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  1. Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.

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    Olson, William; Abdus-Saboor, Ishmail; Cui, Lian; Burdge, Justin; Raabe, Tobias; Ma, Minghong; Luo, Wenqin

    2017-10-12

    The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated Mrgprd CreERT2 mouse line. We found that mouse plantar paw skin is also innervated by a low density of Mrgprd + nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the "enlarged representation" of plantar paw regions in the CNS.

  2. Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

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    Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

    2016-06-01

    Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain

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    Joo Chan-Gyu

    2009-06-01

    Full Text Available Abstract Background In vivo proton magnetic resonance spectroscopy (1H-MRS studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection. Results Changes in the N-acetylaspartate (NAA, choline (Cho, myo-inositol (MI, creatine (Cr and glutamine/glutamate (Glx resonances were quantified both in absolute terms and relative to the creatine resonance. Most abnormalities were observed at the time of peak viremia, 2 weeks post infection (wpi. At that time point, significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex. Cr was significantly elevated only in the white matter. Changes in Cho and Cho/Cr were similar across the brain regions, increasing at 2 wpi, and falling below baseline levels at 4 wpi. MI and MI/Cr levels were increased across all brain regions. Conclusion These data best support the hypothesis that different brain regions have variable intrinsic vulnerabilities to neuronal injury caused by the AIDS virus.

  4. Comparative genomics reveals cotton-specific virulence factors in flexible genomic regions in Verticillium dahliae and evidence of horizontal gene transfer from Fusarium.

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    Chen, Jie-Yin; Liu, Chun; Gui, Yue-Jing; Si, Kai-Wei; Zhang, Dan-Dan; Wang, Jie; Short, Dylan P G; Huang, Jin-Qun; Li, Nan-Yang; Liang, Yong; Zhang, Wen-Qi; Yang, Lin; Ma, Xue-Feng; Li, Ting-Gang; Zhou, Lei; Wang, Bao-Li; Bao, Yu-Ming; Subbarao, Krishna V; Zhang, Geng-Yun; Dai, Xiao-Feng

    2018-01-01

    Verticillium dahliae isolates are most virulent on the host from which they were originally isolated. Mechanisms underlying these dominant host adaptations are currently unknown. We sequenced the genome of V. dahliae Vd991, which is highly virulent on its original host, cotton, and performed comparisons with the reference genomes of JR2 (from tomato) and VdLs.17 (from lettuce). Pathogenicity-related factor prediction, orthology and multigene family classification, transcriptome analyses, phylogenetic analyses, and pathogenicity experiments were performed. The Vd991 genome harbored several exclusive, lineage-specific (LS) genes within LS regions (LSRs). Deletion mutants of the seven genes within one LSR (G-LSR2) in Vd991 were less virulent only on cotton. Integration of G-LSR2 genes individually into JR2 and VdLs.17 resulted in significantly enhanced virulence on cotton but did not affect virulence on tomato or lettuce. Transcription levels of the seven LS genes in Vd991 were higher during the early stages of cotton infection, as compared with other hosts. Phylogenetic analyses suggested that G-LSR2 was acquired from Fusarium oxysporum f. sp. vasinfectum through horizontal gene transfer. Our results provide evidence that horizontal gene transfer from Fusarium to Vd991 contributed significantly to its adaptation to cotton and may represent a significant mechanism in the evolution of an asexual plant pathogen. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  5. Specifics of modernization in Russia’s regions

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    Ol’ga Vladimirovna Aksenova

    2014-11-01

    Full Text Available The article analyzes the specifics of modernization in the Russian regions. The author studies modernization in connection with globalization, that is, with the formation of global networks, high-tech core and archaic periphery. The article shows the main trends of modernization in the Russian regions, identifies the role of local government in their formation. In addition, it reveals a number of specific features of modernization in Russia; in particular, a complex combination of a protective attitude towards innovation and focus on development in local communities. Besides, the article pays special attention to the role of traditional value orientations in the decision making process at the local level

  6. [Intoxications specific to the Aquitaine region].

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    Bédry, R; Gromb, S

    2009-07-01

    Some intoxications are more specifically linked to the Aquitaine region than to other regions of France, due to environmental circumstances (fauna, flora, climate) or traditional activities (gastronomy). Three types of intoxications are particular in this area. Pine processionary caterpillar envenomations (Thaumetopoea pityocampa), a Southern Europe pinewood parasite, are frequently encountered in the Landes' forest. They are responsible of ocular and/or skin lesions with urticaria or contact dermatitis, seldom associated with immediate IgE hypersensitivity. According to the south Atlantic coastal region geology and the marine streams, venomous marine animals are mainly located in Charente-Maritime for jellyfish, in Gironde and in Landes for weeverfish and in Atlantic Pyrenees for sea anemone. Usually not dangerous, first-aid workers treat most cases of these envenomations. Some endemic mushrooms (Tricholoma auratum) which grow on the dunes of the Atlantic coastal region, are usually considered as very good comestibles, but were recently responsible for serious intoxications: T.auratum was responsible of several cases of rhabdomyolysis, without neurological involvement, nor renal or hepatic lesion. Three deaths were notified. Animal studies confirmed the responsibility of the mushrooms.

  7. Gaussian graphical modeling reveals specific lipid correlations in glioblastoma cells

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    Mueller, Nikola S.; Krumsiek, Jan; Theis, Fabian J.; Böhm, Christian; Meyer-Bäse, Anke

    2011-06-01

    Advances in high-throughput measurements of biological specimens necessitate the development of biologically driven computational techniques. To understand the molecular level of many human diseases, such as cancer, lipid quantifications have been shown to offer an excellent opportunity to reveal disease-specific regulations. The data analysis of the cell lipidome, however, remains a challenging task and cannot be accomplished solely based on intuitive reasoning. We have developed a method to identify a lipid correlation network which is entirely disease-specific. A powerful method to correlate experimentally measured lipid levels across the various samples is a Gaussian Graphical Model (GGM), which is based on partial correlation coefficients. In contrast to regular Pearson correlations, partial correlations aim to identify only direct correlations while eliminating indirect associations. Conventional GGM calculations on the entire dataset can, however, not provide information on whether a correlation is truly disease-specific with respect to the disease samples and not a correlation of control samples. Thus, we implemented a novel differential GGM approach unraveling only the disease-specific correlations, and applied it to the lipidome of immortal Glioblastoma tumor cells. A large set of lipid species were measured by mass spectrometry in order to evaluate lipid remodeling as a result to a combination of perturbation of cells inducing programmed cell death, while the other perturbations served solely as biological controls. With the differential GGM, we were able to reveal Glioblastoma-specific lipid correlations to advance biomedical research on novel gene therapies.

  8. PARTICULARS OF REGIONAL DEVELOPEMMENT AND SPECIFIC CAUSES

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    DORU CÎRNU

    2010-09-01

    Full Text Available Regional development is a complex process which supports each territory in building its future on the basis of its own territorial capital and, thus, contributing to reducing disparities between different geographical areas. Regional development policy is a set of planned measures, promoted by local and central public administration authorities, in partnership with different actors (private, public, volunteers used to ensure dynamic and sustainable economic growth by efficiently using regional and local potential to improve living conditions. The main areas of interest of regional policies are: enterprise development, labor market, attracting investment, technology transfer, SME sector development, infrastructure improvement, environmental quality, rural development, health, education, culture.

  9. Spillover Effects of the Russian Economy: Regional Specificity

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    Elena Anatolyevna Fedorova

    2016-03-01

    Full Text Available The purpose of the study is to evaluate the strength and direction of the distribution of the foreign direct investments (FDI in regional economy. The subject matter of the research is FDI to the regions of Russia. The subject of the study is relevant as it makes possible to estimate the long-term consequences from the restrictions of the West countries (in connection with sanctions against the inflow of the foreign capital to the regions of the Russian Federation. The study is based on the following hypotheses: 1. Russian regional economy has horizontal (distribution of effects from FDI within an industry and vertical spillover effects (distribution according to a technological chain, from product suppliers to product consumers. Vertical effects are more important and have greater amplitude than horizontal effects. An industry competition is one of the causes of negative horizontal spillover effect, and the scale of the company is the reason of positive horizontal spillover effect. 2. FDI generates the positive regional spillover effects on the productivity of domestic firms in the Russian economy. 3. Regional industry specificity influences the sign and magnitude of spillovers from FDI. 4. Time sensitivity is revealed for horizontal spillovers, so the regional effects may change the direction. As an empirical basis of the study, the statements of 23567 Russian companies with FDI and 25354 Russian enterprises without FDI for the 5 years were used. The methodology of the research is the calculation of spillover effects, Cobb-Douglas production function and panel data regression. The study has found, that the direct vertical spillover effects are almost absent. That means that industrial consumers do not notice the effect of inward FDI. At the same time, the converse effect related to the product suppliers is positive, but as the direct effect, it is not more important in any group of regions then the horizontal effect. The Russian economy has a

  10. New Normal in Russian Economy: Regional Specificity

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    Yakov Petrovich Silin

    2016-09-01

    Full Text Available The main objective of the article is to study the concepts of “New Normal”, “New Industrialization” and the questions of formation and development of the productions of the fifth and sixth technological modes in the regional economic area. Substantive expansion of “New Normal” concept was argued, it became popular during the global financial and economic crisis of 2008. The logic of transformation to a “New Normal” is true not only for the world economy, individual countries and regions, but also for the Sverdlovsk region. The scientific hypothesis of the article consists in the identifying the characteristics of “New Normal” at the regional level and showing the possible directions of transformation from a «New Normal” situation using the concept of new industrialization for the regional economy. The main features of “New Normal” in the region were identified and analyzed. There are, for example, the slow growth of industrial production, the reducing of the investment climate, the low dynamics of metal prices. It is proved that the realization of the concept of new industrialization in the region can become the most attractive answer to the challenges of «New Normal». The need for the integration of the processes of new industrialization with the formation and development of the productions of the fifth and sixth technological waves is proved. The article is focused on the possibility of the transformation of the Sverdlovsk region in the region of the technological breakthrough of the 21st century. It is demonstrated that during 15–20 years, the priority will be the development of the productions of the fifth and sixth technological waves that will be based on the high-tech production of military-industrial complex, nuclear energy as well as nanotechnology and nanomaterials. It is proved that at this time, the model of innovative development of the region may be realized. It is able to lead the regional economy

  11. Species-Specific Mechanisms of Neuron Subtype Specification Reveal Evolutionary Plasticity of Amniote Brain Development

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    Tadashi Nomura

    2018-03-01

    Full Text Available Summary: Highly ordered brain architectures in vertebrates consist of multiple neuron subtypes with specific neuronal connections. However, the origin of and evolutionary changes in neuron specification mechanisms remain unclear. Here, we report that regulatory mechanisms of neuron subtype specification are divergent in developing amniote brains. In the mammalian neocortex, the transcription factors (TFs Ctip2 and Satb2 are differentially expressed in layer-specific neurons. In contrast, these TFs are co-localized in reptilian and avian dorsal pallial neurons. Multi-potential progenitors that produce distinct neuronal subtypes commonly exist in the reptilian and avian dorsal pallium, whereas a cis-regulatory element of avian Ctip2 exhibits attenuated transcription suppressive activity. Furthermore, the neuronal subtypes distinguished by these TFs are not tightly associated with conserved neuronal connections among amniotes. Our findings reveal the evolutionary plasticity of regulatory gene functions that contribute to species differences in neuronal heterogeneity and connectivity in developing amniote brains. : Neuronal heterogeneity is essential for assembling intricate neuronal circuits. Nomura et al. find that species-specific transcriptional mechanisms underlie diversities of excitatory neuron subtypes in mammalian and non-mammalian brains. Species differences in neuronal subtypes and connections suggest functional plasticity of regulatory genes for neuronal specification during amniote brain evolution. Keywords: Ctip2, Satb2, multi-potential progenitors, transcriptional regulation, neuronal connectivity

  12. Symbolic joint entropy reveals the coupling of various brain regions

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    Ma, Xiaofei; Huang, Xiaolin; Du, Sidan; Liu, Hongxing; Ning, Xinbao

    2018-01-01

    The convergence and divergence of oscillatory behavior of different brain regions are very important for the procedure of information processing. Measurements of coupling or correlation are very useful to study the difference of brain activities. In this study, EEG signals were collected from ten subjects under two conditions, i.e. eyes closed state and idle with eyes open. We propose a nonlinear algorithm, symbolic joint entropy, to compare the coupling strength among the frontal, temporal, parietal and occipital lobes and between two different states. Instead of decomposing the EEG into different frequency bands (theta, alpha, beta, gamma etc.), the novel algorithm is to investigate the coupling from the entire spectrum of brain wave activities above 4Hz. The coupling coefficients in two states with different time delay steps are compared and the group statistics are presented as well. We find that the coupling coefficient of eyes open state with delay consistently lower than that of eyes close state across the group except for one subject, whereas the results without delay are not consistent. The differences between two brain states with non-zero delay can reveal the intrinsic inter-region coupling better. We also use the well-known Hénon map data to validate the algorithm proposed in this paper. The result shows that the method is robust and has a great potential for other physiologic time series.

  13. SECTOR-SPECIFIC STRUCTURE OF THE REGIONAL ECONOMY AS A FACTOR OF ELEVATION OF RISKS TO ITS ECONOMIC SECURITY

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    Rostislav BILYK

    2016-07-01

    Full Text Available The article analyzes a sector-specific specialization of the regional economy in Ukraine. It also reveals possibility and conditions of transformation of a sector-specific specialization of the region and risks to its economic security. The article suggests an assessment of influence of a sector-specific specialization on occurrence of threats to the economic security of the region.

  14. Evaluation of idiopathic transverse myelitis revealing specific myelopathy diagnoses.

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    Zalewski, Nicholas L; Flanagan, Eoin P; Keegan, B Mark

    2018-01-09

    To evaluate specific myelopathy diagnoses made in patients with suspected idiopathic transverse myelitis (ITM). A total of 226 patients 18 years and older were referred to Mayo Clinic Neurology for suspected ITM from December 1, 2010, to December 31, 2015. Electronic medical records were reviewed for detailed clinical presentation and course, laboratory and electrophysiologic investigations, and neuroimaging to determine the etiology. Current diagnostic criteria for ITM and alternative myelopathy diagnoses were applied. All cases where any discrepancy was suspected from the final reported clinical diagnosis were reviewed by each author and a consensus final diagnosis was made. The diagnostic criteria for ITM were met in 41 of 226 patients (18.1%). In 158 patients (69.9%), an alternative specific myelopathy diagnosis was made: multiple sclerosis or clinically isolated syndrome, 75; vascular myelopathy, 41; neurosarcoidosis, 12; neuromyelitis optica spectrum disorder, 12; myelin oligodendrocyte glycoprotein myelopathy, 5; neoplastic, 4; compressive, 3; nutritional, 3; infectious, 2; and other, 2. A myelopathy was not confirmed in 27 patients. Time from symptom onset to final clinical diagnosis in patients without ITM was a median of 9 months (range 0-288). Fifty-five patients (24%) required treatment changes according to their final clinical diagnosis. The majority of patients with suspected ITM have an alternative specific myelopathy diagnosis. A presumptive diagnosis of ITM can lead to premature diagnostic conclusions affecting patient treatment. Copyright © 2017 American Academy of Neurology.

  15. Identifying revealed comparative advantages in an EU regional context

    OpenAIRE

    Cordes, Alexander; Gehrke, Birgit; Römisch, Roman; Rammer, Christian; Schliessler, Paula; Wassmann, Pia

    2015-01-01

    [Introduction ...] Overall, this report is structured as follows: the next chapter (2) briefly outlines the relevance of regional trade indicators for determining the competitiveness of a region. In chapter 3, the methodology for the calculation of regional trade performance indicators is introduced, and the elementary results are described. Chapter 4 presents an econometric analysis relating key regional characteristics to international success of local industries. Based upon the regional di...

  16. Musical minds: attentional blink reveals modality-specific restrictions.

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    Sander Martens

    Full Text Available Formal musical training is known to have positive effects on attentional and executive functioning, processing speed, and working memory. Consequently, one may expect to find differences in the dynamics of temporal attention between musicians and non-musicians. Here we address the question whether that is indeed the case, and whether any beneficial effects of musical training on temporal attention are modality specific or generalize across sensory modalities.When two targets are presented in close temporal succession, most people fail to report the second target, a phenomenon known as the attentional blink (AB. We measured and compared AB magnitude for musicians and non-musicians using auditory or visually presented letters and digits. Relative to non-musicians, the auditory AB was both attenuated and delayed in musicians, whereas the visual AB was larger. Non-musicians with a large auditory AB tended to show a large visual AB. However, neither a positive nor negative correlation was found in musicians, suggesting that at least in musicians, attentional restrictions within each modality are completely separate.AB magnitude within one modality can generalize to another modality, but this turns out not to be the case for every individual. Formal musical training seems to have a domain-general, but modality-specific beneficial effect on selective attention. The results fit with the idea that a major source of attentional restriction as reflected in the AB lies in modality-specific, independent sensory systems rather than a central amodal system. The findings demonstrate that individual differences in AB magnitude can provide important information about the modular structure of human cognition.

  17. Musical minds: attentional blink reveals modality-specific restrictions.

    Science.gov (United States)

    Martens, Sander; Wierda, Stefan M; Dun, Mathijs; de Vries, Michal; Smid, Henderikus G O M

    2015-01-01

    Formal musical training is known to have positive effects on attentional and executive functioning, processing speed, and working memory. Consequently, one may expect to find differences in the dynamics of temporal attention between musicians and non-musicians. Here we address the question whether that is indeed the case, and whether any beneficial effects of musical training on temporal attention are modality specific or generalize across sensory modalities. When two targets are presented in close temporal succession, most people fail to report the second target, a phenomenon known as the attentional blink (AB). We measured and compared AB magnitude for musicians and non-musicians using auditory or visually presented letters and digits. Relative to non-musicians, the auditory AB was both attenuated and delayed in musicians, whereas the visual AB was larger. Non-musicians with a large auditory AB tended to show a large visual AB. However, neither a positive nor negative correlation was found in musicians, suggesting that at least in musicians, attentional restrictions within each modality are completely separate. AB magnitude within one modality can generalize to another modality, but this turns out not to be the case for every individual. Formal musical training seems to have a domain-general, but modality-specific beneficial effect on selective attention. The results fit with the idea that a major source of attentional restriction as reflected in the AB lies in modality-specific, independent sensory systems rather than a central amodal system. The findings demonstrate that individual differences in AB magnitude can provide important information about the modular structure of human cognition.

  18. Age-and Brain Region-Specific Differences in Mitochondrial ...

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    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12 and 24 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

  19. 3-dimensional examination of the adult mouse subventricular zone reveals lineage-specific microdomains.

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    Azim, Kasum; Fiorelli, Roberto; Zweifel, Stefan; Hurtado-Chong, Anahi; Yoshikawa, Kazuaki; Slomianka, Lutz; Raineteau, Olivier

    2012-01-01

    Recent studies suggest that the subventricular zone (SVZ) of the lateral ventricle is populated by heterogeneous populations of stem and progenitor cells that, depending on their exact location, are biased to acquire specific neuronal fates. This newly described heterogeneity of SVZ stem and progenitor cells underlines the necessity to develop methods for the accurate quantification of SVZ stem and progenitor subpopulations. In this study, we provide 3-dimensional topographical maps of slow cycling "stem" cells and progenitors based on their unique cell cycle properties. These maps revealed that both cell populations are present throughout the lateral ventricle wall as well as in discrete regions of the dorsal wall. Immunodetection of transcription factors expressed in defined progenitor populations further reveals that divergent lineages have clear regional enrichments in the rostro-caudal as well as in the dorso-ventral span of the lateral ventricle. Thus, progenitors expressing Tbr2 and Dlx2 were confined to dorsal and dorso-lateral regions of the lateral ventricle, respectively, while Mash1+ progenitors were more homogeneously distributed. All cell populations were enriched in the rostral-most region of the lateral ventricle. This diversity and uneven distribution greatly impede the accurate quantification of SVZ progenitor populations. This is illustrated by measuring the coefficient of error of estimates obtained by using increasing section sampling interval. Based on our empirical data, we provide such estimates for all progenitor populations investigated in this study. These can be used in future studies as guidelines to judge if the precision obtained with a sampling scheme is sufficient to detect statistically significant differences between experimental groups if a biological effect is present. Altogether, our study underlines the need to consider the SVZ of the lateral ventricle as a complex 3D structure and define methods to accurately assess neural

  20. 3-dimensional examination of the adult mouse subventricular zone reveals lineage-specific microdomains.

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    Kasum Azim

    Full Text Available Recent studies suggest that the subventricular zone (SVZ of the lateral ventricle is populated by heterogeneous populations of stem and progenitor cells that, depending on their exact location, are biased to acquire specific neuronal fates. This newly described heterogeneity of SVZ stem and progenitor cells underlines the necessity to develop methods for the accurate quantification of SVZ stem and progenitor subpopulations. In this study, we provide 3-dimensional topographical maps of slow cycling "stem" cells and progenitors based on their unique cell cycle properties. These maps revealed that both cell populations are present throughout the lateral ventricle wall as well as in discrete regions of the dorsal wall. Immunodetection of transcription factors expressed in defined progenitor populations further reveals that divergent lineages have clear regional enrichments in the rostro-caudal as well as in the dorso-ventral span of the lateral ventricle. Thus, progenitors expressing Tbr2 and Dlx2 were confined to dorsal and dorso-lateral regions of the lateral ventricle, respectively, while Mash1+ progenitors were more homogeneously distributed. All cell populations were enriched in the rostral-most region of the lateral ventricle. This diversity and uneven distribution greatly impede the accurate quantification of SVZ progenitor populations. This is illustrated by measuring the coefficient of error of estimates obtained by using increasing section sampling interval. Based on our empirical data, we provide such estimates for all progenitor populations investigated in this study. These can be used in future studies as guidelines to judge if the precision obtained with a sampling scheme is sufficient to detect statistically significant differences between experimental groups if a biological effect is present. Altogether, our study underlines the need to consider the SVZ of the lateral ventricle as a complex 3D structure and define methods to

  1. Isotopes reveal dynamics of groundwater system in Region 2, Philippines

    International Nuclear Information System (INIS)

    Mendoza, N.D.S.; Racadio, C.D.T.; Sucgang, R.J.; Castañeda, S.S.

    2015-01-01

    Steady economic and population growth in Region 2 could lead to an exponential increase freshwater demand. However, region 2’s main source of freshwater is groundwater and, if not checked and managed carefully, it could eventually affect the availability and sustainability of groundwater resources in Water Resource Region 2 (WRR2). Stable isotopes along with Tritium analysis in different water bodies such as rain, shallow and deep groundwater, springs and rivers were used to gain insight about the hydrological process in WRR2. Local meteoric water line for WRR2 was found to be δ2H = 8.6 δ 18O + 13.3 (r = 0.98). The estimated annual mean, which was used as a local index was to be -7.1 ‰ δ “1”8O_v_s_m_o_w_-_s_l_a_p. Shallow wells (20 – 30 m) and production wells (multi-screened wells, max depth of about 100 – 120m) were found to exhibit relatively more enrich than the index (i.e. -7.1‰) with means of -6.2 ‰ (s.d. 1.1‰, n=19) and -6.6 ‰ (s.d. 0.9; n= 151), respectively, which was an indication of infiltration of evaporated waters possibly from river and irrigation waters. Tritium analysis were done on selected sites to identify groundwater age (GWA) and possibly track the flow of groundwater from recharge areas (such as in Nueva Vizcaya, GWA = 3 years) down to the plains (Tuguegarao, GWA range from 9 to 30 years). Groundwaters drawn from production wells in Tuguegarao with ages of more than 30 years suggest that more fraction of water were being drawn from deeper aquifers. Such scenario could mean that were less water in shallow aquifers (e.g. 30 m deep) which are typically younger in age than waters found at deeper aquifers (e.g. 100 m deep). (author)

  2. Region-specific mechanical properties of the human patella tendon

    DEFF Research Database (Denmark)

    Haraldsson, B T; Aagaard, P; Krogsgaard, M

    2004-01-01

    The present study investigated the mechanical properties of tendon fascicles from the anterior and posterior human patellar tendon. Collagen fascicles from the anterior and posterior human patellar tendon in healthy young men (mean +/- SD, 29.0 +/- 4.6 yr, n = 6) were tested in a mechanical rig...... portion of the tendon, indicating region-specific material properties....

  3. Transcription Factor Zbtb20 Controls Regional Specification of Mammalian Archicortex

    DEFF Research Database (Denmark)

    Rosenthal, Eva Helga

    2010-01-01

    Combinatorial expression of sets of transcription factors (TFs) along the mammalian cortex controls its subdivision into functional areas. Unlike neocortex, only few recent data suggest genetic mechanisms controlling the regionalization of the archicortex. TF Emx2 plays a crucial role in patterning...... later on becoming restricted exclusively to postmitotic neurons of hippocampus (Hi) proper, dentate gyrus (DG), and two transitory zones, subiculum (S) and retrosplenial cortex (Rsp). Analysis of Zbtb20-/- mice revealed altered cortical patterning at the border between neocortex and archicortex...

  4. Locally specific measures for employment aimed at regional development

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    Vladimir Cini

    2013-12-01

    Full Text Available The oldest and largest sub-region in the world functioning on the principle of economic union is the European Union. The creation of a single market has initiated the process of conditional adjustment of markets in the EU member states, which has a significant impact on the social welfare of its citizens. It is necessary to tackle this issue by joint efforts within the European Union. As globalization processes push for economic integration and development of competitive advantage, the regions will have to make some challenging adjustments. The development tends to concentrate in highly competitive regions, while regions in the periphery lag behind. However, this pertains not only to the economic lag, but also to a potential negative political situation. Locally specific active employment policy measures are a continuation of the effort to make these measures more flexible. They refer to the Joint Assessment of Employment Policy Priorities and the IPA Human Resources Development Operational Programme - a regional policy instrument of the European Union. Both documents highlight the issue of disproportional development of regions, which requires special local measures and active labour market policy programmes. To reduce regional differences in development, it is necessary to invest more resources in the regions that lag behind. In this particular case, this means the counties in Croatia with high unemployment rates, a large number of registered unemployed persons and low employment rate. Consequently, this paper explains the importance of the adoption of locally specific measures for employment, which unfortunately did not take hold in the Republic of Croatia, and highlights the need for further decentralization of public services, with the aim of balancing regional development

  5. HEROD: a human ethnic and regional specific omics database.

    Science.gov (United States)

    Zeng, Xian; Tao, Lin; Zhang, Peng; Qin, Chu; Chen, Shangying; He, Weidong; Tan, Ying; Xia Liu, Hong; Yang, Sheng Yong; Chen, Zhe; Jiang, Yu Yang; Chen, Yu Zong

    2017-10-15

    Genetic and gene expression variations within and between populations and across geographical regions have substantial effects on the biological phenotypes, diseases, and therapeutic response. The development of precision medicines can be facilitated by the OMICS studies of the patients of specific ethnicity and geographic region. However, there is an inadequate facility for broadly and conveniently accessing the ethnic and regional specific OMICS data. Here, we introduced a new free database, HEROD, a human ethnic and regional specific OMICS database. Its first version contains the gene expression data of 53 070 patients of 169 diseases in seven ethnic populations from 193 cities/regions in 49 nations curated from the Gene Expression Omnibus (GEO), the ArrayExpress Archive of Functional Genomics Data (ArrayExpress), the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Geographic region information of curated patients was mainly manually extracted from referenced publications of each original study. These data can be accessed and downloaded via keyword search, World map search, and menu-bar search of disease name, the international classification of disease code, geographical region, location of sample collection, ethnic population, gender, age, sample source organ, patient type (patient or healthy), sample type (disease or normal tissue) and assay type on the web interface. The HEROD database is freely accessible at http://bidd2.nus.edu.sg/herod/index.php. The database and web interface are implemented in MySQL, PHP and HTML with all major browsers supported. phacyz@nus.edu.sg. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  6. VLBA Reveals Formation Region of Giant Cosmic Jet

    Science.gov (United States)

    1999-10-01

    Astronomers have gained their first glimpse of the mysterious region near a black hole at the heart of a distant galaxy, where a powerful stream of subatomic particles spewing outward at nearly the speed of light is formed into a beam, or jet, that then goes nearly straight for thousands of light-years. The astronomers used radio telescopes in Europe and the U.S., including the National Science Foundation's (NSF) Very Long Baseline Array (VLBA) to make the most detailed images ever of the center of the galaxy M87, some 50 million light-years away. "This is the first time anyone has seen the region in which a cosmic jet is formed into a narrow beam," said Bill Junor of the University of New Mexico, in Albuquerque. "We had always speculated that the jet had to be made by some mechanism relatively near the black hole, but as we looked closer and closer to the center, we kept seeing an already-formed beam. That was becoming embarrassing, because we were running out of places to put the formation mechanism that we knew had to be there." Junor, along with John Biretta and Mario Livio of the Space Telescope Science Institute, in Baltimore, MD, now have shown that M87's jet is formed within a few tenths of a light-year of the galaxy's core, presumed to be a black hole three billion times more massive than the sun. In the formation region, the jet is seen opening widely, at an angle of about 60 degrees, nearest the black hole, but is squeezed down to only 6 degrees a few light-years away. "The 60-degree angle of the inner part of M87's jet is the widest such angle yet seen in any jet in the universe," said Junor. "We found this by being able to see the jet to within a few hundredths of a light-year of the galaxy's core -- an unprecedented level of detail." The scientists reported their findings in the October 28 issue of the journal Nature. At the center of M87, material being drawn inward by the strong gravitation of the black hole is formed into a rapidly-spinning flat

  7. Pyrosequencing data reveals tissue-specific expression of lineage-specific transcripts in chickpea

    OpenAIRE

    Garg, Rohini; Jain, Mukesh

    2011-01-01

    Chickpea is a very important crop legume plant, which provides a protein-rich supplement to cereal-based diets and has the ability to fix atmospheric nitrogen. Despite its economic importance, the functional genomic resources for chickpea are very limited. Recently, we reported the complete transcriptome of chickpea using next generation sequencing technologies. We analyzed the tissue-specific expression of chickpea transcripts based on RNA-seq data. In addition, we identified two sets of lin...

  8. Evidence of educational inadequacies in region-specific musculoskeletal medicine.

    Science.gov (United States)

    Day, Charles S; Yeh, Albert C

    2008-10-01

    Recent studies suggest US medical schools are not effectively addressing musculoskeletal medicine in their curricula. We examined if there were specific areas of weakness by analyzing students' knowledge of and confidence in examining specific anatomic regions. A cross-sectional survey study of third- and fourth-year students at Harvard Medical School was conducted during the 2005 to 2006 academic year. One hundred sixty-two third-year students (88% response) and 87 fourth-year students (57% response) completed the Freedman and Bernstein cognitive mastery examination in musculoskeletal medicine and a survey eliciting their clinical confidence in examining the shoulder, elbow, hand, back, hip, knee, and foot on a one to five Likert scale. We specifically analyzed examination questions dealing with the upper extremity, lower extremity, back, and others, which included more systemic conditions such as arthritis, metabolic bone diseases, and cancer. Students failed to meet the established passing benchmark of 70% in all subgroups except for the others category. Confidence scores in performing a physical examination and in generating a differential diagnosis indicated students felt below adequate confidence (3.0 of 5) in five of the seven anatomic regions. Our study provides evidence that region-specific musculoskeletal medicine is a potential learning gap that may need to be addressed in the undergraduate musculoskeletal curriculum.

  9. Neighbor Detection Induces Organ-Specific Transcriptomes, Revealing Patterns Underlying Hypocotyl-Specific Growth.

    Science.gov (United States)

    Kohnen, Markus V; Schmid-Siegert, Emanuel; Trevisan, Martine; Petrolati, Laure Allenbach; Sénéchal, Fabien; Müller-Moulé, Patricia; Maloof, Julin; Xenarios, Ioannis; Fankhauser, Christian

    2016-12-01

    In response to neighbor proximity, plants increase the growth of specific organs (e.g., hypocotyls) to enhance access to sunlight. Shade enhances the activity of Phytochrome Interacting Factors (PIFs) by releasing these bHLH transcription factors from phytochrome B-mediated inhibition. PIFs promote elongation by inducing auxin production in cotyledons. In order to elucidate spatiotemporal aspects of the neighbor proximity response, we separately analyzed gene expression patterns in the major light-sensing organ (cotyledons) and in rapidly elongating hypocotyls of Arabidopsis thaliana PIFs initiate transcriptional reprogramming in both organs within 15 min, comprising regulated expression of several early auxin response genes. This suggests that hypocotyl growth is elicited by both local and distal auxin signals. We show that cotyledon-derived auxin is both necessary and sufficient to initiate hypocotyl growth, but we also provide evidence for the functional importance of the local PIF-induced response. With time, the transcriptional response diverges increasingly between organs. We identify genes whose differential expression may underlie organ-specific elongation. Finally, we uncover a growth promotion gene expression signature shared between different developmentally regulated growth processes and responses to the environment in different organs. © 2016 American Society of Plant Biologists. All rights reserved.

  10. Crystal structure analysis reveals functional flexibility in the selenocysteine-specific tRNA from mouse.

    Directory of Open Access Journals (Sweden)

    Oleg M Ganichkin

    Full Text Available Selenocysteine tRNAs (tRNA(Sec exhibit a number of unique identity elements that are recognized specifically by proteins of the selenocysteine biosynthetic pathways and decoding machineries. Presently, these identity elements and the mechanisms by which they are interpreted by tRNA(Sec-interacting factors are incompletely understood.We applied rational mutagenesis to obtain well diffracting crystals of murine tRNA(Sec. tRNA(Sec lacking the single-stranded 3'-acceptor end ((ΔGCCARNA(Sec yielded a crystal structure at 2.0 Å resolution. The global structure of (ΔGCCARNA(Sec resembles the structure of human tRNA(Sec determined at 3.1 Å resolution. Structural comparisons revealed flexible regions in tRNA(Sec used for induced fit binding to selenophosphate synthetase. Water molecules located in the present structure were involved in the stabilization of two alternative conformations of the anticodon stem-loop. Modeling of a 2'-O-methylated ribose at position U34 of the anticodon loop as found in a sub-population of tRNA(Secin vivo showed how this modification favors an anticodon loop conformation that is functional during decoding on the ribosome. Soaking of crystals in Mn(2+-containing buffer revealed eight potential divalent metal ion binding sites but the located metal ions did not significantly stabilize specific structural features of tRNA(Sec.We provide the most highly resolved structure of a tRNA(Sec molecule to date and assessed the influence of water molecules and metal ions on the molecule's conformation and dynamics. Our results suggest how conformational changes of tRNA(Sec support its interaction with proteins.

  11. Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Zabel Claus

    2011-09-01

    Full Text Available Abstract Parkinson's disease (PD is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron vulnerability exists, which codetermines the disease progression. To gain insight into the pathomechanism of PD, we investigated protein expression and protein oxidation patterns of three different brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO, in comparison to wild type control mice. The dysfunction of PINK1 presumably affects mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three brain regions investigated are the midbrain, which is the location of substantia nigra; striatum, the major efferent region of substantia nigra; and cerebral cortex, which is more distal to PD pathology. In all three regions, mitochondrial proteins responsible for energy metabolism and membrane potential were significantly altered in the PINK1-KO mice, but with very different region specific accents in terms of up/down-regulations. This suggests that disturbed mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on different brain regions. Specifically, the midbrain tissue seems to be most severely hit by defective mitochondrial turnover, whereas cortex and striatum could compensate for mitophagy nonfunction by feedback stimulation of other catabolic programs. In addition, cerebral cortex tissues showed the mildest level of protein oxidation in both PINK1-KO and wild type mice, indicating either a better oxidative protection or less reactive oxygen species (ROS pressure in this brain region. Ultra-structural histological examination in normal mouse brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in striatum and substantia

  12. Genome wide analysis of acute myeloid leukemia reveal leukemia specific methylome and subtype specific hypomethylation of repeats.

    Directory of Open Access Journals (Sweden)

    Marwa H Saied

    Full Text Available Methylated DNA immunoprecipitation followed by high-throughput sequencing (MeDIP-seq has the potential to identify changes in DNA methylation important in cancer development. In order to understand the role of epigenetic modulation in the development of acute myeloid leukemia (AML we have applied MeDIP-seq to the DNA of 12 AML patients and 4 normal bone marrows. This analysis revealed leukemia-associated differentially methylated regions that included gene promoters, gene bodies, CpG islands and CpG island shores. Two genes (SPHKAP and DPP6 with significantly methylated promoters were of interest and further analysis of their expression showed them to be repressed in AML. We also demonstrated considerable cytogenetic subtype specificity in the methylomes affecting different genomic features. Significantly distinct patterns of hypomethylation of certain interspersed repeat elements were associated with cytogenetic subtypes. The methylation patterns of members of the SINE family tightly clustered all leukemic patients with an enrichment of Alu repeats with a high CpG density (P<0.0001. We were able to demonstrate significant inverse correlation between intragenic interspersed repeat sequence methylation and gene expression with SINEs showing the strongest inverse correlation (R(2 = 0.7. We conclude that the alterations in DNA methylation that accompany the development of AML affect not only the promoters, but also the non-promoter genomic features, with significant demethylation of certain interspersed repeat DNA elements being associated with AML cytogenetic subtypes. MeDIP-seq data were validated using bisulfite pyrosequencing and the Infinium array.

  13. Common brain regions underlying different arithmetic operations as revealed by conjunct fMRI-BOLD activation.

    Science.gov (United States)

    Fehr, Thorsten; Code, Chris; Herrmann, Manfred

    2007-10-03

    The issue of how and where arithmetic operations are represented in the brain has been addressed in numerous studies. Lesion studies suggest that a network of different brain areas are involved in mental calculation. Neuroimaging studies have reported inferior parietal and lateral frontal activations during mental arithmetic using tasks of different complexities and using different operators (addition, subtraction, etc.). Indeed, it has been difficult to compare brain activation across studies because of the variety of different operators and different presentation modalities used. The present experiment examined fMRI-BOLD activity in participants during calculation tasks entailing different arithmetic operations -- addition, subtraction, multiplication and division -- of different complexities. Functional imaging data revealed a common activation pattern comprising right precuneus, left and right middle and superior frontal regions during all arithmetic operations. All other regional activations were operation specific and distributed in prominently frontal, parietal and central regions when contrasting complex and simple calculation tasks. The present results largely confirm former studies suggesting that activation patterns due to mental arithmetic appear to reflect a basic anatomical substrate of working memory, numerical knowledge and processing based on finger counting, and derived from a network originally related to finger movement. We emphasize that in mental arithmetic research different arithmetic operations should always be examined and discussed independently of each other in order to avoid invalid generalizations on arithmetics and involved brain areas.

  14. Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

    Science.gov (United States)

    Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

    2014-07-01

    The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Brain noise is task dependent and region specific.

