillus flavus growth inhibition and altered morphology, as preliminary studies indicated that the essential oil from C. longa inhibited Aspergillus flavus Link aflatoxin production. The concentration of essential oil in the culture media ranged from 0.01% to 5.0% v/v, and the concentration of curcumin was 0.01–0.5% v/v. The effects on sporulation, spore viability, and fungal morphology were determined. The essential oil exhibited stronger antifungal activity than curcumin on A. flavus. The essential oil reduced the fungal growth in a concentration-dependent manner. A. flavus growth rate was reduced by C. longa essential oil at 0.10%, and this inhibition effect was more efficient in concentrations above 0.50%. Germination and sporulation were 100% inhibited in 0.5% oil. Scanning electron microscopy (SEM) of A. flavus exposed to oil showed damage to hyphae membranes and conidiophores. Because the fungus is a plant pathogen and aflatoxin producer, C. longa essential oil may be used in the management of host plants. PMID:24367241

  4. The Inhibitory Effects of Curcuma longa L. Essential Oil and Curcumin on Aspergillus flavus Link Growth and Morphology

    Directory of Open Access Journals (Sweden)

    Flávio Dias Ferreira

    2013-01-01

    Full Text Available The essential oil from Curcuma longa L. was analysed by GC/MS. The major components of the oil were ar-turmerone (33.2%, α-turmerone (23.5% and β-turmerone (22.7%. The antifungal activities of the oil were studied with regard to Aspergillus flavus growth inhibition and altered morphology, as preliminary studies indicated that the essential oil from C. longa inhibited Aspergillus flavus Link aflatoxin production. The concentration of essential oil in the culture media ranged from 0.01% to 5.0% v/v, and the concentration of curcumin was 0.01–0.5% v/v. The effects on sporulation, spore viability, and fungal morphology were determined. The essential oil exhibited stronger antifungal activity than curcumin on A. flavus. The essential oil reduced the fungal growth in a concentration-dependent manner. A. flavus growth rate was reduced by C. longa essential oil at 0.10%, and this inhibition effect was more efficient in concentrations above 0.50%. Germination and sporulation were 100% inhibited in 0.5% oil. Scanning electron microscopy (SEM of A. flavus exposed to oil showed damage to hyphae membranes and conidiophores. Because the fungus is a plant pathogen and aflatoxin producer, C. longa essential oil may be used in the management of host plants.

  5. The inhibitory effects of Curcuma longa L. essential oil and curcumin on Aspergillus flavus link growth and morphology.

    Science.gov (United States)

    Dias Ferreira, Flávio; Mossini, Simone Aparecida Galerani; Dias Ferreira, Francine Maery; Arrotéia, Carla Cristina; da Costa, Christiane Luciana; Nakamura, Celso Vataru; Machinski, Miguel

    2013-01-01

    The essential oil from Curcuma longa L. was analysed by GC/MS. The major components of the oil were ar-turmerone (33.2%), α -turmerone (23.5%) and β -turmerone (22.7%). The antifungal activities of the oil were studied with regard to Aspergillus flavus growth inhibition and altered morphology, as preliminary studies indicated that the essential oil from C. longa inhibited Aspergillus flavus Link aflatoxin production. The concentration of essential oil in the culture media ranged from 0.01% to 5.0% v/v, and the concentration of curcumin was 0.01-0.5% v/v. The effects on sporulation, spore viability, and fungal morphology were determined. The essential oil exhibited stronger antifungal activity than curcumin on A. flavus. The essential oil reduced the fungal growth in a concentration-dependent manner. A. flavus growth rate was reduced by C. longa essential oil at 0.10%, and this inhibition effect was more efficient in concentrations above 0.50%. Germination and sporulation were 100% inhibited in 0.5% oil. Scanning electron microscopy (SEM) of A. flavus exposed to oil showed damage to hyphae membranes and conidiophores. Because the fungus is a plant pathogen and aflatoxin producer, C. longa essential oil may be used in the management of host plants.

  6. Linking Knowledge and Skills to Mission Essential Competency-Based Syllabus Development for Distributed Mission Operations

    National Research Council Canada - National Science Library

    Symons, Steve; France, Michael; Bell, Jeffrey; Bennett, Jr, Winston

    2006-01-01

    ... of Mission Essential Competencies (MECs). MECs are defined as the higher order individual, team, and inter-team competencies that a fully prepared pilot, crew, or flight requires for successful mission completion under adverse conditions...

  7. Biodiversity and human well-being: an essential link for sustainable development.

    Science.gov (United States)

    Naeem, Shahid; Chazdon, Robin; Duffy, J Emmett; Prager, Case; Worm, Boris

    2016-12-14

    As society strives to transition towards more sustainable development pathways, it is important to properly conceptualize the link between biodiversity (i.e. genes, traits, species and other dimensions) and human well-being (HWB; i.e. health, wealth, security and other dimensions). Here, we explore how published conceptual frameworks consider the extent to which the biodiversity-HWB links are being integrated into public discourse and scientific research and the implications of our findings for sustainable development. We find that our understanding has gradually evolved from seeing the value of biodiversity as an external commodity that may influence HWB to biodiversity as fundamental to HWB. Analysis of the literature trends indicates increasing engagement with the terms biodiversity, HWB and sustainable development in the public, science and policy spheres, but largely as independent rather than linked terms. We suggest that a consensus framework for sustainable development should include biodiversity explicitly as a suite of internal variables that both influence and are influenced by HWB. Doing so will enhance clarity and help shape coherent research and policy priorities. We further suggest that the absence of this link in development can inadvertently lead to a ratcheting down of biodiversity by otherwise well-meaning policies. Such biotic impoverishment could lock HWB at minimum levels or lead to its decline and halt or reverse progress in achieving sustainable development. © 2016 The Authors.

  8. Biodiversity and human well-being: an essential link for sustainable development

    Science.gov (United States)

    Chazdon, Robin; Duffy, J. Emmett; Prager, Case; Worm, Boris

    2016-01-01

    As society strives to transition towards more sustainable development pathways, it is important to properly conceptualize the link between biodiversity (i.e. genes, traits, species and other dimensions) and human well-being (HWB; i.e. health, wealth, security and other dimensions). Here, we explore how published conceptual frameworks consider the extent to which the biodiversity–HWB links are being integrated into public discourse and scientific research and the implications of our findings for sustainable development. We find that our understanding has gradually evolved from seeing the value of biodiversity as an external commodity that may influence HWB to biodiversity as fundamental to HWB. Analysis of the literature trends indicates increasing engagement with the terms biodiversity, HWB and sustainable development in the public, science and policy spheres, but largely as independent rather than linked terms. We suggest that a consensus framework for sustainable development should include biodiversity explicitly as a suite of internal variables that both influence and are influenced by HWB. Doing so will enhance clarity and help shape coherent research and policy priorities. We further suggest that the absence of this link in development can inadvertently lead to a ratcheting down of biodiversity by otherwise well-meaning policies. Such biotic impoverishment could lock HWB at minimum levels or lead to its decline and halt or reverse progress in achieving sustainable development. PMID:27928039

  9. Essential gene disruptions reveal complex relationships between phenotypic robustness, pleiotropy, and fitness

    Science.gov (United States)

    Bauer, Christopher R; Li, Shuang; Siegal, Mark L

    2015-01-01

    The concept of robustness in biology has gained much attention recently, but a mechanistic understanding of how genetic networks regulate phenotypic variation has remained elusive. One approach to understand the genetic architecture of variability has been to analyze dispensable gene deletions in model organisms; however, the most important genes cannot be deleted. Here, we have utilized two systems in yeast whereby essential genes have been altered to reduce expression. Using high-throughput microscopy and image analysis, we have characterized a large number of morphological phenotypes, and their associated variation, for the majority of essential genes in yeast. Our results indicate that phenotypic robustness is more highly dependent upon the expression of essential genes than on the presence of dispensable genes. Morphological robustness appears to be a general property of a genotype that is closely related to pleiotropy. While the fitness profile across a range of expression levels is idiosyncratic to each gene, the global pattern indicates that there is a window in which phenotypic variation can be released before fitness effects are observable. PMID:25609648

  10. Analysis of Schizosaccharomyces pombe mediator reveals a set of essential subunits conserved between yeast and metazoan cells

    DEFF Research Database (Denmark)

    Spåhr, H; Samuelsen, C O; Baraznenok, V

    2001-01-01

    . cerevisiae share an essential protein module, which associates with nonessential speciesspecific subunits. In support of this view, sequence analysis of the conserved yeast Mediator components Med4 and Med8 reveals sequence homology to the metazoan Mediator components Trap36 and Arc32. Therefore, 8 of 10...... essential genes conserved between S. pombe and S. cerevisiae also have a metazoan homolog, indicating that an evolutionary conserved Mediator core is present in all eukaryotic cells. Our data suggest a closer functional relationship between yeast and metazoan Mediator than previously anticipated....

  11. Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection.

    Science.gov (United States)

    Côté, Marceline; Misasi, John; Ren, Tao; Bruchez, Anna; Lee, Kyungae; Filone, Claire Marie; Hensley, Lisa; Li, Qi; Ory, Daniel; Chandran, Kartik; Cunningham, James

    2011-08-24

    Ebola virus (EboV) is a highly pathogenic enveloped virus that causes outbreaks of zoonotic infection in Africa. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines in response to infection and in many outbreaks, mortality exceeds 75%. The unpredictable onset, ease of transmission, rapid progression of disease, high mortality and lack of effective vaccine or therapy have created a high level of public concern about EboV. Here we report the identification of a novel benzylpiperazine adamantane diamide-derived compound that inhibits EboV infection. Using mutant cell lines and informative derivatives of the lead compound, we show that the target of the inhibitor is the endosomal membrane protein Niemann-Pick C1 (NPC1). We find that NPC1 is essential for infection, that it binds to the virus glycoprotein (GP), and that antiviral compounds interfere with GP binding to NPC1. Combined with the results of previous studies of GP structure and function, our findings support a model of EboV infection in which cleavage of the GP1 subunit by endosomal cathepsin proteases removes heavily glycosylated domains to expose the amino-terminal domain, which is a ligand for NPC1 and regulates membrane fusion by the GP2 subunit. Thus, NPC1 is essential for EboV entry and a target for antiviral therapy.

  12. Essential oil from lemon peels inhibit key enzymes linked to neurodegenerative conditions and pro-oxidant induced lipid peroxidation.

    Science.gov (United States)

    Oboh, Ganiyu; Olasehinde, Tosin A; Ademosun, Ayokunle O

    2014-01-01

    This study sought to investigate the effects of essential oil from lemon (Citrus limoni) peels on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities in vitro. The essential oil was extracted by hydrodistillation, dried with anhydrous Na2SO4 and characterized using gas chromatography. Antioxidant properties of the oil and inhibition of pro-oxidant-induced lipid peroxidation in rats brain homogenate were also assessed. The essential oil inhibited AChE and BChE activities in a concentration-dependent manner. GC analysis revealed the presence of sabinene, limonene, α-pinene, β-pinene, neral, geranial, 1,8-cineole, linalool, borneol, α-terpineol, terpinen-4-ol, linalyl acetate and β-caryophyllene. Furthermore, the essential oil exhibited antioxidant activities as typified by ferric reducing property, Fe(2+)-chelation and radicals [DPPH, ABTS, OH, NO] scavenging abilities. The inhibition of AChE and BChE activities, inhibition of pro-oxidant induced lipid peroxidation and antioxidant activities could be possible mechanisms for the use of the essential oil in the management and prevention of oxidative stress-induced neurodegeneration.

  13. Pam heterozygous mice reveal essential role for Cu in amygdalar behavioral and synaptic function.

    Science.gov (United States)

    Gaier, Eric D; Eipper, Betty A; Mains, Richard E

    2014-05-01

    Copper (Cu) is an essential element with many biological roles, but its roles in the mammalian nervous system are poorly understood. Mice deficient in the cuproenzyme peptidylglycine α-amidating monooxygenase (Pam(+/-) mice) were initially generated to study neuropeptide amidation. Pam(+/-) mice exhibit profound deficits in a few behavioral tasks, including enhancements in innate fear along with deficits in acquired fear. Interestingly, several Pam(+/-) phenotypes were recapitulated in Cu-restricted wild-type mice and rescued in Cu-supplemented Pam(+/-) mice. These behaviors correspond to enhanced excitability and deficient synaptic plasticity in the amygdala of Pam(+/-) mice, which are also rescued by Cu supplementation. Cu and ATP7A are present at synapses, in key positions to respond to and influence synaptic activity. Further study demonstrated that extracellular Cu is necessary for wild-type synaptic plasticity and sufficient to induce long-term potentiation. These experiments support roles for PAM in Cu homeostasis and for synaptic Cu in amygdalar function. © 2014 New York Academy of Sciences.

  14. Abnormal regional homogeneity in patients with essential tremor revealed by resting-state functional MRI.

    Directory of Open Access Journals (Sweden)

    Weidong Fang

    Full Text Available Essential tremor (ET is one of the most common movement disorders in human adults. It can be characterized as a progressive neurological disorder of which the most recognizable feature is a tremor of the arms or hands that is apparent during voluntary movements such as eating and writing. The pathology of ET remains unclear. Resting-state fMRI (RS-fMRI, as a non-invasive imaging technique, was employed to investigate abnormalities of functional connectivity in ET in the brain. Regional homogeneity (ReHo was used as a metric of RS-fMRI to assess the local functional connectivity abnormality in ET with 20 ET patients and 20 age- and gender-matched healthy controls (HC. The ET group showed decreased ReHo in the anterior and posterior bilateral cerebellar lobes, the bilateral thalamus and the insular lobe, and increased ReHo in the bilateral prefrontal and parietal cortices, the left primary motor cortex and left supplementary motor area. The abnormal ReHo value of ET patients in the bilateral anterior cerebellar lobes and the right posterior cerebellar lobe were negatively correlated with the tremor severity score, while positively correlated with that in the left primary motor cortex. These findings suggest that the abnormality in cerebello-thalamo-cortical motor pathway is involved in tremor generation and propagation, which may be related to motor-related symptoms in ET patients. Meanwhile, the abnormality in the prefrontal and parietal regions may be associated with non-motor symptoms in ET. These findings suggest that the ReHo could be utilized for investigations of functional-pathological mechanism of ET.

  15. A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

    Science.gov (United States)

    Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A

    2016-07-01

    A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ

  16. Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes.

    Directory of Open Access Journals (Sweden)

    Peter Hevezi

    Full Text Available Efforts to unravel the mechanisms underlying taste sensation (gustation have largely focused on rodents. Here we present the first comprehensive characterization of gene expression in primate taste buds. Our findings reveal unique new insights into the biology of taste buds. We generated a taste bud gene expression database using laser capture microdissection (LCM procured fungiform (FG and circumvallate (CV taste buds from primates. We also used LCM to collect the top and bottom portions of CV taste buds. Affymetrix genome wide arrays were used to analyze gene expression in all samples. Known taste receptors are preferentially expressed in the top portion of taste buds. Genes associated with the cell cycle and stem cells are preferentially expressed in the bottom portion of taste buds, suggesting that precursor cells are located there. Several chemokines including CXCL14 and CXCL8 are among the highest expressed genes in taste buds, indicating that immune system related processes are active in taste buds. Several genes expressed specifically in endocrine glands including growth hormone releasing hormone and its receptor are also strongly expressed in taste buds, suggesting a link between metabolism and taste. Cell type-specific expression of transcription factors and signaling molecules involved in cell fate, including KIT, reveals the taste bud as an active site of cell regeneration, differentiation, and development. IKBKAP, a gene mutated in familial dysautonomia, a disease that results in loss of taste buds, is expressed in taste cells that communicate with afferent nerve fibers via synaptic transmission. This database highlights the power of LCM coupled with transcriptional profiling to dissect the molecular composition of normal tissues, represents the most comprehensive molecular analysis of primate taste buds to date, and provides a foundation for further studies in diverse aspects of taste biology.

  17. Potential translational targets revealed by linking mouse grooming behavioral phenotypes to gene expression using public databases.

    Science.gov (United States)

    Roth, Andrew; Kyzar, Evan J; Cachat, Jonathan; Stewart, Adam Michael; Green, Jeremy; Gaikwad, Siddharth; O'Leary, Timothy P; Tabakoff, Boris; Brown, Richard E; Kalueff, Allan V

    2013-01-10

    Rodent self-grooming is an important, evolutionarily conserved behavior, highly sensitive to pharmacological and genetic manipulations. Mice with aberrant grooming phenotypes are currently used to model various human disorders. Therefore, it is critical to understand the biology of grooming behavior, and to assess its translational validity to humans. The present in-silico study used publicly available gene expression and behavioral data obtained from several inbred mouse strains in the open-field, light-dark box, elevated plus- and elevated zero-maze tests. As grooming duration differed between strains, our analysis revealed several candidate genes with significant correlations between gene expression in the brain and grooming duration. The Allen Brain Atlas, STRING, GoMiner and Mouse Genome Informatics databases were used to functionally map and analyze these candidate mouse genes against their human orthologs, assessing the strain ranking of their expression and the regional distribution of expression in the mouse brain. This allowed us to identify an interconnected network of candidate genes (which have expression levels that correlate with grooming behavior), display altered patterns of expression in key brain areas related to grooming, and underlie important functions in the brain. Collectively, our results demonstrate the utility of large-scale, high-throughput data-mining and in-silico modeling for linking genomic and behavioral data, as well as their potential to identify novel neural targets for complex neurobehavioral phenotypes, including grooming. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis

    Science.gov (United States)

    Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.; Du, Niu; Mih, Nathan; Diamond, Spencer; Lee, Jenny J.; Golden, Susan S.; Palsson, Bernhard O.

    2016-01-01

    The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting in the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology. PMID:27911809

  19. Viral Genome-Linked Protein (VPg Is Essential for Translation Initiation of Rabbit Hemorrhagic Disease Virus (RHDV.

    Directory of Open Access Journals (Sweden)

    Jie Zhu

    Full Text Available Rabbit hemorrhagic disease virus (RHDV, the causative agent of rabbit hemorrhagic disease, is an important member of the caliciviridae family. Currently, no suitable tissue culture system is available for proliferating RHDV, limiting the study of the pathogenesis of RHDV. In addition, the mechanisms underlying RHDV translation and replication are largely unknown compared with other caliciviridae viruses. The RHDV replicon recently constructed in our laboratory provides an appropriate model to study the pathogenesis of RHDV without in vitro RHDV propagation and culture. Using this RHDV replicon, we demonstrated that the viral genome-linked protein (VPg is essential for RHDV translation in RK-13 cells for the first time. In addition, we showed that VPg interacts with eukaryotic initiation factor 4E (eIF4E in vivo and in vitro and that eIF4E silencing inhibits RHDV translation, suggesting the interaction between VPg and eIF4E is involved in RHDV translation. Our results support the hypothesis that VPg serves as a novel cap substitute during the initiation of RHDV translation.

  20. Exoproteome analysis reveals higher abundance of proteins linked to alkaline stress in persistent Listeria monocytogenes strains.

    Science.gov (United States)

    Rychli, Kathrin; Grunert, Tom; Ciolacu, Luminita; Zaiser, Andreas; Razzazi-Fazeli, Ebrahim; Schmitz-Esser, Stephan; Ehling-Schulz, Monika; Wagner, Martin

    2016-02-02

    The foodborne pathogen Listeria monocytogenes, responsible for listeriosis a rare but severe infection disease, can survive in the food processing environment for month or even years. So-called persistent L. monocytogenes strains greatly increase the risk of (re)contamination of food products, and are therefore a great challenge for food safety. However, our understanding of the mechanism underlying persistence is still fragmented. In this study we compared the exoproteome of three persistent strains with the reference strain EGDe under mild stress conditions using 2D differential gel electrophoresis. Principal component analysis including all differentially abundant protein spots showed that the exoproteome of strain EGDe (sequence type (ST) 35) is distinct from that of the persistent strain R479a (ST8) and the two closely related ST121 strains 4423 and 6179. Phylogenetic analyses based on multilocus ST genes showed similar grouping of the strains. Comparing the exoproteome of strain EGDe and the three persistent strains resulted in identification of 22 differentially expressed protein spots corresponding to 16 proteins. Six proteins were significantly increased in the persistent L. monocytogenes exoproteomes, among them proteins involved in alkaline stress response (e.g. the membrane anchored lipoprotein Lmo2637 and the NADPH dehydrogenase NamA). In parallel the persistent strains showed increased survival under alkaline stress, which is often provided during cleaning and disinfection in the food processing environments. In addition, gene expression of the proteins linked to stress response (Lmo2637, NamA, Fhs and QoxA) was higher in the persistent strain not only at 37 °C but also at 10 °C. Invasion efficiency of EGDe was higher in intestinal epithelial Caco2 and macrophage-like THP1 cells compared to the persistent strains. Concurrently we found higher expression of proteins involved in virulence in EGDe e.g. the actin-assembly-inducing protein ActA and the

  1. A Systematic Protein Refolding Screen Method using the DGR Approach Reveals that Time and Secondary TSA are Essential Variables.

    Science.gov (United States)

    Wang, Yuanze; van Oosterwijk, Niels; Ali, Ameena M; Adawy, Alaa; Anindya, Atsarina L; Dömling, Alexander S S; Groves, Matthew R

    2017-08-24

    Refolding of proteins derived from inclusion bodies is very promising as it can provide a reliable source of target proteins of high purity. However, inclusion body-based protein production is often limited by the lack of techniques for the detection of correctly refolded protein. Thus, the selection of the refolding conditions is mostly achieved using trial and error approaches and is thus a time-consuming process. In this study, we use the latest developments in the differential scanning fluorimetry guided refolding approach as an analytical method to detect correctly refolded protein. We describe a systematic buffer screen that contains a 96-well primary pH-refolding screen in conjunction with a secondary additive screen. Our research demonstrates that this approach could be applied for determining refolding conditions for several proteins. In addition, it revealed which "helper" molecules, such as arginine and additives are essential. Four different proteins: HA-RBD, MDM2, IL-17A and PD-L1 were used to validate our refolding approach. Our systematic protocol evaluates the impact of the "helper" molecules, the pH, buffer system and time on the protein refolding process in a high-throughput fashion. Finally, we demonstrate that refolding time and a secondary thermal shift assay buffer screen are critical factors for improving refolding efficiency.

  2. Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links

    DEFF Research Database (Denmark)

    Räschle, Markus; Smeenk, Godelieve; Hansen, Rebecca K

    2015-01-01

    DNA interstrand cross-links (ICLs) block replication fork progression by inhibiting DNA strand separation. Repair of ICLs requires sequential incisions, translesion DNA synthesis, and homologous recombination, but the full set of factors involved in these transactions remains unknown. We devised ...

  3. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

    DEFF Research Database (Denmark)

    Lu, Yingchang; Day, Felix R; Gustafsson, Stefan

    2016-01-01

    To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eigh...

  4. Using Regression to Measure Holistic Face Processing Reveals a Strong Link with Face Recognition Ability

    Science.gov (United States)

    DeGutis, Joseph; Wilmer, Jeremy; Mercado, Rogelio J.; Cohan, Sarah

    2013-01-01

    Although holistic processing is thought to underlie normal face recognition ability, widely discrepant reports have recently emerged about this link in an individual differences context. Progress in this domain may have been impeded by the widespread use of subtraction scores, which lack validity due to their contamination with control condition…

  5. Revealing the Link between Structural Relaxation and Dynamic Heterogeneity in Glass-Forming Liquids.

    Science.gov (United States)

    Wang, Lijin; Xu, Ning; Wang, W H; Guan, Pengfei

    2018-03-23

    Despite the use of glasses for thousands of years, the nature of the glass transition is still mysterious. On approaching the glass transition, the growth of dynamic heterogeneity has long been thought to play a key role in explaining the abrupt slowdown of structural relaxation. However, it still remains elusive whether there is an underlying link between structural relaxation and dynamic heterogeneity. Here, we unravel the link by introducing a characteristic time scale hiding behind an identical dynamic heterogeneity for various model glass-forming liquids. We find that the time scale corresponds to the kinetic fragility of liquids. Moreover, it leads to scaling collapse of both the structural relaxation time and dynamic heterogeneity for all liquids studied, together with a characteristic temperature associated with the same dynamic heterogeneity. Our findings imply that studying the glass transition from the viewpoint of dynamic heterogeneity is more informative than expected.

  6. Revealing the Link between Structural Relaxation and Dynamic Heterogeneity in Glass-Forming Liquids

    Science.gov (United States)

    Wang, Lijin; Xu, Ning; Wang, W. H.; Guan, Pengfei

    2018-03-01

    Despite the use of glasses for thousands of years, the nature of the glass transition is still mysterious. On approaching the glass transition, the growth of dynamic heterogeneity has long been thought to play a key role in explaining the abrupt slowdown of structural relaxation. However, it still remains elusive whether there is an underlying link between structural relaxation and dynamic heterogeneity. Here, we unravel the link by introducing a characteristic time scale hiding behind an identical dynamic heterogeneity for various model glass-forming liquids. We find that the time scale corresponds to the kinetic fragility of liquids. Moreover, it leads to scaling collapse of both the structural relaxation time and dynamic heterogeneity for all liquids studied, together with a characteristic temperature associated with the same dynamic heterogeneity. Our findings imply that studying the glass transition from the viewpoint of dynamic heterogeneity is more informative than expected.

  7. Neural computational modeling reveals a major role of corticospinal gating of central oscillations in the generation of essential tremor

    Directory of Open Access Journals (Sweden)

    Hong-en Qu

    2017-01-01

    Full Text Available Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network. A virtual arm model is driven by the central oscillation signal to simulate tremor activity behavior. Cortical descending commands are classified as alpha or gamma through monosynaptic or multisynaptic corticospinal pathways, which converge respectively on alpha or gamma motoneurons in the spinal cord. Several scenarios are evaluated based on the central oscillation signal passing down to the spinal motoneurons via each descending pathway. The simulated behaviors are compared with clinical essential tremor characteristics to identify the corticospinal pathways responsible for transmitting the central oscillation signal. A propriospinal neuron with strong cortical inhibition performs a gating function in the generation of essential tremor. Our results indicate that the propriospinal neuronal network is essential for relaying the central oscillation signal and the production of essential tremor.

  8. Neural computational modeling reveals a major role of corticospinal gating of central oscillations in the generation of essential tremor.

    Science.gov (United States)

    Qu, Hong-En; Niu, Chuanxin M; Li, Si; Hao, Man-Zhao; Hu, Zi-Xiang; Xie, Qing; Lan, Ning

    2017-12-01

    Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network. A virtual arm model is driven by the central oscillation signal to simulate tremor activity behavior. Cortical descending commands are classified as alpha or gamma through monosynaptic or multisynaptic corticospinal pathways, which converge respectively on alpha or gamma motoneurons in the spinal cord. Several scenarios are evaluated based on the central oscillation signal passing down to the spinal motoneurons via each descending pathway. The simulated behaviors are compared with clinical essential tremor characteristics to identify the corticospinal pathways responsible for transmitting the central oscillation signal. A propriospinal neuron with strong cortical inhibition performs a gating function in the generation of essential tremor. Our results indicate that the propriospinal neuronal network is essential for relaying the central oscillation signal and the production of essential tremor.

  9. Metagenomic Analysis of Hot Springs in Central India Reveals Hydrocarbon Degrading Thermophiles and Pathways Essential for Survival in Extreme Environments

    Science.gov (United States)

    Saxena, Rituja; Dhakan, Darshan B.; Mittal, Parul; Waiker, Prashant; Chowdhury, Anirban; Ghatak, Arundhuti; Sharma, Vineet K.

    2017-01-01

    Extreme ecosystems such as hot springs are of great interest as a source of novel extremophilic species, enzymes, metabolic functions for survival and biotechnological products. India harbors hundreds of hot springs, the majority of which are not yet explored and require comprehensive studies to unravel their unknown and untapped phylogenetic and functional diversity. The aim of this study was to perform a large-scale metagenomic analysis of three major hot springs located in central India namely, Badi Anhoni, Chhoti Anhoni, and Tattapani at two geographically distinct regions (Anhoni and Tattapani), to uncover the resident microbial community and their metabolic traits. Samples were collected from seven distinct sites of the three hot spring locations with temperature ranging from 43.5 to 98°C. The 16S rRNA gene amplicon sequencing of V3 hypervariable region and shotgun metagenome sequencing uncovered a unique taxonomic and metabolic diversity of the resident thermophilic microbial community in these hot springs. Genes associated with hydrocarbon degradation pathways, such as benzoate, xylene, toluene, and benzene were observed to be abundant in the Anhoni hot springs (43.5–55°C), dominated by Pseudomonas stutzeri and Acidovorax sp., suggesting the presence of chemoorganotrophic thermophilic community with the ability to utilize complex hydrocarbons as a source of energy. A high abundance of genes belonging to methane metabolism pathway was observed at Chhoti Anhoni hot spring, where methane is reported to constitute >80% of all the emitted gases, which was marked by the high abundance of Methylococcus capsulatus. The Tattapani hot spring, with a high-temperature range (61.5–98°C), displayed a lower microbial diversity and was primarily dominated by a nitrate-reducing archaeal species Pyrobaculum aerophilum. A higher abundance of cell metabolism pathways essential for the microbial survival in extreme conditions was observed at Tattapani. Taken together

  10. Transcriptional Analysis and Subcellular Protein Localization Reveal Specific Features of the Essential WalKR System in Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Olivier Poupel

    Full Text Available The WalKR two-component system, controlling cell wall metabolism, is highly conserved among Bacilli and essential for cell viability. In Staphylococcus aureus, walR and walK are followed by three genes of unknown function: walH, walI and walJ. Sequence analysis and transcript mapping revealed a unique genetic structure for this locus in S. aureus: the last gene of the locus, walJ, is transcribed independently, whereas transcription of the tetra-cistronic walRKHI operon occurred from two independent promoters located upstream from walR. Protein topology analysis and protein-protein interactions in E. coli as well as subcellular localization in S. aureus allowed us to show that WalH and WalI are membrane-bound proteins, which associate with WalK to form a complex at the cell division septum. While these interactions suggest that WalH and WalI play a role in activity of the WalKR regulatory pathway, deletion of walH and/or walI did not have a major effect on genes whose expression is strongly dependent on WalKR or on associated phenotypes. No effect of WalH or WalI was seen on tightly controlled WalKR regulon genes such as sle1 or saouhsc_00773, which encodes a CHAP-domain amidase. Of the genes encoding the two major S. aureus autolysins, AtlA and Sle1, only transcription of atlA was increased in the ΔwalH or ΔwalI mutants. Likewise, bacterial autolysis was not increased in the absence of WalH and/or WalI and biofilm formation was lowered rather than increased. Our results suggest that contrary to their major role as WalK inhibitors in B. subtilis, the WalH and WalI proteins have evolved a different function in S. aureus, where they are more accessory. A phylogenomic analysis shows a striking conservation of the 5 gene wal cluster along the evolutionary history of Bacilli, supporting the key importance of this signal transduction system, and indicating that the walH and walI genes were lost in the ancestor of Streptococcaceae, leading to their

  11. Transcriptional Analysis and Subcellular Protein Localization Reveal Specific Features of the Essential WalKR System in Staphylococcus aureus.

    Science.gov (United States)

    Poupel, Olivier; Moyat, Mati; Groizeleau, Julie; Antunes, Luísa C S; Gribaldo, Simonetta; Msadek, Tarek; Dubrac, Sarah

    2016-01-01

    The WalKR two-component system, controlling cell wall metabolism, is highly conserved among Bacilli and essential for cell viability. In Staphylococcus aureus, walR and walK are followed by three genes of unknown function: walH, walI and walJ. Sequence analysis and transcript mapping revealed a unique genetic structure for this locus in S. aureus: the last gene of the locus, walJ, is transcribed independently, whereas transcription of the tetra-cistronic walRKHI operon occurred from two independent promoters located upstream from walR. Protein topology analysis and protein-protein interactions in E. coli as well as subcellular localization in S. aureus allowed us to show that WalH and WalI are membrane-bound proteins, which associate with WalK to form a complex at the cell division septum. While these interactions suggest that WalH and WalI play a role in activity of the WalKR regulatory pathway, deletion of walH and/or walI did not have a major effect on genes whose expression is strongly dependent on WalKR or on associated phenotypes. No effect of WalH or WalI was seen on tightly controlled WalKR regulon genes such as sle1 or saouhsc_00773, which encodes a CHAP-domain amidase. Of the genes encoding the two major S. aureus autolysins, AtlA and Sle1, only transcription of atlA was increased in the ΔwalH or ΔwalI mutants. Likewise, bacterial autolysis was not increased in the absence of WalH and/or WalI and biofilm formation was lowered rather than increased. Our results suggest that contrary to their major role as WalK inhibitors in B. subtilis, the WalH and WalI proteins have evolved a different function in S. aureus, where they are more accessory. A phylogenomic analysis shows a striking conservation of the 5 gene wal cluster along the evolutionary history of Bacilli, supporting the key importance of this signal transduction system, and indicating that the walH and walI genes were lost in the ancestor of Streptococcaceae, leading to their atypical 3 wal gene

  12. Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina

    DEFF Research Database (Denmark)

    Gallo, G.; Renzone, G.; Alduina, R.

    2010-01-01

    A differential proteomic analysis, based on 2-DE and MS procedures, was performed on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin-like antibiotic balhimycin. A comparison of proteomic profiles before and during balhimycin production characterized differentially...... available over the World Wide Web as interactive web pages (http://www.unipa.it/ampuglia/Abal-proteome-maps). Functional clustering analysis revealed that differentially expressed proteins belong to functional groups involved in central carbon metabolism, amino acid metabolism and protein biosynthesis...... intermediates, were upregulated during antibiotic production. qRT-PCR analysis revealed that 8 out of 14 upregulated genes showed a positive correlation between changes at translational and transcriptional expression level. Furthermore, proteomic analysis of two nonproducing mutants, restricted to a sub...

  13. Chemical Composition and Antimicrobial Activity of the Essential Oils from Three Chemotypes of Origanum vulgare L. ssp. hirtum (Link Ietswaart Growing Wild in Campania (Southern Italy

    Directory of Open Access Journals (Sweden)

    Felice Senatore

    2009-07-01

    Full Text Available Essential oils obtained from inflorescences of three Origanum vulgare L.ssp. hirtum (Link Ietswaart samples, growing wild in different locations in Campania (Southern Italy, were analysed. Three chemotypes were found: the first, with a prevalence of carvacrol/thymol; the second, characterized by the prevalence of thymol/α-terpineol; the third, featuring a prevalence of linalyl acetate and linalool. This chemical study attempts to provide a contribution in shedding light on the relationship between chemical composition and biotypes and/or chemotypes in Origanum vulgare ssp. hirtum. The essential oils were also evaluated for their antibacterial activity against 10 selected microorganisms. The data obtained contribute to the future view to use the essential oils as natural preservatives for food products, due to their positive effect on their safety and shelf life.

  14. Linking the Gauss-Bonnet-Chern theorem, essential HOPF maps and membrane solitons with exotic spin and statistics

    International Nuclear Information System (INIS)

    Tze, Chia-Hsiung

    1989-01-01

    By way of the Gauss-Bonnet-Chern theorem, we present a higher dimensional extension of Polyakov's regularization of Wilson loops of point solitons. Spacetime paths of extended objects become hyper-ribbons with self-linking, twisting and writhing numbers. specifically we discuss the exotic spin and statistical phase entanglements of geometric n-membrane solitons of D-dimensional KP 1 σ-models with an added Hopf-Chern-Simons term where (n, D, K) = (0, 3, C), (2, 7, H), (6, 15, Ω). They are uniquely linked to the complex and quaternion and octonion division algebras. 22 refs

  15. Inhibitory effect of the essential oil of Curcuma longa L. and curcumin on aflatoxin production by Aspergillus flavus Link.

    Science.gov (United States)

    Ferreira, Flavio Dias; Kemmelmeier, Carlos; Arrotéia, Carla Cristina; da Costa, Christiane Luciana; Mallmann, Carlos Augusto; Janeiro, Vanderly; Ferreira, Francine Maery Dias; Mossini, Simone Aparecida Galerani; Silva, Expedito Leite; Machinski, Miguel

    2013-01-15

    Aflatoxins are highly toxic, mutagenic, teratogenic and carcinogenic mycotoxins. Consumption of aflatoxin-contaminated food and commodities poses serious hazards to the health of humans and animals. Turmeric, Curcuma longa L., is a native plant of Southeast Asia and has antimicrobial, antioxidant and antifungal properties. This paper reports the antiaflatoxigenic activities of the essential oil of C. longa and curcumin. The medium tests were prepared with the oil of C. longa, and the curcumin standard at concentrations varied from 0.01% to 5.0%. All doses of the essential oil of the plant and the curcumin standard interfered with mycotoxin production. Both the essential oil and curcumin significantly inhibited the production of aflatoxins; the 0.5% level had a greater than 96% inhibitory effect. The levels of aflatoxin B(1) (AFB(1)) production were 1.0 and 42.7 μg/mL, respectively, for the samples treated with the essential oil of C. longa L. and curcumin at a concentration of 0.5%. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. 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...

  17. Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links

    Science.gov (United States)

    Nicholls, Andrew W.; Salek, Reza M.; Marques-Vidal, Pedro; Morya, Edgard; Sameshima, Koichi; Montoliu, Ivan; Da Silva, Laeticia; Collino, Sebastiano; Martin, François-Pierre; Rezzi, Serge; Steinbeck, Christoph; Waterworth, Dawn M.; Waeber, Gérard; Vollenweider, Peter; Beckmann, Jacques S.; Le Coutre, Johannes; Mooser, Vincent; Bergmann, Sven; Genick, Ulrich K.; Kutalik, Zoltán

    2014-01-01

    Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on 1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10−8) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10−44) and lysine (rs8101881, P = 1.2×10−33), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers. PMID:24586186

  18. High-resolution mapping reveals links of HP1 with active and inactive chromatin components.

    Directory of Open Access Journals (Sweden)

    Elzo de Wit

    2007-03-01

    Full Text Available Heterochromatin protein 1 (HP1 is commonly seen as a key factor of repressive heterochromatin, even though a few genes are known to require HP1-chromatin for their expression. To obtain insight into the targeting of HP1 and its interplay with other chromatin components, we have mapped HP1-binding sites on Chromosomes 2 and 4 in Drosophila Kc cells using high-density oligonucleotide arrays and the DNA adenine methyltransferase identification (DamID technique. The resulting high-resolution maps show that HP1 forms large domains in pericentric regions, but is targeted to single genes on chromosome arms. Intriguingly, HP1 shows a striking preference for exon-dense genes on chromosome arms. Furthermore, HP1 binds along entire transcription units, except for 5' regions. Comparison with expression data shows that most of these genes are actively transcribed. HP1 target genes are also marked by the histone variant H3.3 and dimethylated histone 3 lysine 4 (H3K4me2, which are both typical of active chromatin. Interestingly, H3.3 deposition, which is usually observed along entire transcription units, is limited to the 5' ends of HP1-bound genes. Thus, H3.3 and HP1 are mutually exclusive marks on active chromatin. Additionally, we observed that HP1-chromatin and Polycomb-chromatin are nonoverlapping, but often closely juxtaposed, suggesting an interplay between both types of chromatin. These results demonstrate that HP1-chromatin is transcriptionally active and has extensive links with several other chromatin components.

  19. The kinome of Phytophthora infestans reveals oomycete-specific innovations and links to other taxonomic groups

    Directory of Open Access Journals (Sweden)

    Ah-Fong Audrey MV

    2010-12-01

    Full Text Available Abstract Background Oomycetes are a large group of economically and ecologically important species. Its most notorious member is Phytophthora infestans, the cause of the devastating potato late blight disease. The life cycle of P. infestans involves hyphae which differentiate into spores used for dispersal and host infection. Protein phosphorylation likely plays crucial roles in these stages, and to help understand this we present here a genome-wide analysis of the protein kinases of P. infestans and several relatives. The study also provides new insight into kinase evolution since oomycetes are taxonomically distant from organisms with well-characterized kinomes. Results Bioinformatic searches of the genomes of P. infestans, P. ramorum, and P. sojae reveal they have similar kinomes, which for P. infestans contains 354 eukaryotic protein kinases (ePKs and 18 atypical kinases (aPKs, equaling 2% of total genes. After refining gene models, most were classifiable into families seen in other eukaryotes. Some ePK families are nevertheless unusual, especially the tyrosine kinase-like (TKL group which includes large oomycete-specific subfamilies. Also identified were two tyrosine kinases, which are rare in non-metazoans. Several ePKs bear accessory domains not identified previously on kinases, such as cyclin-dependent kinases with integral cyclin domains. Most ePKs lack accessory domains, implying that many are regulated transcriptionally. This was confirmed by mRNA expression-profiling studies that showed that two-thirds vary significantly between hyphae, sporangia, and zoospores. Comparisons to neighboring taxa (apicomplexans, ciliates, diatoms revealed both clade-specific and conserved features, and multiple connections to plant kinases were observed. The kinome of Hyaloperonospora arabidopsidis, an oomycete with a simpler life cycle than P. infestans, was found to be one-third smaller. Some differences may be attributable to gene clustering, which

  20. Bioenergetics-based modeling of Plasmodium falciparum metabolism reveals its essential genes, nutritional requirements, and thermodynamic bottlenecks

    Science.gov (United States)

    Chiappino-Pepe, Anush; Ataman, Meriç

    2017-01-01

    Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa) of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA). Using previous absolute concentration data of the intraerythrocytic parasite, we applied TFA to iPfa and predicted up to 63 essential genes and 26 essential pairs of genes. Of the 63 genes, 35 have been experimentally validated and reported in the literature, and 28 have not been experimentally tested and include previously hypothesized or novel predictions of essential metabolic capabilities. Without metabolomics data, four of the genes would have been incorrectly predicted to be non-essential. TFA also indicated that substrate channeling should exist in two metabolic pathways to ensure the thermodynamic feasibility of the flux. Finally, analysis of the metabolic capabilities of P. falciparum led to the identification of both the minimal nutritional requirements and the genes that can become indispensable upon substrate inaccessibility. This model provides novel insight into the metabolic needs and capabilities of the malaria parasite and highlights metabolites and pathways that should be measured and characterized to identify potential thermodynamic bottlenecks and substrate channeling. The hypotheses presented seek to guide experimental studies to facilitate a better understanding of the parasite metabolism and the identification of targets for more efficient intervention. PMID:28333921

  1. Bioenergetics-based modeling of Plasmodium falciparum metabolism reveals its essential genes, nutritional requirements, and thermodynamic bottlenecks.

    Directory of Open Access Journals (Sweden)

    Anush Chiappino-Pepe

    2017-03-01

    Full Text Available Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA. Using previous absolute concentration data of the intraerythrocytic parasite, we applied TFA to iPfa and predicted up to 63 essential genes and 26 essential pairs of genes. Of the 63 genes, 35 have been experimentally validated and reported in the literature, and 28 have not been experimentally tested and include previously hypothesized or novel predictions of essential metabolic capabilities. Without metabolomics data, four of the genes would have been incorrectly predicted to be non-essential. TFA also indicated that substrate channeling should exist in two metabolic pathways to ensure the thermodynamic feasibility of the flux. Finally, analysis of the metabolic capabilities of P. falciparum led to the identification of both the minimal nutritional requirements and the genes that can become indispensable upon substrate inaccessibility. This model provides novel insight into the metabolic needs and capabilities of the malaria parasite and highlights metabolites and pathways that should be measured and characterized to identify potential thermodynamic bottlenecks and substrate channeling. The hypotheses presented seek to guide experimental studies to facilitate a better understanding of the parasite metabolism and the identification of targets for more efficient intervention.

  2. Revealing the timing of ocean stratification using remotely-sensed ocean fronts: links with marine predators

    Science.gov (United States)

    Miller, P. I.; Loveday, B. R.

    2016-02-01

    Stratification is of critical importance to the mixing and productivity of the ocean, though currently it can only be measured using in situ sampling, profiling buoys or underwater autonomous vehicles. Stratification is understood to affect the surface aggregation of pelagic fish and hence the foraging behaviour and distribution of their predators such as seabirds and cetaceans. Satellite Earth observation sensors cannot directly detect stratification, but can observe surface features related to the presence of stratification, for example shelf-sea fronts that separate tidally-mixed water from seasonally stratified water. This presentation describes a novel algorithm that accumulates evidence for stratification from a sequence of oceanic front maps, and in certain regions can reveal the timing of the seasonal onset and breakdown of stratification. Initial comparisons will be made with seabird locations acquired through GPS tagging. If successful, a remotely-sensed stratification timing index would augment the ocean front metrics already developed at PML, that have been applied in over 20 journal articles relating marine predators to ocean fronts. The figure below shows a preliminary remotely-sensed 'stratification' index, for 25-31 Jul. 2010, where red indicates water with stronger evidence for stratification.

  3. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

    Science.gov (United States)

    Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

    2016-05-01

    Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Network analysis reveals ecological links between N-fixing bacteria and wood-decaying fungi.

    Science.gov (United States)

    Hoppe, Björn; Kahl, Tiemo; Karasch, Peter; Wubet, Tesfaye; Bauhus, Jürgen; Buscot, François; Krüger, Dirk

    2014-01-01

    Nitrogen availability in dead wood is highly restricted and associations with N-fixing bacteria are thought to enable wood-decaying fungi to meet their nitrogen requirements for vegetative and generative growth. We assessed the diversity of nifH (dinitrogenase reductase) genes in dead wood of the common temperate tree species Fagus sylvatica and Picea abies from differently managed forest plots in Germany using molecular tools. By incorporating these genes into a large compilation of published nifH sequences and subsequent phylogenetic analyses of deduced proteins we verified the presence of diverse pools corresponding to functional nifH, almost all of which are new to science. The distribution of nifH genes strongly correlated with tree species and decay class, but not with forest management, while higher fungal fructification was correlated with decreasing nitrogen content of the dead wood and positively correlated with nifH diversity, especially during the intermediate stage of wood decay. Network analyses based on non-random species co-occurrence patterns revealed interactions among fungi and N-fixing bacteria in the dead wood and strongly indicate the occurrence of at least commensal relationships between these taxa.

  5. Network analysis reveals ecological links between N-fixing bacteria and wood-decaying fungi.

    Directory of Open Access Journals (Sweden)

    Björn Hoppe

    Full Text Available Nitrogen availability in dead wood is highly restricted and associations with N-fixing bacteria are thought to enable wood-decaying fungi to meet their nitrogen requirements for vegetative and generative growth. We assessed the diversity of nifH (dinitrogenase reductase genes in dead wood of the common temperate tree species Fagus sylvatica and Picea abies from differently managed forest plots in Germany using molecular tools. By incorporating these genes into a large compilation of published nifH sequences and subsequent phylogenetic analyses of deduced proteins we verified the presence of diverse pools corresponding to functional nifH, almost all of which are new to science. The distribution of nifH genes strongly correlated with tree species and decay class, but not with forest management, while higher fungal fructification was correlated with decreasing nitrogen content of the dead wood and positively correlated with nifH diversity, especially during the intermediate stage of wood decay. Network analyses based on non-random species co-occurrence patterns revealed interactions among fungi and N-fixing bacteria in the dead wood and strongly indicate the occurrence of at least commensal relationships between these taxa.

  6. Matrilineal Heritage in Southern Iberia Reveals Deep Genetic Links between Continents.

    Science.gov (United States)

    Hernández, Candela L; Calderón, Rosario

    2017-03-01

    Within the Mediterranean Basin, the Iberian Peninsula has been a focus of attraction for several cultures and civilizations from its prehistory and history, making it a target territory for studying human migration patterns and peopling processes using a wide and heterogeneous spectrum of genomic markers. While its Cantabrian fringe represents the most regularly analysed area in terms of its mitochondrial diversity, the absence of monographic surveys on the maternal genetic composition of southern Iberians (i.e., Andalusians) is striking. In this work, we present a comprehensive view of various aspects of the human maternal heritage of the autochthonous Andalusian population regarding specific mitochondrial haplogroups considered key candidates to determine the genetic relationship between Europe and Africa. Data reveal that southern Iberian populations do not have genetically homogeneous mitochondrial DNA profiles, and their observed genetic affinity with north-western African populations represents strong signals of old, sustained and bidirectional human movements between the northern and southern shores of the western Mediterranean. Thorough analyses of African mtDNA haplogroups have shown that the most relevant African contribution within Iberian Peninsula could be explained as a consequence of prehistoric events. The subsequent historic episodes helped to strengthen the ties between both shores. In southern Iberia, mitochondrial and other genetic markers show that the Strait of Gibraltar together with its surrounding maritime areas should be considered a bridge between continents. More broadly, the Mediterranean Sea has acted as a transport surface, that is, as a permeable barrier to human migrations from prehistoric and historic times. In conclusion, this research contributes to our knowledge of processes that have shaped the recent human genetic history in the Mediterranean and, more specifically, of the population dynamics that the inhabitants of southern

  7. An essential role of intestinal cell kinase in lung development is linked to the perinatal lethality of human ECO syndrome

    Science.gov (United States)

    Tong, Yixin; Park, So Hyun; Wu, Di; Xu, Wenhao; Guillot, Stacey J.; Jin, Li; Li, Xudong; Wang, Yalin; Lin, Chyuan-Sheng; Fu, Zheng

    2017-01-01

    Human endocrine-cerebro-osteodysplasia (ECO) syndrome, caused by the loss-of-function mutation R272Q in the ICK (intestinal cell kinase) gene, is a neonatal-lethal developmental disorder. To elucidate the molecular basis of ECO syndrome, we constructed an Ick R272Q knock-in mouse model that recapitulates ECO pathological phenotypes. Newborns bearing Ick R272Q homozygous mutations die at birth due to respiratory distress. Ick mutant lungs exhibit not only impaired branching morphogenesis associated with reduced mesenchymal proliferation, but also significant airspace deficiency in primitive alveoli concomitant with abnormal interstitial mesenchymal differentiation. ICK dysfunction induces elongated primary cilia and perturbs ciliary Hedgehog signaling and autophagy during lung sacculation. Our study identifies an essential role for ICK in lung development and advances the mechanistic understanding of ECO syndrome. PMID:28380258

  8. Pathology Informatics Essentials for Residents: A flexible informatics curriculum linked to Accreditation Council for Graduate Medical Education milestones

    Science.gov (United States)

    Henricks, Walter H; Karcher, Donald S; Harrison, James H; Sinard, John H; Riben, Michael W; Boyer, Philip J; Plath, Sue; Thompson, Arlene; Pantanowitz, Liron

    2016-01-01

    Context: Recognition of the importance of informatics to the practice of pathology has surged. Training residents in pathology informatics have been a daunting task for most residency programs in the United States because faculty often lacks experience and training resources. Nevertheless, developing resident competence in informatics is essential for the future of pathology as a specialty. Objective: The objective of the study is to develop and deliver a pathology informatics curriculum and instructional framework that guides pathology residency programs in training residents in critical pathology informatics knowledge and skills and meets Accreditation Council for Graduate Medical Education Informatics Milestones. Design: The College of American Pathologists, Association of Pathology Chairs, and Association for Pathology Informatics formed a partnership and expert work group to identify critical pathology informatics training outcomes and to create a highly adaptable curriculum and instructional approach, supported by a multiyear change management strategy. Results: Pathology Informatics Essentials for Residents (PIER) is a rigorous approach for educating all pathology residents in important pathology informatics knowledge and skills. PIER includes an instructional resource guide and toolkit for incorporating informatics training into residency programs that vary in needs, size, settings, and resources. PIER is available at http://www.apcprods.org/PIER (accessed April 6, 2016). Conclusions: PIER is an important contribution to informatics training in pathology residency programs. PIER introduces pathology trainees to broadly useful informatics concepts and tools that are relevant to practice. PIER provides residency program directors with a means to implement a standardized informatics training curriculum, to adapt the approach to local program needs, and to evaluate resident performance and progress over time. PMID:27563486

  9. Species-scanning mutagenesis of the serotonin transporter reveals residues essential in selective, high-affinity recognition of antidepressants

    DEFF Research Database (Denmark)

    Mortensen, O.V.; Wiborg, O.; Kristensen, A.S.

    2001-01-01

    )tropane, or for 3,4-methylenedioxymethamphetamine (MDMA). Analysis of six hSERT/bSERT chimeras and subsequent species-scanning mutagenesis of each isoform revealed methionine-180, tyrosine-495, and phenylalanine-513 to be responsible for the increase in citalopram and paroxetine potencies at hSERT and methionine...

  10. [Threshold value for reimbursement of costs of new drugs: cost-effectiveness research and modelling are essential links].

    Science.gov (United States)

    Frederix, Geert W J; Hövels, Anke M; Severens, Johan L; Raaijmakers, Jan A M; Schellens, Jan H M

    2015-01-01

    There is increasing discussion in the Netherlands about the introduction of a threshold value for the costs per extra year of life when reimbursing costs of new drugs. The Medicines Committee ('Commissie Geneesmiddelen'), a division of the Netherlands National Healthcare Institute ('Zorginstituut Nederland'), advises on reimbursement of costs of new drugs. This advice is based upon the determination of therapeutic value of the drug and the results of economic evaluations. Mathematical models that predict future costs and effectiveness are often used in economic evaluations; these models can vary greatly in transparency and quality due to author assumptions. Standardisation of cost-effectiveness models is one solution to overcome the unwanted variation in quality. Discussions about the introduction of a threshold value can only be meaningful if all involved are adequately informed, and by high quality in cost-effectiveness research and, particularly, economic evaluations. Collaboration and discussion between medical specialists, patients or patient organisations, health economists and policy makers, both in development of methods and in standardisation, are essential to improve the quality of decision making.

  11. The ALMA high speed optical communication link is here: an essential component for reliable present and future operations

    Science.gov (United States)

    Filippi, G.; Ibsen, J.; Jaque, S.; Liello, F.; Ovando, N.; Astudillo, A.; Parra, J.; Saldias, Christian

    2016-07-01

    Announced in 2012, started in 2013 and completed in 2015, the ALMA high bandwidth communication system has become a key factor to achieve the operational and scientific goals of ALMA. This paper summarizes the technical, organizational, and operational goals of the ALMA Optical Link Project, focused in the creation and operation of an effective and sustainable communication infrastructure to connect the ALMA Operations Support Facility and Array Operations Site, both located in the Atacama Desert in the Northern region of Chile, with the point of presence of REUNA in Antofagasta, about 400km away, and from there to the Santiago Central Office in the Chilean capital through the optical infrastructure created by the EC-funded EVALSO project and now an integral part of the REUNA backbone. This new infrastructure completed in 2014 and now operated on behalf of ALMA by REUNA, the Chilean National Research and Education Network, uses state of the art technologies, like dark fiber from newly built cables and DWDM transmission, allowing extending the reach of high capacity communication to the remote region where the Observatory is located. The paper also reports on the results obtained during the first year and a half testing and operation period, where different operational set ups have been experienced for data transfer, remote collaboration, etc. Finally, the authors will present a forward look of the impact of it to both the future scientific development of the Chajnantor Plateau, where many installations area are (and will be) located, as well as the potential Chilean scientific backbone long term development.