    Science.gov (United States)

    Misić, Bratislav; Mills, Travis; Taylor, Margot J; McIntosh, Anthony R

    2010-11-01

    The emerging organization of anatomical and functional connections during human brain development is thought to facilitate global integration of information. Recent empirical and computational studies have shown that this enhanced capacity for information processing enables a diversified dynamic repertoire that manifests in neural activity as irregularity and noise. However, transient functional networks unfold over multiple time, scales and the embedding of a particular region depends not only on development, but also on the manner in which sensory and cognitive systems are engaged. Here we show that noise is a facet of neural activity that is also sensitive to the task context and is highly region specific. Children (6-16 yr) and adults (20-41 yr) performed a one-back face recognition task with inverted and upright faces. Neuromagnetic activity was estimated at several hundred sources in the brain by applying a beamforming technique to the magnetoencephalogram (MEG). During development, neural activity became more variable across the whole brain, with most robust increases in medial parietal regions, such as the precuneus and posterior cingulate cortex. For young children and adults, activity evoked by upright faces was more variable and noisy compared with inverted faces, and this effect was reliable only in the right fusiform gyrus. These results are consistent with the notion that upright faces engender a variety of integrative neural computations, such as the relations among facial features and their holistic constitution. This study shows that transient changes in functional integration modulated by task demand are evident in the variability of regional neural activity.

  16. Evaluation of the regional lung function revealed in radioaerosol scintigram of chronic obstructive pulmonary disease, 1

    International Nuclear Information System (INIS)

    Suzuki, Teruyasu

    1980-01-01

    We classified the findings of radioaerosol inhalation scintigrams of patients with various stages of obstructive pulmonary disease (COPD) into 4 grades, according to the extent of peripheral irregularity and central hot spot formation; Stage I represents normal homogeneous distribution, stage II represents peripheral irregularity, stage III represents additional hot spot formation and stage IV represents further regional defect. This aerosol grading criteria was then compared with routine and specific lung function tests. The aerosol grading criterion correlated well with FEV sub(1.0)% which is a good indicator of the severity of COPD. The central hot spot formation correlated well with FEV sub(1.0)% and respiratory resistance (R.p.) determined by the oscillation method, both of which are good indicators of abnormality in central airway resistance. Peripheral irregularity correlated well with: 1) flows at 50%VC and 25%VC in a maximum forced expiratory flow volume curve; 2) closing volume (CV/VC%); 3) delta N 2 %/l in N 2 single washout test; and 4) the regional delay of 133 Xe washout process, all of which are sensitive indicators of small airway disease. It is therefore reasonable to conclude that the radioaerosol scintigram reveals the regional lung function both in terms of airway resistance (R) and compliance (C). This criterion was useful in quantitatively evaluating the regional ventilation distribution of COPD and the therapeutic effect on bronchial asthma. The mechanism of aerosol praticle deposition related to characteristic central hot spot formation accompanied with peripheral irregularity in a radioaerosol scintigram of COPD, needs further exploration concerning the aerodynamic behavior of aerosol particles in the airways both during inspiration and expiration. (author)

  17. Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns

    DEFF Research Database (Denmark)

    Lundby, Alicia; Hansen, Kasper Lage; Weinert, Brian Tate

    2012-01-01

    ,541 proteins and provide the data set as a web-based database. We demonstrate that lysine acetylation displays site-specific sequence motifs that diverge between cellular compartments, with a significant fraction of nuclear sites conforming to the consensus motifs G-AcK and AcK-P. Our data set reveals...

  18. Site specific transfer factor studies for Kaiga region

    International Nuclear Information System (INIS)

    Karunakara, N.

    2012-01-01

    The Radioecology Laboratory of University Science Instrumentation Centre, Mangalore University is engaged in frontline research studies on different aspects of environmental radioactivity and radiation protection for the last 20 years. Extensive studies have been carried out on radiation levels, radionuclides distribution, and transfer of radionuclides through terrestrial, aquatic and atmospheric pathways in the environment of West Coast of India including the Kaiga nuclear power plant. The baseline studies on radioactivity levels around Kaiga region was carried out well before the nuclear power plant became operational and the data generated under these studies are considered to be highly valuable for future impact assessments. The nuclear power plant became operational in the year 1999 and since then this laboratory is involved in radiological impact assessment studies around the nuclear power plant. Detailed Kaiga specific studies are now ongoing to estimate the transfer factors and transfer coefficients for radionuclides for different pathways, such as, (i) soil to rice (ii) soil to different types of vegetables (iii) water/sediment to fish (iv) soil to grass (v) grass to cow milk and (vi) milk to child. For these studies, rice and vegetable fields were developed very close to the nuclear power plant in Kaiga to study the transfer of radionuclides. The water required for this field was drawn from coolant water discharge canal of the power plant. Rice and different types of vegetables were grown in the experimental fields in different seasons of the year and the uptake of radionuclides was studied. For a comparative study, rice and vegetables were also collected from the fields of farmers of nearby villages and analysed. The transfer of artificial radionuclides through pathway involving cow milk was also studied in detail. A grass field was developed and cows were adopted specifically for this study. The cows were allowed to graze freely in this grass field

  19. Boudin trafficking reveals the dynamic internalisation of specific septate junction components in Drosophila.

    Science.gov (United States)

    Tempesta, Camille; Hijazi, Assia; Moussian, Bernard; Roch, Fernando

    2017-01-01

    The maintenance of paracellular barriers in invertebrate epithelia depends on the integrity of specific cell adhesion structures known as septate junctions (SJ). Multiple studies in Drosophila have revealed that these junctions have a stereotyped architecture resulting from the association in the lateral membrane of a large number of components. However, little is known about the dynamic organisation adopted by these multi-protein complexes in living tissues. We have used live imaging techniques to show that the Ly6 protein Boudin is a component of these adhesion junctions and can diffuse systemically to associate with the SJ of distant cells. We also observe that this protein and the claudin Kune-kune are endocytosed in epidermal cells during embryogenesis. Our data reveal that the SJ contain a set of components exhibiting a high membrane turnover, a feature that could contribute in a tissue-specific manner to the morphogenetic plasticity of these adhesion structures.

  20. Direct Lineage Reprogramming Reveals Disease-Specific Phenotypes of Motor Neurons from Human ALS Patients

    Directory of Open Access Journals (Sweden)

    Meng-Lu Liu

    2016-01-01

    Full Text Available Subtype-specific neurons obtained from adult humans will be critical to modeling neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS. Here, we show that adult human skin fibroblasts can be directly and efficiently converted into highly pure motor neurons without passing through an induced pluripotent stem cell stage. These adult human induced motor neurons (hiMNs exhibit the cytological and electrophysiological features of spinal motor neurons and form functional neuromuscular junctions (NMJs with skeletal muscles. Importantly, hiMNs converted from ALS patient fibroblasts show disease-specific degeneration manifested through poor survival, soma shrinkage, hypoactivity, and an inability to form NMJs. A chemical screen revealed that the degenerative features of ALS hiMNs can be remarkably rescued by the small molecule kenpaullone. Taken together, our results define a direct and efficient strategy to obtain disease-relevant neuronal subtypes from adult human patients and reveal their promising value in disease modeling and drug identification.

  1. The Brain–to–Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions

    Science.gov (United States)

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C.; Ali, Almas; Tamarina, Natalia; Philipson, Louis H.; Enquist, Lynn W.; Myers, Martin G.

    2016-01-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. PMID:27207534

  2. The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

    Science.gov (United States)

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

    2016-09-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. © 2016 by the American Diabetes Association.

  3. Analysis of chlorophyll fluorescence reveals stage specific patterns of chloroplast-containing cells during Arabidopsis embryogenesis

    Directory of Open Access Journals (Sweden)

    RICARDO I TEJOS

    2010-01-01

    Full Text Available The basic body plan of a plant is established early in embryogenesis when cells differentiate, giving rise to the apical and basal regions of the embryo. Using chlorophyll fluorescence as a marker for chloroplasts, we have detected specific patterns of chloroplast-containing cells at specific stages of embryogenesis. Non-randomly distributed chloroplast-containing cells are seen as early as the globular stage of embryogenesis in Arabidopsis. In the heart stage of embryogenesis, chloroplast containing cells are detected in epidermal cells as well as a central region of the heart stage embryo, forming a triangular septum of chloroplast-containing cells that divides the embryo into three equal sectors. Torpedo stage embryos have chloroplast-containing epidermal cells and a central band of chloroplast-containing cells in the cortex layer, just below the shoot apical meristem. In the walking-stick stage of embryogenesis, chloroplasts are present in the epidermal, cortex and endodermal cells. The chloroplasts appear reduced or absent from the provascular and columella cells of walking-stick stage embryos. These results suggest that there is a tight regulation of plastid differentiation during embryogenesis that generates specific patterns of chloroplast-containing cells in specific cell layers at specific stages of embryogenesis.

  4. Evaluating EU Regional Policy: Many Empirical Specifications, One (Unpleasant) Result

    DEFF Research Database (Denmark)

    Breidenbach, Philipp; Mitze, Timo; Schmidt, Christoph

    Numerous studies have focused on the role of EU regional policy in fostering growth and convergence among European regions, why conducting another one? We argue that two facts are still lacking in the actual academic debate in order to get a sound empirical identification strategy and reliable...... regions with a GDP p.c. of less than 75% of the EU average. These payments shall represent the main instrument to fulfill the central aim of European regional policy, the boost of convergence and harmonic growth over the EU. They represent about two third of the whole European cohesion policy. In our...... results: First, one should take the theoretical underpinnings of regional growth models more serious, and second, a likewise careful account of the role of spatial dependence in the underlying data is needed. Though research has increasingly become aware of the latter point as important control factor...

  5. Cell-Specific PEAR1 Methylation Studies Reveal a Locus that Coordinates Expression of Multiple Genes

    Directory of Open Access Journals (Sweden)

    Benedetta Izzi

    2018-04-01

    Full Text Available Chromosomal interactions connect distant enhancers and promoters on the same chromosome, activating or repressing gene expression. PEAR1 encodes the Platelet-Endothelial Aggregation Receptor 1, a contact receptor involved in platelet function and megakaryocyte and endothelial cell proliferation. PEAR1 expression during megakaryocyte differentiation is controlled by DNA methylation at its first CpG island. We identified a PEAR1 cell-specific methylation sensitive region in endothelial cells and megakaryocytes that showed strong chromosomal interactions with ISGL20L2, RRNAD1, MRLP24, HDGF and PRCC, using available promoter capture Hi-C datasets. These genes are involved in ribosome processing, protein synthesis, cell cycle and cell proliferation. We next studied the methylation and expression profile of these five genes in Human Umbilical Vein Endothelial Cells (HUVECs and megakaryocyte precursors. While cell-specific PEAR1 methylation corresponded to variability in expression for four out of five genes, no methylation change was observed in their promoter regions across cell types. Our data suggest that PEAR1 cell-type specific methylation changes may control long distance interactions with other genes. Further studies are needed to show whether such interaction data might be relevant for the genome-wide association data that showed a role for non-coding PEAR1 variants in the same region and platelet function, platelet count and cardiovascular risk.

  6. Region-specific involvement of BDNF secretion and synthesis in conditioned taste aversion memory formation.

    Science.gov (United States)

    Ma, Ling; Wang, Dong-Dong; Zhang, Tian-Yi; Yu, Hui; Wang, Yue; Huang, Shu-Hong; Lee, Francis S; Chen, Zhe-Yu

    2011-02-09

    Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB), play a critical role in activity-dependent plasticity processes such as long-term potentiation, learning, and memory. It has been shown that BDNF exerts different or even opposite effects on behavior depending on the neural circuit. However, the detailed role of BDNF in memory process on the basis of its location has not been fully understood. Here, we aim to investigate the regional specific involvement of BDNF/TrkB in hippocampal-independent conditioned taste aversion (CTA) memory processes. We found region-specific changes in BDNF expression during CTA learning. CTA conditioning induced increased BDNF levels in the central nuclei of amygdala (CeA) and insular cortex, but not in the basolateral amygdala (BLA) and ventromedial prefrontal cortex. Interestingly, we found that the enhanced TrkB phosphorylation occurred at the time point before the increased BDNF expression, suggesting rapid induction of activity-dependent BDNF secretion by CTA learning. Moreover, targeted infusion of BDNF antibodies or BDNF antisense oligonucleotides revealed that activity-dependent BDNF secretion and synthesis in the CeA, but not the BLA, was respectively involved in the short- and long-term memory formation of CTA. Finally, we found that infusion of exogenous BDNF into the CeA could enhance CTA learning. These data suggest that region-specific BDNF release and synthesis temporally regulate different CTA memory phases through activation of TrkB receptors.

  7. Ki-67 expression reveals strong, transient influenza specific CD4 T cell responses after adult vaccination

    OpenAIRE

    Li, Xi; Miao, Hongyu; Henn, Alicia; Topham, David J.; Wu, Hulin; Zand, Martin S.; Mosmann, Tim R.

    2012-01-01

    Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4–6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFNγ, IL-2 and/or TNFα in vitro in response to influenza vacc...

  8. Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma

    International Nuclear Information System (INIS)

    Rumbajan, Janette Mareska; Aoki, Shigehisa; Kohashi, Kenichi; Oda, Yoshinao; Hata, Kenichiro; Saji, Tsutomu; Taguchi, Tomoaki; Tajiri, Tatsuro; Soejima, Hidenobu; Joh, Keiichiro; Maeda, Toshiyuki; Souzaki, Ryota; Mitsui, Kazumasa; Higashimoto, Ken; Nakabayashi, Kazuhiko; Yatsuki, Hitomi; Nishioka, Kenichi; Harada, Ryoko

    2013-01-01

    Aberrant methylation at imprinted differentially methylated regions (DMRs) in human 11p15.5 has been reported in many tumors including hepatoblastoma. However, the methylation status of imprinted DMRs in imprinted loci scattered through the human genome has not been analyzed yet in any tumors. The methylation statuses of 33 imprinted DMRs were analyzed in 12 hepatoblastomas and adjacent normal liver tissue by MALDI-TOF MS and pyrosequencing. Uniparental disomy (UPD) and copy number abnormalities were investigated with DNA polymorphisms. Among 33 DMRs analyzed, 18 showed aberrant methylation in at least 1 tumor. There was large deviation in the incidence of aberrant methylation among the DMRs. KvDMR1 and IGF2-DMR0 were the most frequently hypomethylated DMRs. INPP5Fv2-DMR and RB1-DMR were hypermethylated with high frequencies. Hypomethylation was observed at certain DMRs not only in tumors but also in a small number of adjacent histologically normal liver tissue, whereas hypermethylation was observed only in tumor samples. The methylation levels of long interspersed nuclear element-1 (LINE-1) did not show large differences between tumor tissue and normal liver controls. Chromosomal abnormalities were also found in some tumors. 11p15.5 and 20q13.3 loci showed the frequent occurrence of both genetic and epigenetic alterations. Our analyses revealed tumor-specific aberrant hypermethylation at some imprinted DMRs in 12 hepatoblastomas with additional suggestion for the possibility of hypomethylation prior to tumor development. Some loci showed both genetic and epigenetic alterations with high frequencies. These findings will aid in understanding the development of hepatoblastoma

  9. Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins.

    Directory of Open Access Journals (Sweden)

    Eric K Johnson

    Full Text Available Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.

  10. Revealing the Structural Complexity of Component Interactions of Topic-Specific PCK when Planning to Teach

    Science.gov (United States)

    Mavhunga, Elizabeth

    2018-04-01

    Teaching pedagogical content knowledge (PCK) at a topic-specific level requires clarity on the content-specific nature of the components employed, as well as the specific features that bring about the desirable depth in teacher explanations. Such understanding is often hazy; yet, it influences the nature of teacher tasks and learning opportunities afforded to pre-service teachers in a teaching program. The purpose of this study was twofold: firstly, to illuminate the emerging complexity when content-specific components of PCK interact when planning to teach a chemistry topic; and secondly, to identify the kinds of teacher tasks that promote the emergence of such complexity. Data collected were content representations (CoRes) in chemical equilibrium accompanied by expanded lesson outlines from 15 pre-service teachers in their final year of study towards a first degree in teaching (B Ed). The analysis involved extraction of episodes that exhibited component interaction by using a qualitative in-depth analysis method. The results revealed the structure in which the components of PCK in a topic interact among each other to be linear, interwoven, or a combination of the two. The interwoven interactions contained multiple components that connected explanations on different aspects of a concept, all working in a complementary manner. The most sophisticated component interactions emerged from teacher tasks on descriptions of a lesson sequence and a summary of a lesson. Recommendations in this study highlight core practices for making pedagogical transformation of topic content knowledge more accessible.

  11. DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

    Science.gov (United States)

    Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

    2015-10-01

    The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (pentropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Electrical brain responses in language-impaired children reveal grammar-specific deficits.

    Directory of Open Access Journals (Sweden)

    Elisabeth Fonteneau

    2008-03-01

    Full Text Available Scientific and public fascination with human language have included intensive scrutiny of language disorders as a new window onto the biological foundations of language and its evolutionary origins. Specific language impairment (SLI, which affects over 7% of children, is one such disorder. SLI has received robust scientific attention, in part because of its recent linkage to a specific gene and loci on chromosomes and in part because of the prevailing question regarding the scope of its language impairment: Does the disorder impact the general ability to segment and process language or a specific ability to compute grammar? Here we provide novel electrophysiological data showing a domain-specific deficit within the grammar of language that has been hitherto undetectable through behavioural data alone.We presented participants with Grammatical(G-SLI, age-matched controls, and younger child and adult controls, with questions containing syntactic violations and sentences containing semantic violations. Electrophysiological brain responses revealed a selective impairment to only neural circuitry that is specific to grammatical processing in G-SLI. Furthermore, the participants with G-SLI appeared to be partially compensating for their syntactic deficit by using neural circuitry associated with semantic processing and all non-grammar-specific and low-level auditory neural responses were normal.The findings indicate that grammatical neural circuitry underlying language is a developmentally unique system in the functional architecture of the brain, and this complex higher cognitive system can be selectively impaired. The findings advance fundamental understanding about how cognitive systems develop and all human language is represented and processed in the brain.

  13. Pyrosequencing reveals highly diverse and species-specific microbial communities in sponges from the Red Sea

    KAUST Repository

    Lee, Onon

    2010-11-18

    Marine sponges are associated with a remarkable array of microorganisms. Using a tag pyrosequencing technology, this study was the first to investigate in depth the microbial communities associated with three Red Sea sponges, Hyrtios erectus, Stylissa carteri and Xestospongia testudinaria. We revealed highly diverse sponge-associated bacterial communities with up to 1000 microbial operational taxonomic units (OTUs) and richness estimates of up to 2000 species. Altogether, 26 bacterial phyla were detected from the Red Sea sponges, 11 of which were absent from the surrounding sea water and 4 were recorded in sponges for the first time. Up to 100 OTUs with richness estimates of up to 300 archaeal species were revealed from a single sponge species. This is by far the highest archaeal diversity ever recorded for sponges. A non-negligible proportion of unclassified reads was observed in sponges. Our results demonstrated that the sponge-associated microbial communities remained highly consistent in the same sponge species from different locations, although they varied at different degrees among different sponge species. A significant proportion of the tag sequences from the sponges could be assigned to one of the sponge-specific clusters previously defined. In addition, the sponge-associated microbial communities were consistently divergent from those present in the surrounding sea water. Our results suggest that the Red Sea sponges possess highly sponge-specific or even sponge-species-specific microbial communities that are resistant to environmental disturbance, and much of their microbial diversity remains to be explored. © 2011 International Society for Microbial Ecology All rights reserved.

  14. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples.

    Science.gov (United States)

    Gorelick, Daniel A; Iwanowicz, Luke R; Hung, Alice L; Blazer, Vicki S; Halpern, Marnie E

    2014-04-01

    Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart. We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization. We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ERα was expressed in developing heart valves but not in the liver, whereas ERβ2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver. The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

  15. Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes.

    Science.gov (United States)

    Dindar, Gülcin; Anger, Andreas M; Mehlhorn, Christine; Hake, Sandra B; Janzen, Christian J

    2014-11-12

    DOT1 enzymes are conserved methyltransferases that catalyse the methylation of lysine 79 on histone H3 (H3K79). Most eukaryotes contain one DOT1 enzyme, whereas African trypanosomes have two homologues, DOT1A and DOT1B, with different enzymatic activities. DOT1A mediates mono- and dimethylation of H3K76, the homologue of H3K79 in other organisms, whereas DOT1B additionally catalyses H3K76 trimethylation. However, it is unclear how these different enzymatic activities are achieved. Here we employ a trypanosomal nucleosome reconstitution system and structure-guided homology modelling to identify critical residues within and outside the catalytic centre that modulate product specificity. Exchange of these residues transfers the product specificity from one enzyme to the other, and reveals the existence of distinct regulatory domains adjacent to the catalytic centre. Our study provides the first evidence that a few crucial residues in DOT1 enzymes are sufficient to catalyse methyl-state-specific reactions. These results might also have far-reaching consequences for the functional understanding of homologous enzymes in higher eukaryotes.

  16. Massively parallel amplicon sequencing reveals isotype-specific variability of antimicrobial peptide transcripts in Mytilus galloprovincialis.

    Directory of Open Access Journals (Sweden)

    Umberto Rosani

    Full Text Available BACKGROUND: Effective innate responses against potential pathogens are essential in the living world and possibly contributed to the evolutionary success of invertebrates. Taken together, antimicrobial peptide (AMP precursors of defensin, mytilin, myticin and mytimycin can represent about 40% of the hemocyte transcriptome in mussels injected with viral-like and bacterial preparations, and unique profiles of myticin C variants are expressed in single mussels. Based on amplicon pyrosequencing, we have ascertained and compared the natural and Vibrio-induced diversity of AMP transcripts in mussel hemocytes from three European regions. METHODOLOGY/PRINCIPAL FINDINGS: Hemolymph was collected from mussels farmed in the coastal regions of Palavas (France, Vigo (Spain and Venice (Italy. To represent the AMP families known in M. galloprovincialis, nine transcript sequences have been selected, amplified from hemocyte RNA and subjected to pyrosequencing. Hemolymph from farmed (offshore and wild (lagoon Venice mussels, both injected with 10(7 Vibrio cells, were similarly processed. Amplicon pyrosequencing emphasized the AMP transcript diversity, with Single Nucleotide Changes (SNC minimal for mytilin B/C and maximal for arthropod-like defensin and myticin C. Ratio of non-synonymous vs. synonymous changes also greatly differed between AMP isotypes. Overall, each amplicon revealed similar levels of nucleotidic variation across geographical regions, with two main sequence patterns confirmed for mytimycin and no substantial changes after immunostimulation. CONCLUSIONS/SIGNIFICANCE: Barcoding and bidirectional pyrosequencing allowed us to map and compare the transcript diversity of known mussel AMPs. Though most of the genuine cds variation was common to the analyzed samples we could estimate from 9 to 106 peptide variants in hemolymph pools representing 100 mussels, depending on the AMP isoform and sampling site. In this study, no prevailing SNC patterns related

  17. The construction of a library of synthetic promoters revealed some specific features of strong Streptomyces promoters

    DEFF Research Database (Denmark)

    Seghezzi, Nicolas; Amar, Patrick; Købmann, Brian

    2011-01-01

    Streptomyces are bacteria of industrial interest whose genome contains more than 73% of bases GC. In order to define, in these GC-rich bacteria, specific sequence features of strong promoters, a library of synthetic promoters of various sequence composition was constructed in Streptomyces. To do so...... cloned into the promoter-probe plasmid pIJ487 just upstream of the promoter-less aphII gene that confers resistance to neomycin. This synthetic promoter library was transformed into Streptomyces lividans, and the resulting transformants were screened for their ability to grow in the presence of different...... projects. Thirty-eight promoters were sequenced, and the sequences of the 14 weakest and 14 strongest promoters were compared using the WebLogo software with small sample correction. This comparison revealed that the −10 box, the −10 extended motif as well as the spacer of the strong Streptomyces promoters...

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

    Science.gov (United States)

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

    2016-01-12

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

  19. Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.

    Directory of Open Access Journals (Sweden)

    Kristina Kirschner

    2015-03-01

    Full Text Available The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage and chronically activated (in senescent or pro-apoptotic conditions p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.

  20. Regional two-dimensional magnetotelluric profile in West Bohemia/Vogtland reveals deep conductive channel into the earthquake swarm region

    Science.gov (United States)

    Muñoz, Gerard; Weckmann, Ute; Pek, Josef; Kováčiková, Světlana; Klanica, Radek

    2018-03-01

    The West Bohemia/Vogtland region, characterized by the intersection of the Eger (Ohře) Rift and the Mariánské Lázně fault, is a geodynamically active area exhibiting repeated occurrence of earthquake swarms, massive CO2 emanations and mid Pleistocene volcanism. The Eger Rift is the only known intra-continental region in Europe where such deep seated, active lithospheric processes currently take place. We present an image of electrical resistivity obtained from two-dimensional inversion of magnetotelluric (MT) data acquired along a regional profile crossing the Eger Rift. At the near surface, the Cheb basin and the aquifer feeding the mofette fields of Bublák and Hartoušov have been imaged as part of a region of very low resistivity. The most striking resistivity feature, however, is a deep reaching conductive channel which extends from the surface into the lower crust spatially correlated with the hypocentres of the seismic events of the Nový Kostel Focal Zone. This channel has been interpreted as imaging a pathway from a possible mid-crustal fluid reservoir to the surface. The resistivity model reinforces the relation between the fluid circulation along deep-reaching faults and the generation of the earthquakes. Additionally, a further conductive channel has been revealed to the south of the profile. This other feature could be associated to fossil hydrothermal alteration related to Mýtina and/or Neualbenreuth Maar structures or alternatively could be the signature of a structure associated to the suture between the Saxo-Thuringian and Teplá-Barrandian zones, whose surface expression is located only a few kilometres away.

  1. Computational dissection of human episodic memory reveals mental process-specific genetic profiles

    Science.gov (United States)

    Luksys, Gediminas; Fastenrath, Matthias; Coynel, David; Freytag, Virginie; Gschwind, Leo; Heck, Angela; Jessen, Frank; Maier, Wolfgang; Milnik, Annette; Riedel-Heller, Steffi G.; Scherer, Martin; Spalek, Klara; Vogler, Christian; Wagner, Michael; Wolfsgruber, Steffen; Papassotiropoulos, Andreas; de Quervain, Dominique J.-F.

    2015-01-01

    Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory. PMID:26261317

  2. Ki-67 expression reveals strong, transient influenza specific CD4 T cell responses after adult vaccination.

    Science.gov (United States)

    Li, Xi; Miao, Hongyu; Henn, Alicia; Topham, David J; Wu, Hulin; Zand, Martin S; Mosmann, Tim R

    2012-06-29

    Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4-6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFNγ, IL-2 and/or TNFα in vitro in response to influenza vaccine or peptide. Ki-67(+) cell numbers then decline rapidly, and 10 days after vaccination, both Ki-67(+) and overall influenza-specific cell numbers are similar to pre-vaccination levels. These results provide a tool for assessing the quality and quantity of CD4 T cell responses to different influenza vaccines, and raise the possibility that the anti-influenza T cell memory response may be qualitatively altered by vaccination, even if the overall memory cell numbers do not change significantly. Copyright © 2012. Published by Elsevier Ltd.

  3. Computational dissection of human episodic memory reveals mental process-specific genetic profiles.

    Science.gov (United States)

    Luksys, Gediminas; Fastenrath, Matthias; Coynel, David; Freytag, Virginie; Gschwind, Leo; Heck, Angela; Jessen, Frank; Maier, Wolfgang; Milnik, Annette; Riedel-Heller, Steffi G; Scherer, Martin; Spalek, Klara; Vogler, Christian; Wagner, Michael; Wolfsgruber, Steffen; Papassotiropoulos, Andreas; de Quervain, Dominique J-F

    2015-09-01

    Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.

  4. Proteomic Analysis of Lysine Acetylation Sites in Rat Tissues Reveals Organ Specificity and Subcellular Patterns

    Directory of Open Access Journals (Sweden)

    Alicia Lundby

    2012-08-01

    Full Text Available Lysine acetylation is a major posttranslational modification involved in a broad array of physiological functions. Here, we provide an organ-wide map of lysine acetylation sites from 16 rat tissues analyzed by high-resolution tandem mass spectrometry. We quantify 15,474 modification sites on 4,541 proteins and provide the data set as a web-based database. We demonstrate that lysine acetylation displays site-specific sequence motifs that diverge between cellular compartments, with a significant fraction of nuclear sites conforming to the consensus motifs G-AcK and AcK-P. Our data set reveals that the subcellular acetylation distribution is tissue-type dependent and that acetylation targets tissue-specific pathways involved in fundamental physiological processes. We compare lysine acetylation patterns for rat as well as human skeletal muscle biopsies and demonstrate its general involvement in muscle contraction. Furthermore, we illustrate that acetylation of fructose-bisphosphate aldolase and glycerol-3-phosphate dehydrogenase serves as a cellular mechanism to switch off enzymatic activity.

  5. Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species.

    Science.gov (United States)

    Lee, Kim-Chung; Tam, Emily W T; Lo, Ka-Ching; Tsang, Alan K L; Lau, Candy C Y; To, Kelvin K W; Chan, Jasper F W; Lam, Ching-Wan; Yuen, Kwok-Yung; Lau, Susanna K P; Woo, Patrick C Y

    2015-06-17

    Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii) and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu-Glu-Leu-Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid). Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu-Glu-Leu-Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species.

  6. 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

  7. Barcoded pyrosequencing reveals that consumption of galactooligosaccharides results in a highly specific bifidogenic response in humans.

    Directory of Open Access Journals (Sweden)

    Lauren M G Davis

    Full Text Available Prebiotics are selectively fermented ingredients that allow specific changes in the gastrointestinal microbiota that confer health benefits to the host. However, the effects of prebiotics on the human gut microbiota are incomplete as most studies have relied on methods that fail to cover the breadth of the bacterial community. The goal of this research was to use high throughput multiplex community sequencing of 16S rDNA tags to gain a community wide perspective of the impact of prebiotic galactooligosaccharide (GOS on the fecal microbiota of healthy human subjects. Fecal samples from eighteen healthy adults were previously obtained during a feeding trial in which each subject consumed a GOS-containing product for twelve weeks, with four increasing dosages (0, 2.5, 5, and 10 gram of GOS. Multiplex sequencing of the 16S rDNA tags revealed that GOS induced significant compositional alterations in the fecal microbiota, principally by increasing the abundance of organisms within the Actinobacteria. Specifically, several distinct lineages of Bifidobacterium were enriched. Consumption of GOS led to five- to ten-fold increases in bifidobacteria in half of the subjects. Increases in Firmicutes were also observed, however, these changes were detectable in only a few individuals. The enrichment of bifidobacteria was generally at the expense of one group of bacteria, the Bacteroides. The responses to GOS and the magnitude of the response varied between individuals, were reversible, and were in accordance with dosage. The bifidobacteria were the only bacteria that were consistently and significantly enriched by GOS, although this substrate supported the growth of diverse colonic bacteria in mono-culture experiments. These results suggest that GOS can be used to enrich bifidobacteria in the human gastrointestinal tract with remarkable specificity, and that the bifidogenic properties of GOS that occur in vivo are caused by selective fermentation as well as by

  8. Structure and Sequence Analyses of Clustered Protocadherins Reveal Antiparallel Interactions that Mediate Homophilic Specificity.

    Science.gov (United States)

    Nicoludis, John M; Lau, Sze-Yi; Schärfe, Charlotta P I; Marks, Debora S; Weihofen, Wilhelm A; Gaudet, Rachelle

    2015-11-03

    Clustered protocadherin (Pcdh) proteins mediate dendritic self-avoidance in neurons via specific homophilic interactions in their extracellular cadherin (EC) domains. We determined crystal structures of EC1-EC3, containing the homophilic specificity-determining region, of two mouse clustered Pcdh isoforms (PcdhγA1 and PcdhγC3) to investigate the nature of the homophilic interaction. Within the crystal lattices, we observe antiparallel interfaces consistent with a role in trans cell-cell contact. Antiparallel dimerization is supported by evolutionary correlations. Two interfaces, located primarily on EC2-EC3, involve distinctive clustered Pcdh structure and sequence motifs, lack predicted glycosylation sites, and contain residues highly conserved in orthologs but not paralogs, pointing toward their biological significance as homophilic interaction interfaces. These two interfaces are similar yet distinct, reflecting a possible difference in interaction architecture between clustered Pcdh subfamilies. These structures initiate a molecular understanding of clustered Pcdh assemblies that are required to produce functional neuronal networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Region-specific changes in presynaptic agmatine and glutamate levels in the aged rat brain.

    Science.gov (United States)

    Jing, Y; Liu, P; Leitch, B

    2016-01-15

    During the normal aging process, the brain undergoes a range of biochemical and structural alterations, which may contribute to deterioration of sensory and cognitive functions. Age-related deficits are associated with altered efficacy of synaptic neurotransmission. Emerging evidence indicates that levels of agmatine, a putative neurotransmitter in the mammalian brain, are altered in a region-specific manner during the aging process. The gross tissue content of agmatine in the prefrontal cortex (PFC) of aged rat brains is decreased whereas levels in the temporal cortex (TE) are increased. However, it is not known whether these changes in gross tissue levels are also mirrored by changes in agmatine levels at synapses and thus could potentially contribute to altered synaptic function with age. In the present study, agmatine levels in presynaptic terminals in the PFC and TE regions (300 terminals/region) of young (3month; n=3) and aged (24month; n=3) brains of male Sprague-Dawley rats were compared using quantitative post-embedding immunogold electron-microscopy. Presynaptic levels of agmatine were significantly increased in the TE region (60%; pagmatine and glutamate were co-localized in the same synaptic terminals, and quantitative analyses revealed significantly reduced glutamate levels in agmatine-immunopositive synaptic terminals in both regions in aged rats compared to young animals. This study, for the first time, demonstrates differential effects of aging on agmatine and glutamate in the presynaptic terminals of PFC and TE. Future research is required to understand the functional significance of these changes and the underlying mechanisms. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Altered spontaneous brain activity in adolescent boys with pure conduct disorder revealed by regional homogeneity analysis.

    Science.gov (United States)

    Wu, Qiong; Zhang, Xiaocui; Dong, Daifeng; Wang, Xiang; Yao, Shuqiao

    2017-07-01

    Functional magnetic resonance imaging (fMRI) studies have revealed abnormal neural activity in several brain regions of adolescents with conduct disorder (CD) performing various tasks. However, little is known about the spontaneous neural activity in people with CD in a resting state. The aims of this study were to investigate CD-associated regional activity abnormalities and to explore the relationship between behavioral impulsivity and regional activity abnormalities. Resting-state fMRI (rs-fMRI) scans were administered to 28 adolescents with CD and 28 age-, gender-, and IQ-matched healthy controls (HCs). The rs-fMRI data were subjected to regional homogeneity (ReHo) analysis. ReHo can demonstrate the temporal synchrony of regional blood oxygen level-dependent signals and reflect the coordination of local neuronal activity facilitating similar goals or representations. Compared to HCs, the CD group showed increased ReHo bilaterally in the insula as well as decreased ReHo in the right inferior parietal lobule, right middle temporal gyrus and right fusiform gyrus, left anterior cerebellum anterior, and right posterior cerebellum. In the CD group, mean ReHo values in the left and the right insula correlated positively with Barratt Impulsivity Scale (BIS) total scores. The results suggest that CD is associated with abnormal intrinsic brain activity, mainly in the cerebellum and temporal-parietal-limbic cortices, regions that are related to emotional and cognitive processing. BIS scores in adolescents with CD may reflect severity of abnormal neuronal synchronization in the insula.

  11. Structure and Evolution of the Lunar Procellarum Region as Revealed by GRAIL Gravity Data

    Science.gov (United States)

    Andrews-Hanna, Jeffrey C.; Besserer, Jonathan; Head, James W., III; Howett, Carly J. A.; Kiefer, Walter S.; Lucey, Paul J.; McGovern, Patrick J.; Melosh, H. Jay; Neumann, Gregory A.; Phillips, Roger J.; hide

    2014-01-01

    The Procellarum region is a broad area on the nearside of the Moon that is characterized by low elevations, thin crust, and high surface concentrations of the heat-producing elements uranium, thorium, and potassium. The Procellarum region has been interpreted as an ancient impact basin approximately 3200 km in diameter, though supporting evidence at the surface would have been largely obscured as a result of the great antiquity and poor preservation of any diagnostic features. Here we use data from the Gravity Recovery and Interior Laboratory (GRAIL) mission to examine the subsurface structure of Procellarum. The Bouguer gravity anomalies and gravity gradients reveal a pattern of narrow linear anomalies that border the Procellarum region and are interpreted to be the frozen remnants of lava-filled rifts and the underlying feeder dikes that served as the magma plumbing system for much of the nearside mare volcanism. The discontinuous surface structures that were earlier interpreted as remnants of an impact basin rim are shown in GRAIL data to be a part of this continuous set of quasi-rectangular border structures with angular intersections, contrary to the expected circular or elliptical shape of an impact basin. The spatial pattern of magmatic-tectonic structures bounding Procellarum is consistent with their formation in response to thermal stresses produced by the differential cooling of the province relative to its surroundings, coupled with magmatic activity driven by the elevated heat flux in the region.

  12. Lateral and medial ventral occipitotemporal regions interact during the recognition of images revealed from noise

    Directory of Open Access Journals (Sweden)

    Barbara eNordhjem

    2016-01-01

    Full Text Available Several studies suggest different functional roles for the medial and the lateral ventral sections in object recognition. Texture and surface information is processed in medial regions, while shape information is processed in lateral sections. This begs the question whether and how these functionally specialized sections interact with each other and with early visual cortex to facilitate object recognition. In the current research, we set out to answer this question. In an fMRI study, thirteen subjects viewed and recognized images of objects and animals that were gradually revealed from noise while their brains were being scanned. We applied dynamic causal modeling (DCM – a method to characterize network interactions – to determine the modulatory effect of object recognition on a network comprising the primary visual cortex (V1, the lingual gyrus (LG in medial ventral cortex and the lateral occipital cortex (LO. We found that object recognition modulated the bilateral connectivity between LG and LO. Moreover, the feed-forward connectivity from V1 to LG and LO was modulated, while there was no evidence for feedback from these regions to V1 during object recognition. In particular, the interaction between medial and lateral areas supports a framework in which visual recognition of objects is achieved by networked regions that integrate information on image statistics, scene content and shape – rather than by a single categorically specialized region – within the ventral visual cortex.