  12. Vacuum structure revealed by over-improved stout-link smearing compared with the overlap analysis for quenched QCD

    International Nuclear Information System (INIS)

    Ilgenfritz, E.M.; Leinweber, D.; Moran, P.; Koller, K.; Weinberg, V.; Freie Univ. Berlin

    2008-01-01

    A detailed comparison is made between the topological structure of quenched QCD as revealed by the recently proposed over-improved stout-link smearing in conjunction with an improved gluonic definition of the topological density on one hand and a similar analysis made possible by the overlap-fermionic topological charge density both with and without variable ultraviolet cutoff λ cut . The matching is twofold, provided by fitting the density-density two-point functions on one hand and by a point-by-point fitting of the topological densities according to the two methods. We point out the similar cluster structure of the topological density for moderate smearing and 200 MeV cut <600 MeV, respectively. We demonstrate the relation of the gluonic topological density for extensive smearing to the location of the overlap zero modes and the lowest overlap non-zero mode as found for the unsmeared configurations. (orig.)

  13. Vacuum structure revealed by over-improved stout-link smearing compared with the overlap analysis for quenched QCD

    Energy Technology Data Exchange (ETDEWEB)

    Ilgenfritz, E.M.; Leinweber, D.; Moran, P. [Adelaide Univ., SA (AU). Special Research Centre for the Subatomic Structure of Matter (CSSM); Koller, K. [Muenchen Univ. (Germany). Sektion Physik; Schierholz, G. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Weinberg, V. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Freie Univ. Berlin (Germany). Inst. fuer Theoretische Physik

    2008-01-11

    A detailed comparison is made between the topological structure of quenched QCD as revealed by the recently proposed over-improved stout-link smearing in conjunction with an improved gluonic definition of the topological density on one hand and a similar analysis made possible by the overlap-fermionic topological charge density both with and without variable ultraviolet cutoff {lambda}{sub cut}. The matching is twofold, provided by fitting the density-density two-point functions on one hand and by a point-by-point fitting of the topological densities according to the two methods. We point out the similar cluster structure of the topological density for moderate smearing and 200 MeV<{lambda}{sub cut}<600 MeV, respectively. We demonstrate the relation of the gluonic topological density for extensive smearing to the location of the overlap zero modes and the lowest overlap non-zero mode as found for the unsmeared configurations. (orig.)

  14. Fungicidal and anti-aflatoxigenic effects of the essential oil of Cymbopogon citratus (DC.) Stapf. (lemongrass) against Aspergillus flavus Link. isolated from stored rice.

    Science.gov (United States)

    Paranagama, P A; Abeysekera, K H T; Abeywickrama, K; Nugaliyadde, L

    2003-01-01

    To develop a natural fungicide against aflatoxigenic fungi, to protect stored rice, using the essential oil of lemongrass. Aspergillus flavus Link. was isolated from stored rice and identified as an aflatoxigenic strain. Lemongrass oil was tested against A. flavus and the test oil was fungistatic and fungicidal against the test pathogen at 0.6 and 1.0 mg ml(-1), respectively. Aflatoxin production was completely inhibited at 0.1 mg ml(-1). The results obtained from the thin layer chromatographic bioassay and gas chromatography indicated citral a and b as the fungicidal constituents in lemongrass oil. During the fumigant toxicity assay of lemongrass oil, the sporulation and the mycelial growth of the test pathogen were inhibited at the concentrations of 2.80 and 3.46 mg ml(-1), respectively. Lemongrass oil could be used to manage aflatoxin formation and fungal growth of A. flavus in stored rice. Currently, fungicides are not used to control fungal pests or mycotoxin production on stored rice. Rice treated with the essential oil of lemongrass could be used to manage fungal pests as well as the insect pests in stored rice. The essential oil is chemically safe and acceptable to consumers, as synthetic chemical fungicides can cause adverse health effects to consumers.

  15. Depletion of Plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite.

    Science.gov (United States)

    Buchholz, Kathrin; Rahlfs, Stefan; Schirmer, R Heiner; Becker, Katja; Matuschewski, Kai

    2008-06-25

    Proliferation of the pathogenic Plasmodium asexual blood stages in host erythrocytes requires an exquisite capacity to protect the malaria parasite against oxidative stress. This function is achieved by a complex antioxidant defence system composed of redox-active proteins and low MW antioxidants. Here, we disrupted the P. berghei plasmoredoxin gene that encodes a parasite-specific 22 kDa member of the thioredoxin superfamily. The successful generation of plasmoredoxin knockout mutants in the rodent model malaria parasite and phenotypic analysis during life cycle progression revealed a non-vital role in vivo. Our findings suggest that plasmoredoxin fulfils a specialized and dispensable role for Plasmodium and highlights the need for target validation to inform drug development strategies.

  16. Functional and structural insights revealed by molecular dynamics simulations of an essential RNA editing ligase in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Rommie E Amaro

    2007-11-01

    Full Text Available RNA editing ligase 1 (TbREL1 is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high-resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1's function. Differences in local and global motion upon ATP binding suggest that two peripheral loops, unique to the trypanosomes, may be involved in interdomain signaling events. Notably, a significant structural rearrangement of the enzyme's active site occurs during the apo simulations, opening an additional cavity adjacent to the ATP binding site that could be exploited in the development of effective inhibitors directed against this protozoan parasite. Finally, ensemble averaged electrostatics calculations over the MD simulations reveal a novel putative RNA binding site, a discovery that has previously eluded scientists. Ultimately, we use the insights gained through the MD simulations to make several predictions and recommendations, which we anticipate will help direct future experimental studies and structure-based drug discovery efforts against this vital enzyme.

  17. Coral bleaching is linked to the capacity of the animal host to supply essential metals to the symbionts.

    Science.gov (United States)

    Ferrier-Pagès, Christine; Sauzéat, Lucie; Balter, Vincent

    2018-03-23

    Massive coral bleaching events result in extensive coral loss throughout the world. These events are mainly caused by seawater warming, but are exacerbated by the subsequent decrease in nutrient availability in surface waters. It has therefore been shown that nitrogen, phosphorus or iron limitation contribute to the underlying conditions by which thermal stress induces coral bleaching. Generally, information on the trophic ecology of trace elements (micronutrients) in corals, and on how they modulate the coral response to thermal stress is lacking. Here, we demonstrate for the first time that heterotrophic feeding (i.e. the capture of zooplankton prey by the coral host) and thermal stress induce significant changes in micro element concentrations and isotopic signatures of the scleractinian coral Stylophora pistillata. The results obtained first reveal that coral symbionts are the major sink for the heterotrophically acquired micronutrients and accumulate manganese, magnesium and iron from the food. These metals are involved in photosynthesis and antioxidant protection. In addition, we show that fed corals can maintain high micronutrient concentrations in the host tissue during thermal stress and do not bleach, whereas unfed corals experience a significant decrease in copper, zinc, boron, calcium and magnesium in the host tissue and bleach. In addition, the significant increase in δ 65 Cu and δ 66 Zn signature of symbionts and host tissue at high temperature suggests that these isotopic compositions are good proxy for stress in corals. Overall, present findings highlight a new way in which coral heterotrophy and micronutrient availability contribute to coral resistance to global warming and bleaching. © 2018 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    David Judah

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

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

    Science.gov (United States)

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

    2012-01-01

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

  20. An Essential Role for Coagulase in Staphylococcus aureus Biofilm Development Reveals New Therapeutic Possibilities for Device-Related Infections.

    Science.gov (United States)

    Zapotoczna, Marta; McCarthy, Hannah; Rudkin, Justine K; O'Gara, James P; O'Neill, Eoghan

    2015-12-15

    High-level resistance to antimicrobial drugs is a major factor in the pathogenesis of chronic Staphylococcus aureus biofilm-associated, medical device-related infections. Antimicrobial susceptibility analysis revealed that biofilms grown for ≤ 24 hours on biomaterials conditioned with human plasma under venous shear in iron-free cell culture medium were significantly more susceptible to antistaphylococcal antibiotics. Biofilms formed under these physiologically relevant conditions were regulated by SaeRS and dependent on coagulase-catalyzed conversion of fibrinogen into fibrin. In contrast, SarA-regulated biofilms formed on uncoated polystyrene in nutrient-rich bacteriological medium were mediated by the previously characterized biofilm factors poly-N-acetyl glucosamine, fibronectin-binding proteins, or autolytic activity and were antibiotic resistant. Coagulase-mediated biofilms exhibited increased antimicrobial resistance over time (>48 hours) but were always susceptible to dispersal by the fibrinolytic enzymes plasmin or nattokinase. Biofilms recovered from infected central venous catheters in a rat model of device-related infection were dispersed by nattokinase, supporting the important role of the biofilm phenotype and identifying a potentially new therapeutic approach with antimicrobials and fibrinolytic drugs, particularly during the early stages of device-related infection. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Anode biofilm transcriptomics reveals outer surface components essential for high density current production in Geobacter sulfurreducens fuel cells.

    Directory of Open Access Journals (Sweden)

    Kelly P Nevin

    Full Text Available The mechanisms by which Geobacter sulfurreducens transfers electrons through relatively thick (>50 microm biofilms to electrodes acting as a sole electron acceptor were investigated. Biofilms of Geobacter sulfurreducens were grown either in flow-through systems with graphite anodes as the electron acceptor or on the same graphite surface, but with fumarate as the sole electron acceptor. Fumarate-grown biofilms were not immediately capable of significant current production, suggesting substantial physiological differences from current-producing biofilms. Microarray analysis revealed 13 genes in current-harvesting biofilms that had significantly higher transcript levels. The greatest increases were for pilA, the gene immediately downstream of pilA, and the genes for two outer c-type membrane cytochromes, OmcB and OmcZ. Down-regulated genes included the genes for the outer-membrane c-type cytochromes, OmcS and OmcT. Results of quantitative RT-PCR of gene transcript levels during biofilm growth were consistent with microarray results. OmcZ and the outer-surface c-type cytochrome, OmcE, were more abundant and OmcS was less abundant in current-harvesting cells. Strains in which pilA, the gene immediately downstream from pilA, omcB, omcS, omcE, or omcZ was deleted demonstrated that only deletion of pilA or omcZ severely inhibited current production and biofilm formation in current-harvesting mode. In contrast, these gene deletions had no impact on biofilm formation on graphite surfaces when fumarate served as the electron acceptor. These results suggest that biofilms grown harvesting current are specifically poised for electron transfer to electrodes and that, in addition to pili, OmcZ is a key component in electron transfer through differentiated G. sulfurreducens biofilms to electrodes.

  2. Internalisation of uncross-linked rituximab is not essential for the induction of caspase-independent killing in Burkitt lymphoma cell lines.

    Science.gov (United States)

    Turzanski, Julie; Daniels, Ian; Haynes, Andrew P

    2008-08-01

    Characterising the mechanisms underpinning caspase-independent programmed cell death (CI-PCD) induction by uncross-linked rituximab in B-cells may positively impact upon the treatment of disease states in which the classical apoptotic pathway is disabled. The necessity of rituximab internalisation for CI-PCD induction was investigated by flow cytometry and confocal microscopy in human BL cell lines with (e.g. Mutu I) and without (Mutu III) susceptibility to rituximab-induced killing. Flow cytometry demonstrated small, significant and similar amounts of rituximab internalisation by Mutu I cells after 1, 2, 4 and 24 h (p internalisation (p = 0.02, n = 5 and p = 0.0002, n = 6, respectively) in Mutu I cells, but confocal microscopy showed no correlation between internalised rituximab and phosphatidylserine exposure. We conclude that rituximab internalisation is not essential for CI-PCD induction in BL cell lines.

  3. Single-cell analysis reveals a link between CD3- and CD59-mediated signaling pathways in Jurkat T cells

    International Nuclear Information System (INIS)

    Lipp, A. M.

    2012-01-01

    Elevation of intracellular free calcium concentration ([Ca2+]i) is a key signal during T cell activation and is commonly used as a read-out parameter for stimulation of T cell signaling. Upon T cell stimulation a variety of calcium signals is produced by individual cells of the T cell population and the type of calcium signal strongly influences cell fate decisions. The heterogeneous nature of T cells is masked in ensemble measurements, which highlights the need for single-cell measurements. In this study we used single-cell calcium measurements in Jurkat cells to investigate signaling pathways, which are triggered by different proteins, namely CD3 and CD59. By application of an automated cluster algorithm the presented assay provides unbiased analysis of a large data set of individual calcium time traces generated by the whole cell population. By using this method we could demonstrate that the Jurkat population generates heterogeneous calcium signals in a stimulus-dependent manner. Furthermore, our data revealed the existence of a link between CD3- and CD59-mediated signaling pathways. Single-cell calcium measurements in Jurkat cells expressing different levels of the T cell receptor (TCR) complex indicated that CD59-mediated calcium signaling is critically dependent on TCR surface expression levels. In addition, triggering CD59-mediated calcium signaling resulted in down-regulation of TCR surface expression levels, which is known to happen upon direct TCR triggering too. Moreover, by using siRNA-mediated protein knock-downs and protein knock-out Jurkat mutants we could show that CD3- and CD59-mediated calcium signaling require identical key proteins. We therefore explored by which mechanism CD59-mediated signaling couples into TCR-mediated signaling. Fluorescence recovery after photobleaching (FRAP) experiments and live-cell protein-protein interaction assays provided no evidence of a direct physical interaction between CD3- and CD59-mediated signaling pathways

  4. Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex

    Directory of Open Access Journals (Sweden)

    Jason R. Gerstner

    2016-10-01

    Full Text Available Abstract Background Why we sleep is still one of the most perplexing mysteries in biology. Strong evidence indicates that sleep is necessary for normal brain function and that sleep need is a tightly regulated process. Surprisingly, molecular mechanisms that determine sleep need are incompletely described. Moreover, very little is known about transcriptional changes that specifically accompany the accumulation and discharge of sleep need. Several studies have characterized differential gene expression changes following sleep deprivation. Much less is known, however, about changes in gene expression during the compensatory response to sleep deprivation (i.e. recovery sleep. Results In this study we present a comprehensive analysis of the effects of sleep deprivation and subsequent recovery sleep on gene expression in the mouse cortex. We used a non-traditional analytical method for normalization of genome-wide gene expression data, Removal of Unwanted Variation (RUV. RUV improves detection of differential gene expression following sleep deprivation. We also show that RUV normalization is crucial to the discovery of differentially expressed genes associated with recovery sleep. Our analysis indicates that the majority of transcripts upregulated by sleep deprivation require 6 h of recovery sleep to return to baseline levels, while the majority of downregulated transcripts return to baseline levels within 1–3 h. We also find that transcripts that change rapidly during recovery (i.e. within 3 h do so on average with a time constant that is similar to the time constant for the discharge of sleep need. Conclusions We demonstrate that proper data normalization is essential to identify changes in gene expression that are specifically linked to sleep deprivation and recovery sleep. Our results provide the first evidence that recovery sleep is comprised of two waves of transcriptional regulation that occur at different times and affect functionally

  5. The organization structure and regulatory elements of Chlamydomonas histone genes reveal features linking plant and animal genes.

    Science.gov (United States)

    Fabry, S; Müller, K; Lindauer, A; Park, P B; Cornelius, T; Schmitt, R

    1995-09-01

    The genome of the green alga Chlamydomonas reinhardtii contains approximately 15 gene clusters of the nucleosomal (or core) histone H2A, H2B, H3 and H4 genes and at least one histone H1 gene. Seven non-allelic histone gene loci were isolated from a genomic library, physically mapped, and the nucleotide sequences of three isotypes of each core histone gene species and one linked H1 gene determined. The core histone genes are organized in clusters of H2A-H2B and H3-H4 pairs, in which each gene pair shows outwardly divergent transcription from a short (< 300 bp) intercistronic region. These intercistronic regions contain typically conserved promoter elements, namely a TATA-box and the three motifs TGGCCAG-G(G/C)-CGAG, CGTTGACC and CGGTTG. Different from the genes of higher plants, but like those of animals and the related alga Volvox, the 3' untranslated regions contain no poly A signal, but a palindromic sequence (3' palindrome) essential for mRNA processing is present. One single H1 gene was found in close linkage to a H2A-H2B pair. The H1 upstream region contains the octameric promoter element GGTTGACC (also found upstream of the core histone genes) and two specific sequence motifs that are shared only with the Volvox H1 promoters. This suggests differential transcription of the H1 and the core histone genes. The H1 gene is interrupted by two introns. Unlike Volvox H3 genes, the three sequenced H3 isoforms are intron-free. Primer-directed PCR of genomic DNA demonstrated, however, that at least 8 of the about 15 H3 genes do contain one intron at a conserved position. In synchronized C. reinhardtii cells, H4 mRNA levels (representative of all core histone mRNAs) peak during cell division, suggesting strict replication-dependent gene control. The derived peptide sequences place C. reinhardtii core histones closer to plants than to animals, except that the H2A histones are more animal-like. The peptide sequence of histone H1 is closely related to the V. carteri VH1-II

  6. Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor

    Science.gov (United States)

    O'Connell Motherway, Mary; Zomer, Aldert; Leahy, Sinead C.; Reunanen, Justus; Bottacini, Francesca; Claesson, Marcus J.; O'Brien, Frances; Flynn, Kiera; Casey, Patrick G.; Moreno Munoz, Jose Antonio; Kearney, Breda; Houston, Aileen M.; O'Mahony, Caitlin; Higgins, Des G.; Shanahan, Fergus; Palva, Airi; de Vos, Willem M.; Fitzgerald, Gerald F.; Ventura, Marco; O'Toole, Paul W.; van Sinderen, Douwe

    2011-01-01

    Development of the human gut microbiota commences at birth, with bifidobacteria being among the first colonizers of the sterile newborn gastrointestinal tract. To date, the genetic basis of Bifidobacterium colonization and persistence remains poorly understood. Transcriptome analysis of the Bifidobacterium breve UCC2003 2.42-Mb genome in a murine colonization model revealed differential expression of a type IVb tight adherence (Tad) pilus-encoding gene cluster designated “tad2003.” Mutational analysis demonstrated that the tad2003 gene cluster is essential for efficient in vivo murine gut colonization, and immunogold transmission electron microscopy confirmed the presence of Tad pili at the poles of B. breve UCC2003 cells. Conservation of the Tad pilus-encoding locus among other B. breve strains and among sequenced Bifidobacterium genomes supports the notion of a ubiquitous pili-mediated host colonization and persistence mechanism for bifidobacteria. PMID:21690406

  7. Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor.

    Science.gov (United States)

    O'Connell Motherway, Mary; Zomer, Aldert; Leahy, Sinead C; Reunanen, Justus; Bottacini, Francesca; Claesson, Marcus J; O'Brien, Frances; Flynn, Kiera; Casey, Patrick G; Munoz, Jose Antonio Moreno; Kearney, Breda; Houston, Aileen M; O'Mahony, Caitlin; Higgins, Des G; Shanahan, Fergus; Palva, Airi; de Vos, Willem M; Fitzgerald, Gerald F; Ventura, Marco; O'Toole, Paul W; van Sinderen, Douwe

    2011-07-05

    Development of the human gut microbiota commences at birth, with bifidobacteria being among the first colonizers of the sterile newborn gastrointestinal tract. To date, the genetic basis of Bifidobacterium colonization and persistence remains poorly understood. Transcriptome analysis of the Bifidobacterium breve UCC2003 2.42-Mb genome in a murine colonization model revealed differential expression of a type IVb tight adherence (Tad) pilus-encoding gene cluster designated "tad(2003)." Mutational analysis demonstrated that the tad(2003) gene cluster is essential for efficient in vivo murine gut colonization, and immunogold transmission electron microscopy confirmed the presence of Tad pili at the poles of B. breve UCC2003 cells. Conservation of the Tad pilus-encoding locus among other B. breve strains and among sequenced Bifidobacterium genomes supports the notion of a ubiquitous pili-mediated host colonization and persistence mechanism for bifidobacteria.

  8. Molecular contacts for chlorosome envelope proteins revealed by cross-linking studies with chlorosomes from Chlorobium tepidum

    DEFF Research Database (Denmark)

    Li, Hui; Frigaard, Niels-Ulrik; Bryant, Donald A

    2006-01-01

    type and mutants lacking a single chlorosome protein were cross-linked with the zero-length cross-linker 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and analyzed by gel electrophoresis. Similar cross-linking products were observed when the time and temperature were varied or when EDC...... was replaced with glutaraldehyde. Specific interactions between chlorosome proteins in cross-linked products were identified by immunoblotting with polyclonal antibodies raised against recombinant chlorosome proteins. We confirmed these interactions by demonstrating that these products were missing...... in appropriate mutants. Confirming the location of CsmA in the paracrystalline baseplate, cross-linking showed that CsmA forms dimers, trimers, and homomultimers as large as dodecamers and that CsmA directly interacts with the Fenna-Matthews-Olson protein. Cross-linking further suggests that the precursor form...

  9. Essential Genes for In Vitro Growth of the Endophyte Herbaspirillum seropedicae SmR1 as Revealed by Transposon Insertion Site Sequencing.

    Science.gov (United States)

    Rosconi, Federico; de Vries, Stefan P W; Baig, Abiyad; Fabiano, Elena; Grant, Andrew J

    2016-11-15

    The interior of plants contains microorganisms (referred to as endophytes) that are distinct from those present at the root surface or in the surrounding soil. Herbaspirillum seropedicae strain SmR1, belonging to the betaproteobacteria, is an endophyte that colonizes crops, including rice, maize, sugarcane, and sorghum. Different approaches have revealed genes and pathways regulated during the interactions of H. seropedicae with its plant hosts. However, functional genomic analysis of transposon (Tn) mutants has been hampered by the lack of genetic tools. Here we successfully employed a combination of in vivo high-density mariner Tn mutagenesis and targeted Tn insertion site sequencing (Tn-seq) in H. seropedicae SmR1. The analysis of multiple gene-saturating Tn libraries revealed that 395 genes are essential for the growth of H. seropedicae SmR1 in tryptone-yeast extract medium. A comparative analysis with the Database of Essential Genes (DEG) showed that 25 genes are uniquely essential in H. seropedicae SmR1. The Tn mutagenesis protocol developed and the gene-saturating Tn libraries generated will facilitate elucidation of the genetic mechanisms of the H. seropedicae endophytic lifestyle. A focal point in the study of endophytes is the development of effective biofertilizers that could help to reduce the input of agrochemicals in croplands. Besides the ability to promote plant growth, a good biofertilizer should be successful in colonizing its host and competing against the native microbiota. By using a systematic Tn-based gene-inactivation strategy and massively parallel sequencing of Tn insertion sites (Tn-seq), it is possible to study the fitness of thousands of Tn mutants in a single experiment. We have applied the combination of these techniques to the plant-growth-promoting endophyte Herbaspirillum seropedicae SmR1. The Tn mutant libraries generated will enable studies into the genetic mechanisms of H. seropedicae-plant interactions. The approach that we

  10. A novel mass spectrometric strategy "BEMAP" reveals Extensive O-linked protein glycosylation in Enterotoxigenic Escherichia coli

    DEFF Research Database (Denmark)

    Boysen, Anders; Palmisano, Giuseppe; Krogh, Thøger Jensen

    2016-01-01

    The attachment of sugars to proteins via side-chain oxygen atoms (O-linked glycosylation) is seen in all three domains of life. However, a lack of widely-applicable analytical tools has restricted the study of this process, particularly in bacteria. In E. coli, only four O-linked glycoproteins have...... previously been characterized. Here we present a glycoproteomics technique, termed BEMAP, which is based on the beta-elimination of O-linked glycans followed by Michael-addition of a phosphonic acid derivative, and subsequent titanium dioxide enrichment. This strategy allows site-specific mass......-spectrometric identification of proteins with O-linked glycan modifications in a complex biological sample. Using BEMAP we identified cell surface-associated and membrane vesicle glycoproteins from Enterotoxigenic E. coli (ETEC) and non-pathogenic E. coli K-12. We identified 618 glycosylated Serine and Threonine residues...

  11. Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase.

    Science.gov (United States)

    Nishikawa, Hiroyuki; Ooka, Seido; Sato, Ko; Arima, Kei; Okamoto, Joji; Klevit, Rachel E; Fukuda, Mamoru; Ohta, Tomohiko

    2004-02-06

    The breast and ovarian cancer suppressor BRCA1 acquires significant ubiquitin ligase activity when bound to BARD1 as a RING heterodimer. Although the activity may well be important for the role of BRCA1 as a tumor suppressor, the biochemical consequence of the activity is not yet known. Here we report that BRCA1-BARD1 catalyzes Lys-6-linked polyubiquitin chain formation. K6R mutation of ubiquitin dramatically reduces the polyubiquitin products mediated by BRCA1-BARD1 in vitro. BRCA1-BARD1 preferentially utilizes ubiquitin with a single Lys residue at Lys-6 or Lys-29 to mediate autoubiquitination of BRCA1 in vivo. Furthermore, mass spectrometry analysis identified the Lys-6-linked branched ubiquitin fragment from the polyubiquitin chain produced by BRCA1-BARD1 using wild type ubiquitin. The BRCA1-BARD1-mediated Lys-6-linked polyubiquitin chains are deubiquitinated by 26 S proteasome in vitro, whereas autoubiquitinated CUL1 through Lys-48-linked polyubiquitin chains is degraded. Proteasome inhibitors do not alter the steady state level of the autoubiquitinated BRCA1 in vivo. Hence, the results indicate that BRCA1-BARD1 mediates novel polyubiquitin chains that may be distinctly edited by 26 S proteasome from conventional Lys-48-linked polyubiquitin chains.

  12. A Putative O-Linked β-N-Acetylglucosamine Transferase Is Essential for Hormogonium Development and Motility in the Filamentous Cyanobacterium Nostoc punctiforme.

    Science.gov (United States)

    Khayatan, Behzad; Bains, Divleen K; Cheng, Monica H; Cho, Ye Won; Huynh, Jessica; Kim, Rachelle; Omoruyi, Osagie H; Pantoja, Adriana P; Park, Jun Sang; Peng, Julia K; Splitt, Samantha D; Tian, Mason Y; Risser, Douglas D

    2017-05-01

    Most species of filamentous cyanobacteria are capable of gliding motility, likely via a conserved type IV pilus-like system that may also secrete a motility-associated polysaccharide. In a subset of these organisms, motility is achieved only after the transient differentiation of hormogonia, which are specialized filaments that enter a nongrowth state dedicated to motility. Despite the fundamental importance of hormogonia to the life cycles of many filamentous cyanobacteria, the molecular regulation of hormogonium development is largely undefined. To systematically identify genes essential for hormogonium development and motility in the model heterocyst-forming filamentous cyanobacterium Nostoc punctiforme , a forward genetic screen was employed. The first gene identified using this screen, designated ogtA , encodes a putative O-linked β- N -acetylglucosamine transferase (OGT). The deletion of ogtA abolished motility, while ectopic expression of ogtA induced hormogonium development even under hormogonium-repressing conditions. Transcription of ogtA is rapidly upregulated (1 h) following hormogonium induction, and an OgtA-GFPuv fusion protein localized to the cytoplasm. In developing hormogonia, accumulation of PilA but not HmpD is dependent on ogtA Reverse transcription-quantitative PCR (RT-qPCR) analysis indicated equivalent levels of pilA transcript in the wild-type and Δ ogtA mutant strains, while a reporter construct consisting of the intergenic region in the 5' direction of pilA fused to gfp produced lower levels of fluorescence in the Δ ogtA mutant strain than in the wild type. The production of hormogonium polysaccharide in the Δ ogtA mutant strain is reduced compared to that in the wild type but comparable to that in a pilA deletion strain. Collectively, these results imply that O -GlcNAc protein modification regulates the accumulation of PilA via a posttranscriptional mechanism in developing hormogonia. IMPORTANCE Filamentous cyanobacteria are among

  13. A 200K SNP chip reveals a novel Pacific salmon louse genotype linked to differential efficacy of emamectin benzoate.

    Science.gov (United States)

    Messmer, Amber M; Leong, Jong S; Rondeau, Eric B; Mueller, Anita; Despins, Cody A; Minkley, David R; Kent, Matthew P; Lien, Sigbjørn; Boyce, Brad; Morrison, Diane; Fast, Mark D; Norman, Joseph D; Danzmann, Roy G; Koop, Ben F

    2018-04-16

    . Additionally, 478 Pacific louse samples from farmed and wild hosts obtained between 2005 and 2014 were also genotyped on the array. Clustering analysis allowed us to detect the apparent emergence of an otherwise rare genotype at a high frequency among the lice collected from two farms in 2013 that had reported elevated EMB tolerance. This genotype was not observed in louse samples collected from the same farm in 2010, nor in any lice sampled from other locations prior to 2013. However, this genotype was detected at low frequencies in louse samples from farms in two locations reporting elevated EMB tolerance in 2014. These results suggest that a rare genotype present in Pacific lice may be locally expanded in farms after EMB treatment. Supporting this hypothesis, 437 SNPs associated with this genotype were found to be in a region of linkage group 5 that overlaps the region associated with EMB resistance in Atlantic lice. Finally, five of the top diagnostic SNPs within this region were used to screen lice that had been subjected to an EMB survival assay, revealing a significant association between these SNPs and EMB treatment outcome. To our knowledge this work is the first report to identify a genetic link to altered EMB efficacy in L. salmonis in the Pacific Ocean. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Architecture of the RNA polymerase II-TFIIF complex revealed by cross-linking and mass spectrometry

    DEFF Research Database (Denmark)

    Chen, Zhuo Angel; Jawhari, Anass; Fischer, Lutz

    2010-01-01

    Higher-order multi-protein complexes such as RNA polymerase II (Pol II) complexes with transcription initiation factors are often not amenable to X-ray structure determination. Here, we show that protein cross-linking coupled to mass spectrometry (MS) has now sufficiently advanced as a tool to ex...

  15. Integrated in silico Analyses of Regulatory and Metabolic Networks of Synechococcus sp. PCC 7002 Reveal Relationships between Gene Centrality and Essentiality

    Directory of Open Access Journals (Sweden)

    Hyun-Seob Song

    2015-03-01

    Full Text Available Cyanobacteria dynamically relay environmental inputs to intracellular adaptations through a coordinated adjustment of photosynthetic efficiency and carbon processing rates. The output of such adaptations is reflected through changes in transcriptional patterns and metabolic flux distributions that ultimately define growth strategy. To address interrelationships between metabolism and regulation, we performed integrative analyses of metabolic and gene co-expression networks in a model cyanobacterium, Synechococcus sp. PCC 7002. Centrality analyses using the gene co-expression network identified a set of key genes, which were defined here as “topologically important.” Parallel in silico gene knock-out simulations, using the genome-scale metabolic network, classified what we termed as “functionally important” genes, deletion of which affected growth or metabolism. A strong positive correlation was observed between topologically and functionally important genes. Functionally important genes exhibited variable levels of topological centrality; however, the majority of topologically central genes were found to be functionally essential for growth. Subsequent functional enrichment analysis revealed that both functionally and topologically important genes in Synechococcus sp. PCC 7002 are predominantly associated with translation and energy metabolism, two cellular processes critical for growth. This research demonstrates how synergistic network-level analyses can be used for reconciliation of metabolic and gene expression data to uncover fundamental biological principles.

  16. Organization of Subunits in the Membrane Domain of the Bovine F-ATPase Revealed by Covalent Cross-linking.

    Science.gov (United States)

    Lee, Jennifer; Ding, ShuJing; Walpole, Thomas B; Holding, Andrew N; Montgomery, Martin G; Fearnley, Ian M; Walker, John E

    2015-05-22

    The F-ATPase in bovine mitochondria is a membrane-bound complex of about 30 subunits of 18 different kinds. Currently, ∼85% of its structure is known. The enzyme has a membrane extrinsic catalytic domain, and a membrane intrinsic domain where the turning of the enzyme's rotor is generated from the transmembrane proton-motive force. The domains are linked by central and peripheral stalks. The central stalk and a hydrophobic ring of c-subunits in the membrane domain constitute the enzyme's rotor. The external surface of the catalytic domain and membrane subunit a are linked by the peripheral stalk, holding them static relative to the rotor. The membrane domain contains six additional subunits named ATP8, e, f, g, DAPIT (diabetes-associated protein in insulin-sensitive tissues), and 6.8PL (6.8-kDa proteolipid), each with a single predicted transmembrane α-helix, but their orientation and topography are unknown. Mutations in ATP8 uncouple the enzyme and interfere with its assembly, but its roles and the roles of the other five subunits are largely unknown. We have reacted accessible amino groups in the enzyme with bifunctional cross-linking agents and identified the linked residues. Cross-links involving the supernumerary subunits, where the structures are not known, show that the C terminus of ATP8 extends ∼70 Å from the membrane into the peripheral stalk and that the N termini of the other supernumerary subunits are on the same side of the membrane, probably in the mitochondrial matrix. These experiments contribute significantly toward building up a complete structural picture of the F-ATPase. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Organization of Subunits in the Membrane Domain of the Bovine F-ATPase Revealed by Covalent Cross-linking*

    Science.gov (United States)

    Lee, Jennifer; Ding, ShuJing; Walpole, Thomas B.; Holding, Andrew N.; Montgomery, Martin G.; Fearnley, Ian M.; Walker, John E.

    2015-01-01

    The F-ATPase in bovine mitochondria is a membrane-bound complex of about 30 subunits of 18 different kinds. Currently, ∼85% of its structure is known. The enzyme has a membrane extrinsic catalytic domain, and a membrane intrinsic domain where the turning of the enzyme's rotor is generated from the transmembrane proton-motive force. The domains are linked by central and peripheral stalks. The central stalk and a hydrophobic ring of c-subunits in the membrane domain constitute the enzyme's rotor. The external surface of the catalytic domain and membrane subunit a are linked by the peripheral stalk, holding them static relative to the rotor. The membrane domain contains six additional subunits named ATP8, e, f, g, DAPIT (diabetes-associated protein in insulin-sensitive tissues), and 6.8PL (6.8-kDa proteolipid), each with a single predicted transmembrane α-helix, but their orientation and topography are unknown. Mutations in ATP8 uncouple the enzyme and interfere with its assembly, but its roles and the roles of the other five subunits are largely unknown. We have reacted accessible amino groups in the enzyme with bifunctional cross-linking agents and identified the linked residues. Cross-links involving the supernumerary subunits, where the structures are not known, show that the C terminus of ATP8 extends ∼70 Å from the membrane into the peripheral stalk and that the N termini of the other supernumerary subunits are on the same side of the membrane, probably in the mitochondrial matrix. These experiments contribute significantly toward building up a complete structural picture of the F-ATPase. PMID:25851905

  18. One and a half million medical papers reveal a link between author gender and attention to gender and sex analysis

    DEFF Research Database (Denmark)

    Nielsen, Mathias Wullum; Andersen, Jens Peter; Schiebinger, Londa

    2017-01-01

    Gender and sex analysis is increasingly recognized as a key factor in creating better medical research and health care. Using a sample of more than 1.5 million medical research papers, our study examined the potential link between women’s participation in medical science and attention to gender......-related and sex-related factors in disease-specific research. Adjusting for variations across countries, disease topics and medical research areas, we compared the participation of women authors in studies that do and do not involve gender and sex analysis. Overall, our results show a robust positive correlation...... between women’s authorship and the likelihood of a study including gender and sex analysis. These findings corroborate discussions of how women’s participation in medical science links to research outcomes, and show the mutual benefits of promoting both the scientific advancement of women...

  19. Photosensitized UVA-Induced Cross-Linking between Human DNA Repair and Replication Proteins and DNA Revealed by Proteomic Analysis

    Science.gov (United States)

    2016-01-01

    Long wavelength ultraviolet radiation (UVA, 320–400 nm) interacts with chromophores present in human cells to induce reactive oxygen species (ROS) that damage both DNA and proteins. ROS levels are amplified, and the damaging effects of UVA are exacerbated if the cells are irradiated in the presence of UVA photosensitizers such as 6-thioguanine (6-TG), a strong UVA chromophore that is extensively incorporated into the DNA of dividing cells, or the fluoroquinolone antibiotic ciprofloxacin. Both DNA-embedded 6-TG and ciprofloxacin combine synergistically with UVA to generate high levels of ROS. Importantly, the extensive protein damage induced by these photosensitizer+UVA combinations inhibits DNA repair. DNA is maintained in intimate contact with the proteins that effect its replication, transcription, and repair, and DNA–protein cross-links (DPCs) are a recognized reaction product of ROS. Cross-linking of DNA metabolizing proteins would compromise these processes by introducing physical blocks and by depleting active proteins. We describe a sensitive and statistically rigorous method to analyze DPCs in cultured human cells. Application of this proteomics-based analysis to cells treated with 6-TG+UVA and ciprofloxacin+UVA identified proteins involved in DNA repair, replication, and gene expression among those most vulnerable to cross-linking under oxidative conditions. PMID:27654267

  20. A novel low-temperature-active β-glucosidase from symbiotic Serratia sp. TN49 reveals four essential positions for substrate accommodation.

    Science.gov (United States)

    Zhou, Junpei; Zhang, Rui; Shi, Pengjun; Huang, Huoqing; Meng, Kun; Yuan, Tiezheng; Yang, Peilong; Yao, Bin

    2011-10-01

    A 2,373-bp full-length gene (bglA49) encoding a 790-residue polypeptide (BglA49) with a calculated mass of 87.8 kDa was cloned from Serratia sp. TN49, a symbiotic bacterium isolated from the gut of longhorned beetle (Batocera horsfieldi) larvae. The deduced amino acid sequence of BglA49 showed the highest identities of 80.1% with a conceptually translated protein from Pantoea sp. At-9b (EEW02556), 38.3% with the identified glycoside hydrolase (GH) family 3 β-glucosidase from Clostridium stercorarium NCBI 11754 (CAB08072), and sp. G5 (ABL09836) and Paenibacillus sp. C7 (AAX35883). The recombinant enzyme (r-BglA49) was expressed in Escherichia coli and displayed the typical characteristics of low-temperature-active enzymes, such as low temperature optimum (showing apparent optimal activity at 35°C), activity at low temperatures (retaining approximately 60% of its maximum activity at 20°C and approximately 25% at 10°C). Compared with the thermophilic GH 3 β-glucosidase, r-BglA49 had fewer hydrogen bonds and salt bridges and less proline residues. These features might relate to the increased structure flexibility and higher catalytic activity at low temperatures of r-BglA49. The molecular docking study of four GH 3 β-glucosidases revealed five conserved positions contributing to substrate accommodation, among which four positions of r-BglA49 (R192, Y228, D260, and E449) were identified to be essential based on site-directed mutagenesis analysis.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Small interference RNA profiling reveals the essential role of human membrane trafficking genes in mediating the infectious entry of dengue virus

    Directory of Open Access Journals (Sweden)

    Chu Justin

    2010-02-01

    Full Text Available Abstract Background Dengue virus (DENV is the causative agent of Dengue fever and the life-threatening Dengue Haemorrhagic fever or Dengue shock syndrome. In the absence of anti-viral agents or vaccine, there is an urgent need to develop an effective anti-viral strategy against this medically important viral pathogen. The initial interplay between DENV and the host cells may represent one of the potential anti-viral targeting sites. Currently the involvements of human membrane trafficking host genes or factors that mediate the infectious cellular entry of dengue virus are not well defined. Results In this study, we have used a targeted small interfering RNA (siRNA library to identify and profile key cellular genes involved in processes of endocytosis, cytoskeletal dynamics and endosome trafficking that are important and essential for DENV infection. The infectious entry of DENV into Huh7 cells was shown to be potently inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis. The important role of clathrin-mediated endocytosis was confirmed by the expression of well-characterized dominant-negative mutants of genes in this pathway and by using the clathrin endocytosis inhibitor chlorpromazine. Furthermore, DENV infection was shown to be sensitive to the disruption of human genes in regulating the early to late endosomal trafficking as well as the endosomal acidic pH. The importance and involvement of both actin and microtubule dynamics in mediating the infectious entry of DENV was also revealed in this study. Conclusions Together, the findings from this study have provided a detail profiling of the human membrane trafficking cellular genes and the mechanistic insight into the interplay of these host genes with DENV to initiate an infection, hence broadening our understanding on the entry pathway of this medically important viral pathogen. These data may also provide a new potential avenue for development of anti

  3. In vitro reconstitution of sortase-catalyzed pilus polymerization reveals structural elements involved in pilin cross-linking.

    Science.gov (United States)

    Chang, Chungyu; Amer, Brendan R; Osipiuk, Jerzy; McConnell, Scott A; Huang, I-Hsiu; Hsieh, Van; Fu, Janine; Nguyen, Hong H; Muroski, John; Flores, Erika; Ogorzalek Loo, Rachel R; Loo, Joseph A; Putkey, John A; Joachimiak, Andrzej; Das, Asis; Clubb, Robert T; Ton-That, Hung

    2018-06-12

    Covalently cross-linked pilus polymers displayed on the cell surface of Gram-positive bacteria are assembled by class C sortase enzymes. These pilus-specific transpeptidases located on the bacterial membrane catalyze a two-step protein ligation reaction, first cleaving the LPXTG motif of one pilin protomer to form an acyl-enzyme intermediate and then joining the terminal Thr to the nucleophilic Lys residue residing within the pilin motif of another pilin protomer. To date, the determinants of class C enzymes that uniquely enable them to construct pili remain unknown. Here, informed by high-resolution crystal structures of corynebacterial pilus-specific sortase (SrtA) and utilizing a structural variant of the enzyme (SrtA 2M ), whose catalytic pocket has been unmasked by activating mutations, we successfully reconstituted in vitro polymerization of the cognate major pilin (SpaA). Mass spectrometry, electron microscopy, and biochemical experiments authenticated that SrtA 2M synthesizes pilus fibers with correct Lys-Thr isopeptide bonds linking individual pilins via a thioacyl intermediate. Structural modeling of the SpaA-SrtA-SpaA polymerization intermediate depicts SrtA 2M sandwiched between the N- and C-terminal domains of SpaA harboring the reactive pilin and LPXTG motifs, respectively. Remarkably, the model uncovered a conserved TP(Y/L)XIN(S/T)H signature sequence following the catalytic Cys, in which the alanine substitutions abrogated cross-linking activity but not cleavage of LPXTG. These insights and our evidence that SrtA 2M can terminate pilus polymerization by joining the terminal pilin SpaB to SpaA and catalyze ligation of isolated SpaA domains in vitro provide a facile and versatile platform for protein engineering and bio-conjugation that has major implications for biotechnology.

  4. Transcriptome analysis reveals mucin 4 to be highly associated with periodontitis and identifies pleckstrin as a link to systemic diseases

    Science.gov (United States)

    Lundmark, Anna; Davanian, Haleh; Båge, Tove; Johannsen, Gunnar; Koro, Catalin; Lundeberg, Joakim; Yucel-Lindberg, Tülay

    2015-01-01

    The multifactorial chronic inflammatory disease periodontitis, which is characterized by destruction of tooth-supporting tissues, has also been implicated as a risk factor for various systemic diseases. Although periodontitis has been studied extensively, neither disease-specific biomarkers nor therapeutic targets have been identified, nor its link with systemic diseases. Here, we analyzed the global transcriptome of periodontitis and compared its gene expression profile with those of other inflammatory conditions, including cardiovascular disease (CVD), rheumatoid arthritis (RA), and ulcerative colitis (UC). Gingival biopsies from 62 patients with periodontitis and 62 healthy subjects were subjected to RNA sequencing. The up-regulated genes in periodontitis were related to inflammation, wounding and defense response, and apoptosis, whereas down-regulated genes were related to extracellular matrix organization and structural support. The most highly up-regulated gene was mucin 4 (MUC4), and its protein product was confirmed to be over-expressed in periodontitis. When comparing the expression profile of periodontitis with other inflammatory diseases, several gene ontology categories, including inflammatory response, cell death, cell motion, and homeostatic processes, were identified as common to all diseases. Only one gene, pleckstrin (PLEK), was significantly overexpressed in periodontitis, CVD, RA, and UC, implicating this gene as an important networking link between these chronic inflammatory diseases. PMID:26686060

  5. Nucleolar Proteome Analysis and Proteasomal Activity Assays Reveal a Link between Nucleolus and 26S Proteasome in A. thaliana

    Science.gov (United States)

    Montacié, Charlotte; Durut, Nathalie; Opsomer, Alison; Palm, Denise; Comella, Pascale; Picart, Claire; Carpentier, Marie-Christine; Pontvianne, Frederic; Carapito, Christine; Schleiff, Enrico; Sáez-Vásquez, Julio

    2017-01-01

    In all eukaryotic cells, the nucleolus is functionally and structurally linked to rRNA synthesis and ribosome biogenesis. This compartment contains as well factors involved in other cellular activities, but the functional interconnection between non-ribosomal activities and the nucleolus (structure and function) still remains an open question. Here, we report a novel mass spectrometry analysis of isolated nucleoli from Arabidopsis thaliana plants using the FANoS (Fluorescence Assisted Nucleolus Sorting) strategy. We identified many ribosome biogenesis factors (RBF) and proteins non-related with ribosome biogenesis, in agreement with the recognized multi-functionality of the nucleolus. Interestingly, we found that 26S proteasome subunits localize in the nucleolus and demonstrated that proteasome activity and nucleolus organization are intimately linked to each other. Proteasome subunits form discrete foci in the disorganized nucleolus of nuc1.2 plants. Nuc1.2 protein extracts display reduced proteasome activity in vitro compared to WT protein extracts. Remarkably, proteasome activity in nuc1.2 is similar to proteasome activity in WT plants treated with proteasome inhibitors (MG132 or ALLN). Finally, we show that MG132 treatment induces disruption of nucleolar structures in WT but not in nuc1.2 plants. Altogether, our data suggest a functional interconnection between nucleolus structure and proteasome activity. PMID:29104584

  6. Essentialism Promotes Children's Inter-ethnic Bias

    Directory of Open Access Journals (Sweden)

    Gil eDiesendruck

    2015-08-01

    Full Text Available The present study investigated the developmental foundation of the relation between social essentialism and attitudes. Forty-eight Jewish Israeli secular 6-year-olds were exposed to either a story emphasizing essentialism about ethnicity, or stories controlling for the salience of ethnicity or essentialism per se. After listening to a story, children’s attitudes were assessed in a drawing and in an IAT task. Compared to the control conditions, children in the ethnic essentialism condition drew a Jewish and an Arab character as farther apart from each other, and the Jewish character with a more positive affect than the Arab character. Moreover, boys in the ethnic essentialism condition manifested a stronger bias in the IAT. These findings reveal an early link between essentialism and inter-group attitudes.

  7. Sedimentation rates in eastern North America reveal strong links between regional climate, depositional environments, and sediment accumulation

    Science.gov (United States)

    Goring, S. J.; McLachlan, J. S.; Jackson, S. T.; Blaauw, M.; Christen, J.; Marlon, J.; Blois, J.; Williams, J. W.

    2011-12-01

    PalEON is a multidisciplinary project that combines paleo and modern ecological data with state-of-the-art statistical and modelling tools to examine the interactions between climate, fire and vegetation during the past two millennia in the northeastern United States. A fundamental challenge for PalEON (and paleo research more broadly) is to improve age modelling to yield more accurate sediment-core chronologies. To address this challenge, we assessed sedimentation rates and their controls for 218 lakes and mires in the northeastern U.S. Sedimentation rates (yr/cm) were calculated from age-depth models, which were obtained from the Neotoma database (www.neotomadb.org) and other contributed pollen records. The age models were recalibrated to IntCal09 and augmented in some cases using biostratigraphic markers (Picea decline, 16 kcal BP - 10.5 kcal BP; Quercus rise, 12 - 9.1 kcal BP; and Alnus decline, 11.5 - 10.6 kcal BP) as described in Blois et al. (2011). Relationships between sedimentation rates and sediment age, site longitude, and depositional environment (lacustrine or mire) are significant but weak. There are clear and significant links between variations in the NGRIP record of δ18O and sedimentation in mires across the PalEON region, but no links to lacustrine sedimentation rates. This result indicates that super-regional climatic control of primary productivity, and thus autochthonic sediment deposition, dominates in mires while deposition in lacustrine basins may be driven primarily by local and regional factors including watershed size, surficial materials,and regional vegetation. The shape of the gamma probability functions that best describe sedimentation rate distributions are calculated and presented here for use as priors in Bayesian age modelling applications such as BACON (Blaauw and Christen, in press). Future applications of this research are also discussed.

  8. Genetic and biochemical analysis reveals linked QTLs determining natural variation for fruit post-harvest water loss in pepper (Capsicum).

    Science.gov (United States)

    Popovsky-Sarid, Sigal; Borovsky, Yelena; Faigenboim, Adi; Parsons, Eugene P; Lohrey, Gregory T; Alkalai-Tuvia, Sharon; Fallik, Elazar; Jenks, Matthew A; Paran, Ilan

    2017-02-01

    Molecular markers linked to QTLs controlling post-harvest fruit water loss in pepper may be utilized to accelerate breeding for improved shelf life and inhibit over-ripening before harvest. Bell pepper (Capsicum annuum L.) is an important vegetable crop world-wide. However, marketing is limited by the relatively short shelf life of the fruit due to water loss and decay that occur during prolonged storage. Towards breeding pepper with reduced fruit post-harvest water loss (PWL), we studied the genetic, physiological and biochemical basis for natural variation of PWL. We performed quantitative trait locus (QTL) mapping of fruit PWL in multiple generations of an interspecific cross of pepper, which resulted in the identification of two linked QTLs on chromosome 10 that control the trait. We further developed near-isogenic lines (NILs) for characterization of the QTL effects. Transcriptome analysis of the NILs allowed the identification of candidate genes associated with fruit PWL-associated traits such as cuticle biosynthesis, cell wall metabolism and fruit ripening. Significant differences in PWL between the NILs in the immature fruit stage, differentially expressed cuticle-associated genes and differences in the content of specific chemical constituents of the fruit cuticle, indicated a likely influence of cuticle composition on the trait. Reduced PWL in the NILs was associated with delayed over-ripening before harvest, low total soluble solids before storage, and reduced fruit softening after storage. Our study enabled a better understanding of the genetic and biological processes controlling natural variation in fruit PWL in pepper. Furthermore, the genetic materials and molecular markers developed in this study may be utilized to breed peppers with improved shelf life and inhibited over-ripening before harvest.

  9. Somatosensory BOLD fMRI reveals close link between salient blood pressure changes and the murine neuromatrix.

    Science.gov (United States)

    Reimann, Henning Matthias; Todiras, Mihail; Hodge, Russ; Huelnhagen, Till; Millward, Jason Michael; Turner, Robert; Seeliger, Erdmann; Bader, Michael; Pohlmann, Andreas; Niendorf, Thoralf

    2018-05-15

    The neuromatrix, or "pain matrix", is a network of cortical brain areas which is activated by noxious as well as salient somatosensory stimulation. This has been studied in mice and humans using blood oxygenation level-dependent (BOLD) fMRI. Here we demonstrate that BOLD effects observed in the murine neuromatrix in response to salient somatosensory stimuli are prone to reflect mean arterial blood pressure (MABP) changes, rather than neural activity. We show that a standard electrostimulus typically used in murine somatosensory fMRI can induce substantial elevations in MABP. Equivalent drug-induced MABP changes - without somatosensory stimulation - evoked BOLD patterns in the neuromatrix strikingly similar to those evoked by electrostimulation. This constitutes a serious caveat for murine fMRI. The regional specificity of these BOLD patterns can be attributed to the co-localization of the neuromatrix with large draining veins. Based on these findings we propose a cardiovascular support mechanism whereby abrupt elevations in MABP provide additional energy supply to the neuromatrix and other essential brain areas in fight-or-flight situations. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Comparative genomic analyses of copper transporters and cuproproteomes reveal evolutionary dynamics of copper utilization and its link to oxygen.

    Directory of Open Access Journals (Sweden)

    Perry G Ridge

    2008-01-01

    Full Text Available Copper is an essential trace element in many organisms and is utilized in all domains of life. It is often used as a cofactor of redox proteins, but is also a toxic metal ion. Intracellular copper must be carefully handled to prevent the formation of reactive oxygen species which pose a threat to DNA, lipids, and proteins. In this work, we examined patterns of copper utilization in prokaryotes by analyzing the occurrence of copper transporters and copper-containing proteins. Many organisms, including those that lack copper-dependent proteins, had copper exporters, likely to protect against copper ions that inadvertently enter the cell. We found that copper use is widespread among prokaryotes, but also identified several phyla that lack cuproproteins. This is in contrast to the use of other trace elements, such as selenium, which shows more scattered and reduced usage, yet larger selenoproteomes. Copper transporters had different patterns of occurrence than cuproproteins, suggesting that the pathways of copper utilization and copper detoxification are independent of each other. We present evidence that organisms living in oxygen-rich environments utilize copper, whereas the majority of anaerobic organisms do not. In addition, among copper users, cuproproteomes of aerobic organisms were larger than those of anaerobic organisms. Prokaryotic cuproproteomes were small and dominated by a single protein, cytochrome c oxidase. The data are consistent with the idea that proteins evolved to utilize copper following the oxygenation of the Earth.

  11. Transcriptional program of ciliated epithelial cells reveals new cilium and centrosome components and links to human disease.

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    Ramona A Hoh

    Full Text Available Defects in the centrosome and cilium are associated with a set of human diseases having diverse phenotypes. To further characterize the components that define the function of these organelles we determined the transcriptional profile of multiciliated tracheal epithelial cells. Cultures of mouse tracheal epithelial cells undergoing differentiation in vitro were derived from mice expressing GFP from the ciliated-cell specific FOXJ1 promoter (FOXJ1:GFP. The transcriptional profile of ciliating GFP+ cells from these cultures was defined at an early and a late time point during differentiation and was refined by subtraction of the profile of the non-ciliated GFP- cells. We identified 649 genes upregulated early, when most cells were forming basal bodies, and 73 genes genes upregulated late, when most cells were fully ciliated. Most, but not all, of known centrosome proteins are transcriptionally upregulated early, particularly Plk4, a master regulator of centriole formation. We found that three genes associated with human disease states, Mdm1, Mlf1, and Dyx1c1, are upregulated during ciliogenesis and localize to centrioles and cilia. This transcriptome for mammalian multiciliated epithelial cells identifies new candidate centrosome and cilia proteins, highlights similarities between components of motile and primary cilia, and identifies new links between cilia proteins and human disease.

  12. The Pseudomonas community in metal-contaminated sediments as revealed by quantitative PCR: a link with metal bioavailability.

    Science.gov (United States)

    Roosa, Stéphanie; Wauven, Corinne Vander; Billon, Gabriel; Matthijs, Sandra; Wattiez, Ruddy; Gillan, David C

    2014-10-01

    Pseudomonas bacteria are ubiquitous Gram-negative and aerobic microorganisms that are known to harbor metal resistance mechanisms such as efflux pumps and intracellular redox enzymes. Specific Pseudomonas bacteria have been quantified in some metal-contaminated environments, but the entire Pseudomonas population has been poorly investigated under these conditions, and the link with metal bioavailability was not previously examined. In the present study, quantitative PCR and cell cultivation were used to monitor and characterize the Pseudomonas population at 4 different sediment sites contaminated with various levels of metals. At the same time, total metals and metal bioavailability (as estimated using an HCl 1 m extraction) were measured. It was found that the total level of Pseudomonas, as determined by qPCR using two different genes (oprI and the 16S rRNA gene), was positively and significantly correlated with total and HCl-extractable Cu, Co, Ni, Pb and Zn, with high correlation coefficients (>0.8). Metal-contaminated sediments featured isolates of the Pseudomonas putida, Pseudomonas fluorescens, Pseudomonas lutea and Pseudomonas aeruginosa groups, with other bacterial genera such as Mycobacterium, Klebsiella and Methylobacterium. It is concluded that Pseudomonas bacteria do proliferate in metal-contaminated sediments, but are still part of a complex community. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  13. Segmental allotetraploidy and allelic interactions in buffelgrass (Pennisetum ciliare (L.) Link syn. Cenchrus ciliaris L.) as revealed by genome mapping.