  13. Multi-region and single-cell sequencing reveal variable genomic heterogeneity in rectal cancer.

    Science.gov (United States)

    Liu, Mingshan; Liu, Yang; Di, Jiabo; Su, Zhe; Yang, Hong; Jiang, Beihai; Wang, Zaozao; Zhuang, Meng; Bai, Fan; Su, Xiangqian

    2017-11-23

    Colorectal cancer is a heterogeneous group of malignancies with complex molecular subtypes. While colon cancer has been widely investigated, studies on rectal cancer are very limited. Here, we performed multi-region whole-exome sequencing and single-cell whole-genome sequencing to examine the genomic intratumor heterogeneity (ITH) of rectal tumors. We sequenced nine tumor regions and 88 single cells from two rectal cancer patients with tumors of the same molecular classification and characterized their mutation profiles and somatic copy number alterations (SCNAs) at the multi-region and the single-cell levels. A variable extent of genomic heterogeneity was observed between the two patients, and the degree of ITH increased when analyzed on the single-cell level. We found that major SCNAs were early events in cancer development and inherited steadily. Single-cell sequencing revealed mutations and SCNAs which were hidden in bulk sequencing. In summary, we studied the ITH of rectal cancer at regional and single-cell resolution and demonstrated that variable heterogeneity existed in two patients. The mutational scenarios and SCNA profiles of two patients with treatment naïve from the same molecular subtype are quite different. Our results suggest each tumor possesses its own architecture, which may result in different diagnosis, prognosis, and drug responses. Remarkable ITH exists in the two patients we have studied, providing a preliminary impression of ITH in rectal cancer.

  14. Nonlinear responses within the medial prefrontal cortex reveal when specific implicit information influences economic decision making.

    Science.gov (United States)

    Deppe, Michael; Schwindt, Wolfram; Kugel, Harald; Plassmann, Hilke; Kenning, Peter

    2005-04-01

    The authors used functional magnetic resonance imaging (fMRI) to investigate how individual economic decisions are influenced by implicit memory contributions. Twenty-two participants were asked to make binary decisions between different brands of sensorily nearly undistinguishable consumer goods. Changes of brain activity comparing decisions in the presence or absence of a specific target brand were detected by fMRI. Only when the tar get brand was the participant's favorite one did the authors find reduced activation in the dorsolateral prefrontal, posterior parietal, and occipital cortices and the left premotor area (Brodmann areas [BA] 9, 46, 7/19, and 6). Simultaneously, activity was increased in the inferior precuneus and posterior cingulate (BA 7), right superior frontal gyrus (BA 10), right supramarginal gyrus (BA 40), and, most pronounced, in the ventromedial prefrontal cortex (BA 10). For products mainly distinguishable by brand information, the authors revealed a nonlinear winner-take-all effect for a participant's favorite brand characterized, on one hand, by reduced activation in brain areas associated with working memory and reasoning and, on the other hand, increased activation in areas involved in processing of emotions and self-reflections during decision making.

  15. Comparative analysis of alfalfa (Medicago sativa L.) leaf transcriptomes reveals genotype-specific salt tolerance mechanisms.

    Science.gov (United States)

    Lei, Yunting; Xu, Yuxing; Hettenhausen, Christian; Lu, Chengkai; Shen, Guojing; Zhang, Cuiping; Li, Jing; Song, Juan; Lin, Honghui; Wu, Jianqiang

    2018-02-15

    Soil salinity is an important factor affecting growth, development, and productivity of almost all land plants, including the forage crop alfalfa (Medicago sativa). However, little is known about how alfalfa responds and adapts to salt stress, particularly among different salt-tolerant cultivars. Among seven alfalfa cultivars, we found that Zhongmu-1 (ZM) is relatively salt-tolerant and Xingjiang Daye (XJ) is salt-sensitive. Compared to XJ, ZM showed slower growth under low-salt conditions, but exhibited stronger tolerance to salt stress. RNA-seq analysis revealed 2237 and 1125 differentially expressed genes (DEGs) between ZM and XJ in the presence and absence of salt stress, among which many genes are involved in stress-related pathways. After salt treatment, compared with the controls, the number of DEGs in XJ (19373) was about four times of that in ZM (4833). We also detected specific differential gene expression patterns: In response to salt stress, compared with XJ, ZM maintained relatively more stable expression levels of genes related to the ROS and Ca 2+ pathways, phytohormone biosynthesis, and Na + /K + transport. Notably, several salt resistance-associated genes always showed greater levels of expression in ZM than in XJ, including a transcription factor. Consistent with the suppression of plant growth resulting from salt stress, the expression of numerous photosynthesis- and growth hormone-related genes decreased more dramatically in XJ than in ZM. By contrast, the expression levels of photosynthetic genes were lower in ZM under low-salt conditions. Compared with XJ, ZM is a salt-tolerant alfalfa cultivar possessing specific regulatory mechanisms conferring exceptional salt tolerance, likely by maintaining high transcript levels of abiotic and biotic stress resistance-related genes. Our results suggest that maintaining this specific physiological status and/or plant adaptation to salt stress most likely arises by inhibition of plant growth in ZM through

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

    Directory of Open Access Journals (Sweden)

    Yong Guo

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

  17. Endometrial natural killer (NK) cells reveal a tissue-specific receptor repertoire.

    Science.gov (United States)

    Feyaerts, D; Kuret, T; van Cranenbroek, B; van der Zeeuw-Hingrez, S; van der Heijden, O W H; van der Meer, A; Joosten, I; van der Molen, R G

    2018-02-13

    Is the natural killer (NK) cell receptor repertoire of endometrial NK (eNK) cells tissue-specific? The NK cell receptor (NKR) expression profile in pre-pregnancy endometrium appears to have a unique tissue-specific phenotype, different from that found in NK cells in peripheral blood, suggesting that these cells are finely tuned towards the reception of an allogeneic fetus. NK cells are important for successful pregnancy. After implantation, NK cells encounter extravillous trophoblast cells and regulate trophoblast invasion. NK cell activity is amongst others regulated by C-type lectin heterodimer (CD94/NKG2) and killer cell immunoglobulin-like (KIR) receptors. KIR expression on decidual NK cells is affected by the presence of maternal HLA-C and biased towards KIR2D expression. However, little is known about NKR expression on eNK cells prior to pregnancy. In this study, matched peripheral and menstrual blood (a source of endometrial cells) was obtained from 25 healthy females with regular menstrual cycles. Menstrual blood was collected during the first 36 h of menstruation using a menstrual cup, a non-invasive technique to obtain endometrial cells. KIR and NKG2 receptor expression on eNK cells was characterized by 10-color flow cytometry, and compared to matched pbNK cells of the same female. KIR and HLA-C genotypes were determined by PCR-SSOP techniques. Anti-CMV IgG antibodies in plasma were measured by chemiluminescence immunoassay. KIR expression patterns of eNK cells collected from the same female do not differ over consecutive menstrual cycles. The percentage of NK cells expressing KIR2DL2/L3/S2, KIR2DL3, KIR2DL1, LILRB1 and/or NKG2A was significantly higher in eNK cells compared to pbNK cells, while no significant difference was observed for NKG2C, KIR2DL1/S1, and KIR3DL1. The NKR repertoire of eNK cells was clearly different from pbNK cells, with eNK cells co-expressing more than three NKR simultaneously. In addition, outlier analysis revealed 8 and 15 NKR

  18. Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits.

    Science.gov (United States)

    Kohara, Keigo; Pignatelli, Michele; Rivest, Alexander J; Jung, Hae-Yoon; Kitamura, Takashi; Suh, Junghyup; Frank, Dominic; Kajikawa, Koichiro; Mise, Nathan; Obata, Yuichi; Wickersham, Ian R; Tonegawa, Susumu

    2014-02-01

    The formation and recall of episodic memory requires precise information processing by the entorhinal-hippocampal network. For several decades, the trisynaptic circuit entorhinal cortex layer II (ECII)→dentate gyrus→CA3→CA1 and the monosynaptic circuit ECIII→CA1 have been considered the primary substrates of the network responsible for learning and memory. Circuits linked to another hippocampal region, CA2, have only recently come to light. Using highly cell type-specific transgenic mouse lines, optogenetics and patch-clamp recordings, we found that dentate gyrus cells, long believed to not project to CA2, send functional monosynaptic inputs to CA2 pyramidal cells through abundant longitudinal projections. CA2 innervated CA1 to complete an alternate trisynaptic circuit, but, unlike CA3, projected preferentially to the deep, rather than to the superficial, sublayer of CA1. Furthermore, contrary to existing knowledge, ECIII did not project to CA2. Our results allow a deeper understanding of the biology of learning and memory.

  19. Clostridium difficile Infection and Patient-Specific Antimicrobial Resistance Testing Reveals a High Metronidazole Resistance Rate.

    Science.gov (United States)

    Barkin, Jodie A; Sussman, Daniel A; Fifadara, Nimita; Barkin, Jamie S

    2017-04-01

    Clostridium difficile (CD) infection (CDI) causes marked morbidity and mortality, accounting for large healthcare expenditures annually. Current CDI treatment guidelines focus on clinical markers of patient severity to determine the preferred antibiotic regimen of metronidazole versus vancomycin. The antimicrobial resistance patterns for patients with CD are currently unknown. The aim of this study was to define the antimicrobial resistance patterns for CD. This study included all patients with stools sent for CD testing to a private laboratory (DRG Laboratory, Alpharetta, Georgia) in a 6-month period from across the USA. Patient data was de-identified, with only age, gender, and zip-code available per laboratory protocol. All samples underwent PCR testing followed by hybridization for CD toxin regions A and B. Only patients with CD-positive PCR were analyzed. Antimicrobial resistance testing using stool genomic DNA evaluated presence of imidazole- and vancomycin-resistant genes using multiplex PCR gene detection. Of 2743, 288 (10.5%) stool samples were positive for CD. Six were excluded per protocol. Of 282, 193 (69.4%) were women, and average age was 49.4 ± 18.7 years. Of 282, 62 were PCR positive for toxins A and B, 160 for toxin A positive alone, and 60 for toxin B positive alone. Antimicrobial resistance testing revealed 134/282 (47.5%) patients resistant to imidazole, 17 (6.1%) resistant to vancomycin, and 9 (3.2%) resistant to imidazole and vancomycin. CD-positive patients with presence of imidazole-resistant genes from stool DNA extract was a common phenomenon, while vancomycin resistance was uncommon. Similar to treatment of other infections, antimicrobial resistance testing should play a role in CDI clinical decision-making algorithms to enable more expedited and cost-effective delivery of patient care.

  20. Regionally specific white matter disruptions of fornix and cingulum in schizophrenia.

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    Muhammad Farid Abdul-Rahman

    Full Text Available Limbic circuitry disruptions have been implicated in the psychopathology and cognitive deficits of schizophrenia, which may involve white matter disruptions of the major tracts of the limbic system, including the fornix and the cingulum. Our study aimed to investigate regionally specific abnormalities of the fornix and cingulum in schizophrenia using diffusion tensor imaging (DTI. We determined the fractional anisotropy (FA, radial diffusivity (RD, and axial diffusivity (AD profiles along the fornix and cingulum tracts using a fibertracking technique and a brain mapping algorithm, the large deformation diffeomorphic metric mapping (LDDMM, in the DTI scans of 33 patients with schizophrenia and 31 age-, gender-, and handedness-matched healthy controls. We found that patients with schizophrenia showed reduction in FA and increase in RD in bilateral fornix, and increase in RD in left anterior cingulum when compared to healthy controls. In addition, tract-based analysis revealed specific loci of these white matter differences in schizophrenia, that is, FA reductions and AD and RD increases occur in the region of the left fornix further from the hippocampus, FA reductions and RD increases occur in the rostral portion of the left anterior cingulum, and RD and AD increases occur in the anterior segment of the left middle cingulum. In patients with schizophrenia, decreased FA in the specific loci of the left fornix and increased AD in the right cingulum adjoining the hippocampus correlated with greater severity of psychotic symptoms. These findings support precise disruptions of limbic-cortical integrity in schizophrenia and disruption of these structural networks may contribute towards the neural basis underlying the syndrome of schizophrenia and clinical symptomatology.

  1. Gender-specific spatial interactions on Dutch regional labour markets and the gender employment gap

    NARCIS (Netherlands)

    Noback, Inge; Broersma, Lourens; Van Dijk, Jouke

    2013-01-01

    Gender-specific spatial interactions on Dutch regional labour markets and the gender employment gap, Regional Studies. This paper analyses gender-specific employment rates and the gender employment gap in Dutch municipalities for 2002. The novelty of this analysis is that it takes into account the

  2. Different levels of food restriction reveal genotype-specific differences in learning a visual discrimination task.

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    Kalina Makowiecki

    Full Text Available In behavioural experiments, motivation to learn can be achieved using food rewards as positive reinforcement in food-restricted animals. Previous studies reduce animal weights to 80-90% of free-feeding body weight as the criterion for food restriction. However, effects of different degrees of food restriction on task performance have not been assessed. We compared learning task performance in mice food-restricted to 80 or 90% body weight (BW. We used adult wildtype (WT; C57Bl/6j and knockout (ephrin-A2⁻/⁻ mice, previously shown to have a reverse learning deficit. Mice were trained in a two-choice visual discrimination task with food reward as positive reinforcement. When mice reached criterion for one visual stimulus (80% correct in three consecutive 10 trial sets they began the reverse learning phase, where the rewarded stimulus was switched to the previously incorrect stimulus. For the initial learning and reverse phase of the task, mice at 90%BW took almost twice as many trials to reach criterion as mice at 80%BW. Furthermore, WT 80 and 90%BW groups significantly differed in percentage correct responses and learning strategy in the reverse learning phase, whereas no differences between weight restriction groups were observed in ephrin-A2⁻/⁻ mice. Most importantly, genotype-specific differences in reverse learning strategy were only detected in the 80%BW groups. Our results indicate that increased food restriction not only results in better performance and a shorter training period, but may also be necessary for revealing behavioural differences between experimental groups. This has important ethical and animal welfare implications when deciding extent of diet restriction in behavioural studies.

  3. Brain-to-brain hyperclassification reveals action-specific motor mapping of observed actions in humans.

    Science.gov (United States)

    Smirnov, Dmitry; Lachat, Fanny; Peltola, Tomi; Lahnakoski, Juha M; Koistinen, Olli-Pekka; Glerean, Enrico; Vehtari, Aki; Hari, Riitta; Sams, Mikko; Nummenmaa, Lauri

    2017-01-01

    Seeing an action may activate the corresponding action motor code in the observer. It remains unresolved whether seeing and performing an action activates similar action-specific motor codes in the observer and the actor. We used novel hyperclassification approach to reveal shared brain activation signatures of action execution and observation in interacting human subjects. In the first experiment, two "actors" performed four types of hand actions while their haemodynamic brain activations were measured with 3-T functional magnetic resonance imaging (fMRI). The actions were videotaped and shown to 15 "observers" during a second fMRI experiment. Eleven observers saw the videos of one actor, and the remaining four observers saw the videos of the other actor. In a control fMRI experiment, one of the actors performed actions with closed eyes, and five new observers viewed these actions. Bayesian canonical correlation analysis was applied to functionally realign observers' and actors' fMRI data. Hyperclassification of the seen actions was performed with Bayesian logistic regression trained on actors' data and tested with observers' data. Without the functional realignment, between-subjects accuracy was at chance level. With the realignment, the accuracy increased on average by 15 percentage points, exceeding both the chance level and the accuracy without functional realignment. The highest accuracies were observed in occipital, parietal and premotor cortices. Hyperclassification exceeded chance level also when the actor did not see her own actions. We conclude that the functional brain activation signatures underlying action execution and observation are partly shared, yet these activation signatures may be anatomically misaligned across individuals.

  4. Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease.

    Science.gov (United States)

    Lewis, Wesley R; Malarkey, Erik B; Tritschler, Douglas; Bower, Raqual; Pasek, Raymond C; Porath, Jonathan D; Birket, Susan E; Saunier, Sophie; Antignac, Corinne; Knowles, Michael R; Leigh, Margaret W; Zariwala, Maimoona A; Challa, Anil K; Kesterson, Robert A; Rowe, Steven M; Drummond, Iain A; Parant, John M; Hildebrandt, Friedhelm; Porter, Mary E; Yoder, Bradley K; Berbari, Nicolas F

    2016-07-01

    Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh) signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400). While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8). GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC) protein 4 (DRC4) where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR) to generate one of these human missense variants in

  5. Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease.

    Directory of Open Access Journals (Sweden)

    Wesley R Lewis

    2016-07-01

    Full Text Available Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400. While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8. GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC protein 4 (DRC4 where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR to generate one of these human missense

  6. Regional Atmospheric CO2 Inversion Reveals Seasonal and Geographic Differences in Amazon Net Biome Exchange

    Science.gov (United States)

    Alden, Caroline B.; Miller, John B.; Gatti, Luciana V.; Gloor, Manuel M.; Guan, Kaiyu; Michalak, Anna M.; van der Laan-Luijkx, Ingrid; Touma, Danielle; Andrews, Arlyn; Basso, Luana G.; hide

    2016-01-01

    Understanding tropical rainforest carbon exchange and its response to heat and drought is critical for quantifying the effects of climate change on tropical ecosystems, including global climate carbon feedbacks. Of particular importance for the global carbon budget is net biome exchange of CO2 with the atmosphere (NBE), which represents nonfire carbon fluxes into and out of biomass and soils. Subannual and sub-Basin Amazon NBE estimates have relied heavily on process-based biosphere models, despite lack of model agreement with plot-scale observations. We present a new analysis of airborne measurements that reveals monthly, regional-scale (Approx.1-8 x 10(exp -6) km2) NBE variations. We develop a regional atmospheric CO2 inversion that provides the first analysis of geographic and temporal variability in Amazon biosphere-atmosphere carbon exchange and that is minimally influenced by biosphere model-based first guesses of seasonal and annual mean fluxes. We find little evidence for a clear seasonal cycle in Amazon NBE but do find NBE sensitivity to aberrations from long-term mean climate. In particular, we observe increased NBE (more carbon emitted to the atmosphere) associated with heat and drought in 2010, and correlations between wet season NBE and precipitation (negative correlation) and temperature (positive correlation). In the eastern Amazon, pulses of increased NBE persisted through 2011, suggesting legacy effects of 2010 heat and drought. We also identify regional differences in postdrought NBE that appear related to long-term water availability. We examine satellite proxies and find evidence for higher gross primary productivity (GPP) during a pulse of increased carbon uptake in 2011, and lower GPP during a period of increased NBE in the 2010 dry season drought, but links between GPP and NBE changes are not conclusive. These results provide novel evidence of NBE sensitivity to short-term temperature and moisture extremes in the Amazon, where monthly and sub

  7. Complex and region-specific changes in astroglial markers in the aging brain.

    Science.gov (United States)

    Rodríguez, José J; Yeh, Chia-Yu; Terzieva, Slavica; Olabarria, Markel; Kulijewicz-Nawrot, Magdalena; Verkhratsky, Alexei

    2014-01-01

    Morphological aging of astrocytes was investigated in entorhinal cortex (EC), dentate gyrus (DG), and cornu ammonis 1 (CA1) regions of hippocampus of male SV129/C57BL6 mice of different age groups (3, 9, 18, and 24 months). Astroglial profiles were visualized by immunohistochemistry by using glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and s100β staining; these profiles were imaged using confocal or light microscopy for subsequent morphometric analysis. GFAP-positive profiles in the DG and the CA1 of the hippocampus showed progressive age-dependent hypertrophy, as indicated by an increase in surface, volume, and somata volume at 24 months of age compared with 3-month-old mice. In contrast with the hippocampal regions, aging induced a decrease in GFAP-positive astroglial profiles in the EC: the surface, volume, and cell body volume of astroglial cells at 24 months of age were decreased significantly compared with the 3-month group. The GS-positive astrocytes displayed smaller cellular surface areas at 24 months compared with 3-month-old animals in both areas of hippocampus, whereas GS-positive profiles remained unchanged in the EC of old mice. The morphometry of s100β-immunoreactive profiles revealed substantial increase in the EC, more moderate increase in the DG, and no changes in the CA1 area. Based on the morphological analysis of 3 astroglial markers, we conclude that astrocytes undergo a complex age-dependent remodeling in a brain region-specific manner. Copyright © 2014. Published by Elsevier Inc.

  8. Reverse Conservation Analysis Reveals the Specificity Determining Residues of Cytochrome P450 Family 2 (CYP 2

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    Tai-Sung Lee

    2008-01-01

    Full Text Available The concept of conservation of amino acids is widely used to identify important alignment positions of orthologs. The assumption is that important amino acid residues will be conserved in the protein family during the evolutionary process. For paralog alignment, on the other hand, the opposite concept can be used to identify residues that are responsible for specificity. Assuming that the function-specific or ligand-specific residue positions will have higher diversity since they are under evolutionary pressure to fit the target specificity, these function-specific or ligand-specific residues positions will have a lower degree of conservation than other positions in a highly conserved paralog alignment. This study assessed the ability of reverse conservation analysis to identify function-specific and ligand-specific residue positions in closely related paralog. Reverse conservation analysis of paralog alignments successfully identified all six previously reported substrate recognition sites (SRSs in cytochrome P450 family 2 (CYP 2. Further analysis of each subfamily identified the specificity-determining residues (SDRs that have been experimentally found. New potential SDRs were also predicted and await confirmation by further experiments or modeling calculations. This concept may be also applied to identify SDRs in other protein families.

  9. Regional specific groundwater arsenic levels and neuropsychological functioning: a cross-sectional study.

    Science.gov (United States)

    Edwards, Melissa; Johnson, Leigh; Mauer, Cortney; Barber, Robert; Hall, James; O'Bryant, Sid

    2014-01-01

    The purpose of the study was to examine the link between geographic information system (GIS)-estimated regional specific groundwater levels and neuropsychological functioning in a sample of individuals with and without cognitive impairment. This cross-sectional study design analyzed data from 1390 participants (733 Alzheimer's disease, 127 Mild Cognitive Impairment, and 530 with normal cognition) enrolled in the Texas Alzheimer's Research and Care Consortium. GISs analyses were used to estimate regional specific groundwater arsenic concentrations using the Environmental Systems Research Institute and arsenic concentrations from the Texas Water Development Board. In the full cohort, regional specific arsenic concentrations were positively associated with language abilities (p = 0.008), but associated with poorer verbal memory, immediate (p = 0.008), and delayed (p arsenic being related with cognition most prominently among mild cognitive impairment cases. Overall, estimated regional specific groundwater arsenic levels were negatively associated with neuropsychological performance.

  10. Concordance of gene expression in human protein complexes reveals tissue specificity and pathology

    DEFF Research Database (Denmark)

    Börnigen, Daniela; Pers, Tune Hannes; Thorrez, Lieven

    2013-01-01

    Disease-causing variants in human genes usually lead to phenotypes specific to only a few tissues. Here, we present a method for predicting tissue specificity based on quantitative deregulation of protein complexes. The underlying assumption is that the degree of coordinated expression among prot...

  11. Migration of Frosts from High-Albedo Regions of Pluto: what New Horizons Reveals

    Science.gov (United States)

    Buratti, Bonnie J.; Stern, S. A.; Weaver, Hal A.; Young, Leslie A.; Olkin, Cathy B.; Ennico, Kimberly; Binzel, Richard P.; Zangari, Amanda; Earle, Alissa M.

    2015-11-01

    With its high eccentricity and obliquity, Pluto should exhibit seasonal volatile transport on its surface. Several lines of evidence support this transport: doubling of Pluto’s atmospheric pressure over the past two decades (Young et al., 2013, Ap. J. 766, L22; Olkin et al., 2015, Icarus 246, 230); changes in its historical rotational light curve, once all variations due to viewing geometry have been modelled (Buratti et al., 2015; Ap. J. 804, L6); and changes in HST albedo maps (Buie et al., 2010, Astron. J. 139, 1128). New Horizons LORRI images reveal that the region of greatest albedo change is not the polar cap(s) of Pluto, but the feature informally named Tombaugh Regio (TR). This feature has a normal reflectance as high as ~0.8 in some places, and it is superposed on older, lower-albedo pre-existing terrain with an albedo of only ~0.10. This contrast is larger than any other body in the Solar System, except for Iapetus. This albedo dichotomy leads to a complicated system of cold-trapping and thermal segregation, beyond the simple picture of seasonal volatile transport. Whatever the origin of TR, it initially acted as a cold trap, as the temperature differential between the high and low albedo regions could be enormous, possibly approaching 20K, based on their albedo differences and assuming their normalized phase curves are similar. This latter assumption will be refined as the full New Horizons data set is returned.Over six decades of ground-based photometry suggest that TR has been decreasing in albedo over the last 25 years. Possible causes include changing insolation angles, or sublimation from the edges where the high-albedo material impinges on a much warmer substrate.Funding by the NASA New Horizons Project acknowledged.

  12. Probing region-specific microstructure of human cortical areas using high angular and spatial resolution diffusion MRI.

    Science.gov (United States)

    Aggarwal, Manisha; Nauen, David W; Troncoso, Juan C; Mori, Susumu

    2015-01-15

    Regional heterogeneity in cortical cyto- and myeloarchitecture forms the structural basis of mapping of cortical areas in the human brain. In this study, we investigate the potential of diffusion MRI to probe the microstructure of cortical gray matter and its region-specific heterogeneity across cortical areas in the fixed human brain. High angular resolution diffusion imaging (HARDI) data at an isotropic resolution of 92-μm and 30 diffusion-encoding directions were acquired using a 3D diffusion-weighted gradient-and-spin-echo sequence, from prefrontal (Brodmann area 9), primary motor (area 4), primary somatosensory (area 3b), and primary visual (area 17) cortical specimens (n=3 each) from three human subjects. Further, the diffusion MR findings in these cortical areas were compared with histological silver impregnation of the same specimens, in order to investigate the underlying architectonic features that constitute the microstructural basis of diffusion-driven contrasts in cortical gray matter. Our data reveal distinct and region-specific diffusion MR contrasts across the studied areas, allowing delineation of intracortical bands of tangential fibers in specific layers-layer I, layer VI, and the inner and outer bands of Baillarger. The findings of this work demonstrate unique sensitivity of diffusion MRI to differentiate region-specific cortical microstructure in the human brain, and will be useful for myeloarchitectonic mapping of cortical areas as well as to achieve an understanding of the basis of diffusion NMR contrasts in cortical gray matter. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. A Comparison of Regional and SiteSpecific Volume Estimation Equations

    Science.gov (United States)

    Joe P. McClure; Jana Anderson; Hans T. Schreuder

    1987-01-01

    Regression equations for volume by region and site class were examined for lobiolly pine. The regressions for the Coastal Plain and Piedmont regions had significantly different slopes. The results shared important practical differences in percentage of confidence intervals containing the true total volume and in percentage of estimates within a specific proportion of...

  14. Comparative transcriptomics reveal host-specific nucleotide variation in entomophthoralean fungi

    DEFF Research Database (Denmark)

    de Fine Licht, Henrik Hjarvard; Jensen, Annette Bruun; Eilenberg, Jørgen

    2017-01-01

    of toxins that interfere with the host immune response. Phylogenetic comparison with the nonobligate generalist insect-pathogenic fungus Conidiobolus coronatus revealed a gene-family expansion of trehalase enzymes in E. muscae. The main sugar in insect haemolymph is trehalose, and efficient sugar...

  15. Mitochondrial DNA reveals regional and interregional importance of the central Mediterranean African shelf for loggerhead sea turtles (Caretta caretta

    Directory of Open Access Journals (Sweden)

    Paolo Casale

    2008-09-01

    Full Text Available The wide north African continental shelf in the central Mediterranean is known to be one of the few important areas in the basin for loggerhead turtles in the neritic stage. In order to assess the origin of these turtles, sequences of the mtDNA control region were obtained from 70 turtles caught by bottom trawlers in the area, and compared with known sequences from turtles from Mediterranean and Atlantic nesting sites. Five haplotypes were identified (Haplotype diversity = 0.262; nucleotide diversity = 5.4×10-3. Specific haplotypes indicate contributions from distant rookeries such as Turkey and the Atlantic, which shows that Atlantic turtles entering the Mediterranean while in the oceanic phase use at least one Mediterranean continental shelf as a neritic foraging ground. A new haplotype and another one previously found only in foraging areas, highlight the genetic information gaps for nesting sites, which undermine powerful mixed stock analyses. Despite these limitations, the results reveal the regional importance of the study area as a neritic foraging ground for turtles that are probably from most of the Mediterranean nesting aggregates. Therefore, reducing turtle mortality resulting from the high fishing effort in the area should be regarded as key for Mediterranean turtle conservation and is also possibly important for Atlantic populations.

  16. Genetic analysis of Aedes albopictus (Diptera, Culicidae) reveals a deep divergence in the original regions.

    Science.gov (United States)

    Ruiling, Zhang; Tongkai, Liu; Zhendong, Huang; Guifen, Zhuang; Dezhen, Ma; Zhong, Zhang

    2018-05-02

    Aedes albopictus has been described as one of the 100 worst invasive species in the world. This mosquito originated from southeastern Asia and currently has a widespread presence in every continent except Antarctica. The rapid global expansion of Ae. albopictus has increased public health concerns about arbovirus-related disease threats. Adaptation, adaption to novel areas is a biological challenge for invasive species, and the underlying processes can be studied at the molecular level. In this study, genetic analysis was performed using mitochondrial gene NADH dehydrogenase subunit 5 (ND5), based on both native and invasive populations. Altogether, 38 haplotypes were detected with H1 being the dominant and widely distributed in 21 countries. Both phylogenetic and network analyses supported the existence of five clades, with only clade I being involved in the subsequent global spread of Asian tiger mosquito. The other four clades (II, III, IV and V) were restricted to their original regions, which could be ancestral populations that had diverged from clade I in the early stages of evolution. Neutrality tests suggested that most of the populations had experienced recent expansion. Analysis of molecular variance and the population-pair statistic F ST revealed that most populations lacked genetic structure, while high variability was detected within populations. Multiple and independent human-mediated introductions may explain the present results. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Substrate specificity changes for human reticulocyte and epithelial 15-lipoxygenases reveal allosteric product regulation.

    Science.gov (United States)

    Wecksler, Aaron T; Kenyon, Victor; Deschamps, Joshua D; Holman, Theodore R

    2008-07-15

    Human reticulocyte 15-lipoxygenase (15-hLO-1) and epithelial 15-lipoxygenase (15-hLO-2) have been implicated in a number of human diseases, with differences in their substrate specificity potentially playing a central role. In this paper, we present a novel method for accurately measuring the substrate specificity of the two 15-hLO isozymes and demonstrate that both cholate and specific LO products affect substrate specificity. The linoleic acid (LA) product, 13-hydroperoxyoctadienoic acid (13-HPODE), changes the ( k cat/ K m) (AA)/( k cat/ K m) (LA) ratio more than 5-fold for 15-hLO-1 and 3-fold for 15-hLO-2, while the arachidonic acid (AA) product, 12-( S)-hydroperoxyeicosatetraenoic acid (12-HPETE), affects only the ratio of 15-hLO-1 (more than 5-fold). In addition, the reduced products, 13-( S)-hydroxyoctadecadienoic acid (13-HODE) and 12-( S)-hydroxyeicosatetraenoic acid (12-HETE), also affect substrate specificity, indicating that iron oxidation is not responsible for the change in the ( k cat/ K m) (AA)/( k cat/ K m) (LA) ratio. These results, coupled with the dependence of the 15-hLO-1 k cat/ K m kinetic isotope effect ( (D) k cat/ K m) on the presence of 12-HPETE and 12-HETE, indicate that the allosteric site, previously identified in 15-hLO-1 [Mogul, R., Johansen, E., and Holman, T. R. (1999) Biochemistry 39, 4801-4807], is responsible for the change in substrate specificity. The ability of LO products to regulate substrate specificity may be relevant with respect to cancer progression and warrants further investigation into the role of this product-feedback loop in the cell.

  18. Transcriptional decomposition reveals active chromatin architectures and cell specific regulatory interactions

    DEFF Research Database (Denmark)

    Rennie, Sarah; Dalby, Maria; van Duin, Lucas

    2018-01-01

    Transcriptional regulation is tightly coupled with chromosomal positioning and three-dimensional chromatin architecture. However, it is unclear what proportion of transcriptional activity is reflecting such organisation, how much can be informed by RNA expression alone and how this impacts disease...... proportion of total levels and is highly informative of topological associating domain activities and organisation, revealing boundaries and chromatin compartments. Furthermore, expression data alone accurately predict individual enhancer-promoter interactions, drawing features from expression strength...... between transcription and chromatin architecture....

  19. Interaction studies reveal specific recognition of an anti-inflammatory polyphosphorhydrazone dendrimer by human monocytes.

    Science.gov (United States)

    Ledall, Jérémy; Fruchon, Séverine; Garzoni, Matteo; Pavan, Giovanni M; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Blanzat, Muriel; Poupot, Rémy

    2015-11-14

    Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes.

  20. Molecular Subtyping of Primary Prostate Cancer Reveals Specific and Shared Target Genes of Different ETS Rearrangements

    Directory of Open Access Journals (Sweden)

    Paula Paulo

    2012-07-01

    Full Text Available This work aimed to evaluate whether ETS transcription factors frequently involved in rearrangements in prostate carcinomas (PCa, namely ERG and ETV1, regulate specific or shared target genes. We performed differential expression analysis on nine normal prostate tissues and 50 PCa enriched for different ETS rearrangements using exon-level expression microarrays, followed by in vitro validation using cell line models. We found specific deregulation of 57 genes in ERG-positive PCa and 15 genes in ETV1-positive PCa, whereas deregulation of 27 genes was shared in both tumor subtypes. We further showed that the expression of seven tumor-associated ERG target genes (PLA1A, CACNA1D, ATP8A2, HLA-DMB, PDE3B, TDRD1, and TMBIM1 and two tumor-associated ETV1 target genes (FKBP10 and GLYATL2 was significantly affected by specific ETS silencing in VCaP and LNCaP cell line models, respectively, whereas the expression of three candidate ERG and ETV1 shared targets (GRPR, KCNH8, and TMEM45B was significantly affected by silencing of either ETS. Interestingly, we demonstrate that the expression of TDRD1, the topmost overexpressed gene of our list of ERG-specific candidate targets, is inversely correlated with the methylation levels of a CpG island found at -66 bp of the transcription start site in PCa and that TDRD1 expression is regulated by direct binding of ERG to the CpG island in VCaP cells. We conclude that ETS transcription factors regulate specific and shared target genes and that TDRD1, FKBP10, and GRPR are promising therapeutic targets and can serve as diagnostic markers for molecular subtypes of PCa harboring specific fusion gene rearrangements.

  1. Bacterial Preferences for Specific Soil Particle Size Fractions Revealed by Community Analyses

    DEFF Research Database (Denmark)

    Hemkemeyer, Michael; Dohrmann, Anja B.; Christensen, Bent Tolstrup

    2018-01-01

    Genetic fingerprinting demonstrated in previous studies that differently sized soil particle fractions (PSFs; clay, silt, and sand with particulate organic matter (POM)) harbor microbial communities that differ in structure, functional potentials and sensitivity to environmental conditions....... To elucidate whether specific bacterial or archaeal taxa exhibit preference for specific PSFs, we examined the diversity of PCR-amplified 16S rRNA genes by high-throughput sequencing using total DNA extracted from three long-term fertilization variants (unfertilized, fertilized with minerals, and fertilized...

  2. Somatic sex-specific transcriptome differences in Drosophila revealed by whole transcriptome sequencing

    Directory of Open Access Journals (Sweden)

    Arbeitman Michelle N

    2011-07-01

    Full Text Available Abstract Background Understanding animal development and physiology at a molecular-biological level has been advanced by the ability to determine at high resolution the repertoire of mRNA molecules by whole transcriptome resequencing. This includes the ability to detect and quantify rare abundance transcripts and isoform-specific mRNA variants produced from a gene. The sex hierarchy consists of a pre-mRNA splicing cascade that directs the production of sex-specific transcription factors that specify nearly all sexual dimorphism. We have used deep RNA sequencing to gain insight into how the Drosophila sex hierarchy generates somatic sex differences, by examining gene and transcript isoform expression differences between the sexes in adult head tissues. Results Here we find 1,381 genes that differ in overall expression levels and 1,370 isoform-specific transcripts that differ between males and females. Additionally, we find 512 genes not regulated downstream of transformer that are significantly more highly expressed in males than females. These 512 genes are enriched on the × chromosome and reside adjacent to dosage compensation complex entry sites, which taken together suggests that their residence on the × chromosome might be sufficient to confer male-biased expression. There are no transcription unit structural features, from a set of features, that are robustly significantly different in the genes with significant sex differences in the ratio of isoform-specific transcripts, as compared to random isoform-specific transcripts, suggesting that there is no single molecular mechanism that generates isoform-specific transcript differences between the sexes, even though the sex hierarchy is known to include three pre-mRNA splicing factors. Conclusions We identify thousands of genes that show sex-specific differences in overall gene expression levels, and identify hundreds of additional genes that have differences in the abundance of isoform-specific

  3. Discovery of novel isoforms of huntingtin reveals a new hominid-specific exon.

    Directory of Open Access Journals (Sweden)

    Albert Ruzo

    Full Text Available Huntington's disease (HD is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT. HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease.

  4. Discovery of Novel Isoforms of Huntingtin Reveals a New Hominid-Specific Exon

    Science.gov (United States)

    Popowski, Melissa; Haremaki, Tomomi; Croft, Gist F.; Deglincerti, Alessia; Brivanlou, Ali H.

    2015-01-01

    Huntington’s disease (HD) is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT). HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC) lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease. PMID:26010866

  5. Understanding Conservation Delays in Children with Specific Language Impairment: Task Representations Revealed in Speech and Gesture

    Science.gov (United States)

    Mainela-Arnold, Elina; Evans, Julia L.; Alibali, Martha W.

    2006-01-01

    Purpose: The authors investigated mental representations of Piagetian conservation tasks in children with specific language impairment (SLI) and typically developing peers. Children with SLI have normal nonverbal intelligence; however, they exhibit difficulties in Piagetian conservation tasks. The authors tested the hypothesis that conservation…

  6. Bacterial Preferences for Specific Soil Particle Size Fractions Revealed by Community Analyses

    DEFF Research Database (Denmark)

    Hemkemeyer, Michael; Dohrmann, Anja B.; Christensen, Bent Tolstrup

    2018-01-01

    , while Gemmatimonadales preferred coarse silt, Actinobacteria and Nitrosospira fine silt, and Planctomycetales clay. Firmicutes were depleted in the sand-sized fraction. In contrast, archaea, which represented 0.8% of all 16S rRNA gene sequences, showed only little preference for specific PSFs. We...

  7. Quantitative analysis of commensal Escherichia coli populations reveals host-specific enterotypes at the intra-species level.