    Science.gov (United States)

    Jessup, R W; Burson, B L; Burow, O; Wang, Y W; Chang, C; Li, Z; Paterson, A H; Hussey, M A

    2003-04-01

    Linkage analyses increasingly complement cytological and traditional plant breeding techniques by providing valuable information regarding genome organization and transmission genetics of complex polyploid species. This study reports a genome map of buffelgrass (Pennisetum ciliare (L.) Link syn. Cenchrus ciliaris L.). Maternal and paternal maps were constructed with restriction fragment length polymorphisms (RFLPs) segregating in 87 F1 progeny from an intraspecific cross between two heterozygous genotypes. A survey of 862 heterologous cDNAs and gDNAs from across the Poaceae, as well as 443 buffelgrass cDNAs, yielded 100 and 360 polymorphic probes, respectively. The maternal map included 322 RFLPs, 47 linkage groups, and 3464 cM, whereas the paternal map contained 245 RFLPs, 42 linkage groups, and 2757 cM. Approximately 70 to 80% of the buffelgrass genome was covered, and the average marker spacing was 10.8 and 11.3 cM on the respective maps. Preferential pairing was indicated between many linkage groups, which supports cytological reports that buffelgrass is a segmental allotetraploid. More preferential pairing (disomy) was found in the maternal than paternal parent across linkage groups (55 vs. 38%) and loci (48 vs. 15%). Comparison of interval lengths in 15 allelic bridges indicated significantly less meiotic recombination in paternal gametes. Allelic interactions were detected in four regions of the maternal map and were absent in the paternal map.

  14. Analysis of temporal transcription expression profiles reveal links between protein function and developmental stages of Drosophila melanogaster.

    Science.gov (United States)

    Wan, Cen; Lees, Jonathan G; Minneci, Federico; Orengo, Christine A; Jones, David T

    2017-10-01

    Accurate gene or protein function prediction is a key challenge in the post-genome era. Most current methods perform well on molecular function prediction, but struggle to provide useful annotations relating to biological process functions due to the limited power of sequence-based features in that functional domain. In this work, we systematically evaluate the predictive power of temporal transcription expression profiles for protein function prediction in Drosophila melanogaster. Our results show significantly better performance on predicting protein function when transcription expression profile-based features are integrated with sequence-derived features, compared with the sequence-derived features alone. We also observe that the combination of expression-based and sequence-based features leads to further improvement of accuracy on predicting all three domains of gene function. Based on the optimal feature combinations, we then propose a novel multi-classifier-based function prediction method for Drosophila melanogaster proteins, FFPred-fly+. Interpreting our machine learning models also allows us to identify some of the underlying links between biological processes and developmental stages of Drosophila melanogaster.

  15. Analysis of temporal transcription expression profiles reveal links between protein function and developmental stages of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Cen Wan

    2017-10-01

    Full Text Available Accurate gene or protein function prediction is a key challenge in the post-genome era. Most current methods perform well on molecular function prediction, but struggle to provide useful annotations relating to biological process functions due to the limited power of sequence-based features in that functional domain. In this work, we systematically evaluate the predictive power of temporal transcription expression profiles for protein function prediction in Drosophila melanogaster. Our results show significantly better performance on predicting protein function when transcription expression profile-based features are integrated with sequence-derived features, compared with the sequence-derived features alone. We also observe that the combination of expression-based and sequence-based features leads to further improvement of accuracy on predicting all three domains of gene function. Based on the optimal feature combinations, we then propose a novel multi-classifier-based function prediction method for Drosophila melanogaster proteins, FFPred-fly+. Interpreting our machine learning models also allows us to identify some of the underlying links between biological processes and developmental stages of Drosophila melanogaster.

  16. Mechanistic Insight into the Pathology of Polyalanine Expansion Disorders Revealed by a Mouse Model for X Linked Hypopituitarism

    Science.gov (United States)

    Hughes, James; Piltz, Sandra; Rogers, Nicholas; McAninch, Dale; Rowley, Lynn; Thomas, Paul

    2013-01-01

    Polyalanine expansions in transcription factors have been associated with eight distinct congenital human diseases. It is thought that in each case the polyalanine expansion causes misfolding of the protein that abrogates protein function. Misfolded proteins form aggregates when expressed in vitro; however, it is less clear whether aggregation is of relevance to these diseases in vivo. To investigate this issue, we used targeted mutagenesis of embryonic stem (ES) cells to generate mice with a polyalanine expansion mutation in Sox3 (Sox3-26ala) that is associated with X-linked Hypopituitarism (XH) in humans. By investigating both ES cells and chimeric mice, we show that endogenous polyalanine expanded SOX3 does not form protein aggregates in vivo but rather is present at dramatically reduced levels within the nucleus of mutant cells. Importantly, the residual mutant protein of chimeric embryos is able to rescue a block in gastrulation but is not sufficient for normal development of the hypothalamus, a region that is functionally compromised in Sox3 null embryos and individuals with XH. Together, these data provide the first definitive example of a disease-relevant PA mutant protein that is both nuclear and functional, thereby manifesting as a partial loss-of-function allele. PMID:23505376

  17. Functional Roles of Neural Preparatory Processes in a Cued Stroop Task Revealed by Linking Electrophysiology with Behavioral Performance.

    Science.gov (United States)

    Wang, Chao; Ding, Mingzhou; Kluger, Benzi M

    2015-01-01

    performance provides a functional link between neural markers and the cognitive processes they index.

  18. Functional Roles of Neural Preparatory Processes in a Cued Stroop Task Revealed by Linking Electrophysiology with Behavioral Performance.

    Directory of Open Access Journals (Sweden)

    Chao Wang

    performance provides a functional link between neural markers and the cognitive processes they index.

  19. Museum specimen data reveal emergence of a plant disease may be linked to increases in the insect vector population.

    Science.gov (United States)

    Zeilinger, Adam R; Rapacciuolo, Giovanni; Turek, Daniel; Oboyski, Peter T; Almeida, Rodrigo P P; Roderick, George K

    2017-09-01

    The emergence rate of new plant diseases is increasing due to novel introductions, climate change, and changes in vector populations, posing risks to agricultural sustainability. Assessing and managing future disease risks depends on understanding the causes of contemporary and historical emergence events. Since the mid-1990s, potato growers in the western United States, Mexico, and Central America have experienced severe yield loss from Zebra Chip disease and have responded by increasing insecticide use to suppress populations of the insect vector, the potato psyllid, Bactericera cockerelli (Hemiptera: Triozidae). Despite the severe nature of Zebra Chip outbreaks, the causes of emergence remain unknown. We tested the hypotheses that (1) B. cockerelli occupancy has increased over the last century in California and (2) such increases are related to climate change, specifically warmer winters. We compiled a data set of 87,000 museum specimen occurrence records across the order Hemiptera collected between 1900 and 2014. We then analyzed changes in B. cockerelli distribution using a hierarchical occupancy model using changes in background species lists to correct for collecting effort. We found evidence that B. cockerelli occupancy has increased over the last century. However, these changes appear to be unrelated to climate changes, at least at the scale of our analysis. To the extent that species occupancy is related to abundance, our analysis provides the first quantitative support for the hypothesis that B. cockerelli population abundance has increased, but further work is needed to link B. cockerelli population dynamics to Zebra Chip epidemics. Finally, we demonstrate how this historical macro-ecological approach provides a general framework for comparative risk assessment of future pest and insect vector outbreaks. © 2017 by the Ecological Society of America.

  20. A linked lake system beneath Thwaites Glacier, West Antarctica reveals an efficient mechanism for subglacial water flow.

    Science.gov (United States)

    Smith, B. E.; Gourmelen, N.; Huth, A.; Joughin, I. R.

    2016-12-01

    In this presentation we show the results of a multi-sensor survey of a system of subglacial lakes beneath Thwaites Glacier, West Antarctica. This is the first substantial active (meaning draining or filling on annual time scales) lake system detected under the fast-flowing glaciers of the Amundsen Coast. Altimetry data show that over the 2013 calendar year, four subglacial lakes drained, essentially simultaneously, with the bulk of the drainage taking place over the course the first three months of the year. The largest of the lakes appears to have drained around 3.7 km3 of water, with the others each draining less than 1 km3. The high-resolution radar surveys conducted in this area by NASA's IceBridge program allow detailed analysis of the subglacial hydrologic potential, which shows that the potential map in this area is characterized by small closed basins that should not, under the common assumption that water flow is directed down the gradient of the hydropotential, allow long-range water transport. The lakes' discharge demonstrates that, at least in some cases, water can flow out of apparently closed hydropotential basins. Combining a basal-flow routing map with a map of basal melt production suggests that the largest drainage event could recur as often as every 22 years, provided that overflow or leakage of mapped hydropotential basins allows melt water transport to refill the lake. An analysis of ice-surface speed records both around the lakes and at the Thwaites grounding line shows small changes in ice speed, but none clearly associated with the drainage event, suggesting that, at least in this area where subglacial melt is abundant, the addition of further water to the subglacial hydrologic system need not have any significant effect on ice flow. It is likely that the main impact of the lake system on the glacier is that as an efficient mechanism to remove meltwater from the system, it drains water that would otherwise flow through less efficient

  1. Linked functional network abnormalities during intrinsic and extrinsic activity in schizophrenia as revealed by a data-fusion approach.

    Science.gov (United States)

    Hashimoto, Ryu-Ichiro; Itahashi, Takashi; Okada, Rieko; Hasegawa, Sayaka; Tani, Masayuki; Kato, Nobumasa; Mimura, Masaru

    2018-01-01

    Abnormalities in functional brain networks in schizophrenia have been studied by examining intrinsic and extrinsic brain activity under various experimental paradigms. However, the identified patterns of abnormal functional connectivity (FC) vary depending on the adopted paradigms. Thus, it is unclear whether and how these patterns are inter-related. In order to assess relationships between abnormal patterns of FC during intrinsic activity and those during extrinsic activity, we adopted a data-fusion approach and applied partial least square (PLS) analyses to FC datasets from 25 patients with chronic schizophrenia and 25 age- and sex-matched normal controls. For the input to the PLS analyses, we generated a pair of FC maps during the resting state (REST) and the auditory deviance response (ADR) from each participant using the common seed region in the left middle temporal gyrus, which is a focus of activity associated with auditory verbal hallucinations (AVHs). PLS correlation (PLS-C) analysis revealed that patients with schizophrenia have significantly lower loadings of a component containing positive FCs in default-mode network regions during REST and a component containing positive FCs in the auditory and attention-related networks during ADR. Specifically, loadings of the REST component were significantly correlated with the severities of positive symptoms and AVH in patients with schizophrenia. The co-occurrence of such altered FC patterns during REST and ADR was replicated using PLS regression, wherein FC patterns during REST are modeled to predict patterns during ADR. These findings provide an integrative understanding of altered FCs during intrinsic and extrinsic activity underlying core schizophrenia symptoms.

  2. Linking social and spatial networks to viral community phylogenetics reveals subtype-specific transmission dynamics in African lions.

    Science.gov (United States)

    Fountain-Jones, Nicholas M; Packer, Craig; Troyer, Jennifer L; VanderWaal, Kimberly; Robinson, Stacie; Jacquot, Maude; Craft, Meggan E

    2017-10-01

    Heterogeneity within pathogen species can have important consequences for how pathogens transmit across landscapes; however, discerning different transmission routes is challenging. Here, we apply both phylodynamic and phylogenetic community ecology techniques to examine the consequences of pathogen heterogeneity on transmission by assessing subtype-specific transmission pathways in a social carnivore. We use comprehensive social and spatial network data to examine transmission pathways for three subtypes of feline immunodeficiency virus (FIV Ple ) in African lions (Panthera leo) at multiple scales in the Serengeti National Park, Tanzania. We used FIV Ple molecular data to examine the role of social organization and lion density in shaping transmission pathways and tested to what extent vertical (i.e., father- and/or mother-offspring relationships) or horizontal (between unrelated individuals) transmission underpinned these patterns for each subtype. Using the same data, we constructed subtype-specific FIV Ple co-occurrence networks and assessed what combination of social networks, spatial networks or co-infection best structured the FIV Ple network. While social organization (i.e., pride) was an important component of FIV Ple transmission pathways at all scales, we find that FIV Ple subtypes exhibited different transmission pathways at within- and between-pride scales. A combination of social and spatial networks, coupled with consideration of subtype co-infection, was likely to be important for FIV Ple transmission for the two major subtypes, but the relative contribution of each factor was strongly subtype-specific. Our study provides evidence that pathogen heterogeneity is important in understanding pathogen transmission, which could have consequences for how endemic pathogens are managed. Furthermore, we demonstrate that community phylogenetic ecology coupled with phylodynamic techniques can reveal insights into the differential evolutionary pressures acting

  3. Heterogeneity revealed through meta-analysis might link geographical differences with nasopharyngeal carcinoma incidence in Han Chinese populations

    International Nuclear Information System (INIS)

    Su, Wen-Hui; Chiu, Chi-Cking; Yao Shugart, Yin

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is an epithelial malignancy highly prevalent in southern China, and incidence rates among Han Chinese people vary according to geographic region. Recently, three independent genome-wide association studies (GWASs) confirmed that HLA-A is the main risk gene for NPC. However, the results of studies conducted in regions with dissimilar incidence rates contradicted the claims that HLA-A is the sole risk gene and that the association of rs29232 is independent of the HLA-A effect in the chromosome 6p21.3 region. We performed a meta-analysis, selecting five single-nucleotide polymorphisms (SNPs) in chromosome 6p21.3 mapped in three published GWASs and four case–control studies. The studies involved 8994 patients with NPC and 11,157 healthy controls, all of whom were Han Chinese. The rs2517713 SNP located downstream of HLA-A was significantly associated with NPC (P = 1.08 × 10 −91 , odds ratio [OR] = 0.58, 95 % confidence interval [CI] = 0.55–0.61). The rs29232 SNP exhibited a moderate level of heterogeneity (I 2 = 47 %) that disappeared (I 2 = 0 %) after stratification by moderate- and high-incidence NPC regions. Our results suggested that the HLA-A gene is strongly associated with NPC risk. In addition, the heterogeneity revealed by the meta-analysis of rs29232 might be associated with regional differences in NPC incidence among Han Chinese people. The higher OR of rs29232 and the fact that rs29232 was independent of the HLA-A effect in the moderate-incidence population suggested that rs29232 might have greater relevance to NPC incidence in a moderate-incidence population than in a high-incidence population. The online version of this article (doi:10.1186/s12885-015-1607-0) contains supplementary material, which is available to authorized users

  4. Ty1-copia elements reveal diverse insertion sites linked to polymorphisms among flax (Linum usitatissimum L.) accessions.

    Science.gov (United States)

    Galindo-González, Leonardo; Mhiri, Corinne; Grandbastien, Marie-Angèle; Deyholos, Michael K

    2016-12-07

    Initial characterization of the flax genome showed that Ty1-copia retrotransposons are abundant, with several members being recently inserted, and in close association with genes. Recent insertions indicate a potential for ongoing transpositional activity that can create genomic diversity among accessions, cultivars or varieties. The polymorphisms generated constitute a good source of molecular markers that may be associated with phenotype if the insertions alter gene activity. Flax, where accessions are bred mainly for seed nutritional properties or for fibers, constitutes a good model for studying the relationship of transpositional activity with diversification and breeding. In this study, we estimated copy number and used a type of transposon display known as Sequence-Specific Amplification Polymorphisms (SSAPs), to characterize six families of Ty1-copia elements across 14 flax accessions. Polymorphic insertion sites were sequenced to find insertions that could potentially alter gene expression, and a preliminary test was performed with selected genes bearing transposable element (TE) insertions. Quantification of six families of Ty1-copia elements indicated different abundances among TE families and between flax accessions, which suggested diverse transpositional histories. SSAPs showed a high level of polymorphism in most of the evaluated retrotransposon families, with a trend towards higher levels of polymorphism in low-copy number families. Ty1-copia insertion polymorphisms among cultivars allowed a general distinction between oil and fiber types, and between spring and winter types, demonstrating their utility in diversity studies. Characterization of polymorphic insertions revealed an overwhelming association with genes, with insertions disrupting exons, introns or within 1 kb of coding regions. A preliminary test on the potential transcriptional disruption by TEs of four selected genes evaluated in three different tissues, showed one case of significant

  5. Whole blood transcriptional profiling reveals significant down-regulation of human leukocyte antigen class I and II genes in essential thrombocythemia, polycythemia vera and myelofibrosis

    DEFF Research Database (Denmark)

    Skov, Vibe; Riley, Caroline Hasselbalch; Thomassen, Mads

    2013-01-01

    Gene expression profiling studies in the Philadelphia-negative chronic myeloproliferative neoplasms have revealed significant deregulation of several immune and inflammation genes that might be of importance for clonal evolution due to defective tumor immune surveillance. Other mechanisms might b...

  6. Genetic Disruption of the Sh3pxd2a Gene Reveals an Essential Role in Mouse Development and the Existence of a Novel Isoform of Tks5

    OpenAIRE

    Cejudo-Martin, Pilar; Yuen, Angela; Vlahovich, Nicole; Lock, Peter; Courtneidge, Sara A.; Díaz, Begoña

    2014-01-01

    Tks5 is a scaffold protein and Src substrate involved in cell migration and matrix degradation through its essential role in invadosome formation and function. We have previously described that Tks5 is fundamental for zebrafish neural crest cell migration in vivo. In the present study, we sought to investigate the function of Tks5 in mammalian development by analyzing mice mutant for sh3pxd2a, the gene encoding Tks5. Homozygous disruption of the sh3pxd2a gene by gene-trapping in mouse resulte...

  7. Structure–function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination

    Science.gov (United States)

    Zhao, Liang; Ng, Ee Ting; Davidson, Tara-Lynne; Longmuss, Enya; Urschitz, Johann; Elston, Marlee; Moisyadi, Stefan; Bowles, Josephine; Koopman, Peter

    2014-01-01

    The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry’s ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function. PMID:25074915

  8. Structure-function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination.

    Science.gov (United States)

    Zhao, Liang; Ng, Ee Ting; Davidson, Tara-Lynne; Longmuss, Enya; Urschitz, Johann; Elston, Marlee; Moisyadi, Stefan; Bowles, Josephine; Koopman, Peter

    2014-08-12

    The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry's ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function.

  9. 2500 high-quality genomes reveal that the biogeochemical cycles of C, N, S and H are cross-linked by metabolic handoffs in the terrestrial subsurface

    Science.gov (United States)

    Anantharaman, K.; Brown, C. T.; Hug, L. A.; Sharon, I.; Castelle, C. J.; Shelton, A.; Bonet, B.; Probst, A. J.; Thomas, B. C.; Singh, A.; Wilkins, M.; Williams, K. H.; Tringe, S. G.; Beller, H. R.; Brodie, E.; Hubbard, S. S.; Banfield, J. F.

    2015-12-01

    Microorganisms drive the transformations of carbon compounds in the terrestrial subsurface, a key reservoir of carbon on earth, and impact other linked biogeochemical cycles. Our current knowledge of the microbial ecology in this environment is primarily based on 16S rRNA gene sequences that paint a biased picture of microbial community composition and provide no reliable information on microbial metabolism. Consequently, little is known about the identity and metabolic roles of the uncultivated microbial majority in the subsurface. In turn, this lack of understanding of the microbial processes that impact the turnover of carbon in the subsurface has restricted the scope and ability of biogeochemical models to capture key aspects of the carbon cycle. In this study, we used a culture-independent, genome-resolved metagenomic approach to decipher the metabolic capabilities of microorganisms in an aquifer adjacent to the Colorado River, near Rifle, CO, USA. We sequenced groundwater and sediment samples collected across fifteen different geochemical regimes. Sequence assembly, binning and manual curation resulted in the recovery of 2,542 high-quality genomes, 27 of which are complete. These genomes represent 1,300 non-redundant organisms comprising both abundant and rare community members. Phylogenetic analyses involving ribosomal proteins and 16S rRNA genes revealed the presence of up to 34 new phyla that were hitherto unknown. Less than 11% of all genomes belonged to the 4 most commonly represented phyla that constitute 93% of all currently available genomes. Genome-specific analyses of metabolic potential revealed the co-occurrence of important functional traits such as carbon fixation, nitrogen fixation and use of electron donors and electron acceptors. Finally, we predict that multiple organisms are often required to complete redox pathways through a complex network of metabolic handoffs that extensively cross-link subsurface biogeochemical cycles.

  10. Mapping the transcription start points of the Staphylococcus aureus eap, emp, and vwb promoters reveals a conserved octanucleotide sequence that is essential for expression of these genes.

    Science.gov (United States)

    Harraghy, Niamh; Homerova, Dagmar; Herrmann, Mathias; Kormanec, Jan

    2008-01-01

    Mapping the transcription start points of the eap, emp, and vwb promoters revealed a conserved octanucleotide sequence (COS). Deleting this sequence abolished the expression of eap, emp, and vwb. However, electrophoretic mobility shift assays gave no evidence that this sequence was a binding site for SarA or SaeR, known regulators of eap and emp.

  11. VIB1, a link between glucose signaling and carbon catabolite repression, is essential for plant cell wall degradation by Neurospora crassa.

    Directory of Open Access Journals (Sweden)

    Yi Xiong

    2014-08-01

    Full Text Available Filamentous fungi that thrive on plant biomass are the major producers of hydrolytic enzymes used to decompose lignocellulose for biofuel production. Although induction of cellulases is regulated at the transcriptional level, how filamentous fungi sense and signal carbon-limited conditions to coordinate cell metabolism and regulate cellulolytic enzyme production is not well characterized. By screening a transcription factor deletion set in the filamentous fungus Neurospora crassa for mutants unable to grow on cellulosic materials, we identified a role for the transcription factor, VIB1, as essential for cellulose utilization. VIB1 does not directly regulate hydrolytic enzyme gene expression or function in cellulosic inducer signaling/processing, but affects the expression level of an essential regulator of hydrolytic enzyme genes, CLR2. Transcriptional profiling of a Δvib-1 mutant suggests that it has an improper expression of genes functioning in metabolism and energy and a deregulation of carbon catabolite repression (CCR. By characterizing new genes, we demonstrate that the transcription factor, COL26, is critical for intracellular glucose sensing/metabolism and plays a role in CCR by negatively regulating cre-1 expression. Deletion of the major player in CCR, cre-1, or a deletion of col-26, did not rescue the growth of Δvib-1 on cellulose. However, the synergistic effect of the Δcre-1; Δcol-26 mutations circumvented the requirement of VIB1 for cellulase gene expression, enzyme secretion and cellulose deconstruction. Our findings support a function of VIB1 in repressing both glucose signaling and CCR under carbon-limited conditions, thus enabling a proper cellular response for plant biomass deconstruction and utilization.

  12. Does health facility service environment matter for the receipt of essential newborn care? Linking health facility and household survey data in Malawi.

    Science.gov (United States)

    Carvajal-Aguirre, Liliana; Mehra, Vrinda; Amouzou, Agbessi; Khan, Shane M; Vaz, Lara; Guenther, Tanya; Kalino, Maggie; Zaka, Nabila

    2017-12-01

    Health facility service environment is an important factor for newborns survival and well-being in general and in particular in high mortality settings such as Malawi where despite high coverage of essential interventions, neonatal mortality remains high. The aim of this study is to assess whether the quality of the health service environment at birth is associated with quality of care received by the newborn. We used data from the Malawi Millennium Development Goals Endline household survey conducted as part of MICS survey program and Service Provision Assessment Survey carried out in 2014. The analysis is based on 6218 facility births that occurred during the past 2 years. Descriptive statistics, bivariate and multivariate random effect models are used to assess the association of health facility service readiness score for normal deliveries and newborn care with newborns receiving appropriate newborn care, defined for this analysis as receiving 5 out of 6 recommended interventions during the first 2 days after birth. Newborns in districts with top facility service readiness score have 1.5 higher odds of receiving appropriate newborn care (adjusted odds ratio (aOR) = 1.52, 95% confidence interval CI = 1.19-1.95, P  = 0.001), as compared to newborns in districts with a lower facility score after adjusting for potential confounders. Newborns in the Northern region were two times more likely to receive 5 newborn care interventions as compared to newborns in the Southern region (aOR = 2.06, 95% CI = 1.50-2.83, P  < 0.001). Living in urban or rural areas did not have an impact on receiving appropriate newborn care. There is need to increase the level of service readiness across all facilities, so that all newborns irrespective of the health facility, district or region of delivery are able to receive all recommended essential interventions. Investments in health systems in Malawi should concentrate on increasing training and availability of

  13. In-depth comparative analysis of malaria parasite genomes reveals protein-coding genes linked to human disease in Plasmodium falciparum genome.

    Science.gov (United States)

    Liu, Xuewu; Wang, Yuanyuan; Liang, Jiao; Wang, Luojun; Qin, Na; Zhao, Ya; Zhao, Gang

    2018-05-02

    Plasmodium falciparum is the most virulent malaria parasite capable of parasitizing human erythrocytes. The identification of genes related to this capability can enhance our understanding of the molecular mechanisms underlying human malaria and lead to the development of new therapeutic strategies for malaria control. With the availability of several malaria parasite genome sequences, performing computational analysis is now a practical strategy to identify genes contributing to this disease. Here, we developed and used a virtual genome method to assign 33,314 genes from three human malaria parasites, namely, P. falciparum, P. knowlesi and P. vivax, and three rodent malaria parasites, namely, P. berghei, P. chabaudi and P. yoelii, to 4605 clusters. Each cluster consisted of genes whose protein sequences were significantly similar and was considered as a virtual gene. Comparing the enriched values of all clusters in human malaria parasites with those in rodent malaria parasites revealed 115 P. falciparum genes putatively responsible for parasitizing human erythrocytes. These genes are mainly located in the chromosome internal regions and participate in many biological processes, including membrane protein trafficking and thiamine biosynthesis. Meanwhile, 289 P. berghei genes were included in the rodent parasite-enriched clusters. Most are located in subtelomeric regions and encode erythrocyte surface proteins. Comparing cluster values in P. falciparum with those in P. vivax and P. knowlesi revealed 493 candidate genes linked to virulence. Some of them encode proteins present on the erythrocyte surface and participate in cytoadhesion, virulence factor trafficking, or erythrocyte invasion, but many genes with unknown function were also identified. Cerebral malaria is characterized by accumulation of infected erythrocytes at trophozoite stage in brain microvascular. To discover cerebral malaria-related genes, fast Fourier transformation (FFT) was introduced to extract

  14. Structure-Based Mutagenesis of Sulfolobus Turreted Icosahedral Virus B204 Reveals Essential Residues in the Virion-Associated DNA-Packaging ATPase.

    Science.gov (United States)

    Dellas, Nikki; Snyder, Jamie C; Dills, Michael; Nicolay, Sheena J; Kerchner, Keshia M; Brumfield, Susan K; Lawrence, C Martin; Young, Mark J

    2015-12-23

    Sulfolobus turreted icosahedral virus (STIV), an archaeal virus that infects the hyperthermoacidophile Sulfolobus solfataricus, is one of the most well-studied viruses of the domain Archaea. STIV shares structural, morphological, and sequence similarities with viruses from other domains of life, all of which are thought to belong to the same viral lineage. Several of these common features include a conserved coat protein fold, an internal lipid membrane, and a DNA-packaging ATPase. B204 is the ATPase encoded by STIV and is thought to drive packaging of viral DNA during the replication process. Here, we report the crystal structure of B204 along with the biochemical analysis of B204 mutants chosen based on structural information and sequence conservation patterns observed among members of the same viral lineage and the larger FtsK/HerA superfamily to which B204 belongs. Both in vitro ATPase activity assays and transfection assays with mutant forms of B204 confirmed the essentiality of conserved and nonconserved positions. We also have identified two distinct particle morphologies during an STIV infection that differ in the presence or absence of the B204 protein. The biochemical and structural data presented here are not only informative for the STIV replication process but also can be useful in deciphering DNA-packaging mechanisms for other viruses belonging to this lineage. STIV is a virus that infects a host from the domain Archaea that replicates in high-temperature, acidic environments. While STIV has many unique features, there exist several striking similarities between this virus and others that replicate in different environments and infect a broad range of hosts from Bacteria and Eukarya. Aside from structural features shared by viruses from this lineage, there exists a significant level of sequence similarity between the ATPase genes carried by these different viruses; this gene encodes an enzyme thought to provide energy that drives DNA packaging into

  15. Genetic disruption of the sh3pxd2a gene reveals an essential role in mouse development and the existence of a novel isoform of tks5.

    Science.gov (United States)

    Cejudo-Martin, Pilar; Yuen, Angela; Vlahovich, Nicole; Lock, Peter; Courtneidge, Sara A; Díaz, Begoña

    2014-01-01

    Tks5 is a scaffold protein and Src substrate involved in cell migration and matrix degradation through its essential role in invadosome formation and function. We have previously described that Tks5 is fundamental for zebrafish neural crest cell migration in vivo. In the present study, we sought to investigate the function of Tks5 in mammalian development by analyzing mice mutant for sh3pxd2a, the gene encoding Tks5. Homozygous disruption of the sh3pxd2a gene by gene-trapping in mouse resulted in neonatal death and the presence of a complete cleft of the secondary palate. Interestingly, embryonic fibroblasts from homozygous gene-trap sh3pxd2a mice lacked only the highest molecular weight band of the characteristic Tks5 triplet observed in protein extracts, leaving the lower molecular weight bands unaffected. This finding, together with the existence of two human Expressed Sequence Tags lacking the first 5 exons of SH3PXD2A, made us hypothesize about the presence of a second alternative transcription start site located in intron V. We performed 5'RACE on mouse fibroblasts and isolated a new transcript of the sh3pxd2a gene encoding a novel Tks5 isoform, that we named Tks5β. This novel isoform diverges from the long form of Tks5 in that it lacks the PX-domain, which confers affinity for phosphatidylinositol-3,4-bisphosphate. Instead, Tks5β has a short unique amino terminal sequence encoded by the newly discovered exon 6β; this exon includes a start codon located 29 bp from the 5'-end of exon 6. Tks5β mRNA is expressed in MEFs and all mouse adult tissues analyzed. Tks5β is a substrate for the Src tyrosine kinase and its expression is regulated through the proteasome degradation pathway. Together, these findings indicate the essentiality of the larger Tks5 isoform for correct mammalian development and the transcriptional complexity of the sh3pxd2a gene.

  16. Genetic disruption of the sh3pxd2a gene reveals an essential role in mouse development and the existence of a novel isoform of tks5.

    Directory of Open Access Journals (Sweden)

    Pilar Cejudo-Martin

    Full Text Available Tks5 is a scaffold protein and Src substrate involved in cell migration and matrix degradation through its essential role in invadosome formation and function. We have previously described that Tks5 is fundamental for zebrafish neural crest cell migration in vivo. In the present study, we sought to investigate the function of Tks5 in mammalian development by analyzing mice mutant for sh3pxd2a, the gene encoding Tks5. Homozygous disruption of the sh3pxd2a gene by gene-trapping in mouse resulted in neonatal death and the presence of a complete cleft of the secondary palate. Interestingly, embryonic fibroblasts from homozygous gene-trap sh3pxd2a mice lacked only the highest molecular weight band of the characteristic Tks5 triplet observed in protein extracts, leaving the lower molecular weight bands unaffected. This finding, together with the existence of two human Expressed Sequence Tags lacking the first 5 exons of SH3PXD2A, made us hypothesize about the presence of a second alternative transcription start site located in intron V. We performed 5'RACE on mouse fibroblasts and isolated a new transcript of the sh3pxd2a gene encoding a novel Tks5 isoform, that we named Tks5β. This novel isoform diverges from the long form of Tks5 in that it lacks the PX-domain, which confers affinity for phosphatidylinositol-3,4-bisphosphate. Instead, Tks5β has a short unique amino terminal sequence encoded by the newly discovered exon 6β; this exon includes a start codon located 29 bp from the 5'-end of exon 6. Tks5β mRNA is expressed in MEFs and all mouse adult tissues analyzed. Tks5β is a substrate for the Src tyrosine kinase and its expression is regulated through the proteasome degradation pathway. Together, these findings indicate the essentiality of the larger Tks5 isoform for correct mammalian development and the transcriptional complexity of the sh3pxd2a gene.

  17. Zebrafish Models for the Mechanosensory Hair Cell Dysfunction in Usher Syndrome 3 Reveal That Clarin-1 Is an Essential Hair Bundle Protein.

    Science.gov (United States)

    Gopal, Suhasini R; Chen, Daniel H-C; Chou, Shih-Wei; Zang, Jingjing; Neuhauss, Stephan C F; Stepanyan, Ruben; McDermott, Brian M; Alagramam, Kumar N

    2015-07-15

    Usher syndrome type III (USH3) is characterized by progressive loss of hearing and vision, and varying degrees of vestibular dysfunction. It is caused by mutations that affect the human clarin-1 protein (hCLRN1), a member of the tetraspanin protein family. The missense mutation CLRN1(N48K), which affects a conserved N-glycosylation site in hCLRN1, is a common causative USH3 mutation among Ashkenazi Jews. The affected individuals hear at birth but lose that function over time. Here, we developed an animal model system using zebrafish transgenesis and gene targeting to provide an explanation for this phenotype. Immunolabeling demonstrated that Clrn1 localized to the hair cell bundles (hair bundles). The clrn1 mutants generated by zinc finger nucleases displayed aberrant hair bundle morphology with diminished function. Two transgenic zebrafish that express either hCLRN1 or hCLRN1(N48K) in hair cells were produced to examine the subcellular localization patterns of wild-type and mutant human proteins. hCLRN1 localized to the hair bundles similarly to zebrafish Clrn1; in contrast, hCLRN1(N48K) largely mislocalized to the cell body with a small amount reaching the hair bundle. We propose that this small amount of hCLRN1(N48K) in the hair bundle provides clarin-1-mediated function during the early stages of life; however, the presence of hCLRN1(N48K) in the hair bundle diminishes over time because of intracellular degradation of the mutant protein, leading to progressive loss of hair bundle integrity and hair cell function. These findings and genetic tools provide an understanding and path forward to identify therapies to mitigate hearing loss linked to the CLRN1 mutation. Mutations in the clarin-1 gene affect eye and ear function in humans. Individuals with the CLRN1(N48K) mutation are born able to hear but lose that function over time. Here, we develop an animal model system using zebrafish transgenesis and gene targeting to provide an explanation for this phenotype

  18. Studies of UCP2 transgenic and knockout mice reveal that liver UCP2 is not essential for the antiobesity effects of fish oil.

    Science.gov (United States)

    Tsuboyama-Kasaoka, Nobuyo; Sano, Kayo; Shozawa, Chikako; Osaka, Toshimasa; Ezaki, Osamu

    2008-03-01

    Uncoupling protein 2 (UCP2) is a possible target molecule for energy dissipation. Many dietary fats, including safflower oil and lard, induce obesity in C57BL/6 mice, whereas fish oil does not. Fish oil increases UCP2 expression in hepatocytes and may enhance UCP2 activity by activating the UCP2 molecule or altering the lipid bilayer environment. To examine the role of liver UCP2 in obesity, we created transgenic mice that overexpressed human UCP2 in hepatocytes and examined whether UCP2 transgenic mice showed less obesity when fed a high-fat diet (safflower oil or lard). In addition, we examined whether fish oil had antiobesity effects in UCP2 knockout mice. UCP2 transgenic and wild-type mice fed a high-fat diet (safflower oil or lard) developed obesity to a similar degree. UCP2 knockout and wild-type mice fed fish oil had lower rates of obesity than mice fed safflower oil. Remarkably, safflower oil did not induce obesity in female UCP2 knockout mice, an unexpected phenotype for which we presently have no explanation. However, this unexpected effect was not observed in male UCP2 knockout mice or in UCP2 knockout mice fed a high-lard diet. These data indicate that liver UCP2 is not essential for fish oil-induced decreases in body fat.

  19. Structure of a prokaryotic sodium channel pore reveals essential gating elements and an outer ion binding site common to eukaryotic channels.

    Science.gov (United States)

    Shaya, David; Findeisen, Felix; Abderemane-Ali, Fayal; Arrigoni, Cristina; Wong, Stephanie; Nurva, Shailika Reddy; Loussouarn, Gildas; Minor, Daniel L

    2014-01-23

    Voltage-gated sodium channels (NaVs) are central elements of cellular excitation. Notwithstanding advances from recent bacterial NaV (BacNaV) structures, key questions about gating and ion selectivity remain. Here, we present a closed conformation of NaVAe1p, a pore-only BacNaV derived from NaVAe1, a BacNaV from the arsenite oxidizer Alkalilimnicola ehrlichei found in Mono Lake, California, that provides insight into both fundamental properties. The structure reveals a pore domain in which the pore-lining S6 helix connects to a helical cytoplasmic tail. Electrophysiological studies of full-length BacNaVs show that two elements defined by the NaVAe1p structure, an S6 activation gate position and the cytoplasmic tail "neck", are central to BacNaV gating. The structure also reveals the selectivity filter ion entry site, termed the "outer ion" site. Comparison with mammalian voltage-gated calcium channel (CaV) selectivity filters, together with functional studies, shows that this site forms a previously unknown determinant of CaV high-affinity calcium binding. Our findings underscore commonalities between BacNaVs and eukaryotic voltage-gated channels and provide a framework for understanding gating and ion permeation in this superfamily. © 2013. Published by Elsevier Ltd. All rights reserved.

  20. Accounting for eXentricities: analysis of the X chromosome in GWAS reveals X-linked genes implicated in autoimmune diseases.

    Directory of Open Access Journals (Sweden)

    Diana Chang

    Full Text Available Many complex human diseases are highly sexually dimorphic, suggesting a potential contribution of the X chromosome to disease risk. However, the X chromosome has been neglected or incorrectly analyzed in most genome-wide association studies (GWAS. We present tailored analytical methods and software that facilitate X-wide association studies (XWAS, which we further applied to reanalyze data from 16 GWAS of different autoimmune and related diseases (AID. We associated several X-linked genes with disease risk, among which (1 ARHGEF6 is associated with Crohn's disease and replicated in a study of ulcerative colitis, another inflammatory bowel disease (IBD. Indeed, ARHGEF6 interacts with a gastric bacterium that has been implicated in IBD. (2 CENPI is associated with three different AID, which is compelling in light of known associations with AID of autosomal genes encoding centromere proteins, as well as established autosomal evidence of pleiotropy between autoimmune diseases. (3 We replicated a previous association of FOXP3, a transcription factor that regulates T-cell development and function, with vitiligo; and (4 we discovered that C1GALT1C1 exhibits sex-specific effect on disease risk in both IBDs. These and other X-linked genes that we associated with AID tend to be highly expressed in tissues related to immune response, participate in major immune pathways, and display differential gene expression between males and females. Combined, the results demonstrate the importance of the X chromosome in autoimmunity, reveal the potential of extensive XWAS, even based on existing data, and provide the tools and incentive to properly include the X chromosome in future studies.

  1. Functional genomics reveals an essential and specific role for Stat1 in protection of the central nervous system following herpes simplex virus corneal infection.

    Science.gov (United States)

    Pasieka, Tracy Jo; Cilloniz, Cristian; Carter, Victoria S; Rosato, Pamela; Katze, Michael G; Leib, David A

    2011-12-01

    indicated an essential role for normal Stat1-dependent signaling in mediating a nonpathological immune response to viral CNS infection.

  2. A crystal structure of the Dengue virus NS5 protein reveals a novel inter-domain interface essential for protein flexibility and virus replication.

    Directory of Open Access Journals (Sweden)

    Yongqian Zhao

    2015-03-01

    Full Text Available Flavivirus RNA replication occurs within a replication complex (RC that assembles on ER membranes and comprises both non-structural (NS viral proteins and host cofactors. As the largest protein component within the flavivirus RC, NS5 plays key enzymatic roles through its N-terminal methyltransferase (MTase and C-terminal RNA-dependent-RNA polymerase (RdRp domains, and constitutes a major target for antivirals. We determined a crystal structure of the full-length NS5 protein from Dengue virus serotype 3 (DENV3 at a resolution of 2.3 Å in the presence of bound SAH and GTP. Although the overall molecular shape of NS5 from DENV3 resembles that of NS5 from Japanese Encephalitis Virus (JEV, the relative orientation between the MTase and RdRp domains differs between the two structures, providing direct evidence for the existence of a set of discrete stable molecular conformations that may be required for its function. While the inter-domain region is mostly disordered in NS5 from JEV, the NS5 structure from DENV3 reveals a well-ordered linker region comprising a short 310 helix that may act as a swivel. Solution Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS analysis reveals an increased mobility of the thumb subdomain of RdRp in the context of the full length NS5 protein which correlates well with the analysis of the crystallographic temperature factors. Site-directed mutagenesis targeting the mostly polar interface between the MTase and RdRp domains identified several evolutionarily conserved residues that are important for viral replication, suggesting that inter-domain cross-talk in NS5 regulates virus replication. Collectively, a picture for the molecular origin of NS5 flexibility is emerging with profound implications for flavivirus replication and for the development of therapeutics targeting NS5.

  3. Essential Tremor

    Science.gov (United States)

    ... Treatment There is no definitive cure for essential tremor. Symptomatic drug therapy may include propranolol or other beta blockers and primidone, an anticonvulsant drug. Eliminating tremor "triggers" ...

  4. Identifying off-target effects of etomoxir reveals that carnitine palmitoyltransferase I is essential for cancer cell proliferation independent of β-oxidation.

    Directory of Open Access Journals (Sweden)

    Cong-Hui Yao

    2018-03-01

    Full Text Available It has been suggested that some cancer cells rely upon fatty acid oxidation (FAO for energy. Here we show that when FAO was reduced approximately 90% by pharmacological inhibition of carnitine palmitoyltransferase I (CPT1 with low concentrations of etomoxir, the proliferation rate of various cancer cells was unaffected. Efforts to pharmacologically inhibit FAO more than 90% revealed that high concentrations of etomoxir (200 μM have an off-target effect of inhibiting complex I of the electron transport chain. Surprisingly, however, when FAO was reduced further by genetic knockdown of CPT1, the proliferation rate of these same cells decreased nearly 2-fold and could not be restored by acetate or octanoic acid supplementation. Moreover, CPT1 knockdowns had altered mitochondrial morphology and impaired mitochondrial coupling, whereas cells in which CPT1 had been approximately 90% inhibited by etomoxir did not. Lipidomic profiling of mitochondria isolated from CPT1 knockdowns showed depleted concentrations of complex structural and signaling lipids. Additionally, expression of a catalytically dead CPT1 in CPT1 knockdowns did not restore mitochondrial coupling. Taken together, these results suggest that transport of at least some long-chain fatty acids into the mitochondria by CPT1 may be required for anabolic processes that support healthy mitochondrial function and cancer cell proliferation independent of FAO.

  5. Data structures I essentials

    CERN Document Server

    Smolarski, Dennis C

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Data Structures I includes scalar variables, arrays and records, elementary sorting, searching, linked lists, queues, and appendices of binary notation and subprogram parameter passi

  6. A Dense Brown Trout (Salmo trutta) Linkage Map Reveals Recent Chromosomal Rearrangements in the Salmo Genus and the Impact of Selection on Linked Neutral Diversity

    Science.gov (United States)

    Leitwein, Maeva; Guinand, Bruno; Pouzadoux, Juliette; Desmarais, Erick; Berrebi, Patrick; Gagnaire, Pierre-Alexandre

    2017-01-01

    High-density linkage maps are valuable tools for conservation and eco-evolutionary issues. In salmonids, a complex rediploidization process consecutive to an ancient whole genome duplication event makes linkage maps of prime importance for investigating the evolutionary history of chromosome rearrangements. Here, we developed a high-density consensus linkage map for the brown trout (Salmo trutta), a socioeconomically important species heavily impacted by human activities. A total of 3977 ddRAD markers were mapped and ordered in 40 linkage groups using sex- and lineage-averaged recombination distances obtained from two family crosses. Performing map comparison between S. trutta and its sister species, S. salar, revealed extensive chromosomal rearrangements. Strikingly, all of the fusion and fission events that occurred after the S. salar/S. trutta speciation happened in the Atlantic salmon branch, whereas the brown trout remained closer to the ancestral chromosome structure. Using the strongly conserved synteny within chromosome arms, we aligned the brown trout linkage map to the Atlantic salmon genome sequence to estimate the local recombination rate in S. trutta at 3721 loci. A significant positive correlation between recombination rate and within-population nucleotide diversity (π) was found, indicating that selection constrains variation at linked neutral sites in brown trout. This new high-density linkage map provides a useful genomic resource for future aquaculture, conservation, and eco-evolutionary studies in brown trout. PMID:28235829

  7. A Dense Brown Trout (Salmo trutta Linkage Map Reveals Recent Chromosomal Rearrangements in the Salmo Genus and the Impact of Selection on Linked Neutral Diversity

    Directory of Open Access Journals (Sweden)

    Maeva Leitwein

    2017-04-01

    Full Text Available High-density linkage maps are valuable tools for conservation and eco-evolutionary issues. In salmonids, a complex rediploidization process consecutive to an ancient whole genome duplication event makes linkage maps of prime importance for investigating the evolutionary history of chromosome rearrangements. Here, we developed a high-density consensus linkage map for the brown trout (Salmo trutta, a socioeconomically important species heavily impacted by human activities. A total of 3977 ddRAD markers were mapped and ordered in 40 linkage groups using sex- and lineage-averaged recombination distances obtained from two family crosses. Performing map comparison between S. trutta and its sister species, S. salar, revealed extensive chromosomal rearrangements. Strikingly, all of the fusion and fission events that occurred after the S. salar/S. trutta speciation happened in the Atlantic salmon branch, whereas the brown trout remained closer to the ancestral chromosome structure. Using the strongly conserved synteny within chromosome arms, we aligned the brown trout linkage map to the Atlantic salmon genome sequence to estimate the local recombination rate in S. trutta at 3721 loci. A significant positive correlation between recombination rate and within-population nucleotide diversity (π was found, indicating that selection constrains variation at linked neutral sites in brown trout. This new high-density linkage map provides a useful genomic resource for future aquaculture, conservation, and eco-evolutionary studies in brown trout.

  8. 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

  9. KNIME essentials

    CERN Document Server

    Bakos, Gábor

    2013-01-01

    KNIME Essentials is a practical guide aimed at getting the results you want, as quickly as possible.""Knime Essentials"" is written for data analysts looking to quickly get up to speed using the market leader in data processing tools, KNIME. No knowledge of KNIME is required, but we will assume that you have some background in data processing.

  10. Astronomy essentials

    CERN Document Server

    Brass, Charles O

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Astronomy includes the historical perspective of astronomy, sky basics and the celestial coordinate systems, a model and the origin of the solar system, the sun, the planets, Kepler'

  11. A novel whole-bacterial enzyme linked-immunosorbant assay to quantify Chlamydia trachomatis specific antibodies reveals distinct differences between systemic and genital compartments.

    Directory of Open Access Journals (Sweden)

    Hannah L Albritton

    Full Text Available Chlamydia trachomatis (CT is the leading sexually transmitted bacterial infection. The continued global burden of CT infection strongly predicates the need for a vaccine to supplement current chlamydial control programs. The correlates of protection against CT are currently unknown, but they must be carefully defined to guide vaccine design. The localized nature of chlamydial infection in columnar epithelial cells of the genital tract necessitates investigation of immunity at the site of infection. The purpose of this study was to develop a sensitive whole bacterial enzyme-linked immunosorbent assay (ELISA to quantify and compare CT-specific IgG and IgA in sera and genital secretions from CT-infected women. To achieve this, elementary bodies (EBs from two of the most common genital serovars (D and E were attached to poly-L-lysine-coated microtiter plates with glutaraldehyde. EB attachment and integrity were verified by the presence of outer membrane antigens and the absence of bacterial cytoplasmic antigens. EB-specific IgG and IgA standards were developed by pooling sera with high titers of CT-specific antibodies from infected women. Serum, endocervical and vaginal secretions, and endocervical cytobrush specimens from CT-infected women were used to quantify CT-specific IgG and IgA which were then normalized to total IgG and IgA, respectively. Analyses of paired serum and genital samples revealed significantly higher proportions of EB-specific antibodies in genital secretions compared to sera. Cervical and vaginal secretions and cytobrush specimens had similar proportions of EB-specific antibodies, suggesting any one of these genital sampling techniques could be used to quantify CT-specific antibodies when appropriate normalization methodologies are implemented. Overall, these results illustrate the need to investigate genital tract CT antibody responses, and our assay provides a useful quantitative tool to assess natural immunity in defined

  12. Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in Caenorhabditis elegans

    Science.gov (United States)

    Zhang, Xinxing; Jones, Rachel A.; Bruner, Steven D.; Butcher, Rebecca A.

    2016-01-01

    Caenorhabditis elegans secretes ascarosides as pheromones to communicate with other worms and to coordinate the development and behavior of the population. Peroxisomal β-oxidation cycles shorten the side chains of ascaroside precursors to produce the short-chain ascaroside pheromones. Acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, have different side chain-length specificities and enable C. elegans to regulate the production of specific ascaroside pheromones. Here, we determine the crystal structure of the acyl-CoA oxidase 1 (ACOX-1) homodimer and the ACOX-2 homodimer bound to its substrate. Our results provide a molecular basis for the substrate specificities of the acyl-CoA oxidases and reveal why some of these enzymes have a very broad substrate range, whereas others are quite specific. Our results also enable predictions to be made for the roles of uncharacterized acyl-CoA oxidases in C. elegans and in other nematode species. Remarkably, we show that most of the C. elegans acyl-CoA oxidases that participate in ascaroside biosynthesis contain a conserved ATP-binding pocket that lies at the dimer interface, and we identify key residues in this binding pocket. ATP binding induces a structural change that is associated with tighter binding of the FAD cofactor. Mutations that disrupt ATP binding reduce FAD binding and reduce enzyme activity. Thus, ATP may serve as a regulator of acyl-CoA oxidase activity, thereby directly linking ascaroside biosynthesis to ATP concentration and metabolic state. PMID:27551084

  13. Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in Caenorhabditis elegans.

    Science.gov (United States)

    Zhang, Xinxing; Li, Kunhua; Jones, Rachel A; Bruner, Steven D; Butcher, Rebecca A

    2016-09-06

    Caenorhabditis elegans secretes ascarosides as pheromones to communicate with other worms and to coordinate the development and behavior of the population. Peroxisomal β-oxidation cycles shorten the side chains of ascaroside precursors to produce the short-chain ascaroside pheromones. Acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, have different side chain-length specificities and enable C. elegans to regulate the production of specific ascaroside pheromones. Here, we determine the crystal structure of the acyl-CoA oxidase 1 (ACOX-1) homodimer and the ACOX-2 homodimer bound to its substrate. Our results provide a molecular basis for the substrate specificities of the acyl-CoA oxidases and reveal why some of these enzymes have a very broad substrate range, whereas others are quite specific. Our results also enable predictions to be made for the roles of uncharacterized acyl-CoA oxidases in C. elegans and in other nematode species. Remarkably, we show that most of the C. elegans acyl-CoA oxidases that participate in ascaroside biosynthesis contain a conserved ATP-binding pocket that lies at the dimer interface, and we identify key residues in this binding pocket. ATP binding induces a structural change that is associated with tighter binding of the FAD cofactor. Mutations that disrupt ATP binding reduce FAD binding and reduce enzyme activity. Thus, ATP may serve as a regulator of acyl-CoA oxidase activity, thereby directly linking ascaroside biosynthesis to ATP concentration and metabolic state.

  14. Hybridisation-based resequencing of 17 X-linked intellectual disability genes in 135 patients reveals novel mutations in ATRX, SLC6A8 and PQBP1

    NARCIS (Netherlands)

    Jensen, L.R.; Chen, W.; Moser, B.; Lipkowitz, B.; Schroeder, C.; Musante, L.; Tzschach, A.; Kalscheuer, V.M.M.; Meloni, I.; Raynaud, M.; Esch, H. van; Chelly, J.; Brouwer, A.P. de; Hackett, A.; Haar, S. van der; Henn, W.; Gecz, J.; Riess, O.; Bonin, M.; Reinhardt, R.; Ropers, H.H.; Kuss, A.W.

    2011-01-01

    X-linked intellectual disability (XLID), also known as X-linked mental retardation, is a highly genetically heterogeneous condition for which mutations in >90 different genes have been identified. In this study, we used a custom-made sequencing array based on the Affymetrix 50k platform for mutation

  15. Principal States of Dynamic Functional Connectivity Reveal the Link Between Resting-State and Task-State Brain: An fMRI Study.

    Science.gov (United States)

    Cheng, Lin; Zhu, Yang; Sun, Junfeng; Deng, Lifu; He, Naying; Yang, Yang; Ling, Huawei; Ayaz, Hasan; Fu, Yi; Tong, Shanbao

    2018-01-25

    Task-related reorganization of functional connectivity (FC) has been widely investigated. Under classic static FC analysis, brain networks under task and rest have been demonstrated a general similarity. However, brain activity and cognitive process are believed to be dynamic and adaptive. Since static FC inherently ignores the distinct temporal patterns between rest and task, dynamic FC may be more a suitable technique to characterize the brain's dynamic and adaptive activities. In this study, we adopted [Formula: see text]-means clustering to investigate task-related spatiotemporal reorganization of dynamic brain networks and hypothesized that dynamic FC would be able to reveal the link between resting-state and task-state brain organization, including broadly similar spatial patterns but distinct temporal patterns. In order to test this hypothesis, this study examined the dynamic FC in default-mode network (DMN) and motor-related network (MN) using Blood-Oxygenation-Level-Dependent (BOLD)-fMRI data from 26 healthy subjects during rest (REST) and a hand closing-and-opening (HCO) task. Two principal FC states in REST and one principal FC state in HCO were identified. The first principal FC state in REST was found similar to that in HCO, which appeared to represent intrinsic network architecture and validated the broadly similar spatial patterns between REST and HCO. However, the second FC principal state in REST with much shorter "dwell time" implied the transient functional relationship between DMN and MN during REST. In addition, a more frequent shifting between two principal FC states indicated that brain network dynamically maintained a "default mode" in the motor system during REST, whereas the presence of a single principal FC state and reduced FC variability implied a more temporally stable connectivity during HCO, validating the distinct temporal patterns between REST and HCO. Our results further demonstrated that dynamic FC analysis could offer unique

  16. Essential AOP

    DEFF Research Database (Denmark)

    De Fraine, Bruno; Ernst, Erik; Südholt, Mario

    2010-01-01

    Aspect-oriented programming (AOP) has produced interesting language designs, but also ad hoc semantics that needs clarification. We contribute to this clarification with a calculus that models essential AOP, both simpler and more general than existing formalizations. In AOP, advice may intercept...

  17. Highcharts essentials

    CERN Document Server

    Shahid, Bilal

    2014-01-01

    If you are a web developer with a basic knowledge of HTML, CSS, and JavaScript and want to quickly get started with this web charting technology, this is the book for you. This book will also serve as an essential guide to those who have probably used a similar library and are now looking at migrating to Highcharts.