    Science.gov (United States)

    Smati, Mounira; Clermont, Olivier; Bleibtreu, Alexandre; Fourreau, Frédéric; David, Anthony; Daubié, Anne-Sophie; Hignard, Cécile; Loison, Odile; Picard, Bertrand; Denamur, Erick

    2015-08-01

    The primary habitat of the Escherichia coli species is the gut of warm-blooded vertebrates. The E. coli species is structured into four main phylogenetic groups A, B1, B2, and D. We estimated the relative proportions of these phylogroups in the feces of 137 wild and domesticated animals with various diets living in the Ile de France (Paris) region by real-time PCR. We distinguished three main clusters characterized by a particular abundance of two or more phylogroups within the E. coli animal commensal populations, which we called "enterocolitypes" by analogy with the enterotypes defined in the human gut microbiota at the genus level. These enterocolitypes were characterized by a dominant (>50%) B2, B1, or A phylogroup and were associated with different host species, diets, and habitats: wild and herbivorous species (wild rabbits and deer), domesticated herbivorous species (domesticated rabbits, horses, sheep, and cows), and omnivorous species (boar, pigs, and chickens), respectively. By analyzing retrospectively the data obtained using the same approach from 98 healthy humans living in Ile de France (Smati et al. 2013, Appl. Environ. Microbiol. 79, 5005-5012), we identified a specific human enterocolitype characterized by the dominant and/or exclusive (>90%) presence of phylogroup B2. We then compared B2 strains isolated from animals and humans, and revealed that human and animal strains differ regarding O-type and B2 subgroup. Moreover, two genes, sfa/foc and clbQ, were associated with the exclusive character of strains, observed only in humans. In conclusion, a complex network of interactions exists at several levels (genus and intra-species) within the intestinal microbiota. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  8. Greenhouse gas emissions from cities and regions: International implications revealed by Hong Kong

    International Nuclear Information System (INIS)

    Harris, Paul G.; Chow, Alice S.Y.; Symons, Jonathan

    2012-01-01

    The diversity of greenhouse gas (GHG) accounting methodologies currently utilized by cities around the world make meaningful comparisons of their emissions almost impossible. Consequently, the 2010 United Nations International Standard for Determining Greenhouse Gas Emissions for Cities promotes a “harmonized protocol for quantifying the GHG emissions attributable to cities and local regions.” The UN's common standard has important implications for comparison, benchmarking and policy assessment related to energy policies. This paper uses Hong Kong as a case study to illustrate these implications. Hong Kong's per capita contribution to GHG emissions are among the highest in the world, yet the local government's official statistics indicate emissions that are far below those reported by most affluent economies. This discrepancy arises from a reporting methodology that does not require inclusion of GHG emissions linked to consumption of imported goods or emissions from aviation and shipping. The Hong Kong case reveals that current inventories do not provide sufficient information to guide policymaking related to energy and climate change. They also do not provide adequate information for comparing policies of cities internationally. Alternative emissions-reporting standards that focus more on pollution from consumption will create avenues for more effective climate-related policies. - Highlights: ► Flawed GHG inventory methodologies can lead cities to adopt misguided policies. ► Diverse GHG inventory methodologies make meaningful comparisons among cities difficult. ► A Hong Kong case study highlights that GHG inventories can misrepresent cities' climate impacts. ► City inventories often exclude GHG emissions linked to imports, aviation and shipping. ► The International Standard for Determining GHG Emissions for Cities can assist climate policy.

  9. Is Drosophila-microbe association species-specific or region specific? A study undertaken involving six Indian Drosophila species.

    Science.gov (United States)

    Singhal, Kopal; Khanna, Radhika; Mohanty, Sujata

    2017-06-01

    The present work aims to identify the microbial diversity associated with six Indian Drosophila species using next generation sequencing (NGS) technology and to discover the nature of their distribution across species and eco-geographic regions. Whole fly gDNA of six Drosophila species were used to generate sequences in an Illumina platform using NGS technology. De novo based assembled raw reads were blasted against the NR database of NCBI using BLASTn for identification of their bacterial loads. We have tried to include Drosophila species from different taxonomical groups and subgroups and from three different eco-climatic regions India; four species belong to Central India, while the rest two, D. melanogaster and D. ananassae, belong to West and South India to determine both their species-wise and region-wide distribution. We detected the presence of 33 bacterial genera across all six study species, predominated by the class Proteobacteria. Amongst all, D. melanogaster was found to be the most diverse by carrying around 85% of the bacterial diversity. Our findings infer both species-specific and environment-specific nature of the bacterial species inhabiting the Drosophila host. Though the present results are consistent with most of the earlier studies, they also remain incoherent with some. The present study outcome on the host-bacteria association and their species specific adaptation may provide some insight to understand the host-microbial interactions and the phenotypic implications of microbes on the host physiology. The knowledge gained may be importantly applied into the recent insect and pest population control strategy going to implement through gut microflora in India and abroad.

  10. Synthesis of Isomeric Phosphoubiquitin Chains Reveals that Phosphorylation Controls Deubiquitinase Activity and Specificity

    Directory of Open Access Journals (Sweden)

    Nicolas Huguenin-Dezot

    2016-07-01

    Full Text Available Ubiquitin is post-translationally modified by phosphorylation at several sites, but the consequences of these modifications are largely unknown. Here, we synthesize multi-milligram quantities of ubiquitin phosphorylated at serine 20, serine 57, and serine 65 via genetic code expansion. We use these phosphoubiquitins for the enzymatic assembly of 20 isomeric phosphoubiquitin dimers, with different sites of isopeptide linkage and/or phosphorylation. We discover that phosphorylation of serine 20 on ubiquitin converts UBE3C from a dual-specificity E3 ligase into a ligase that primarily synthesizes K48 chains. We profile the activity of 31 deubiquitinases on the isomeric phosphoubiquitin dimers in 837 reactions, and we discover that phosphorylation at distinct sites in ubiquitin can activate or repress cleavage of a particular linkage by deubiquitinases and that phosphorylation at a single site in ubiquitin can control the specificity of deubiquitinases for distinct ubiquitin linkages.

  11. Constrained dansyl derivatives reveal bacterial specificity of highly conserved thymidylate synthases.

    Science.gov (United States)

    Calò, Sanuele; Tondi, Donatella; Ferrari, Stefania; Venturelli, Alberto; Ghelli, Stefano; Costi, Maria Paola

    2008-03-25

    The elucidation of the structural/functional specificities of highly conserved enzymes remains a challenging area of investigation, and enzymes involved in cellular replication are important targets for functional studies and drug discovery. Thymidylate synthase (TS, ThyA) governs the synthesis of thymidylate for use in DNA synthesis. The present study focused on Lactobacillus casei TS (LcTS) and Escherichia coli TS (EcTS), which exhibit 50 % sequence identity and strong folding similarity. We have successfully designed and validated a chemical model in which linear, but not constrained, dansyl derivatives specifically complement the LcTS active site. Conversely, chemically constrained dansyl derivatives showed up to 1000-fold improved affinity for EcTS relative to the inhibitory activity of linear derivatives. This study demonstrates that the accurate design of small ligands can uncover functional features of highly conserved enzymes.

  12. Communication: High pressure specific heat spectroscopy reveals simple relaxation behavior of glass forming molecular liquid

    DEFF Research Database (Denmark)

    Roed, Lisa Anita; Niss, Kristine; Jakobsen, Bo

    2015-01-01

    The frequency dependent specific heat has been measured under pressure for the molecular glass forming liquid 5-polyphenyl-4-ether in the viscous regime close to the glass transition. The temperature and pressure dependences of the characteristic time scale associated with the specific heat...... is compared to the equivalent time scale from dielectric spectroscopy performed under identical conditions. It is shown that the ratio between the two time scales is independent of both temperature and pressure. This observation is non-trivial and demonstrates the existence of specially simple molecular...... liquids in which different physical relaxation processes are both as function of temperature and pressure/density governed by the same underlying “inner clock.” Furthermore, the results are discussed in terms of the recent conjecture that van der Waals liquids, like the measuredliquid, comply...

  13. Revealing context-specific conditioned fear memories with full immersion virtual reality

    Directory of Open Access Journals (Sweden)

    Nicole eHuff

    2011-11-01

    Full Text Available The extinction of conditioned fear is known to be context specific, and often referred to as more robustly contextually bound than the fear memory itself (Bouton, 2004. Yet, recent findings in rodents have challenged the notion that contextual fear retention is initially generalized. The context specificity of a cued-fear memory to the learning context has not been addressed in the human literature largely due to limitations in methodology. Here we adapt a novel technology to test the context specificity of cued fear conditioning using full immersion 3-dimensional virtual reality (VR. During acquisition training, healthy participants navigated through virtual environments containing dynamic snake and spider conditioned stimuli (CSs, one of which was paired with electrical wrist stimulation. During a 24-hour delayed retention test, one group returned to the same context as acquisition training whereas another group experienced the CSs in a novel context. Unconditioned stimulus (US expectancy ratings were assayed on-line during fear acquisition as an index of contingency awareness. Skin conductance responses (SCR time-locked to CS onset were the dependent measure of cued fear, and skin conductance levels during the interstimulus interval were an index of context fear. Findings indicate that early in acquisition training, participants express contingency awareness as well as differential contextual fear, whereas differential cued fear emerged later in acquisition. During the retention test, differential cued fear retention was enhanced in the group who returned to the same context as acquisition training relative to the context shift group. The results extend recent rodent work to illustrate differences in cued and context fear acquisition and the contextual specificity of recent fear memories. Findings support the use of full immersion VR as a novel tool in cognitive neuroscience to bridge rodent models of contextual phenomena underlying human

  14. Specific gene expression responses to parasite genotypes reveal redundancy of innate immunity in vertebrates.

    Directory of Open Access Journals (Sweden)

    David Haase

    Full Text Available Vertebrate innate immunity is the first line of defense against an invading pathogen and has long been assumed to be largely unspecific with respect to parasite/pathogen species. However, recent phenotypic evidence suggests that immunogenetic variation, i.e. allelic variability in genes associated with the immune system, results in host-parasite genotype-by-genotype interactions and thus specific innate immune responses. Immunogenetic variation is common in all vertebrate taxa and this reflects an effective immunological function in complex environments. However, the underlying variability in host gene expression patterns as response of innate immunity to within-species genetic diversity of macroparasites in vertebrates is unknown. We hypothesized that intra-specific variation among parasite genotypes must be reflected in host gene expression patterns. Here we used high-throughput RNA-sequencing to examine the effect of parasite genotypes on gene expression patterns of a vertebrate host, the three-spined stickleback (Gasterosteus aculeatus. By infecting naïve fish with distinct trematode genotypes of the species Diplostomum pseudospathaceum we show that gene activity of innate immunity in three-spined sticklebacks depended on the identity of an infecting macroparasite genotype. In addition to a suite of genes indicative for a general response against the trematode we also find parasite-strain specific gene expression, in particular in the complement system genes, despite similar infection rates of single clone treatments. The observed discrepancy between infection rates and gene expression indicates the presence of alternative pathways which execute similar functions. This suggests that the innate immune system can induce redundant responses specific to parasite genotypes.

  15. Cell-specific STORM superresolution imaging reveals nanoscale organization of cannabinoid signaling

    Science.gov (United States)

    Szabó, Szilárd I.; Szabadits, Eszter; Pintér, Balázs; Woodhams, Stephen G.; Henstridge, Christopher M.; Balla, Gyula Y.; Nyilas, Rita; Varga, Csaba; Lee, Sang-Hun; Matolcsi, Máté; Cervenak, Judit; Kacskovics, Imre; Watanabe, Masahiko; Sagheddu, Claudia; Melis, Miriam; Pistis, Marco; Soltesz, Ivan; Katona, István

    2014-01-01

    A major challenge in neuroscience is to determine the nanoscale position and quantity of signaling molecules in a cell-type-, and subcellular compartment-specific manner. We therefore developed a novel approach combining cell-specific physiological and anatomical characterization with superresolution imaging, and studied the molecular and structural parameters shaping the physiological properties of synaptic endocannabinoid signaling in the mouse hippocampus. We found that axon terminals of perisomatically-projecting GABAergic interneurons possess increased CB1 receptor number, active-zone complexity, and receptor/effector ratio compared to dendritically-projecting interneurons, in agreement with higher efficiency of cannabinoid signaling at somatic versus dendritic synapses. Furthermore, chronic Δ9-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked dramatic CB1-downregulation in a dose-dependent manner. Full receptor recovery required several weeks after cessation of Δ9-tetrahydrocannabinol treatment. These findings demonstrate that cell-type-specific nanoscale analysis of endogenous protein distribution is possible in brain circuits, and identify novel molecular properties controlling endocannabinoid signaling and cannabis-induced cognitive dysfunction. PMID:25485758

  16. Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling.

    Science.gov (United States)

    Dudok, Barna; Barna, László; Ledri, Marco; Szabó, Szilárd I; Szabadits, Eszter; Pintér, Balázs; Woodhams, Stephen G; Henstridge, Christopher M; Balla, Gyula Y; Nyilas, Rita; Varga, Csaba; Lee, Sang-Hun; Matolcsi, Máté; Cervenak, Judit; Kacskovics, Imre; Watanabe, Masahiko; Sagheddu, Claudia; Melis, Miriam; Pistis, Marco; Soltesz, Ivan; Katona, István

    2015-01-01

    A major challenge in neuroscience is to determine the nanoscale position and quantity of signaling molecules in a cell type- and subcellular compartment-specific manner. We developed a new approach to this problem by combining cell-specific physiological and anatomical characterization with super-resolution imaging and studied the molecular and structural parameters shaping the physiological properties of synaptic endocannabinoid signaling in the mouse hippocampus. We found that axon terminals of perisomatically projecting GABAergic interneurons possessed increased CB1 receptor number, active-zone complexity and receptor/effector ratio compared with dendritically projecting interneurons, consistent with higher efficiency of cannabinoid signaling at somatic versus dendritic synapses. Furthermore, chronic Δ(9)-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked marked CB1 downregulation in a dose-dependent manner. Full receptor recovery required several weeks after the cessation of Δ(9)-tetrahydrocannabinol treatment. These findings indicate that cell type-specific nanoscale analysis of endogenous protein distribution is possible in brain circuits and identify previously unknown molecular properties controlling endocannabinoid signaling and cannabis-induced cognitive dysfunction.

  17. Compartment-Specific Biosensors Reveal a Complementary Subcellular Distribution of Bioactive Furin and PC7

    Directory of Open Access Journals (Sweden)

    Pierpaolo Ginefra

    2018-02-01

    Full Text Available Furin trafficking, and that of related proprotein convertases (PCs, may regulate which substrates are accessible for endoproteolysis, but tools to directly test this hypothesis have been lacking. Here, we develop targeted biosensors that indicate Furin activity in endosomes is 10-fold less inhibited by decanoyl-RVKR-chloromethylketone and enriched >3-fold in endosomes compared to the trans-Golgi network (TGN. Endogenous PC7, which resists this inhibitor, was active in distinct vesicles. Only overexpressed PC7 activity reached the cell surface, endosomes, and the TGN. A PLC motif in the cytosolic tail of PC7 was dispensable for endosomal activity, but it was specifically required for TGN recycling and to rescue proActivin-A cleavage in Furin-depleted B16F1 melanoma cells. In sharp contrast, PC7 complemented Furin in cleaving Notch1 independently of PLC-mediated TGN access. Our study provides a proof in principle that compartment-specific biosensors can be used to gain insight into the regulation of PC trafficking and to map the tropism of PC-specific inhibitors.

  18. About the nature of regional thermal anomaly in the Semipalatinsk Test Site region revealed basing on remote space sensing data

    International Nuclear Information System (INIS)

    Melent'ev, M.I.; Velikanov, A.E.

    2003-01-01

    A thermal anomaly, (more than 20,000 sq. km) discovered in the Semipalatinsk Test Site region in the pictures from space, is observed every year on certain days mainly in winter-spring season. Appearance of the thermal anomaly often coincides with days of intensive fall of atmospheric precipitation and possible thawing of snow cover together with decreasing of ozone concentration in atmosphere. The explanation of thermal anomaly in the Semipalatinsk Test Site region due to nuclear reaction caused by the energy of radionuclide radioactive decay deposited in a soil layer after ground and air nuclear explosions and radiolysis processes in soil solutions is given in this article. (author)

  19. RNAi screen reveals host cell kinases specifically involved in Listeria monocytogenes spread from cell to cell.

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    Ryan Chong

    Full Text Available Intracellular bacterial pathogens, such as Listeria monocytogenes and Rickettsia conorii display actin-based motility in the cytosol of infected cells and spread from cell to cell through the formation of membrane protrusions at the cell cortex. Whereas the mechanisms supporting cytosolic actin-based motility are fairly well understood, it is unclear whether specific host factors may be required for supporting the formation and resolution of membrane protrusions. To address this gap in knowledge, we have developed high-throughput fluorescence microscopy and computer-assisted image analysis procedures to quantify pathogen spread in human epithelial cells. We used the approach to screen a siRNA library covering the human kinome and identified 7 candidate kinases whose depletion led to severe spreading defects in cells infected with L. monocytogenes. We conducted systematic validation procedures with redundant silencing reagents and confirmed the involvement of the serine/threonine kinases, CSNK1A1 and CSNK2B. We conducted secondary assays showing that, in contrast with the situation observed in CSNK2B-depleted cells, L. monocytogenes formed wild-type cytosolic tails and displayed wild-type actin-based motility in the cytosol of CSNK1A1-depleted cells. Furthermore, we developed a protrusion formation assay and showed that the spreading defect observed in CSNK1A1-depleted cells correlated with the formation of protrusion that did not resolve into double-membrane vacuoles. Moreover, we developed sending and receiving cell-specific RNAi procedures and showed that CSNK1A was required in the sending cells, but was dispensable in the receiving cells, for protrusion resolution. Finally, we showed that the observed defects were specific to Listeria monocytogenes, as Rickettsia conorii displayed wild-type cell-to-cell spread in CSNK1A1- and CSNK2B-depleted cells. We conclude that, in addition to the specific host factors supporting cytosolic actin

  20. Comparison of human glutamate carboxypeptidases II and III reveals their divergent substrate specificities

    Czech Academy of Sciences Publication Activity Database

    Navrátil, Michal; Tykvart, Jan; Schimer, Jiří; Pachl, Petr; Navrátil, Václav; Rokob, T. A.; Hlouchová, Klára; Rulíšek, Lubomír; Konvalinka, Jan

    2016-01-01

    Roč. 283, č. 13 (2016), s. 2528-2545 ISSN 1742-464X R&D Projects: GA ČR(CZ) GBP208/12/G016; GA ČR(CZ) GA14-31419S; GA MŠk LO1302; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : arene-binding site * GCPIII * prostate -specific membrane antigen * QM/MM calculations * beta-citryl-L-glutamate Subject RIV: CE - Biochemistry Impact factor: 3.902, year: 2016

  1. Simplified immunoassay for rapid Dengue serotype diagnosis, revealing insensitivity to non-specific binding interference

    Directory of Open Access Journals (Sweden)

    Fernanda C.C.L. Loureiro

    2017-04-01

    Full Text Available Proof of concept of an immunoassay, which is easy to implement, for rapid Dengue virus (DENV serotype diagnosis, in the early infection stage, is reported. The four-layer assay is immobilized onto a thin gold film and relies on a low cost, disposable polymer biochip for optical surface plasmon resonance sensing and detection. The protocol comprises Neutravidin-Biotin mediated monoclonal antibody (MAB attachment as the functionalized sensing element. Formation of the MAB-DENV complex results in a pronounced thickness change that is optically recorded in real time, employing a microfluidic set-up. Virus presence is confirmed by atomic force microscopy from the same sample. Serum samples were collected from a patient in acute febrile state. Simultaneous serological analysis by means of the reverse transcription polymerase chain reaction, independently, confirmed presence of DENV2 and DENV3. The protocol proved applicable in presence of strong non-specific binding interference that originates from, and is caused by, various blood, serum and other body fluid constituents. False positive indications for both, negative serum and blood control samples were not observed. The achievable limit of detection was estimated to be 2×104 particles/ml. Eventually, the method can be modified towards detection of other viruses by using the same protocol. Keywords: Immuno-assay, Dengue virus detection, Non-specific binding

  2. Species-specific separation of lake plankton reveals divergent food assimilation patterns in rotifers.

    Science.gov (United States)

    Burian, Alfred; Kainz, Martin J; Schagerl, Michael; Yasindi, Andrew

    2014-06-01

    1. The analysis of functional groups with a resolution to the individual species level is a basic requirement to better understand complex interactions in aquatic food webs. Species-specific stable isotope analyses are currently applied to analyse the trophic role of large zooplankton or fish species, but technical constraints complicate their application to smaller-sized plankton. 2. We investigated rotifer food assimilation during a short-term microzooplankton bloom in the East African soda lake Nakuru by developing a method for species-specific sampling of rotifers. 3. The two dominant rotifers, Brachionus plicatilis and Brachionus dimidiatus , were separated to single-species samples (purity >95%) and significantly differed in their isotopic values (4.1‰ in δ 13 C and 1.5‰ in δ 15 N). Bayesian mixing models indicated that isotopic differences were caused by different assimilation of filamentous cyanobacteria and particles plicatilis (48%), whereas it was hardly ingested by B. dimidiatus . Overall, A . fusiformis was, relative to its biomass, assimilated to small extents, demonstrating a high grazing resistance of this species. 5. In combination with high population densities, these results demonstrate a strong potential of rotifer blooms to shape phytoplankton communities and are the first in situ demonstration of a quantitatively important direct trophic link between rotifers and filamentous cyanobacteria.

  3. Screening in larval zebrafish reveals tissue-specific distribution of fifteen fluorescent compounds

    Directory of Open Access Journals (Sweden)

    Yuxiao Yao

    2017-09-01

    Full Text Available The zebrafish is a prominent vertebrate model for low-cost in vivo whole organism screening. In our recent screening of the distribution patterns of fluorescent compounds in live zebrafish larvae, fifteen compounds with tissue-specific distributions were identified. Several compounds were observed to accumulate in tissues where they were reported to induce side-effects, and compounds with similar structures tended to be enriched in the same tissues, with minor differences. In particular, we found three novel red fluorescent bone-staining dyes: purpurin, lucidin and 3-hydroxy-morindone; purpurin can effectively label bones in both larval and adult zebrafish, as well as in postnatal mice, without significantly affecting bone mass and density. Moreover, two structurally similar chemotherapeutic compounds, doxorubicin and epirubicin, were observed to have distinct distribution preferences in zebrafish. Epirubicin maintained a relatively higher concentration in the liver, and performed better in inhibiting hepatic hyperplasia caused by the over-expression of krasG12V. In total, our study suggests that the transparent zebrafish larvae serve as valuable tools for identifying tissue-specific distributions of fluorescent compounds.

  4. Mixed infections reveal virulence differences between host-specific bee pathogens.

    Science.gov (United States)

    Klinger, Ellen G; Vojvodic, Svjetlana; DeGrandi-Hoffman, Gloria; Welker, Dennis L; James, Rosalind R

    2015-07-01

    Dynamics of host-pathogen interactions are complex, often influencing the ecology, evolution and behavior of both the host and pathogen. In the natural world, infections with multiple pathogens are common, yet due to their complexity, interactions can be difficult to predict and study. Mathematical models help facilitate our understanding of these evolutionary processes, but empirical data are needed to test model assumptions and predictions. We used two common theoretical models regarding mixed infections (superinfection and co-infection) to determine which model assumptions best described a group of fungal pathogens closely associated with bees. We tested three fungal species, Ascosphaera apis, Ascosphaera aggregata and Ascosphaera larvis, in two bee hosts (Apis mellifera and Megachile rotundata). Bee survival was not significantly different in mixed infections vs. solo infections with the most virulent pathogen for either host, but fungal growth within the host was significantly altered by mixed infections. In the host A. mellifera, only the most virulent pathogen was present in the host post-infection (indicating superinfective properties). In M. rotundata, the most virulent pathogen co-existed with the lesser-virulent one (indicating co-infective properties). We demonstrated that the competitive outcomes of mixed infections were host-specific, indicating strong host specificity among these fungal bee pathogens. Published by Elsevier Inc.

  5. Ultrafast hydrogen exchange reveals specific structural events during the initial stages of folding of cytochrome c.

    Science.gov (United States)

    Fazelinia, Hossein; Xu, Ming; Cheng, Hong; Roder, Heinrich

    2014-01-15

    Many proteins undergo a sharp decrease in chain dimensions during early stages of folding, prior to the rate-limiting step in folding. However, it remains unclear whether compact states are the result of specific folding events or a general hydrophobic collapse of the poly peptide chain driven by the change in solvent conditions. To address this fundamental question, we extended the temporal resolution of NMR-detected H/D exchange labeling experiments into the microsecond regime by adopting a microfluidics approach. By observing the competition between H/D exchange and folding as a function of labeling pH, coupled with direct measurement of exchange rates in the unfolded state, we were able to monitor hydrogen-bond formation for over 50 individual backbone NH groups within the initial 140 microseconds of folding of horse cytochrome c. Clusters of solvent-shielded amide protons were observed in two α-helical segments in the C-terminal half of the protein, while the N-terminal helix remained largely unstructured, suggesting that proximity in the primary structure is a major factor in promoting helix formation and association at early stages of folding, while the entropically more costly long-range contacts between the N- and C-terminal helices are established only during later stages. Our findings clearly indicate that the initial chain condensation in cytochrome c is driven by specific interactions among a subset of α-helical segments rather than a general hydrophobic collapse.

  6. Recurrent activity in higher order, modality non-specific brain regions

    DEFF Research Database (Denmark)

    Lou, Hans Olav Christensen; Joensson, Morten; Biermann-Ruben, Katja

    2011-01-01

    It has been proposed that the workings of the brain are mainly intrinsically generated recurrent neuronal activity, with sensory inputs as modifiers of such activity in both sensory and higher order modality non-specific regions. This is supported by the demonstration of recurrent neuronal activity...... in the visual system as a response to visual stimulation. In contrast recurrent activity has never been demonstrated before in higher order modality non-specific regions. Using magneto-encephalography and Granger causality analysis, we tested in a paralimbic network the hypothesis that stimulation may enhance...... causal recurrent interaction between higher-order, modality non-specific regions. The network includes anterior cingulate/medial prefrontal and posterior cingulate/medial parietal cortices together with pulvinar thalami, a network known to be effective in autobiographic memory retrieval and self...

  7. Analysis of tissue-specific region in sericin 1 gene promoter of Bombyx mori

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Liu [College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027 (China); Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Lian, Yu [College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027 (China); Zhejiang Province Key Laboratory of Preventive Veterinary Medicine, Institute of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310029 (China); Xiuyang, Guo [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Tingqing, Guo [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Shengpeng, Wang [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Changde, Lu [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

    2006-03-31

    The gene encoding sericin 1 (Ser1) of silkworm (Bombyx mori) is specifically expressed in the middle silk gland cells. To identify element involved in this transcription-dependent spatial restriction, truncation of the 5' terminal from the sericin 1 (Ser1) promoter is studied in vivo. A 209 bp DNA sequence upstream of the transcriptional start site (-586 to -378) is found to be responsible for promoting tissue-specific transcription. Analysis of this 209 bp region by overlapping deletion studies showed that a 25 bp region (-500 to -476) suppresses the ectopic expression of the Ser1 promoter. An unknown factor abundant in fat body nuclear extracts is shown to bind to this 25 bp fragment. These results suggest that this 25 bp region and the unknown factor are necessary for determining the tissue-specificity of the Ser1 promoter.

  8. Transcript specificity in yeast pre-mRNA splicing revealed by mutations in core spliceosomal components.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Pleiss

    2007-04-01

    Full Text Available Appropriate expression of most eukaryotic genes requires the removal of introns from their pre-messenger RNAs (pre-mRNAs, a process catalyzed by the spliceosome. In higher eukaryotes a large family of auxiliary factors known as SR proteins can improve the splicing efficiency of transcripts containing suboptimal splice sites by interacting with distinct sequences present in those pre-mRNAs. The yeast Saccharomyces cerevisiae lacks functional equivalents of most of these factors; thus, it has been unclear whether the spliceosome could effectively distinguish among transcripts. To address this question, we have used a microarray-based approach to examine the effects of mutations in 18 highly conserved core components of the spliceosomal machinery. The kinetic profiles reveal clear differences in the splicing defects of particular pre-mRNA substrates. Most notably, the behaviors of ribosomal protein gene transcripts are generally distinct from other intron-containing transcripts in response to several spliceosomal mutations. However, dramatically different behaviors can be seen for some pairs of transcripts encoding ribosomal protein gene paralogs, suggesting that the spliceosome can readily distinguish between otherwise highly similar pre-mRNAs. The ability of the spliceosome to distinguish among its different substrates may therefore offer an important opportunity for yeast to regulate gene expression in a transcript-dependent fashion. Given the high level of conservation of core spliceosomal components across eukaryotes, we expect that these results will significantly impact our understanding of how regulated splicing is controlled in higher eukaryotes as well.

  9. The effect of patient-specific factors on radiation-induced regional lung injury

    International Nuclear Information System (INIS)

    Garipagaoglu, Melahat; Munley, Michael T.; Hollis, Donna; Poulson, Jean M.; Bentel, Gunilla C.; Sibley, Gregory; Anscher, Mitchell S.; Fan Ming; Jaszczak, Ronald J.; Coleman, R. Edward; Marks, Lawrence B.

    1999-01-01

    Purpose: To assess the impact of patient-specific factors on radiation (RT)-induced reductions in regional lung perfusion. Methods: Fifty patients (32 lung carcinoma, 7 Hodgkin's disease, 9 breast carcinoma and 2 other thoracic tumors) had pre-RT and ≥24-week post-RT single photon emission computed tomography (SPECT) perfusion images to assess the dose dependence of RT-induced reductions in regional lung perfusion. The SPECT data were analyzed using a normalized and non-normalized approach. Furthermore, two different mathematical methods were used to assess the impact of patient-specific factors on the dose-response curve (DRC). First, DRCs for different patient subgroups were generated and compared. Second, in a more formal statistical approach, individual DRCs for regional lung injury for each patient were fit to a linear-quadratic model (reduction = coefficient 1 x dose + coefficient 2 x dose 2 ). Multiple patient-specific factors including tobacco history, pre-RT diffusion capacity to carbon monoxide (DLCO), transforming growth factor-beta (TGF-β), chemotherapy exposure, disease type, and mean lung dose were explored in a multivariate analysis to assess their impact on the coefficients. Results: None of the variables tested had a consistent impact on the radiation sensitivity of regional lung (i.e., the slope of the DRC). In the formal statistical analysis, there was a suggestion of a slight increase in radiation sensitivity in the dose range >40 Gy for nonsmokers (vs. smokers) and in those receiving chemotherapy (vs. no chemotherapy). However, this finding was very dependent on the specific statistical and normalization method used. Conclusion: Patient-specific factors do not have a dramatic effect on RT-induced reduction in regional lung perfusion. Additional studies are underway to better clarify this issue. We continue to postulate that patient-specific factors will impact on how the summation of regional injury translates into whole organ injury

  10. Uncoupling of dynamin polymerization and GTPase activity revealed by the conformation-specific nanobody dynab.

    Science.gov (United States)

    Galli, Valentina; Sebastian, Rafael; Moutel, Sandrine; Ecard, Jason; Perez, Franck; Roux, Aurélien

    2017-10-12

    Dynamin is a large GTPase that forms a helical collar at the neck of endocytic pits, and catalyzes membrane fission (Schmid and Frolov, 2011; Ferguson and De Camilli, 2012). Dynamin fission reaction is strictly dependent on GTP hydrolysis, but how fission is mediated is still debated (Antonny et al., 2016): GTP energy could be spent in membrane constriction required for fission, or in disassembly of the dynamin polymer to trigger fission. To follow dynamin GTP hydrolysis at endocytic pits, we generated a conformation-specific nanobody called dynab, that binds preferentially to the GTP hydrolytic state of dynamin-1. Dynab allowed us to follow the GTPase activity of dynamin-1 in real-time. We show that in fibroblasts, dynamin GTP hydrolysis occurs as stochastic bursts, which are randomly distributed relatively to the peak of dynamin assembly. Thus, dynamin disassembly is not coupled to GTPase activity, supporting that the GTP energy is primarily spent in constriction.

  11. Functional and structural analysis of yeast trx system reveals structural elements of substrate specificity

    International Nuclear Information System (INIS)

    Oliveira, Marcos Antonio; Discola, Karen Fulan; Alves, Simone Vidigal; Netto, Luis Eduardo Soares; Amorim, Gisele Cardoso; Pinheiro, Anderson Sa; Valente, Ana Paula; Almeida, Fabio Ceneviva Lacerda; Medrano, Francisco Javier; Guimaraes, Beatriz Gomes

    2006-01-01

    Thioredoxin reductases (Trr) are members of the nucleotide pyridine disulfide oxide reductase family, which includes glutathione reductase (Gr), alkyl hydroperoxide reductase F (AhpF) and lipoamide dehydrogenase (Lpd). Constituents of this family are homodimeric flavoproteins containing one redoxactive disulfide and one tightly bound flavin adenine dinucleotide (FAD) per subunit. Trr catalyzes the disulfide reduction of oxidized Thioredoxin (Trx) using nicotinamide adenine dinucleotide phosphate (NADPH) via a FAD molecule and a redox-active cysteine motif. In this context, FAD transfers the reducing equivalents from NADPH molecule to the reactive cysteines and then to the Trx. Trx, Trr and NADPH comprise the Trx system. Trx are low molecular weight proteins (∼12 KDa) which are involved in several thiol-dependent cellular reactions such as synthesis of deoxyribonucleotides, sulphur metabolism, regulation of the gene expression and oxidative stress defenses. Remarkably, Trr - Trx interactions presents high species and organelle specificities. (author)

  12. Co-expression networks reveal the tissue-specific regulation of transcription and splicing.

    Science.gov (United States)

    Saha, Ashis; Kim, Yungil; Gewirtz, Ariel D H; Jo, Brian; Gao, Chuan; McDowell, Ian C; Engelhardt, Barbara E; Battle, Alexis

    2017-11-01

    Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. © 2017 Saha et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Principal component analysis reveals gender-specific predictors of cardiometabolic risk in 6th graders

    Directory of Open Access Journals (Sweden)

    Peterson Mark D

    2012-11-01

    Full Text Available Abstract Background The purpose of this study was to determine the sex-specific pattern of pediatric cardiometabolic risk with principal component analysis, using several biological, behavioral and parental variables in a large cohort (n = 2866 of 6th grade students. Methods Cardiometabolic risk components included waist circumference, fasting glucose, blood pressure, plasma triglycerides levels and HDL-cholesterol. Principal components analysis was used to determine the pattern of risk clustering and to derive a continuous aggregate score (MetScore. Stratified risk components and MetScore were analyzed for association with age, body mass index (BMI, cardiorespiratory fitness (CRF, physical activity (PA, and parental factors. Results In both boys and girls, BMI and CRF were associated with multiple risk components, and overall MetScore. Maternal smoking was associated with multiple risk components in girls and boys, as well as MetScore in boys, even after controlling for children’s BMI. Paternal family history of early cardiovascular disease (CVD and parental age were associated with increased blood pressure and MetScore for girls. Children’s PA levels, maternal history of early CVD, and paternal BMI were also indicative for various risk components, but not MetScore. Conclusions Several biological and behavioral factors were independently associated with children’s cardiometabolic disease risk, and thus represent a unique gender-specific risk profile. These data serve to bolster the independent contribution of CRF, PA, and family-oriented healthy lifestyles for improving children’s health.

  14. Stage-specific histone modification profiles reveal global transitions in the Xenopus embryonic epigenome.

    Directory of Open Access Journals (Sweden)

    Tobias D Schneider

    Full Text Available Vertebrate embryos are derived from a transitory pool of pluripotent cells. By the process of embryonic induction, these precursor cells are assigned to specific fates and differentiation programs. Histone post-translational modifications are thought to play a key role in the establishment and maintenance of stable gene expression patterns underlying these processes. While on gene level histone modifications are known to change during differentiation, very little is known about the quantitative fluctuations in bulk histone modifications during development. To investigate this issue we analysed histones isolated from four different developmental stages of Xenopus laevis by mass spectrometry. In toto, we quantified 59 modification states on core histones H3 and H4 from blastula to tadpole stages. During this developmental period, we observed in general an increase in the unmodified states, and a shift from histone modifications associated with transcriptional activity to transcriptionally repressive histone marks. We also compared these naturally occurring patterns with the histone modifications of murine ES cells, detecting large differences in the methylation patterns of histone H3 lysines 27 and 36 between pluripotent ES cells and pluripotent cells from Xenopus blastulae. By combining all detected modification transitions we could cluster their patterns according to their embryonic origin, defining specific histone modification profiles (HMPs for each developmental stage. To our knowledge, this data set represents the first compendium of covalent histone modifications and their quantitative flux during normogenesis in a vertebrate model organism. The HMPs indicate a stepwise maturation of the embryonic epigenome, which may be causal to the progressing restriction of cellular potency during development.

  15. Collective Dynamics of Specific Gene Ensembles Crucial for Neutrophil Differentiation: The Existence of Genome Vehicles Revealed

    Science.gov (United States)

    Giuliani, Alessandro; Tomita, Masaru

    2010-01-01

    Cell fate decision remarkably generates specific cell differentiation path among the multiple possibilities that can arise through the complex interplay of high-dimensional genome activities. The coordinated action of thousands of genes to switch cell fate decision has indicated the existence of stable attractors guiding the process. However, origins of the intracellular mechanisms that create “cellular attractor” still remain unknown. Here, we examined the collective behavior of genome-wide expressions for neutrophil differentiation through two different stimuli, dimethyl sulfoxide (DMSO) and all-trans-retinoic acid (atRA). To overcome the difficulties of dealing with single gene expression noises, we grouped genes into ensembles and analyzed their expression dynamics in correlation space defined by Pearson correlation and mutual information. The standard deviation of correlation distributions of gene ensembles reduces when the ensemble size is increased following the inverse square root law, for both ensembles chosen randomly from whole genome and ranked according to expression variances across time. Choosing the ensemble size of 200 genes, we show the two probability distributions of correlations of randomly selected genes for atRA and DMSO responses overlapped after 48 hours, defining the neutrophil attractor. Next, tracking the ranked ensembles' trajectories, we noticed that only certain, not all, fall into the attractor in a fractal-like manner. The removal of these genome elements from the whole genomes, for both atRA and DMSO responses, destroys the attractor providing evidence for the existence of specific genome elements (named “genome vehicle”) responsible for the neutrophil attractor. Notably, within the genome vehicles, genes with low or moderate expression changes, which are often considered noisy and insignificant, are essential components for the creation of the neutrophil attractor. Further investigations along with our findings might

  16. Heart structure-specific transcriptomic atlas reveals conserved microRNA-mRNA interactions.

    Science.gov (United States)

    Vacchi-Suzzi, Caterina; Hahne, Florian; Scheubel, Philippe; Marcellin, Magali; Dubost, Valerie; Westphal, Magdalena; Boeglen, Catherine; Büchmann-Møller, Stine; Cheung, Ming Sin; Cordier, André; De Benedetto, Christopher; Deurinck, Mark; Frei, Moritz; Moulin, Pierre; Oakeley, Edward; Grenet, Olivier; Grevot, Armelle; Stull, Robert; Theil, Diethilde; Moggs, Jonathan G; Marrer, Estelle; Couttet, Philippe

    2013-01-01

    MicroRNAs are short non-coding RNAs that regulate gene expression at the post-transcriptional level and play key roles in heart development and cardiovascular diseases. Here, we have characterized the expression and distribution of microRNAs across eight cardiac structures (left and right ventricles, apex, papillary muscle, septum, left and right atrium and valves) in rat, Beagle dog and cynomolgus monkey using microRNA sequencing. Conserved microRNA signatures enriched in specific heart structures across these species were identified for cardiac valve (miR-let-7c, miR-125b, miR-127, miR-199a-3p, miR-204, miR-320, miR-99b, miR-328 and miR-744) and myocardium (miR-1, miR-133b, miR-133a, miR-208b, miR-30e, miR-499-5p, miR-30e*). The relative abundance of myocardium-enriched (miR-1) and valve-enriched (miR-125b-5p and miR-204) microRNAs was confirmed using in situ hybridization. MicroRNA-mRNA interactions potentially relevant for cardiac functions were explored using anti-correlation expression analysis and microRNA target prediction algorithms. Interactions between miR-1/Timp3, miR-125b/Rbm24, miR-204/Tgfbr2 and miR-208b/Csnk2a2 were identified and experimentally investigated in human pulmonary smooth muscle cells and luciferase reporter assays. In conclusion, we have generated a high-resolution heart structure-specific mRNA/microRNA expression atlas for three mammalian species that provides a novel resource for investigating novel microRNA regulatory circuits involved in cardiac molecular physiopathology.

  17. Heart structure-specific transcriptomic atlas reveals conserved microRNA-mRNA interactions.

    Directory of Open Access Journals (Sweden)

    Caterina Vacchi-Suzzi

    Full Text Available MicroRNAs are short non-coding RNAs that regulate gene expression at the post-transcriptional level and play key roles in heart development and cardiovascular diseases. Here, we have characterized the expression and distribution of microRNAs across eight cardiac structures (left and right ventricles, apex, papillary muscle, septum, left and right atrium and valves in rat, Beagle dog and cynomolgus monkey using microRNA sequencing. Conserved microRNA signatures enriched in specific heart structures across these species were identified for cardiac valve (miR-let-7c, miR-125b, miR-127, miR-199a-3p, miR-204, miR-320, miR-99b, miR-328 and miR-744 and myocardium (miR-1, miR-133b, miR-133a, miR-208b, miR-30e, miR-499-5p, miR-30e*. The relative abundance of myocardium-enriched (miR-1 and valve-enriched (miR-125b-5p and miR-204 microRNAs was confirmed using in situ hybridization. MicroRNA-mRNA interactions potentially relevant for cardiac functions were explored using anti-correlation expression analysis and microRNA target prediction algorithms. Interactions between miR-1/Timp3, miR-125b/Rbm24, miR-204/Tgfbr2 and miR-208b/Csnk2a2 were identified and experimentally investigated in human pulmonary smooth muscle cells and luciferase reporter assays. In conclusion, we have generated a high-resolution heart structure-specific mRNA/microRNA expression atlas for three mammalian species that provides a novel resource for investigating novel microRNA regulatory circuits involved in cardiac molecular physiopathology.

  18. Functional dissection of the promoter of the pollen-specific gene NTP303 reveals a novel pollen-specific, and conserved cis-regulatory element.

    Science.gov (United States)

    Weterings, K; Schrauwen, J; Wullems, G; Twell, D

    1995-07-01

    Regulatory elements within the promoter of the pollen-specific NTP303 gene from tobacco were analysed by transient and stable expression analyses. Analysis of precisely targeted mutations showed that the NTP303 promoter is not regulated by any of the previously described pollen-specific cis-regulatory elements. However, two adjacent regions from -103 to -86 bp and from -86 to -59 bp were shown to contain sequences which positively regulated the NTP303 promoter. Both of these regions were capable of driving pollen-specific expression from a heterologous promoter, independent of orientation and in an additive manner. The boundaries of the minimal, functional NTP303 promoter were determined to lie within the region -86 to -51 bp. The sequence AAATGA localized from -94 to -89 bp was identified as a novel cis-acting element, of which the TGA triplet was shown to comprise an active part. This element was shown to be completely conserved in the similarly regulated promoter of the Bp 10 gene from Brassica napus encoding a homologue of the NTP303 gene.

  19. Torque measurements reveal sequence-specific cooperative transitions in supercoiled DNA

    Science.gov (United States)

    Oberstrass, Florian C.; Fernandes, Louis E.; Bryant, Zev

    2012-01-01

    B-DNA becomes unstable under superhelical stress and is able to adopt a wide range of alternative conformations including strand-separated DNA and Z-DNA. Localized sequence-dependent structural transitions are important for the regulation of biological processes such as DNA replication and transcription. To directly probe the effect of sequence on structural transitions driven by torque, we have measured the torsional response of a panel of DNA sequences using single molecule assays that employ nanosphere rotational probes to achieve high torque resolution. The responses of Z-forming d(pGpC)n sequences match our predictions based on a theoretical treatment of cooperative transitions in helical polymers. “Bubble” templates containing 50–100 bp mismatch regions show cooperative structural transitions similar to B-DNA, although less torque is required to disrupt strand–strand interactions. Our mechanical measurements, including direct characterization of the torsional rigidity of strand-separated DNA, establish a framework for quantitative predictions of the complex torsional response of arbitrary sequences in their biological context. PMID:22474350

  20. Sleep Stage Transition Dynamics Reveal Specific Stage 2 Vulnerability in Insomnia.

    Science.gov (United States)

    Wei, Yishul; Colombo, Michele A; Ramautar, Jennifer R; Blanken, Tessa F; van der Werf, Ysbrand D; Spiegelhalder, Kai; Feige, Bernd; Riemann, Dieter; Van Someren, Eus J W

    2017-09-01

    Objective sleep impairments in insomnia disorder (ID) are insufficiently understood. The present study evaluated whether whole-night sleep stage dynamics derived from polysomnography (PSG) differ between people with ID and matched controls and whether sleep stage dynamic features discriminate them better than conventional sleep parameters. Eighty-eight participants aged 21-70 years, including 46 with ID and 42 age- and sex-matched controls without sleep complaints, were recruited through www.sleepregistry.nl and completed two nights of laboratory PSG. Data of 100 people with ID and 100 age- and sex-matched controls from a previously reported study were used to validate the generalizability of findings. The second night was used to obtain, in addition to conventional sleep parameters, probabilities of transitions between stages and bout duration distributions of each stage. Group differences were evaluated with nonparametric tests. People with ID showed higher empirical probabilities to transition from stage N2 to the lighter sleep stage N1 or wakefulness and a faster decaying stage N2 bout survival function. The increased transition probability from stage N2 to stage N1 discriminated people with ID better than any of their deviations in conventional sleep parameters, including less total sleep time, less sleep efficiency, more stage N1, and more wake after sleep onset. Moreover, adding this transition probability significantly improved the discriminating power of a multiple logistic regression model based on conventional sleep parameters. Quantification of sleep stage dynamics revealed a particular vulnerability of stage N2 in insomnia. The feature characterizes insomnia better than-and independently of-any conventional sleep parameter. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  1. Patterns of hybrid loss of imprinting reveal tissue- and cluster-specific regulation.

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    Christopher D Wiley

    Full Text Available Crosses between natural populations of two species of deer mice, Peromyscus maniculatus (BW, and P. polionotus (PO, produce parent-of-origin effects on growth and development. BW females mated to PO males (bwxpo produce growth-retarded but otherwise healthy offspring. In contrast, PO females mated to BW males (POxBW produce overgrown and severely defective offspring. The hybrid phenotypes are pronounced in the placenta and include POxBW conceptuses which lack embryonic structures. Evidence to date links variation in control of genomic imprinting with the hybrid defects, particularly in the POxBW offspring. Establishment of genomic imprinting is typically mediated by gametic DNA methylation at sites known as gDMRs. However, imprinted gene clusters vary in their regulation by gDMR sequences.Here we further assess imprinted gene expression and DNA methylation at different cluster types in order to discern patterns. These data reveal POxBW misexpression at the Kcnq1ot1 and Peg3 clusters, both of which lose ICR methylation in placental tissues. In contrast, some embryonic transcripts (Peg10, Kcnq1ot1 reactivated the silenced allele with little or no loss of DNA methylation. Hybrid brains also display different patterns of imprinting perturbations. Several cluster pairs thought to use analogous regulatory mechanisms are differentially affected in the hybrids.These data reinforce the hypothesis that placental and somatic gene regulation differs significantly, as does that between imprinted gene clusters and between species. That such epigenetic regulatory variation exists in recently diverged species suggests a role in reproductive isolation, and that this variation is likely to be adaptive.

  2. High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia.

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    Baufeld, Caroline; Osterloh, Anja; Prokop, Stefan; Miller, Kelly R; Heppner, Frank L

    2016-09-01

    Diets high in fat (HFD) are known to cause an immune response in the periphery as well as the central nervous system. In peripheral adipose tissue, this immune response is primarily mediated by macrophages that are recruited to the tissue. Similarly, reactivity of microglia, the innate immune cells of the brain, has been shown to occur in the hypothalamus of mice fed a high-fat diet. To characterize the nature of the microglial response to diets high in fat in a temporal fashion, we studied the phenotypic spectrum of hypothalamic microglia of mice fed high-fat diet for 3 days and 8 weeks by assessing their tissue reaction and inflammatory signature. While we observed a significant increase in Iba1+ myeloid cells and a reaction of GFAP+ astrocytes in the hypothalamus after 8 weeks of HFD feeding, we found the hypothalamic myeloid cell reaction to be limited to endogenous microglia and not mediated by infiltrating myeloid cells. Moreover, obese humans were found to present with signs of hypothalamic gliosis and exacerbated microglia dystrophy, suggesting a targeted microglia response to diet in humans as well. Notably, the glial reaction occurring in the mouse hypothalamus was not accompanied by an increase in pro-inflammatory cytokines, but rather by an anti-inflammatory reaction. Gene expression analyses of isolated microglia not only confirmed this observation, but also revealed a downregulation of microglia genes important for sensing signals in the microenvironment. Finally, we demonstrate that long-term exposure of microglia to HFD in vivo does not impair the cell's ability to respond to additional stimuli, like lipopolysaccharide. Taken together, our findings support the notion that microglia react to diets high in fat in a region-specific manner in rodents as well as in humans; however, this response changes over time as it is not exclusively pro-inflammatory nor does exposure to HFD prime microglia in the hypothalamus.

  3. Diversity and structure of soil bacterial communities in the Fildes Region (maritime Antarctica as revealed by 454 pyrosequencing

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    Neng Fei eWang

    2015-10-01

    Full Text Available This study assessed the diversity and composition of bacterial communities in four different soils (human-, penguin-, seal-colony impacted soils and pristine soil in the Fildes Region (King George Island, Antarctica using 454 pyrosequencing with bacterial-specific primers targeting the 16S rRNA gene. Proteobacteria, Actinobacteria, Acidobacteria, and Verrucomicrobia were abundant phyla in almost all the soil samples. The four types of soils were significantly different in geochemical properties and bacterial community structure. Thermotogae, Cyanobacteria, Fibrobacteres, Deinococcus-Thermus, and Chlorobi obviously varied in their abundance among the 4 soil types. Considering all the samples together, members of the genera Gaiella, Chloracidobacterium, Nitrospira, Polaromonas, Gemmatimonas, Sphingomonas and Chthoniobacter were found to predominate, whereas members of the genera Chamaesiphon, Herbaspirillum, Hirschia, Nevskia, Nitrosococcus, Rhodococcus, Rhodomicrobium, and Xanthomonas varied obviously in their abundance among the four soil types. Distance-based redundancy analysis revealed that pH (p < 0.01, phosphate phosphorus (p < 0.01, organic carbon (p < 0.05, and organic nitrogen (p < 0.05 were the most significant factors that correlated with the community distribution of soil bacteria. To our knowledge, this is the first study to explore the soil bacterial communities in human-, penguin-, and seal- colony impacted soils from ice-free areas in maritime Antarctica using high-throughput pyrosequencing.

  4. Spatio-temporal dynamics of ocean conditions and forage taxa reveal regional structuring of seabird–prey relationships.

    Science.gov (United States)

    Santora, Jarrod A; Schroeder, Isaac D; Field, John C; Wells, Brian K; Sydeman, William J

    Studies of predator–prey demographic responses and the physical drivers of such relationships are rare, yet essential for predicting future changes in the structure and dynamics of marine ecosystems. Here, we hypothesize that predator–prey relationships vary spatially in association with underlying physical ocean conditions, leading to observable changes in demographic rates, such as reproduction. To test this hypothesis, we quantified spatio-temporal variability in hydrographic conditions, krill, and forage fish to model predator (seabird) demographic responses over 18 years (1990–2007). We used principal component analysis and spatial correlation maps to assess coherence among ocean conditions, krill, and forage fish, and generalized additive models to quantify interannual variability in seabird breeding success relative to prey abundance. The first principal component of four hydrographic measurements yielded an index that partitioned “warm/weak upwelling” and “cool/strong upwelling” years. Partitioning of krill and forage fish time series among shelf and oceanic regions yielded spatially explicit indicators of prey availability. Krill abundance within the oceanic region was remarkably consistent between years, whereas krill over the shelf showed marked interannual fluctuations in relation to ocean conditions. Anchovy abundance varied on the shelf, and was greater in years of strong stratification, weak upwelling and warmer temperatures. Spatio-temporal variability of juvenile forage fish co-varied strongly with each other and with krill, but was weakly correlated with hydrographic conditions. Demographic responses between seabirds and prey availability revealed spatially variable associations indicative of the dynamic nature of “predator–habitat” relationships. Quantification of spatially explicit demographic responses, and their variability through time, demonstrate the possibility of delineating specific critical areas where the

  5. Standardized orthotopic xenografts in zebrafish reveal glioma cell-line-specific characteristics and tumor cell heterogeneity

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    Alessandra M. Welker

    2016-02-01

    Full Text Available Glioblastoma (GBM is a deadly brain cancer, for which few effective drug treatments are available. Several studies have used zebrafish models to study GBM, but a standardized approach to modeling GBM in zebrafish was lacking to date, preventing comparison of data across studies. Here, we describe a new, standardized orthotopic xenotransplant model of GBM in zebrafish. Dose-response survival assays were used to define the optimal number of cells for tumor formation. Techniques to measure tumor burden and cell spread within the brain over real time were optimized using mouse neural stem cells as control transplants. Applying this standardized approach, we transplanted two patient-derived GBM cell lines, serum-grown adherent cells and neurospheres, into the midbrain region of embryonic zebrafish and analyzed transplanted larvae over time. Progressive brain tumor growth and premature larval death were observed using both cell lines; however, fewer transplanted neurosphere cells were needed for tumor growth and lethality. Tumors were heterogeneous, containing both cells expressing stem cell markers and cells expressing markers of differentiation. A small proportion of transplanted neurosphere cells expressed glial fibrillary acidic protein (GFAP or vimentin, markers of more differentiated cells, but this number increased significantly during tumor growth, indicating that these cells undergo differentiation in vivo. By contrast, most serum-grown adherent cells expressed GFAP and vimentin at the earliest times examined post-transplant. Both cell types produced brain tumors that contained Sox2+ cells, indicative of tumor stem cells. Transplanted larvae were treated with currently used GBM therapeutics, temozolomide or bortezomib, and this resulted in a reduction in tumor volume in vivo and an increase in survival. The standardized model reported here facilitates robust and reproducible analysis of glioblastoma tumor cells in real time and provides a

  6. DNA methylation profiling reveals the presence of population-specific signatures correlating with phenotypic characteristics.

    Science.gov (United States)

    Giri, Anil K; Bharadwaj, Soham; Banerjee, Priyanka; Chakraborty, Shraddha; Parekatt, Vaisak; Rajashekar, Donaka; Tomar, Abhishek; Ravindran, Aarthi; Basu, Analabha; Tandon, Nikhil; Bharadwaj, Dwaipayan

    2017-06-01

    Phenotypic characteristics are known to vary substantially among different ethnicities around the globe. These variations are mediated by number of stochastic events and cannot be attributed to genetic architecture alone. DNA methylation is a well-established mechanism that sculpts our epigenome influencing phenotypic variation including disease manifestation. Since DNA methylation is an important determinant for health issues of a population, it demands a thorough investigation of the natural differences in genome wide DNA methylation patterns across different ethnic groups. This study is based on comparative analyses of methylome from five different ethnicities with major focus on Indian subjects. The current study uses hierarchical clustering approaches, principal component analysis and locus specific differential methylation analysis on Illumina 450K methylation data to compare methylome of different ethnic subjects. Our data indicates that the variations in DNA methylation patterns of Indians are less among themselves compared to other global population. It empirically correlated with dietary, cultural and demographical divergences across different ethnic groups. Our work further suggests that Indians included in this study, despite their genetic similarity with the Caucasian population, are in close proximity with Japanese in terms of their methylation signatures.

  7. Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates.

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    Jean-Luc Picq

    Full Text Available The mouse lemur (Microcebus murinus is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12 and aged (n = 8 adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination.

  8. RNAi Reveals Phase-Specific Global Regulators of Human Somatic Cell Reprogramming

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    Cheng-Xu Delon Toh

    2016-06-01

    Full Text Available Incomplete knowledge of the mechanisms at work continues to hamper efforts to maximize reprogramming efficiency. Here, we present a systematic genome-wide RNAi screen to determine the global regulators during the early stages of human reprogramming. Our screen identifies functional repressors and effectors that act to impede or promote the reprogramming process. Repressors and effectors form close interacting networks in pathways, including RNA processing, G protein signaling, protein ubiquitination, and chromatin modification. Combinatorial knockdown of five repressors (SMAD3, ZMYM2, SFRS11, SAE1, and ESET synergistically resulted in ∼85% TRA-1-60-positive cells. Removal of the novel splicing factor SFRS11 during reprogramming is accompanied by rapid acquisition of pluripotency-specific spliced forms. Mechanistically, SFRS11 regulates exon skipping and mutually exclusive splicing of transcripts in genes involved in cell differentiation, mRNA splicing, and chromatin modification. Our study provides insights into the reprogramming process, which comprises comprehensive and multi-layered transcriptional, splicing, and epigenetic machineries.

  9. Screening of recombinant glycosyltransferases reveals the broad acceptor specificity of stevia UGT-76G1.

    Science.gov (United States)

    Dewitte, Griet; Walmagh, Maarten; Diricks, Margo; Lepak, Alexander; Gutmann, Alexander; Nidetzky, Bernd; Desmet, Tom

    2016-09-10

    UDP-glycosyltransferases (UGTs) are a promising class of biocatalysts that offer a sustainable alternative for chemical glycosylation of natural products. In this study, we aimed to characterize plant-derived UGTs from the GT-1 family with an emphasis on their acceptor promiscuity and their potential application in glycosylation processes. Recombinant expression in E. coli provided sufficient amounts of enzyme for the in-depth characterization of the salicylic acid UGT from Capsella rubella (UGT-SACr) and the stevia UGT from Stevia rebaudiana (UGT-76G1Sr). The latter was found to have a remarkably broad specificity with activities on a wide diversity of structures, from aliphatic and branched alcohols, over small phenolics to larger flavonoids, terpenoids and even higher glycoside compounds. As an example for its industrial potential, the glycosylation of curcumin was thoroughly evaluated. Under optimized conditions, 96% of curcumin was converted within 24h into the corresponding curcumin β-glycosides. In addition, the reaction was performed in a coupled system with sucrose synthase from Glycine max, to enable the cost-efficient (re)generation of UDP-Glc from sucrose as abundant and renewable resource. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Specific neural traces for intonational discourse categories as revealed by human-evoked potentials.

    Science.gov (United States)

    Borràs-Comes, Joan; Costa-Faidella, Jordi; Prieto, Pilar; Escera, Carles

    2012-04-01

    The neural representation of segmental and tonal phonological distinctions has been shown by means of the MMN ERP, yet this is not the case for intonational discourse contrasts. In Catalan, a rising-falling intonational sequence can be perceived as a statement or as a counterexpectational question, depending exclusively on the size of the pitch range interval of the rising movement. We tested here, using the MMN, whether such categorical distinctions elicited distinct neurophysiological patterns of activity, supporting their specific neural representation. From a behavioral identification experiment, we set the boundary between the two categories and defined four stimuli across the continuum. Although the physical distance between each pair of stimuli was kept constant, the central pair represented an across-category contrast, whereas the other pairs represented within-category contrasts. These four auditory stimuli were contrasted by pairs in three different oddball blocks. The mean amplitude of the MMN was larger for the across-category contrast, suggesting that intonational contrasts in the target language can be encoded automatically in the auditory cortex. These results are in line with recent findings in other fields of linguistics, showing that, when a boundary between categories is crossed, the MMN response is not just larger but rather includes a separate subcomponent.

  11. Diverse Requirements for Microglial Survival, Specification, and Function Revealed by Defined-Medium Cultures.

    Science.gov (United States)

    Bohlen, Christopher J; Bennett, F Chris; Tucker, Andrew F; Collins, Hannah Y; Mulinyawe, Sara B; Barres, Ben A

    2017-05-17

    Microglia, the resident macrophages of the CNS, engage in various CNS-specific functions that are critical for development and health. To better study microglia and the properties that distinguish them from other tissue macrophage populations, we have optimized serum-free culture conditions to permit robust survival of highly ramified adult microglia under defined-medium conditions. We find that astrocyte-derived factors prevent microglial death ex vivo and that this activity results from three primary components, CSF-1/IL-34, TGF-β2, and cholesterol. Using microglial cultures that have never been exposed to serum, we demonstrate a dramatic and lasting change in phagocytic capacity after serum exposure. Finally, we find that mature microglia rapidly lose signature gene expression after isolation, and that this loss can be reversed by engrafting cells back into an intact CNS environment. These data indicate that the specialized gene expression profile of mature microglia requires continuous instructive signaling from the intact CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Comparative proteome analysis reveals pathogen specific outer membrane proteins of Leptospira.

    Science.gov (United States)

    Dhandapani, Gunasekaran; Sikha, Thoduvayil; Rana, Aarti; Brahma, Rahul; Akhter, Yusuf; Gopalakrishnan Madanan, Madathiparambil

    2018-04-10

    Proteomes of pathogenic Leptospira interrogans and L. borgpetersenii and the saprophytic L. biflexa were filtered through computational tools to identify Outer Membrane Proteins (OMPs) that satisfy the required biophysical parameters for their presence on the outer membrane. A total of 133, 130, and 144 OMPs were identified in L. interrogans, L. borgpetersenii, and L. biflexa, respectively, which forms approximately 4% of proteomes. A holistic analysis of transporting and pathogenic characteristics of OMPs together with Clusters of Orthologous Groups (COGs) among the OMPs and their distribution across 3 species was made and put forward a set of 21 candidate OMPs specific to pathogenic leptospires. It is also found that proteins homologous to the candidate OMPs were also present in other pathogenic species of leptospires. Six OMPs from L. interrogans and 2 from L. borgpetersenii observed to have similar COGs while those were not found in any intermediate or saprophytic forms. These OMPs appears to have role in infection and pathogenesis and useful for anti-leptospiral strategies. © 2018 Wiley Periodicals, Inc.

  13. Colony-specific investigations reveal highly variable responses among individual corals to ocean acidification and warming.

    Science.gov (United States)

    Kavousi, Javid; Reimer, James Davis; Tanaka, Yasuaki; Nakamura, Takashi

    2015-08-01

    As anthropogenic climate change is an ongoing concern, scientific investigations on its impacts on coral reefs are increasing. Although impacts of combined ocean acidification (OA) and temperature stress (T) on reef-building scleractinian corals have been studied at the genus, species and population levels, there are little data available on how individual corals respond to combined OA and anomalous temperatures. In this study, we exposed individual colonies of Acropora digitifera, Montipora digitata and Porites cylindrica to four pCO2-temperature treatments including 400 μatm-28 °C, 400 μatm-31 °C, 1000 μatm-28 °C and 1000 μatm-31 °C for 26 days. Physiological parameters including calcification, protein content, maximum photosynthetic efficiency, Symbiodinium density, and chlorophyll content along with Symbiodinium type of each colony were examined. Along with intercolonial responses, responses of individual colonies versus pooled data to the treatments were investigated. The main results were: 1) responses to either OA or T or their combination were different between individual colonies when considering physiological functions; 2) tolerance to either OA or T was not synonymous with tolerance to the other parameter; 3) tolerance to both OA and T did not necessarily lead to tolerance of OA and T combined (OAT) at the same time; 4) OAT had negative, positive or no impacts on physiological functions of coral colonies; and 5) pooled data were not representative of responses of all individual colonies. Indeed, the pooled data obscured actual responses of individual colonies or presented a response that was not observed in any individual. From the results of this study we recommend improving experimental designs of studies investigating physiological responses of corals to climate change by complementing them with colony-specific examinations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Characterisation of monotreme caseins reveals lineage-specific expansion of an ancestral casein locus in mammals.

    Science.gov (United States)

    Lefèvre, Christophe M; Sharp, Julie A; Nicholas, Kevin R

    2009-01-01

    Using a milk-cell cDNA sequencing approach we characterised milk-protein sequences from two monotreme species, platypus (Ornithorhynchus anatinus) and echidna (Tachyglossus aculeatus) and found a full set of caseins and casein variants. The genomic organisation of the platypus casein locus is compared with other mammalian genomes, including the marsupial opossum and several eutherians. Physical linkage of casein genes has been seen in the casein loci of all mammalian genomes examined and we confirm that this is also observed in platypus. However, we show that a recent duplication of beta-casein occurred in the monotreme lineage, as opposed to more ancient duplications of alpha-casein in the eutherian lineage, while marsupials possess only single copies of alpha- and beta-caseins. Despite this variability, the close proximity of the main alpha- and beta-casein genes in an inverted tail-tail orientation and the relative orientation of the more distant kappa-casein genes are similar in all mammalian genome sequences so far available. Overall, the conservation of the genomic organisation of the caseins indicates the early, pre-monotreme development of the fundamental role of caseins during lactation. In contrast, the lineage-specific gene duplications that have occurred within the casein locus of monotremes and eutherians but not marsupials, which may have lost part of the ancestral casein locus, emphasises the independent selection on milk provision strategies to the young, most likely linked to different developmental strategies. The monotremes therefore provide insight into the ancestral drivers for lactation and how these have adapted in different lineages.

  15. Lineage-specific evolution of the vertebrate Otopetrin gene family revealed by comparative genomic analyses

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    Ryan Joseph F

    2011-01-01

    Full Text Available Abstract Background Mutations in the Otopetrin 1 gene (Otop1 in mice and fish produce an unusual bilateral vestibular pathology that involves the absence of otoconia without hearing impairment. The encoded protein, Otop1, is the only functionally characterized member of the Otopetrin Domain Protein (ODP family; the extended sequence and structural preservation of ODP proteins in metazoans suggest a conserved functional role. Here, we use the tools of sequence- and cytogenetic-based comparative genomics to study the Otop1 and the Otop2-Otop3 genes and to establish their genomic context in 25 vertebrates. We extend our evolutionary study to include the gene mutated in Usher syndrome (USH subtype 1G (Ush1g, both because of the head-to-tail clustering of Ush1g with Otop2 and because Otop1 and Ush1g mutations result in inner ear phenotypes. Results We established that OTOP1 is the boundary gene of an inversion polymorphism on human chromosome 4p16 that originated in the common human-chimpanzee lineage more than 6 million years ago. Other lineage-specific evolutionary events included a three-fold expansion of the Otop genes in Xenopus tropicalis and of Ush1g in teleostei fish. The tight physical linkage between Otop2 and Ush1g is conserved in all vertebrates. To further understand the functional organization of the Ushg1-Otop2 locus, we deduced a putative map of binding sites for CCCTC-binding factor (CTCF, a mammalian insulator transcription factor, from genome-wide chromatin immunoprecipitation-sequencing (ChIP-seq data in mouse and human embryonic stem (ES cells combined with detection of CTCF-binding motifs. Conclusions The results presented here clarify the evolutionary history of the vertebrate Otop and Ush1g families, and establish a framework for studying the possible interaction(s of Ush1g and Otop in developmental pathways.

  16. Comparing the Healthy Nose and Nasopharynx Microbiota Reveals Continuity As Well As Niche-Specificity

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    Ilke De Boeck

    2017-11-01

    Full Text Available To improve our understanding of upper respiratory tract (URT diseases and the underlying microbial pathogenesis, a better characterization of the healthy URT microbiome is crucial. In this first large-scale study, we obtained more insight in the URT microbiome of healthy adults. Hereto, we collected paired nasal and nasopharyngeal swabs from 100 healthy participants in a citizen-science project. High-throughput 16S rRNA gene V4 amplicon sequencing was performed and samples were processed using the Divisive Amplicon Denoising Algorithm 2 (DADA2 algorithm. This allowed us to identify the bacterial richness and diversity of the samples in terms of amplicon sequence variants (ASVs, with special attention to intragenus variation. We found both niches to have a low overall species richness and uneven distribution. Moreover, based on hierarchical clustering, nasopharyngeal samples could be grouped into some bacterial community types at genus level, of which four were supported to some extent by prediction strength evaluation: one intermixed type with a higher bacterial diversity where Staphylococcus, Corynebacterium, and Dolosigranulum appeared main bacterial members in different relative abundances, and three types dominated by either Moraxella, Streptococcus, or Fusobacterium. Some of these bacterial community types such as Streptococcus and Fusobacterium were nasopharynx-specific and never occurred in the nose. No clear association between the nasopharyngeal bacterial profiles at genus level and the variables age, gender, blood type, season of sampling, or common respiratory allergies was found in this study population, except for smoking showing a positive association with Corynebacterium and Staphylococcus. Based on the fine-scale resolution of the ASVs, both known commensal and potential pathogenic bacteria were found within several genera – particularly in Streptococcus and Moraxella – in our healthy study population. Of interest, the

  17. Comparative analysis of chromatin landscape in regulatory regions of human housekeeping and tissue specific genes

    Directory of Open Access Journals (Sweden)

    Dasgupta Dipayan

    2005-05-01

    Full Text Available Abstract Background Global regulatory mechanisms involving chromatin assembly and remodelling in the promoter regions of genes is implicated in eukaryotic transcription control especially for genes subjected to spatial and temporal regulation. The potential to utilise global regulatory mechanisms for controlling gene expression might depend upon the architecture of the chromatin in and around the gene. In-silico analysis can yield important insights into this aspect, facilitating comparison of two or more classes of genes comprising of a large number of genes within each group. Results In the present study, we carried out a comparative analysis of chromatin characteristics in terms of the scaffold/matrix attachment regions, nucleosome formation potential and the occurrence of repetitive sequences, in the upstream regulatory regions of housekeeping and tissue specific genes. Our data show that putative scaffold/matrix attachment regions are more abundant and nucleosome formation potential is higher in the 5' regions of tissue specific genes as compared to the housekeeping genes. Conclusion The differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression. The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression. This could partially explain the lower number of genes estimated in the human genome.

  18. Database specification for the Worldwide Port System (WPS) Regional Integrated Cargo Database (ICDB)

    Energy Technology Data Exchange (ETDEWEB)

    Faby, E.Z.; Fluker, J.; Hancock, B.R.; Grubb, J.W.; Russell, D.L. [Univ. of Tennessee, Knoxville, TN (United States); Loftis, J.P.; Shipe, P.C.; Truett, L.F. [Oak Ridge National Lab., TN (United States)

    1994-03-01

    This Database Specification for the Worldwide Port System (WPS) Regional Integrated Cargo Database (ICDB) describes the database organization and storage allocation, provides the detailed data model of the logical and physical designs, and provides information for the construction of parts of the database such as tables, data elements, and associated dictionaries and diagrams.

  19. Region-specific adaptations in determinants of rat skeletal muscle oxygenation to chronic hypoxia.

    NARCIS (Netherlands)

    Wust, R.C.; Jaspers, R.T.; Heyst, A.F.J. van; Hopman, M.T.E.; Hoofd, L.J.C.; Laarse, W.J. van der; Degens, H.

    2009-01-01

    Chronic exposure to hypoxia is associated with muscle atrophy (i.e., a reduction in muscle fiber cross-sectional area), reduced oxidative capacity, and capillary growth. It is controversial whether these changes are muscle and fiber type specific. We hypothesized that different regions of the same

  20. Proof of region-specific multipotent progenitors in human breast epithelia

    DEFF Research Database (Denmark)

    Fridriksdottir, Agla J; Villadsen, René; Morsing, Mikkel

    2017-01-01

    in luminal progenitors to interrogate the differentiation repertoire of candidate stem cells in TDLUs. We show that stem-like activity in serial passage culture and in vivo breast morphogenesis relies on the preservation of a myoepithelial phenotype. By enrichment for region-specific progenitors, we identify...

  1. Alternative supply specifications and estimates of regional supply and demand for stumpage.

    Science.gov (United States)

    Kent P. Connaughton; David H. Jackson; Gerard A. Majerus

    1988-01-01

    Four plausible sets of stumpage supply and demand equations were developed and estimated; the demand equation was the same for each set, although the supply equation differed. The supply specifications varied from the model of regional excess demand in which National Forest harvest levels were assumed fixed to a more realistic model in which the harvest on the National...

  2. Sequencing analysis reveals a unique gene organization in the gyrB region of Mycoplasma hominis

    DEFF Research Database (Denmark)

    Ladefoged, Søren; Christiansen, Gunna

    1994-01-01

    of which showed similarity to that which encodes the LicA protein of Haemophilus influenzae. The organization of the genes in the region showed no resemblance to that in the corresponding regions of other bacteria sequenced so far. The gyrA gene was mapped 35 kb downstream from the gyrB gene.......The homolog of the gyrB gene, which has been reported to be present in the vicinity of the initiation site of replication in bacteria, was mapped on the Mycoplasma hominis genome, and the region was subsequently sequenced. Five open reading frames were identified flanking the gyrB gene, one...

  3. Specificity of high-rise construction and real estate markets in the regional economy: an analysis of Russian practice (example of St. Petersburg)

    Science.gov (United States)

    Vilken, Viktoriya; Kalinina, Olga; Dubgorn, Alissa

    2018-03-01

    In paper features of the regional markets of construction the commercial and residential real estate on the example of St. Petersburg are defined. The current situation is analysed, the specific features of branch are revealed. The major factors influencing investors making decisions on construction of various types of objects are defined. The main methods of advance of real estate objects are considered.

  4. Restriction of neural precursor ability to respond to Nurr1 by early regional specification.

    Directory of Open Access Journals (Sweden)

    Chiara Soldati

    Full Text Available During neural development, spatially regulated expression of specific transcription factors is crucial for central nervous system (CNS regionalization, generation of neural precursors (NPs and subsequent differentiation of specific cell types within defined regions. A critical role in dopaminergic differentiation in the midbrain (MB has been assigned to the transcription factor Nurr1. Nurr1 controls the expression of key genes involved in dopamine (DA neurotransmission, e.g. tyrosine hydroxylase (TH and the DA transporter (DAT, and promotes the dopaminergic phenotype in embryonic stem cells. We investigated whether cells derived from different areas of the mouse CNS could be directed to differentiate into dopaminergic neurons in vitro by forced expression of the transcription factor Nurr1. We show that Nurr1 overexpression can promote dopaminergic cell fate specification only in NPs obtained from E13.5 ganglionic eminence (GE and MB, but not in NPs isolated from E13.5 cortex (CTX and spinal cord (SC or from the adult subventricular zone (SVZ. Confirming previous studies, we also show that Nurr1 overexpression can increase the generation of TH-positive neurons in mouse embryonic stem cells. These data show that Nurr1 ability to induce a dopaminergic phenotype becomes restricted during CNS development and is critically dependent on the region of NPs derivation. Our results suggest that the plasticity of NPs and their ability to activate a dopaminergic differentiation program in response to Nurr1 is regulated during early stages of neurogenesis, possibly through mechanisms controlling CNS regionalization.

  5. Differential requirements for Gli2 and Gli3 in the regional specification of the mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    Roberta eHaddad-Tóvolli

    2015-03-01

    Full Text Available Secreted protein Sonic hedgehog (Shh ventralizes the neural tube by modulating the crucial balance between activating and repressing functions (GliA, GliR of transcription factors Gli2 and Gli3. This balance—the Shh-Gli code—is species- and context-dependent and has been elucidated for the mouse spinal cord. The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation. Here we asked if particular combinations of Gli2 and Gli3 and of GliA and GliR functions contribute to the variety of hypothalamic regions, i.e. we wanted to clarify the hypothalamic version of the Shh-Gli code. Based on mouse mutant analysis, we show that: 1 hypothalamic regional heterogeneity is based in part on differentially stringent requirements for Gli2 or Gli3; 2 another source of diversity are differential requirements for Shh of neural vs non-neural origin; 3 Gli2 is indispensable for the specification of a medial progenitor domain generating several essential hypothalamic nuclei plus the pituitary and median eminence; 4 the suppression of Gli3R by neural and non-neural Shh is essential for hypothalamic specification. Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions. Our data confirm the model and are explained by it.

  6. Structural diversity and evolution of the N-terminal isoform-specific region of ecdysone receptor-A and -B1 isoforms in insects

    Directory of Open Access Journals (Sweden)

    Kubo Takeo

    2010-02-01

    Full Text Available Abstract Background The ecdysone receptor (EcR regulates various cellular responses to ecdysteroids during insect development. Insects have multiple EcR isoforms with different N-terminal A/B domains that contain the isoform-specific activation function (AF-1 region. Although distinct physiologic functions of the EcR isoforms have been characterized in higher holometabolous insects, they remain unclear in basal direct-developing insects, in which only A isoform has been identified. To examine the structural basis of the EcR isoform-specific AF-1 regions, we performed a comprehensive structural comparison of the isoform-specific region of the EcR-A and -B1 isoforms in insects. Results The EcR isoforms were newly identified in 51 species of insects and non-insect arthropods, including direct-developing ametabolous and hemimetabolous insects. The comprehensive structural comparison revealed that the isoform-specific region of each EcR isoform contained evolutionally conserved microdomain structures and insect subgroup-specific structural modifications. The A isoform-specific region generally contained four conserved microdomains, including the SUMOylation motif and the nuclear localization signal, whereas the B1 isoform-specific region contained three conserved microdomains, including an acidic activator domain-like motif. In addition, the EcR-B1 isoform of holometabolous insects had a novel microdomain at the N-terminal end. Conclusions Given that the nuclear receptor AF-1 is involved in cofactor recruitment and transcriptional regulation, the microdomain structures identified in the isoform-specific A/B domains might function as signature motifs and/or as targets for cofactor proteins that play essential roles in the EcR isoform-specific AF-1 regions. Moreover, the novel microdomain in the isoform-specific region of the holometabolous insect EcR-B1 isoform suggests that the holometabolous insect EcR-B1 acquired additional transcriptional

  7. Region-specific protein misfolding cyclic amplification reproduces brain tropism of prion strains.

    Science.gov (United States)

    Privat, Nicolas; Levavasseur, Etienne; Yildirim, Serfildan; Hannaoui, Samia; Brandel, Jean-Philippe; Laplanche, Jean-Louis; Béringue, Vincent; Seilhean, Danielle; Haïk, Stéphane

    2017-10-06

    Human prion diseases such as Creutzfeldt-Jakob disease are transmissible brain proteinopathies, characterized by the accumulation of a misfolded isoform of the host cellular prion protein (PrP) in the brain. According to the prion model, prions are defined as proteinaceous infectious particles composed solely of this abnormal isoform of PrP (PrP Sc ). Even in the absence of genetic material, various prion strains can be propagated in experimental models. They can be distinguished by the pattern of disease they produce and especially by the localization of PrP Sc deposits within the brain and the spongiform lesions they induce. The mechanisms involved in this strain-specific targeting of distinct brain regions still are a fundamental, unresolved question in prion research. To address this question, we exploited a prion conversion in vitro assay, protein misfolding cyclic amplification (PMCA), by using experimental scrapie and human prion strains as seeds and specific brain regions from mice and humans as substrates. We show here that region-specific PMCA in part reproduces the specific brain targeting observed in experimental, acquired, and sporadic Creutzfeldt-Jakob diseases. Furthermore, we provide evidence that, in addition to cellular prion protein, other region- and species-specific molecular factors influence the strain-dependent prion conversion process. This important step toward understanding prion strain propagation in the human brain may impact research on the molecular factors involved in protein misfolding and the development of ultrasensitive methods for diagnosing prion disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Regional and site-specific absolute humidity data for use in tritium dose calculations

    International Nuclear Information System (INIS)

    Etnier, E.L.