  18. Swift essentials

    CERN Document Server

    Blewitt, Alex

    2014-01-01

    Whether you are a seasoned Objective-C developer or new to the Xcode platform, Swift Essentials will provide you with all you need to know to get started with the language. Prior experience with iOS development is not necessary, but will be helpful to get the most out of the book.

  19. Symmetrical dimer of the human dopamine transporter revealed by cross-linking Cys-306 at the extracellular end of the sixth transmembrane segment.

    Science.gov (United States)

    Hastrup, H; Karlin, A; Javitch, J A

    2001-08-28

    There is evidence both for and against Na(+)- and Cl(-)-dependent neurotransmitter transporters forming oligomers. We found that cross-linking the human dopamine transporter (DAT), which is heterologously expressed in human embryonic kidney 293 cells, either with copper phenanthroline (CuP) or the bifunctional reagent bis-(2-methanethiosulfonatoethyl)amine hydrochloride (bis-EA) increased the apparent molecular mass determined with nonreducing SDS/PAGE from approximately 85 to approximately 195 kDa. After cross-linking, but not before, coexpressed, differentially epitope-tagged DAT molecules, solubilized in Triton X-100, were coimmunoprecipitated. Thus, the 195-kDa complex was a homodimer. Cross-linking of DAT did not affect tyramine uptake. Replacement of Cys-306 with Ala prevented cross-linking. Replacement of all of the non-disulfide-bonded cysteines in the extracellular and membrane domains, except for Cys-306, did not prevent cross-linking. We conclude that the cross-link is between Cys-306 at the extracellular end of TM6 in each of the two DATs. The motif GVXXGVXXA occurs at the intracellular end of TM6 in DAT and is found in a number of other neurotransmitter transporters. This sequence was originally found at the dimerization interface in glycophorin A, and it promotes dimerization in model systems. Mutation of either glycine disrupted DAT expression and function. The intracellular end of TM6, like the extracellular end, is likely to be part of the dimerization interface.

  20. In-Culture Cross-Linking of Bacterial Cells Reveals Large-Scale Dynamic Protein-Protein Interactions at the Peptide Level.

    Science.gov (United States)

    de Jong, Luitzen; de Koning, Edward A; Roseboom, Winfried; Buncherd, Hansuk; Wanner, Martin J; Dapic, Irena; Jansen, Petra J; van Maarseveen, Jan H; Corthals, Garry L; Lewis, Peter J; Hamoen, Leendert W; de Koster, Chris G

    2017-07-07

    Identification of dynamic protein-protein interactions at the peptide level on a proteomic scale is a challenging approach that is still in its infancy. We have developed a system to cross-link cells directly in culture with the special lysine cross-linker bis(succinimidyl)-3-azidomethyl-glutarate (BAMG). We used the Gram-positive model bacterium Bacillus subtilis as an exemplar system. Within 5 min extensive intracellular cross-linking was detected, while intracellular cross-linking in a Gram-negative species, Escherichia coli, was still undetectable after 30 min, in agreement with the low permeability in this organism for lipophilic compounds like BAMG. We were able to identify 82 unique interprotein cross-linked peptides with cross-links occur in assemblies involved in transcription and translation. Several of these interactions are new, and we identified a binding site between the δ and β' subunit of RNA polymerase close to the downstream DNA channel, providing a clue into how δ might regulate promoter selectivity and promote RNA polymerase recycling. Our methodology opens new avenues to investigate the functional dynamic organization of complex protein assemblies involved in bacterial growth. Data are available via ProteomeXchange with identifier PXD006287.

  1. Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca²⁺ signals at key decision points in the life cycle of malaria parasites.

    Directory of Open Access Journals (Sweden)

    Mathieu Brochet

    2014-03-01

    Full Text Available Many critical events in the Plasmodium life cycle rely on the controlled release of Ca²⁺ from intracellular stores to activate stage-specific Ca²⁺-dependent protein kinases. Using the motility of Plasmodium berghei ookinetes as a signalling paradigm, we show that the cyclic guanosine monophosphate (cGMP-dependent protein kinase, PKG, maintains the elevated level of cytosolic Ca²⁺ required for gliding motility. We find that the same PKG-dependent pathway operates upstream of the Ca²⁺ signals that mediate activation of P. berghei gametocytes in the mosquito and egress of Plasmodium falciparum merozoites from infected human erythrocytes. Perturbations of PKG signalling in gliding ookinetes have a marked impact on the phosphoproteome, with a significant enrichment of in vivo regulated sites in multiple pathways including vesicular trafficking and phosphoinositide metabolism. A global analysis of cellular phospholipids demonstrates that in gliding ookinetes PKG controls phosphoinositide biosynthesis, possibly through the subcellular localisation or activity of lipid kinases. Similarly, phosphoinositide metabolism links PKG to egress of P. falciparum merozoites, where inhibition of PKG blocks hydrolysis of phosphatidylinostitol (4,5-bisphosphate. In the face of an increasing complexity of signalling through multiple Ca²⁺ effectors, PKG emerges as a unifying factor to control multiple cellular Ca²⁺ signals essential for malaria parasite development and transmission.

  2. Vertical and interhemispheric links in the stratosphere-mesosphere as revealed by the day-to-day variability of Aura-MLS temperature data

    Directory of Open Access Journals (Sweden)

    X. Xu

    2009-09-01

    Full Text Available The coupling processes in the middle atmosphere have been a subject of intense research activity because of their effects on atmospheric circulation, structure, variability, and the distribution of chemical constituents. In this study, the day-to-day variability of Aura-MLS (Microwave Limb Sounder temperature data are used to reveal the vertical and interhemispheric coupling processes in the stratosphere-mesosphere during four Northern Hemisphere winters (2004/2005–2007/2008. The UKMO (United Kingdom Meteorological Office assimilated data and mesospheric winds from MF (medium frequency radars are also applied to help highlight the coupling processes.

    In this study, a clear vertical link can be seen between the stratosphere and mesosphere during winter months. The coolings and reversals of northward meridional winds in the polar winter mesosphere are often observed in relation to warming events (Sudden Stratospheric Warming, SSW for short and the associated changes in zonal winds in the polar winter stratosphere. An upper-mesospheric cooling usually precedes the beginning of the warming in the stratosphere by 1–2 days.

    Inter-hemispheric coupling has been identified initially by a correlation analysis using the year-to-year monthly zonal mean temperature. Then the correlation analyses are performed based upon the daily zonal mean temperature. From the original time sequences, significant positive (negative correlations are generally found between zonal mean temperatures at the Antarctic summer mesopause and in the Arctic winter stratosphere (mesosphere during northern mid-winters, although these correlations are dominated by the low frequency variability (i.e. the seasonal trend. Using the short-term oscillations (less than 15 days, the statistical result, by looking for the largest magnitude of correlation within a range of time-lags (0 to 10 days; positive lags mean that the Antarctic summer mesopause is lagging, indicates

  3. Vertical and interhemispheric links in the stratosphere-mesosphere as revealed by the day-to-day variability of Aura-MLS temperature data

    Directory of Open Access Journals (Sweden)

    X. Xu

    2009-09-01

    Full Text Available The coupling processes in the middle atmosphere have been a subject of intense research activity because of their effects on atmospheric circulation, structure, variability, and the distribution of chemical constituents. In this study, the day-to-day variability of Aura-MLS (Microwave Limb Sounder temperature data are used to reveal the vertical and interhemispheric coupling processes in the stratosphere-mesosphere during four Northern Hemisphere winters (2004/2005–2007/2008. The UKMO (United Kingdom Meteorological Office assimilated data and mesospheric winds from MF (medium frequency radars are also applied to help highlight the coupling processes. In this study, a clear vertical link can be seen between the stratosphere and mesosphere during winter months. The coolings and reversals of northward meridional winds in the polar winter mesosphere are often observed in relation to warming events (Sudden Stratospheric Warming, SSW for short and the associated changes in zonal winds in the polar winter stratosphere. An upper-mesospheric cooling usually precedes the beginning of the warming in the stratosphere by 1–2 days. Inter-hemispheric coupling has been identified initially by a correlation analysis using the year-to-year monthly zonal mean temperature. Then the correlation analyses are performed based upon the daily zonal mean temperature. From the original time sequences, significant positive (negative correlations are generally found between zonal mean temperatures at the Antarctic summer mesopause and in the Arctic winter stratosphere (mesosphere during northern mid-winters, although these correlations are dominated by the low frequency variability (i.e. the seasonal trend. Using the short-term oscillations (less than 15 days, the statistical result, by looking for the largest magnitude of correlation within a range of time-lags (0 to 10 days; positive lags mean that the Antarctic summer mesopause is lagging, indicates that the temporal

  4. ESSENTIAL DYNAMICS OF PROTEINS

    NARCIS (Netherlands)

    AMADEI, A; LINSSEN, ABM; BERENDSEN, HJC

    1993-01-01

    Analysis of extended molecular dynamics (MD) simulations of lysozyme in vacuo and in aqueous solution reveals that it is possible to separate the configurational space into two subspaces: (1) an ''essential'' subspace containing only a few degrees of freedom in which anharmonic motion occurs that

  5. Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

    DEFF Research Database (Denmark)

    Basse, Astrid L.; Dixen, Karen; Yadav, Rachita

    2015-01-01

    . Conclusions: Using global gene expression profiling of the postnatal BAT to WAT transformation in sheep, we provide novel insight into adipose tissue plasticity in a large mammal, including identification of novel transcriptional components linked to adipose tissue remodeling. Moreover, our data set provides...... NR1H3, MYC, KLF4, ESR1, RELA and BCL6, which were linked to the overall changes in gene expression during the adipose tissue remodeling. Finally, the perirenal adipose tissue expressed both brown and brite/beige adipocyte marker genes at birth, the expression of which changed substantially over time...

  6. Population genetics of Phytophthora infestans in Denmark reveals dominantly clonal populations and specific alleles linked to metalaxyl-M resistance

    DEFF Research Database (Denmark)

    Montes, M. S.; Nielsen, Bent Jørgen; Schmidt, S. G.

    2016-01-01

    population of P. infestans was characterized over the course of the 2013 growing season, as was the population genetic structure, using simple sequence repeat (SSR) genotypes and single nucleotide polymorphism (SNP)-based mitochondrial haplotyping of over 80 isolates. Both mating types A1 and A2 were present...... in most fields, but tests for recombination showed that clonal reproduction dominates in Danish populations. Genotype was not linked to haplotype and no differentiation was observed at the haplotype level, but rather between fields. Resistance phenotypes were linked to specific SSR alleles, demonstrating...

  7. Linux Essentials

    CERN Document Server

    Smith, Roderick W

    2012-01-01

    A unique, full-color introduction to Linux fundamentals Serving as a low-cost, secure alternative to expensive operating systems, Linux is a UNIX-based, open source operating system. Full-color and concise, this beginner's guide takes a learning-by-doing approach to understanding the essentials of Linux. Each chapter begins by clearly identifying what you will learn in the chapter, followed by a straightforward discussion of concepts that leads you right into hands-on tutorials. Chapters conclude with additional exercises and review questions, allowing you to reinforce and measure your underst

  8. Essential SQLAlchemy

    CERN Document Server

    Copeland, Rick

    2008-01-01

    Essential SQLAlchemy introduces a high-level open-source code library that makes it easier for Python programmers to access relational databases such as Oracle, DB2, MySQL, PostgreSQL, and SQLite. SQLAlchemy has become increasingly popular since its release, but it still lacks good offline documentation. This practical book fills the gap, and because a developer wrote it, you get an objective look at SQLAlchemy's tools rather than an advocate's description of all the "cool" features. SQLAlchemy includes both a database server-independent SQL expression language and an object-relational mappe

  9. Prezi essentials

    CERN Document Server

    Sinclair, Domi

    2014-01-01

    If you want to learn Prezi, and specifically design within Prezi, this is the book for you. Perhaps you already know a bit about Prezi but have never used it, or perhaps you have used Prezi before but want to learn how to incorporate your own custom design elements. In either case, this book will get you up and running quickly. It would be helpful to have a bit of familiarity with basic design concepts and the use of Prezi, but prior experience is not essential.

  10. Hybridisation-based resequencing of 17 X-linked intellectual disability genes in 135 patients reveals novel mutations in ATRX, SLC6A8 and PQBP1

    Science.gov (United States)

    Jensen, Lars R; Chen, Wei; Moser, Bettina; Lipkowitz, Bettina; Schroeder, Christopher; Musante, Luciana; Tzschach, Andreas; Kalscheuer, Vera M; Meloni, Ilaria; Raynaud, Martine; van Esch, Hilde; Chelly, Jamel; de Brouwer, Arjan P M; Hackett, Anna; van der Haar, Sigrun; Henn, Wolfram; Gecz, Jozef; Riess, Olaf; Bonin, Michael; Reinhardt, Richard; Ropers, Hans-Hilger; Kuss, Andreas W

    2011-01-01

    X-linked intellectual disability (XLID), also known as X-linked mental retardation, is a highly genetically heterogeneous condition for which mutations in >90 different genes have been identified. In this study, we used a custom-made sequencing array based on the Affymetrix 50k platform for mutation screening in 17 known XLID genes in patients from 135 families and found eight single-nucleotide changes that were absent in controls. For four mutations affecting ATRX (p.1761M>T), PQBP1 (p.155R>X) and SLC6A8 (p.390P>L and p.477S>L), we provide evidence for a functional involvement of these changes in the aetiology of intellectual disability. PMID:21267006

  11. Applicability of a particularly simple model to nonlinear elasticity of slide-ring gels with movable cross-links as revealed by unequal biaxial deformation.

    Science.gov (United States)

    Kondo, Yuuki; Urayama, Kenji; Kidowaki, Masatoshi; Mayumi, Koichi; Takigawa, Toshikazu; Ito, Kohzo

    2014-10-07

    The strain energy density function (F) of the polyrotaxane-based slide-ring (SR) gels with movable cross-links along the network strands is characterized by unequal biaxial stretching which can achieve various types of deformation. The SR gels as prepared without any post-preparation complication exhibit considerably smaller values of the ratio of the stresses (σy/σx) in the stretched (x) and constrained (y) directions in planar extension than classical chemical gels with heterogeneous and nearly homogeneous network structures do. This feature of the SR gels leads to the peculiar characteristic that the strain energy density function (F) has no explicit cross term of strains in different directions, which is in contrast to F with explicit strain cross terms for most chemical gels and elastomers. The biaxial stress-strain data of the SR gels are successfully described by F of the Gent model with only two parameters (small-strain shear modulus and a parameter representing ultimate elongation), which introduces the finite extensibility effect into the neo-Hookean model with no explicit cross term of strain. The biaxial data of the deswollen SR gels examined in previous study, which underwent a considerable reduction in volume from the preparation state, are also well described by the Gent model, which is in contrast to the case of the classical chemical gels that the stress-strain relations before and after large deswelling are not described by a common type of F due to a significant degree of collapse of the network strands in the deswollen state. These intriguing features of nonlinear elasticity of the SR gels originate from a novel function of the slidable cross-links that can maximize the arrangement entropy of cross-linked and non-cross-linked cyclic molecules in the deformed networks.

  12. Essential astrophysics

    CERN Document Server

    Lang, Kenneth R

    2013-01-01

    Essential Astrophysics is a book to learn or teach from, as well as a fundamental reference volume for anyone interested in astronomy and astrophysics. It presents astrophysics from basic principles without requiring any previous study of astronomy or astrophysics. It serves as a comprehensive introductory text, which takes the student through the field of astrophysics in lecture-sized chapters of basic physical principles applied to the cosmos. This one-semester overview will be enjoyed by undergraduate students with an interest in the physical sciences, such as astronomy, chemistry, engineering or physics, as well as by any curious student interested in learning about our celestial science. The mathematics required for understanding the text is on the level of simple algebra, for that is all that is needed to describe the fundamental principles. The text is of sufficient breadth and depth to prepare the interested student for more advanced specialized courses in the future. Astronomical examples are provide...

  13. A genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat.

    Science.gov (United States)

    Xu, Rong; Wang, QuanQiu; Li, Li

    2015-01-01

    Dietary intakes of red meat and fat are established risk factors for both colorectal cancer (CRC) and cardiovascular disease (CVDs). Recent studies have shown a mechanistic link between TMAO, an intestinal microbial metabolite of red meat and fat, and risk of CVDs. Data linking TMAO directly to CRC is, however, lacking. Here, we present an unbiased data-driven network-based systems approach to uncover a potential genetic relationship between TMAO and CRC. We constructed two different epigenetic interaction networks (EINs) using chemical-gene, disease-gene and protein-protein interaction data from multiple large-scale data resources. We developed a network-based ranking algorithm to ascertain TMAO-related diseases from EINs. We systematically analyzed disease categories among TMAO-related diseases at different ranking cutoffs. We then determined which genetic pathways were associated with both TMAO and CRC. We show that CVDs and their major risk factors were ranked highly among TMAO-related diseases, confirming the newly discovered mechanistic link between CVDs and TMAO, and thus validating our algorithms. CRC was ranked highly among TMAO-related disease retrieved from both EINs (top 0.02%, #1 out of 4,372 diseases retrieved based on Mendelian genetics and top 10.9% among 882 diseases based on genome-wide association genetics), providing strong supporting evidence for our hypothesis that TMAO is genetically related to CRC. We have also identified putative genetic pathways that may link TMAO to CRC, which warrants further investigation. Through systematic disease enrichment analysis, we also demonstrated that TMAO is related to metabolic syndromes and cancers in general. Our genome-wide analysis demonstrates that systems approaches to studying the epigenetic interactions among diet, microbiome metabolisms, and disease genetics hold promise for understanding disease pathogenesis. Our results show that TMAO is genetically associated with CRC. This study suggests that

  14. Disease-linked mutations in factor H reveal pivotal role of cofactor activity in self-surface-selective regulation of complement activation.

    Science.gov (United States)

    Kerr, Heather; Wong, Edwin; Makou, Elisavet; Yang, Yi; Marchbank, Kevin; Kavanagh, David; Richards, Anna; Herbert, Andrew P; Barlow, Paul N

    2017-08-11

    Spontaneous activation enables the complement system to respond very rapidly to diverse threats. This activation is efficiently suppressed by complement factor H (CFH) on self-surfaces but not on foreign surfaces. The surface selectivity of CFH, a soluble protein containing 20 complement-control protein modules (CCPs 1-20), may be compromised by disease-linked mutations. However, which of the several functions of CFH drives this self-surface selectivity remains unknown. To address this, we expressed human CFH mutants in Pichia pastoris We found that recombinant I62-CFH (protective against age-related macular degeneration) and V62-CFH functioned equivalently, matching or outperforming plasma-derived CFH, whereas R53H-CFH, linked to atypical hemolytic uremic syndrome (aHUS), was defective in C3bBb decay-accelerating activity (DAA) and factor I cofactor activity (CA). The aHUS-linked CCP 19 mutant D1119G-CFH had virtually no CA on (self-like) sheep erythrocytes ( E S ) but retained DAA. The aHUS-linked CCP 20 mutant S1191L/V1197A-CFH (LA-CFH) had dramatically reduced CA on E S but was less compromised in DAA. D1119G-CFH and LA-CFH both performed poorly at preventing complement-mediated hemolysis of E S PspCN, a CFH-binding Streptococcus pneumoniae protein domain, binds CFH tightly and increases accessibility of CCPs 19 and 20. PspCN did not improve the DAA of any CFH variant on E S Conversely, PspCN boosted the CA, on E S , of I62-CFH, R53H-CFH, and LA-CFH and also enhanced hemolysis protection by I62-CFH and LA-CFH. We conclude that CCPs 19 and 20 are critical for efficient CA on self-surfaces but less important for DAA. Exposing CCPs 19 and 20 with PspCN and thus enhancing CA on self-surfaces may reverse deficiencies of some CFH variants. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Medroxyprogesterone acetate-treated human, primary endometrial epithelial cells reveal unique gene expression signature linked to innate immunity and HIV-1 susceptibility.

    Science.gov (United States)

    Woods, Matthew W; Zahoor, Muhammad Atif; Dizzell, Sara; Verschoor, Chris P; Kaushic, Charu

    2018-01-01

    Medroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, has been linked to increased human immunodeficiency virus (HIV-1) susceptibility. Genital epithelial cells (GECs) form the mucosal lining of the female genital tract (FGT) and provide the first line of protection against HIV-1. The impact of endogenous sex hormones or MPA on the gene expression profile of GECs has not been comprehensively documented. Using microarray analysis, we characterized the transcriptional profile of primary endometrial epithelial cells grown in physiological levels of E2, P4, and MPA. Each hormone treatment altered the gene expression profile of GECs in a unique manner. Interestingly, although MPA is a progestogen, the gene expression profile induced by it was distinct from P4. MPA increased gene expression of genes related to inflammation and cholesterol synthesis linked to innate immunity and HIV-1 susceptibility. The analysis of gene expression profiles provides insights into the effects of sex hormones and MPA on GECs and allows us to posit possible mechanisms of the MPA-mediated increase in HIV-1 acquisition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. A Bioinformatics Analysis Reveals a Group of MocR Bacterial Transcriptional Regulators Linked to a Family of Genes Coding for Membrane Proteins

    Directory of Open Access Journals (Sweden)

    Teresa Milano

    2016-01-01

    Full Text Available The MocR bacterial transcriptional regulators are characterized by an N-terminal domain, 60 residues long on average, possessing the winged-helix-turn-helix (wHTH architecture responsible for DNA recognition and binding, linked to a large C-terminal domain (350 residues on average that is homologous to fold type-I pyridoxal 5′-phosphate (PLP dependent enzymes like aspartate aminotransferase (AAT. These regulators are involved in the expression of genes taking part in several metabolic pathways directly or indirectly connected to PLP chemistry, many of which are still uncharacterized. A bioinformatics analysis is here reported that studied the features of a distinct group of MocR regulators predicted to be functionally linked to a family of homologous genes coding for integral membrane proteins of unknown function. This group occurs mainly in the Actinobacteria and Gammaproteobacteria phyla. An analysis of the multiple sequence alignments of their wHTH and AAT domains suggested the presence of specificity-determining positions (SDPs. Mapping of SDPs onto a homology model of the AAT domain hinted at possible structural/functional roles in effector recognition. Likewise, SDPs in wHTH domain suggested the basis of specificity of Transcription Factor Binding Site recognition. The results reported represent a framework for rational design of experiments and for bioinformatics analysis of other MocR subgroups.

  17. A modified anthrax toxin-based enzyme-linked immunospot assay reveals robust T cell responses in symptomatic and asymptomatic Ebola virus exposed individuals.

    Science.gov (United States)

    Herrera, Bobby Brooke; Hamel, Donald J; Oshun, Philip; Akinsola, Rolake; Akanmu, Alani S; Chang, Charlotte A; Eromon, Philomena; Folarin, Onikepe; Adeyemi, Kayode T; Happi, Christian T; Lu, Yichen; Ogunsola, Folasade; Kanki, Phyllis J

    2018-05-01

    Ebola virus (EBOV) caused more than 11,000 deaths during the 2013-2016 epidemic in West Africa without approved vaccines or immunotherapeutics. Despite its high lethality in some individuals, EBOV infection can produce little to no symptoms in others. A better understanding of the immune responses in individuals who experienced minimally symptomatic and asymptomatic infection could aid the development of more effective vaccines and antivirals against EBOV and related filoviruses. Between August and November 2017, blood samples were collected from 19 study participants in Lagos, Nigeria, including 3 Ebola virus disease (EVD) survivors, 10 individuals with documented close contact with symptomatic EVD patients, and 6 control healthcare workers for a cross-sectional serosurvey and T cell analysis. The Lagos samples, as well as archived serum collected from healthy individuals living in surrounding areas of the 1976 Democratic Republic of Congo (DRC) epidemic, were tested for EBOV IgG using commercial enzyme-linked immunosorbent assays (ELISAs) and Western blots. We detected antibodies in 3 out of 3 Lagos survivors and identified 2 seropositive individuals not known to have ever been infected. Of the DRC samples tested, we detected antibodies in 9 out of 71 (12.7%). To characterize the T cell responses in the Lagos samples, we developed an anthrax toxin-based enzyme-linked immunospot (ELISPOT) assay. The seropositive asymptomatic individuals had T cell responses against EBOV nucleoprotein, matrix protein, and glycoprotein 1 that were stronger in magnitude compared to the survivors. Our data provide further evidence of EBOV exposure in individuals without EVD-like illness and, for the first time, demonstrate that these individuals have T cell responses that are stronger in magnitude compared to severe cases. These findings suggest that T cell immunity may protect against severe EVD, which has important implications for vaccine development.

  18. Model Studies of the Histidine-Tyrosine Cross-Link in Cytochrome c Oxidase Reveal the Flexible Substituent Effect of the Imidazole Moiety

    Science.gov (United States)

    Pratt, Derek A.; Pesavento, Russell P.; van der Donk, Wilfred A.

    2010-01-01

    Experimental and theoretical studies were carried out to interrogate the effect of an imidazole substituent in each of the ortho, meta, and para positions on the pKa, E°, and O–H BDE of phenol. The results reveal that imidazole substitution lowers the pKa of phenol and increases the E° of phenoxide due to its σ-electron withdrawing ability (σp− = +0.21, σm− = +0.45) but decreases the O–H BDE and E° of phenol due to its σ-electron-donating ability (σp+ = −0.45). PMID:15957934

  19. Pupil Dilation and EEG Alpha Frequency Band Power Reveal Load on Executive Functions for Link-Selection Processes during Text Reading.

    Directory of Open Access Journals (Sweden)

    Christian Scharinger

    Full Text Available Executive working memory functions play a central role in reading comprehension. In the present research we were interested in additional load imposed on executive functions by link-selection processes during computer-based reading. For obtaining process measures, we used a methodology of concurrent electroencephalographic (EEG and eye-tracking data recording that allowed us to compare epochs of pure text reading with epochs of hyperlink-like selection processes in an online reading situation. Furthermore, this methodology allowed us to directly compare the two physiological load-measures EEG alpha frequency band power and pupil dilation. We observed increased load on executive functions during hyperlink-like selection processes on both measures in terms of decreased alpha frequency band power and increased pupil dilation. Surprisingly however, the two measures did not correlate. Two additional experiments were conducted that excluded potential perceptual, motor, or structural confounds. In sum, EEG alpha frequency band power and pupil dilation both turned out to be sensitive measures for increased load during hyperlink-like selection processes in online text reading.

  20. Targeted inactivation of integrin-linked kinase in hair follicle stem cells reveals an important modulatory role in skin repair after injury.

    Science.gov (United States)

    Nakrieko, Kerry-Ann; Rudkouskaya, Alena; Irvine, Timothy S; D'Souza, Sudhir J A; Dagnino, Lina

    2011-07-15

    Integrin-linked kinase (ILK) is key for normal epidermal morphogenesis, but little is known about its role in hair follicle stem cells and epidermal regeneration. Hair follicle stem cells are important contributors to newly formed epidermis following injury. We inactivated the Ilk gene in the keratin 15--expressing stem cell population of the mouse hair follicle bulge. Loss of ILK expression in these cells resulted in impaired cutaneous wound healing, with substantially decreased wound closure rates. ILK-deficient stem cells produced very few descendants that moved toward the epidermal surface and into the advancing epithelium that covers the wound. Furthermore, those few mutant cells that homed in the regenerated epidermis exhibited a reduced residence time. Paradoxically, ILK-deficient bulge stem cells responded to anagen growth signals and contributed to newly regenerated hair follicles during this phase of hair follicle growth. Thus ILK plays an important modulatory role in the normal contribution of hair follicle stem cell progeny to the regenerating epidermis following injury.

  1. Targeting allergen to FcgammaRI reveals a novel T(H)2 regulatory pathway linked to thymic stromal lymphopoietin receptor.

    Science.gov (United States)

    Hulse, Kathryn E; Reefer, Amanda J; Engelhard, Victor H; Patrie, James T; Ziegler, Steven F; Chapman, Martin D; Woodfolk, Judith A

    2010-01-01

    The molecule H22-Fel d 1, which targets cat allergen to FcgammaRI on dendritic cells (DCs), has the potential to treat cat allergy because of its T-cell modulatory properties. We sought to investigate whether the T-cell response induced by H22-Fel d 1 is altered in the presence of the T(H)2-promoting cytokine thymic stromal lymphopoietin (TSLP). Studies were performed in subjects with cat allergy with and without atopic dermatitis. Monocyte-derived DCs were primed with H22-Fel d 1 in the presence or absence of TSLP, and the resulting T-cell cytokine repertoire was analyzed by flow cytometry. The capacity for H22-Fel d 1 to modulate TSLP receptor expression on DCs was examined by flow cytometry in the presence or absence of inhibitors of Fc receptor signaling molecules. Surprisingly, TSLP alone was a weak inducer of T(H)2 responses irrespective of atopic status; however, DCs coprimed with TSLP and H22-Fel d 1 selectively and synergistically amplified T(H)2 responses in highly atopic subjects. This effect was OX40 ligand independent, pointing to an unconventional TSLP-mediated pathway. Expression of TSLP receptor was upregulated on atopic DCs primed with H22-Fel d 1 through a pathway regulated by FcgammaRI-associated signaling components, including src-related tyrosine kinases and Syk, as well as the downstream molecule phosphoinositide 3-kinase. Inhibition of TSLP receptor upregulation triggered by H22-Fel d 1 blocked TSLP-mediated T(H)2 responses. Discovery of a novel T(H)2 regulatory pathway linking FcgammaRI signaling to TSLP receptor upregulation and consequent TSLP-mediated effects questions the validity of receptor-targeted allergen vaccines. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  2. A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD.

    Science.gov (United States)

    Davidsen, Peter K; Herbert, John M; Antczak, Philipp; Clarke, Kim; Ferrer, Elisabet; Peinado, Victor I; Gonzalez, Constancio; Roca, Josep; Egginton, Stuart; Barberá, Joan A; Falciani, Francesco

    2014-01-01

    CXCL10 and CXCL9 are promising candidate inflammatory signals linked to the regulation of central metabolism genes in skeletal muscles. On a methodological level, our work also shows that a system level analysis of animal models of diseases can be very effective to generate clinically relevant hypothesis.

  3. Synergetic Use of Principal Component Analysis Applied to Normed Physicochemical Measurements and GC × GC-MS to Reveal the Stabilization Effect of Selected Essential Oils on Heated Rapeseed Oil.

    Science.gov (United States)

    Sghaier, Lilia; Cordella, Christophe B Y; Rutledge, Douglas N; Lefèvre, Fanny; Watiez, Mickaël; Breton, Sylvie; Sassiat, Patrick; Thiebaut, Didier; Vial, Jérôme

    2017-06-01

    Lipid oxidation leads to the formation of volatile compounds and very often to off-flavors. In the case of the heating of rapeseed oil, unpleasant odors, characterized as a fishy odor, are emitted. In this study, 2 different essential oils (coriander and nutmeg essential oils) were added to refined rapeseed oil as odor masking agents. The aim of this work was to determine a potential antioxidant effect of these essential oils on the thermal stability of rapeseed oil subject to heating cycles between room temperature and 180 °C. For this purpose, normed determinations of different parameters (peroxide value, anisidine value, and the content of total polar compounds, free fatty acids and tocopherols) were carried out to examine the differences between pure and degraded oil. No significant difference was observed between pure rapeseed oil and rapeseed oil with essential oils for each parameter separately. However, a stabilizing effect of the essential oils, with a higher effect for the nutmeg essential oil was highlighted by principal component analysis applied on physicochemical dataset. Moreover, the analysis of the volatile compounds performed by GC × GC showed a substantial loss of the volatile compounds of the essential oils from the first heating cycle. © 2017 Institute of Food Technologists®.

  4. Genome-wide analysis of the phosphoinositide kinome from two ciliates reveals novel evolutionary links for phosphoinositide kinases in eukaryotic cells.

    Directory of Open Access Journals (Sweden)

    George Leondaritis

    Full Text Available BACKGROUND: The complexity of phosphoinositide signaling in higher eukaryotes is partly due to expansion of specific families and types of phosphoinositide kinases (PIKs that can generate all phosphoinositides via multiple routes. This is particularly evident in the PI3Ks and PIPKs, and it is considered an evolutionary trait associated with metazoan diversification. Yet, there are limited comprehensive studies on the PIK repertoire of free living unicellular organisms. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a genome-wide analysis of putative PIK genes in two free living ciliated cells, Tetrahymena and Paramecium. The Tetrahymena thermophila and Paramecium tetraurelia genomes were probed with representative kinases from all families and types. Putative homologs were verified by EST, microarray and deep RNA sequencing database searches and further characterized for domain structure, catalytic efficiency, expression patterns and phylogenetic relationships. In total, we identified and characterized 22 genes in the Tetrahymena thermophila genome and 62 highly homologues genes in Paramecium tetraurelia suggesting a tight evolutionary conservation in the ciliate lineage. Comparison to the kinome of fungi reveals a significant expansion of PIK genes in ciliates. CONCLUSIONS/SIGNIFICANCE: Our study highlights four important aspects concerning ciliate and other unicellular PIKs. First, ciliate-specific expansion of PI4KIII-like genes. Second, presence of class I PI3Ks which, at least in Tetrahymena, are associated with a metazoan-type machinery for PIP3 signaling. Third, expansion of divergent PIPK enzymes such as the recently described type IV transmembrane PIPKs. Fourth, presence of possible type II PIPKs and presumably inactive PIKs (hence, pseudo-PIKs not previously described. Taken together, our results provide a solid framework for future investigation of the roles of PIKs in ciliates and indicate that novel functions and novel regulatory

  5. Functional MRI examination of empathy for pain in people with schizophrenia reveals abnormal activation related to cognitive perspective-taking but typical activation linked to affective sharing

    Science.gov (United States)

    Vistoli, Damien; Lavoie, Marie-Audrey; Sutliff, Stephanie; Jackson, Philip L.; Achim, Amélie M.

    2017-01-01

    Background Schizophrenia is associated with important disturbances in empathy that are related to everyday functioning. Empathy is classically defined as including affective (sharing others’ emotions) and cognitive (taking others’ cognitive perspectives) processes. In healthy individuals, studies on empathy for pain revealed specific brain systems associated with these sets of processes, notably the anterior middle cingulate (aMCC) and anterior insula (AI) for affective sharing and the bilateral temporoparietal junction (TPJ) for the cognitive processes, but the integrity of these systems in patients with schizophrenia remains uncertain. Methods Patients with schizophrenia and healthy controls performed a pain empathy task while undergoing fMRI scanning. Participants observed pictures of hands in either painful or nonpainful situations and rated the level of pain while imagining either themselves (self) or an unknown person (other) in these situations. Results We included 27 patients with schizophrenia and 21 healthy controls in our analyses. For the pain versus no pain contrast, patients showed overall typical activation patterns in the aMCC and AI, with only a small part of the aMCC showing reduced activation compared with controls. For the other versus self contrast, patients showed an abnormal modulation of activation in the TPJ bilaterally (extending to the posterior superior temporal sulcus, referred to as the TPJ/pSTS). Limitations The design included an unnecessary manipulation of the visual perspective that reduced the number of trials for analysis. The sample size may not account for the heterogeneity of schizophrenia. Conclusion People with schizophrenia showed relatively intact brain activation when observing others’ pain, but showed abnormalities when asked to take the cognitive perspectives of others. PMID:28556774

  6. Increased sensitivity of transforming growth factor (TGF) beta 1 null cells to alkylating agents reveals a novel link between TGFbeta signaling and O(6)-methylguanine methyltransferase promoter hypermethylation.

    Science.gov (United States)

    Yamada, H; Vijayachandra, K; Penner, C; Glick, A

    2001-06-01

    Inactivation of the transforming growth factor beta (TGFbeta)-signaling pathway and gene silencing through hypermethylation of promoter CpG islands are two frequent alterations in human and experimental cancers. Here we report that nonneoplastic TGFbeta1-/- keratinocyte cell lines exhibit increased sensitivity to cell killing by alkylating agents, and this is due to lack of expression of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT). In TGFbeta1-/- but not TGFbeta1+/- cell lines, the CpG dinucleotides in the MGMT promoter are hypermethylated, as measured by restriction enzyme analysis and methylation specific polymerase chain reaction. In one unstable TGFbeta1+/- cell line, loss of the wild type TGFbeta1 allele correlates with the appearance of methylation in the MGMT promoter. Bisulfite sequencing shows that in the KO3 TGFbeta1-/- cell line nearly all of the 28 CpG sites in the MGMT promoter 475 base pairs upstream of the start site of transcription are methylated, whereas most are unmethylated in the H1 TGFbeta1+/- line. Treatment of the TGFbeta1-/- cell lines with 5-azacytidine causes reexpression of MGMT mRNA and demethylation of CpG islands in the promoter. Analysis of the time course of methylation using methylation-specific polymerase chain reaction shows a lack of methylation in primary TGFbeta1-/- keratinocytes and increasing methylation with passage number of immortalized clones. Subcloning of early passage clones reveals a remarkable heterogeneity and instability of the methylation state in the TGFbeta1-/- keratinocytes. Thus, the TGFbeta1-/- genotype does not directly regulate MGMT methylation but predisposes cells to immortalization-associated MGMT hypermethylation.

  7. Transcriptional analysis of abdominal fat in genetically fat and lean chickens reveals adipokines, lipogenic genes and a link between hemostasis and leanness

    Science.gov (United States)

    2013-01-01

    Background This descriptive study of the abdominal fat transcriptome takes advantage of two experimental lines of meat-type chickens (Gallus domesticus), which were selected over seven generations for a large difference in abdominal (visceral) fatness. At the age of selection (9 wk), the fat line (FL) and lean line (LL) chickens exhibit a 2.5-fold difference in abdominal fat weight, while their feed intake and body weight are similar. These unique avian models were originally created to unravel genetic and endocrine regulation of adiposity and lipogenesis in meat-type chickens. The Del-Mar 14K Chicken Integrated Systems microarray was used for a time-course analysis of gene expression in abdominal fat of FL and LL chickens during juvenile development (1–11 weeks of age). Results Microarray analysis of abdominal fat in FL and LL chickens revealed 131 differentially expressed (DE) genes (FDR≤0.05) as the main effect of genotype, 254 DE genes as an interaction of age and genotype and 3,195 DE genes (FDR≤0.01) as the main effect of age. The most notable discoveries in the abdominal fat transcriptome were higher expression of many genes involved in blood coagulation in the LL and up-regulation of numerous adipogenic and lipogenic genes in FL chickens. Many of these DE genes belong to pathways controlling the synthesis, metabolism and transport of lipids or endocrine signaling pathways activated by adipokines, retinoid and thyroid hormones. Conclusions The present study provides a dynamic view of differential gene transcription in abdominal fat of chickens genetically selected for fatness (FL) or leanness (LL). Remarkably, the LL chickens over-express a large number of hemostatic genes that could be involved in proteolytic processing of adipokines and endocrine factors, which contribute to their higher lipolysis and export of stored lipids. Some of these changes are already present at 1 week of age before the divergence in fatness. In contrast, the FL chickens have

  8. Cooperative protein structural dynamics of homodimeric hemoglobin linked to water cluster at subunit interface revealed by time-resolved X-ray solution scattering

    Directory of Open Access Journals (Sweden)

    Jong Goo Kim

    2016-03-01

    Full Text Available Homodimeric hemoglobin (HbI consisting of two subunits is a good model system for investigating the allosteric structural transition as it exhibits cooperativity in ligand binding. In this work, as an effort to extend our previous study on wild-type and F97Y mutant HbI, we investigate structural dynamics of a mutant HbI in solution to examine the role of well-organized interfacial water cluster, which has been known to mediate intersubunit communication in HbI. In the T72V mutant of HbI, the interfacial water cluster in the T state is perturbed due to the lack of Thr72, resulting in two less interfacial water molecules than in wild-type HbI. By performing picosecond time-resolved X-ray solution scattering experiment and kinetic analysis on the T72V mutant, we identify three structurally distinct intermediates (I1, I2, and I3 and show that the kinetics of the T72V mutant are well described by the same kinetic model used for wild-type and F97Y HbI, which involves biphasic kinetics, geminate recombination, and bimolecular CO recombination. The optimized kinetic model shows that the R-T transition and bimolecular CO recombination are faster in the T72V mutant than in the wild type. From structural analysis using species-associated difference scattering curves for the intermediates, we find that the T-like deoxy I3 intermediate in solution has a different structure from deoxy HbI in crystal. In addition, we extract detailed structural parameters of the intermediates such as E-F distance, intersubunit rotation angle, and heme-heme distance. By comparing the structures of protein intermediates in wild-type HbI and the T72V mutant, we reveal how the perturbation in the interfacial water cluster affects the kinetics and structures of reaction intermediates of HbI.

  9. Human immunodeficiency virus type 1 enhancer-binding protein 3 is essential for the expression of asparagine-linked glycosylation 2 in the regulation of osteoblast and chondrocyte differentiation.

    Science.gov (United States)

    Imamura, Katsuyuki; Maeda, Shingo; Kawamura, Ichiro; Matsuyama, Kanehiro; Shinohara, Naohiro; Yahiro, Yuhei; Nagano, Satoshi; Setoguchi, Takao; Yokouchi, Masahiro; Ishidou, Yasuhiro; Komiya, Setsuro

    2014-04-04

    Human immunodeficiency virus type 1 enhancer-binding protein 3 (Hivep3) suppresses osteoblast differentiation by inducing proteasomal degradation of the osteogenesis master regulator Runx2. In this study, we tested the possibility of cooperation of Hivep1, Hivep2, and Hivep3 in osteoblast and/or chondrocyte differentiation. Microarray analyses with ST-2 bone stroma cells demonstrated that expression of any known osteochondrogenesis-related genes was not commonly affected by the three Hivep siRNAs. Only Hivep3 siRNA promoted osteoblast differentiation in ST-2 cells, whereas all three siRNAs cooperatively suppressed differentiation in ATDC5 chondrocytes. We further used microarray analysis to identify genes commonly down-regulated in both MC3T3-E1 osteoblasts and ST-2 cells upon knockdown of Hivep3 and identified asparagine-linked glycosylation 2 (Alg2), which encodes a mannosyltransferase residing on the endoplasmic reticulum. The Hivep3 siRNA-mediated promotion of osteoblast differentiation was negated by forced Alg2 expression. Alg2 suppressed osteoblast differentiation and bone formation in cultured calvarial bone. Alg2 was immunoprecipitated with Runx2, whereas the combined transfection of Runx2 and Alg2 interfered with Runx2 nuclear localization, which resulted in suppression of Runx2 activity. Chondrocyte differentiation was promoted by Hivep3 overexpression, in concert with increased expression of Creb3l2, whose gene product is the endoplasmic reticulum stress transducer crucial for chondrogenesis. Alg2 silencing suppressed Creb3l2 expression and chondrogenesis of ATDC5 cells, whereas infection of Alg2-expressing virus promoted chondrocyte maturation in cultured cartilage rudiments. Thus, Alg2, as a downstream mediator of Hivep3, suppresses osteogenesis, whereas it promotes chondrogenesis. To our knowledge, this study is the first to link a mannosyltransferase gene to osteochondrogenesis.

  10. Pinus Roxburghii essential oil anticancer activity and chemical composition evaluation.

    Science.gov (United States)

    Sajid, Arfaa; Manzoor, Qaisar; Iqbal, Munawar; Tyagi, Amit Kumar; Sarfraz, Raja Adil; Sajid, Anam

    2018-01-01

    The present study was conducted to appraise the anticancer activity of Pinus roxburghii essential oil along with chemical composition evaluation. MTT assay revealed cytotoxicity induction in colon, leukemia, multiple myeloma, pancreatic, head and neck and lung cancer cells exposed to essential oil. Cancer cell death was also observed through live/dead cell viability assay and FACS analysis. Apoptosis induced by essential oil was confirmed by cleavage of PARP and caspase-3 that suppressed the colony-forming ability of tumor cells and 50 % inhibition occurred at a dose of 25 μg/mL. Moreover, essential oil inhibited the activation of inflammatory transcription factor NF-κB and inhibited expression of NF-κB regulated gene products linked to cell survival (survivin, c-FLIP, Bcl-2, Bcl-xL, c-Myc, c-IAP2), proliferation (Cyclin D1) and metastasis (MMP-9). P. roxburghii essential oil has considerable anticancer activity and could be used as anticancer agent, which needs further investigation to identify and purify the bioactive compounds followed by in vivo studies.

  11. MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors

    Science.gov (United States)

    Firacative, Carolina; Roe, Chandler C.; Malik, Richard; Ferreira-Paim, Kennio; Escandón, Patricia; Sykes, Jane E.; Castañón-Olivares, Laura Rocío; Contreras-Peres, Cudberto; Samayoa, Blanca; Sorrell, Tania C.; Castañeda, Elizabeth; Lockhart, Shawn R.; Engelthaler, David M.; Meyer, Wieland

    2016-01-01

    The emerging pathogen Cryptococcus gattii causes life-threatening disease in immunocompetent and immunocompromised hosts. Of the four major molecular types (VGI-VGIV), the molecular type VGIII has recently emerged as cause of disease in otherwise healthy individuals, prompting a need to investigate its population genetic structure to understand if there are potential genotype-dependent characteristics in its epidemiology, environmental niche(s), host range and clinical features of disease. Multilocus sequence typing (MLST) of 122 clinical, environmental and veterinary C. gattii VGIII isolates from Australia, Colombia, Guatemala, Mexico, New Zealand, Paraguay, USA and Venezuela, and whole genome sequencing (WGS) of 60 isolates representing all established MLST types identified four divergent sub-populations. The majority of the isolates belong to two main clades, corresponding either to serotype B or C, indicating an ongoing species evolution. Both major clades included clinical, environmental and veterinary isolates. The C. gattii VGIII population was genetically highly diverse, with minor differences between countries, isolation source, serotype and mating type. Little to no recombination was found between the two major groups, serotype B and C, at the whole and mitochondrial genome level. C. gattii VGIII is widespread in the Americas, with sporadic cases occurring elsewhere, WGS revealed Mexico and USA as a likely origin of the serotype B VGIII population and Colombia as a possible origin of the serotype C VGIII population. Serotype B isolates are more virulent than serotype C isolates in a murine model of infection, causing predominantly pulmonary cryptococcosis. No specific link between genotype and virulence was observed. Antifungal susceptibility testing against six antifungal drugs revealed that serotype B isolates are more susceptible to azoles than serotype C isolates, highlighting the importance of strain typing to guide effective treatment to improve the

  12. Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump's activity

    Directory of Open Access Journals (Sweden)

    T.I. Omotayo

    2015-04-01

    Full Text Available The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe2+-mediated in vitro oxidative stress model. The results show that Fe2+ inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe2+ inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe2+ may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe2+ and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump.

  13. Integrative Analyses of miRNA-mRNA Interactions Reveal let-7b, miR-128 and MAPK Pathway Involvement in Muscle Mass Loss in Sex-Linked Dwarf Chickens

    Science.gov (United States)

    Luo, Wen; Lin, Shumao; Li, Guihuan; Nie, Qinghua; Zhang, Xiquan

    2016-01-01

    The sex-linked dwarf (SLD) chicken is an ideal model system for understanding growth hormone (GH)-action and growth hormone receptor (GHR) function because of its recessive mutation in the GHR gene. Skeletal muscle mass is reduced in the SLD chicken with a smaller muscle fiber diameter. Our previous study has presented the mRNA and miRNA expression profiles of the SLD chicken and normal chicken between embryo day 14 and seven weeks of age. However, the molecular mechanism of GHR-deficient induced muscle mass loss is still unclear, and the key molecules and pathways underlying the GHR-deficient induced muscle mass loss also remain to be illustrated. Here, by functional network analysis of the differentially expressed miRNAs and mRNAs between the SLD and normal chickens, we revealed that let-7b, miR-128 and the MAPK pathway might play key roles in the GHR-deficient induced muscle mass loss, and that the reduced cell division and growth are potential cellular processes during the SLD chicken skeletal muscle development. Additionally, we also found some genes and miRNAs involved in chicken skeletal muscle development, through the MAPK, PI3K-Akt, Wnt and Insulin signaling pathways. This study provides new insights into the molecular mechanism underlying muscle mass loss in the SLD chickens, and some regulatory networks that are crucial for chicken skeletal muscle development. PMID:26927061

  14. First report on an X-linked hypohidrotic ectodermal dysplasia family with X chromosome inversion: Breakpoint mapping reveals the pathogenic mechanism and preimplantation genetics diagnosis achieves an unaffected birth.

    Science.gov (United States)

    Wu, Tonghua; Yin, Biao; Zhu, Yuanchang; Li, Guangui; Ye, Lijun; Liang, Desheng; Zeng, Yong

    2017-12-01

    To investigate the etiology of X-linked hypohidrotic ectodermal dysplasia (XLHED) in a family with an inversion of the X chromosome [inv(X)(p21q13)] and to achieve a healthy birth following preimplantation genetic diagnosis (PGD). Next generation sequencing (NGS) and Sanger sequencing analysis were carried out to define the inversion breakpoint. Multiple displacement amplification, amplification of breakpoint junction fragments, Sanger sequencing of exon 1 of ED1, haplotyping of informative short tandem repeat markers and gender determination were performed for PGD. NGS data of the proband sample revealed that the size of the possible inverted fragment was over 42Mb, spanning from position 26, 814, 206 to position 69, 231, 915 on the X chromosome. The breakpoints were confirmed by Sanger sequencing. A total of 5 blastocyst embryos underwent trophectoderm biopsy. Two embryos were diagnosed as carriers and three were unaffected. Two unaffected blastocysts were transferred and a singleton pregnancy was achieved. Following confirmation by prenatal diagnosis, a healthy baby was delivered. This is the first report of an XLHED family with inv(X). ED1 is disrupted by the X chromosome inversion in this XLHED family and embryos with the X chromosomal abnormality can be accurately identified by means of PGD. Copyright © 2017. Published by Elsevier B.V.

  15. In-Depth Temporal Transcriptome Profiling Reveals a Crucial Developmental Switch with Roles for RNA Processing and Organelle Metabolism That Are Essential for Germination in Arabidopsis1[W][OA

    Science.gov (United States)

    Narsai, Reena; Law, Simon R.; Carrie, Chris; Xu, Lin; Whelan, James

    2011-01-01

    Germination represents a rapid transition from dormancy to a high level of metabolic activity. In-depth transcriptomic profiling at 10 time points in Arabidopsis (Arabidopsis thaliana), including fresh seed, ripened seed, during stratification, germination, and postgermination per se, revealed specific temporal expression patterns that to our knowledge have not previously been identified. Over 10,000 transcripts were differentially expressed during cold stratification, with subequal numbers up-regulated as down-regulated, revealing an active period in preparing seeds for germination, where transcription and RNA degradation both play important roles in regulating the molecular sequence of events. A previously unidentified transient expression pattern was observed for a group of genes, whereby a significant rise in expression was observed at the end of stratification and significantly lower expression was observed 6 h later. These genes were further defined as germination specific, as they were most highly expressed at this time in germination, in comparison with all developmental tissues in the AtGenExpress data set. Functional analysis of these genes using genetic inactivation revealed that they displayed a significant enrichment for embryo-defective or -arrested phenotype. This group was enriched in genes encoding mitochondrial and nuclear RNA-processing proteins, including more than 45% of all pentatricopeptide domain-containing proteins expressed during germination. The presence of mitochondrial DNA replication factors and RNA-processing functions in this germination-specific subset represents the earliest events in organelle biogenesis, preceding any changes associated with energy metabolism. Green fluorescent protein analysis also confirmed organellar localization for 65 proteins, largely showing germination-specific expression. These results suggest that mitochondrial biogenesis involves a two-step process to produce energetically active organelles: an

  16. Treatment of Essential Tremor

    Science.gov (United States)

    ... for PATIENTS and their FAMILIES TREATMENT OF ESSENTIAL TREMOR This fact sheet is provided to help you understand which therapies help treat essential tremor. Neurologists from the American Academy of Neurology are ...

  17. Operative Links

    DEFF Research Database (Denmark)

    Wistoft, Karen; Højlund, Holger

    2012-01-01

    educational goals, learning content, or value clarification. Health pedagogy is often a matter of retrospective rationalization rather than the starting point of planning. Health and risk behaviour approaches override health educational approaches. Conclusions: Operational links between health education......, health professionalism, and management strategies pose the foremost challenge. Operational links indicates cooperative levels that facilitate a creative and innovative effort across traditional professional boundaries. It is proposed that such links are supported by network structures, shared semantics...

  18. Structure and expression of GSL1 and GSL2 genes encoding gibberellin stimulated-like proteins in diploid and highly heterozygous tetraploid potato reveals their highly conserved and essential status.

    Science.gov (United States)

    Meiyalaghan, Sathiyamoorthy; Thomson, Susan J; Fiers, Mark W E J; Barrell, Philippa J; Latimer, Julie M; Mohan, Sara; Jones, E Eirian; Conner, Anthony J; Jacobs, Jeanne M E

    2014-01-02

    -down expression of GSL1 and GSL2, coupled with the rare incidence of SNPs in these genes, suggests an essential role for this gene family. These features are consistent with the GSL protein family playing a role in several aspects of plant development in addition to plant defence against biotic stresses.

  19. Volatile constituents of essential oils of Eleocharis pauciflora (Light ...

    African Journals Online (AJOL)

    The investigation of the volatile compounds of essential oils of Eleocharis pauciflora (Light) Link and Eleocharis uniglumis (Link) J.A. Shultes by gas chromatography/mass spectrometry (GC/MS) led to the identification of 20 and 23 compounds, respectively. The presented essential oils were characterized by the abundance ...

  20. Electric circuits essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electric Circuits I includes units, notation, resistive circuits, experimental laws, transient circuits, network theorems, techniques of circuit analysis, sinusoidal analysis, polyph

  1. Calculus III essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Calculus III includes vector analysis, real valued functions, partial differentiation, multiple integrations, vector fields, and infinite series.

  2. Statistics I essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Statistics I covers include frequency distributions, numerical methods of describing data, measures of variability, parameters of distributions, probability theory, and distributions.

  3. Pre-calculus essentials

    CERN Document Server

    Woodward, Ernest

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Pre-Calculus reviews sets, numbers, operations and properties, coordinate geometry, fundamental algebraic topics, solving equations and inequalities, functions, trigonometry, exponents

  4. Transport phenomena II essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Transport Phenomena II covers forced convention, temperature distribution, free convection, diffusitivity and the mechanism of mass transfer, convective mass transfer, concentration

  5. Differential equations I essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Differential Equations I covers first- and second-order equations, series solutions, higher-order linear equations, and the Laplace transform.

  6. Heat transfer II essentials

    CERN Document Server

    REA, The Editors of

    1988-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Heat Transfer II reviews correlations for forced convection, free convection, heat exchangers, radiation heat transfer, and boiling and condensation.

  7. Numerical analysis II essentials

    CERN Document Server

    REA, The Editors of; Staff of Research Education Association

    1989-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Numerical Analysis II covers simultaneous linear systems and matrix methods, differential equations, Fourier transformations, partial differential equations, and Monte Carlo methods.

  8. Algebra & trigonometry II essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Algebra & Trigonometry II includes logarithms, sequences and series, permutations, combinations and probability, vectors, matrices, determinants and systems of equations, mathematica

  9. Modern algebra essentials

    CERN Document Server

    Lutfiyya, Lutfi A

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Modern Algebra includes set theory, operations, relations, basic properties of the integers, group theory, and ring theory.