    1980-01-01

    Due to the potential variability in average absolute humidity over the continental U.S., and the dependence of atmospheric 3 H specific activity on absolute humidity, availability of regional absolute humidity data is of value in estimating the radiological significance of 3 H releases. Most climatological data are in the form of relative humidity, which must be converted to absolute humidity for dose calculations. Absolute humidity was calculated for 218 points across the U.S., using the 1977 annual summary of U.S. Climatological Data, and is given in a table. Mean regional values are shown on a map. (author)

  9. AFLPs reveal genomic regions not detected by RFLPs: a case study in tomato

    NARCIS (Netherlands)

    Bonnema, G.; Berg, van den P.; Lindhout, P.

    2002-01-01

    A set of three tomato chromosome 7 introgression lines (ILs) containing overlapping segments of Lycopersicon pennellii DNA was screened with a set of 10 EcoRI–MseI and 10 PstI–MseI AFLP primer combinations. A large number of markers were identified that mapped to one of the four regions of

  10. Earthquake occurrence reveals magma ascent beneath volcanoes and seamounts in the Banda Region

    Czech Academy of Sciences Publication Activity Database

    Špičák, Aleš; Kuna, Václav; Vaněk, Jiří

    2013-01-01

    Roč. 75, č. 777 (2013), 777/1-777/8 ISSN 0258-8900 R&D Projects: GA MŠk ME09011 Institutional support: RVO:67985530 Keywords : Banda region * global seismological data * earthquake swarm Subject RIV: DC - Siesmology, Volcanology, Earth Structure Impact factor: 2.667, year: 2013

  11. Patterns of hypothalamic regionalization in amphibians and reptiles: common traits revealed by a genoarchitectonic approach

    Directory of Open Access Journals (Sweden)

    Laura eDominguez

    2015-02-01

    Full Text Available Most studies in mammals and birds have demonstrated common patterns of hypothalamic development highlighted by the combination of developmental regulatory genes (genoarchitecture, supporting the notion of the hypothalamus as a component of the secondary prosencephalon, topologically rostral to the diencephalon. In our comparative analysis we have summarized the data on the expression patterns of different transcription factors and neuroactive substances, used as anatomical markers, in the developing hypothalamus of the amphibian Xenopus laevis and the juvenile turtle Pseudemys scripta. This analysis served to highlight the organization of the hypothalamus in the anamniote/amniotic transition. We have identified supraoptoparaventricular and the suprachiasmatic regions in the alar part of the hypothalamus, and tuberal and mammillary regions in the basal hypothalamus. Shared features in the two species are: 1 The supraoptoparaventricular region is defined by the expression of Otp and the lack of Nkx2.1/Isl1. It is subdivided into rostral, rich in Otp and Nkx2.2, and caudal, only Otp-positive, portions. 2 The suprachiasmatic area contains catecholaminergic cell groups and lacks Otp, and can be further divided into rostral (rich in Nkx2.1 and Nkx2.2 and a caudal (rich in Isl1 and devoid of Nkx2.1 portions. 3 Expression of Nkx2.1 and Isl1 define the tuberal hypothalamus and only the rostral portion expresses Otp. 4 Its caudal boundary is evident by the lack of Isl1 in the adjacent mammillary region, which expresses Nkx2.1 and Otp. Differences in the anamnio-amniote transition were noted since in the turtle, like in other amniotes, the boundary between the alar hypothalamus and the telencephalic preoptic area shows distinct Nkx2.2 and Otp expressions but not in the amphibian (anamniote, and the alar supraoptoparaventricular region is defined by the expression of Otp/Pax6, whereas in Xenopus only Otp is expressed.

  12. Local-scale models reveal ecological niche variability in amphibian and reptile communities from two contrasting biogeographic regions

    Directory of Open Access Journals (Sweden)

    Alberto Muñoz

    2016-10-01

    Full Text Available Ecological Niche Models (ENMs are widely used to describe how environmental factors influence species distribution. Modelling at a local scale, compared to a large scale within a high environmental gradient, can improve our understanding of ecological species niches. The main goal of this study is to assess and compare the contribution of environmental variables to amphibian and reptile ENMs in two Spanish national parks located in contrasting biogeographic regions, i.e., the Mediterranean and the Atlantic area. The ENMs were built with maximum entropy modelling using 11 environmental variables in each territory. The contributions of these variables to the models were analysed and classified using various statistical procedures (Mann–Whitney U tests, Principal Components Analysis and General Linear Models. Distance to the hydrological network was consistently the most relevant variable for both parks and taxonomic classes. Topographic variables (i.e., slope and altitude were the second most predictive variables, followed by climatic variables. Differences in variable contribution were observed between parks and taxonomic classes. Variables related to water availability had the larger contribution to the models in the Mediterranean park, while topography variables were decisive in the Atlantic park. Specific response curves to environmental variables were in accordance with the biogeographic affinity of species (Mediterranean and non-Mediterranean species and taxonomy (amphibians and reptiles. Interestingly, these results were observed for species located in both parks, particularly those situated at their range limits. Our findings show that ecological niche models built at local scale reveal differences in habitat preferences within a wide environmental gradient. Therefore, modelling at local scales rather than assuming large-scale models could be preferable for the establishment of conservation strategies for herptile species in natural

  13. Local-scale models reveal ecological niche variability in amphibian and reptile communities from two contrasting biogeographic regions

    Science.gov (United States)

    Santos, Xavier; Felicísimo, Ángel M.

    2016-01-01

    Ecological Niche Models (ENMs) are widely used to describe how environmental factors influence species distribution. Modelling at a local scale, compared to a large scale within a high environmental gradient, can improve our understanding of ecological species niches. The main goal of this study is to assess and compare the contribution of environmental variables to amphibian and reptile ENMs in two Spanish national parks located in contrasting biogeographic regions, i.e., the Mediterranean and the Atlantic area. The ENMs were built with maximum entropy modelling using 11 environmental variables in each territory. The contributions of these variables to the models were analysed and classified using various statistical procedures (Mann–Whitney U tests, Principal Components Analysis and General Linear Models). Distance to the hydrological network was consistently the most relevant variable for both parks and taxonomic classes. Topographic variables (i.e., slope and altitude) were the second most predictive variables, followed by climatic variables. Differences in variable contribution were observed between parks and taxonomic classes. Variables related to water availability had the larger contribution to the models in the Mediterranean park, while topography variables were decisive in the Atlantic park. Specific response curves to environmental variables were in accordance with the biogeographic affinity of species (Mediterranean and non-Mediterranean species) and taxonomy (amphibians and reptiles). Interestingly, these results were observed for species located in both parks, particularly those situated at their range limits. Our findings show that ecological niche models built at local scale reveal differences in habitat preferences within a wide environmental gradient. Therefore, modelling at local scales rather than assuming large-scale models could be preferable for the establishment of conservation strategies for herptile species in natural parks. PMID

  14. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    International Nuclear Information System (INIS)

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona; Husain, Nuzhat; Srivastava, Savita; Rathore, Ram K.S.; Sarma, Manoj K.; Malik, Gyanendra K.; Das, Vinita; Pradhan, Mandakini; Pandey, Chandra M.; Narayana, Ponnada A.

    2009-01-01

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA ≤ 28 weeks for frontal cortical region and GA≤22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  15. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    Energy Technology Data Exchange (ETDEWEB)

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona [Sanjay Gandhi Post Graduate Institute of Medical Sciences, Department of Radiodiagnosis, Lucknow, UP (India); Husain, Nuzhat; Srivastava, Savita [CSM Medical University, Department of Pathology, Lucknow (India); Rathore, Ram K.S.; Sarma, Manoj K. [Indian Institute of Technology, Department of Mathematics and Statistics, Kanpur (India); Malik, Gyanendra K. [CSM Medical University, Department of Pediatrics, Lucknow (India); Das, Vinita [CSM Medical University, Department of Obstetrics and Gynecology, Lucknow (India); Pradhan, Mandakini [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Medical Genetics, Lucknow (India); Pandey, Chandra M. [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Biostatistics, Lucknow (India); Narayana, Ponnada A. [University of Texas Medical School at Houston, Department of Diagnostic and Interventional Imaging, Houston, TX (United States)

    2009-09-15

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA {<=} 28 weeks for frontal cortical region and GA{<=}22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  16. City-specific vehicle emission control strategies to achieve stringent emission reduction targets in China's Yangtze River Delta region.

    Science.gov (United States)

    Zhang, Shaojun; Wu, Ye; Zhao, Bin; Wu, Xiaomeng; Shu, Jiawei; Hao, Jiming

    2017-01-01

    The Yangtze River Delta (YRD) region is one of the most prosperous and densely populated regions in China and is facing tremendous pressure to mitigate vehicle emissions and improve air quality. Our assessment has revealed that mitigating vehicle emissions of NOx would be more difficult than reducing the emissions of other major vehicular pollutants (e.g., CO, HC and PM 2.5 ) in the YRD region. Even in Shanghai, where the emission control implemented are more stringent than in Jiangsu and Zhejiang, we observed little to no reduction in NOx emissions from 2000 to 2010. Emission-reduction targets for HC, NOx and PM 2.5 are determined using a response surface modeling tool for better air quality. We design city-specific emission control strategies for three vehicle-populated cities in the YRD region: Shanghai and Nanjing and Wuxi in Jiangsu. Our results indicate that even if stringent emission control consisting of the Euro 6/VI standards, the limitation of vehicle population and usage, and the scrappage of older vehicles is applied, Nanjing and Wuxi will not be able to meet the NOx emissions target by 2020. Therefore, additional control measures are proposed for Nanjing and Wuxi to further mitigate NOx emissions from heavy-duty diesel vehicles. Copyright © 2016. Published by Elsevier B.V.

  17. Region-specific study of the electric utility industry: problem identification, analysis, and recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Pochan, M.J.

    1985-07-01

    A number of problems were identified that could stand in the way of maintaining an adequate, reliable and economic supply of electric power for the United States in the future. The problems were analyzed by studying a specific region, VACAR (Virginia-Carolinas), in some detail. It was concluded that the future power supply is in jeopardy, but that drastic changes in the present system of investor-owned utilities, specifically, deregulation or government ownership, were not justified. It was recommended that the present electric system be modified and strengthened to meet future needs. 2 refs., 8 figs., 15 tabs.

  18. Region-specific study of the electric utility industry: problem identification, analysis, and recommendations

    International Nuclear Information System (INIS)

    Pochan, M.J.

    1985-07-01

    A number of problems were identified that could stand in the way of maintaining an adequate, reliable and economic supply of electric power for the United States in the future. The problems were analyzed by studying a specific region, VACAR (Virginia-Carolinas), in some detail. It was concluded that the future power supply is in jeopardy, but that drastic changes in the present system of investor-owned utilities, specifically, deregulation or government ownership, were not justified. It was recommended that the present electric system be modified and strengthened to meet future needs. 2 refs., 8 figs., 15 tabs

  19. Multi-species sequence comparison reveals dynamic evolution of the elastin gene that has involved purifying selection and lineage-specific insertions/deletions

    Directory of Open Access Journals (Sweden)

    Green Eric D

    2004-05-01

    Full Text Available Abstract Background The elastin gene (ELN is implicated as a factor in both supravalvular aortic stenosis (SVAS and Williams Beuren Syndrome (WBS, two diseases involving pronounced complications in mental or physical development. Although the complete spectrum of functional roles of the processed gene product remains to be established, these roles are inferred to be analogous in human and mouse. This view is supported by genomic sequence comparison, in which there are no large-scale differences in the ~1.8 Mb sequence block encompassing the common region deleted in WBS, with the exception of an overall reversed physical orientation between human and mouse. Results Conserved synteny around ELN does not translate to a high level of conservation in the gene itself. In fact, ELN orthologs in mammals show more sequence divergence than expected for a gene with a critical role in development. The pattern of divergence is non-conventional due to an unusually high ratio of gaps to substitutions. Specifically, multi-sequence alignments of eight mammalian sequences reveal numerous non-aligning regions caused by species-specific insertions and deletions, in spite of the fact that the vast majority of aligning sites appear to be conserved and undergoing purifying selection. Conclusions The pattern of lineage-specific, in-frame insertions/deletions in the coding exons of ELN orthologous genes is unusual and has led to unique features of the gene in each lineage. These differences may indicate that the gene has a slightly different functional mechanism in mammalian lineages, or that the corresponding regions are functionally inert. Identified regions that undergo purifying selection reflect a functional importance associated with evolutionary pressure to retain those features.

  20. Construction of physical maps for the sex-specific regions of papaya sex chromosomes

    Directory of Open Access Journals (Sweden)

    Na Jong-Kuk

    2012-05-01

    Full Text Available Abstract Background Papaya is a major fruit crop in tropical and subtropical regions worldwide. It is trioecious with three sex forms: male, female, and hermaphrodite. Sex determination is controlled by a pair of nascent sex chromosomes with two slightly different Y chromosomes, Y for male and Yh for hermaphrodite. The sex chromosome genotypes are XY (male, XYh (hermaphrodite, and XX (female. The papaya hermaphrodite-specific Yh chromosome region (HSY is pericentromeric and heterochromatic. Physical mapping of HSY and its X counterpart is essential for sequencing these regions and uncovering the early events of sex chromosome evolution and to identify the sex determination genes for crop improvement. Results A reiterate chromosome walking strategy was applied to construct the two physical maps with three bacterial artificial chromosome (BAC libraries. The HSY physical map consists of 68 overlapped BACs on the minimum tiling path, and covers all four HSY-specific Knobs. One gap remained in the region of Knob 1, the only knob structure shared between HSY and X, due to the lack of HSY-specific sequences. This gap was filled on the physical map of the HSY corresponding region in the X chromosome. The X physical map consists of 44 BACs on the minimum tiling path with one gap remaining in the middle, due to the nature of highly repetitive sequences. This gap was filled on the HSY physical map. The borders of the non-recombining HSY were defined genetically by fine mapping using 1460 F2 individuals. The genetically defined HSY spanned approximately 8.5 Mb, whereas its X counterpart extended about 5.4 Mb including a 900 Kb region containing the Knob 1 shared by the HSY and X. The 8.5 Mb HSY corresponds to 4.5 Mb of its X counterpart, showing 4 Mb (89% DNA sequence expansion. Conclusion The 89% increase of DNA sequence in HSY indicates rapid expansion of the Yh chromosome after genetic recombination was suppressed 2–3 million years ago. The

  1. Comment on "Satellites reveal contrasting responses of regional climate to the widespread greening of Earth".

    Science.gov (United States)

    Li, Yue; Zeng, Zhenzhong; Huang, Ling; Lian, Xu; Piao, Shilong

    2018-06-15

    Forzieri et al (Reports, 16 June 2017, p. 1180) used satellite data to show that boreal greening caused regional warming. We show that this positive sensitivity of temperature to the greening can be derived from the positive response of vegetation to boreal warming, which indicates that results from a statistical regression with satellite data should be carefully interpreted. Copyright © 2018, American Association for the Advancement of Science.

  2. Regional drivers of clutch loss reveal important trade-offs for beach-nesting birds.

    Science.gov (United States)

    Maslo, Brooke; Schlacher, Thomas A; Weston, Michael A; Huijbers, Chantal M; Anderson, Chris; Gilby, Ben L; Olds, Andrew D; Connolly, Rod M; Schoeman, David S

    2016-01-01

    Coastal birds are critical ecosystem constituents on sandy shores, yet are threatened by depressed reproductive success resulting from direct and indirect anthropogenic and natural pressures. Few studies examine clutch fate across the wide range of environments experienced by birds; instead, most focus at the small site scale. We examine survival of model shorebird clutches as an index of true clutch survival at a regional scale (∼200 km), encompassing a variety of geomorphologies, predator communities, and human use regimes in southeast Queensland, Australia. Of the 132 model nests deployed and monitored with cameras, 45 (34%) survived the experimental exposure period. Thirty-five (27%) were lost to flooding, 32 (24%) were depredated, nine (7%) buried by sand, seven (5%) destroyed by people, three (2%) failed by unknown causes, and one (1%) was destroyed by a dog. Clutch fate differed substantially among regions, particularly with respect to losses from flooding and predation. 'Topographic' exposure was the main driver of mortality of nests placed close to the drift line near the base of dunes, which were lost to waves (particularly during storms) and to a lesser extent depredation. Predators determined the fate of clutches not lost to waves, with the depredation probability largely influenced by region. Depredation probability declined as nests were backed by higher dunes and were placed closer to vegetation. This study emphasizes the scale at which clutch fate and survival varies within a regional context, the prominence of corvids as egg predators, the significant role of flooding as a source of nest loss, and the multiple trade-offs faced by beach-nesting birds and those that manage them.

  3. Regional drivers of clutch loss reveal important trade-offs for beach-nesting birds

    Directory of Open Access Journals (Sweden)

    Brooke Maslo

    2016-09-01

    Full Text Available Coastal birds are critical ecosystem constituents on sandy shores, yet are threatened by depressed reproductive success resulting from direct and indirect anthropogenic and natural pressures. Few studies examine clutch fate across the wide range of environments experienced by birds; instead, most focus at the small site scale. We examine survival of model shorebird clutches as an index of true clutch survival at a regional scale (∼200 km, encompassing a variety of geomorphologies, predator communities, and human use regimes in southeast Queensland, Australia. Of the 132 model nests deployed and monitored with cameras, 45 (34% survived the experimental exposure period. Thirty-five (27% were lost to flooding, 32 (24% were depredated, nine (7% buried by sand, seven (5% destroyed by people, three (2% failed by unknown causes, and one (1% was destroyed by a dog. Clutch fate differed substantially among regions, particularly with respect to losses from flooding and predation. ‘Topographic’ exposure was the main driver of mortality of nests placed close to the drift line near the base of dunes, which were lost to waves (particularly during storms and to a lesser extent depredation. Predators determined the fate of clutches not lost to waves, with the depredation probability largely influenced by region. Depredation probability declined as nests were backed by higher dunes and were placed closer to vegetation. This study emphasizes the scale at which clutch fate and survival varies within a regional context, the prominence of corvids as egg predators, the significant role of flooding as a source of nest loss, and the multiple trade-offs faced by beach-nesting birds and those that manage them.

  4. A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation

    Science.gov (United States)

    McGarvey, Alison C.; Souilhol, Céline; Rice, Ritva; Hills, David; Rice, David; Tomlinson, Simon R.

    2017-01-01

    In the developing embryo, hematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region, but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA sequencing over these spatiotemporal transitions in the AGM region and supportive OP9 cell line. Screening several proteins through an ex vivo reaggregate culture system, we identify BMPER as a novel positive regulator of HSC development. We demonstrate that BMPER is associated with BMP signaling inhibition, but is transcriptionally induced by BMP4, suggesting that BMPER contributes to the precise control of BMP activity within the AGM region, enabling the maturation of HSCs within a BMP-negative environment. These findings and the availability of our transcriptional data through an accessible interface should provide insight into the maintenance and potential derivation of HSCs in culture. PMID:29093060

  5. Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming.

    Directory of Open Access Journals (Sweden)

    Yiping Fan

    Full Text Available Neural stem/progenitor cells (NSC have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ of the adult brain. It is not known whether NSC can be found in all parts of the developing mid-trimester central nervous system (CNS when the brain undergoes massive transformation and growth. Multipotent NSC from the mid-trimester cerebra, thalamus, SVZ, hippocampus, thalamus, cerebellum, brain stem and spinal cord can be derived and propagated as clonal neurospheres with increasing frequencies with increasing gestations. These NSC can undergo multi-lineage differentiation both in vitro and in vivo, and engraft in a developmental murine model. Regionally-derived NSC are phenotypically distinct, with hippocampal NSC having a significantly higher neurogenic potential (53.6% over other sources (range of 0%-27.5%, p<0.004. Whole genome expression analysis showed differential gene expression between these regionally-derived NSC, which involved the Notch, epidermal growth factor as well as interleukin pathways. We have shown the presence of phenotypically-distinct regionally-derived NSC from the mid-trimester CNS, which may reflect the ontological differences occurring within the CNS. Aside from informing on the role of such cells during fetal growth, they may be useful for different cellular therapy applications.

  6. Environmental impact assessment: use of literature data versus use of specific local and regional data

    International Nuclear Information System (INIS)

    Rochedo, Elaine R.R.; Wasserman, Maria Angelica

    2000-01-01

    The environmental radiological impact assessment methodology includes a large number of parameters to simulate the environmental transfer and population exposure. Local and regional data are often not available, particularly for tropical regions, which leads to the use of literature data, mostly determined at temperate climate countries. Since 1993, IRD has been developing radioecological studies aiming the determination soil-plant transfer factors, which showed the possibility of finding values up to one order of magnitude higher than those found at temperate climate countries literature. This paper compares dose results for several scenarios, using regional and literature data, assessing the relevance of using site specific data for radiological impact assessments, for both practices and intervention situations. (author)

  7. Chemical probing of the human sirtuin 5 active site reveals its substrate acyl specificity and peptide-based inhibitors.

    Science.gov (United States)

    Roessler, Claudia; Nowak, Theresa; Pannek, Martin; Gertz, Melanie; Nguyen, Giang T T; Scharfe, Michael; Born, Ilona; Sippl, Wolfgang; Steegborn, Clemens; Schutkowski, Mike

    2014-09-26

    Sirtuins are NAD(+)-dependent deacetylases acting as sensors in metabolic pathways and stress response. In mammals there are seven isoforms. The mitochondrial sirtuin 5 is a weak deacetylase but a very efficient demalonylase and desuccinylase; however, its substrate acyl specificity has not been systematically analyzed. Herein, we investigated a carbamoyl phosphate synthetase 1 derived peptide substrate and modified the lysine side chain systematically to determine the acyl specificity of Sirt5. From that point we designed six potent peptide-based inhibitors that interact with the NAD(+) binding pocket. To characterize the interaction details causing the different substrate and inhibition properties we report several X-ray crystal structures of Sirt5 complexed with these peptides. Our results reveal the Sirt5 acyl selectivity and its molecular basis and enable the design of inhibitors for Sirt5. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Meteorite Source Regions as Revealed by the Near-Earth Object Population

    Science.gov (United States)

    Binzel, Richard P.; DeMeo, Francesca E.; Burt, Brian J.; Polishook, David; Burbine, Thomas H.; Bus, Schelte J.; Tokunaga, Alan; Birlan, Mirel

    2014-11-01

    Spectroscopic and taxonomic information is now available for 1000 near-Earth objects, having been obtained through both targeted surveys (e.g. [1], [2], [3]) or resulting from all-sky surveys (e.g. [4]). We determine their taxonomic types in the Bus-DeMeo system [5] [6] and subsequently examine meteorite correlations based on spectral analysis (e.g. [7],[8]). We correlate our spectral findings with the source region probabilities calculated using the methods of Bottke et al. [9]. In terms of taxonomy, very clear sources are indicated: Q-, Sq-, and S-types most strongly associated with ordinary chondrite meteorites show clear source signatures through the inner main-belt. V-types are relatively equally balanced between nu6 and 3:1 resonance sources, consistent with the orbital dispersion of the Vesta family. B- and C-types show distinct source region preferences for the outer belt and for Jupiter family comets. A Jupiter family comet source predominates for the D-type near-Earth objects, implying these "asteroidal" bodies may be extinct or dormant comets [10]. Similarly, near-Earth objects falling in the spectrally featureless "X-type" category also show a strong outer belt and Jupiter family comet source region preference. Finally the Xe-class near-Earth objects, which most closely match the spectral properties of enstatite achondrite (aubrite) meteorites seen in the Hungaria region[11], show a source region preference consistent with a Hungaria origin by entering near-Earth space through the Mars crossing and nu6 resonance pathways. This work supported by the National Science Foundation Grant 0907766 and NASA Grant NNX10AG27G.[1] Lazzarin, M. et al. (2004), Mem. S. A. It. Suppl. 5, 21. [2] Thomas, C. A. et al. (2014), Icarus 228, 217. [3] Tokunaga, A. et al. (2006) BAAS 38, 59.07. [4] Hasselmann, P. H., Carvano, J. M., Lazzaro, D. (2011) NASA PDS, EAR-A-I0035-5-SDSSTAX-V1.0. [5] Bus, S.J., Binzel, R.P. (2002). Icarus 158, 146. [6] DeMeo, F.E. et al. (2009), Icarus

  9. Radiation hybrids from human chromosome 3: A basis for the construction of region and specific sublibraries

    International Nuclear Information System (INIS)

    Atchison, L.; Cosmis, R.L.; Atchison, M.L.

    1990-01-01

    The authors are interested in identifying genes on human chromosome involved in disease processes. To date at least 20 different loci on this chromosome are implicated with various disease states. DNA libraries containing clones derived from a small chromosomal subregion implicated in a particular disease would greatly assist these studies. They have utilized the radiation hybrid (RH) technique to generate a series of somatic cell hybrids that contain small segments of human chromosome 3 as the only human genetic material. A Chinese hamster-human cell hybrid (Q314-2) containing only human chromosome 3 was used to prepare radiation hybrids. Cells were lethally X-irradiated with 6,000 rads and fused to Urd(??) Chinese hamster cells by PEG 1000 treatment. The majority of hybrids (>72%) analyzed retained portions of chromosome 3. The amount of chromosome 3 in each hybrid ranged from nearly all of the chromosome to very little. Currently these hybrids are being further characterized with single copy probes of known map location in order to isolate regions of chromosome 3 that contain specific disease locus. These reduced hybrids can then be used for the construction of region specific libraries and for the generation of new DNA probes from the specific region of interest

  10. Site-specific estimates of water yield applied in regional acid sensitivity surveys across western Canada

    Directory of Open Access Journals (Sweden)

    Patrick D. SHAW

    2010-08-01

    Full Text Available Runoff or water yield is an important input to the Steady-State Water Chemistry (SSWC model for estimating critical loads of acidity. Herein, we present site-specific water yield estimates for a large number of lakes (779 across three provinces of western Canada (Manitoba, Saskatchewan, and British Columbia using an isotope mass balance (IMB approach. We explore the impact of applying site-specific hydrology as compared to use of regional runoff estimates derived from gridded datasets in assessing critical loads of acidity to these lakes. In general, the average water yield derived from IMB is similar to the long-term average runoff; however, IMB results suggest a much larger range in hydrological settings of the lakes, attributed to spatial heterogeneity in watershed characteristics and landcover. The comparison of critical loads estimates from the two methods suggests that use of average regional runoff data in the SSWC model may overestimate critical loads for the majority of lakes due to systematic skewness in the actual runoff distributions. Implications for use of site-specific hydrology in regional critical loads assessments across western Canada are discussed.

  11. Specific metabolomics adaptations define a differential regional vulnerability in the adult human cerebral cortex

    Directory of Open Access Journals (Sweden)

    Rosanna Cabré

    2016-12-01

    Full Text Available Brain neurons offer diverse responses to stresses and detrimental factors during development and aging, and as a result of both neurodegenerative and neuropsychiatric disorders. This multiplicity of responses can be ascribed to the great diversity among neuronal populations. Here we have determined the metabolomic profile of three healthy adult human brain regions—entorhinal cortex, hippocampus, and frontal cortex—using mass spectrometry-based technologies. Our results show the existence of a lessened energy demand, mitochondrial stress, and lower one-carbon metabolism (particularly restricted to the methionine cycle specifically in frontal cortex. These findings, along with the better antioxidant capacity and lower mTOR signaling also seen in frontal cortex, suggest that this brain region is especially resistant to stress compared to the entorhinal cortex and hippocampus, which are more vulnerable regions. Globally, our results show the presence of specific metabolomics adaptations in three mature, healthy human brain regions, confirming the existence of cross-regional differences in cell vulnerability in the human cerebral cortex.

  12. Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.

    Science.gov (United States)

    Kumar, Vibhor; Rayan, Nirmala Arul; Muratani, Masafumi; Lim, Stefan; Elanggovan, Bavani; Xin, Lixia; Lu, Tess; Makhija, Harshyaa; Poschmann, Jeremie; Lufkin, Thomas; Ng, Huck Hui; Prabhakar, Shyam

    2016-05-01

    Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation. © 2016 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Factor analysis of regional brain activation in bipolar and healthy individuals reveals a consistent modular structure.

    Science.gov (United States)

    Fleck, David E; Welge, Jeffrey A; Eliassen, James C; Adler, Caleb M; DelBello, Melissa P; Strakowski, Stephen M

    2018-07-01

    The neurophysiological substrates of cognition and emotion, as seen with fMRI, are generally explained using modular structures. The present study was designed to probe the modular structure of cognitive-emotional processing in bipolar and healthy individuals using factor analysis and compare the results with current conceptions of the neurophysiology of bipolar disorder. Exploratory factor analysis was used to assess patterns of covariation among brain regions-of-interest activated during the Continuous Performance Task with Emotional and Neutral Distractors in healthy and bipolar individuals without a priori constraints on the number or composition of latent factors. Results indicated a common cognitive-emotional network consisting of prefrontal, medial temporal, limbic, parietal, anterior cingulate and posterior cingulate modules. However, reduced brain activation to emotional stimuli in the frontal, medial temporal and limbic modules was apparent in the bipolar relative to the healthy group, potentially accounting for emotional dysregulation in bipolar disorder. This study is limited by a relatively small sample size recruited at a single site. The results have yet to be validated on a larger independent sample. Although the modular structure of cognitive-emotional processing is similar in bipolar and healthy individuals, activation in response to emotional/neutral cues varies. These findings are not only consistent with recent conceptions of mood regulation in bipolar disorder, but also suggest that regional activation can be considered within tighter modular structures without compromising data interpretation. This demonstration may serve as a template for data reduction in future region-of-interest analyses to increase statistical power. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Automated identification of complementarity determining regions (CDRs) reveals peculiar characteristics of CDRs and B cell epitopes.

    Science.gov (United States)

    Ofran, Yanay; Schlessinger, Avner; Rost, Burkhard

    2008-11-01

    Exact identification of complementarity determining regions (CDRs) is crucial for understanding and manipulating antigenic interactions. One way to do this is by marking residues on the antibody that interact with B cell epitopes on the antigen. This, of course, requires identification of B cell epitopes, which could be done by marking residues on the antigen that bind to CDRs, thus requiring identification of CDRs. To circumvent this vicious circle, existing tools for identifying CDRs are based on sequence analysis or general biophysical principles. Often, these tools, which are based on partial data, fail to agree on the boundaries of the CDRs. Herein we present an automated procedure for identifying CDRs and B cell epitopes using consensus structural regions that interact with the antigens in all known antibody-protein complexes. Consequently, we provide the first comprehensive analysis of all CDR-epitope complexes of known three-dimensional structure. The CDRs we identify only partially overlap with the regions suggested by existing methods. We found that the general physicochemical properties of both CDRs and B cell epitopes are rather peculiar. In particular, only four amino acids account for most of the sequence of CDRs, and several types of amino acids almost never appear in them. The secondary structure content and the conservation of B cell epitopes are found to be different than previously thought. These characteristics of CDRs and epitopes may be instrumental in choosing which residues to mutate in experimental search for epitopes. They may also assist in computational design of antibodies and in predicting B cell epitopes.

  15. Regional passive seismic monitoring reveals dynamic glacier activity on Spitsbergen, Svalbard

    Directory of Open Access Journals (Sweden)

    Andreas Köhler

    2015-12-01

    Full Text Available Dynamic glacier activity is increasingly observed through passive seismic monitoring. We analysed near-regional-scale seismicity on the Arctic archipelago of Svalbard to identify seismic icequake signals and to study their spatial–temporal distribution within the 14-year period from 2000 until 2013. This is the first study that uses seismic data recorded on permanent broadband stations to detect and locate icequakes in different regions of Spitsbergen, the main island of the archipelago. A temporary local seismic network and direct observations of glacier calving and surging were used to identify icequake sources. We observed a high number of icequakes with clear spectral peaks between 1 and 8 Hz in different parts of Spitsbergen. Spatial clusters of icequakes could be associated with individual grounded tidewater glaciers and exhibited clear seasonal variability each year with more signals observed during the melt season. Locations at the termini of glaciers, and correlation with visual calving observations in situ at Kronebreen, a glacier in the Kongsfjorden region, show that these icequakes were caused dominantly by calving. Indirect evidence for glacier surging through increased calving seismicity was found in 2003 at Tunabreen, a glacier in central Spitsbergen. Another type of icequake was observed in the area of the Nathorstbreen glacier system. Seismic events occurred upstream of the glacier within a short time period between January and May 2009 during the initial phase of a major glacier surge. This study is the first step towards the generation and implementation of an operational seismic monitoring strategy for glacier dynamics in Svalbard.

  16. Crustal Structure and Deformation of the Sichuan-Yunnan Region Revealed by receiver Function Data

    Science.gov (United States)

    Zeng, S.; Zheng, Y.

    2017-12-01

    Sichuan-Yunnan and its surrounding areas locates in the southeast side to the Tibetan Plateau, due to the intrusion of the Indian Plate under the Tibetan Plateau, materials escape from the Tibetan Plateau and flow southward to southeastward. Because of such tectonic environment, the Sichuan-Yunnan region is experiencing high tectonic movement, and is capable of highly diffused seismicity. Based on dynamic simulation and field survey investigations, tectonic and geological studies proposed a decoupling model in this region and lower crustal flow may inflate in the crust. However, this idea needs more evidences, especially anisotropic structures to support it, since the anisotropic structures are usually directly related to the movement of materials, or to the tectonic distributions. In the past several years, a number of works have been done on the anisotropic structures in the Tibetan Plateau and its surroundings. In usually, previous studies were mainly carried out by two kinds of methods. First, the shear wave splitting of SKS, which mainly reflects the accumulation effect of the anisotropy of the crust to the mantle; the other way is use surface wave to investigate the anisotropic features at different azimuths and depths. In the recent years, receiver function is used to determine the inclination and anisotropy of the subsurface structure, comparing with the other two methods, receiver functions can provide higher resolution and reliable anisotropic features in the crust. Following the method of Liu and Niu(2012), we collected teleseismic data from the Himalayan first term network, and picked out high quality data based on the waveform SNR ratio, as well as the azimuthal distributions. Comparing with previous work (e.g., Sun et al.,2012), our work can provide more receiver functions results with higher reliability. We find that the crust beneath the Sichuan-Yunnan region has a thickness of 30-60 km and Vp/Vs ratio of 1.70-1.80. The Moho depth from northwest to

  17. Central nervous system PET-CT imaging reveals regional impairments in pediatric patients with Wolfram syndrome.

    Directory of Open Access Journals (Sweden)

    Agnieszka Zmyslowska

    Full Text Available Wolfram syndrome (WFS is inherited as an autosomal recessive disease with main clinical features of diabetes mellitus, optic atrophy, diabetes insipidus and deafness. However, various neurological defects may also be detected. The aim of this study was to evaluate aspects of brain structure and function using PET-CT (positron emission tomography and computed tomography and MRI (magnetic resonance imaging in pediatric patients with WFS. Regional changes in brain glucose metabolism were measured using standardized uptake values (SUVs based on images of (18F fluorodeoxyglucose (FDG uptake in 7 WFS patients aged 10.1-16.0 years (mean 12.9±2.4 and in 20 healthy children aged 3-17.9 years (mean 12.8±4.1. In all patients the diagnosis of WFS was confirmed by DNA sequencing of the WFS1 gene. Hierarchical clustering showed remarkable similarities of glucose uptake patterns among WFS patients and their differences from the control group. SUV data were subsequently standardized for age groups 13 years old to account for developmental differences. Reduced SUVs in WFS patients as compared to the control group for the bilateral brain regions such as occipital lobe (-1.24±1.20 vs. -0.13±1.05; p = 0.028 and cerebellum (-1.11±0.69 vs. -0.204±1.00; p = 0.036 were observed and the same tendency for cingulate (-1.13±1.05 vs. -0.15±1.12; p = 0.056, temporal lobe (-1.10±0.98 vs. -0.15±1.10; p = 0.057, parietal lobe (-1.06±1.20 vs. -0.08±1.08; p = 0.058, central region (-1.01±1.04 vs. -0.09±1.06; p = 0.060, basal ganglia (-1.05±0.74 vs. -0.20±1.07; p = 0.066 and mesial temporal lobe (-1.06±0.82 vs. -0.26±1.08; p = 0.087 was also noticed. After adjusting for multiple hypothesis testing, the differences in glucose uptake were non-significant. For the first time, regional differences in brain glucose metabolism among patients with WFS were shown using PET-CT imaging.

  18. Emergence of differentially regulated pathways associated with the development of regional specificity in chicken skin.

    Science.gov (United States)

    Chang, Kai-Wei; Huang, Nancy A; Liu, I-Hsuan; Wang, Yi-Hui; Wu, Ping; Tseng, Yen-Tzu; Hughes, Michael W; Jiang, Ting Xin; Tsai, Mong-Hsun; Chen, Chien-Yu; Oyang, Yen-Jen; Lin, En-Chung; Chuong, Cheng-Ming; Lin, Shau-Ping

    2015-01-23

    Regional specificity allows different skin regions to exhibit different characteristics, enabling complementary functions to make effective use of the integumentary surface. Chickens exhibit a high degree of regional specificity in the skin and can serve as a good model for when and how these regional differences begin to emerge. We used developing feather and scale regions in embryonic chickens as a model to gauge the differences in their molecular pathways. We employed cosine similarity analysis to identify the differentially regulated and co-regulated genes. We applied low cell techniques for expression validation and chromatin immunoprecipitation (ChIP)-based enhancer identification to overcome limited cell availabilities from embryonic chicken skin. We identified a specific set of genes demonstrating a high correlation as being differentially expressed during feather and scale development and maturation. Some members of the WNT, TGF-beta/BMP, and Notch family known to be involved in feathering skin differentiation were found to be differentially regulated. Interestingly, we also found genes along calcium channel pathways that are differentially regulated. From the analysis of differentially regulated pathways, we used calcium signaling pathways as an example for further verification. Some voltage-gated calcium channel subunits, particularly CACNA1D, are expressed spatio-temporally in the skin epithelium. These calcium signaling pathway members may be involved in developmental decisions, morphogenesis, or epithelial maturation. We further characterized enhancers associated with histone modifications, including H3K4me1, H3K27ac, and H3K27me3, near calcium channel-related genes and identified signature intensive hotspots that may be correlated with certain voltage-gated calcium channel genes. We demonstrated the applicability of cosine similarity analysis for identifying novel regulatory pathways that are differentially regulated during development. Our study

  19. Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Brault

    2016-08-01

    Full Text Available The recent Zika outbreak in South America and French Polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. Other members of the Flavivirus genus, including West Nile virus (WNV, can cause encephalitis but were not demonstrated to cause microcephaly. It remains unclear whether Zika virus (ZIKV and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. Here, we describe an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4. We show that this tissue is able to support viral replication of ZIKV and WNV, but not DENV-4. Cell fate analysis reveals a remarkable tropism of ZIKV infection for neural stem cells. Closely related WNV displays a very different tropism of infection, with a bias towards neurons. We further show that ZIKV infection, but not WNV infection, impairs cell cycle progression of neural stem cells. Both viruses inhibited apoptosis at early stages of infection. This work establishes a powerful comparative approach to identify ZIKV-specific alterations in the developing neocortex and reveals specific preferential infection of neural stem cells by ZIKV.