  10. Business statistics I essentials

    CERN Document Server

    Clark, Louise

    2014-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Business Statistics I includes descriptive statistics, introduction to probability, probability distributions, sampling and sampling distributions, interval estimation, and hypothesis t

  11. Computer science I essentials

    CERN Document Server

    Raus, Randall

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Computer Science I includes fundamental computer concepts, number representations, Boolean algebra, switching circuits, and computer architecture.

  12. Essential Bacillus subtilis genes

    DEFF Research Database (Denmark)

    Kobayashi, K.; Ehrlich, S.D.; Albertini, A.

    2003-01-01

    To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...... predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related...... to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from...

  13. "Essential Principles of Economics:" A Hypermedia Textbook.

    Science.gov (United States)

    McCain, Roger A.

    2000-01-01

    Discusses an electronic textbook called "Essential Principles of Economics." Explains that economic concepts are found by following links from the table of contents, while each chapter includes both expository information and interactive material including online multiple-choice drill questions. States that the textbook is a "work…

  14. Operative Links

    DEFF Research Database (Denmark)

    Wistoft, Karen; Højlund, Holger

    2012-01-01

    and have been the object of great expectations concerning the ability to incorporate health concerns into every welfare area through health promotion strategies. The paper draws on results and analyses of a collective research project funded by the Danish National Research Council and carried out...... links' that indicate cooperative levels which facilitate a creative and innovative effort in disease prevention and health promotion targeted at children and adolescents - across traditional professional boundaries. It is proposed that such links are supported by network structures, shared semantics...

  15. Physics I essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Physics I includes vectors and scalars, one-dimensional motion, plane motion, dynamics of a particle, work and energy, conservation of energy, dynamics of systems of particles, rotation

  16. Electronics II essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electronics II covers operational amplifiers, feedback and frequency compensation of OP amps, multivibrators, logic gates and families, Boolean algebra, registers, counters, arithmet

  17. Thermodynamics I essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Thermodynamics I includes review of properties and states of a pure substance, work and heat, energy and the first law of thermodynamics, entropy and the second law of thermodynamics

  18. C programming language essentials

    CERN Document Server

    Ackermann, Ernest C

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. C Programming Language discusses fundamental notions, data types and objects, expressions, statements, declarations, function and program structure, the preprocessor, and the standar

  19. Electronics I essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electronics I covers fundamentals of semiconductor devices, junction diodes, bipolar junction transistors, power supplies, multitransistor circuits, small signals, low-frequency anal

  20. Thermodynamics II essentials

    CERN Document Server

    REA, The Editors of

    2013-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Thermodynamics II includes review of thermodynamic relations, power and refrigeration cycles, mixtures and solutions, chemical reactions, chemical equilibrium, and flow through nozzl

  1. Group theory I essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Group Theory I includes sets and mapping, groupoids and semi-groups, groups, isomorphisms and homomorphisms, cyclic groups, the Sylow theorems, and finite p-groups.

  2. Boolean algebra essentials

    CERN Document Server

    Solomon, Alan D

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Boolean Algebra includes set theory, sentential calculus, fundamental ideas of Boolean algebras, lattices, rings and Boolean algebras, the structure of a Boolean algebra, and Boolean

  3. Laplace transforms essentials

    CERN Document Server

    Shafii-Mousavi, Morteza

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Laplace Transforms includes the Laplace transform, the inverse Laplace transform, special functions and properties, applications to ordinary linear differential equations, Fourier tr

  4. Physical chemistry II essentials

    CERN Document Server

    REA, The Editors of

    1992-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Physical Chemistry II includes reaction mechanisms, theoretical approaches to chemical kinetics, gravitational work, electrical and magnetic work, surface work, kinetic theory, collisional and transport properties of gases, statistical mechanics, matter and waves, quantum mechanics, and rotations and vibrations of atoms and molecules.

  5. Statistics II essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Statistics II discusses sampling theory, statistical inference, independent and dependent variables, correlation theory, experimental design, count data, chi-square test, and time se

  6. Algebra & trigonometry I essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Algebra & Trigonometry I includes sets and set operations, number systems and fundamental algebraic laws and operations, exponents and radicals, polynomials and rational expressions, eq

  7. Geometry I essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Geometry I includes methods of proof, points, lines, planes, angles, congruent angles and line segments, triangles, parallelism, quadrilaterals, geometric inequalities, and geometric

  8. Transport phenomena I essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Transport Phenomena I includes viscosity, flow of Newtonian fluids, velocity distribution in laminar flow, velocity distributions with more than one independent variable, thermal con

  9. Data structures II essentials

    CERN Document Server

    Smolarski, Dennis C

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Data Structures II includes sets, trees, advanced sorting, elementary graph theory, hashing, memory management and garbage collection, and appendices on recursion vs. iteration, alge

  10. Computer science II essentials

    CERN Document Server

    Raus, Randall

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Computer Science II includes organization of a computer, memory and input/output, coding, data structures, and program development. Also included is an overview of the most commonly

  11. Set theory essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Set Theory includes elementary logic, sets, relations, functions, denumerable and non-denumerable sets, cardinal numbers, Cantor's theorem, axiom of choice, and order relations.

  12. Linked data and user interaction

    CERN Document Server

    Cervone, H Frank

    2015-01-01

    This collection of research papers provides extensive information on deploying services, concepts, and approaches for using open linked data from libraries and other cultural heritage institutions. With a special emphasis on how libraries and other cultural heritage institutions can create effective end user interfaces using open, linked data or other datasets. These papers are essential reading for any one interesting in user interface design or the semantic web.

  13. Scandinavian links

    DEFF Research Database (Denmark)

    Matthiessen, Christian Wichmann; Knowles, Richard D.

    2014-01-01

    are impressive mega structures spanning international waterways. These waterways between the Baltic Sea and the North Sea have played major roles in history. The length of each of the crossings are around 20 km. The fixed links closes gaps between the Scandinavian and European motorway and rail networks...

  14. Roitt's essential immunology

    National Research Council Canada - National Science Library

    Delves, Peter J; Roitt, Ivan M

    2011-01-01

    ... of the immune system, the hallmark easy-reading style of Roitt's Essential Immunology clearly explains the key principles needed by medical and health sciences students, from the basis of immunity to clinical applications...

  15. Benign Essential Blepharospasm

    Science.gov (United States)

    ... the same for many years; and, in rare cases, improve spontaneously. Clinical Trials Throughout the U.S. and Worldwide NINDS Clinical Trials Related ... Definition Benign essential blepharospasm (BEB) is a progressive neurological ...

  16. Marketingmanagement : De essentie

    NARCIS (Netherlands)

    Kotler, P.J.; Keller, K.; Robben, H.S.J.

    2007-01-01

    'Marketingmanagement, de essentie' biedt een volledige introductie in modern marketingmanagement. De nieuwste concepten en onderzoeksresultaten komen aan bod. Zo wordt veel aandacht besteed aan holistische marketing en is de impact van technologische ontwikkelingen op hedendaagse marketing in deze

  17. Marketing management : De essentie

    NARCIS (Netherlands)

    Kotler, P.J.; Keller, K.; Robben, H.S.J.

    2010-01-01

    'Marketingmanagement, de essentie' biedt een volledige introductie in modern marketingmanagement. De nieuwste concepten en onderzoeksresultaten komen aan bod. Zo wordt veel aandacht besteed aan holistische marketing en is de impact van technologische ontwikkelingen op hedendaagse marketing in deze

  18. Essential software architecture

    CERN Document Server

    Gorton, Ian

    2011-01-01

    Job titles like ""Technical Architect"" and ""Chief Architect"" nowadays abound in software industry, yet many people suspect that ""architecture"" is one of the most overused and least understood terms in professional software development. Gorton's book tries to resolve this dilemma. It concisely describes the essential elements of knowledge and key skills required to be a software architect. The explanations encompass the essentials of architecture thinking, practices, and supporting technologies. They range from a general understanding of structure and quality attributes through technical i

  19. Python essential reference

    CERN Document Server

    Beazley, David M

    2009-01-01

    Python Essential Reference is the definitive reference guide to the Python programming language — the one authoritative handbook that reliably untangles and explains both the core Python language and the most essential parts of the Python library. Designed for the professional programmer, the book is concise, to the point, and highly accessible. It also includes detailed information on the Python library and many advanced subjects that is not available in either the official Python documentation or any other single reference source. Thoroughly updated to reflect the significant new programming language features and library modules that have been introduced in Python 2.6 and Python 3, the fourth edition of Python Essential Reference is the definitive guide for programmers who need to modernize existing Python code or who are planning an eventual migration to Python 3. Programmers starting a new Python project will find detailed coverage of contemporary Python programming idioms.

  20. Essential travel medicine

    CERN Document Server

    Zuckerman, Jane N; Leggat, Peter

    2015-01-01

    This 1st edition of Essential Travel Medicine provides an excellent concise introduction to the specialty of Travel Medicine. This core text will enable health care practitioners particularly those new to the clinical practice of Travel Medicine, to gain a fundamental understanding of the diverse and complex issues which can potentially affect the health of the many millions of people who undertake international travel. Jane N Zuckerman is joined by Gary W Brunette from CDC and Peter A Leggat from Australia as Editors. Leading international specialists in their fields have contributed authoritative chapters reflecting current knowledge to facilitate best clinical practice in the different aspects of travel medicine. The aim of Essential Travel Medicine is to provide a comprehensive guide to Travel Medicine as well as a fundamental knowledge base to support international undergraduate and postgraduate specialty training programmes in the discipline of Travel Medicine. The 1st edition of Essential Travel ...

  1. Physics Essentials For Dummies

    CERN Document Server

    Holzner, Steven

    2010-01-01

    For students who just need to know the vital concepts of physics, whether as a refresher, for exam prep, or as a reference, Physics Essentials For Dummies is a must-have guide. Free of ramp-up and ancillary material, Physics Essentials For Dummies contains content focused on key topics only. It provides discrete explanations of critical concepts taught in an introductory physics course, from force and motion to momentum and kinetics. This guide is also a perfect reference for parents who need to review critical physics concepts as they help high school students with homework assignments, as we

  2. Essentials of Computational Electromagnetics

    CERN Document Server

    Sheng, Xin-Qing

    2012-01-01

    Essentials of Computational Electromagnetics provides an in-depth introduction of the three main full-wave numerical methods in computational electromagnetics (CEM); namely, the method of moment (MoM), the finite element method (FEM), and the finite-difference time-domain (FDTD) method. Numerous monographs can be found addressing one of the above three methods. However, few give a broad general overview of essentials embodied in these methods, or were published too early to include recent advances. Furthermore, many existing monographs only present the final numerical results without specifyin

  3. Essential Palatal Myoclonus

    Directory of Open Access Journals (Sweden)

    Bhuwan Raj Pandey

    2017-06-01

    Full Text Available Introduction: Palatal myoclonus is a rare condition presenting with clicking sound in ear or muscle tremor in pharynx. There are two varieties: essential and symptomatic. Various treatment options exists ranging from watchful observation to botulinum toxin injection. We have not found any reported case of palatal myoclonus from our country. Here we present a case of essential palatal myoclonus managed with clonazepam. Case report: A young female presented in Ear Nose and Throat clinic with complain of auditory click and spontaneous rhythmic movement of throat muscles for eight months. On examination, there was involuntary, rhythmic contraction of bilateral soft-palate, uvula, and base of tongue. Neurological, eye, and peripheral examination were normal. A diagnosis of essential palatal myoclonus was made. It was managed successfully with clonazepam; patient was still on low dose clonazepam at the time of making this report. Conclusion: Essential palatal myoclonus can be clinically diagnosed and managed even in settings where MRI is not available or affordable.

  4. The 2003 essential. AREVA

    International Nuclear Information System (INIS)

    2004-07-01

    This document presents the essential activities of the Areva Group, a world nuclear industry leader. This group proposes technological solutions to produce the nuclear energy and to transport the electric power. It develops connection systems for the telecommunication, the computers and the automotive industry. Key data on the program management, the sustainable development activities and the different divisions are provided. (A.L.B.)

  5. Essentials of Risk Theory

    NARCIS (Netherlands)

    Roeser, S.; Hillerbrand, R.; Sandin, P.; Peterson, M.B.

    2012-01-01

    Risk has become one of the main topics in fields as diverse as engineering, medicine and economics, and it is also studied by social scientists, psychologists and legal scholars. This Springer Essentials version offers an overview of the in-depth handbook and highlights some of the main points

  6. Essential trichomegaly: case report

    Directory of Open Access Journals (Sweden)

    Julia Dutra Rossetto

    2013-02-01

    Full Text Available The present study reports two cases of symptomatic essential trichomegaly. Trichomegaly may develop in various diseases, including anorexia nervosa, hypothyroidism, pregnancy, pretibial myxedema, systemic lupus erythematosus, vernal keratoconjunctivitis, and uveitis. The exact incidence trichomegaly is unknown, and the condition remains sporadically reported. Two cases of symptomatic trichomegaly without any associated systemic disorder are presented in this paper.

  7. Genetically based location from triploid populations and gene ontology of a 3.3-mb genome region linked to Alternaria brown spot resistance in citrus reveal clusters of resistance genes.

    Directory of Open Access Journals (Sweden)

    José Cuenca

    Full Text Available Genetic analysis of phenotypical traits and marker-trait association in polyploid species is generally considered as a challenge. In the present work, different approaches were combined taking advantage of the particular genetic structures of 2n gametes resulting from second division restitution (SDR to map a genome region linked to Alternaria brown spot (ABS resistance in triploid citrus progeny. ABS in citrus is a serious disease caused by the tangerine pathotype of the fungus Alternaria alternata. This pathogen produces ACT-toxin, which induces necrotic lesions on fruit and young leaves, defoliation and fruit drop in susceptible genotypes. It is a strong concern for triploid breeding programs aiming to produce seedless mandarin cultivars. The monolocus dominant inheritance of susceptibility, proposed on the basis of diploid population studies, was corroborated in triploid progeny. Bulk segregant analysis coupled with genome scan using a large set of genetically mapped SNP markers and targeted genetic mapping by half tetrad analysis, using SSR and SNP markers, allowed locating a 3.3 Mb genomic region linked to ABS resistance near the centromere of chromosome III. Clusters of resistance genes were identified by gene ontology analysis of this genomic region. Some of these genes are good candidates to control the dominant susceptibility to the ACT-toxin. SSR and SNP markers were developed for efficient early marker-assisted selection of ABS resistant hybrids.

  8. Genetically based location from triploid populations and gene ontology of a 3.3-mb genome region linked to Alternaria brown spot resistance in citrus reveal clusters of resistance genes.

    Science.gov (United States)

    Cuenca, José; Aleza, Pablo; Vicent, Antonio; Brunel, Dominique; Ollitrault, Patrick; Navarro, Luis

    2013-01-01

    Genetic analysis of phenotypical traits and marker-trait association in polyploid species is generally considered as a challenge. In the present work, different approaches were combined taking advantage of the particular genetic structures of 2n gametes resulting from second division restitution (SDR) to map a genome region linked to Alternaria brown spot (ABS) resistance in triploid citrus progeny. ABS in citrus is a serious disease caused by the tangerine pathotype of the fungus Alternaria alternata. This pathogen produces ACT-toxin, which induces necrotic lesions on fruit and young leaves, defoliation and fruit drop in susceptible genotypes. It is a strong concern for triploid breeding programs aiming to produce seedless mandarin cultivars. The monolocus dominant inheritance of susceptibility, proposed on the basis of diploid population studies, was corroborated in triploid progeny. Bulk segregant analysis coupled with genome scan using a large set of genetically mapped SNP markers and targeted genetic mapping by half tetrad analysis, using SSR and SNP markers, allowed locating a 3.3 Mb genomic region linked to ABS resistance near the centromere of chromosome III. Clusters of resistance genes were identified by gene ontology analysis of this genomic region. Some of these genes are good candidates to control the dominant susceptibility to the ACT-toxin. SSR and SNP markers were developed for efficient early marker-assisted selection of ABS resistant hybrids.

  9. Urban High School Teachers' Beliefs Concerning Essential Science Teaching Dispositions

    Science.gov (United States)

    Miranda, Rommel

    2012-01-01

    This qualitative study addresses the link between urban high school science teachers' beliefs about essential teaching dispositions and student learning outcomes. The findings suggest that in order to help students to do well in science in urban school settings, science teachers should possess essential teaching dispositions which include…

  10. Genetics Home Reference: essential tremor

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Essential tremor Essential tremor Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Essential tremor is a movement disorder that causes involuntary, rhythmic ...

  11. Essentials of artificial intelligence

    CERN Document Server

    Ginsberg, Matt

    1993-01-01

    Since its publication, Essentials of Artificial Intelligence has beenadopted at numerous universities and colleges offering introductory AIcourses at the graduate and undergraduate levels. Based on the author'scourse at Stanford University, the book is an integrated, cohesiveintroduction to the field. The author has a fresh, entertaining writingstyle that combines clear presentations with humor and AI anecdotes. At thesame time, as an active AI researcher, he presents the materialauthoritatively and with insight that reflects a contemporary, first hand

  12. Moodle administration essentials

    CERN Document Server

    Henrick, Gavin

    2015-01-01

    If you are an experienced system administrator and know how to manage servers and set up web environments but now want to explore Moodle, this book is perfect for you. You'll get to grips with the basics and learn to manage Moodle quickly, focusing on essential tasks. Having prior knowledge of virtual learning environments would be beneficial, but is not mandatory to make the most of this book.

  13. Essentials of Endodontic Microsurgery

    Science.gov (United States)

    2010-04-01

    Holtzman DJ, et al. Quality of root-end preparations using ultrasonic and rotary instrumentation in cadavers. J Endod 2000;26:281. 39. Peters CI...00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Essentials of Endodontic Microsurgery 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT... Endodontic Program,Harvard School of Dental Medicine,Boston,MA 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND

  14. Process Improvement Essentials

    CERN Document Server

    Persse, James R

    2006-01-01

    Process Improvement Essentials combines the foundation needed to understand process improvement theory with the best practices to help individuals implement process improvement initiatives in their organization. The three leading programs: ISO 9001:2000, CMMI, and Six Sigma--amidst the buzz and hype--tend to get lumped together under a common label. This book delivers a combined guide to all three programs, compares their applicability, and then sets the foundation for further exploration.

  15. IPv6 Essentials

    CERN Document Server

    Hagen, Silvia

    2006-01-01

    IPv6 Essentials, Second Edition provides a succinct, in-depth tour of all the new features and functions in IPv6. It guides you through everything you need to know to get started, including how to configure IPv6 on hosts and routers and which applications currently support IPv6. Aimed at system and network administrators, engineers, network designers, and IT managers, this book will help you understand, plan for, design, and integrate IPv6 into your current IPv4 infrastructure

  16. Android application security essentials

    CERN Document Server

    Rai, Pragati

    2013-01-01

    Android Application Security Essentials is packed with examples, screenshots, illustrations, and real world use cases to secure your apps the right way.If you are looking for guidance and detailed instructions on how to secure app data, then this book is for you. Developers, architects, managers, and technologists who wish to enhance their knowledge of Android security will find this book interesting. Some prior knowledge of development on the Android stack is desirable but not required.

  17. Rake task management essentials

    CERN Document Server

    Koleshko, Andrey

    2014-01-01

    A step-by-step and interactive approach explaining the Rake essentials along with code examples and advanced features. If you are a developer who is acquainted with the Ruby language and want to speed up writing the code concerned with files, then this book is for you. To start reading this book, basic Ruby knowledge is required; however, a huge amount of experience with the language is not necessary.

  18. 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

  19. Antioxidant attributes of four lamiaceae essential oils

    International Nuclear Information System (INIS)

    Hussain, A.I.; Anwar, A.; Iqbal, T.; Bhatti, I.A.

    2011-01-01

    The present study was conducted to investigate the antioxidant and radical scavenging activities of essential oils of four Lamiaceae plants i.e. Pogostemon cablin, Lavandula angustifolia, Melissa officinalis, and Salvia officinalis native to Pakistan. The essential oil contents from the aerial parts of P. cablin, L. angustifolia, M. officinalis and S. officinalis were found to be 1.98, 0.58, 0.25 and 0.46%, respectively. The principal chemical constituent established in P. cablin L. angustifolia, M. officinalis, and S. officinalis essential oils, were patchouli alcohol, linalool, citronellal, and 1,8-cineol, respectively. The antioxidant activity was evaluated by scavenging of 2,2-diphenyl-1-picryl hydrazyl radical (DPPH), percent inhibition of linoleic acid oxidation and bleaching beta-carotene in linoleic acid system. The essential oils possessed appreciable antioxidant and radical scavenging activities revealing potential for therapeutic applications. (author)

  20. Samii's essentials in neurosurgery

    International Nuclear Information System (INIS)

    Ramina, Ricardo; Pontifical Catholic Univ. of Parana, Curitiba; Pires Aguiar, Paulo Henrique; Sao Paulo Univ.; Hospital Santa Paula, Sao Paulo; Tatagiba, Marcos

    2008-01-01

    'Samii's Essentials in Neurosurgery' contains selected papers written by internationally recognized contributors who were trained by Professor Madjid Samii in Hannover, Germany. The main topics deal with cutting-edge technology in neurosurgery, skull-base surgery, and specific peripheral nerve, spine, and vascular surgeries. The texts and a wealth of illustrations review and reinforce guidelines on the diagnosis and management of situations that readers are likely to encounter in everyday practice. This book will be of great interest to neurosurgeons, neurologists, ENT surgeons, neuroradiologists, and neurophysiotherapists. (orig.)

  1. Geometry essentials for dummies

    CERN Document Server

    Ryan, Mark

    2011-01-01

    Just the critical concepts you need to score high in geometry This practical, friendly guide focuses on critical concepts taught in a typical geometry course, from the properties of triangles, parallelograms, circles, and cylinders, to the skills and strategies you need to write geometry proofs. Geometry Essentials For Dummies is perfect for cramming or doing homework, or as a reference for parents helping kids study for exams. Get down to the basics - get a handle on the basics of geometry, from lines, segments, and angles, to vertices, altitudes, and diagonals Conque

  2. Essentials of cloud computing

    CERN Document Server

    Chandrasekaran, K

    2014-01-01

    ForewordPrefaceComputing ParadigmsLearning ObjectivesPreambleHigh-Performance ComputingParallel ComputingDistributed ComputingCluster ComputingGrid ComputingCloud ComputingBiocomputingMobile ComputingQuantum ComputingOptical ComputingNanocomputingNetwork ComputingSummaryReview PointsReview QuestionsFurther ReadingCloud Computing FundamentalsLearning ObjectivesPreambleMotivation for Cloud ComputingThe Need for Cloud ComputingDefining Cloud ComputingNIST Definition of Cloud ComputingCloud Computing Is a ServiceCloud Computing Is a Platform5-4-3 Principles of Cloud computingFive Essential Charact

  3. Autodesk Maya 2014 essentials

    CERN Document Server

    Naas, Paul

    2013-01-01

    The premiere book on getting started with Maya 2014 Whether you're just beginning, or migrating from another 3D application, this step-by-step guide is what you need to get a good working knowledge of Autodesk Maya 2014. Beautifully illustrated with full-color examples and screenshots, Autodesk Maya 2014 Essentials explains the basics of Maya as well as modeling, texturing, animating, setting a scene, and creating visual effects. You'll absorb important concepts and techniques, and learn how to confidently use Maya tools the way professionals do. Each chapter includes fun and cha

  4. Essential dynamics and relativity

    CERN Document Server

    O'Donnell, Peter J

    2014-01-01

    Essential Dynamics & Relativity provides students with an introduction to the core aspects of dynamics and special relativity. The author reiterates important ideas and terms throughout and covers concepts that are often missing from other textbooks at this level. He also places each topic within the wider constructs of the theory, without jumping from topic to topic to illustrate a point.The first section of the book focuses on dynamics, discussing the basic aspects of single particle motion and analyzing the motion of multi-particle systems. The book also explains the dynamical behavior of b

  5. 3D Animation Essentials

    CERN Document Server

    Beane, Andy

    2012-01-01

    The essential fundamentals of 3D animation for aspiring 3D artists 3D is everywhere--video games, movie and television special effects, mobile devices, etc. Many aspiring artists and animators have grown up with 3D and computers, and naturally gravitate to this field as their area of interest. Bringing a blend of studio and classroom experience to offer you thorough coverage of the 3D animation industry, this must-have book shows you what it takes to create compelling and realistic 3D imagery. Serves as the first step to understanding the language of 3D and computer graphics (CG)Covers 3D anim

  6. Twisted network programming essentials

    CERN Document Server

    Fettig, Abe

    2005-01-01

    Twisted Network Programming Essentials from O'Reilly is a task-oriented look at this new open source, Python-based technology. The book begins with recommendations for various plug-ins and add-ons to enhance the basic package as installed. It then details Twisted's collection simple network protocols, and helper utilities. The book also includes projects that let you try out the Twisted framework for yourself. For example, you'll find examples of using Twisted to build web services applications using the REST architecture, using XML-RPC, and using SOAP. Written for developers who want to s

  7. The essential David Bohm

    CERN Document Server

    Nichol, Lee

    2002-01-01

    There are few scientists of the twentieth century whose life's work has created more excitement and controversy than that of physicist David Bohm (1917-1992). For the first time in a single volume, The Essential David Bohm offers a comprehensive overview of Bohm's original works from a non-technical perspective. Including three chapters of previously unpublished material, and a forward by the Dalai Lama, each reading has been selected to highlight some aspect of the implicate order process, and to provide an introduction to one of the most provocative thinkers of our time.

  8. Microsoft Windows Security Essentials

    CERN Document Server

    Gibson, Darril

    2011-01-01

    Windows security concepts and technologies for IT beginners IT security can be a complex topic, especially for those new to the field of IT. This full-color book, with a focus on the Microsoft Technology Associate (MTA) program, offers a clear and easy-to-understand approach to Windows security risks and attacks for newcomers to the world of IT. By paring down to just the essentials, beginners gain a solid foundation of security concepts upon which more advanced topics and technologies can be built. This straightforward guide begins each chapter by laying out a list of topics to be discussed,

  9. Microsoft Windows networking essentials

    CERN Document Server

    Gibson, Darril

    2011-01-01

    The core concepts and technologies of Windows networking Networking can be a complex topic, especially for those new to the field of IT. This focused, full-color book takes a unique approach to teaching Windows networking to beginners by stripping down a network to its bare basics, thereby making each topic clear and easy to understand. Focusing on the new Microsoft Technology Associate (MTA) program, this book pares down to just the essentials, showing beginners how to gain a solid foundation for understanding networking concepts upon which more advanced topics and technologies can be built.

  10. Cisco Networking Essentials

    CERN Document Server

    McMillan, Troy

    2011-01-01

    An engaging approach for anyone beginning a career in networking As the world leader of networking products and services, Cisco products are constantly growing in demand. Yet, few books are aimed at those who are beginning a career in IT--until now. Cisco Networking Essentials provides a solid foundation on the Cisco networking products and services with thorough coverage of fundamental networking concepts. Author Troy McMillan applies his years of classroom instruction to effectively present high-level topics in easy-to-understand terms for beginners. With this indispensable full-color resour

  11. French essentials for dummies

    CERN Document Server

    Lawless, Laura K

    2011-01-01

    Just the core concepts you need to write and speak French correctly If you have some knowledge of French and want to polish your skills, French Essentials For Dummies focuses on just the core concepts you need to communicate effectively. From conjugating verbs to understanding tenses, this easy-to-follow guide lets you skip the suffering and score high at exam time. French 101 - get the lowdown on the basics, from expressing dates and times to identifying parts of speech Gender matters - see how a noun's gender determines the articles, adjectives, and pronouns y

  12. Surface chemistry essentials

    CERN Document Server

    Birdi, K S

    2013-01-01

    Surface chemistry plays an important role in everyday life, as the basis for many phenomena as well as technological applications. Common examples range from soap bubbles, foam, and raindrops to cosmetics, paint, adhesives, and pharmaceuticals. Additional areas that rely on surface chemistry include modern nanotechnology, medical diagnostics, and drug delivery. There is extensive literature on this subject, but most chemistry books only devote one or two chapters to it. Surface Chemistry Essentials fills a need for a reference that brings together the fundamental aspects of surface chemistry w

  13. Cisco networking essentials

    CERN Document Server

    McMillan, Troy

    2015-01-01

    Start a career in networking Cisco Networking Essentials, 2nd Edition provides the latest for those beginning a career in networking. This book provides the fundamentals of networking and leads you through the concepts, processes, and skills you need to master fundamental networking concepts. Thinking of taking the CCENT Cisco Certified Entry Networking Technician ICND1 Exam 100-101? This book has you covered! With coverage of important topics and objectives, each chapter outlines main points and provides clear, engaging discussion that will give you a sound understanding of core topics and c

  14. RabbitMQ essentials

    CERN Document Server

    Dossot, David

    2014-01-01

    This book is a quick and concise introduction to RabbitMQ. Follow the unique case study of Clever Coney Media as they progressively discover how to fully utilize RabbitMQ, containing clever examples and detailed explanations.Whether you are someone who develops enterprise messaging products professionally or a hobbyist who is already familiar with open source Message Queuing software and you are looking for a new challenge, then this is the book for you. Although you should be familiar with Java, Ruby, and Python to get the most out of the examples, RabbitMQ Essentials will give you the push y

  15. Calcium, essential for health

    Science.gov (United States)

    Martínez de Victoria, Emilio

    2016-07-12

    Calcium (Ca) is the most abundant mineral element in our body. It accounts for about 2% of body weight. The functions of calcium are: a) functions skeletal and b) regulatory functions. Bone consists of a protein matrix that mineralizes mainly with calcium (the most abundant), phosphate and magnesium, for it is essential an adequate dietary intake of Ca, phosphorus and vitamin D. The ionic Ca (Ca2+) is essential to maintain and / or perform different specialized functions of, virtually, all body cells cellular. Because of its important functions Ca2+ must be closely regulated, keeping plasma concentrations within narrow ranges. For this reason there is an accurate response against hypocalcemia or hypercalcemia in which the parathormone, calcitriol, calcitonin and vitamin K are involved. Ca intakes in the Spanish population are low in a significant percentage of the older adult’s population, especially in women. The main source of Ca in the diet is milk and milk derivatives. Green leafy vegetables, fruits and legumes can be important sources of Ca in a Mediterranean dietary pattern. The bioavailability of dietary Ca depends on physiological and dietary factors. Physiological include age, physiological status (gestation and lactation) Ca and vitamin D status and disease. Several studies relate Ca intake in the diet and various diseases, such as osteoporosis, cancer, cardiovascular disease and obesity.

  16. Essential numerical computer methods

    CERN Document Server

    Johnson, Michael L

    2010-01-01

    The use of computers and computational methods has become ubiquitous in biological and biomedical research. During the last 2 decades most basic algorithms have not changed, but what has is the huge increase in computer speed and ease of use, along with the corresponding orders of magnitude decrease in cost. A general perception exists that the only applications of computers and computer methods in biological and biomedical research are either basic statistical analysis or the searching of DNA sequence data bases. While these are important applications they only scratch the surface of the current and potential applications of computers and computer methods in biomedical research. The various chapters within this volume include a wide variety of applications that extend far beyond this limited perception. As part of the Reliable Lab Solutions series, Essential Numerical Computer Methods brings together chapters from volumes 210, 240, 321, 383, 384, 454, and 467 of Methods in Enzymology. These chapters provide ...

  17. DSP Architecture Design Essentials

    CERN Document Server

    Marković, Dejan

    2012-01-01

    In DSP Architecture Design Essentials, authors Dejan Marković and Robert W. Brodersen cover a key subject for the successful realization of DSP algorithms for communications, multimedia, and healthcare applications. The book addresses the need for DSP architecture design that maps advanced DSP algorithms to hardware in the most power- and area-efficient way. The key feature of this text is a design methodology based on a high-level design model that leads to hardware implementation with minimum power and area. The methodology includes algorithm-level considerations such as automated word-length reduction and intrinsic data properties that can be leveraged to reduce hardware complexity. From a high-level data-flow graph model, an architecture exploration methodology based on linear programming is used to create an array of architectural solutions tailored to the underlying hardware technology. The book is supplemented with online material: bibliography, design examples, CAD tutorials and custom software.

  18. Are Archetypes Essential?

    Science.gov (United States)

    Colman, Warren

    2018-06-01

    This paper distinguishes between Jung's theoretical discourse regarding the archetypes and his phenomenological account of numinous experience. For this author, the initial attraction of 'my Jung' came from both the vivid Romanticism of his descriptions of the anima and the apparent 'ground of being' offered by his theory of archetypes. However, the essentialism inherent to archetypal theory in general and the anima in particular has necessitated a re-evaluation of Jung's theory in terms of emergence theory. My own version of this emphasises the role of symbols in the constitution of affect through collective human action in the world. In this reconfiguration, the visceral energy of numinous experience is retained while the problematic theory of archetypes is no longer needed. © 2018, The Society of Analytical Psychology.

  19. Essential French grammar

    CERN Document Server

    Thacker, Mike

    2014-01-01

    Essential French Grammar is an innovative reference grammar and workbook for intermediate and advanced undergraduate students of French (CEFR levels B2 to C1). Its clear explanations of grammar are supported by contemporary examples and lively cartoon drawings.  Each chapter contains: * real-life language examples in French, with English translations * a 'key points' box and tables that summarise grammar concepts * a variety of exercises to reinforce learning * a contemporary primary source or literary extract to illustrate grammar in context. To aid your understanding, this book also contains a glossary of grammatical terms in French and English, useful verb tables and a key to the exercises. Together, these features all help you to grasp complex points of grammar and develop your French language skills.

  20. Essentials of nonlinear optics

    CERN Document Server

    Murti, Y V G S

    2014-01-01

    Current literature on Nonlinear Optics varies widely in terms of content, style, and coverage of specific topics, relative emphasis of areas and the depth of treatment. While most of these books are excellent resources for the researchers, there is a strong need for books appropriate for presenting the subject at the undergraduate or postgraduate levels in Universities. The need for such a book to serve as a textbook at the level of the bachelors and masters courses was felt by the authors while teaching courses on nonlinear optics to students of both science and engineering during the past two decades. This book has emerged from an attempt to address the requirement of presenting the subject at college level. A one-semester course covering the essentials can effectively be designed based on this.

  1. Essential real analysis

    CERN Document Server

    Field, Michael

    2017-01-01

    This book provides a rigorous introduction to the techniques and results of real analysis, metric spaces and multivariate differentiation, suitable for undergraduate courses. Starting from the very foundations of analysis, it offers a complete first course in real analysis, including topics rarely found in such detail in an undergraduate textbook such as the construction of non-analytic smooth functions, applications of the Euler-Maclaurin formula to estimates, and fractal geometry.  Drawing on the author’s extensive teaching and research experience, the exposition is guided by carefully chosen examples and counter-examples, with the emphasis placed on the key ideas underlying the theory. Much of the content is informed by its applicability: Fourier analysis is developed to the point where it can be rigorously applied to partial differential equations or computation, and the theory of metric spaces includes applications to ordinary differential equations and fractals. Essential Real Analysis will appeal t...

  2. TQM: the essential concepts.

    Science.gov (United States)

    Chambers, D W

    1998-01-01

    This is an introduction to the major concepts in total quality management, a loose collection of management approaches that focus on continuous improvement of processes, guided by routine data collection and adjustment of the processes. Customer focus and involvement of all members of an organization are also characteristics commonly found in TQM. The seventy-five-year history of the movement is sketched from its beginning in statistical work on quality assurance through the many improvements and redefinitions added by American and Japanese thinkers. Essential concepts covered include: control cycles, focus on the process rather than the defects, the GEAR model, importance of the customer, upstream quality, just-in-time, kaizen, and service quality.

  3. HAB1–SWI3B Interaction Reveals a Link between Abscisic Acid Signaling and Putative SWI/SNF Chromatin-Remodeling Complexes in Arabidopsis[C][W

    Science.gov (United States)

    Saez, Angela; Rodrigues, Americo; Santiago, Julia; Rubio, Silvia; Rodriguez, Pedro L.

    2008-01-01

    Abscisic acid (ABA) has an important role for plant growth, development, and stress adaptation. HYPERSENSITIVE TO ABA1 (HAB1) is a protein phosphatase type 2C that plays a key role as a negative regulator of ABA signaling; however, the molecular details of HAB1 action in this process are not known. A two-hybrid screen revealed that SWI3B, an Arabidopsis thaliana homolog of the yeast SWI3 subunit of SWI/SNF chromatin-remodeling complexes, is a prevalent interacting partner of HAB1. The interaction mapped to the N-terminal half of SWI3B and required an intact protein phosphatase catalytic domain. Bimolecular fluorescence complementation and coimmunoprecipitation assays confirmed the interaction of HAB1 and SWI3B in the nucleus of plant cells. swi3b mutants showed a reduced sensitivity to ABA-mediated inhibition of seed germination and growth and reduced expression of the ABA-responsive genes RAB18 and RD29B. Chromatin immunoprecipitation experiments showed that the presence of HAB1 in the vicinity of RD29B and RAB18 promoters was abolished by ABA, which suggests a direct involvement of HAB1 in the regulation of ABA-induced transcription. Additionally, our results uncover SWI3B as a novel positive regulator of ABA signaling and suggest that HAB1 modulates ABA response through the regulation of a putative SWI/SNF chromatin-remodeling complex. PMID:19033529

  4. Sex-linked dominant

    Science.gov (United States)

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

  5. [Linking learning theory with practice].

    Science.gov (United States)

    Ávalos-Carranza, María Teresa; Amador-Olvera, Eric; Zerón-Gutiérrez, Lydia

    2016-01-01

    It is often said that it is easier to learn what is observed and practiced on a daily basis; to the need to effectively link theory with practice considered in the process of teaching and learning, many strategies have been developed to allow this process to be carried out in a more efficiently maner. It is, therefore, very important to recognize that an appropriate teacher/student relationship is essential for students to acquire the skills and abilities required.

  6. 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.

  7. Rhetoric and Essentially Contested Arguments

    Science.gov (United States)

    Garver, Eugene

    1978-01-01

    Draws a connection between Gallie's essentially contested concepts and Aristotle's account of rhetorical argument by presenting a definition of Essentially Contested Argument which is used as the connecting term between rhetoric and essentially contested concepts and by demonstrating the value of making this connection. (JF)

  8. Copyright for librarians the essential handbook

    CERN Document Server

    Berkman Center for Internet and Society

    2012-01-01

    "Copyright for Librarians" (CFL) is an online open curriculum on copyright law that was developed jointly with Harvard’s Berkman Center for Internet and Society. Re-designed as a brand new textbook, "Copyright for Librarians: the essential handbook" can be used as a stand-alone resource or as an adjunct to the online version which contains additional links and references for students who wish to pursue any topic in greater depth. Delve into copyright theory or explore enforcement. With a new index and a handy Glossary, the Handbook is essential reading for librarians who want to hone their skills in 2013, and for anyone learning about or teaching copyright law in the information field.

  9. Essential Requirements for Digital Annotation Systems

    Directory of Open Access Journals (Sweden)

    ADRIANO, C. M.

    2012-06-01

    Full Text Available Digital annotation systems are usually based on partial scenarios and arbitrary requirements. Accidental and essential characteristics are usually mixed in non explicit models. Documents and annotations are linked together accidentally according to the current technology, allowing for the development of disposable prototypes, but not to the support of non-functional requirements such as extensibility, robustness and interactivity. In this paper we perform a careful analysis on the concept of annotation, studying the scenarios supported by digital annotation tools. We also derived essential requirements based on a classification of annotation systems applied to existing tools. The analysis performed and the proposed classification can be applied and extended to other type of collaborative systems.

  10. Developing and Implementing an Assessment Technique to Measure Linked Concepts

    Science.gov (United States)

    Ye, Li; Oueini, Razanne; Lewis, Scott E.

    2015-01-01

    The links students make among chemistry content is considered essential for a robust, enduring understanding in multiple learning theories. This article describes the development and implementation of an assessment technique, termed a Measure of Linked Concepts, designed to inform instructors on students' understanding of linking content…

  11. Essential Neuroscience in Immunology.

    Science.gov (United States)

    Chavan, Sangeeta S; Tracey, Kevin J

    2017-05-01

    The field of immunology is principally focused on the molecular mechanisms by which hematopoietic cells initiate and maintain innate and adaptive immunity. That cornerstone of attention has been expanded by recent discoveries that neuronal signals occupy a critical regulatory niche in immunity. The discovery is that neuronal circuits operating reflexively regulate innate and adaptive immunity. One particularly well-characterized circuit regulating innate immunity, the inflammatory reflex, is dependent upon action potentials transmitted to the reticuloendothelial system via the vagus and splenic nerves. This field has grown significantly with the identification of several other reflexes regulating discrete immune functions. As outlined in this review, the delineation of these mechanisms revealed a new understanding of immunity, enabled a first-in-class clinical trial using bioelectronic devices to inhibit cytokines and inflammation in rheumatoid arthritis patients, and provided a mosaic view of immunity as the integration of hematopoietic and neural responses to infection and injury. Copyright © 2017 by The American Association of Immunologists, Inc.

  12. Essential oils and anxiolytic aromatherapy.

    Science.gov (United States)

    Setzer, William N

    2009-09-01

    A number of essential oils are currently in use as aromatherapy agents to relieve anxiety, stress, and depression. Popular anxiolytic oils include lavender (Lavandula angustifolia), rose (Rosa damascena), orange (Citrus sinensis), bergamot (Citrus aurantium), lemon (Citrus limon), sandalwood (Santalum album), clary sage (Salvia sclarea), Roman chamomile (Anthemis nobilis), and rose-scented geranium (Pelargonium spp.). This review discusses the chemical constituents and CNS effects of these aromatherapeutic essential oils, as well as recent studies on additional essential oils with anxiolytic activities.

  13. Essential Oils and Antifungal Activity

    Science.gov (United States)

    Coppola, Raffaele; De Feo, Vincenzo

    2017-01-01

    Since ancient times, folk medicine and agro-food science have benefitted from the use of plant derivatives, such as essential oils, to combat different diseases, as well as to preserve food. In Nature, essential oils play a fundamental role in protecting the plant from biotic and abiotic attacks to which it may be subjected. Many researchers have analyzed in detail the modes of action of essential oils and most of their components. The purpose of this brief review is to describe the properties of essential oils, principally as antifungal agents, and their role in blocking cell communication mechanisms, fungal biofilm formation, and mycotoxin production. PMID:29099084

  14. Essentialism goes social: belief in social determinism as a component of psychological essentialism.

    Science.gov (United States)

    Rangel, Ulrike; Keller, Johannes

    2011-06-01

    Individuals tend to explain the characteristics of others with reference to an underlying essence, a tendency that has been termed psychological essentialism. Drawing on current conceptualizations of essentialism as a fundamental mode of social thinking, and on prior studies investigating belief in genetic determinism (BGD) as a component of essentialism, we argue that BGD cannot constitute the sole basis of individuals' essentialist reasoning. Accordingly, we propose belief in social determinism (BSD) as a complementary component of essentialism, which relies on the belief that a person's essential character is shaped by social factors (e.g., upbringing, social background). We developed a scale to measure this social component of essentialism. Results of five correlational studies indicate that (a) BGD and BSD are largely independent, (b) BGD and BSD are related to important correlates of essentialist thinking (e.g., dispositionism, perceived group homogeneity), (c) BGD and BSD are associated with indicators of fundamental epistemic and ideological motives, and (d) the endorsement of each lay theory is associated with vital social-cognitive consequences (particularly stereotyping and prejudice). Two experimental studies examined the idea that the relationship between BSD and prejudice is bidirectional in nature. Study 6 reveals that rendering social-deterministic explanations salient results in increased levels of ingroup favoritism in individuals who chronically endorse BSD. Results of Study 7 show that priming of prejudice enhances endorsement of social-deterministic explanations particularly in persons habitually endorsing prejudiced attitudes. 2011 APA, all rights reserved

  15. Selenoproteins are essential for proper keratinocyte function and skin development.

    Directory of Open Access Journals (Sweden)

    Aniruddha Sengupta

    2010-08-01

    Full Text Available Dietary selenium is known to protect skin against UV-induced damage and cancer and its topical application improves skin surface parameters in humans, while selenium deficiency compromises protective antioxidant enzymes in skin. Furthermore, skin and hair abnormalities in humans and rodents may be caused by selenium deficiency, which are overcome by dietary selenium supplementation. Most important biological functions of selenium are attributed to selenoproteins, proteins containing selenium in the form of the amino acid, selenocysteine (Sec. Sec insertion into proteins depends on Sec tRNA; thus, knocking out the Sec tRNA gene (Trsp ablates selenoprotein expression. We generated mice with targeted removal of selenoproteins in keratin 14 (K14 expressing cells and their differentiated descendents. The knockout progeny had a runt phenotype, developed skin abnormalities and experienced premature death. Lack of selenoproteins in epidermal cells led to the development of hyperplastic epidermis and aberrant hair follicle morphogenesis, accompanied by progressive alopecia after birth. Further analyses revealed that selenoproteins are essential antioxidants in skin and unveiled their role in keratinocyte growth and viability. This study links severe selenoprotein deficiency to abnormalities in skin and hair and provides genetic evidence for the role of these proteins in keratinocyte function and cutaneous development.

  16. Attention in essential tremor: evidence from event-related potentials.

    Science.gov (United States)

    Pauletti, C; Mannarelli, D; Locuratolo, N; Vanacore, N; De Lucia, M C; Mina, C; Fattapposta, F

    2013-07-01

    Clinically subtle executive dysfunctions have recently been described in essential tremor (ET), though the presence of attentional deficits is still unclear. We investigated the psychophysiological aspects of attention in ET, using event-related potentials (ERPs). Twenty-one non-demented patients with ET and 21 age- and sex-matched healthy controls underwent a psychophysiological evaluation. P300 components and the Contingent Negative Variation (CNV) were recorded. The latencies and amplitudes of the P3a and P3b subcomponents and CNV areas were evaluated. Possible correlations between clinical parameters and ERP data were investigated. P3a latency was significantly longer in the ET group (p attentive circuits, while the memory context-updating process appears to be spared. This selective cognitive dysfunction does not appear to interfere with the attentional set linked to the expectancy evaluated during a complex choice-reaction time task, which is preserved in ET. This multitask psychophysiological approach reveals the presence of a peculiar attentional deficit in patients with ET, thus expanding the clinical features of this disease.

  17. Linked data management

    CERN Document Server

    Hose, Katja; Schenkel, Ralf

    2014-01-01

    Linked Data Management presents techniques for querying and managing Linked Data that is available on today’s Web. The book shows how the abundance of Linked Data can serve as fertile ground for research and commercial applications. The text focuses on aspects of managing large-scale collections of Linked Data. It offers a detailed introduction to Linked Data and related standards, including the main principles distinguishing Linked Data from standard database technology. Chapters also describe how to generate links between datasets and explain the overall architecture of data integration systems based on Linked Data. A large part of the text is devoted to query processing in different setups. After presenting methods to publish relational data as Linked Data and efficient centralized processing, the book explores lookup-based, distributed, and parallel solutions. It then addresses advanced topics, such as reasoning, and discusses work related to read-write Linked Data for system interoperation. Desp...

  18. BENEFITS OF LINKED DATA FOR INTEROPERABILITY DURING CRISIS MANAGEMENT

    Directory of Open Access Journals (Sweden)

    R. Roller

    2015-08-01

    Full Text Available Floodings represent a permanent risk to the Netherlands in general and to her power supply in particular. Data sharing is essential within this crisis scenario as a power cut affects a great variety of interdependant sectors. Currently used data sharing systems have been shown to hamper interoperability between stakeholders since they lack flexibility and there is no consensus in term definitions and interpretations. The study presented in this paper addresses these challenges by proposing a new data sharing solution based on Linked Data, a method of interlinking data points in a structured way on the web. A conceptual model for two data sharing parties in a flood-caused power cut crisis management scenario was developed to which relevant data were linked. The analysis revealed that the presented data sharing solution burderns its user with extra costs in the short run, but saves resources in the long run by overcoming interoperability problems of the legacy systems. The more stakeholders adopt Linked Data the stronger its benefits for data sharing will become.

  19. Characterization equipment essential drawing plan

    International Nuclear Information System (INIS)

    WILSON, G.W.

    1999-01-01

    The purpose of this document is to list the Characterization equipment drawings that are classified as Essential Drawings. Essential Drawings: Are those drawings identified by the facility staff as necessary to directly support the safe operation of the facility or equipment (HNF 1997a). The Characterization equipment drawings identified in this report are deemed essential drawings as defined in HNF-PRO-242, Engineering Drawing Requirements (HNF 1997a). These drawings will be prepared, revised, and maintained per HNF-PRO-440, Engineering Document Change Control (HNF 1997b). All other Characterization equipment drawings not identified in this document will be considered Support drawings until the Characterization Equipment Drawing Evaluation Report is completed

  20. Do people essentialize emotions? Individual differences in emotion essentialism and emotional experience.

    Science.gov (United States)

    Lindquist, Kristen A; Gendron, Maria; Oosterwijk, Suzanne; Barrett, Lisa Feldman

    2013-08-01

    Many scientific models of emotion assume that emotion categories are natural kinds that carve nature at its joints. These beliefs remain strong, despite the fact that the empirical record on the issue has remained equivocal for over a century. In this research, the authors examined one reason for this situation: People essentialize emotion categories by assuming that members of the same category (e.g., fear) have a shared metaphysical essence (i.e., a common causal mechanism). In Study 1, the authors found that lay people essentialize emotions by assuming that instances of the same emotion category have a shared essence that defines them, even when their surface features differ. Study 2 extended these findings, demonstrating that lay people tend to essentialize categories the more a category is of the body (vs. the mind). In Study 3, we examined the links between emotion essentialism and the complexity of actual emotional experiences. In particular, we predicted and found that individuals who hold essentialist beliefs about emotions describe themselves as experiencing highly differentiated emotional experiences but do not show evidence of stronger emotional differentiation in their momentary ratings of experience in everyday life. Implications for the science of emotion are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  1. Essential idempotents and simplex codes

    Directory of Open Access Journals (Sweden)

    Gladys Chalom

    2017-01-01

    Full Text Available We define essential idempotents in group algebras and use them to prove that every mininmal abelian non-cyclic code is a repetition code. Also we use them to prove that every minimal abelian code is equivalent to a minimal cyclic code of the same length. Finally, we show that a binary cyclic code is simplex if and only if is of length of the form $n=2^k-1$ and is generated by an essential idempotent.

  2. Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Joseph Landry

    2008-10-01

    Full Text Available We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor, the largest subunit of NURF (Nucleosome Remodeling Factor in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf(-/- embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf(-/- embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo.

  3. Essentials of periodontal medicine in preventive medicine.

    Science.gov (United States)

    Gulati, Minkle; Anand, Vishal; Jain, Nikil; Anand, Bhargavi; Bahuguna, Rohit; Govila, Vivek; Rastogi, Pavitra

    2013-09-01

    Influence of systemic disorders on periodontal diseases is well established. However, of growing interest is the effect of periodontal diseases on numerous systemic diseases or conditions like cardiovascular disease, cerebrovascular disease, diabetes, pre-term low birth weight babies, preeclampsia, respiratory infections and others including osteoporosis, cancer, rheumatoid arthritis, erectile dysfunction, Alzheimer's disease, gastrointestinal disease, prostatitis, renal diseases, which has also been scientifically validated. This side of the oral-systemic link has been termed Periodontal Medicine and is potentially of great public health significance, as periodontal disease is largely preventable and in many instances readily treatable, hence, providing many new opportunities for preventing and improving prognosis of several systemic pathologic conditions. This review article highlights the importance of prevention and treatment of periodontal diseases as an essential part of preventive medicine to circumvent its deleterious effects on general health.

  4. Essentials of periodontal medicine in preventive medicine

    Directory of Open Access Journals (Sweden)

    Minkle Gulati

    2013-01-01

    Full Text Available Influence of systemic disorders on periodontal diseases is well established. However, of growing interest is the effect of periodontal diseases on numerous systemic diseases or conditions like cardiovascular disease, cerebrovascular disease, diabetes, pre-term low birth weight babies, preeclampsia, respiratory infections and others including osteoporosis, cancer, rheumatoid arthritis, erectile dysfunction, Alzheimer′s disease, gastrointestinal disease, prostatitis, renal diseases, which has also been scientifically validated. This side of the oral-systemic link has been termed Periodontal Medicine and is potentially of great public health significance, as periodontal disease is largely preventable and in many instances readily treatable, hence, providing many new opportunities for preventing and improving prognosis of several systemic pathologic conditions. This review article highlights the importance of prevention and treatment of periodontal diseases as an essential part of preventive medicine to circumvent its deleterious effects on general health.

  5. Levels of essential and non-essential elements in commercially ...

    African Journals Online (AJOL)

    The focus of this study was to assess the quality of commercially packaged moringa tea brands available in the retail markets in Nigerian cities on the basis of the essential and nonessential elemental content in their tissues. Four different brands of moringa tea comprising two locally processed teas and two imported teas ...

  6. Levels of Essential and Non-Essential Elements in Commercially ...

    African Journals Online (AJOL)

    Enebi Jasper

    INTRODUCTION. Plants have been ... plant metabolism and biosynthesis and act as cofactors for ... plant body. 3 . Some metals are essential nutrients (zinc, iron, copper, and chromium), ... non-destructive analysis, increased total speed, ... oleifera play both a curative and preventive ... maintenance of cardiac rhythm. 16.

  7. Essentials of Career Interest Assessment. Essentials of Psychological Assessment Series.

    Science.gov (United States)

    Prince, Jeffrey P.; Heiser, Lisa J.

    This book is a quick reference source to guide the career professional through the essentials of using the most popular career interest tools. It summarizes important technical aspects of each inventory, and offers step-by-step guidance in the interpretation and use of the various inventories. The chapters are: (1) "Overview"; (2)…

  8. Dynamic link: user's manual

    International Nuclear Information System (INIS)

    Harada, Hiroo; Asai, Kiyoshi; Kihara, Kazuhisa.

    1981-09-01

    The purpose of dynamic link facility is to link a load module dynamically only when it is used in execution time. The facility is very useful for development, execution and maintenance of a large scale computer program which is too big to be saved as one load module in main memory, or it is poor economy to save it due to many unused subroutines depending on an input. It is also useful for standardization and common utilization of programs. Standard usage of dynamic link facility of FACOM M-200 computer system, a software tool which analyzes the effect of dynamic link facility and application of dynamic link to nuclear codes are described. (author)

  9. Essential Medicines in a High Income Country: Essential to Whom?

    Science.gov (United States)

    Duong, Mai; Moles, Rebekah J; Chaar, Betty; Chen, Timothy F

    2015-01-01

    To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an "essential" medicine, and how the Essential Medicines List (EML) concept functions in a high income country context. In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach. Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain. This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach. The wide range of views of what stakeholders

  10. Essential Medicines in a High Income Country: Essential to Whom?

    Directory of Open Access Journals (Sweden)

    Mai Duong

    Full Text Available To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an "essential" medicine, and how the Essential Medicines List (EML concept functions in a high income country context.In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach.Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain.This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach. The wide range of views of

  11. Tank farms essential drawing plan

    International Nuclear Information System (INIS)

    Domnoske-Rauch, L.A.

    1998-01-01

    The purpose of this document is to define criteria for selecting Essential Drawings, Support Drawings, and Controlled Print File (CPF) drawings and documents for facilities that are part of East and West Tank Farms. Also, the drawings and documents that meet the criteria are compiled separate listings. The Essential Drawing list and the Support Drawing list establish a priority for updating technical baseline drawings. The CPF drawings, denoted by an asterisk (*), defined the drawings and documents that Operations is required to maintain per the TWRS Administration Manual. The Routing Boards in Buildings 272-WA and 272-AW are not part of the CPF

  12. Analgesic Potential of Essential Oils

    Directory of Open Access Journals (Sweden)

    José Ferreira Sarmento-Neto

    2015-12-01

    Full Text Available Pain is an unpleasant sensation associated with a wide range of injuries and diseases, and affects approximately 20% of adults in the world. The discovery of new and more effective drugs that can relieve pain is an important research goal in both the pharmaceutical industry and academia. This review describes studies involving antinociceptive activity of essential oils from 31 plant species. Botanical aspects of aromatic plants, mechanisms of action in pain models and chemical composition profiles of the essential oils are discussed. The data obtained in these studies demonstrate the analgesic potential of this group of natural products for therapeutic purposes.

  13. Essential Medicines in National Constitutions

    Science.gov (United States)

    Toebes, Brigit; Hogerzeil, Hans

    2016-01-01

    Abstract A constitutional guarantee of access to essential medicines has been identified as an important indicator of government commitment to the progressive realization of the right to the highest attainable standard of health. The objective of this study was to evaluate provisions on access to essential medicines in national constitutions, to identify comprehensive examples of constitutional text on medicines that can be used as a model for other countries, and to evaluate the evolution of constitutional medicines-related rights since 2008. Relevant articles were selected from an inventory of constitutional texts from WHO member states. References to states’ legal obligations under international human rights law were evaluated. Twenty-two constitutions worldwide now oblige governments to protect and/or to fulfill accessibility of, availability of, and/or quality of medicines. Since 2008, state responsibilities to fulfill access to essential medicines have expanded in five constitutions, been maintained in four constitutions, and have regressed in one constitution. Government commitments to essential medicines are an important foundation of health system equity and are included increasingly in state constitutions. PMID:27781006

  14. Intellectual Workers and Essential Freedoms.

    Science.gov (United States)

    Edley, Christopher Jr.

    2000-01-01

    Journalists and college professors deserve certain privileges, including freedom of speech and academic freedom, but they must adapt their work to increasingly diverse populations. They must confront public mistrust, convince people that these freedoms are worthwhile, and protect essential public rights through what they study and teach and to…

  15. Essential Fluid Dynamics for Scientists

    Science.gov (United States)

    Braithwaite, Jonathan

    2017-12-01

    The book is an introduction to the subject of fluid mechanics, essential for students and researchers in many branches of science. It illustrates its fundamental principles with a variety of examples drawn mainly from astrophysics and geophysics as well as from everyday experience. Prior familiarity with basic thermodynamics and vector calculus is assumed.

  16. Essential oils in broiler nutrition

    NARCIS (Netherlands)

    Lee, Kyung-woo

    2002-01-01

    Dietary antibiotics at low, subtherapeutic levels have been shown to improve growth performance in farm animals. However, there is a trend to look for alternatives to dietary antibiotics, due to occurrence of antibiotic-resistance bacteria. The present thesis explored the essential oils as the

  17. Essentials of supply chain management

    CERN Document Server

    Hugos, Michael H

    2011-01-01

    The latest thinking, strategies, developments, and technologies to stay current in supply chain management Presenting the core concepts and techniques of supply chain management in a clear, concise and easily readable style, the Third Edition of Essentials of Supply Chain Management outlines the most crucial tenets and concepts of supply chain management.

  18. Essentials for the Teacher's Toolbox

    Science.gov (United States)

    Uhler, Jennifer

    2012-01-01

    Every profession has a set of essential tools for carrying out its work. Airplane mechanics cannot repair engines without sophisticated diagnostics, wrenches, and pliers. Surgeons cannot operate without scalpels and clamps. In contrast, teaching has often been perceived as a profession requiring only students, chalk, and a blackboard in order for…

  19. Diversity - Essential quality for agronomy

    Science.gov (United States)

    Diversity is an essential quality for success in agronomy because agronomy touches everyone, everywhere in some way, and food production is crucial for every society around the world. Consider, for example, our membership, which is diverse in almost every way imaginable. This diversity brings differ...

  20. Hyper-V Replica essentials

    CERN Document Server

    Krstevski, Vangel

    2013-01-01

    a in various deployment scenarios.Hyper-V Replica Essentials is for Windows Server administrators who want to improve their system availability and speed up disaster recovery. You will need experience in Hyper-V deployment because Hyper-V Replica is built in the Hyper-V platform.

  1. Visualisierung von typisierten Links in Linked Data

    Directory of Open Access Journals (Sweden)

    Georg Neubauer

    2017-09-01

    Full Text Available Das Themengebiet der Arbeit behandelt Visualisierungen von typisierten Links in Linked Data. Die wissenschaftlichen Gebiete, die im Allgemeinen den Inhalt des Beitrags abgrenzen, sind das Semantic Web, das Web of Data und Informationsvisualisierung. Das Semantic Web, das von Tim Berners Lee 2001 erfunden wurde, stellt eine Erweiterung zum World Wide Web (Web 2.0 dar. Aktuelle Forschungen beziehen sich auf die Verknüpfbarkeit von Informationen im World Wide Web. Um es zu ermöglichen, solche Verbindungen wahrnehmen und verarbeiten zu können sind Visualisierungen die wichtigsten Anforderungen als Hauptteil der Datenverarbeitung. Im Zusammenhang mit dem Sematic Web werden Repräsentationen von zuhammenhängenden Informationen anhand von Graphen gehandhabt. Der Grund des Entstehens dieser Arbeit ist in erster Linie die Beschreibung der Gestaltung von Linked Data-Visualisierungskonzepten, deren Prinzipien im Rahmen einer theoretischen Annäherung eingeführt werden. Anhand des Kontexts führt eine schrittweise Erweiterung der Informationen mit dem Ziel, praktische Richtlinien anzubieten, zur Vernetzung dieser ausgearbeiteten Gestaltungsrichtlinien. Indem die Entwürfe zweier alternativer Visualisierungen einer standardisierten Webapplikation beschrieben werden, die Linked Data als Netzwerk visualisiert, konnte ein Test durchgeführt werden, der deren Kompatibilität zum Inhalt hatte. Der praktische Teil behandelt daher die Designphase, die Resultate, und zukünftige Anforderungen des Projektes, die durch die Testung ausgearbeitet wurden.

  2. Linking open vocabularies

    CERN Document Server

    Greifender, Elke; Seadle, Michael

    2013-01-01

    Linked Data (LD), Linked Open Data (LOD) and generating a web of data, present the new knowledge sharing frontier. In a philosophical context, LD is an evolving environment that reflects humankinds' desire to understand the world by drawing on the latest technologies and capabilities of the time. LD, while seemingly a new phenomenon did not emerge overnight; rather it represents the natural progression by which knowledge structures are developed, used, and shared. Linked Open Vocabularies is a significant trajectory of LD. Linked Open Vocabularies targets vocabularies that have traditionally b

  3. Shifting ground : The variable use of essentialism in contexts of inclusion and exclusion

    NARCIS (Netherlands)

    Morton, T.A; Hornsey, J.M.; Postmes, T.

    Past research has demonstrated a broad association between prejudice and essentialism. However, research has also shown that essentialism and prejudice are not always linked in the same way - sometimes essentialist thinking is associated with prejudice, but sometimes it is not. The aim of the

  4. Lantana montevidensis Essential Oil: Chemical Composition and Mosquito Repellent Activity against Aedes aegypti

    Science.gov (United States)

    The essential oil (EO) of Lantana montevidensis (Spreng.) Briq. (L. sellowiana Link & Otto) was investigated for its chemical composition and mosquito repellent activity. The essential oil obtained by hydrodistillation of aerial plant parts was analyzed by GC-FID and GC-MS. The major constituents we...

  5. Essentials of radiation heat transfer

    CERN Document Server

    Balaji

    2014-01-01

    Essentials of Radiation Heat Transfer is a textbook presenting the essential, fundamental information required to gain an understanding of radiation heat transfer and equips the reader with enough knowledge to be able to tackle more challenging problems. All concepts are reinforced by carefully chosen and fully worked examples, and exercise problems are provided at the end of every chapter. In a significant departure from other books on this subject, this book completely dispenses with the network method to solve problems of radiation heat transfer in surfaces. It instead presents the powerful radiosity-irradiation method and shows how this technique can be used to solve problems of radiation in enclosures made of one to any number of surfaces. The network method is not easily scalable. Secondly, the book introduces atmospheric radiation, which is now being considered as a potentially important area, in which engineers can contribute to the technology of remote sensing and atmospheric sciences in general, b...

  6. Communication: essential strategies for success.

    Science.gov (United States)

    O'Connor, Mary

    2013-06-01

    This department highlights change management strategies that may be successful in strategically planning and executing organizational change initiatives. With the goal of presenting practical approaches helpful to nurse leaders advance organizational change, content includes evidence-based projects, tool, and resources that mobilize and sustain organizational change initiatives. In this article, the author discusses strategies for communication for change processes, whether large or small. Intentional planning and development of a communication strategy alongside, not as an afterthought, to change initiatives are essential.

  7. Essentials of nuclear medicine imaging

    CERN Document Server

    Mettler, Fred A. Jr

    2012-01-01

    Essentials of Nuclear Medicine Imaging, by Drs. Fred A Mettler and Milton J Guiberteau, provides the practical and comprehensive guidance you need to master key nuclear imaging techniques. From physics, instrumentation, quality control, and legal requirements to hot topics such as sodium fluoride, radiopharmaceuticals, and recommended pediatric administered doses and guidelines, this sixth edition covers the fundamentals and recent developments in the practice of nuclear medicine.

  8. Essential themes in Personnel economics

    OpenAIRE

    Josheski, Dushko

    2014-01-01

    In this paper are presented essential themes in the subject of personnel economics. In the first part analysis has been conducted on the impact of peer pressure on workplace behaviour. Then again models for compensation structures within firms, and their influence on the utility of work by employees. In the final section of the paper the productivity spillover effect has been analyzed, and the causes of existence of spillovers and their impact on workers’ productivity

  9. Essentials of natural gas microturbines

    CERN Document Server

    Boicea, Valentin A

    2013-01-01

    Addressing a field which, until now, has not been sufficiently investigated, Essentials of Natural Gas Microturbines thoroughly examines several natural gas microturbine technologies suitable not only for distributed generation but also for the automotive industry. An invaluable resource for power systems, electrical, and computer science engineers as well as operations researchers, microturbine operators, policy makers, and other industry professionals, the book: Explains the importance of natural gas microturbines and their use in distributed energy resource (DER) systemsDiscusses the histor

  10. Repelling mosquitoes with essential oils

    Science.gov (United States)

    Riley, L.

    2017-12-01

    Mosquitoes carry diseases than can lead to serious illness and death. According to the World Health Organization, mosquitoes infect over 300 million people a year with Malaria and Dengue Fever, two life threatening diseases vectored by mosquitoes. Although insecticides are the most effective way to control mosquitoes, they are not always environmentally friendly. Therefore, alternative tactics should be considered. In this study, we looked at the repellency of various essential oils on female Aedes aegypti through a series of laboratory assays.

  11. Let's "Downscale" Linked Data

    NARCIS (Netherlands)

    Gueret, C.D.M.; de Boer, V.; Schlobach, K.S.

    2014-01-01

    Open data policies and linked data publication are powerful tools for increasing transparency, participatory governance, and accountability. The linked data community proudly emphasizes the economic and societal impact such technology shows. But a closer look proves that the design and deployment of

  12. Let's "Downscale" Linked Data

    NARCIS (Netherlands)

    Gueret, Christophe; de Boer, Victor; Schlobach, Stefan

    2014-01-01

    Open data policies and linked data publication are powerful tools for increasing transparency, participatory governance, and accountability. A closer look at linked data technologies, however, proves that their design and deployment exclude the majority of the world’s population. It will take small

  13. Weierstrass polynomials for links

    DEFF Research Database (Denmark)

    Hansen, Vagn Lundsgaard

    1997-01-01

    There is a natural way of identifying links in3-space with polynomial covering spaces over thecircle. Thereby any link in 3-space can be definedby a Weierstrass polynomial over the circle. Theequivalence relation for covering spaces over thecircle is, however, completely different from...

  14. Autophagy is essential for hearing in mice.

    Science.gov (United States)

    Fujimoto, Chisato; Iwasaki, Shinichi; Urata, Shinji; Morishita, Hideaki; Sakamaki, Yuriko; Fujioka, Masato; Kondo, Kenji; Mizushima, Noboru; Yamasoba, Tatsuya

    2017-05-11

    Hearing loss is the most frequent sensory disorder in humans. Auditory hair cells (HCs) are postmitotic at late-embryonic differentiation and postnatal stages, and their damage is the major cause of hearing loss. There is no measurable HC regeneration in the mammalian cochlea, and the maintenance of cell function is crucial for preservation of hearing. Here we generated mice deficient in autophagy-related 5 (Atg5), a gene essential for autophagy, in the HCs to investigate the effect of basal autophagy on hearing acuity. Deletion of Atg5 resulted in HC degeneration and profound congenital hearing loss. In autophagy-deficient HCs, polyubiquitinated proteins and p62/SQSTM1, an autophagy substrate, accumulated as inclusion bodies during the first postnatal week, and these aggregates increased in number. These findings revealed that basal autophagy has an important role in maintenance of HC morphology and hearing acuity.

  15. An efficient method for sampling the essential subspace of proteins

    NARCIS (Netherlands)

    Amadei, A; Linssen, A.B M; de Groot, B.L.; van Aalten, D.M.F.; Berendsen, H.J.C.

    A method is presented for a more efficient sampling of the configurational space of proteins as compared to conventional sampling techniques such as molecular dynamics. The method is based on the large conformational changes in proteins revealed by the ''essential dynamics'' analysis. A form of

  16. Essential oils of Zingiber cassumunar Roxb. from Northeast India

    NARCIS (Netherlands)

    Bordoloi, A.K.; Sperkova, J.; Leclercq, P.A.

    1999-01-01

    The essential oils of Zingiber cassumunar, Zingiberaceae, were isolated from its rhizomes and leaves by hydrodistillation. Analysis of the oils by GC and GC/MS revealed that the rhizome oil contained terpinen-4-ol (50.5%), (E)-1-(3,4-dimethoxyphenyl)buta-1,3-diene 09.1%),

  17. Problem Based Learning - Linking Students and Industry

    DEFF Research Database (Denmark)

    Fink, Flemming K.

    2006-01-01

    WG2_G4 Problem based learning – linking students and industry: a case study from Aalborg, Denmark Flemming K. Flink ELITE Aalborg University In Aalborg University, Denmark, all study programmes are organised around inter-disciplinary project work in groups. Up to 50% of the study work is problem-...... is essentially problem solving. The presentation looks into on campus POPBL and the Facilitated Work Based Learning (FBL) for continuing education. It also presents case examples of POPBL work....

  18. Characterization of Starch Edible Films with Different Essential Oils Addition

    Directory of Open Access Journals (Sweden)

    Šuput Danijela

    2016-12-01

    Full Text Available This study investigated properties of starch-based edible films with oregano and black cumin essential oil addition. Essential oils addition positively affected film swelling (decreased due to essential oil addition, mechanical properties (tensile strength decreased while elongation at break increased, and water vapor barrier properties (decreased along with essential oils addition. Control film did not have any biological activity, which proves the need for essential oils addition in order to obtain active packaging. Oregano oil was more effective in terms of biological activity. Endothermal peak, above 200°C, represents total thermal degradation of edible films. Diffraction pattern of control film showed significant destruction of A-type crystal structure. Addition of essential oils resulted in peak shape change: diffraction peaks became narrower. Principal Component Analysis has been used to assess the effect of essential oils addition on final starch-based edible films characteristics with the aim to reveal directions for the film characteristics improvement, since the next phase will be optimal film application for food packaging.

  19. Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration

    Energy Technology Data Exchange (ETDEWEB)

    Simarro, Maria [Division of Rheumatology, Immunology and Allergy, Brigham and Women' s Hospital, and Department of Medicine, Harvard Medical School, Boston, MA 02115 (United States); Gimenez-Cassina, Alfredo [Department of Cancer Biology at Dana Farber Institute, Boston, MA 02115 (United States); Kedersha, Nancy [Division of Rheumatology, Immunology and Allergy, Brigham and Women' s Hospital, and Department of Medicine, Harvard Medical School, Boston, MA 02115 (United States); Lazaro, Jean-Bernard; Adelmant, Guillaume O.; Marto, Jarrod A. [Department of Cancer Biology at Dana Farber Institute, Boston, MA 02115 (United States); Rhee, Kirsten [Division of Rheumatology, Immunology and Allergy, Brigham and Women' s Hospital, and Department of Medicine, Harvard Medical School, Boston, MA 02115 (United States); Tisdale, Sarah; Danial, Nika [Department of Cancer Biology at Dana Farber Institute, Boston, MA 02115 (United States); Benarafa, Charaf [Theodor Kocher Institute, University of Bern, 3012 Bern (Switzerland); Orduna, Anonio [Unidad de Investigacion, Hospital Clinico Universitario de Valladolid, 47005 Valladolid (Spain); Anderson, Paul, E-mail: panderson@rics.bwh.harvard.edu [Division of Rheumatology, Immunology and Allergy, Brigham and Women' s Hospital, and Department of Medicine, Harvard Medical School, Boston, MA 02115 (United States)

    2010-10-22

    Research highlights: {yields} Five members of the FAST kinase domain-containing proteins are localized to mitochondria in mammalian cells. {yields} The FASTKD3 interactome includes proteins involved in various aspects of mitochondrial metabolism. {yields} Targeted knockdown of FASTKD3 significantly reduces basal and maximal mitochondrial oxygen consumption. -- Abstract: Fas-activated serine/threonine phosphoprotein (FAST) is the founding member of the FAST kinase domain-containing protein (FASTKD) family that includes FASTKD1-5. FAST is a sensor of mitochondrial stress that modulates protein translation to promote the survival of cells exposed to adverse conditions. Mutations in FASTKD2 have been linked to a mitochondrial encephalomyopathy that is associated with reduced cytochrome c oxidase activity, an essential component of the mitochondrial electron transport chain. We have confirmed the mitochondrial localization of FASTKD2 and shown that all FASTKD family members are found in mitochondria. Although human and mouse FASTKD1-5 genes are expressed ubiquitously, some of them are most abundantly expressed in mitochondria-enriched tissues. We have found that RNA interference-mediated knockdown of FASTKD3 severely blunts basal and stress-induced mitochondrial oxygen consumption without disrupting the assembly of respiratory chain complexes. Tandem affinity purification reveals that FASTKD3 interacts with components of mitochondrial respiratory and translation machineries. Our results introduce FASTKD3 as an essential component of mitochondrial respiration that may modulate energy balance in cells exposed to adverse conditions by functionally coupling mitochondrial protein synthesis to respiration.

  20. Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing.

    Directory of Open Access Journals (Sweden)

    Olivier J Becherel

    2013-04-01

    Full Text Available Senataxin, mutated in the human genetic disorder ataxia with oculomotor apraxia type 2 (AOA2, plays an important role in maintaining genome integrity by coordination of transcription, DNA replication, and the DNA damage response. We demonstrate that senataxin is essential for spermatogenesis and that it functions at two stages in meiosis during crossing-over in homologous recombination and in meiotic sex chromosome inactivation (MSCI. Disruption of the Setx gene caused persistence of DNA double-strand breaks, a defect in disassembly of Rad51 filaments, accumulation of DNA:RNA hybrids (R-loops, and ultimately a failure of crossing-over. Senataxin localised to the XY body in a Brca1-dependent manner, and in its absence there was incomplete localisation of DNA damage response proteins to the XY chromosomes and ATR was retained on the axial elements of these chromosomes, failing to diffuse out into chromatin. Furthermore persistence of RNA polymerase II activity, altered ubH2A distribution, and abnormal XY-linked gene expression in Setx⁻/⁻ revealed an essential role for senataxin in MSCI. These data support key roles for senataxin in coordinating meiotic crossing-over with transcription and in gene silencing to protect the integrity of the genome.

  1. Activation of the JNK pathway is essential for transformation by the Met oncogene.

    Science.gov (United States)

    Rodrigues, G A; Park, M; Schlessinger, J

    1997-05-15

    The Met/Hepatocyte Growth Factor (HGF) receptor tyrosine kinase is oncogenically activated through a rearrangement that creates a hybrid gene Tpr-Met. The resultant chimeric p65(Tpr-Met) protein is constitutively phosphorylated on tyrosine residues in vivo and associates with a number of SH2-containing signaling molecules including the p85 subunit of PI-3 kinase and the Grb2 adaptor protein, which couples receptor tyrosine kinases to the Ras signaling pathway. Mutation of the binding site for Grb2 impairs the ability of Tpr-Met oncoprotein to transform fibroblasts, suggesting that the activation of the Ras/MAP kinase signaling pathway through Grb2 may be essential for cellular transformation. To test this hypothesis dominant-negative mutants of Grb2 with deletions of the SH3 domains were introduced into Tpr-Met transformed fibroblasts. Cells overexpressing the mutants were found to be morphologically reverted and exhibited reduced growth in soft agar. Surprisingly, the Grb2 mutants blocked activation of the JNK/SAPK but not MAP kinase activity induced by the Tpr-Met oncoprotein. Additionally, cells expressing dominant-negative Grb2 mutants had reduced PI-3-kinase activity and dominant-negative mutants of Rac1 blocked both Tpr-Met-induced transformation and activation of JNK. These experiments reveal a novel link between Met and the JNK pathway, which is essential for transformation by this oncogene.

  2. Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration

    International Nuclear Information System (INIS)

    Simarro, Maria; Gimenez-Cassina, Alfredo; Kedersha, Nancy; Lazaro, Jean-Bernard; Adelmant, Guillaume O.; Marto, Jarrod A.; Rhee, Kirsten; Tisdale, Sarah; Danial, Nika; Benarafa, Charaf; Orduna, Anonio; Anderson, Paul

    2010-01-01

    Research highlights: → Five members of the FAST kinase domain-containing proteins are localized to mitochondria in mammalian cells. → The FASTKD3 interactome includes proteins involved in various aspects of mitochondrial metabolism. → Targeted knockdown of FASTKD3 significantly reduces basal and maximal mitochondrial oxygen consumption. -- Abstract: Fas-activated serine/threonine phosphoprotein (FAST) is the founding member of the FAST kinase domain-containing protein (FASTKD) family that includes FASTKD1-5. FAST is a sensor of mitochondrial stress that modulates protein translation to promote the survival of cells exposed to adverse conditions. Mutations in FASTKD2 have been linked to a mitochondrial encephalomyopathy that is associated with reduced cytochrome c oxidase activity, an essential component of the mitochondrial electron transport chain. We have confirmed the mitochondrial localization of FASTKD2 and shown that all FASTKD family members are found in mitochondria. Although human and mouse FASTKD1-5 genes are expressed ubiquitously, some of them are most abundantly expressed in mitochondria-enriched tissues. We have found that RNA interference-mediated knockdown of FASTKD3 severely blunts basal and stress-induced mitochondrial oxygen consumption without disrupting the assembly of respiratory chain complexes. Tandem affinity purification reveals that FASTKD3 interacts with components of mitochondrial respiratory and translation machineries. Our results introduce FASTKD3 as an essential component of mitochondrial respiration that may modulate energy balance in cells exposed to adverse conditions by functionally coupling mitochondrial protein synthesis to respiration.

  3. Cyber essentials a pocket guide

    CERN Document Server

    Calder, Alan

    2014-01-01

    Every year, thousands of computer systems in the UK are compromised. The majority fall victim to easily preventable cyber attacks, carried out with tools which are freely available on the Internet.   Cyber Essentials is the UK Government's reaction to the proliferation of these attacks. It requires that organisations put basic security measures in place, enabling them to reliably counter the most common tactics employed by cyber criminals. From 1 October 2014, all suppliers bidding for a range of government ICT contracts - in particu

  4. Microsoft Windows Operating System Essentials

    CERN Document Server

    Carpenter, Tom

    2012-01-01

    A full-color guide to key Windows 7 administration concepts and topics Windows 7 is the leading desktop software, yet it can be a difficult concept to grasp, especially for those new to the field of IT. Microsoft Windows Operating System Essentials is an ideal resource for anyone new to computer administration and looking for a career in computers. Delving into areas such as fundamental Windows 7 administration concepts and various desktop OS topics, this full-color book addresses the skills necessary for individuals looking to break into a career in IT. Each chapter begins with a list of topi

  5. Axure RP 6 Prototyping Essentials

    CERN Document Server

    Schwartz, Ezra

    2012-01-01

    Axure RP 6 Prototyping Essentials is a detailed, practical primer on the leading rapid prototyping tool. Short on jargon and high on concepts, real-life scenarios and step-by-step guidance through hands-on examples, this book will show you how to integrate Axure into your UX workflow. This book is written for UX practitioners, business analysts, product managers, and anyone else who is involved in UX projects. The book assumes that you have no or very little familiarity with Axure. It will help you if you are evaluating the tool for an upcoming project or are required to quickly get up to spee

  6. Linear feedback controls the essentials

    CERN Document Server

    Haidekker, Mark A

    2013-01-01

    The design of control systems is at the very core of engineering. Feedback controls are ubiquitous, ranging from simple room thermostats to airplane engine control. Helping to make sense of this wide-ranging field, this book provides a new approach by keeping a tight focus on the essentials with a limited, yet consistent set of examples. Analysis and design methods are explained in terms of theory and practice. The book covers classical, linear feedback controls, and linear approximations are used when needed. In parallel, the book covers time-discrete (digital) control systems and juxtapos

  7. Overview of the essential tools

    International Nuclear Information System (INIS)

    Mount, R.P.

    1989-01-01

    The essential tools needed for the analysis of HEP experiments are software, networking, data handling, and CPU power. Leaving most software topics to other papers, this paper describes how we can use today's hardware effectively for HEP data analysis. It describes a new but viable model for HEP computing and data handling on a single site, and outlines the challenge of extending this environment to the wider university-based community. Finally it touches on the revolution in software design that may be triggered by the revolution in computing technology. (orig.)

  8. Essentials of Electromagnetics for Engineering

    Science.gov (United States)

    de Wolf, David A.

    2000-11-01

    Essentials of Electromagnetics for Engineering introduces the key physical and engineering principles of electromagnetics. Throughout the book, David de Wolf describes the intermediate steps in mathematical derivations that many other textbooks leave out. He covers in depth the concepts of fields and potentials and then progresses to magnetostatics, Maxwell's equations, electrodynamics and wave propagation, waveguides, transmission lines, and antennas. At each stage, de Wolf stresses the physical principles underlying the mathematical results. He also includes homework exercises, a separate chapter on numerical methods in electromagnetics, and a broad range of worked examples to illustrate important concepts. Solutions manual available.

  9. Evaluating Antimicrobial Effects of Centaurea Plant’s Essential Oil on Pathogenic Bacteria: Staphylococcus Aureus, Staphylococcus Epidermidis, and Escherichia Coli Isolated from Clinical Specimens

    Directory of Open Access Journals (Sweden)

    Haedeh Mobaiyen

    2016-03-01

    Full Text Available Background & Objectives :Nowadays, development of drug resistance against chemical antimicrobial drugs has attracted attention using medicinal plants in treatment of infections. The aim of this study is to evaluate the antimicrobial effects of two species of Centaurea plant’s essential oil on drug resistant clinical isolates of three pathogenic isolates. Materials & Methods :The studied plants were collected from Marand city in East Azerbaijan, Iran and were confirmed as Centaurea Depressa M.B. and Centaurea Cyanus L. by botanists of Iran Agriculture Organization. The essential oil of these plants (Stems and leaf were extracted via steam distillation method by Clevenger, and their antimicrobial effects were studied by well diffusion method in the abovementioned bacteria. The components of essential oil were identified by injection to gas chromatography linked to mass spectrometry (GC/M. Results :The results of this study prove that the essential oils from the abovementioned plants have bactericidal effects. The most antibacterial effect is observed in Escherichia coli strains. The results of GC/MS chromatography reveal that the essential oils of Centaurea Depressa M.B. and Centaurea Cyanus L. have 28 and 32 compounds, respectively. Conclusion: This study confirmed that the grasses could be used in medicinal plants group with antibacterial properties. However, their effects in vivo must be evaluated and the most effective component of them must be identified carefully so that they can be applied commonly as an alternative synthetic drug in treating infections.

  10. Protein cross-linking by chlorinated polyamines and transglutamylation stabilizes neutrophil extracellular traps.

    Science.gov (United States)

    Csomós, Krisztián; Kristóf, Endre; Jakob, Bernadett; Csomós, István; Kovács, György; Rotem, Omri; Hodrea, Judit; Bagoly, Zsuzsa; Muszbek, Laszlo; Balajthy, Zoltán; Csősz, Éva; Fésüs, László

    2016-08-11

    Neutrophil extracellular trap (NET) ejected from activated dying neutrophils is a highly ordered structure of DNA and selected proteins capable to eliminate pathogenic microorganisms. Biochemical determinants of the non-randomly formed stable NETs have not been revealed so far. Studying the formation of human NETs we have observed that polyamines were incorporated into the NET. Inhibition of myeloperoxidase, which is essential for NET formation and can generate reactive chlorinated polyamines through hypochlorous acid, decreased polyamine incorporation. Addition of exogenous primary amines that similarly to polyamines inhibit reactions catalyzed by the protein cross-linker transglutaminases (TGases) has similar effect. Proteomic analysis of the highly reproducible pattern of NET components revealed cross-linking of NET proteins through chlorinated polyamines and ɛ(γ-glutamyl)lysine as well as bis-γ-glutamyl polyamine bonds catalyzed by the TGases detected in neutrophils. Competitive inhibition of protein cross-linking by monoamines disturbed the cross-linking pattern of NET proteins, which resulted in the loss of the ordered structure of the NET and significantly reduced capacity to trap bacteria. Our findings provide explanation of how NETs are formed in a reproducible and ordered manner to efficiently neutralize microorganisms at the first defense line of the innate immune system.

  11. Essentials of applied dynamic analysis

    CERN Document Server

    Jia, Junbo

    2014-01-01

    This book presents up-to-date knowledge of dynamic analysis in engineering world. To facilitate the understanding of the topics by readers with various backgrounds, general principles are linked to their applications from different angles. Special interesting topics such as statistics of motions and loading, damping modeling and measurement, nonlinear dynamics, fatigue assessment, vibration and buckling under axial loading, structural health monitoring, human body vibrations, and vehicle-structure interactions etc., are also presented. The target readers include industry professionals in civil, marine and mechanical engineering, as well as researchers and students in this area.

  12. Health communication, genetic determinism, and perceived control: the roles of beliefs about susceptibility and severity versus disease essentialism.

    Science.gov (United States)

    Parrott, Roxanne; Kahl, Mary L; Ndiaye, Khadidiatou; Traeder, Tara

    2012-08-01

    This research examined the lay public's beliefs about genes and health that might be labeled deterministic. The goals of this research were to sort through the divergent and contested meanings of genetic determinism in an effort to suggest directions for public health genomic communication. A survey conducted in community-based settings of 717 participants included 267 who self-reported race as African American and 450 who self-reported race as Caucasian American. The survey results revealed that the structure of genetic determinism included 2 belief sets. One set aligned with perceived threat, encompassing susceptibility and severity beliefs linked to genes and health. The other set represents beliefs about biological essentialism linked to the role of genes for health. These concepts were found to be modestly positively related. Threat beliefs predicted perceived control over genes. Public health efforts to communicate about genes and health should consider effects of these messages for (a) perceived threat relating to susceptibility and severity and (b) perceptions of disease essentialism. Perceived threat may enhance motivation to act in health protective ways, whereas disease essentialist beliefs may contribute to a loss of motivation associated with control over health.

  13. Emerging treatments for essential thrombocythemia

    Directory of Open Access Journals (Sweden)

    Okoli S

    2011-12-01

    Full Text Available Steven Okoli, Claire HarrisonDepartment of Haematology, Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UKAbstract: In 1934, Epstein and Goedel used the term hemorrhagic thrombocythemia to describe a disorder characterized by permanent elevation of a platelet count to more than three times normal, hyperplasia of megakaryocytes, and the tendency for venous thrombosis and spontaneous hemorrhage. Over the last 75 years, and particularly in the past 6 years, major progress has been made in our understanding of essential thrombocythemia (ET and its pathogenesis with the identification of the highly prevalent JAK-2 V617F and other mutations. Current management of this condition is based upon historical data and with treatments that have not changed significantly for nearly two decades. This study discusses this and recent progress, highlighting exciting new data with old and new drugs, as well as which patients in particular should be evaluated for these new therapies.Keywords: essential thrombocythemia, interferon, JAK inhibitor

  14. Economic demand and essential value.

    Science.gov (United States)

    Hursh, Steven R; Silberberg, Alan

    2008-01-01

    The strength of a rat's eating reflex correlates with hunger level when strength is measured by the response frequency that precedes eating (B. F. Skinner, 1932a, 1932b). On the basis of this finding, Skinner argued response frequency could index reflex strength. Subsequent work documented difficulties with this notion because responding was affected not only by the strengthening properties of the reinforcer but also by the rate-shaping effects of the schedule. This article obviates this problem by measuring strength via methods from behavioral economics. This approach uses demand curves to map how reinforcer consumption changes with changes in the "price" different ratio schedules impose. An exponential equation is used to model these demand curves. The value of this exponential's rate constant is used to scale the strength or essential value of a reinforcer, independent of the scalar dimensions of the reinforcer. Essential value determines the consumption level to be expected at particular prices and the response level that will occur to support that consumption. This approach permits comparing reinforcers that differ in kind, contributing toward the goal of scaling reinforcer value. (c) 2008 APA, all rights reserved

  15. Essential Tremor: A Neurodegenerative Disease?

    Directory of Open Access Journals (Sweden)

    Julian Benito-Leon

    2014-07-01

    Full Text Available Background: Essential tremor (ET is one of the most common neurological disorders among adults, and is the most common of the many tremor disorders. It has classically been viewed as a benign monosymptomatic condition, yet over the past decade, a growing body of evidence indicates that ET is a progressive condition that is clinically heterogeneous, as it may be associated with a spectrum of clinical features, with both motor and non‐motor elements. In this review, I will describe the most significant emerging milestones in research which, when taken together, suggest that ET is a neurodegenerative condition.Methods: A PubMed search conducted in June 2014 crossing the terms “essential tremor” (ET and “neurodegenerative” yielded 122 entries, 20 of which included the term “neurodegenerative” in the article title. This was supplemented by articles in the author's files that pertained to this topic.Results/Discussion: There is an open and active dialogue in the medical community as to whether ET is a neurodegenerative disease, with considerable evidence in favor of this. Specifically, ET is a progressive disorder of aging associated with neuronal loss (reduction in Purkinje cells as well as other post‐mortem changes that occur in traditional neurodegenerative disorders. Along with this, advanced neuroimaging techniques are now demonstrating distinct structural changes, several of which are consistent with neuronal loss, in patients with ET. However, further longitudinal clinical and neuroimaging longitudinal studies to assess progression are required.

  16. Interplay between human high mobility group protein 1 and replication protein A on psoralen-cross-linked DNA

    DEFF Research Database (Denmark)

    Reddy, Madhava C; Christensen, Jesper; Vasquez, Karen M

    2005-01-01

    -DNA interstrand cross-link (ICL) to a specific site to determine the effect of HMGB proteins on recognition of these lesions. Our results reveal that human HMGB1 (but not HMGB2) binds with high affinity and specificity to psoralen ICLs, and interacts with the essential NER protein, replication protein A (RPA......), at these lesions. RPA, shown previously to bind tightly to these lesions, also binds in the presence of HMGB1, without displacing HMGB1. A discrete ternary complex is formed, containing HMGB1, RPA, and psoralen-damaged DNA. Thus, HMGB1 has the ability to recognize ICLs, can cooperate with RPA in doing so...

  17. Levels of essential and non-essential metals in ginger (Zingiber officinale) cultivated in Ethiopia.

    Science.gov (United States)

    Wagesho, Yohannes; Chandravanshi, Bhagwan Singh

    2015-01-01

    Ginger (Zingiber officinale Roscoe) is a common condiment for various foods and beverages and widely used worldwide as a spice. Its extracts are used extensively in the food, beverage, and confectionary industries in the production of products such as marmalade, pickles, chutney, ginger beer, ginger wine, liquors, biscuits, and other bakery products. In Ethiopia, it is among the important spices used in every kitchen to flavor stew, tea, bread and local alcoholic drinks. It is also chiefly used medicinally for indigestion, stomachache, malaria, fevers, common cold, and motion sickness. The literature survey revealed that there is no study conducted on the determination of metals in ginger cultivated in Ethiopia. Hence it is worthwhile to determine the levels of essential and non-essential metals in ginger cultivated in Ethiopia. The levels of essential (Ca, Mg, Fe, Zn, Cu, Co, Cr, Mn, and Ni) and non-essential (Cd and Pb) metals in ginger (Zingiber officinale Roscoe) cultivated in four different regions of Ethiopia and the soil where it was grown were determined by flame atomic absorption spectrometry. 0.5 g of oven dried ginger and soil samples were digested using 3 mL of HNO3 and 1 mL of HClO4 at 210°C for 3 h and a mixture of 6 mL aqua-regia and 1.5 mL H2O2 at 270°C for 3 h, respectively. The mean metal concentration (μg/g dry weight basis) ranged in the ginger and soil samples, respectively, were: Ca (2000-2540, 1770-3580), Mg (2700-4090, 1460-2440), Fe (41.8-89.0, 21700-46900), Zn (38.5-55.2, 255-412), Cu (1.1-4.8, 3.80-33.9), Co (2.0-7.6, 48.5-159), Cr (6.0-10.8, 110-163), Mn (184-401, 1760-6470), Ni (5.6-8.4, 14.1-79.3) and Cd (0.38-0.97, 0.24-1.1). The toxic metal Pb was not detected in both the ginger and soil samples. There was good correlation between some metals in ginger and soil samples while poor correlation between other metals (Fe, Ni, Cu). This study revealed that Ethiopian gingers are good source of essential metals and free from toxic

  18. Link to paper

    Data.gov (United States)

    U.S. Environmental Protection Agency — Link to the paper. This dataset is associated with the following publication: Naile, J., A.W. Garrison, J. Avants, and J. Washington. Isomers/enantiomers of...

  19. [Disappearance of essential neck tremor after pontine base infarction].

    Science.gov (United States)

    Urushitani, M; Inoue, H; Kawamura, K; Kageyama, T; Fujisawa, M; Nishinaka, K; Udaka, F; Kameyama, M

    1996-08-01

    Mechanism of essential tremor remains unknown. Central oscillators, postulated in thalamus, inferior olive, and spinal cord are thought to be important to form rhythmicity, and finally to stimulate spinal or medullary motor cells, leading trembling muscle contraction, tremor. Among several subtypes of essential familial tremor, including hand tremor, neck tremor, and voice tremor, essential neck tremor is a common disorder, and its pathophysiology seems different from that of typical essential hand tremor, since patients with essential hand tremor are responsive to beta blocker, whereas those with neck tremor are usually not. We experienced a 41-year-old left handed woman with essential neck tremor in whom neck titubation disappeared shortly after pontine base infarct. She was our patient in the outpatient clinic with the diagnosis of essential neck tremor. The tremor developed when she was teenage, and has been localized in the neck muscles. Alcohol intake had apparently diminished it transiently. Her mother also had the tremor in her neck. She was admitted to our hospital with sudden onset of right-sided limb weakness and speech disturbance. Neurological examination showed right hemiparesis including the ipsilateral face, scanning speech, and cerebellar limb ataxia on the same side. In addition, there was no tremor in her neck. Brain MR imaging revealed a pontine base infarct at the level of middle pons, which was consistent with paramedian artery territory. The hemiparesis and speech disturbance improved almost completely after treatment, and her neck tremor has never occurred in one year follow-up. In our patient, efficacy of alcohol imply that essential neck tremor and hand tremor had same central nervous pathway including central oscillator in common, and descending cortical fibers is seemingly associated with diminishing patient's tremor. Pathophysiology of essential neck tremor was discussed with reviewing previous literature.

  20. Focusing on the essentials: learning for performance.

    Science.gov (United States)

    Murphy, Catherine J

    2008-12-10

    As The World health report 2006 emphasized, there is increasing consensus that training programmes should focus on "know-how" instead of "know-all." Health workers need to know how to do the job they will be expected to do. IntraHealth International's Learning for performance: a guide and toolkit for health worker training and education programs offers a step-by-step, customizable approach designed to develop the right skills linked to job responsibilities. Using Learning for performance (LFP) yields more efficient training that focuses on what is essential for health workers to do their jobs and on effective learning methods, while addressing the factors that ensure application of new skills on the job. This brief communication describes the Learning for performance approach and initial findings from its application for pre-service education and in-service training in three countries: India, Mali and Bangladesh. Based on IntraHealth's experiences, the author provides thoughts on how LFP's performance-based learning approach can be a useful tool in training scale-up to strengthen human resources for health.

  1. Focusing on the essentials: learning for performance

    Directory of Open Access Journals (Sweden)

    Murphy Catherine J

    2008-12-01

    Full Text Available Abstract As The World health report 2006 emphasized, there is increasing consensus that training programmes should focus on "know-how" instead of "know-all." Health workers need to know how to do the job they will be expected to do. IntraHealth International's Learning for performance: a guide and toolkit for health worker training and education programs offers a step-by-step, customizable approach designed to develop the right skills linked to job responsibilities. Using Learning for performance (LFP yields more efficient training that focuses on what is essential for health workers to do their jobs and on effective learning methods, while addressing the factors that ensure application of new skills on the job. This brief communication describes the Learning for performance approach and initial findings from its application for pre-service education and in-service training in three countries: India, Mali and Bangladesh. Based on IntraHealth's experiences, the author provides thoughts on how LFP's performance-based learning approach can be a useful tool in training scale-up to strengthen human resources for health.

  2. The Missing Link

    DEFF Research Database (Denmark)

    Schultz, Laura Luise

    2014-01-01

    Paper presented at A Valentine to Gertrude Stein. The Reception of Gertrude Stein in the Arts and Humanities, held at the University of Copenhagen 8. - 10. May 2014, in collaboration with the universities of Ghent and Linköping......Paper presented at A Valentine to Gertrude Stein. The Reception of Gertrude Stein in the Arts and Humanities, held at the University of Copenhagen 8. - 10. May 2014, in collaboration with the universities of Ghent and Linköping...

  3. Essential AOP: The A Calculus

    DEFF Research Database (Denmark)

    De Fraine, Bruno; Ernst, Erik; Südholt, Mario

    2012-01-01

    Aspect-oriented programming (AOP) has produced interesting language designs, but also ad hoc semantics that needs clarification. We contribute to this clarification with a calculus that models essential AOP, both simpler and more general than existing formalizations. In AOP, advice may intercept......-oriented code. Two well-known pointcut categories, call and execution, are commonly considered similar.We formally expose their differences, and resolve the associated soundness problem. Our calculus includes type ranges, an intuitive and concise alternative to explicit type variables that allows advice...... to be polymorphic over intercepted methods. We use calculus parameters to cover type safety for a wide design space of other features. Type soundness is verified in Coq....

  4. Linked Ocean Data

    Science.gov (United States)

    Leadbetter, Adam; Arko, Robert; Chandler, Cynthia; Shepherd, Adam

    2014-05-01

    "Linked Data" is a term used in Computer Science to encapsulate a methodology for publishing data and metadata in a structured format so that links may be created and exploited between objects. Berners-Lee (2006) outlines the following four design principles of a Linked Data system: Use Uniform Resource Identifiers (URIs) as names for things. Use HyperText Transfer Protocol (HTTP) URIs so that people can look up those names. When someone looks up a URI, provide useful information, using the standards (Resource Description Framework [RDF] and the RDF query language [SPARQL]). Include links to other URIs so that they can discover more things. In 2010, Berners-Lee revisited his original design plan for Linked Data to encourage data owners along a path to "good Linked Data". This revision involved the creation of a five star rating system for Linked Data outlined below. One star: Available on the web (in any format). Two stars: Available as machine-readable structured data (e.g. An Excel spreadsheet instead of an image scan of a table). Three stars: As two stars plus the use of a non-proprietary format (e.g. Comma Separated Values instead of Excel). Four stars: As three stars plus the use of open standards from the World Wide Web Commission (W3C) (i.e. RDF and SPARQL) to identify things, so that people can point to your data and metadata. Five stars: All the above plus link your data to other people's data to provide context Here we present work building on the SeaDataNet common vocabularies served by the NERC Vocabulary Server, connecting projects such as the Rolling Deck to Repository (R2R) and the Biological and Chemical Oceanography Data Management Office (BCO-DMO) and other vocabularies such as the Marine Metadata Interoperability Ontology Register and Repository and the NASA Global Change Master Directory to create a Linked Ocean Data cloud. Publishing the vocabularies and metadata in standard RDF XML and exposing SPARQL endpoints renders them five-star Linked

  5. Essential oil of Algerian Eucalyptus citriodora: Chemical composition, antifungal activity.

    Science.gov (United States)

    Tolba, H; Moghrani, H; Benelmouffok, A; Kellou, D; Maachi, R

    2015-12-01

    Essential oil of Eucalyptus citriodora is a natural product which has been attributed for various medicinal uses. In the present investigation, E. citriodora essential oil was used to evaluate its antifungal effect against medically important dermatophytes. Essential oil from the Algerian E. citriodora leaves was analyzed by GC and GC/MS. The antifungal effect of E. citriodora essential oil was evaluated against four dermatophytes: Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes, Trichophyton rubrum using disc diffusion method, disc volatilization method, and agar dilution method. The chemical composition of the oil revealed the presence of 22 compounds accounting for 95.27% of the oil. The dominant compounds were citronellal (69.77%), citronellol (10.63%) and isopulegol (4.66%). The disc diffusion method, MIC and MFC determination, indicated that E. citriodora essential oil had a higher antifungal potential against the tested strains with inhibition zone diameter which varied from (12 to 90mm) and MIC and MFC values ranged from (0.6 to 5μL/mL and 1.25 to 5μL/mL) respectively. The M. gypseum was the most resistant to the oil. The results of the present study indicated that E. citriodora essential oil may be used as a new antifungal agent recommended by the pharmaceutical industries. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Yeasts are essential for cocoa bean fermentation.

    Science.gov (United States)

    Ho, Van Thi Thuy; Zhao, Jian; Fleet, Graham

    2014-03-17

    Cocoa beans (Theobroma cacao) are the major raw material for chocolate production and fermentation of the beans is essential for the development of chocolate flavor precursors. In this study, a novel approach was used to determine the role of yeasts in cocoa fermentation and their contribution to chocolate quality. Cocoa bean fermentations were conducted with the addition of 200ppm Natamycin to inhibit the growth of yeasts, and the resultant microbial ecology and metabolism, bean chemistry and chocolate quality were compared with those of normal (control) fermentations. The yeasts Hanseniaspora guilliermondii, Pichia kudriavzevii and Kluyveromyces marxianus, the lactic acid bacteria Lactobacillus plantarum and Lactobacillus fermentum and the acetic acid bacteria Acetobacter pasteurianus and Gluconobacter frateurii were the major species found in the control fermentation. In fermentations with the presence of Natamycin, the same bacterial species grew but yeast growth was inhibited. Physical and chemical analyses showed that beans fermented without yeasts had increased shell content, lower production of ethanol, higher alcohols and esters throughout fermentation and lesser presence of pyrazines in the roasted product. Quality tests revealed that beans fermented without yeasts were purplish-violet in color and not fully brown, and chocolate prepared from these beans tasted more acid and lacked characteristic chocolate flavor. Beans fermented with yeast growth were fully brown in color and gave chocolate with typical characters which were clearly preferred by sensory panels. Our findings demonstrate that yeast growth and activity were essential for cocoa bean fermentation and the development of chocolate characteristics. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  7. De Sedibus et Causis Morborum: is Essential Tremor a Primary Disease of the Cerebellum?

    Science.gov (United States)

    Louis, Elan D

    2016-06-01

    Morgagni's 1761 publication of De sedibus et causis morborum (i.e., of the Seats and Causes of Diseases) represented a paradigmatic moment in the history of medicine. The book ushered in a new way of conceptualizing human disease, shattering old dogma, and linking constellations of symptoms and signs (i.e., clinical disease) with anatomic pathology in specific organs (i.e., organ disease). This was the anatomical-clinical method, and it attempted to unveil "the seat" of each disease in a specific organ. Essential tremor (ET) is among the most common neurological diseases. There is little debate that the origin of ET lies in the brain, but if one tries to delve more deeply than this, things become murky. The dogma for the past 40 years has been that the seat of ET is the inferior olivary nucleus. Closer scrutiny of this model, however, has revealed its many flaws, and the model, based on little if any empiric evidence, has increasingly lost favor. Arising from a wealth of research in recent years is a growing body of knowledge that links ET to a disarrangement of the cerebellum. Data from a variety of sources reviewed in this issue (clinical, neuroimaging, neurochemical, animal model, physiological, and pathological) link ET to the cerebellum. That the cerebellum is involved in an abnormal brain loop that is responsible for ET is not debated. The tantalizing question is whether an abnormality in the cerebellum is the prime mover, and whether the cerebellum is the seat of this particular disease.

  8. Learning Neuroimaging. 100 essential cases

    International Nuclear Information System (INIS)

    Asis Bravo-Rodriguez, Francisco de; Diaz-Aguilera, Rocio; Hygino da Cruz, Luiz Celso

    2012-01-01

    Neuroradiology is the branch of radiology that comprises both imaging and invasive procedures related to the brain, spine and spinal cord, head, neck, organs of special sense (eyes, ears, nose), cranial and spinal nerves, and cranial, cervical, and spinal vessels. Special training and skills are required to enable the neuroradiologist to function as an expert diagnostic and therapeutic consultant and practitioner. In addition to knowledge of imaging findings, the neuroradiologist is required to learn the fundamentals of structural and functional neuroanatomy, neuropathology, and neuropathophysiology as well as the clinical manifestations of diseases of the brain, spine and spinal cord, head, neck, and organs of special sense. This book is intended as an introduction to neuroradiology and aims to provide the reader with a comprehensive overview of this highly specialized radiological subspecialty. One hundred illustrated cases from clinical practice are presented in a standard way. Each case is supported by representative images and is divided into three parts: a brief summary of the patient's medical history, a discussion of the disease, and a description of the most characteristic imaging features of the disorder. The focus is not only on common neuroradiological entities such as stroke and acute head trauma but also on less frequent disorders that the practitioner should recognize. Learning Neuroimaging: 100 Essential Cases is an ideal resource for neuroradiology and radiology residents, neurology residents, neurosurgery residents, nurses, radiology technicians, and medical students. (orig.)

  9. Learning Neuroimaging. 100 essential cases

    Energy Technology Data Exchange (ETDEWEB)

    Asis Bravo-Rodriguez, Francisco de [Reina Sofia University Hospital, Cordoba (Spain). Diagnostic and Therapeutics Neuroradiology; Diaz-Aguilera, Rocio [Alto Guadalquivir Hospital, Andujar, Jaen (Spain). Dept. of Radiology; Hygino da Cruz, Luiz Celso [Universidade Federal do Rio de Janeiro (Brazil). CDPI and IRM Ressonancia Magnetica

    2012-07-01

    Neuroradiology is the branch of radiology that comprises both imaging and invasive procedures related to the brain, spine and spinal cord, head, neck, organs of special sense (eyes, ears, nose), cranial and spinal nerves, and cranial, cervical, and spinal vessels. Special training and skills are required to enable the neuroradiologist to function as an expert diagnostic and therapeutic consultant and practitioner. In addition to knowledge of imaging findings, the neuroradiologist is required to learn the fundamentals of structural and functional neuroanatomy, neuropathology, and neuropathophysiology as well as the clinical manifestations of diseases of the brain, spine and spinal cord, head, neck, and organs of special sense. This book is intended as an introduction to neuroradiology and aims to provide the reader with a comprehensive overview of this highly specialized radiological subspecialty. One hundred illustrated cases from clinical practice are presented in a standard way. Each case is supported by representative images and is divided into three parts: a brief summary of the patient's medical history, a discussion of the disease, and a description of the most characteristic imaging features of the disorder. The focus is not only on common neuroradiological entities such as stroke and acute head trauma but also on less frequent disorders that the practitioner should recognize. Learning Neuroimaging: 100 Essential Cases is an ideal resource for neuroradiology and radiology residents, neurology residents, neurosurgery residents, nurses, radiology technicians, and medical students. (orig.)

  10. Link til hjemmesider

    DEFF Research Database (Denmark)

    Bervild, Charlotte

    2015-01-01

    Link til læringsobjekter/undervisningsportalhttp://videoportal.ucc.dk/channel/10492641/charlotte-bervilds-undervisninghttp://videoportal.ucc.dk/video/8248508/3d-printer-v-lektor-charlotte-bervildFotoblog:http://charlottebervild.blogspot.dk/2008/10/fotocollager-af-charlotte-bervild.html......Link til læringsobjekter/undervisningsportalhttp://videoportal.ucc.dk/channel/10492641/charlotte-bervilds-undervisninghttp://videoportal.ucc.dk/video/8248508/3d-printer-v-lektor-charlotte-bervildFotoblog:http://charlottebervild.blogspot.dk/2008/10/fotocollager-af-charlotte-bervild.html...

  11. Essential Tremor Is More Than a Tremor

    Science.gov (United States)

    ... Giving Options Donate Prev Next IETF > About Essential Tremor > Video Video Click to share on Facebook (Opens ... Click to print (Opens in new window) Essential Tremor is More Than a Tremor Providing a voice ...

  12. Essential Tremor Is More Than a Tremor

    Medline Plus

    Full Text Available ... Giving Options Donate Prev Next IETF > About Essential Tremor > Video Video Click to share on Facebook (Opens ... Click to print (Opens in new window) Essential Tremor is More Than a Tremor Providing a voice ...

  13. Essential Tremor Is More Than a Tremor

    Medline Plus

    Full Text Available Home About the IETF Volunteer For Healthcare Providers Giving Options Donate Prev Next IETF > About Essential Tremor > ... for Grants Relevant to Essential Tremor IETF Champion Home About the IETF Volunteer For Healthcare Providers Giving ...

  14. Essential Palatal Tremor Managed by Cognitive Behavioral Therapy

    Directory of Open Access Journals (Sweden)

    Tomohisa Kitamura

    2015-01-01

    Full Text Available Background. Essential palatal tremor is a disorder of unknown etiology involving involuntary movement of the uvula and soft palate. Treatment attempts including drugs or surgery have been conducted to cease the rhythmical movement. Case Report. A 55-year-old female visited our department complaining of a sudden, noticeable, intermittent, and rhythmical clicking noise in her throat for five years. Oral examination revealed rhythmical contractions of the soft palate with clicking at the frequency of 120 per min. Magnetic resonance imaging (MRI examination of the brain performed after consulting with the department of neuropathic internal medicine showed no abnormalities. Thus, essential palatal tremor was diagnosed. The symptoms improved with cognitive behavioral therapy without drugs or surgical treatments. The patient is now able to stop the rhythmical movement voluntarily. Discussion. Cognitive behavioral therapy might be suitable as first-line therapy for essential palatal tremor because the therapy is noninvasive.