  20. Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity

    Science.gov (United States)

    Schoggins, John W.; MacDuff, Donna A.; Imanaka, Naoko; Gainey, Maria D.; Shrestha, Bimmi; Eitson, Jennifer L.; Mar, Katrina B.; Richardson, R. Blake; Ratushny, Alexander V.; Litvak, Vladimir; Dabelic, Rea; Manicassamy, Balaji; Aitchison, John D.; Aderem, Alan; Elliott, Richard M.; García-Sastre, Adolfo; Racaniello, Vincent; Snijder, Eric J.; Yokoyama, Wayne M.; Diamond, Michael S.; Virgin, Herbert W.; Rice, Charles M.

    2014-01-01

    The type I interferon (IFN) response protects cells from viral infection by inducing hundreds of interferon-stimulated genes (ISGs), some of which encode direct antiviral effectors. Recent screening studies have begun to catalogue ISGs with antiviral activity against several RNA and DNA viruses. However, antiviral ISG specificity across multiple distinct classes of viruses remains largely unexplored. Here we used an ectopic expression assay to screen a library of more than 350 human ISGs for effects on 14 viruses representing 7 families and 11 genera. We show that 47 genes inhibit one or more viruses, and 25 genes enhance virus infectivity. Comparative analysis reveals that the screened ISGs target positive-sense single-stranded RNA viruses more effectively than negative-sense single-stranded RNA viruses. Gene clustering highlights the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS, also known as MB21D1) as a gene whose expression also broadly inhibits several RNA viruses. In vitro, lentiviral delivery of enzymatically active cGAS triggers a STING-dependent, IRF3-mediated antiviral program that functions independently of canonical IFN/STAT1 signalling. In vivo, genetic ablation of murine cGAS reveals its requirement in the antiviral response to two DNA viruses, and an unappreciated contribution to the innate control of an RNA virus. These studies uncover new paradigms for the preferential specificity of IFN-mediated antiviral pathways spanning several virus families.

  1. Taxon-specific metagenomics of Trichoderma reveals a narrow community of opportunistic species that regulate each other’s development

    Science.gov (United States)

    Friedl, Martina A.

    2012-01-01

    In this paper, we report on the in situ diversity of the mycotrophic fungus Trichoderma (teleomorph Hypocrea, Ascomycota, Dikarya) revealed by a taxon-specific metagenomic approach. We designed a set of genus-specific internal transcribed spacer (ITS)1 and ITS2 rRNA primers and constructed a clone library containing 411 molecular operational taxonomic units (MOTUs). The overall species composition in the soil of the two distinct ecosystems in the Danube floodplain consisted of 15 known species and two potentially novel taxa. The latter taxa accounted for only 1.5 % of all MOTUs, suggesting that almost no hidden or uncultivable Hypocrea/Trichoderma species are present at least in these temperate forest soils. The species were unevenly distributed in vertical soil profiles although no universal factors controlling the distribution of all of them (chemical soil properties, vegetation type and affinity to rhizosphere) were revealed. In vitro experiments simulating infrageneric interactions between the pairs of species that were detected in the same soil horizon showed a broad spectrum of reactions from very strong competition over neutral coexistence to the pronounced synergism. Our data suggest that only a relatively small portion of Hypocrea/Trichoderma species is adapted to soil as a habitat and that the interaction between these species should be considered in a screening for Hypocrea/Trichoderma as an agent(s) of biological control of pests. PMID:22075025

  2. Transcriptional profiling reveals gland-specific differential expression in the three major salivary glands of the adult mouse.

    Science.gov (United States)

    Gao, Xin; Oei, Maria S; Ovitt, Catherine E; Sincan, Murat; Melvin, James E

    2018-04-01

    RNA-Seq was used to better understand the molecular nature of the biological differences among the three major exocrine salivary glands in mammals. Transcriptional profiling found that the adult murine parotid, submandibular, and sublingual salivary glands express greater than 14,300 protein-coding genes, and nearly 2,000 of these genes were differentially expressed. Principle component analysis of the differentially expressed genes revealed three distinct clusters according to gland type. The three salivary gland transcriptomes were dominated by a relatively few number of highly expressed genes (6.3%) that accounted for more than 90% of transcriptional output. Of the 912 transcription factors expressed in the major salivary glands, greater than 90% of them were detected in all three glands, while expression for ~2% of them was enriched in an individual gland. Expression of these unique transcription factors correlated with sublingual and parotid specific subsets of both highly expressed and differentially expressed genes. Gene ontology analyses revealed that the highly expressed genes common to all glands were associated with global functions, while many of the genes expressed in a single gland play a major role in the function of that gland. In summary, transcriptional profiling of the three murine major salivary glands identified a limited number of highly expressed genes, differentially expressed genes, and unique transcription factors that represent the transcriptional signatures underlying gland-specific biological properties.

  3. The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions

    Energy Technology Data Exchange (ETDEWEB)

    Ruan, Jiapeng [Northwestern University, 320 E. Superior Street, Morton 7-601, Chicago, IL 60611 (United States); Mouveaux, Thomas [Université Lille Nord de France, (France); Light, Samuel H.; Minasov, George; Anderson, Wayne F. [Northwestern University, 320 E. Superior Street, Morton 7-601, Chicago, IL 60611 (United States); Tomavo, Stanislas [Université Lille Nord de France, (France); Ngô, Huân M., E-mail: h-ngo@northwestern.edu [Northwestern University, 320 E. Superior Street, Morton 7-601, Chicago, IL 60611 (United States); BrainMicro LLC, 21 Pendleton Street, New Haven, CT 06511 (United States)

    2015-03-01

    The second crystal structure of a parasite protein preferentially enriched in the brain cyst of T. gondii has been solved at 2.75 Å resolution. Bradyzoite enolase 1 is reported to have differential functions as a glycolytic enzyme and a transcriptional regulator in bradyzoites. In addition to catalyzing a central step in glycolysis, enolase assumes a remarkably diverse set of secondary functions in different organisms, including transcription regulation as documented for the oncogene c-Myc promoter-binding protein 1. The apicomplexan parasite Toxoplasma gondii differentially expresses two nuclear-localized, plant-like enolases: enolase 1 (TgENO1) in the latent bradyzoite cyst stage and enolase 2 (TgENO2) in the rapidly replicative tachyzoite stage. A 2.75 Å resolution crystal structure of bradyzoite enolase 1, the second structure to be reported of a bradyzoite-specific protein in Toxoplasma, captures an open conformational state and reveals that distinctive plant-like insertions are located on surface loops. The enolase 1 structure reveals that a unique residue, Glu164, in catalytic loop 2 may account for the lower activity of this cyst-stage isozyme. Recombinant TgENO1 specifically binds to a TTTTCT DNA motif present in the cyst matrix antigen 1 (TgMAG1) gene promoter as demonstrated by gel retardation. Furthermore, direct physical interactions of both nuclear TgENO1 and TgENO2 with the TgMAG1 gene promoter are demonstrated in vivo using chromatin immunoprecipitation (ChIP) assays. Structural and biochemical studies reveal that T. gondii enolase functions are multifaceted, including the coordination of gene regulation in parasitic stage development. Enolase 1 provides a potential lead in the design of drugs against Toxoplasma brain cysts.

  4. Characterization of multiple light damage paradigms reveals regional differences in photoreceptor loss.

    Science.gov (United States)

    Thomas, Jennifer L; Nelson, Craig M; Luo, Xixia; Hyde, David R; Thummel, Ryan

    2012-04-01

    Zebrafish provide an attractive model to study the retinal response to photoreceptor apoptosis due to its remarkable ability to spontaneously regenerate retinal neurons following damage. There are currently two widely-used light-induced retinal degeneration models to damage photoreceptors in the adult zebrafish. One model uses constant bright light, whereas the other uses a short exposure to extremely intense ultraviolet light. Although both models are currently used, it is unclear whether they differ in regard to the extent of photoreceptor damage or the subsequent regeneration response. Here we report a thorough analysis of the photoreceptor damage and subsequent proliferation response elicited by each individual treatment, as well as by the concomitant use of both treatments. We show a differential loss of rod and cone photoreceptors with each treatment. Additionally, we show that the extent of proliferation observed in the retina directly correlates with the severity of photoreceptor loss. We also demonstrate that both the ventral and posterior regions of the retina are partially protected from light damage. Finally, we show that combining a short ultraviolet exposure followed by a constant bright light treatment largely eliminates the neuroprotected regions, resulting in widespread loss of rod and cone photoreceptors and a robust regenerative response throughout the retina. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Specific Midgut Region Controlling the Symbiont Population in an Insect-Microbe Gut Symbiotic Association

    Science.gov (United States)

    Kim, Jiyeun Kate; Kim, Na Hyang; Jang, Ho Am; Kikuchi, Yoshitomo; Kim, Chan-Hee

    2013-01-01

    Many insects possess symbiotic bacteria that affect the biology of the host. The level of the symbiont population in the host is a pivotal factor that modulates the biological outcome of the symbiotic association. Hence, the symbiont population should be maintained at a proper level by the host's control mechanisms. Several mechanisms for controlling intracellular symbionts of insects have been reported, while mechanisms for controlling extracellular gut symbionts of insects are poorly understood. The bean bug Riptortus pedestris harbors a betaproteobacterial extracellular symbiont of the genus Burkholderia in the midgut symbiotic organ designated the M4 region. We found that the M4B region, which is directly connected to the M4 region, also harbors Burkholderia symbiont cells, but the symbionts therein are mostly dead. A series of experiments demonstrated that the M4B region exhibits antimicrobial activity, and the antimicrobial activity is specifically potent against the Burkholderia symbiont but not the cultured Burkholderia and other bacteria. The antimicrobial activity of the M4B region was detected in symbiotic host insects, reaching its highest point at the fifth instar, but not in aposymbiotic host insects, which suggests the possibility of symbiont-mediated induction of the antimicrobial activity. This antimicrobial activity was not associated with upregulation of antimicrobial peptides of the host. Based on these results, we propose that the M4B region is a specialized gut region of R. pedestris that plays a critical role in controlling the population of the Burkholderia gut symbiont. The molecular basis of the antimicrobial activity is of great interest and deserves future study. PMID:24038695

  6. The Revealed Competitiveness of Major Ports in the East Asian Region: An Additive Market Share Analysis

    Directory of Open Access Journals (Sweden)

    Tae Seung Kim

    2015-12-01

    Full Text Available In the single cargo market, the ordinary market share analysis method has been the representative tool for revealed competitiveness analysis. This paper develops and employs an applied market share index called the additive market share (AMS. Data are collected from 15 major container ports for the 1998-2013 period. In comparison to the results of an ordinary market share analysis, the highest AMS is observed for the Bohai Rim port cluster from 2008, not for the Yangtze River cluster or the Pearl River cluster. There are substitutable relationships between Yangtze River and non-Chinese ports and between Pearl River and Bohai Rim ports from 2001. Finally, there is an internal competition at Pearl River and Yangtze River ports, whereas Bohai Rim and non-Chinese ports show internally complementary relationships.

  7. Structure-guided investigation of lipopolysaccharide O-antigen chain length regulators reveals regions critical for modal length control.

    Science.gov (United States)

    Kalynych, Sergei; Ruan, Xiang; Valvano, Miguel A; Cygler, Miroslaw

    2011-08-01

    The O-antigen component of the lipopolysaccharide (LPS) represents a population of polysaccharide molecules with nonrandom (modal) chain length distribution. The number of the repeat O units in each individual O-antigen polymer depends on the Wzz chain length regulator, an inner membrane protein belonging to the polysaccharide copolymerase (PCP) family. Different Wzz proteins confer vastly different ranges of modal lengths (4 to >100 repeat units), despite having remarkably conserved structural folds. The molecular mechanism responsible for the selective preference for a certain number of O units is unknown. Guided by the three-dimensional structures of PCPs, we constructed a panel of chimeric molecules containing parts of two closely related Wzz proteins from Salmonella enterica and Shigella flexneri which confer different O-antigen chain length distributions. Analysis of the O-antigen length distribution imparted by each chimera revealed the region spanning amino acids 67 to 95 (region 67 to 95), region 200 to 255, and region 269 to 274 as primarily affecting the length distribution. We also showed that there is no synergy between these regions. In particular, region 269 to 274 also influenced chain length distribution mediated by two distantly related PCPs, WzzB and FepE. Furthermore, from the 3 regions uncovered in this study, region 269 to 274 appeared to be critical for the stability of the oligomeric form of Wzz, as determined by cross-linking experiments. Together, our data suggest that chain length determination depends on regions that likely contribute to stabilize a supramolecular complex.

  8. Russian Specifics of Dacha Suburbanization Process: Case Study of the Moscow Region

    Directory of Open Access Journals (Sweden)

    Aleksandr Valer’evich Rusanov

    2015-12-01

    Full Text Available Topical issues related to the planning of urban agglomerations development include registration and analysis of changes in suburban areas in the process of socio-economic development. It is manifest, among other things, in urbanization, which in relation to larger cities is replaced by suburbanization. Suburbanization process has been developing to the greatest extent in North America and Western Europe. Scientific research confirms that the majority of large urban agglomerations are in the stage of suburbanization. The pace of suburbanization in the world is different – the authorities of individual countries, regions or cities often take measures to limit or simplify it: they reconstruct central cities, set limits to the construction in peripheral areas, etc. In Russia, the process of suburbanization started to develop rapidly only after the socio-economic transformation of the 1990s that led to the emergence of the free market of housing and land. The aim of the present work is to determine the specifics of suburbanization in Russia on the example of the Moscow Region. Suburbanization in Russia is mainly seasonal; therefore, the paper examines suburbanization specific for Russia and related to the distribution of population and its economic activities in the organized summer house settlements in suburban areas, i.e. in dachas. A kind of this activity popular in Russia is gardening and vegetable and fruit farming in the settlements located on specially designated lands. The paper examines the factors determining suburbanization in the Moscow Region, and demonstrates the influence of these factors taking two key areas as examples. Scientific novelty of the work consists in the fact that it clarifies the content of suburbanization factors as applied to the Moscow Region; in addition, it considers the development of dacha-related suburbanization, highlights its characteristics on the example of the Moscow Region, examines current distribution

  9. Identification and characterization of a liver stage-specific promoter region of the malaria parasite Plasmodium.

    Directory of Open Access Journals (Sweden)

    Susanne Helm

    Full Text Available During the blood meal of a Plasmodium-infected mosquito, 10 to 100 parasites are inoculated into the skin and a proportion of these migrate via the bloodstream to the liver where they infect hepatocytes. The Plasmodium liver stage, despite its clinical silence, represents a highly promising target for antimalarial drug and vaccine approaches. Successfully invaded parasites undergo a massive proliferation in hepatocytes, producing thousands of merozoites that are transported into a blood vessel to infect red blood cells. To successfully develop from the liver stage into infective merozoites, a tight regulation of gene expression is needed. Although this is a very interesting aspect in the biology of Plasmodium, little is known about gene regulation in Plasmodium parasites in general and in the liver stage in particular. We have functionally analyzed a novel promoter region of the rodent parasite Plasmodium berghei that is exclusively active during the liver stage of the parasite. To prove stage-specific activity of the promoter, GFP and luciferase reporter assays have been successfully established, allowing both qualitative and accurate quantitative analysis. To further characterize the promoter region, the transcription start site was mapped by rapid amplification of cDNA ends (5'-RACE. Using promoter truncation experiments and site-directed mutagenesis within potential transcription factor binding sites, we suggest that the minimal promoter contains more than one binding site for the recently identified parasite-specific ApiAP2 transcription factors. The identification of a liver stage-specific promoter in P. berghei confirms that the parasite is able to tightly regulate gene expression during its life cycle. The identified promoter region might now be used to study the biology of the Plasmodium liver stage, which has thus far proven problematic on a molecular level. Stage-specific expression of dominant-negative mutant proteins and

  10. 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.

  11. GPS-seismograms reveal amplified shaking in California's San Joaquin Delta region

    Science.gov (United States)

    Johanson, I. A.

    2014-12-01

    The March 10, 2014, the Mw6.8 Ferndale earthquake occurred off the coast of Northern California, near the Mendocino Triple Junction. Aftershocks suggest a northeast striking fault plane for the strike-slip earthquake, oriented such that the California coast is roughly perpendicular to the rupture plane. Consequently, large amplitude Love waves were observed at seismic stations and continuous GPS stations throughout Northern California. While GPS is less sensitive then broadband instruments, in Northern California their station density is much higher, potentially providing valuable detail. A total of 269 GPS stations that have high-rate (1 sps) data available were used to generate GPS-seismograms. These include stations from the Bay Area Regional Deformation (BARD) network, the Plate Boundary Observatory (PBO, operated by UNAVCO), and the USGS, Menlo Park. The Track software package was used to generate relative displacements between pairs of stations, determined using Delaunay triangulation. This network-based approach allows for higher precision than absolute positioning, because common noise sources, in particular atmospheric noise, are cancelled out. A simple least-squares network adjustment with a stable centroid constraint is performed to transform the mesh of relative motions into absolute motions at individual GPS stations. This approach to generating GPS-seismograms is validated by the good agreement between time series records at 16 BARD stations that are co-located with broadband seismometers from the Berkeley Digital Seismic Network (BDSN). While the distribution of peak dynamic displacements is dominated in long periods by the radiation pattern, at shorter periods other patterns become visible. In particular, stations in the San Joaquin Delta (SJD) region show higher peak dynamic displacements than those in surrounding areas, as well as longer duration shaking. SJD stations also have higher dynamic displacements on the radial component than surrounding

  12. Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions.

    Science.gov (United States)

    Akiba, Hiroki; Tsumoto, Kouhei

    2015-07-01

    Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody-antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  13. Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development.

    Science.gov (United States)

    Szabo, Linda; Morey, Robert; Palpant, Nathan J; Wang, Peter L; Afari, Nastaran; Jiang, Chuan; Parast, Mana M; Murry, Charles E; Laurent, Louise C; Salzman, Julia

    2015-06-16

    The pervasive expression of circular RNA is a recently discovered feature of gene expression in highly diverged eukaryotes, but the functions of most circular RNAs are still unknown. Computational methods to discover and quantify circular RNA are essential. Moreover, discovering biological contexts where circular RNAs are regulated will shed light on potential functional roles they may play. We present a new algorithm that increases the sensitivity and specificity of circular RNA detection by discovering and quantifying circular and linear RNA splicing events at both annotated and un-annotated exon boundaries, including intergenic regions of the genome, with high statistical confidence. Unlike approaches that rely on read count and exon homology to determine confidence in prediction of circular RNA expression, our algorithm uses a statistical approach. Using our algorithm, we unveiled striking induction of general and tissue-specific circular RNAs, including in the heart and lung, during human fetal development. We discover regions of the human fetal brain, such as the frontal cortex, with marked enrichment for genes where circular RNA isoforms are dominant. The vast majority of circular RNA production occurs at major spliceosome splice sites; however, we find the first examples of developmentally induced circular RNAs processed by the minor spliceosome, and an enriched propensity of minor spliceosome donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, these results suggest a potentially significant role for circular RNA in human development.

  14. Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. IV. Further evidence for regional and behavioral specificity

    International Nuclear Information System (INIS)

    Berman, K.F.; Illowsky, B.P.; Weinberger, D.R.

    1988-01-01

    In previous studies we found that patients with chronic schizophrenia had lower regional cerebral blood flow (rCBF) in dorsolateral prefrontal cortex (DLPFC) than did normal subjects during performance of the Wisconsin Card Sort Test, an abstract reasoning task linked to DLPFC function. This was not the case during less complex tasks. To examine further whether this finding represented regionally circumscribed pathophysiology or a more general correlate of abstract cognition, 24 medication-free patients and 25 age- and sex-matched normal control subjects underwent rCBF measurements with the xenon 133 technique while they performed two tasks: Raven's Progressive Matrices (RPM) and an active baseline control task. While performing RPM, normal subjects activated posterior cortical areas over baseline, but did not activate DLPFC, as had been seen during the Wisconsin Card Sort Test. Like normal subjects, patients showed maximal rCBF elevations posteriorly and, moreover, they had no significant DLPFC or other cortical deficit while performing RPM. These results suggest that DLPFC dysfunction in schizophrenia is linked to pathophysiology of a regionally specific neural system rather than to global cortical dysfunction, and that this pathophysiology is most apparent under prefrontally specific cognitive demand

  15. Sequencing the CHO DXB11 genome reveals regional variations in genomic stability and haploidy

    DEFF Research Database (Denmark)

    Kaas, Christian Schrøder; Kristensen, Claus; Betenbaugh, Michael J.

    2015-01-01

    Background: The DHFR negative CHO DXB11 cell line (also known as DUX-B11 and DUKX) was historically the first CHO cell line to be used for large scale production of heterologous proteins and is still used for production of a number of complex proteins.  Results: Here we present the genomic sequence...... of the CHO DXB11 genome sequenced to a depth of 33x. Overall a significant genomic drift was seen favoring GC -> AT point mutations in line with the chemical mutagenesis strategy used for generation of the cell line. The sequencing depth for each gene in the genome revealed distinct peaks at sequencing...... in eight additional analyzed CHO genomes (15-20% haploidy) but not in the genome of the Chinese hamster. The dhfr gene is confirmed to be haploid in CHO DXB11; transcriptionally active and the remaining allele contains a G410C point mutation causing a Thr137Arg missense mutation. We find similar to 2...

  16. Climate Impacts of Ozone and Sulfate Air Pollution from Specific Emissions Sectors and Regions

    Science.gov (United States)

    Unger, N.; Koch, D. M.; Shindell, D. T.; Streets, D. G.

    2006-12-01

    The secondary air pollutants ozone (O3) and sulfate aerosol are generated by human activities and affect the Earth's climate system. The global mean radiative forcings of these short-lived species depend on the location of the precursor gas emissions, which has so far prevented their incorporation into climate-motivated policy agreements. O3 and sulfate aerosol are strongly coupled through tropospheric photochemistry and yet air quality control efforts consider each species separately. Previous modeling work to assess climate impacts of O3 has focused on individual precursors, such as nitrogen oxides, even though policy action would target a particular sector. We use the G-PUCCINI atmospheric composition-climate model to isolate the O3 and sulfate direct radiative forcing impacts of 6 specific emissions sectors (industry, transport, power, domestic biofuel, domestic fossil fuel and biomass burning) from 7 geographic regions (North America, Europe, South Asia, East Asia, North Africa and the Middle East, Central and South Africa and South America) for the near future 2030 atmosphere. The goal of the study is to identify specific source sectors and regions that present the most effective opportunities to mitigate global warming. At 2030, the industry and power sectors dominate the sulfate forcing across all regions, with East Asia, South Asia and North Africa and Middle East contributing the largest sulfate forcings (-100 to 120 mWm-2). The transport sector represents an important O3 forcing from all regions ranging from 5 mWm-2 (Europe) to 12 mWm-2 (East Asia). Domestic biofuel O3 forcing is important for the East Asia (13 mWm-2), South Asia (7 mWm-2) and Central and South Africa (10 mWm-2) regions. Biomass burning contributes large O3 forcings for the Central and South Africa (15 mWm-2) and South America (11 mWm-2) regions. In addition, the power sector O3 forcings from East Asia (14 mWm-2) and South Asia (8 mWm-2) are also substantial. Considering the sum of the O

  17. Enrichment of short interspersed transposable elements to embryonic stem cell-specific hypomethylated gene regions.

    Science.gov (United States)

    Muramoto, Hiroki; Yagi, Shintaro; Hirabayashi, Keiji; Sato, Shinya; Ohgane, Jun; Tanaka, Satoshi; Shiota, Kunio

    2010-08-01

    Embryonic stem cells (ESCs) have a distinctive epigenome, which includes their genome-wide DNA methylation modification status, as represented by the ESC-specific hypomethylation of tissue-dependent and differentially methylated regions (T-DMRs) of Pou5f1 and Nanog. Here, we conducted a genome-wide investigation of sequence characteristics associated with T-DMRs that were differentially methylated between ESCs and somatic cells, by focusing on transposable elements including short interspersed elements (SINEs), long interspersed elements (LINEs) and long terminal repeats (LTRs). We found that hypomethylated T-DMRs were predominantly present in SINE-rich/LINE-poor genomic loci. The enrichment for SINEs spread over 300 kb in cis and there existed SINE-rich genomic domains spreading continuously over 1 Mb, which contained multiple hypomethylated T-DMRs. The characterization of sequence information showed that the enriched SINEs were relatively CpG rich and belonged to specific subfamilies. A subset of the enriched SINEs were hypomethylated T-DMRs in ESCs at Dppa3 gene locus, although SINEs are overall methylated in both ESCs and the liver. In conclusion, we propose that SINE enrichment is the genomic property of regions harboring hypomethylated T-DMRs in ESCs, which is a novel aspect of the ESC-specific epigenomic information.

  18. Aboriginal mitogenomes reveal 50,000 years of regionalism in Australia.

    Science.gov (United States)

    Tobler, Ray; Rohrlach, Adam; Soubrier, Julien; Bover, Pere; Llamas, Bastien; Tuke, Jonathan; Bean, Nigel; Abdullah-Highfold, Ali; Agius, Shane; O'Donoghue, Amy; O'Loughlin, Isabel; Sutton, Peter; Zilio, Fran; Walshe, Keryn; Williams, Alan N; Turney, Chris S M; Williams, Matthew; Richards, Stephen M; Mitchell, Robert J; Kowal, Emma; Stephen, John R; Williams, Lesley; Haak, Wolfgang; Cooper, Alan

    2017-04-13

    Aboriginal Australians represent one of the longest continuous cultural complexes known. Archaeological evidence indicates that Australia and New Guinea were initially settled approximately 50 thousand years ago (ka); however, little is known about the processes underlying the enormous linguistic and phenotypic diversity within Australia. Here we report 111 mitochondrial genomes (mitogenomes) from historical Aboriginal Australian hair samples, whose origins enable us to reconstruct Australian phylogeographic history before European settlement. Marked geographic patterns and deep splits across the major mitochondrial haplogroups imply that the settlement of Australia comprised a single, rapid migration along the east and west coasts that reached southern Australia by 49-45 ka. After continent-wide colonization, strong regional patterns developed and these have survived despite substantial climatic and cultural change during the late Pleistocene and Holocene epochs. Remarkably, we find evidence for the continuous presence of populations in discrete geographic areas dating back to around 50 ka, in agreement with the notable Aboriginal Australian cultural attachment to their country.

  19. Airborne methane remote measurements reveal heavy-tail flux distribution in Four Corners region.

    Science.gov (United States)

    Frankenberg, C.

    2016-12-01

    Methane (CH4) impacts climate as the second strongest anthropogenic greenhouse gas and air quality by influencing tropospheric ozone levels. Space-based observations have identified the Four Corners region in the Southwest United States as an area of large CH4 enhancements. We conducted an airborne campaign in Four Corners during April 2015 with the next-generation Airborne Visible/Infrared Imaging Spectrometer (near-infrared) and Hyperspectral Thermal Emission Spectrometer (thermal infrared) imaging spectrometers to better understand the source of methane by measuring methane plumes at 1- to 3-m spatial resolution. Our analysis detected more than 250 individual methane plumes from fossil fuel harvesting, processing, and distributing infrastructures, spanning an emission range from the detection limit ˜ 2 kg/h to 5 kg/h through ˜ 5,000 kg/h. Observed sources include gas processing facilities, storage tanks, pipeline leaks, natural seeps and well pads, as well as a coal mine venting shaft. Overall, plume enhancements and inferred fluxes follow a lognormal distribution, with the top 10% emitters contributing 49 to 66% to the inferred total point source flux of 0.23 Tg/y to 0.39 Tg/y. We will summarize the campaign results and provide an overview of how airborne remote sensing can be used to detect and infer methane fluxes over widespread geographic areas and how new instrumentation could be used to perform similar observations from space.

  20. Insights into bird wing evolution and digit specification from polarizing region fate maps.

    Science.gov (United States)

    Towers, Matthew; Signolet, Jason; Sherman, Adrian; Sang, Helen; Tickle, Cheryll

    2011-08-09

    The proposal that birds descended from theropod dinosaurs with digits 2, 3 and 4 was recently given support by short-term fate maps, suggesting that the chick wing polarizing region-a group that Sonic hedgehog-expressing cells-gives rise to digit 4. Here we show using long-term fate maps that Green fluorescent protein-expressing chick wing polarizing region grafts contribute only to soft tissues along the posterior margin of digit 4, supporting fossil data that birds descended from theropods that had digits 1, 2 and 3. In contrast, digit IV of the chick leg with four digits (I-IV) arises from the polarizing region. To determine how digit identity is specified over time, we inhibited Sonic hedgehog signalling. Fate maps show that polarizing region and adjacent cells are specified in parallel through a series of anterior to posterior digit fates-a process of digit specification that we suggest is involved in patterning all vertebrate limbs with more than three digits.

  1. Comparative phylogeography reveals deep lineages and regional evolutionary hotspots in the Mojave and Sonoran Deserts

    Science.gov (United States)

    Wood, Dustin A.; Vandergast, Amy G.; Barr, Kelly R.; Inman, Richard D.; Esque, Todd C.; Nussear, Kenneth E.; Fisher, Robert N.

    2013-01-01

    Aim: We explored lineage diversification within desert-dwelling fauna. Our goals were (1) to determine whether phylogenetic lineages and population expansions were consistent with younger Pleistocene climate fluctuation hypotheses or much older events predicted by pre-Pleistocene vicariance hypotheses, (2) to assess concordance in spatial patterns of genetic divergence and diversity among species and (3) to identify regional evolutionary hotspots of divergence and diversity and assess their conservation status. Location: Mojave, Colorado, and Sonoran Deserts, USA. Methods: We analysed previously published gene sequence data for twelve species. We used Bayesian gene tree methods to estimate lineages and divergence times. Within each lineage, we tested for population expansion and age of expansion using coalescent approaches. We mapped interpopulation genetic divergence and intra-population genetic diversity in a GIS to identify hotspots of highest genetic divergence and diversity and to assess whether protected lands overlapped with evolutionary hotspots. Results: In seven of the 12 species, lineage divergence substantially predated the Pleistocene. Historical population expansion was found in eight species, but expansion events postdated the Last Glacial Maximum (LGM) in only four. For all species assessed, six hotspots of high genetic divergence and diversity were concentrated in the Colorado Desert, along the Colorado River and in the Mojave/Sonoran ecotone. At least some proportion of the land within each recovered hotspot was categorized as protected, yet four of the six also overlapped with major areas of human development. Main conclusions: Most of the species studied here diversified into distinct Mojave and Sonoran lineages prior to the LGM – supporting older diversification hypotheses. Several evolutionary hotspots were recovered but are not strategically paired with areas of protected land. Long-term preservation of species-level biodiversity would

  2. Whole-Genome Analysis of Three Yeast Strains Used for Production of Sherry-Like Wines Revealed Genetic Traits Specific to Flor Yeasts

    Science.gov (United States)

    Eldarov, Mikhail A.; Beletsky, Alexey V.; Tanashchuk, Tatiana N.; Kishkovskaya, Svetlana A.; Ravin, Nikolai V.; Mardanov, Andrey V.

    2018-01-01

    Flor yeast strains represent a specialized group of Saccharomyces cerevisiae yeasts used for biological wine aging. We have sequenced the genomes of three flor strains originated from different geographic regions and used for production of sherry-like wines in Russia. According to the obtained phylogeny of 118 yeast strains, flor strains form very tight cluster adjacent to the main wine clade. SNP analysis versus available genomes of wine and flor strains revealed 2,270 genetic variants in 1,337 loci specific to flor strains. Gene ontology analysis in combination with gene content evaluation revealed a complex landscape of possibly adaptive genetic changes in flor yeast, related to genes associated with cell morphology, mitotic cell cycle, ion homeostasis, DNA repair, carbohydrate metabolism, lipid metabolism, and cell wall biogenesis. Pangenomic analysis discovered the presence of several well-known “non-reference” loci of potential industrial importance. Events of gene loss included deletions of asparaginase genes, maltose utilization locus, and FRE-FIT locus involved in iron transport. The latter in combination with a flor-yeast-specific mutation in the Aft1 transcription factor gene is likely to be responsible for the discovered phenotype of increased iron sensitivity and improved iron uptake of analyzed strains. Expansion of the coding region of the FLO11 flocullin gene and alteration of the balance between members of the FLO gene family are likely to positively affect the well-known propensity of flor strains for velum formation. Our study provides new insights in the nature of genetic variation in flor yeast strains and demonstrates that different adaptive properties of flor yeast strains could have evolved through different mechanisms of genetic variation. PMID:29867869

  3. B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies.

    Science.gov (United States)

    Xiao, Gang; Chan, Lai N; Klemm, Lars; Braas, Daniel; Chen, Zhengshan; Geng, Huimin; Zhang, Qiuyi Chen; Aghajanirefah, Ali; Cosgun, Kadriye Nehir; Sadras, Teresa; Lee, Jaewoong; Mirzapoiazova, Tamara; Salgia, Ravi; Ernst, Thomas; Hochhaus, Andreas; Jumaa, Hassan; Jiang, Xiaoyan; Weinstock, David M; Graeber, Thomas G; Müschen, Markus

    2018-04-05

    B cell activation during normal immune responses and oncogenic transformation impose increased metabolic demands on B cells and their ability to retain redox homeostasis. While the serine/threonine-protein phosphatase 2A (PP2A) was identified as a tumor suppressor in multiple types of cancer, our genetic studies revealed an essential role of PP2A in B cell tumors. Thereby, PP2A redirects glucose carbon utilization from glycolysis to the pentose phosphate pathway (PPP) to salvage oxidative stress. This unique vulnerability reflects constitutively low PPP activity in B cells and transcriptional repression of G6PD and other key PPP enzymes by the B cell transcription factors PAX5 and IKZF1. Reflecting B-cell-specific transcriptional PPP-repression, glucose carbon utilization in B cells is heavily skewed in favor of glycolysis resulting in lack of PPP-dependent antioxidant protection. These findings reveal a gatekeeper function of the PPP in a broad range of B cell malignancies that can be efficiently targeted by small molecule inhibition of PP2A and G6PD. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure

    International Nuclear Information System (INIS)

    Soreq, H.; Ben-Aziz, R.; Prody, C.A.; Seidman, S.; Gnatt, A.; Neville, L.; Lieman-Hurwitz, J.; Lev-Lehman, E.; Ginzberg, D.; Lapidot-Lifson, Y.; Zakut, H.

    1990-01-01

    To study the primary structure of human acetylcholinesterase and its gene expression and amplification, cDNA libraries from human tissues expressing oocyte-translatable AcChoEase mRNA were constructed and screened with labeled oligodeoxynucleotide probes. Several cDNA clones were isolated that encoded a polypeptide with ≥50% identically aligned amino acids to Torpedo AcChoEase and human butyrylcholinesterase. However, these cDNA clones were all truncated within a 300-nucleotide-long G + C-rich region with a predicted pattern of secondary structure having a high Gibbs free energy downstream from the expected 5' end of the coding region. Screening of a genomic DNA library revealed the missing 5' domain. When ligated to the cDNA and constructed into a transcription vector, this sequence encoded a synthetic mRNA translated in microinjected oocytes into catalytically active AcChoEase with marked preference for acetylthiocholine over butyrylthiocholine as a substrate, susceptibility to inhibition by the AcChoEase inhibitor BW284C51, and resistance to the AcChoEase inhibitor tetraisopropylpyrophosphoramide. Blot hybridization of genomic DNA from different individuals carrying amplified AcChoEase genes revealed variable intensities and restriction patterns with probes from the regions upstream and downstream from the predicted G + C-rich structure. Thus, the human AcChoEase gene includes a putative G + C-rich attenuator domain and is subject to structural alterations in cases of AcChoEase gene amplification

  5. Air pollution exposure, cause-specific deaths and hospitalizations in a highly polluted Italian region.

    Science.gov (United States)

    Carugno, Michele; Consonni, Dario; Randi, Giorgia; Catelan, Dolores; Grisotto, Laura; Bertazzi, Pier Alberto; Biggeri, Annibale; Baccini, Michela

    2016-05-01

    The Lombardy region in northern Italy ranks among the most air polluted areas of Europe. Previous studies showed air pollution short-term effects on all-cause mortality. We examine here the effects of particulate matter with aerodynamic diameter ≤10µm (PM10) and nitrogen dioxide (NO2) exposure on deaths and hospitalizations from specific causes, including cardiac, cerebrovascular and respiratory diseases. We considered air pollution, mortality and hospitalization data for a non-opportunistic sample of 18 highly polluted and most densely populated areas of the region in the years 2003-2006. We obtained area-specific effect estimates for PM10 and NO2 from a Poisson regression model on the daily number of total deaths or cause-specific hospitalizations and then combined them in a Bayesian random-effects meta-analysis. For cause-specific mortality, we applied a case-crossover analysis. Age- and season-specific analyses were also performed. Effect estimates were expressed as percent variation in mortality or hospitalizations associated with a 10µg/m(3) increase in PM10 or NO2 concentration. Natural mortality was positively associated with both pollutants (0.30%, 90% Credibility Interval [CrI]: -0.31; 0.78 for PM10; 0.70%, 90%CrI: 0.10; 1.27 for NO2). Cardiovascular deaths showed a higher percent variation in association with NO2 (1.12%, 90% Confidence Interval [CI]: 0.14; 2.11), while the percent variation for respiratory mortality was highest in association with PM10 (1.64%, 90%CI: 0.35; 2.93). The effect of both pollutants was more evident in the summer season. Air pollution was also associated to hospitalizations, the highest variations being 0.77% (90%CrI: 0.22; 1.43) for PM10 and respiratory diseases, and 1.70% (90%CrI: 0.39; 2.84) for NO2 and cerebrovascular diseases. The effect of PM10 on respiratory hospital admissions appeared to increase with age. For both pollutants, effects on cerebrovascular hospitalizations were more evident in subjects aged less than

  6. Gravity waves, Tides and Planetary wave characteristics revealed by network of MLT radars over Indian region

    Science.gov (United States)

    Venkat Ratnam, Madineni; Karanam, Kishore Kumar; Sunkara, Eswaraiah; Vijaya Bhaskara Rao, S.; Subrahmanyam, K. V.; Ramanjaneyulu, L.