  15. Helically linked mirror arrangement

    International Nuclear Information System (INIS)

    Ranjan, P.

    1986-08-01

    A scheme is described for helical linking of mirror sections, which endeavors to combine the better features of toroidal and mirror devices by eliminating the longitudinal loss of mirror machines, having moderately high average β and steady state operation. This scheme is aimed at a device, with closed magnetic surfaces having rotational transform for equilibrium, one or more axisymmetric straight sections for reduced radial loss, a simple geometrical axis for the links and an overall positive magnetic well depth for stability. We start by describing several other attempts at linking of mirror sections, made both in the past and the present. Then a description of our helically linked mirror scheme is given. This example has three identical straight sections connected by three sections having helical geometric axes. A theoretical analysis of the magnetic field and single-particle orbits in them leads to the conclusion that most of the passing particles would be confined in the device and they would have orbits independent of pitch angle under certain conditions. Numerical results are presented, which agree well with the theoretical results as far as passing particle orbits are concerned

  16. Essential climatic variables estimation with satellite imagery

    Science.gov (United States)

    Kolotii, A.; Kussul, N.; Shelestov, A.; Lavreniuk, M. S.

    2016-12-01

    According to Sendai Framework for Disaster Risk Reduction 2015 - 2030 Leaf Area Index (LAI) is considered as one of essential climatic variables. This variable represents the amount of leaf material in ecosystems and controls the links between biosphere and atmosphere through various processes and enables monitoring and quantitative assessment of vegetation state. LAI has added value for such important global resources monitoring tasks as drought mapping and crop yield forecasting with use of data from different sources [1-2]. Remote sensing data from space can be used to estimate such biophysical parameter at regional and national scale. High temporal satellite imagery is usually required to capture main parameters of crop growth [3]. Sentinel-2 mission launched in 2015 be ESA is a source of high spatial and temporal resolution satellite imagery for mapping biophysical parameters. Products created with use of automated Sen2-Agri system deployed during Sen2-Agri country level demonstration project for Ukraine will be compared with our independent results of biophysical parameters mapping. References Shelestov, A., Kolotii, A., Camacho, F., Skakun, S., Kussul, O., Lavreniuk, M., & Kostetsky, O. (2015, July). Mapping of biophysical parameters based on high resolution EO imagery for JECAM test site in Ukraine. In 2015 IEEE International Geoscience and Remote Sensing Symposium (IGARSS), 1733-1736 Kolotii, A., Kussul, N., Shelestov, A., Skakun, S., Yailymov, B., Basarab, R., ... & Ostapenko, V. (2015). Comparison of biophysical and satellite predictors for wheat yield forecasting in Ukraine. The International Archives of Photogrammetry, Remote Sensing and Spatial Information Sciences, 40(7), 39-44. Kussul, N., Lemoine, G., Gallego, F. J., Skakun, S. V., Lavreniuk, M., & Shelestov, A. Y. Parcel-Based Crop Classification in Ukraine Using Landsat-8 Data and Sentinel-1A Data. IEEE Journal of Selected Topics in Applied Earth Observations and Remote Sensing , 9 (6), 2500-2508.

  17. The nature of tremor circuits in parkinsonian and essential tremor

    Science.gov (United States)

    Cagnan, Hayriye; Little, Simon; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Cheeran, Binith; Fitzgerald, James; Green, Alexander L.; Aziz, Tipu

    2014-01-01

    Tremor is a cardinal feature of Parkinson’s disease and essential tremor, the two most common movement disorders. Yet, the mechanisms underlying tremor generation remain largely unknown. We hypothesized that driving deep brain stimulation electrodes at a frequency closely matching the patient’s own tremor frequency should interact with neural activity responsible for tremor, and that the effect of stimulation on tremor should reveal the role of different deep brain stimulation targets in tremor generation. Moreover, tremor responses to stimulation might reveal pathophysiological differences between parkinsonian and essential tremor circuits. Accordingly, we stimulated 15 patients with Parkinson’s disease with either thalamic or subthalamic electrodes (13 male and two female patients, age: 50–77 years) and 10 patients with essential tremor with thalamic electrodes (nine male and one female patients, age: 34–74 years). Stimulation at near-to tremor frequency entrained tremor in all three patient groups (ventrolateral thalamic stimulation in Parkinson’s disease, P = 0.0078, subthalamic stimulation in Parkinson’s disease, P = 0.0312; ventrolateral thalamic stimulation in essential tremor, P = 0.0137; two-tailed paired Wilcoxon signed-rank tests). However, only ventrolateral thalamic stimulation in essential tremor modulated postural tremor amplitude according to the timing of stimulation pulses with respect to the tremor cycle (e.g. P = 0.0002 for tremor amplification, two-tailed Wilcoxon rank sum test). Parkinsonian rest and essential postural tremor severity (i.e. tremor amplitude) differed in their relative tolerance to spontaneous changes in tremor frequency when stimulation was not applied. Specifically, the amplitude of parkinsonian rest tremor remained unchanged despite spontaneous changes in tremor frequency, whereas that of essential postural tremor reduced when tremor frequency departed from median values. Based on these results we conclude that

  18. Uncovering missing links with cold ends

    Science.gov (United States)

    Zhu, Yu-Xiao; Lü, Linyuan; Zhang, Qian-Ming; Zhou, Tao

    2012-11-01

    To evaluate the performance of prediction of missing links, the known data are randomly divided into two parts, the training set and the probe set. We argue that this straightforward and standard method may lead to terrible bias, since in real biological and information networks, missing links are more likely to be links connecting low-degree nodes. We therefore study how to uncover missing links with low-degree nodes, namely links in the probe set are of lower degree products than a random sampling. Experimental analysis on ten local similarity indices and four disparate real networks reveals a surprising result that the Leicht-Holme-Newman index [E.A. Leicht, P. Holme, M.E.J. Newman, Vertex similarity in networks, Phys. Rev. E 73 (2006) 026120] performs the best, although it was known to be one of the worst indices if the probe set is a random sampling of all links. We further propose an parameter-dependent index, which considerably improves the prediction accuracy. Finally, we show the relevance of the proposed index to three real sampling methods: acquaintance sampling, random-walk sampling and path-based sampling.

  19. Antitumor Activity of Monoterpenes Found in Essential Oils

    Directory of Open Access Journals (Sweden)

    Marianna Vieira Sobral

    2014-01-01

    Full Text Available Cancer is a complex genetic disease that is a major public health problem worldwide, accounting for about 7 million deaths each year. Many anticancer drugs currently used clinically have been isolated from plant species or are based on such substances. Accumulating data has revealed anticancer activity in plant-derived monoterpenes. In this review the antitumor activity of 37 monoterpenes found in essential oils is discussed. Chemical structures, experimental models, and mechanisms of action for bioactive substances are presented.

  20. Saramago’s Death with Interruptions: A Path to Reconsider Essential Dilemmas Linked to Health Law

    Directory of Open Access Journals (Sweden)

    Sandra Mabel Wierzba

    2014-12-01

    Full Text Available What would happen if somewhere people would stop dying? In Saramago’s Death with interruptions, after the initial joy associated to the possibility of eternal life, anxiety and conflict invade the community. The end of death not only shakes Philosophy and Religion foundations, but it impacts on various legal institutions as well. In this paper, we consider the notion of Justice from the Right to Health perspective. In particular, we analyse the concept of “euthanasia" and the current role of insurance from the private law viewpoint, taking into account its “constitutionalization" process. We remark the wisdom of the parable built by the author because of the simplicity, sharpness and versatility when addressing dilemmas that Law cannot fully solve. ¿Qué ocurriría si en algún lugar la gente dejara de morir? En Las intermitencias de la muerte de Saramago, tras la alegría inicial por la posibilidad de la vida eterna, la ansiedad y el conflicto predominan en la comunidad. El final de la muerte no sólo sacude los cimientos de la Filosofía y Religión, pero también afecta a diversas instituciones jurídicas. En este artículo se considera el concepto de Justicia desde la perspectiva de derecho a la salud. En particular, se analiza el concepto de “eutanasia” y el papel actual de los seguros desde el punto de vista del derecho privado, teniendo en cuenta su proceso de “constitucionalización”. Se destaca la sensatez de la parábola construida por el autor por su simplicidad, nitidez y versatilidad al abordar los dilemas que la Ley no puede resolver completamente. DOWNLOAD THIS PAPER FROM SSRN: http://ssrn.com/abstract=2520437

  1. Essential Features of Serious Games Design in Higher Education: Linking Learning Attributes to Game Mechanics

    Science.gov (United States)

    Lameras, Petros; Arnab, Sylvester; Dunwell, Ian; Stewart, Craig; Clarke, Samantha; Petridis, Panagiotis

    2017-01-01

    This paper consolidates evidence and material from a range of specialist and disciplinary fields to provide an evidence-based review and synthesis on the design and use of serious games in higher education. Search terms identified 165 papers reporting conceptual and empirical evidence on how learning attributes and game mechanics may be planned,…

  2. Linking Bacterial Endophytic Communities to Essential Oils: Clues from Lavandula angustifolia Mill

    Science.gov (United States)

    Emiliani, Giovanni; Maida, Isabel; Perrin, Elena; Chiellini, Carolina; Fondi, Marco; Gallo, Eugenia; Gori, Luigi; Maggini, Valentina; Vannacci, Alfredo; Biffi, Sauro; Firenzuoli, Fabio; Fani, Renato

    2014-01-01

    Endophytic bacteria play a crucial role in plant life and are also drawing much attention for their capacity to produce bioactive compounds of relevant biotechnological interest. Here we present the characterisation of the cultivable endophytic bacteria of Lavandula angustifolia Mill.—a species used since antiquity for its therapeutic properties—since the production of bioactive metabolites from medical plants may reside also in the activity of bacterial endophytes through their direct production, PGPR activity on host, and/or elicitation of plant metabolism. Lavender tissues are inhabited by a tissue specific endophytic community dominated by Proteobacteria, highlighting also their difference from the rhizosphere environment where Actinobacteria and Firmicutes are also found. Leaves' endophytic community resulted as the most diverse from the other ecological niches. Overall, the findings reported here suggest: (i) the existence of different entry points for the endophytic community, (ii) its differentiation on the basis of the ecological niche variability, and (iii) a two-step colonization process for roots endophytes. Lastly, many isolates showed a strong inhibition potential against human pathogens and the molecular characterization demonstrated also the presence of not previously described isolates that may constitute a reservoir of bioactive compounds relevant in the field of pathogen control, phytoremediation, and human health. PMID:24971151

  3. Saramago’s Death with Interruptions: A Path to Reconsider Essential Dilemmas Linked to Health Law

    OpenAIRE

    Sandra Mabel Wierzba

    2014-01-01

    What would happen if somewhere people would stop dying? In Saramago’s Death with interruptions, after the initial joy associated to the possibility of eternal life, anxiety and conflict invade the community. The end of death not only shakes Philosophy and Religion foundations, but it impacts on various legal institutions as well. In this paper, we consider the notion of Justice from the Right to Health perspective. In particular, we analyse the concept of “euthanasia" and the curr...

  4. Linking Essential Learning Outcomes and Interprofessional Collaborative Practice Competency in Health Science Undergraduates

    Science.gov (United States)

    Reed, Carole-Rae; Garcia, Luis Ivan; Slusser, Margaret M.; Konowitz, Sharon; Yep, Jewelry

    2017-01-01

    Assessing student learning outcomes and determining achievement of the Interprofessional Collaborative Practice (IPCEP) Core Competency of Values/Ethics in a generic pre-professional Bachelor of Science in Health Science (BSHS) program is challenging. A course level Student Learning Outcome (SLO) is: "….articulate the impact of personal…

  5. Screening for Antiviral Activities of Isolated Compounds from Essential Oils

    Directory of Open Access Journals (Sweden)

    Akram Astani

    2011-01-01

    Full Text Available Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, β-eudesmol, farnesol, β-caryophyllene and β-caryophyllene oxide, which are present in many essential oils, were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1 in vitro. Antiviral activity was analyzed by plaque reduction assays and mode of antiviral action was determined by addition of the drugs to uninfected cells, to the virus prior to infection or to herpesvirus-infected cells. Star anise oil reduced viral infectivity by >99%, phenylpropanoids inhibited HSV infectivity by about 60–80% and sesquiterpenes suppressed herpes virus infection by 40–98%. Both, star anise essential oil and all isolated compounds exhibited anti-HSV-1 activity by direct inactivation of free virus particles in viral suspension assays. All tested drugs interacted in a dose-dependent manner with herpesvirus particles, thereby inactivating viral infectivity. Star anise oil, rich in trans-anethole, revealed a high selectivity index of 160 against HSV, whereas among the isolated compounds only β-caryophyllene displayed a high selectivity index of 140. The presence of β-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV.

  6. Rosmarinus officinalis essential oil: antiproliferative, antioxidant and antibacterial activities

    Directory of Open Access Journals (Sweden)

    Abdullah Ijaz Hussain

    2010-12-01

    Full Text Available The aim of this work was to investigate and compare the antiproliferative, antioxidant and antibacterial activities of Rosmarinus officinalis essential oil, native to Pakistan. The essential oil content from the leaves of R. officinalis was 0.93 g 100g-1. The GC and GC-MS analysis revealed that the major components determined in R. officinalis essential oil were 1,8-cineol (38.5%, camphor (17.1%, α-pinene (12.3%, limonene (6.23%, camphene (6.00% and linalool (5.70%. The antiproliferative activity was tested against two cancer (MCF-7 and LNCaP and one fibroblast cell line (NIH-3T3 using the MTT assay, while, the antioxidant activity was evaluated by the reduction of 2, 2-diphenyl-1-picryl hydrazyl (DPPH and measuring percent inhibition of peroxidation in linoleic acid system. The disc diffusion and modified resazurin microtitre-plate assays were used to evaluate the inhibition zones (IZ and minimum inhibitory concentration (MIC of R. officinalis essential oil, respectively. It is concluded from the results that Rosmarinus officinalis essential oil exhibited antiproliferative, antioxidant and antibacterial activities.

  7. Essential oil composition of wild growing Sage from R. Macedonia

    Directory of Open Access Journals (Sweden)

    Gjoshe Stefkov

    2012-03-01

    Full Text Available The main objective of this study was to analyze and identify the essential oil composition of S. officinalis populations growing in Republic of Macedonia and to evaluate these data according to different standards’ requirements for, commercially most utilized, Dalmatian sage. The essential oil yield, obtained after hydrodestilation from leaves, of three different populations of Salvia officinalis L. from Republic of Macedonia was determined, varying from 1.40 to 3.46%. The GC/FID/MS analysis of the composition of the essential oils revealed 63, 57 and 51 components in Galicica Mtn., Jablanica Mtn. and Karaorman Mtn. sage populations, respectively. The main components of the oil, in all three samples, were the terpene hydrocarbons, encompassing the monoterpenes: camphor (13.15 - 25.91%, α-thujone (19.25 - 26.33%, β-thujone (2.03 - 5.28%, 1,8-cineole (6.51 – 13.60%, α-pinene (0.93 – 1.47%, borneol (1.07 – 4.67%, then sesquiterpenes: trans (E-caryophyllene (1.72 – 5.33%, α-humulene (2.89 – 7.99%, viridiflorol (4.27 – 7.99%, and the diterpene manool (2.13 - 3.79%. Thus, our results for the essential oil composition of sage complied with the reference values specified in the DAC 86 monograph for Salvia essential oil.

  8. Website Policies / Important Links | DOepatents

    Science.gov (United States)

    Links Website Policies / Important Links Javascript Not Enabled OSTI Security Website Policies and first) Publication Date (oldest first) Close Clear All Find DOepatents Website Policies / Important Important Links Some links on this page may take you to non-federal websites. Their policies may differ from

  9. A Tendon Cell Specific RNAi Screen Reveals Novel Candidates Essential for Muscle Tendon Interaction.

    Directory of Open Access Journals (Sweden)

    Prabhat Tiwari

    Full Text Available Tendons are fibrous connective tissue which connect muscles to the skeletal elements thus acting as passive transmitters of force during locomotion and provide appropriate body posture. Tendon-derived cues, albeit poorly understood, are necessary for proper muscle guidance and attachment during development. In the present study, we used dorsal longitudinal muscles of Drosophila and their tendon attachment sites to unravel the molecular nature of interactions between muscles and tendons. We performed a genetic screen using RNAi-mediated knockdown in tendon cells to find out molecular players involved in the formation and maintenance of myotendinous junction and found 21 candidates out of 2507 RNAi lines screened. Of these, 19 were novel molecules in context of myotendinous system. Integrin-βPS and Talin, picked as candidates in this screen, are known to play important role in the cell-cell interaction and myotendinous junction formation validating our screen. We have found candidates with enzymatic function, transcription activity, cell adhesion, protein folding and intracellular transport function. Tango1, an ER exit protein involved in collagen secretion was identified as a candidate molecule involved in the formation of myotendinous junction. Tango1 knockdown was found to affect development of muscle attachment sites and formation of myotendinous junction. Tango1 was also found to be involved in secretion of Viking (Collagen type IV and BM-40 from hemocytes and fat cells.

  10. Factors Essential for Prostate Cancer Metastasis Revealed Through a Novel 3D Microtissue Assay

    Science.gov (United States)

    2016-06-01

    with Ob-niche spheroid and then conducted confocal microscopic analysis with frozen sections for HRE -mediated GFP expression. The results...activity in response to CoCl2. (B) The microscopic images demonstrate the HRE -dependent expression of GFP in a spheroid-specific manner. (C) The...io n C om bi ne d A375 MB231 Fr oz en s ec . 582 µm B C D SecNLuc Puro 4x HRE 0 5 10 15 None 100 A375 0 1 2 3 4 5 6 None 100

  11. Bottom-linked innovation

    DEFF Research Database (Denmark)

    Kristensen, Catharina Juul

    2018-01-01

    hitherto been paid little explicit attention, namely collaboration between middle managers and employees in innovation processes. In contrast to most studies, middle managers and employees are here both subjects of explicit investigation. The collaboration processes explored in this article are termed...... ‘bottom-linked innovation’. The empirical analysis is based on an in-depth qualitative study of bottom-linked innovation in a public frontline institution in Denmark. By combining research on employee-driven innovation and middle management, the article offers new insights into such collaborative......Employee-driven innovation is gaining ground as a strategy for developing sustainable organisations in the public and private sector. This type of innovation is characterised by active employee participation, and the bottom-up perspective is often emphasised. This article explores an issue that has...

  12. Dimensional enrichment of statistical linked open data

    DEFF Research Database (Denmark)

    Varga, Jovan; Vaisman, Alejandro; Romero, Oscar

    2016-01-01

    On-Line Analytical Processing (OLAP) is a data analysis technique typically used for local and well-prepared data. However, initiatives like Open Data and Open Government bring new and publicly available data on the web that are to be analyzed in the same way. The use of semantic web technologies...... for this context is especially encouraged by the Linked Data initiative. There is already a considerable amount of statistical linked open data sets published using the RDF Data Cube Vocabulary (QB) which is designed for these purposes. However, QB lacks some essential schema constructs (e.g., dimension levels......) to support OLAP. Thus, the QB4OLAP vocabulary has been proposed to extend QB with the necessary constructs and be fully compliant with OLAP. In this paper, we focus on the enrichment of an existing QB data set with QB4OLAP semantics. We first thoroughly compare the two vocabularies and outline the benefits...

  13. Essentials aspects on macroeconomic variables and their correlations

    OpenAIRE

    Constantin ANGHELACHE; Alexandru MANOLE; Mădălina Gabriela ANGHEL; Aurelian DIACONU

    2016-01-01

    The measurement of the correlations between macroeconomic variables, including the cause-effect links, provide useful information for policy makers in the government and public agencies. Especially important is the system of relationships that reveals the influence of certain factors on the Gross Domestic Product. This paper outlines the influence of the unemployment, measured through the unemployment rate, the inflation. Also, the authors discuss the correlations of the econom...

  14. Links between nuclear medicine and radiopharmacy

    International Nuclear Information System (INIS)

    Pelegrin, M.; Francois-Joubert, A.; Chassel, M.L.; Desruet, M.D.; Bolot, C.; Lao, S.

    2010-01-01

    Radiopharmaceuticals are nowadays under the responsibility of the radio-pharmacist because of their medicinal product status. Radiopharmacy belongs to the hospital pharmacy department, nevertheless, interactions with nuclear medicine department are important: rooms are included or located near nuclear medicine departments in order to respect radiation protection rules, more over staff, a part of the material and some activities are shared between the two departments. Consequently, it seems essential to formalize links between the radiopharmacy and the nuclear medicine department, setting the goals to avoid conflicts and to ensure patients' security. Modalities chosen for this formalization will depend on the establishment's organization. (authors)

  15. Linking lab and field

    International Nuclear Information System (INIS)

    Cronje, P.B.

    1988-01-01

    The multitude of different supplements recommended for animals grazing natural pastures, which testifies to the need for a metabolic basis for supplementary feeding practices. The first approach to this problem was to simulate different feeding conditions in the laboratory, where the metabolic responses of body tissues to changes in the supply of purified nutrients could be studied using radioisotope techniques. The second step was to link these fundamental studies to field conditions. The results of these studies suggest that the efficiency of feed conversion and growth rates of ruminants grazing winter pastures in the highveld region of South Africa could be substantially improved by strategic supplementation with glucose precursors. Acetate clearance rate represents a valuable link in the process of applying information obtained from controlled laboratory experiments to field conditions. As this technique is inexpensive, quick and simple to carry out, it is ideally suited to application under field conditions where the use of isotopes is impractical. By providing a link with field conditions, it greatly extended the scope and practical application of isotope tracer techniques

  16. Reveal quantum correlation in complementary bases

    OpenAIRE

    Shengjun Wu; Zhihao Ma; Zhihua Chen; Sixia Yu

    2014-01-01

    An essential feature of genuine quantum correlation is the simultaneous existence of correlation in complementary bases. We reveal this feature of quantum correlation by defining measures based on invariance under a basis change. For a bipartite quantum state, the classical correlation is the maximal correlation present in a certain optimum basis, while the quantum correlation is characterized as a series of residual correlations in the mutually unbiased bases. Compared with other approaches ...

  17. Against essential normativity of the mental

    DEFF Research Database (Denmark)

    Steglich-Petersen, Asbjørn

    2008-01-01

    A number of authors have recently developed and defended various versions of ‘normative essentialism’ about the mental, i.e. the claim that propositional attitudes are constitutively or essentially governed by normative principles. I present two arguments to the effect that this claim cannot be r...... essentially normative, propositional attitude ascriptions could not support normative rationality judgments, which would remove the central appeal of normative essentialism....

  18. Biological activities of Lavandula angustifolia essential oil

    OpenAIRE

    Bílková, Zuzana

    2013-01-01

    Zuzana Bílková, Biological activities of Lavandula angustifolia essential oil, Thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, thesis author: PharmDr. Jan Martin, PhD., Hradec Králové, 2013, 72 pages. The thesis called "Biological activities of Lavandula angustifolia essential oil" is interested in biological activities of Lavandula angustifolia essential oil, specifically antifungal, antioxidant, anti-inflammatory, cytotoxicity, nematicidal and repellency activit...

  19. Treatment of essential tremor with arotinolol.

    Science.gov (United States)

    Kuroda, Y; Kakigi, R; Shibasaki, H

    1988-04-01

    We investigated the effect of arotinolol, a new peripherally acting beta-adrenergic blocker, in 15 patients with essential tremor. The patients received 30 mg per day of arotinolol for 8 weeks. Accelerometer readings showed a significant reduction in amplitude of postural tremor after treatment. Action tremor also improved to essentially the same degree as postural tremor. The present findings support the view that the therapeutic effect of beta-blockers in essential tremor is mediated by peripheral beta-adrenergic receptors.

  20. Linking flow, water quality and potential effects on aquatic biota ...

    African Journals Online (AJOL)

    Linking the potential effects of altered water quality on aquatic biota, that may result from a change in the flow (discharge) regime, is an essential step in the maintenance of riverine ecological functioning. Determination of the environmental flow requirement of a river (as well as other activities, such as classifying the ...

  1. [Essentialism and typological thinking in biological systematics].

    Science.gov (United States)

    Vasil'eva, L N

    2003-01-01

    In biological literature, essentialism and typological thinking are believed to be incompatible with evolutionary ideas. At present, the same considerations underlay the claims to abandon the Linnaean hierarchy, or the fundamental classificatory structure rooted in essentialism. This paper suggests to reconsider the negative views of Plato's typology and Aristotle's essentialism following the narrow interpretations that have nothing to do with the classification of living beings. Plato's theory of 'ideas' (or 'forms') is the basis of classificatory theory; it provided such concepts as 'species', 'genus', 'essence', 'dichotomous division' but the development of this theory in the framework of moral and esthetic values could not be beneficial to biology. Aristotle's essentialism is more complicated and exists in two forms; one of these, or classificatory essentialism, is a modification of Plato's typology; another one, or organismal essentialism, represents the shift of 'essence' from the world of relations between objects to the realm of particular things, where the concept of essence lost its basic meaning. It is senseless to look for unreal 'type of an organism' ('essence of a thing') but precisely this kind of essentialism is attractive for biologists and philosophers. Organismal essentialism is the underlying basis of so-called 'individuality thesis' that is used as a weapon against classificatory essentialism. The same thesis is associated with an extensional vision of taxa that also explains the criticism of Linnaean hierarchy, while the latter is the intentional structure and the first tool suggested for the rank coordination of many unequal taxa.

  2. Essential Connectivity Areas - CEHC, (Raster) [ds620

    Data.gov (United States)

    California Natural Resource Agency — The California Department of Transportation (Caltrans) and California Department of Fish and Game (CDFG) commissioned the California Essential Habitat Connectivity...

  3. Autodesk 3ds Max 2012 Essentials

    CERN Document Server

    Derakhshani, Randi L

    2011-01-01

    Get a jump-start on Autodesk 3ds Max 2012 essentials-with the Essentials! The new Essentials books from Sybex are beautiful, task-based, full-color Autodesk Official Training Guides that help you get up to speed on Autodesk topics quickly and easily. Autodesk 3ds Max 2012 Essentials thoroughly covers the fundamentals of this popular 3D animation effects, and visualization software, teaching you what you need to become quickly productive. By following the book's clear explanations, practical tutorials, and step-by-step exercises, you'll cover all the bases. Topics include modeling, animation,

  4. Medical significance of the essential biological metals

    International Nuclear Information System (INIS)

    Davies, I.J.T.

    1977-01-01

    The medical significance of the essential biological metals such as zinc, copper and molybdenum as well as their nutritional and biochemical importance are reviewed. The following topics are treated: biochemical actions of the essential biological metals; the concept of essentiality; the development of knowledge about the essential biological metals. Data are given on zinc deficiency and hypogonadismi in humans, zinc and acrodermatitis enterophatica, zinc and the skin, zinc in diabetes mellitus, zinc and insulin, zinc and the liver; copper functions, copper deficiency - ''sway back'' in sheep, copper and haemopoiesis, copper and the function of blood vessels; molybdenum and dental caries in humans, oesophageal carcinoma and molybdenum deficiency in humans. (T.G.)

  5. HAIR HEAVY METAL AND ESSENTIAL TRACE ELEMENT CONCENTRATION IN CHILDREN WITH AUTISM SPECTRUM DISORDER.

    Science.gov (United States)

    Tabatadze, T; Zhorzholiani, L; Kherkheulidze, M; Kandelaki, E; Ivanashvili, T

    2015-11-01

    Our study aims evaluation of level of essential trace elements and heavy metals in the hair samples of children with autistic spectrum disorder (ASD) and identification of changes that are associated with autistic spectrum disorders. Case-control study was conducted at Child Development Center of Iashvili Children's Central Hospital (LD).We studied 60 children aged from 4 to 5 years old. The concentrations of 28 elements among (Ca,Zn, K, Fe, Cu, Se, Mn, Cr, S, Br, Cl, Co, Ag, V, Ni, Rb, Mo, Sr, Ti, Ba, Pb, As, Hg, Cd, Sb, Zr, Sn, Bi) them trace elements and toxic metals) were determined in scalp hair samples of children (n=30) with autistic spectrum disorder (ASD) and from control group of healthy children (n=30) with matched sex and age. Micro-elemental status was detected in the hair, with roentgen-fluorescence spectrometer method (Method MBИ 081/12-4502-000, Apparatus ALVAX- CIP, USA - UKRAIN) .To achieve the similarity of study and control groups, pre and postnatal as well as family and social history were assessed and similar groups were selected. Children with genetic problems, malnourished children, children from families with social problems were excluded from the study. The diagnosis of ASD were performed by pediatrician and psychologist (using M-CHAT and ADOS) according to DSM IV (Diagnostic and Statistical Manual of Mental Disorders from the American Psychiatric association) criteria. The study was statistically analyzed using computer program SPSS 19. Deficiencies of essential trace microelements revealed in both group, but there was significant difference between control and studied groups. The most deficient element was zinc (92% in target and 20% in control), then - manganese (55% and 8%) and selenium (38% and 4%). In case of cooper study revealed excess concentration of this element only in target group in 50% of cases. The contaminations to heavy metals were detected in case of lead (78% and 16), mercury (43% and 10%) and cadmium (38% and 8%). The

  6. LinkedIn Marketing An Hour a Day

    CERN Document Server

    von Rosen, Viveka

    2012-01-01

    A step-by-step guide for succeeding on the for ''business'' social media network LinkedIn Marketing: An Hour a Day helps you create, customize, and optimize a presence on LinkedIn, the world's largest social network for professionals. In this detailed, step-by-step book, LinkedIn expert Viveka von Rosen reveals how to use this powerful platform to ensure that you or your company get noticed by the right audience. Discover previously undocumented tips and tricks for community growth and management, including how to best use Groups, events, and other LinkedIn features and applications. Offers a

  7. Linking consumer experiences

    DEFF Research Database (Denmark)

    Smed, Karina Madsen

    become part of the individual self, worldview, and behaviour. This paper seeks to explore links between consumer experiences through the exploration of narrative sequences in travel blogs. Findings indicate that non-consumption is a central element to the bloggers and also indicative of a community......Consumers consume products in various ways serving a number of purposes. Much attention has been paid to experiences attached to consumption, sometimes very explicitly, e.g. in tourism, the essence of which is experiences of various sorts, but often also implicitly as internalised experiences...

  8. Knots and links

    CERN Document Server

    Rolfsen, Dale

    2003-01-01

    Rolfsen's beautiful book on knots and links can be read by anyone, from beginner to expert, who wants to learn about knot theory. Beginners with a basic background find an inviting introduction to the elements of topology, emphasizing the tools needed for understanding knots, the fundamental group and van Kampen's theorem, for example, which are then applied to concrete problems, such as computing knot groups. For experts, Rolfsen explains advanced topics, such as the connections between knot theory and surgery and how they are useful to understanding three-manifolds. Besides providing a guide

  9. A generalized theory of preferential linking

    Science.gov (United States)

    Hu, Haibo; Guo, Jinli; Liu, Xuan; Wang, Xiaofan

    2014-12-01

    There are diverse mechanisms driving the evolution of social networks. A key open question dealing with understanding their evolution is: How do various preferential linking mechanisms produce networks with different features? In this paper we first empirically study preferential linking phenomena in an evolving online social network, find and validate the linear preference. We propose an analyzable model which captures the real growth process of the network and reveals the underlying mechanism dominating its evolution. Furthermore based on preferential linking we propose a generalized model reproducing the evolution of online social networks, and present unified analytical results describing network characteristics for 27 preference scenarios. We study the mathematical structure of degree distributions and find that within the framework of preferential linking analytical degree distributions can only be the combinations of finite kinds of functions which are related to rational, logarithmic and inverse tangent functions, and extremely complex network structure will emerge even for very simple sublinear preferential linking. This work not only provides a verifiable origin for the emergence of various network characteristics in social networks, but bridges the micro individuals' behaviors and the global organization of social networks.

  10. Structural view of the helicase reveals that Zika virus uses a conserved mechanism for unwinding RNA.

    Science.gov (United States)

    Li, Lei; Wang, Jin; Jia, Zhihui; Shaw, Neil

    2018-04-01

    Recent studies suggest a link between infection by Zika virus (ZIKV) and the development of neurological complications. The lack of ZIKV-specific therapeutics has alarmed healthcare professionals worldwide. Here, crystal structures of apo and AMPPNP- and Mn 2+ -bound forms of the essential helicase of ZIKV refined to 1.78 and 1.3 Å resolution, respectively, are reported. The structures reveal a conserved trimodular topology of the helicase. ATP and Mn 2+ are tethered between two RecA-like domains by conserved hydrogen-bonding interactions. The binding of ligands induces the movement of backbone Cα and side-chain atoms. Numerous solvent molecules are observed in the vicinity of the AMPPNP, suggesting a role in catalysis. These high-resolution structures could be useful for the design of inhibitors targeting the helicase of ZIKV for the treatment of infections caused by ZIKV.

  11. Inter-ring rotations of AAA ATPase p97 revealed by electron cryomicroscopy.

    Science.gov (United States)

    Yeung, Heidi O; Förster, Andreas; Bebeacua, Cecilia; Niwa, Hajime; Ewens, Caroline; McKeown, Ciarán; Zhang, Xiaodong; Freemont, Paul S

    2014-03-05

    The type II AAA+ protein p97 is involved in numerous cellular activities, including endoplasmic reticulum-associated degradation, transcription activation, membrane fusion and cell-cycle control. These activities are at least in part regulated by the ubiquitin system, in which p97 is thought to target ubiquitylated protein substrates within macromolecular complexes and assist in their extraction or disassembly. Although ATPase activity is essential for p97 function, little is known about how ATP binding or hydrolysis is coupled with p97 conformational changes and substrate remodelling. Here, we have used single-particle electron cryomicroscopy (cryo-EM) to study the effect of nucleotides on p97 conformation. We have identified conformational heterogeneity within the cryo-EM datasets from which we have resolved two major p97 conformations. A comparison of conformations reveals inter-ring rotations upon nucleotide binding and hydrolysis that may be linked to the remodelling of target protein complexes.

  12. Combined Toxicity of Three Essential Oils Against Aedes aegypti (Diptera: Culicidae) Larvae.

    Science.gov (United States)

    Muturi, Ephantus J; Ramirez, Jose L; Doll, Kenneth M; Bowman, Michael J

    2017-11-07

    Essential oils are potential alternatives to synthetic insecticides because they have low mammalian toxicity, degrade rapidly in the environment, and possess complex mixtures of bioactive constituents with multi-modal activity against the target insect populations. Twenty-one essential oils were initially screened for their toxicity against Aedes aegypti (L.) larvae and three out of the seven most toxic essential oils (Manuka, oregano, and clove bud essential oils) were examined for their chemical composition and combined toxicity against Ae. aegypti larvae. Manuka essential oil interacted synergistically with oregano essential oil and antagonistically with clove bud essential oil. GC-MS analysis revealed the presence of 21 components in Manuka essential oil and three components each in oregano and clove bud essential oils. Eugenol (84.9%) and eugenol acetate (9.6%) were the principal constituents in clove bud essential oil while carvacrol (75.8%) and m-isopropyltoluene (15.5%) were the major constituents in oregano essential oil. The major constituents in Manuka essential oil were calamenene (20%) and 3-dodecyl-furandione (11.4%). Manuka essential oil interacted synergistically with eugenol acetate and antagonistically with eugenol, suggesting that eugenol was a major contributor to the antagonistic interaction between Manuka and clove bud essential oils. In addition, Manuka interacted synergistically with carvacrol suggesting its contribution to the synergistic interaction between Manuka and oregano essential oils. These findings provide novel insights that can be used to develop new and safer alternatives to synthetic insecticides. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  13. Using ecological production functions to link ecological processes to ecosystem services.

    Science.gov (United States)

    Ecological production functions (EPFs) link ecosystems, stressors, and management actions to ecosystem services (ES) production. Although EPFs are acknowledged as being essential to improve environmental management, their use in ecological risk assessment has received relatively ...

  14. Maintenance optimization plan for essential equipment reliability

    International Nuclear Information System (INIS)

    Steffen, D.H.

    1996-02-01

    The Maintenance Optimization Plan (MOP) for Essential Equipment Reliability will furnish Tank Waste Remediation System (TWRS) management with a pro-active, forward-thinking process for maintaining essential structures, systems, and components (ESSC) at the Hanford Site tank farms in their designed condition, and to ensure optimum ESSC availability and reliability

  15. Reconciling Anti-essentialism and Quantitative Methodology

    DEFF Research Database (Denmark)

    Jensen, Mathias Fjællegaard

    2017-01-01

    Quantitative methodology has a contested role in feminist scholarship which remains almost exclusively qualitative. Considering Irigaray’s notion of mimicry, Spivak’s strategic essentialism, and Butler’s contingent foundations, the essentialising implications of quantitative methodology may prove...... the potential to reconcile anti-essentialism and quantitative methodology, and thus, to make peace in the quantitative/qualitative Paradigm Wars....

  16. essential oil as hatching egg disinfectant

    African Journals Online (AJOL)

    STORAGESEVER

    2010-04-26

    Apr 26, 2010 ... disinfectant for hatching egg obtained from broiler breeder flock. Oregano essential ... contamination rate, hatchability of fertile egg, body weight at 21 and 42 days, body weight gain and total feed ... successful healthy hatchlings. Several ...... Insecticidal properties of essential plant oils against the mosquito.

  17. Essential Oils and Fragrances from Natural Sources

    Indian Academy of Sciences (India)

    physiological, psychological and spiritual. Our body uses the aromatic molecules (essential oils) in two ways: (1) through our olfactory system which is connected to the brain where our most primal feelings, urges and emotions reside, and (2) by absorp- tion of the low molecular weight compounds of essential oils through ...

  18. Four Essential Dimensions of Workplace Learning

    Science.gov (United States)

    Hopwood, Nick

    2014-01-01

    Purpose: This conceptual paper aims to argue that times, spaces, bodies and things constitute four essential dimensions of workplace learning. It examines how practices relate or hang together, taking Gherardi's texture of practices or connectedness in action as the foundation for making visible essential but often overlooked dimensions of…

  19. Transient receptor potential channels in essential hypertension

    DEFF Research Database (Denmark)

    Liu, Daoyan; Scholze, Alexandra; Zhu, Zhiming

    2006-01-01

    The role of nonselective cation channels of the transient receptor potential channel (TRPC) family in essential hypertension has not yet been investigated.......The role of nonselective cation channels of the transient receptor potential channel (TRPC) family in essential hypertension has not yet been investigated....

  20. Synergic antibacterial activity of some essential oils from Lamiaceae

    Directory of Open Access Journals (Sweden)

    Sh. Fahimi

    2015-05-01

    Full Text Available Background and objectives: Despite the vast production of new antibiotics in the last three decades, resistance to these drugs by microorganisms has increased and essential oils (EOs have been recognized to possess antimicrobial properties. Methods:  In the present study, EOs obtained from aerial parts of Thymus vulgaris L., Lavandula angustifolia Mill., Rosmarinus officinalis L. and Mentha piperita L., were evaluated for their single and binary combined antibacterial activities against four Gram-positive and Gram-negative pathogenic bacteria: Staphylococcus aureus, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. Results: The results exhibited that some of the tested essential oils revealed antibacterial activities against the examined pathogens using broth microdilution method. Maximum activity of the testedessential oils was obtained from the combination of T. vulgaris and M. piperita essential oils against Staphylococcus aureus (MIC= 0.625 mg/mL. Conclusion: Combinations of the essential oils in this study showed synergic action against some pathogenic microorganisms which could be considered in medical and food industries as preservatives.

  1. Redefining the essential trafficking pathway for outer membrane lipoproteins

    Science.gov (United States)

    Grabowicz, Marcin; Silhavy, Thomas J.

    2017-01-01

    The outer membrane (OM) of Gram-negative bacteria is a permeability barrier and an intrinsic antibiotic resistance factor. Lipoproteins are OM components that function in cell wall synthesis, diverse secretion systems, and antibiotic efflux pumps. Moreover, each of the essential OM machines that assemble the barrier requires one or more lipoproteins. This dependence is thought to explain the essentiality of the periplasmic chaperone LolA and its OM receptor LolB that traffic lipoproteins to the OM. However, we show that in strains lacking substrates that are toxic when mislocalized, both LolA and LolB can be completely bypassed by activating an envelope stress response without compromising trafficking of essential lipoproteins. We identify the Cpx stress response as a monitor of lipoprotein trafficking tasked with protecting the cell from mislocalized lipoproteins. Moreover, our findings reveal that an alternate trafficking pathway exists that can, under certain conditions, bypass the functions of LolA and LolB, implying that these proteins do not perform any truly essential mechanistic steps in lipoprotein trafficking. Instead, these proteins’ key function is to prevent lethal accumulation of mislocalized lipoproteins. PMID:28416660

  2. Redefining the essential trafficking pathway for outer membrane lipoproteins.

    Science.gov (United States)

    Grabowicz, Marcin; Silhavy, Thomas J

    2017-05-02

    The outer membrane (OM) of Gram-negative bacteria is a permeability barrier and an intrinsic antibiotic resistance factor. Lipoproteins are OM components that function in cell wall synthesis, diverse secretion systems, and antibiotic efflux pumps. Moreover, each of the essential OM machines that assemble the barrier requires one or more lipoproteins. This dependence is thought to explain the essentiality of the periplasmic chaperone LolA and its OM receptor LolB that traffic lipoproteins to the OM. However, we show that in strains lacking substrates that are toxic when mislocalized, both LolA and LolB can be completely bypassed by activating an envelope stress response without compromising trafficking of essential lipoproteins. We identify the Cpx stress response as a monitor of lipoprotein trafficking tasked with protecting the cell from mislocalized lipoproteins. Moreover, our findings reveal that an alternate trafficking pathway exists that can, under certain conditions, bypass the functions of LolA and LolB, implying that these proteins do not perform any truly essential mechanistic steps in lipoprotein trafficking. Instead, these proteins' key function is to prevent lethal accumulation of mislocalized lipoproteins.

  3. Composition and Antimicrobial Activity of Euphrasia rostkoviana Hayne Essential Oil

    Science.gov (United States)

    Novy, Pavel; Davidova, Hana; Serrano-Rojero, Cecilia Suqued; Rondevaldova, Johana; Pulkrabek, Josef

    2015-01-01

    Eyebright, Euphrasia rostkoviana Hayne (Scrophulariaceae), is a medicinal plant traditionally used in Europe for the treatment of various health disorders, especially as eyewash to treat eye ailments such as conjunctivitis and blepharitis that can be associated with bacterial infections. Some Euphrasia species have been previously reported to contain essential oil. However, the composition and bioactivity of E. rostkoviana oil are unknown. Therefore, in this study, we investigated the chemical composition and antimicrobial activity of the eyebright essential oil against some organisms associated with eye infections: Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, and Candida albicans. GC-MS analysis revealed more than 70 constituents, with n-hexadecanoic acid (18.47%) as the main constituent followed by thymol (7.97%), myristic acid (4.71%), linalool (4.65%), and anethole (4.09%). The essential oil showed antimicrobial effect against all organisms tested with the exception of P. aeruginosa. The best activity was observed against all Gram-positive bacteria tested with the minimum inhibitory concentrations of 512 µg/mL. This is the first report on the chemical composition of E. rostkoviana essential oil and its antimicrobial activity. PMID:26000025

  4. Composition and Antimicrobial Activity of Euphrasia rostkoviana Hayne Essential Oil.

    Science.gov (United States)

    Novy, Pavel; Davidova, Hana; Serrano-Rojero, Cecilia Suqued; Rondevaldova, Johana; Pulkrabek, Josef; Kokoska, Ladislav

    2015-01-01

    Eyebright, Euphrasia rostkoviana Hayne (Scrophulariaceae), is a medicinal plant traditionally used in Europe for the treatment of various health disorders, especially as eyewash to treat eye ailments such as conjunctivitis and blepharitis that can be associated with bacterial infections. Some Euphrasia species have been previously reported to contain essential oil. However, the composition and bioactivity of E. rostkoviana oil are unknown. Therefore, in this study, we investigated the chemical composition and antimicrobial activity of the eyebright essential oil against some organisms associated with eye infections: Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, and Candida albicans. GC-MS analysis revealed more than 70 constituents, with n-hexadecanoic acid (18.47%) as the main constituent followed by thymol (7.97%), myristic acid (4.71%), linalool (4.65%), and anethole (4.09%). The essential oil showed antimicrobial effect against all organisms tested with the exception of P. aeruginosa. The best activity was observed against all Gram-positive bacteria tested with the minimum inhibitory concentrations of 512 µg/mL. This is the first report on the chemical composition of E. rostkoviana essential oil and its antimicrobial activity.

  5. Composition and Antimicrobial Activity of Euphrasia rostkoviana Hayne Essential Oil

    Directory of Open Access Journals (Sweden)

    Pavel Novy

    2015-01-01

    Full Text Available Eyebright, Euphrasia rostkoviana Hayne (Scrophulariaceae, is a medicinal plant traditionally used in Europe for the treatment of various health disorders, especially as eyewash to treat eye ailments such as conjunctivitis and blepharitis that can be associated with bacterial infections. Some Euphrasia species have been previously reported to contain essential oil. However, the composition and bioactivity of E. rostkoviana oil are unknown. Therefore, in this study, we investigated the chemical composition and antimicrobial activity of the eyebright essential oil against some organisms associated with eye infections: Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, and Candida albicans. GC-MS analysis revealed more than 70 constituents, with n-hexadecanoic acid (18.47% as the main constituent followed by thymol (7.97%, myristic acid (4.71%, linalool (4.65%, and anethole (4.09%. The essential oil showed antimicrobial effect against all organisms tested with the exception of P. aeruginosa. The best activity was observed against all Gram-positive bacteria tested with the minimum inhibitory concentrations of 512 µg/mL. This is the first report on the chemical composition of E. rostkoviana essential oil and its antimicrobial activity.

  6. A family with Parkinsonism, essential tremor, restless legs syndrome, and depression.

    Science.gov (United States)

    Puschmann, A; Pfeiffer, R F; Stoessl, A J; Kuriakose, R; Lash, J L; Searcy, J A; Strongosky, A J; Vilariño-Güell, C; Farrer, M J; Ross, O A; Dickson, D W; Wszolek, Z K

    2011-05-10

    Previous epidemiologic and genetic studies have suggested a link between Parkinson disease (PD), essential tremor (ET), and restless legs syndrome (RLS). We describe the clinical, PET, and pathologic characteristics of an extensive kindred from Arkansas with hereditary PD, ET, and RLS. The pedigree contains 138 individuals. Sixty-five family members were examined neurologically up to 3 times from 2004 to 2010. Clinical data were collected from medical records and questionnaires. Genetic studies were performed. Five family members underwent multitracer PET. Two individuals with PD were examined postmortem. Eleven family members had PD with generally mild and slowly progressive symptoms. Age at onset was between 39 and 74 years (mean 59.1, SD 13.4). All individuals treated with l-dopa responded positively. Postural or action tremor was present in 6 individuals with PD, and in 19 additional family members. Fifteen persons reported symptoms of RLS. PET showed reduced presynaptic dopamine function typical of sporadic PD in a patient with PD and ET, but not in persons with ET or RLS. The inheritance pattern was autosomal dominant for PD and RLS. No known pathogenic mutation in PD-related genes was found. Fourteen of the family members with PD, ET, or RLS had depression. Neuropathologic examination revealed pallidonigral pigment spheroid degeneration with ubiquitin-positive axonal spheroids, TDP43-positive pathology in the basal ganglia, hippocampus, and brainstem, and only sparse Lewy bodies. Familial forms of PD, ET, RLS, and depression occur in this family. The genetic cause remains to be elucidated.

  7. Phosphatidylserine-exposing blood and endothelial cells contribute to the hypercoagulable state in essential thrombocythemia patients.

    Science.gov (United States)

    Tong, Dongxia; Yu, Muxin; Guo, Li; Li, Tao; Li, Jihe; Novakovic, Valerie A; Dong, Zengxiang; Tian, Ye; Kou, Junjie; Bi, Yayan; Wang, Jinghua; Zhou, Jin; Shi, Jialan

    2018-04-01

    The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex and not well defined. Our objective was to explore whether phosphatidylserine (PS) exposure on blood cells and endothelial cells (ECs) can account for the increased thrombosis and distinct thrombotic risks among mutational subtypes in ET. Using flow cytometry and confocal microscopy, we found that the levels of PS-exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all P cells and serum-cultured ECs led to markedly shortened coagulation time and dramatically increased levels of FXa, thrombin, and fibrin production. This procoagulant activity could be largely blocked by addition of lactadherin (approx. 70% inhibition). Confocal microscopy showed that the FVa/FXa complex and fibrin fibrils colocalized with PS on ET serum-cultured ECs. Additionally, we found a relationship between D-dimer, prothrombin fragment F1 + 2, and PS exposure. Our study reveals a previously unrecognized link between hypercoagulability and exposed PS on cells, which might also be associated with distinct thrombotic risks among mutational subtypes in ET. Thus, blocking PS-binding sites may represent a new therapeutic target for preventing thrombosis in ET.

  8. Looking at a contrast object before speaking boosts referential informativeness, but is not essential.

    Science.gov (United States)

    Davies, Catherine; Kreysa, Helene

    2017-07-01

    Variation in referential form has traditionally been accounted for by theoretical frameworks focusing on linguistic and discourse features. Despite the explosion of interest in eye tracking methods in psycholinguistics, the role of visual scanning behaviour in informative reference production is yet to be comprehensively investigated. Here we examine the relationship between speakers' fixations to relevant referents and the form of the referring expressions they produce. Overall, speakers were fully informative across simple and (to a lesser extent) more complex displays, providing appropriately modified referring expressions to enable their addressee to locate the target object. Analysis of contrast fixations revealed that looking at a contrast object boosts but is not essential for full informativeness. Contrast fixations which take place immediately before speaking provide the greatest boost. Informative referring expressions were also associated with later speech onsets than underinformative ones. Based on the finding that fixations during speech planning facilitate but do not fully predict informative referring, direct visual scanning is ruled out as a prerequisite for informativeness. Instead, pragmatic expectations of informativeness may play a more important role. Results are consistent with a goal-based link between eye movements and language processing, here applied for the first time to production processes. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Essential oil content and composition of aniseed

    Directory of Open Access Journals (Sweden)

    Aćimović Milica G.

    2015-01-01

    Full Text Available The field experiments were carried out during 2011 and 2012 in three localities in Vojvodina (Serbia with the application of six different fertilizer regimes aimed at determining the content and composition of the aniseed essential oil. It was found that the average essential oil content of aniseed, obtained by hydrodistillation, was 3.72%. The weather conditions during the year and the locality had a statistically significant effect on the essential oil content, while different source of fertilizers was not statistically significant for the essential oil content and its composition. Essential oil composition was determined using GC-MS technique, and a total of 15 compounds were identified. It was found that the major component was trans-anethole, 94.78% on the average, and the coefficient of variation was 2%. The second most abundant component was γ-himachalene with 2.53% (CV 28%. All other components were present in less than 1%.

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved November 2017. How are Drug Misuse and HIV Related? Drug misuse and addiction ...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the link between drug misuse and HIV infection. It contains information for young people, parents and teachers, ... present time. The virus (HIV) and the disease it causes (AIDS) are often linked and referred to ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... teens and young adults have never known a world without it. NIDA’s "Learn the Link" campaign continues ... for HIV infection through risky sexual behaviors. NIDA researchers have studied and continue to study the links ...

  13. The HANDSS-55 Linking Equipment

    International Nuclear Information System (INIS)

    Crosby, S.

    2001-01-01

    The Bucket Translation Unit (BTU) and the Drum Handler are two of the HANDSS-55 subsystems identified as linking components. Both subsystems link other modules together by moving material to or from another module

  14. Phosphorylation of human link proteins

    International Nuclear Information System (INIS)

    Oester, D.A.; Caterson, B.; Schwartz, E.R.

    1986-01-01

    Three link proteins of 48, 44 and 40 kDa were purified from human articular cartilage and identified with monoclonal anti-link protein antibody 8-A-4. Two sets of lower molecular weight proteins of 30-31 kDa and 24-26 kDa also contained link protein epitopes recognized by the monoclonal antibody and were most likely degradative products of the intact link proteins. The link proteins of 48 and 40 kDa were identified as phosphoproteins while the 44 kDa link protein did not contain 32 P. The phosphorylated 48 and 40 kDa link proteins contained approximately 2 moles PO 4 /mole link protein

  15. Combining Shigella Tn-seq data with gold-standard E. coli gene deletion data suggests rare transitions between essential and non-essential gene functionality.

    Science.gov (United States)

    Freed, Nikki E; Bumann, Dirk; Silander, Olin K

    2016-09-06

    Gene essentiality - whether or not a gene is necessary for cell growth - is a fundamental component of gene function. It is not well established how quickly gene essentiality can change, as few studies have compared empirical measures of essentiality between closely related organisms. Here we present the results of a Tn-seq experiment designed to detect essential protein coding genes in the bacterial pathogen Shigella flexneri 2a 2457T on a genome-wide scale. Superficial analysis of this data suggested that 481 protein-coding genes in this Shigella strain are critical for robust cellular growth on rich media. Comparison of this set of genes with a gold-standard data set of essential genes in the closely related Escherichia coli K12 BW25113 revealed that an excessive number of genes appeared essential in Shigella but non-essential in E. coli. Importantly, and in converse to this comparison, we found no genes that were essential in E. coli and non-essential in Shigella, implying that many genes were artefactually inferred as essential in Shigella. Controlling for such artefacts resulted in a much smaller set of discrepant genes. Among these, we identified three sets of functionally related genes, two of which have previously been implicated as critical for Shigella growth, but which are dispensable for E. coli growth. The data presented here highlight the small number of protein coding genes for which we have strong evidence that their essentiality status differs between the closely related bacterial taxa E. coli and Shigella. A set of genes involved in acetate utilization provides a canonical example. These results leave open the possibility of developing strain-specific antibiotic treatments targeting such differentially essential genes, but suggest that such opportunities may be rare in closely related bacteria.

  16. Identification of hybrid node and link communities in complex networks.

    Science.gov (United States)

    He, Dongxiao; Jin, Di; Chen, Zheng; Zhang, Weixiong

    2015-03-02

    Identifying communities in complex networks is an effective means for analyzing complex systems, with applications in diverse areas such as social science, engineering, biology and medicine. Finding communities of nodes and finding communities of links are two popular schemes for network analysis. These schemes, however, have inherent drawbacks and are inadequate to capture complex organizational structures in real networks. We introduce a new scheme and an effective approach for identifying complex mixture structures of node and link communities, called hybrid node-link communities. A central piece of our approach is a probabilistic model that accommodates node, link and hybrid node-link communities. Our extensive experiments on various real-world networks, including a large protein-protein interaction network and a large network of semantically associated words, illustrated that the scheme for hybrid communities is superior in revealing network characteristics. Moreover, the new approach outperformed the existing methods for finding node or link communities separately.

  17. Identification of hybrid node and link communities in complex networks

    Science.gov (United States)

    He, Dongxiao; Jin, Di; Chen, Zheng; Zhang, Weixiong

    2015-03-01

    Identifying communities in complex networks is an effective means for analyzing complex systems, with applications in diverse areas such as social science, engineering, biology and medicine. Finding communities of nodes and finding communities of links are two popular schemes for network analysis. These schemes, however, have inherent drawbacks and are inadequate to capture complex organizational structures in real networks. We introduce a new scheme and an effective approach for identifying complex mixture structures of node and link communities, called hybrid node-link communities. A central piece of our approach is a probabilistic model that accommodates node, link and hybrid node-link communities. Our extensive experiments on various real-world networks, including a large protein-protein interaction network and a large network of semantically associated words, illustrated that the scheme for hybrid communities is superior in revealing network characteristics. Moreover, the new approach outperformed the existing methods for finding node or link communities separately.

  18. Hubble Images Reveal Jupiter's Auroras

    Science.gov (United States)

    1996-01-01

    These images, taken by the Hubble Space Telescope, reveal changes in Jupiter's auroral emissions and how small auroral spots just outside the emission rings are linked to the planet's volcanic moon, Io. The images represent the most sensitive and sharply-detailed views ever taken of Jovian auroras.The top panel pinpoints the effects of emissions from Io, which is about the size of Earth's moon. The black-and-white image on the left, taken in visible light, shows how Io and Jupiter are linked by an invisible electrical current of charged particles called a 'flux tube.' The particles - ejected from Io (the bright spot on Jupiter's right) by volcanic eruptions - flow along Jupiter's magnetic field lines, which thread through Io, to the planet's north and south magnetic poles. This image also shows the belts of clouds surrounding Jupiter as well as the Great Red Spot.The black-and-white image on the right, taken in ultraviolet light about 15 minutes later, shows Jupiter's auroral emissions at the north and south poles. Just outside these emissions are the auroral spots. Called 'footprints,' the spots are created when the particles in Io's 'flux tube' reach Jupiter's upper atmosphere and interact with hydrogen gas, making it fluoresce. In this image, Io is not observable because it is faint in the ultraviolet.The two ultraviolet images at the bottom of the picture show how the auroral emissions change in brightness and structure as Jupiter rotates. These false-color images also reveal how the magnetic field is offset from Jupiter's spin axis by 10 to 15 degrees. In the right image, the north auroral emission is rising over the left limb; the south auroral oval is beginning to set. The image on the left, obtained on a different date, shows a full view of the north aurora, with a strong emission inside the main auroral oval.The images were taken by the telescope's Wide Field and Planetary Camera 2 between May 1994 and September 1995.This image and other images and data

  19. The bacteriostatic activity of essential oils for some specimen Millefolium Koch. genus Achillea L.

    Directory of Open Access Journals (Sweden)

    G. P. Smoilovskaya

    2014-12-01

    Full Text Available Pharmacologic effect of herbal drugs is associated with the availability in its composition the complex of biologically active substances, particularly, the essential oils, which are capable to suppress the multiplication of many microorganisms, fungi, viruses. Aim. To determine the bacteriostatic activity of essential oils of Millefolium subvulgare and Millefolium setaceum have been studied physic – chemical characters, identification and quantitative content of constituents of the essential oils obtained has been carried out by gas chromatography mass-spectrometry. Methods and results. It has been identified in the composition of the essential oil from Achillea setacea Waldst. et Kit 63 substances, 57 substances for Achillea submillefolium Klok. et Krytzka, azulene derivatives were predominant. The subsequent bacteriostatic studies for essential oils revealed their pronounced bacteriostatic activity for Staphylococcus aureus, mixt- flore1, Pseudomonas aeruginosa, Streptococcus pyogenes, Escherichia coli. Conclusion. The essential oil from Millefolium subvulgare demonstrated the more intensive activity associated with the predominance of azulene derivatives.

  20. ITK optical links backup document

    CERN Document Server

    Huffman, B T; The ATLAS collaboration; Flick, T; Ye, J

    2013-01-01

    This document describes the proposed optical links to be used for the ITK in the phase II upgrade. The current R&D for optical links pursued in the Versatile Link group is reviewed. In particular the results demonstrating the radiation tolerance of all the on-detector components are documented. The bandwidth requirements and the resulting numerology are given.

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... for young people, parents and teachers, and the media with links to our latest research findings and news updates. Read on to Learn the Link between ... to this site at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . ... Social Media Send the message to young people and to ...

  2. Seismic link at plate boundary

    Indian Academy of Sciences (India)

    time series to determine the causality and related orientation. The resulting link ... Triggering causes changes in the Coulomb stress on a specified fault, which is ... work link shows that the alignment of the links is parallel to the Honshu Trench ...

  3. Fermions and link invariants

    International Nuclear Information System (INIS)

    Kauffman, L.; Saleur, H.

    1991-01-01

    Various aspects of knot theory are discussed when fermionic degrees of freedom are taken into account in the braid group representations and in the state models. It is discussed how the R matrix for the Alexander polynomial arises from the Fox differential calculus, and how it is related to the quantum group U q gl(1,1). New families of solutions of the Yang Baxter equation obtained from ''linear'' representations of the braid group and exterior algebra are investigated. State models associated with U q sl(n,m), and in the case n=m=1 a state model for the multivariable Alexander polynomial are studied. Invariants of links in solid handlebodies are considered and it is shown how the non trivial topology lifts the boson fermion degeneracy is present in S 3 . (author) 36 refs

  4. Multilevel DC link inverter

    Science.gov (United States)

    Su, Gui-Jia

    2003-06-10

    A multilevel DC link inverter and method for improving torque response and current regulation in permanent magnet motors and switched reluctance motors having a low inductance includes a plurality of voltage controlled cells connected in series for applying a resulting dc voltage comprised of one or more incremental dc voltages. The cells are provided with switches for increasing the resulting applied dc voltage as speed and back EMF increase, while limiting the voltage that is applied to the commutation switches to perform PWM or dc voltage stepping functions, so as to limit current ripple in the stator windings below an acceptable level, typically 5%. Several embodiments are disclosed including inverters using IGBT's, inverters using thyristors. All of the inverters are operable in both motoring and regenerating modes.

  5. Linking Wayfinding and Wayfaring

    DEFF Research Database (Denmark)

    Lanng, Ditte Bendix; Jensen, Ole B.

    2016-01-01

    In this chapter we propose to expand and enhance the understanding of wayfi nding beyond the strictly “instrumental” (i.e., getting from point A to point B), to include the qualities and multi-sensorial inputs that inform and shape people’s movement through space. We take as a point of departure...... of environmental information , which includes the embodied, multi-sensorial experience of moving through physical space. We base our examination in part on the classic positions of the wayfi nding literature—for example, Lynch’s seminal study, The Image of the City ( 1960 ). However, we also examine the so......-called mobilities turn in which mobility is viewed as a complex, multilayered process that entails much more than simply getting from point A to point B (see Cresswell 2006 ; Jensen 2013 ; Urry 2007 ).The structure of the chapter is simple: We fi rst introduce the concepts that are key to linking wayfi nding...

  6. LinkLights

    DEFF Research Database (Denmark)

    Grönvall, Erik; Kramp, Gunnar

    2011-01-01

    The project described in this paper aims to provide assistive tools to support elderly people affected by vestibular dysfunction (i.e. a form of balance disorder leading to dizziness and nausea) in their home-based rehabilitation activities. Challenges emerge as the rehabilitation moves from...... a supervised hospital setting to private homes. Our studies have shown that the elderly people are less motivated to perform the training at home. This paper presents a tangible, portable, two dimensional modular platform called LinkLights that has been developed to sustain the home-based rehabilitation......, giving clear guidelines what to do, adding motivational cues and elements of variation and surprise in the activity. Furthermore, a set of challenges for successful translocation of the therapeutic regimen from a supervised, hospital setting to an unsupervised home-based setting together with some early...

  7. Named Entity Linking Algorithm

    Directory of Open Access Journals (Sweden)

    M. F. Panteleev

    2017-01-01

    Full Text Available In the tasks of processing text in natural language, Named Entity Linking (NEL represents the task to define and link some entity, which is found in the text, with some entity in the knowledge base (for example, Dbpedia. Currently, there is a diversity of approaches to solve this problem, but two main classes can be identified: graph-based approaches and machine learning-based ones. Graph and Machine Learning approaches-based algorithm is proposed accordingly to the stated assumptions about the interrelations of named entities in a sentence and in general.In the case of graph-based approaches, it is necessary to solve the problem of identifying an optimal set of the related entities according to some metric that characterizes the distance between these entities in a graph built on some knowledge base. Due to limitations in processing power, to solve this task directly is impossible. Therefore, its modification is proposed. Based on the algorithms of machine learning, an independent solution cannot be built due to small volumes of training datasets relevant to NEL task. However, their use can contribute to improving the quality of the algorithm. The adaptation of the Latent Dirichlet Allocation model is proposed in order to obtain a measure of the compatibility of attributes of various entities encountered in one context.The efficiency of the proposed algorithm was experimentally tested. A test dataset was independently generated. On its basis the performance of the model was compared using the proposed algorithm with the open source product DBpedia Spotlight, which solves the NEL problem.The mockup, based on the proposed algorithm, showed a low speed as compared to DBpedia Spotlight. However, the fact that it has shown higher accuracy, stipulates the prospects for work in this direction.The main directions of development were proposed in order to increase the accuracy of the system and its productivity.

  8. Polymer nanoparticles containing essential oils: new options for mosquito control.

    Science.gov (United States)

    Werdin González, Jorge Omar; Jesser, Emiliano Nicolás; Yeguerman, Cristhian Alan; Ferrero, Adriana Alicia; Fernández Band, Beatriz

    2017-07-01

    Mosquitoes (Diptera: Culicidae) are vectors of important parasites and pathogens causing death, poverty and social disability worldwide. The overuse of synthetic insecticides to control mosquito vectors lead to resistance, adverse environmental effects and high operational costs. Therefore, the development of eco-friendly control tools is an important public health challenge. In this study, two different essential oils (EO) (geranium, Geranium maculatum, and bergamot, Citrus bergamia) loaded polymeric nanoparticle (PN) were elaborated using polyethylene glycol (PEG) and chitosan (Qx) as the polymeric matrix/coating. In addition, the mosquito larvicidal acute and residual activity of the PN was evaluated on Culex pipiens pipiens. The physicochemical characterization of PN revealed that PEG-PN had sizes nanoparticles containing essential oil are a promising source of eco-friendly mosquito larvicidal products.

  9. Essential Oils for Alternative Teak Rust Control

    Directory of Open Access Journals (Sweden)

    Pedro Raymundo Argüelles Osorio

    2018-03-01

    Full Text Available ABSTRACT The objectives of this study were to evaluate the effect of lemon grass, citronella grass, Mexican-tea and noni essential oils on urediniospore germination of Olivea neotectonae , the agent responsible for rust in Teak (Tectona grandis L.f.; to evaluate the phytotoxic effect of these essential oils on teak seedlings; and to evaluate the use of essential oils to control rust in teak plants when preventively and curatively applied. We found that the noni and lemon grass essential oils inhibited 100% of urediniospore germination. On the other hand, the essential oils from noni and lemon grass caused phytotoxicity when applied to seedlings at concentrations of 2000 and 1500 μL L-1, respectively. The major constituents found in lemon grass essential oil were Geranial and Neral, while Octanoic Acid was found in noni oil. Lower values in the area below the rust progress curve were observed with the preventive application of lemon grass and noni essential oils.

  10. Cross-link guided molecular modeling with ROSETTA.

    Directory of Open Access Journals (Sweden)

    Abdullah Kahraman

    Full Text Available Chemical cross-links identified by mass spectrometry generate distance restraints that reveal low-resolution structural information on proteins and protein complexes. The technology to reliably generate such data has become mature and robust enough to shift the focus to the question of how these distance restraints can be best integrated into molecular modeling calculations. Here, we introduce three workflows for incorporating distance restraints generated by chemical cross-linking and mass spectrometry into ROSETTA protocols for comparative and de novo modeling and protein-protein docking. We demonstrate that the cross-link validation and visualization software Xwalk facilitates successful cross-link data integration. Besides the protocols we introduce XLdb, a database of chemical cross-links from 14 different publications with 506 intra-protein and 62 inter-protein cross-links, where each cross-link can be mapped on an experimental structure from the Protein Data Bank. Finally, we demonstrate on a protein-protein docking reference data set the impact of virtual cross-links on protein docking calculations and show that an inter-protein cross-link can reduce on average the RMSD of a docking prediction by 5.0 Å. The methods and results presented here provide guidelines for the effective integration of chemical cross-link data in molecular modeling calculations and should advance the structural analysis of particularly large and transient protein complexes via hybrid structural biology methods.

  11. Chemical composition, antimicrobial and antioxidant properties of Mentha longifolia (L. Huds. essential oil

    Directory of Open Access Journals (Sweden)

    Haris Nikšić

    2012-12-01

    Full Text Available Introduction: Present study describes the antimicrobial activity and free radical scavenging capacity (RSC of essential oil from Mentha longifolia (L. Huds. Aim of this study to investigate the quality, antimicrobial andantioxidant activity of wild species Mentha longifolia essential oil from Bosnia and Herzegovina.Methods: The chemical profi le of essential oil was evaluated by the means of gas chromatography-mass spectrometry (GC-MS and thin-layer chromatography (TLC. Antimicrobial activity was tested against 6bacterial strains. RSC was assessed by measuring the scavenging activity of essential oils on 2,2- diphenyl-1-picrylhydrazil (DPPH.Results: The main constituents of the essential oil of M. longifoliae folium were oxygenated monoterpenes,piperitone oxide (63.58% and 1,8-cineole (12.03%. Essential oil exhibited very strong antibacterial activity.The most important antibacterial activity essential oil was expressed on Gram negative strains: Escherichia coli, Pseudomonas aerginosa and Salmonella enterica. subsp.enterica serotype ABONY. Antioxidant activity was evaluated as a RSC. Investigated essential oil was able to reduce DPPH radicals into the neutral DPPHH form (IC50=10.5 μg/ml and this activity was dose –dependent.Conclusion: The study revealed signifi cant antimicrobial activity of the investigated essential oil. The examined oil exhibited high RSC, which was found to be in correlation to the content of mainly monoterpeneketones and aldehydes. These results indicate that essential oils could serve as safe antioxidant and antiseptic supplements in pharmaceuticals.

  12. Phytotoxic Activities of Mediterranean Essential Oils

    Directory of Open Access Journals (Sweden)

    Luiz Fernando Rolim de Almeida

    2010-06-01

    Full Text Available Twelve essential oils from Mediterranean aromatic plants were tested for their phytotoxic activity, at different doses, against the germination and the initial radicle growth of seeds of Raphanus sativus, Lactuca sativa and Lepidium sativum. The essential oils were obtained from Hyssopus officinalis, Lavandula angustifolia, Majorana hortensis, Melissa officinalis, Ocimum basilicum, Origanum vulgare, Salvia officinalis and Thymus vulgaris (Lamiaceae, Verbena officinalis (Verbenaceae, Pimpinella anisum, Foeniculum vulgare and Carum carvi (Apiaceae. The germination and radicle growth of tested seeds were affected in different ways by the oils. Thyme, balm, vervain and caraway essential oils were more active against both germination and radicle elongation.

  13. Essential thrombocythemia: a rare disease in childhood

    Directory of Open Access Journals (Sweden)

    Julia Maimone Beatrice

    2013-01-01

    Full Text Available Essential thrombocythemia is an acquired myeloproliferative disorder characterized by the proliferation of megakaryocytes in bone marrow, leading to a persistent increase in the number of circulating platelets and thus increasing the risk for thrombotic and hemorrhagic events. The disease features leukocytosis, splenomegaly, vascular occlusive events, hemorrhages and vasomotor disorders. The intricate mechanisms underlying the molecular pathogenesis of this disorder are not completely understood and are still a matter of discussion. Essential thrombocythemia is an extremely rare disorder during childhood. We report on a case of essential thrombocythemia in a child and discuss the diagnostic approach and treatment strategy.

  14. Too Many Links in the Horizon; What is Next? Linked Views and Linked History

    NARCIS (Netherlands)

    E. Liarou (Erietta); S. Idreos (Stratos)

    2011-01-01

    textabstractThe trend for more online linked data becomes stronger. Foreseeing a future where ``everything" will be online and linked, we ask the critical question; what is next? We envision that managing, querying and storing large amounts of links and data is far from yet another query

  15. The metabolic responses to aerial diffusion of essential oils.

    Directory of Open Access Journals (Sweden)

    Yani Wu

    Full Text Available Anxiety disorders are the most prevalent psychiatric disorders and affect a great number of people worldwide. Essential oils, take effects through inhalation or topical application, are believed to enhance physical, emotional, and spiritual well-being. Although clinical studies suggest that the use of essential oils may have therapeutic potential, evidence for the efficacy of essential oils in treating medical conditions remains poor, with a particular lack of studies employing rigorous analytical methods that capture its identifiable impact on human biology. Here, we report a comprehensive gas chromatography time-of-flight mass spectrometry (GC-TOFMS based metabonomics study that reveals the aromas-induced metabolic changes and the anxiolytic effect of aromas in elevated plus maze (EPM induced anxiety model rats. The significant alteration of metabolites in the EPM group was attenuated by aromas treatment, concurrent with the behavioral improvement with significantly increased open arms time and open arms entries. Brain tissue and urinary metabonomic analysis identified a number of altered metabolites in response to aromas intervention. These metabolic changes included the increased carbohydrates and lowered levels of neurotransmitters (tryptophan, serine, glycine, aspartate, tyrosine, cysteine, phenylalanine, hypotaurine, histidine, and asparagine, amino acids, and fatty acids in the brain. Elevated aspartate, carbohydrates (sucrose, maltose, fructose, and glucose, nucleosides and organic acids such as lactate and pyruvate were also observed in the urine. The EPM induced metabolic differences observed in urine or brain tissue was significantly reduced after 10 days of aroma inhalation, as noted with the loss of statistical significance on many of the metabolites in the aroma-EPM group. This study demonstrates, for the first time, that the metabonomics approach can capture the subtle metabolic changes resulting from exposure to essential oils

  16. Nutrigenomics of essential oils and their potential domestic use for improving health.

    Science.gov (United States)

    Cayuela Sánchez, José Antonio; Elamrani, Abdelaziz

    2014-11-01

    The use of essential oils as industrial food additives is notorious, like their medicinal properties. However, their use in household food spicing is for now limited. In this work, we have made a review to reveal the nutrigenomic actions exerted by their bioactive components, to promote awareness of their modulating gene expression ability and the potential that this implies. Also considered is how essential oils can be used as flavoring and seasoning after cooking and before consumption, such as diet components which can improve human health. Genetic mechanisms involved in the medicinal properties of essential oils for food use are identified from literature. These genetic mechanisms reveal nutrigenomic actions. Reviews on the medicinal properties of essential oils have been particularly considered. A wide diversity of nutrigenomic effects from essential oils useful potentially for food spicing is reviewed. General ideas are discussed about essential oils and their properties, such as anti-inflammatory, analgesic, immunomodulatory, anticancer, hepatoprotective, hypolipidemic, anti-diabetic, antioxidant, bone-reparation, anti-depressant and mitigatory for Alzheimer's disease. The essential oils for food use are potentially promoting health agents, and, therefore, worth using as flavoring and condiments. Becoming aware of the modulating gene expression actions from essential oils is important for understanding their potential for use in household dishes as spices to improve health.

  17. A Linked Model for Simulating Stand Development and Growth Processes of Loblolly Pine

    Science.gov (United States)

    V. Clark Baldwin; Phillip M. Dougherty; Harold E. Burkhart

    1998-01-01

    Linking models of different scales (e.g., process, tree-stand-ecosystem) is essential for furthering our understanding of stand, climatic, and edaphic effects on tree growth and forest productivity. Moreover, linking existing models that differ in scale and levels of resolution quickly identifies knowledge gaps in information required to scale from one level to another...

  18. Lifetime Benchmarking of Two DC-link Passive Filtering Configurations in Adjustable Speed Drives

    DEFF Research Database (Denmark)

    Wang, Haoran; Davari, Pooya; Wang, Huai

    2018-01-01

    Electrolytic capacitors with a DC-side inductor, and the slim DC-link capacitor are two typical filtering configurations in Adjustable Speed Drives (ASDs). The reliability performance of these capacitive DC-link solutions is an essential aspect to be considered, which depends on both component in...

  19. Essential Tremor Is More Than a Tremor

    Medline Plus

    Full Text Available ... About the IETF Volunteer For Healthcare Providers Giving Options Donate Prev Next IETF > About Essential Tremor > Video ... About the IETF Volunteer For Healthcare Providers Giving Options Donate Privacy Policy Contact Us Send to Email ...

  20. Autodesk Robot Structural Analysis Professional 2016 essentials

    CERN Document Server

    Marsh, Ken

    2016-01-01

    Autodesk Robot Structural Analysis Professional 2016 - Essentials is an excellent introduction to the essential features, functions, and workflows of Autodesk Robot Structural Analysis Professional. Master the tools you will need to make Robot work for you: Go from zero to proficiency with this thorough and detailed introduction to the essential concepts and workflows of Robot Structural Analysis Professional 2016. - Demystify the interface - Manipulate and manage Robot tables like a pro - Learn how to use Robot's modeling tools - Master loading techniques - Harness Robot automated load combinations - Decipher simplified seismic loading - Discover workflows for steel and concrete design - Gain insights to help troubleshoot issues Guided exercises are provided to help cement fundamental concepts in Robot Structural Analysis and drive home key functions. Get up to speed quickly with this essential text and add Robot Structural Analysis Professional 2016 to your analysis and design toolbox. New in 2016: AWC-NDS ...

  1. IEA Energy Technology Essentials: Biofuel Production

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-01-15

    The IEA Energy Technology Essentials series offers concise four-page updates on the different technologies for producing, transporting and using energy. Biofuel Production is the topic covered in this edition.

  2. Essential Tremor Is More Than a Tremor

    Medline Plus

    Full Text Available Home About the IETF Volunteer For Healthcare Providers Giving Options Donate Prev Next IETF > About Essential Tremor > ... Mild Hereditary Tremor No Big Deal Raving Fan Home About the IETF Volunteer For Healthcare Providers Giving ...

  3. Genetics Home Reference: benign essential blepharospasm

    Science.gov (United States)

    ... eyes, and eye irritation that is aggravated by wind, air pollution, sunlight, and other irritants. These symptoms ... find a genetics professional in my area? Other Names for This Condition essential blepharospasm eyelid twitching primary ...

  4. Essential Tremor Is More Than a Tremor

    Medline Plus

    Full Text Available ... More Than a Tremor Providing a voice for people with essential tremor means also reaching out to ... six-minute video tells the stories of six people living with ET. It goes beyond diagnosis and ...

  5. Essential Tremor Is More Than a Tremor

    Medline Plus

    Full Text Available ... Essential Tremor > Video Video Click to share on Facebook (Opens in new window) Click to share on ... IETF Volunteer For Healthcare Providers Giving Options Donate Privacy Policy Contact Us Send to Email Address Your ...

  6. IEA Energy Technology Essentials: Nuclear Power

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-03-15

    The IEA Energy Technology Essentials series offers concise four-page updates on the different technologies for producing, transporting and using energy. Nuclear power is the topic covered in this edition.

  7. Early Childhood Physical Education. The Essential Elements.

    Science.gov (United States)

    Gabbard, Carl

    1988-01-01

    Details are presented regarding the essential elements of an effective early childhood physical education curriculum. Components include movement awareness, fundamental locomotor skills, fundamental nonlocomotor skills, fundamental manipulative skills, and health-related fitness. (CB)

  8. IEA Energy Technology Essentials: Fuel Cells

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-04-15

    The IEA Energy Technology Essentials series offers concise four-page updates on the different technologies for producing, transporting and using energy. Fuel cells is the topic covered in this edition.

  9. Essential Oils and Fragrances from Natural Sources

    Indian Academy of Sciences (India)

    Essential oils should be subjected to both qualitative and quan- ... Several methods are employed in modern perfumery. A perfume is a ... Three types of hydro- ..... Applied Research, Proceedings of the 27th International Symposium on.

  10. Essential Outdoor Sun Safety Tips for Winter

    Science.gov (United States)

    ... Weekend Warriors expand/collapse Vitamin D Essential Outdoor Sun Safety Tips for Winter Winter sports enthusiasts are ... skiing! Be Mindful of Time Spent in the Sun, Regardless of the Season If possible, ski early ...

  11. Essential Tremor Is More Than a Tremor

    Medline Plus

    Full Text Available Home About the IETF Volunteer For Healthcare Providers Giving Options Donate Prev Next IETF > About Essential Tremor > Video Video Click to share on Facebook (Opens in new window) Click ...

  12. Deploying Linked Open Vocabulary (LOV to Enhance Library Linked Data

    Directory of Open Access Journals (Sweden)

    Oh, Sam Gyun

    2015-06-01

    Full Text Available Since the advent of Linked Data (LD as a method for building webs of data, there have been many attempts to apply and implement LD in various settings. Efforts have been made to convert bibliographic data in libraries into Linked Data, thereby generating Library Linked Data (LLD. However, when memory institutions have tried to link their data with external sources based on principles suggested by Tim Berners-Lee, identifying appropriate vocabularies for use in describing their bibliographic data has proved challenging. The objective of this paper is to discuss the potential role of Linked Open Vocabularies (LOV in providing better access to various open datasets and facilitating effective linking. The paper will also examine the ways in which memory institutions can utilize LOV to enhance the quality of LLD and LLD-based ontology design.

  13. Link for Injured Kids

    Science.gov (United States)

    Ramirez, Marizen; Toussaint, Maisha; Woods-Jaeger, Briana; Harland, Karisa; Wetjen, Kristel; Wilgenbusch, Tammy; Pitcher, Graeme; Jennissen, Charles

    2017-01-01

    Objective Injury, the most common type of pediatric trauma, can lead to a number of adverse psychosocial outcomes, including posttraumatic stress disorder. Currently, few evidence-based parent programs exist to support children hospitalized after a traumatic injury. Using methods in evaluation and intervention research, we completed a formative research study to develop a new program of psychological first aid, Link for Injured Kids, aimed to educate parents in supporting their children after a severe traumatic injury. Methods Using qualitative methods, we held focus groups with parents and pediatric trauma providers of children hospitalized at a Level I Children's Hospital because of an injury in 2012. We asked focus group participants to describe reactions to trauma and review drafts of our intervention materials. Results Health professionals and caregivers reported a broad spectrum of emotional responses by their children or patients; however, difficulties were experienced during recovery at home and upon returning to school. All parents and health professionals recommended that interventions be offered to parents either in the emergency department or close to discharge among admissions. Conclusions Results from this study strongly indicate a need for posttrauma interventions, particularly in rural settings, to support families of children to address the psychosocial outcomes in the aftermath of an injury. Findings presented here describe the process of intervention development that responds to the needs of an affected population. PMID:26428077

  14. The CMS link system

    International Nuclear Information System (INIS)

    Vila, I.

    1999-01-01

    The Compact Muon Solenoid (CMS) is a multi-purpose detector that is going to be installed in the future Large Hadron Collider (LHC) at CERN. Muons are one of the main physical signatures of the expected new physics. The muons are going to be detected by the Central Tracker (CT) and the Muon Spectrometer (MS). Both, the CT and MS can provide an independent muon momentum measurement, but for all η and momentum values the highest precision for muon momentum measurement is achieved when the muon tracks are reconstructed using both tracking detectors. The calorimeters and the solenoid volumes separate about three meters the CT and the MS. It has been shown that the alignment of the CT with respect to the MS can not be guaranteed by a software alignment in a reasonable time scale. Therefore, an opto-mechanical system (the multipoint link system) have been designed to monitor, on-line, the relative position of both sub-detectors providing a common reference frame for both of them. The local alignment of the muon barrel spectrometer determines the relative position of the muon chambers with respect to themselves and also with respect to a carbon fiber rigid structure called MAB (Module for the Alignment of the Barrel). There are a total of 36 MABs distributed in the boundary planes of each muon spectrometer sector. This paper describes all the equipment and presents the principle of measurement. (author)

  15. Diabetes and dementia links

    Directory of Open Access Journals (Sweden)

    Paula Jankowska

    2018-06-01

    Full Text Available Introduction The number of patients suffering from diabetes mellitus is growing globally. It is expected to observe 253.4 million sufferers in geriatric population in 2045. In this time, also 131.5 million of people is going to have dementia and other cognitive problems. In people aged over 65 these two diseases are concomitant quite often. What are the connections in the area of etiology and treatment? Aim The purpose of this study is to present links between dementia and diabetes are depicted in professional literature. Results Diabetes and dementia are associated on many levels. These conditions have common risk factors. Diabetes may contribute to cognitive impairment in many ways, promoting development of atherosclerosis, brain vessel damage and vascular dementia. Alzheimer disease may be promoted by hyperglycemia and hyperinsulinemia. On contrary also hypoglycaemia, often met in elderly diabetic patients has negative impact on cognitive function. Dementia seriously affects treatment of diabetes. The main problems are not satisfying adherence and diabetes self-management. Conclusions Prevention of diabetes and dementia risk factors can be performed simultaneously as the are common for both diseases. Enhancing physical activity, reducing saturated fats consumption, levels of cholesterol and body mass are considered to be beneficial in the context of described conditions. Furthermore, treatment of diabetes is strongly affected by cognitive dysfunction. Management of dementive diabetics requires individualization and using long-acting drugs. It is crucial to reduce risk of life-threatening hypoglycaemias and to create wide team to take care of these patients.

  16. Hierarchical Linked Views

    Energy Technology Data Exchange (ETDEWEB)

    Erbacher, Robert; Frincke, Deb

    2007-07-02

    Coordinated views have proven critical to the development of effective visualization environments. This results from the fact that a single view or representation of the data cannot show all of the intricacies of a given data set. Additionally, users will often need to correlate more data parameters than can effectively be integrated into a single visual display. Typically, development of multiple-linked views results in an adhoc configuration of views and associated interactions. The hierarchical model we are proposing is geared towards more effective organization of such environments and the views they encompass. At the same time, this model can effectively integrate much of the prior work on interactive and visual frameworks. Additionally, we expand the concept of views to incorporate perceptual views. This is related to the fact that visual displays can have information encoded at various levels of focus. Thus, a global view of the display provides overall trends of the data while focusing in on individual elements provides detailed specifics. By integrating interaction and perception into a single model, we show how one impacts the other. Typically, interaction and perception are considered separately, however, when interaction is being considered at a fundamental level and allowed to direct/modify the visualization directly we must consider them simultaneously and how they impact one another.

  17. Linking to the Future

    Science.gov (United States)

    Moore, John W.

    1999-09-01

    of JCE in the mail each month, and I expect you do too. I can glance at the cover to get an overview of an issue's content, and I usually am enticed inside by intriguing cover art. I can scan the table of contents to find articles I want to read, or I can just browse through the issue to see what looks interesting. Usually the editors have juxtaposed related articles so that I often find a small treasure trove. The printed Journal is quite portable and can be read in a car or airplane. It will last a long time, and until the paper deteriorates, I will never have a problem reading back issues. I have almost every issue from the first day I subscribed and have even added some older ones from collections of retired colleagues who no longer had shelf space for them. I certainly would not want to give up my printed copies, and I want to keep getting them. I find that JCE Online provides a different kind of resource that is equally valuable. It contains more information, and information that is more appropriate in electronic form. It links related ideas into a much more complex web of information than is possible in print. And it opens pathways to lots of information that is not part of JCE but resides elsewhere. Using this issue as an example, let's take a tour of what JCE Online can do. Point your Web browser to http://jchemed.chem.wisc.edu Click on Journal and then on Current Issue (unless September 1999 is no longer the current issue, in which case you will find it in Past Issues). In the table of contents, find the article "UV Catalysis, Cyanotype Photography, and Sunscreens". Click on the title. When the abstract appears, click on Full Text (PDF) to see the article, just as it appears on page 1199 in this issue. When you are prompted, enter the name and subscriber number from your address label. At the end of the article you will find that supplementary materials are available (including a procedure for testing sunscreens) and you can click on the link to view them

  18. Object linking in repositories

    Science.gov (United States)

    Eichmann, David (Editor); Beck, Jon; Atkins, John; Bailey, Bill

    1992-01-01

    This topic is covered in three sections. The first section explores some of the architectural ramifications of extending the Eichmann/Atkins lattice-based classification scheme to encompass the assets of the full life cycle of software development. A model is considered that provides explicit links between objects in addition to the edges connecting classification vertices in the standard lattice. The second section gives a description of the efforts to implement the repository architecture using a commercially available object-oriented database management system. Some of the features of this implementation are described, and some of the next steps to be taken to produce a working prototype of the repository are pointed out. In the final section, it is argued that design and instantiation of reusable components have competing criteria (design-for-reuse strives for generality, design-with-reuse strives for specificity) and that providing mechanisms for each can be complementary rather than antagonistic. In particular, it is demonstrated how program slicing techniques can be applied to customization of reusable components.

  19. Growth regulators and essential oil production

    OpenAIRE

    Prins, Cláudia L; Vieira, Ivo J. C; Freitas, Silvério P

    2010-01-01

    The aroma and fragrance industry is a billion-dollar world market which grows annually. Essential oils comprise the majority of compounds used by these industries. These sets of metabolites are formed mainly by monoterpenes, which are products of the plants' secondary metabolism. Biosynthesized from mevalonate and methylerythitol phosphate, the essential oil production depends not only on genetic factors and the developmental stage of plants, but also on environmental factors which could resu...

  20. Essentials of Project and Systems Engineering Management

    CERN Document Server

    Eisner, Howard S

    2008-01-01

    The Third Edition of Essentials of Project and Systems Engineering Management enables readers to manage the design, development, and engineering of systems effectively and efficiently. The book both defines and describes the essentials of project and systems engineering management and, moreover, shows the critical relationship and interconnection between project management and systems engineering. The author's comprehensive presentation has proven successful in enabling both engineers and project managers to understand their roles, collaborate, and quickly grasp and apply all the basic princip

  1. Study of quantitative and qualitative variations in essential oils of Sicilian Rosmarinus officinalis L.

    Science.gov (United States)

    Tuttolomondo, Teresa; Dugo, Giacomo; Ruberto, Giuseppe; Leto, Claudio; Napoli, Edoardo M; Cicero, Nicola; Gervasi, Teresa; Virga, Giuseppe; Leone, Raffaele; Licata, Mario; La Bella, Salvatore

    2015-01-01

    In this study the chemical characterisation of 10 Sicilian Rosmarinus officinalis L. biotypes essential oils is reported. The main goal of this work was to analyse the relationship between the essential oils yield and the geographical distribution of the species plants. The essential oils were analysed by GC-FID and GC-MS. Hierarchical cluster analysis and principal component analysis statistical methods were used to cluster biotypes according to the essential oils chemical composition. The essential oil yield ranged from 0.8 to 2.3 (v/w). In total 82 compounds have been identified, these represent 96.7-99.9% of the essential oil. The most represented compounds in the essential oils were 1.8-cineole, linalool, α-terpineol, verbenone, α-pinene, limonene, bornyl acetate and terpinolene. The results show that the essential oil yield of the 10 biotypes is affected by the environmental characteristics of the sampling sites while the chemical composition is linked to the genetic characteristics of different biotypes.

  2. EarthCube GeoLink: Semantics and Linked Data for the Geosciences

    Science.gov (United States)

    Arko, R. A.; Carbotte, S. M.; Chandler, C. L.; Cheatham, M.; Fils, D.; Hitzler, P.; Janowicz, K.; Ji, P.; Jones, M. B.; Krisnadhi, A.; Lehnert, K. A.; Mickle, A.; Narock, T.; O'Brien, M.; Raymond, L. M.; Schildhauer, M.; Shepherd, A.; Wiebe, P. H.

    2015-12-01

    The NSF EarthCube initiative is building next-generation cyberinfrastructure to aid geoscientists in collecting, accessing, analyzing, sharing, and visualizing their data and knowledge. The EarthCube GeoLink Building Block project focuses on a specific set of software protocols and vocabularies, often characterized as the Semantic Web and "Linked Data", to publish data online in a way that is easily discoverable, accessible, and interoperable. GeoLink brings together specialists from the computer science, geoscience, and library science domains, and includes data from a network of NSF-funded repositories that support scientific studies in marine geology, marine ecosystems, biogeochemistry, and paleoclimatology. We are working collaboratively with closely-related Building Block projects including EarthCollab and CINERGI, and solicit feedback from RCN projects including Cyberinfrastructure for Paleogeosciences (C4P) and iSamples. GeoLink has developed a modular ontology that describes essential geoscience research concepts; published data from seven collections (to date) on the Web as geospatially-enabled Linked Data using this ontology; matched and mapped data between collections using shared identifiers for investigators, repositories, datasets, funding awards, platforms, research cruises, physical specimens, and gazetteer features; and aggregated the results in a shared knowledgebase that can be queried via a standard SPARQL endpoint. Client applications have been built around the knowledgebase, including a Web/map-based data browser using the Leaflet JavaScript library and a simple query service using the OpenSearch format. Future development will include extending and refining the GeoLink ontology, adding content from additional repositories, developing semi-automated algorithms to enhance metadata, and further work on client applications.

  3. Divestiture: strategy's missing link.

    Science.gov (United States)

    Dranikoff, Lee; Koller, Tim; Schneider, Antoon

    2002-05-01

    Although most companies dedicate considerable time and attention to acquiring and creating businesses, few devote much effort to divestitures. But regularly divesting businesses--even good, healthy ones--ensures that remaining units reach their potential and that the overall company grows stronger. Drawing on extensive research into corporate performance over the last decade, McKinsey consultants Lee Dranikoff, Tim Koller, and Antoon Schneider show that an active divestiture strategy is essential to a corporation's long-term health and profitability. In particular, they say that companies that actively manage their businesses through acquisitions and divestitures create substantially more shareholder value than those that passively hold on to their businesses. Therefore, companies should avoid making divestitures only in response to pressure and instead make them part of a well-thought-out strategy. This article presents a five-step process for doing just that: prepare the organization, identify the best candidates for divestiture, execute the best deal, communicate the decision, and create new businesses. As the fifth step suggests, divestiture is not an end in itself. Rather, it is a means to a larger end: building a company that can grow and prosper over the long haul. Wise executives divest so that they can create new businesses and expand existing ones. All of the funds, management time, and support-function capacity that a divestiture frees up should therefore be reinvested in creating shareholder value. In some cases, this will mean returning money to shareholders. But more likely than not, it will mean investing in attractive growth opportunities. In companies as in the marketplace, creation and destruction go hand in hand; neither flourishes without the other.

  4. Harm mediates the disgust-immorality link.

    Science.gov (United States)

    Schein, Chelsea; Ritter, Ryan S; Gray, Kurt

    2016-09-01

    Many acts are disgusting, but only some of these acts are immoral. Dyadic morality predicts that disgusting acts should be judged as immoral to the extent that they seem harmful. Consistent with this prediction, 3 studies reveal that perceived harm mediates the link between feelings of disgust and moral condemnation-even for ostensibly harmless "purity" violations. In many cases, accounting for perceived harm completely eliminates the link between disgust and moral condemnation. Analyses also reveal the predictive power of anger and typicality/weirdness in moral judgments of disgusting acts. The mediation of disgust by harm holds across diverse acts including gay marriage, sex acts, and religious blasphemy. Revealing the endogenous presence and moral relevance of harm within disgusting-but-ostensibly harmless acts argues against modular accounts of moral cognition such as moral foundations theory. Instead, these data support pluralistic conceptions of harm and constructionist accounts of morality and emotion. Implications for moral cognition and the concept of "purity" are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  5. Revealing the programming process

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael Edelgaard

    2005-01-01

    One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because...... the textbook medium is static and therefore ill-suited to expose the process of programming. We have found that process recordings in the form of captured narrated programming sessions are a simple, cheap, and efficient way of providing the revelation.We identify seven different elements of the programming...

  6. TypeScript revealed

    CERN Document Server

    Maharry, Dan

    2013-01-01

    TypeScript Revealed is a quick 100-page guide to Anders Hejlsberg's new take on JavaScript. With this brief, fast-paced introduction to TypeScript, .NET, Web and Windows 8 application developers who are already familiar with JavaScript will easily get up to speed with TypeScript and decide whether or not to start incorporating it into their own development. TypeScript is 'JavaScript for Application-scale development'; a superset of JavaScript that brings to it an additional object-oriented-like syntax familiar to .NET programmers that compiles down into simple, clean JavaScript that any browse

  7. Inhibition of cholinesterase by essential oil from food plant.

    Science.gov (United States)

    Chaiyana, Wantida; Okonogi, Siriporn

    2012-06-15

    Inhibition of cholinesterase has attracted much attention recently because of its potential for the treatment of Alzheimer's disease. In this work, the anticholinesterase activities of plant oils were investigated using Ellman's colorimetric method. The results indicate that essential oils obtained from Melissa officinalis leaf and Citrus aurantifolia leaf showed high acetylcholinesterase and butyrylcholinesterase co-inhibitory activities. C. aurantifolia leaf oil revealed in this study has an IC(50) value on acetylcholinesterase and butyrylcholinesterase of 139 ± 35 and 42 ± 5 μg/ml, respectively. GC/MS analysis revealed that the major constituents of C. aurantifolia leaf oil are monoterpenoids including limonene, l-camphor, citronellol, o-cymene and 1,8-cineole. Copyright © 2012 Elsevier GmbH. All rights reserved.

  8. Pedagogy as influencing nursing students' essentialized understanding of culture.

    Science.gov (United States)

    Gregory, David; Harrowing, Jean; Lee, Bonnie; Doolittle, Lisa; O'Sullivan, Patrick S

    2010-01-01

    In this qualitative study, we explored how students understood "culture." Participants defined culture and wrote narratives regarding specific cultural encounters. The sample comprised both nursing (n=14) and non-nursing (n=8) students to allow for comparison groups. Content analysis of the narratives revealed two broad paradigms of cultural understanding: essentialist and constructivist. Essentialist narratives comprised four themes: determinism (culture defied individual resistance); relativism (the possibility of making value judgments disappeared); Othering (culture was equated to exotica, and emphasized difference); and, reductionism (personhood was eclipsed by culture). In contrast, the constructivist narratives were characterized by influence (non-determinism), dynamism (culture was dynamic and evolutionary); and, relationship-building. The unintended negative consequences of essentialist notions of culture were revealed in the nursing students' narratives. Pedagogy is implicated in nursing students' essentialized understanding of culture.

  9. The Chromium is an essential element in the human

    International Nuclear Information System (INIS)

    Alvarado Gamez, A.; Blanco Saenz, R.; Mora Morales, E.

    2002-01-01

    The Chromium is an essential element for human and animals, because it a preponderant function in the insulin metabolism as a glucose tolerance factor (GTF). The deficiency of chromium engenders a deterioration in the glucose metabolism due to bad efficiency of insulin. Because the importance of this element an exhaustive reference review was made and this presents some studies realized in laboratory animals and in human beings where it is prove with resuits the effect of chromium over the improvement of patients with non-insulin dependant diabetes. Three substances are presented as chromium active biological forms: a material rich in chromium known as glucose tolerance factor, chromium picolinate and a substance of low molecular weight LMWCr in its forms of apo and holo that contains chromium and it links the insulin receptor and improves its activity. Also this paper presents information about the condition of diabetes in Costa Rica. (Author) [es

  10. Postharvest quality of essential oil treated roses

    Directory of Open Access Journals (Sweden)

    Guilherme Mariano Manfredini

    2017-07-01

    Full Text Available The loss of commercial quality during storage and transportation of roses is one of the factors that reflect on production costs, leading producers to preventively apply harmful chemicals, mainly to hamper Botrytis cinerea development and reduce further losses. An alternative to increase flower longevity without contaminating the environment with harmful chemicals is the use of natural products, such as essential oils, which have fungistatic and insecticide properties, as well as low toxicity. The objective of this study was to evaluate the effect of essential oils on the vase life of Rosa cv. Avalanche: 12 treatments were tested, resulting from the combination of 5 types of essential oils plus the control in two cold storage periods (2 to 6 days at 1 °C, 90-95% RH. The essential oils tested were eucalyptus, cinnamon, lemongrass and peppermint (1%, clove (0.1%, plus a control with distilled water. Application was made by spraying the flower buds. After storage at low temperatures, the flower stems were kept in a room (16 °C, 70% RH during 10 days for evaluation. Flower stems stored for 2 days in a cold chamber showed better means for darkening, turgor and bent neck, as well as a lower weight loss by the stems. The application of lemongrass essential oil at 1% caused burns on the petals, compromising quality and pot life. The essential oils of peppermint and eucalyptus allowed flower quality maintenance until the 10th day of evaluation. It is possible to conclude that post-harvest spraying with peppermint or eucalyptus essential oil at 1%, combined with cold storage for 2 days, provided greater longevity and quality for cv. Avalanche roses.

  11. Essential oil from Artemisia phaeolepis: chemical composition and antimicrobial activities.

    Science.gov (United States)

    Ben Hsouna, Anis; Ben Halima, Nihed; Abdelkafi, Slim; Hamdi, Naceur

    2013-01-01

    Artemisia phaeolepis, a perennial herb with a strong volatile odor, grows on the grasslands of Mediterranean region. Essential oil obtained from Artemisia phaeolepis was analyzed by gas chromatography-flame ionization detection and gas chromatography-mass spectrometry. A total of 79 components representing 98.19% of the total oil were identified, and the main compounds in the oil were found to be eucalyptol (11.30%), camphor (8.21%), terpine-4-ol (7.32%), germacrene D (6.39), caryophyllene oxide (6.34%), and caryophyllene (5.37%). The essential oil showed definite inhibitory activity against 10 strains of test microorganisms. Eucalyptol, camphor, terpine-4-ol, caryophyllene, germacrene D and caryophyllene oxide were also examined as the major components of the oil. Camphor showed the strongest antimicrobial activity; terpine-4-ol, eucalyptol, caryophyllene and germacrene D were moderately active and caryophyllene oxide was weakly active. The study revealed that the antimicrobial properties of the essential oil can be attributed to the synergistic effects of its diverse major and minor components.

  12. Essential protein discovery based on a combination of modularity and conservatism.

    Science.gov (United States)

    Zhao, Bihai; Wang, Jianxin; Li, Xueyong; Wu, Fang-Xiang

    2016-11-01

    Essential proteins are indispensable for the survival of a living organism and play important roles in the emerging field of synthetic biology. Many computational methods have been proposed to identify essential proteins by using the topological features of interactome networks. However, most of these methods ignored intrinsic biological meaning of proteins. Researches show that essentiality is tied not only to the protein or gene itself, but also to the molecular modules to which that protein belongs. The results of this study reveal the modularity of essential proteins. On the other hand, essential proteins are more evolutionarily conserved than nonessential proteins and frequently bind each other. That is to say, conservatism is another important feature of essential proteins. Multiple networks are constructed by integrating protein-protein interaction (PPI) networks, time course gene expression data and protein domain information. Based on these networks, a new essential protein identification method is proposed based on a combination of modularity and conservatism of proteins. Experimental results show that the proposed method outperforms other essential protein identification methods in terms of a number essential protein out of top ranked candidates. Copyright © 2016. Published by Elsevier Inc.

  13. Chemical Composition, Antimicrobial and Antioxidant Activities of Essential Oils from Organically Cultivated Fennel Cultivars

    OpenAIRE

    Shahat, Abdelaaty A.; Ibrahim, Abeer Y.; Hendawy, Saber F.; Omer, Elsayed A.; Hammouda, Faiza M.; Abdel-Rahman, Fawzia H.; Saleh, Mahmoud A.

    2011-01-01

    Essential oils of the fruits of three organically grown cultivars of Egyptian fennel (Foeniculum vulgare var. azoricum, Foeniculum vulgare var. dulce and Foeniculum vulgare var. vulgare) were examined for their chemical constituents, antimicrobial and antioxidant activities. Gas chromatography/mass spectrometry analysis of the essential oils revealed the presence of 18 major monoterpenoids in all three cultivars but their percentage in each oil were greatly different. trans-Anethole, estragol...

  14. Characterization equipment essential/support drawing plan

    International Nuclear Information System (INIS)

    WILSON, G.W.

    1999-01-01

    The purpose of this document is to list the Characterization equipment drawings that are classified as Essential Drawings and Support Drawings. Essential Drawings: Are those drawings identified by the facility staff as necessary to directly support the safe operation of the facility or equipment (HNF 1997a). Support Drawings: Are those drawings identified by facility staff that further describe the design details of structures, systems, or components shown on essential drawings. (HNF 1997a) The Characterization equipment drawings identified in this report are deemed essential drawings as defined in HNF-PRO-242, Engineering Drawing Requirements (HNF 1997a). These drawings will be prepared, revised, and maintained per HNF-PRO-440, Engineering Document Change Control (HNF 1997b). All other Characterization equipment drawings not identified in this document will be considered General drawings until the Characterization Equipment Drawing Evaluation Report (Wilson 1998) is updated during fiscal year 1999. Trucks 1 and 2 drawings are not included in this revision of the essential drawing list due to uncertainty about future use

  15. Essential hypertension vs. secondary hypertension among children.

    Science.gov (United States)

    Gupta-Malhotra, Monesha; Banker, Ashish; Shete, Sanjay; Hashmi, Syed Sharukh; Tyson, John E; Barratt, Michelle S; Hecht, Jacqueline T; Milewicz, Diane M; Boerwinkle, Eric

    2015-01-01

    The aim was to determine the proportions and correlates of essential hypertension among children in a tertiary pediatric hypertension clinic. We evaluated 423 consecutive children and collected demographic and clinical history by retrospective chart review. We identified 275 (65%) hypertensive children (blood pressure >95th percentile per the "Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents") from 423 children referred to the clinic for history of elevated blood pressure. The remainder of the patients had normotension (11%), white coat hypertension (11%), prehypertension (10%), and pending diagnosis (3%). Among the 275 hypertensive children, 43% (n = 119; boys = 56%; median age = 12 years; range = 3-17 years) had essential hypertension and 57% (n = 156; boys = 66%; median age = 9 years; range = 0.08-19 years) had secondary hypertension. When compared with those with secondary hypertension, those with essential hypertension had a significantly older age at diagnosis (P = 0.0002), stronger family history of hypertension (94% vs. 68%; P secondary hypertension. The phenotype of essential hypertension can present as early as 3 years of age and is the predominant form of hypertension in children after age of 6 years. Among children with hypertension, those with essential hypertension present at an older age, have a stronger family history of hypertension, and have lower prevalence of preterm birth. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Kif4 Is Essential for Mouse Oocyte Meiosis.

    Science.gov (United States)

    Camlin, Nicole J; McLaughlin, Eileen A; Holt, Janet E

    2017-01-01

    Progression through the meiotic cell cycle must be strictly regulated in oocytes to generate viable embryos and offspring. During mitosis, the kinesin motor protein Kif4 is indispensable for chromosome condensation and separation, midzone formation and cytokinesis. Additionally, the bioactivity of Kif4 is dependent on phosphorylation via Aurora Kinase B and Cdk1, which regulate Kif4 function throughout mitosis. Here, we examine the role of Kif4 in mammalian oocyte meiosis. Kif4 localized in the cytoplasm throughout meiosis I and II, but was also observed to have a dynamic subcellular distribution, associating with both microtubules and kinetochores at different stages of development. Co-localization and proximity ligation assays revealed that the kinetochore proteins, CENP-C and Ndc80, are potential Kif4 interacting proteins. Functional analysis of Kif4 in oocytes via antisense knock-down demonstrated that this protein was not essential for meiosis I completion. However, Kif4 depleted oocytes displayed enlarged polar bodies and abnormal metaphase II spindles, indicating an essential role for this protein for correct asymmetric cell division in meiosis I. Further investigation of the phosphoregulation of meiotic Kif4 revealed that Aurora Kinase and Cdk activity is critical for Kif4 kinetochore localization and interaction with Ndc80 and CENP-C. Finally, Kif4 protein but not gene expression was found to be upregulated with age, suggesting a role for this protein in the decline of oocyte quality with age.

  17. Chemistry of plutonium revealed

    International Nuclear Information System (INIS)

    Connick, R.E.

    1992-01-01

    In 1941 one goal of the Manhattan Project was to unravel the chemistry of the synthetic element plutonium as rapidly as possible. In this paper the work carried out at Berkeley from the spring of 1942 to the summer of 1945 is described briefly. The aqueous chemistry of plutonium is quite remarkable. Important insights were obtained from tracer experiments, but the full complexity was not revealed until macroscopic amounts (milligrams) became available. Because processes for separation from fission products were based on aqueous solutions, such solution chemistry was emphasized, particularly precipitation and oxidation-reduction behavior. The latter turned out to be unusually intricate when it was discovered that two more oxidation states existed in aqueous solution than had previously been suspected. Further, an equilibrium was rapidly established among the four aqueous oxidation states, while at the same time any three were not in equilibrium. These and other observations made while doing a crash study of a previously unknown element are reported

  18. Android Emotions Revealed

    DEFF Research Database (Denmark)

    Vlachos, Evgenios; Schärfe, Henrik

    2012-01-01

    This work presents a method for designing facial interfaces for sociable android robots with respect to the fundamental rules of human affect expression. Extending the work of Paul Ekman towards a robotic direction, we follow the judgment-based approach for evaluating facial expressions to test...... findings are based on the results derived from a number of judgments, and suggest that before programming the facial expressions of a Geminoid, the Original should pass through the proposed procedure. According to our recommendations, the facial expressions of an android should be tested by judges, even...... in which case an android robot like the Geminoid|DK –a duplicate of an Original person- reveals emotions convincingly; when following an empirical perspective, or when following a theoretical one. The methodology includes the processes of acquiring the empirical data, and gathering feedback on them. Our...

  19. Chemical identification of Tagetes minuta Linnaeus (Asteraceae) essential oil and its acaricidal effect on ticks.

    Science.gov (United States)

    Garcia, Marcos Valério; Matias, Jaqueline; Barros, Jacqueline Cavalcante; de Lima, Dênis Pires; Lopes, Rosângela da Silva; Andreotti, Renato

    2012-01-01

    The control of tick species that affect animal production is vital for the economic welfare of the cattle industry. This study focused on testing the acaricidal activity of the essential oil from the leaves and stems of Tagetes minuta against several Brazilian tick species, including Rhipicephalus (Boophilus) microplus, Rhipicephalus sanguineus, Amblyomma cajennense and Argas miniatus. The chemical composition of the essential oil was determined by chromatography and spectroscopy analyses, which revealed the presence of monoterpenes. The adult immersion test (AIT) and the larval packet test (LPT) were used to evaluate the efficacy of T. minuta essential oil in tick management at concentrations of 2.5, 5, 10, 20 and 40%. The results demonstrated that the T. minuta essential oil had over 95% efficacy against four species of ticks at a concentration of 20%. These results suggest that the essential oil of T. minuta could be used as an environmentally friendly acaricide.

  20. Energy/war: breaking the nuclear link

    International Nuclear Information System (INIS)

    Lovins, A.B.; Lovins, L.H.

    1980-01-01

    Policies to control the spread of nuclear weapons have assumed that the rapid worldwide spread of nuclear power is essential to replace oil, is both economically desirable and inevitable, and that the international political order must remain inherently discriminatory and dominated by the nuclear arms race. These assumptions are challenged as contrary to economic fact and market behavior. The authors feel that the link between nuclear reactors and nuclear bombs is inextricable, making proliferation inevitable and nuclear power a dangerous and costly alternative to oil. Instead, they suggest that nuclear power will collapse in response to market forces because only a few centrally-planned economies can override economic pressures. Acknowledgement of this collapse should be encouraged and the benefits of nuclear power accepted as illusory, according to the authors. 349 references, 2 figures