    2016-07-01

    Mesosphere and Lower Thermosphere (MLT) mean winds, gravity waves, tidal and planetary wave characteristics are investigated using two years (2013-2015) of advanced meteor radar installed at Tirupathi (13.63oN, 79.4oE), India. The observations reveal the presence of high frequency gravity waves (30-120 minutes), atmospheric tides (diurnal, semi-diurnal and terr-diurnal) along with long period oscillations in both zonal and meridional winds. Background mean zonal winds show clear semi-annual oscillation in the mesosphere, whereas meridional winds are characterized by annual oscillation as expected. Diurnal tide amplitudes are significantly larger (60-80 m/s) than semi-diurnal (10-20 m/s) and terr-diurnal (5-8 m/s) tides and larger in meridional than zonal winds. The measured meridional components are in good agreement with Global Scale Wave Model (GSWM-09) predictions than zonal up to ~90 km in all the seasons, except fall equinox. Diurnal tidal phase matches well than the amplitudes between observations and model predictions. However, no similarity is being found in the semi-diurnal tides between observations and model. The measurements are further compared with nearby Thumba meteor radar (8.5oN, 77oE) observations. Some differences do exist between the measurements from Tirupati and Thumba meteor radar and model outputs at greater heights and the possible reasons are discussed. SVU meteor radar observations clearly showed the dominance of well-known ultra-fast kelvin waves (3.5 days), 5-8 day, 16 day, 27 day, and 30-40 day oscillations. Due to higher meteor count extending up to 110 km, we could investigate the variability of these PWs and oscillations covering wider range (70-110 km) for the first time. Significant change above 100 km is noticed in all the above mentioned PW activity and oscillations. We also used ERA-Interim reanalysis data sets available at 0.125x0.125 degree grids for investigating the characteristics of these PW right from surface to 1 h

  7. Quantitative Molecular Imaging with a Single Gd-Based Contrast Agent Reveals Specific Tumor Binding and Retention in Vivo.

    Science.gov (United States)

    Johansen, Mette L; Gao, Ying; Hutnick, Melanie A; Craig, Sonya E L; Pokorski, Jonathan K; Flask, Chris A; Brady-Kalnay, Susann M

    2017-06-06

    Magnetic resonance imaging (MRI) has become an indispensable tool in the diagnosis and treatment of many diseases, especially cancer. However, the poor sensitivity of MRI relative to other imaging modalities, such as PET, has hindered the development and clinical use of molecular MRI contrast agents that could provide vital diagnostic information by specifically locating a molecular target altered in the disease process. This work describes the specific and sustained in vivo binding and retention of a protein tyrosine phosphatase mu (PTPμ)-targeted, molecular magnetic resonance (MR) contrast agent with a single gadolinium (Gd) chelate using a quantitative MRI T 1 mapping technique in glioma xenografts. Quantitative T 1 mapping is an imaging method used to measure the longitudinal relaxation time, the T 1 relaxation time, of protons in a magnetic field after excitation by a radiofrequency pulse. T 1 relaxation times can in turn be used to calculate the concentration of a gadolinium-containing contrast agent in a region of interest, thereby allowing the retention or clearance of an agent to be quantified. In this context, retention is a measure of molecular contrast agent binding. Using conventional peptide chemistry, a PTPμ-targeted peptide was linked to a chelator that had been conjugated to a lysine residue. Following complexation with Gd, this PTPμ-targeted molecular contrast agent containing a single Gd ion showed significant tumor enhancement and a sustained increase in Gd concentration in both heterotopic and orthotopic tumors using dynamic quantitative MRI. This single Gd-containing PTPμ agent was more effective than our previous version with three Gd ions. Differences between nonspecific and specific agents, due to specific tumor binding, can be determined within the first 30 min after agent administration by examining clearance rates. This more facile chemistry, when combined with quantitative MR techniques, allows for widespread adoption by academic

  8. Bacterial communities of two ubiquitous Great Barrier Reef corals reveals both site- and species-specificity of common bacterial associates.

    Directory of Open Access Journals (Sweden)

    E Charlotte E Kvennefors

    Full Text Available BACKGROUND: Coral-associated bacteria are increasingly considered to be important in coral health, and altered bacterial community structures have been linked to both coral disease and bleaching. Despite this, assessments of bacterial communities on corals rarely apply sufficient replication to adequately describe the natural variability. Replicated data such as these are crucial in determining potential roles of bacteria on coral. METHODOLOGY/PRINCIPAL FINDINGS: Denaturing Gradient Gel Electrophoresis (DGGE of the V3 region of the 16S ribosomal DNA was used in a highly replicated approach to analyse bacterial communities on both healthy and diseased corals. Although site-specific variations in the bacterial communities of healthy corals were present, host species-specific bacterial associates within a distinct cluster of gamma-proteobacteria could be identified, which are potentially linked to coral health. Corals affected by "White Syndrome" (WS underwent pronounced changes in their bacterial communities in comparison to healthy colonies. However, the community structure and bacterial ribotypes identified in diseased corals did not support the previously suggested theory of a bacterial pathogen as the causative agent of the syndrome. CONCLUSIONS/SIGNIFICANCE: This is the first study to employ large numbers of replicated samples to assess the bacterial communities of healthy and diseased corals, and the first culture-independent assessment of bacterial communities on WS affected Acroporid corals on the GBR. Results indicate that a minimum of 6 replicate samples are required in order to draw inferences on species, spatial or health-related changes in community composition, as a set of clearly distinct bacterial community profiles exist in healthy corals. Coral bacterial communities may be both site and species specific. Furthermore, a cluster of gamma-proteobacterial ribotypes may represent a group of specific common coral and marine

  9. Large scale gene expression meta-analysis reveals tissue-specific, sex-biased gene expression in humans

    Directory of Open Access Journals (Sweden)

    Benjamin Mayne

    2016-10-01

    Full Text Available The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analysed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes, followed by the heart (375 genes, kidney (224 genes, colon (218 genes and thyroid (163 genes. More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.

  10. Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural basis for cytidine deamination and specificity.

    Science.gov (United States)

    Kouno, Takahide; Silvas, Tania V; Hilbert, Brendan J; Shandilya, Shivender M D; Bohn, Markus F; Kelch, Brian A; Royer, William E; Somasundaran, Mohan; Kurt Yilmaz, Nese; Matsuo, Hiroshi; Schiffer, Celia A

    2017-04-28

    Nucleic acid editing enzymes are essential components of the immune system that lethally mutate viral pathogens and somatically mutate immunoglobulins, and contribute to the diversification and lethality of cancers. Among these enzymes are the seven human APOBEC3 deoxycytidine deaminases, each with unique target sequence specificity and subcellular localization. While the enzymology and biological consequences have been extensively studied, the mechanism by which APOBEC3s recognize and edit DNA remains elusive. Here we present the crystal structure of a complex of a cytidine deaminase with ssDNA bound in the active site at 2.2 Å. This structure not only visualizes the active site poised for catalysis of APOBEC3A, but pinpoints the residues that confer specificity towards CC/TC motifs. The APOBEC3A-ssDNA complex defines the 5'-3' directionality and subtle conformational changes that clench the ssDNA within the binding groove, revealing the architecture and mechanism of ssDNA recognition that is likely conserved among all polynucleotide deaminases, thereby opening the door for the design of mechanistic-based therapeutics.

  11. Interactions between Casein kinase Iepsilon (CKIepsilon and two substrates from disparate signaling pathways reveal mechanisms for substrate-kinase specificity.

    Directory of Open Access Journals (Sweden)

    Caroline Lund Dahlberg

    Full Text Available Members of the Casein Kinase I (CKI family of serine/threonine kinases regulate diverse biological pathways. The seven mammalian CKI isoforms contain a highly conserved kinase domain and divergent amino- and carboxy-termini. Although they share a preferred target recognition sequence and have overlapping expression patterns, individual isoforms often have specific substrates. In an effort to determine how substrates recognize differences between CKI isoforms, we have examined the interaction between CKIepsilon and two substrates from different signaling pathways.CKIepsilon, but not CKIalpha, binds to and phosphorylates two proteins: Period, a transcriptional regulator of the circadian rhythms pathway, and Disheveled, an activator of the planar cell polarity pathway. We use GST-pull-down assays data to show that two key residues in CKIalpha's kinase domain prevent Disheveled and Period from binding. We also show that the unique C-terminus of CKIepsilon does not determine Dishevelled's and Period's preference for CKIepsilon nor is it essential for binding, but instead plays an auxillary role in stabilizing the interactions of CKIepsilon with its substrates. We demonstrate that autophosphorylation of CKIepsilon's C-terminal tail prevents substrate binding, and use mass spectrometry and chemical crosslinking to reveal how a phosphorylation-dependent interaction between the C-terminal tail and the kinase domain prevents substrate phosphorylation and binding.The biochemical interactions between CKIepsilon and Disheveled, Period, and its own C-terminus lead to models that explain CKIepsilon's specificity and regulation.

  12. Genome-Wide Comparison of Magnaporthe Species Reveals a Host-Specific Pattern of Secretory Proteins and Transposable Elements.

    Directory of Open Access Journals (Sweden)

    Meghana Deepak Shirke

    Full Text Available Blast disease caused by the Magnaporthe species is a major factor affecting the productivity of rice, wheat and millets. This study was aimed at generating genomic information for rice and non-rice Magnaporthe isolates to understand the extent of genetic variation. We have sequenced the whole genome of the Magnaporthe isolates, infecting rice (leaf and neck, finger millet (leaf and neck, foxtail millet (leaf and buffel grass (leaf. Rice and finger millet isolates infecting both leaf and neck tissues were sequenced, since the damage and yield loss caused due to neck blast is much higher as compared to leaf blast. The genome-wide comparison was carried out to study the variability in gene content, candidate effectors, repeat element distribution, genes involved in carbohydrate metabolism and SNPs. The analysis of repeat element footprints revealed some genes such as naringenin, 2-oxoglutarate 3-dioxygenase being targeted by Pot2 and Occan, in isolates from different host species. Some repeat insertions were host-specific while other insertions were randomly shared between isolates. The distributions of repeat elements, secretory proteins, CAZymes and SNPs showed significant variation across host-specific lineages of Magnaporthe indicating an independent genome evolution orchestrated by multiple genomic factors.

  13. Sex-specific automatic responses to infant cries: TMS reveals greater excitability in females than males in motor evoked potentials

    Directory of Open Access Journals (Sweden)

    Irene eMessina

    2016-01-01

    Full Text Available Neuroimaging reveals that infant cries activate parts of the premotor cortical system. To validate this effect in a more direct way, we used event-related transcranial magnetic stimulation (TMS. Here, we investigated the presence and the time course of modulation of motor cortex excitability in young adults who listened to infant cries. Specifically, we recorded motor evoked potentials (MEPs from the biceps brachii (BB and interosseus dorsalis primus (ID1 muscles as produced by TMS delivered from 0 to 250 ms from sound onset in six steps of 50 ms in 10 females and 10 males. We observed an excitatory modulation of MEPs at 100 ms from the onset of the infant cry specific to females and to the ID1 muscle. We regard this modulation as a response to natural cry sounds because it was delayed, attenuated to stimuli increasingly different from natural cry, and was absent in a separate group of females who listened to non-cry stimuli physically matched to natural infant cries. Furthermore, the 100-ms latency of this modulation is not compatible with a voluntary reaction to the stimulus but suggests an automatic, bottom-up audiomotor association. The brains of adult females appear to be tuned to respond to infant cries with automatic motor excitation. This effect may reflect the greater and longstanding burden on females in caregiving infants.

  14. Specific default mode subnetworks support mentalizing as revealed through opposing network recruitment by social and semantic FMRI tasks.

    Science.gov (United States)

    Hyatt, Christopher J; Calhoun, Vince D; Pearlson, Godfrey D; Assaf, Michal

    2015-08-01

    The ability to attribute mental states to others, or "mentalizing," is posited to involve specific subnetworks within the overall default mode network (DMN), but this question needs clarification. To determine which default mode (DM) subnetworks are engaged by mentalizing processes, we assessed task-related recruitment of DM subnetworks. Spatial independent component analysis (sICA) applied to fMRI data using relatively high-order model (75 components). Healthy participants (n = 53, ages 17-60) performed two fMRI tasks: an interactive game involving mentalizing (Domino), a semantic memory task (SORT), and a resting state fMRI scan. sICA of the two tasks split the DMN into 10 subnetworks located in three core regions: medial prefrontal cortex (mPFC; five subnetworks), posterior cingulate/precuneus (PCC/PrC; three subnetworks), and bilateral temporoparietal junction (TPJ). Mentalizing events increased recruitment in five of 10 DM subnetworks, located in all three core DMN regions. In addition, three of these five DM subnetworks, one dmPFC subnetwork, one PCC/PrC subnetwork, and the right TPJ subnetwork, showed reduced recruitment by semantic memory task events. The opposing modulation by the two tasks suggests that these three DM subnetworks are specifically engaged in mentalizing. Our findings, therefore, suggest the unique involvement of mentalizing processes in only three of 10 DM subnetworks, and support the importance of the dmPFC, PCC/PrC, and right TPJ in mentalizing as described in prior studies. © 2015 Wiley Periodicals, Inc.

  15. Individual differences in personality traits reflect structural variance in specific brain regions.

    Science.gov (United States)

    Gardini, Simona; Cloninger, C Robert; Venneri, Annalena

    2009-06-30

    Personality dimensions such as novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (PER) are said to be heritable, stable across time and dependent on genetic and neurobiological factors. Recently a better understanding of the relationship between personality traits and brain structures/systems has become possible due to advances in neuroimaging techniques. This Magnetic Resonance Imaging (MRI) study investigated if individual differences in these personality traits reflected structural variance in specific brain regions. A large sample of eighty five young adult participants completed the Three-dimensional Personality Questionnaire (TPQ) and had their brain imaged with MRI. A voxel-based correlation analysis was carried out between individuals' personality trait scores and grey matter volume values extracted from 3D brain scans. NS correlated positively with grey matter volume in frontal and posterior cingulate regions. HA showed a negative correlation with grey matter volume in orbito-frontal, occipital and parietal structures. RD was negatively correlated with grey matter volume in the caudate nucleus and in the rectal frontal gyrus. PER showed a positive correlation with grey matter volume in the precuneus, paracentral lobule and parahippocampal gyrus. These results indicate that individual differences in the main personality dimensions of NS, HA, RD and PER, may reflect structural variance in specific brain areas.

  16. Kinetics and regional specificity of irinotecan-induced gene expression in the gastrointestinal tract

    International Nuclear Information System (INIS)

    Bowen, Joanne M.; Tsykin, Anna; Stringer, Andrea M.; Logan, Richard M.; Gibson, Rachel J.; Keefe, Dorothy M.K.

    2010-01-01

    Gastrointestinal toxicity remains a significant and dose-limiting complication of cancer treatment. While the pathophysiology is becoming clearer, considerable gaps in the knowledge remain surrounding the timing and site-specific gene changes which occur in response to insult. As such, this study aimed to assess gene expression profiles in a number of regions along the gastrointestinal tract following treatment with the chemotherapy agent, irinotecan, and correlate them with markers of cell death and tissue damage. Data analysis of microarray results found that genes involved in apoptosis, mitogen activated kinase (MAPK) signalling and inflammation were upregulated within 6 h, while genes involved in cell proliferation, wound healing and blood vessel formation were upregulated at later time points up to 72 h. Cell death was significantly increased at 6 and 24 h, and the stomach showed the lowest severity of overt tissue damage. Real time PCR of MAPK signalling pathway genes found that the jejunum and colon had significantly increased expression in a number of genes at 72 h, where as the stomach was unchanged. These results indicate that overall severity of tissue damage may be determined by precisely timed target gene responses specific to each region. Therapeutic targeting of key gene responses at the appropriate time point may prove to be effective for prevention of chemotherapy-induced gastrointestinal damage.

  17. Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

    Science.gov (United States)

    Liu, Xiao; Li, Jitao; Guo, Chunmei; Wang, Hongli; Sun, Yaxin; Wang, Han; Su, Yun-Ai; Li, Keqing; Si, Tianmei

    2018-01-01

    Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine. PMID:29375333

  18. Tract-Specific Diffusion Tensor Imaging Reveals Laterality of Neurological Symptoms in Patients with Cervical Compression Myelopathy.

    Science.gov (United States)

    Maki, Satoshi; Koda, Masao; Saito, Junya; Takahashi, Sho; Inada, Taigo; Kamiya, Koshiro; Ota, Mitsutoshi; Iijima, Yasushi; Masuda, Yoshitada; Matsumoto, Koji; Kojima, Masatoshi; Takahashi, Kazuhisa; Obata, Takayuki; Yamazaki, Masashi; Furuya, Takeo

    2016-12-01

    Patients with cervical compression myelopathy (CCM) generally present bilateral neurological symptoms in their extremities. However, a substantial portion of patients with CCM exhibit laterality of neurological symptoms. The aim of this study was to assess the correlation between intrinsic structural damage and laterality of symptoms using spinal cord diffusion tensor imaging (DTI) of the corticospinal tract. We enrolled 10 healthy volunteers and 40 patients with CCM in this study. We evaluated motor function using the American Spinal Injury Association (ASIA) motor score for left and right extremities. For DTI acquisitions, a 3.0-T magnetic resonance imaging system with diffusion-weighted spin-echo sequence was used. Regions-of-interest in the lateral column tracts were determined. We determined the correlations between fractional anisotropy (FA) and ASIA motor scores. An FA asymmetry index was calculated using left and right regions-of-interest. Four patients exhibited laterality of symptoms in their extremities, for which left and right ASIA scores correlated moderately with FA in the left and right lateral columns, respectively (left: ρ = 0.64, P laterality of symptoms. Using tract-specific DTI, we demonstrated that microstructural damages in the left and right corticospinal tracts correlated with corresponding neurological symptoms in the ipsilateral side and the FA asymmetry index could indicate laterality in neurological symptoms of patients with CCM. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. 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

  20. Ex-vivo diffusion MRI reveals microstructural alterations in stress-sensitive brain regions: A chronic mild stress recovery study

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Hansen, Brian; Wiborg, Ove

    Depression is a leading cause of disability worldwide and causes significant microstructural alterations in stress-sensitive brain regions. However, the potential recovery of these microstructural alterations has not previously been investigated, which we, therefore, set out to do using diffusion...... MRI (d-MRI) in the chronic mild stress (CMS) rat model of depression. This study reveals significant microstructural alterations after 8 weeks of recovery, in the opposite direction to change induced by stress in the acute phase of the experiment. Such findings may be useful in the prognosis...... of depression or for monitoring treatment response....

  1. Undertaking cause-specific mortality measurement in an unregistered population: an example from Tigray Region, Ethiopia

    Directory of Open Access Journals (Sweden)

    Hagos Godefay

    2014-09-01

    Full Text Available Background: The lack of adequate documentation of deaths, and particularly their cause, is often noted in African and Asian settings, but practical solutions for addressing the problem are not always clear. Verbal autopsy methods (interviewing witnesses after a death have developed rapidly, but there remains a lack of clarity as to how these methods can be effectively applied to large unregistered populations. This paper sets out practical details for undertaking a representative survey of cause-specific mortality in a population of several million, taking Tigray Region in Ethiopia as a prototype. Sampling: Sampling was designed around an expected level of maternal mortality ratio of 400 per 100,000 live births, which needed measuring within a 95% confidence interval of approximately ±100. Taking a stratified cluster sample within the region at the district level for logistic reasons, and allowing for a design effect of 2, this required a population of around 900,000 people, equating to six typical districts. Since the region is administered in six geographic zones, one district per zone was randomly selected. Implementation: The survey was implemented as a two-stage process: first, to trace deaths that occurred in the sampled districts within the preceding year, and second to follow them up with verbal autopsy interviews. The field work for both stages was undertaken by health extension workers, working in their normally assigned areas. Most of the work was associated with tracing the deaths, rather than undertaking the verbal autopsy interviews. Discussion: This approach to measuring cause-specific mortality in an unregistered Ethiopian population proved to be feasible and effective. Although it falls short of the ideal situation of continuous civil registration and vital statistics, a survey-based strategy of this kind may prove to be a useful intermediate step on the road towards full civil registration and vital statistics implementation.

  2. Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013

    NARCIS (Netherlands)

    Geleijnse, J.M.

    2015-01-01

    Background

    Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188

  3. Nuclear Bombs and Coral: Guam Coral Core Reveals Operation-Specific Radiocarbon Signals from the Pacific Proving Grounds

    Science.gov (United States)

    Andrews, A. H.

    2016-12-01

    Radiocarbon (14C) analyses on a coral core extracted from the western Central Pacific (Guam) has revealed a series of early peaks in the marine bomb 14C record. The typical marine bomb 14C signal, one that is phase lagged and attenuated relative to atmospheric bomb 14C, is present in the coral core and is consistent with other North Pacific records. However, 14C levels that are well above what can be explained by air-sea diffusion alone punctuate this pattern. This anomaly has been demonstrated to a limited extent in other coral cores of the Indo-Pacific region, but is unmatched relative to the magnitude and temporal resolution recorded in the Guam coral core. Other records have shown an early Δ14C rise on the order of 40-50‰ above pre-bomb levels, with a subsequent decline before continuing the gradual Δ14C rise that is indicative of air-sea diffusion of 14CO2. The Guam coral Δ14C record provided three strong pulses in 1954-55, 1956-57, and 1958-59 that are superimposed on the pre-bomb to initial Δ14C rise from atmospheric bomb 14C. Each of these peaks can be directly linked to testing of thermonuclear devices in the Pacific Proving Grounds at Eniwetok and Bikini Atoll of the Marshall Islands. The measurable lag in reaching Guam can be tied to ocean surface currents and can be traced to other regional Δ14C records from corals, providing a transport timeline to places as distant as the Indonesian throughflow, Okinawa and Palmyra.

  4. High-resolution whole-genome sequencing reveals that specific chromatin domains from most human chromosomes associate with nucleoli.

    Science.gov (United States)

    van Koningsbruggen, Silvana; Gierlinski, Marek; Schofield, Pietá; Martin, David; Barton, Geoffey J; Ariyurek, Yavuz; den Dunnen, Johan T; Lamond, Angus I

    2010-11-01

    The nuclear space is mostly occupied by chromosome territories and nuclear bodies. Although this organization of chromosomes affects gene function, relatively little is known about the role of nuclear bodies in the organization of chromosomal regions. The nucleolus is the best-studied subnuclear structure and forms around the rRNA repeat gene clusters on the acrocentric chromosomes. In addition to rDNA, other chromatin sequences also surround the nucleolar surface and may even loop into the nucleolus. These additional nucleolar-associated domains (NADs) have not been well characterized. We present here a whole-genome, high-resolution analysis of chromatin endogenously associated with nucleoli. We have used a combination of three complementary approaches, namely fluorescence comparative genome hybridization, high-throughput deep DNA sequencing and photoactivation combined with time-lapse fluorescence microscopy. The data show that specific sequences from most human chromosomes, in addition to the rDNA repeat units, associate with nucleoli in a reproducible and heritable manner. NADs have in common a high density of AT-rich sequence elements, low gene density and a statistically significant enrichment in transcriptionally repressed genes. Unexpectedly, both the direct DNA sequencing and fluorescence photoactivation data show that certain chromatin loci can specifically associate with either the nucleolus, or the nuclear envelope.

  5. Region-specific study of the electric utility industry: financial history and future power requirements for the VACAR region

    International Nuclear Information System (INIS)

    Pochan, M.J.

    1985-07-01

    Financial data for the period 1966 to 1981 are presented for the four investor-owned electric utilities in the VACAR (Virginia-Carolinas) region. This region was selected as representative for the purpose of assessing the availability, reliability, and cost of electric power for the future in the United States. The estimated demand for power and planned additions to generating capacity for the region through the year 2000 are also given

  6. Multisensory and Modality Specific Processing of Visual Speech in Different Regions of the Premotor Cortex

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    Daniel eCallan

    2014-05-01

    Full Text Available Behavioral and neuroimaging studies have demonstrated that brain regions involved with speech production also support speech perception, especially under degraded conditions. The premotor cortex has been shown to be active during both observation and execution of action (‘Mirror System’ properties, and may facilitate speech perception by mapping unimodal and multimodal sensory features onto articulatory speech gestures. For this functional magnetic resonance imaging (fMRI study, participants identified vowels produced by a speaker in audio-visual (saw the speaker’s articulating face and heard her voice, visual only (only saw the speaker’s articulating face, and audio only (only heard the speaker’s voice conditions with varying audio signal-to-noise ratios in order to determine the regions of the premotor cortex involved with multisensory and modality specific processing of visual speech gestures. The task was designed so that identification could be made with a high level of accuracy from visual only stimuli to control for task difficulty and differences in intelligibility. The results of the fMRI analysis for visual only and audio-visual conditions showed overlapping activity in inferior frontal gyrus and premotor cortex. The left ventral inferior premotor cortex showed properties of multimodal (audio-visual enhancement with a degraded auditory signal. The left inferior parietal lobule and right cerebellum also showed these properties. The left ventral superior and dorsal premotor cortex did not show this multisensory enhancement effect, but there was greater activity for the visual only over audio-visual conditions in these areas. The results suggest that the inferior regions of the ventral premotor cortex are involved with integrating multisensory information, whereas, more superior and dorsal regions of the premotor cortex are involved with mapping unimodal (in this case visual sensory features of the speech signal with

  7. Detection of selection signatures of population-specific genomic regions selected during domestication process in Jinhua pigs.

    Science.gov (United States)

    Li, Zhengcao; Chen, Jiucheng; Wang, Zhen; Pan, Yuchun; Wang, Qishan; Xu, Ningying; Wang, Zhengguang

    2016-12-01

    Chinese pigs have been undergoing both natural and artificial selection for thousands of years. Jinhua pigs are of great importance, as they can be a valuable model for exploring the genetic mechanisms linked to meat quality and other traits such as disease resistance, reproduction and production. The purpose of this study was to identify distinctive footprints of selection between Jinhua pigs and other breeds utilizing genome-wide SNP data. Genotyping by genome reducing and sequencing was implemented in order to perform cross-population extended haplotype homozygosity to reveal strong signatures of selection for those economically important traits. This work was performed at a 2% genome level, which comprised 152 006 SNPs genotyped in a total of 517 individuals. Population-specific footprints of selective sweeps were searched for in the genome of Jinhua pigs using six native breeds and three European breeds as reference groups. Several candidate genes associated with meat quality, health and reproduction, such as GH1, CRHR2, TRAF4 and CCK, were found to be overlapping with the significantly positive outliers. Additionally, the results revealed that some genomic regions associated with meat quality, immune response and reproduction in Jinhua pigs have evolved directionally under domestication and subsequent selections. The identified genes and biological pathways in Jinhua pigs showed different selection patterns in comparison with the Chinese and European breeds. © 2016 Stichting International Foundation for Animal Genetics.

  8. Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets

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    Max Lam

    2017-11-01

    Full Text Available Here, we present a large (n = 107,207 genome-wide association study (GWAS of general cognitive ability (“g”, further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum. Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth.

  9. Mouse Nkrp1-Clr gene cluster sequence and expression analyses reveal conservation of tissue-specific MHC-independent immunosurveillance.

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    Qiang Zhang

    Full Text Available The Nkrp1 (Klrb1-Clr (Clec2 genes encode a receptor-ligand system utilized by NK cells as an MHC-independent immunosurveillance strategy for innate immune responses. The related Ly49 family of MHC-I receptors displays extreme allelic polymorphism and haplotype plasticity. In contrast, previous BAC-mapping and aCGH studies in the mouse suggest the neighboring and related Nkrp1-Clr cluster is evolutionarily stable. To definitively compare the relative evolutionary rate of Nkrp1-Clr vs. Ly49 gene clusters, the Nkrp1-Clr gene clusters from two Ly49 haplotype-disparate inbred mouse strains, BALB/c and 129S6, were sequenced. Both Nkrp1-Clr gene cluster sequences are highly similar to the C57BL/6 reference sequence, displaying the same gene numbers and order, complete pseudogenes, and gene fragments. The Nkrp1-Clr clusters contain a strikingly dissimilar proportion of repetitive elements compared to the Ly49 clusters, suggesting that certain elements may be partly responsible for the highly disparate Ly49 vs. Nkrp1 evolutionary rate. Focused allelic polymorphisms were found within the Nkrp1b/d (Klrb1b, Nkrp1c (Klrb1c, and Clr-c (Clec2f genes, suggestive of possible immune selection. Cell-type specific transcription of Nkrp1-Clr genes in a large panel of tissues/organs was determined. Clr-b (Clec2d and Clr-g (Clec2i showed wide expression, while other Clr genes showed more tissue-specific expression patterns. In situ hybridization revealed specific expression of various members of the Clr family in leukocytes/hematopoietic cells of immune organs, various tissue-restricted epithelial cells (including intestinal, kidney tubular, lung, and corneal progenitor epithelial cells, as well as myocytes. In summary, the Nkrp1-Clr gene cluster appears to evolve more slowly relative to the related Ly49 cluster, and likely regulates innate immunosurveillance in a tissue-specific manner.

  10. Longevity Genes Revealed by Integrative Analysis of Isoform-Specific daf-16/FoxO Mutants of Caenorhabditis elegans.

    Science.gov (United States)

    Chen, Albert Tzong-Yang; Guo, Chunfang; Itani, Omar A; Budaitis, Breane G; Williams, Travis W; Hopkins, Christopher E; McEachin, Richard C; Pande, Manjusha; Grant, Ana R; Yoshina, Sawako; Mitani, Shohei; Hu, Patrick J

    2015-10-01

    FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation. Integration of these datasets enabled the prioritization of a subset of 92 DAF-16/FoxO target genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific target genes significantly influenced longevity. A loss-of-function mutation in the conserved gene gst-20, which is induced by DAF-16A, reduced life span extension in the context of daf-2/IGFR RNAi without influencing longevity in animals subjected to control RNAi. Therefore, gst-20 promotes DAF-16/FoxO-dependent longevity. Conversely, a loss-of-function mutation in srr-4, a gene encoding a seven-transmembrane-domain receptor family member that is repressed by DAF-16A, extended life span in control animals, indicating that DAF-16/FoxO may extend life span at least in part by reducing srr-4 expression. Our discovery of new longevity genes underscores the efficacy of our integrative strategy while providing a general framework for identifying specific downstream gene regulatory events that contribute substantially to transcription factor functions. As FoxO transcription factors have conserved functions in promoting longevity and may be dysregulated in aging-related diseases, these findings promise to illuminate fundamental

  11. Specific patterns of gene space organisation revealed in wheat by using the combination of barley and wheat genomic resources

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    Waugh Robbie

    2010-12-01

    Full Text Available Abstract Background Because of its size, allohexaploid nature and high repeat content, the wheat genome has always been perceived as too complex for efficient molecular studies. We recently constructed the first physical map of a wheat chromosome (3B. However gene mapping is still laborious in wheat because of high redundancy between the three homoeologous genomes. In contrast, in the closely related diploid species, barley, numerous gene-based markers have been developed. This study aims at combining the unique genomic resources developed in wheat and barley to decipher the organisation of gene space on wheat chromosome 3B. Results Three dimensional pools of the minimal tiling path of wheat chromosome 3B physical map were hybridised to a barley Agilent 15K expression microarray. This led to the fine mapping of 738 barley orthologous genes on wheat chromosome 3B. In addition, comparative analyses revealed that 68% of the genes identified were syntenic between the wheat chromosome 3B and barley chromosome 3 H and 59% between wheat chromosome 3B and rice chromosome 1, together with some wheat-specific rearrangements. Finally, it indicated an increasing gradient of gene density from the centromere to the telomeres positively correlated with the number of genes clustered in islands on wheat chromosome 3B. Conclusion Our study shows that novel structural genomics resources now available in wheat and barley can be combined efficiently to overcome specific problems of genetic anchoring of physical contigs in wheat and to perform high-resolution comparative analyses with rice for deciphering the organisation of the wheat gene space.

  12. Gene expression profiling, pathway analysis and subtype classification reveal molecular heterogeneity in hepatocellular carcinoma and suggest subtype specific therapeutic targets.

    Science.gov (United States)

    Agarwal, Rahul; Narayan, Jitendra; Bhattacharyya, Amitava; Saraswat, Mayank; Tomar, Anil Kumar

    2017-10-01

    A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis. The differential gene expression analysis using non-parametric Wilcoxon test revealed a total of 479 up-regulated and 91 down-regulated genes in HCC compared to controls. The list of top differentially expressed genes mainly consists of tumor/cancer associated genes, such as AFP, THBS4, LCN2, GPC3, NUF2, etc. The genes over-expressed in HCC were mainly associated with cell cycle pathways. In total, 59 kinases associated genes were found over-expressed in HCC, including TTK, MELK, BUB1, NEK2, BUB1B, AURKB, PLK1, CDK1, PKMYT1, PBK, etc. Overall four distinct HCC subtypes were predicted using consensus clustering method. Each subtype was unique in terms of gene expression, pathway enrichment and median survival. Conclusively, this study has exposed a number of interesting genes which can be exploited in future as potential markers of HCC, diagnostic as well as prognostic and subtype classification may guide for improved and specific therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Spatiotemporal maps reveal regional differences in the effects on gut motility for Lactobacillus reuteri and rhamnosus strains.

    Science.gov (United States)

    Wu, R Y; Pasyk, M; Wang, B; Forsythe, P; Bienenstock, J; Mao, Y-K; Sharma, P; Stanisz, A M; Kunze, W A

    2013-03-01

    Commensal bacteria such as probiotics that are neuroactive acutely affect the amplitudes of intestinal migrating motor complexes (MMCs). What is lacking for an improved understanding of these motility effects are region specific measurements of velocity and frequency. We have combined intraluminal pressure recordings with spatiotemporal diameter maps to analyze more completely effects of different strains of beneficial bacteria on motility. Intraluminal peak pressure (PPr) was measured and video recordings made of mouse ex vivo jejunum and colon segments before and after intraluminal applications of Lactobacillus rhamnosus (JB-1) or Lactobacillus reuteri (DSM 17938). Migrating motor complex frequency and velocity were calculated. JB-1 decreased jejunal frequencies by 56% and 34% in colon. Jejunal velocities increased 171%, but decreased 31% in colon. Jejunal PPr decreased by 55% and in colon by 21%. DSM 17938 increased jejunal frequencies 63% and in colon 75%; jejunal velocity decreased 57%, but increased in colon 146%; jejunal PPr was reduced 26% and 12% in colon. TRAM-34 decreased frequency by 71% and increased velocity 200% for jejunum, but increased frequency 46% and velocity 50% for colon; PPr was decreased 59% for jejunum and 39% for colon. The results show that probiotics and other beneficial bacteria have strain and region-specific actions on gut motility that can be successfully discriminated using spatiotemporal mapping of diameter changes. Effects are not necessarily the same in colon and jejunum. Further research is needed on the detailed effects of the strains on enteric neuron currents for each gut region. © 2013 Blackwell Publishing Ltd.

  14. Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner.

    Science.gov (United States)

    Bollinger, Justin L; Collins, Kaitlyn E; Patel, Rushi; Wellman, Cara L

    2017-01-01

    Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress

  15. Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner

    Science.gov (United States)

    Bollinger, Justin L.; Collins, Kaitlyn E.; Patel, Rushi

    2017-01-01

    Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress

  16. Platyhelminth Venom Allergen-Like (VAL) proteins: revealing structural diversity, class-specific features and biological associations across the phylum

    Science.gov (United States)

    CHALMERS, IAIN W.; HOFFMANN, KARL F.

    2012-01-01

    SUMMARY During platyhelminth infection, a cocktail of proteins is released by the parasite to aid invasion, initiate feeding, facilitate adaptation and mediate modulation of the host immune response. Included amongst these proteins is the Venom Allergen-Like (VAL) family, part of the larger sperm coating protein/Tpx-1/Ag5/PR-1/Sc7 (SCP/TAPS) superfamily. To explore the significance of this protein family during Platyhelminthes development and host interactions, we systematically summarize all published proteomic, genomic and immunological investigations of the VAL protein family to date. By conducting new genomic and transcriptomic interrogations to identify over 200 VAL proteins (228) from species in all 4 traditional taxonomic classes (Trematoda, Cestoda, Monogenea and Turbellaria), we further expand our knowledge related to platyhelminth VAL diversity across the phylum. Subsequent phylogenetic and tertiary structural analyses reveal several class-specific VAL features, which likely indicate a range of roles mediated by this protein family. Our comprehensive analysis of platyhelminth VALs represents a unifying synopsis for understanding diversity within this protein family and a firm context in which to initiate future functional characterization of these enigmatic members. PMID:22717097

  17. Functional specificity of cardiolipin synthase revealed by the identification of a cardiolipin synthase CrCLS1 in Chlamydomonas reinhardtii

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    Chun-Hsien eHung

    2016-01-01

    Full Text Available Phosphatidylglycerol (PG and cardiolipin (CL are two essential classes of phospholipid in plants and algae. Phosphatidylglycerophosphate synthase (PGPS and cardiolipin synthase (CLS involved in the biosynthesis of PG and CL belong to CDP-alcohol phosphotransferase and share overall amino acid sequence homology. However, it remains elusive whether PGPS and CLS are functionally distinct in vivo. Here, we report identification of a gene encoding CLS in Chlamydomonas reinhardtii, CrCLS1, and its functional compatibility. Whereas CrCLS1 did not complement the growth phenotype of a PGPS mutant of Synechocystis sp. PCC 6803, it rescued the temperature-sensitive growth phenotype, growth profile with different carbon sources, phospholipid composition and enzyme activity of ∆crd1, a CLS mutant of Saccharomyces cerevisiae. These results suggest that CrCLS1 encodes a functional CLS of C. reinhardtii as the first identified algal CLS, whose enzyme function is distinct from that of PGPSs from C. reinhardtii. Comparison of CDP-alcohol phosphotransferase motif between PGPS and CLS among different species revealed a possible additional motif that might define the substrate specificity of these closely related enzymes.

  18. High-Throughput Sequencing Reveals Diverse Sets of Conserved, Nonconserved, and Species-Specific miRNAs in Jute

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    Md. Tariqul Islam

    2015-01-01

    Full Text Available MicroRNAs play a pivotal role in regulating a broad range of biological processes, acting by cleaving mRNAs or by translational repression. A group of plant microRNAs are evolutionarily conserved; however, others are expressed in a species-specific manner. Jute is an agroeconomically important fibre crop; nonetheless, no practical information is available for microRNAs in jute to date. In this study, Illumina sequencing revealed a total of 227 known microRNAs and 17 potential novel microRNA candidates in jute, of which 164 belong to 23 conserved families and the remaining 63 belong to 58 nonconserved families. Among a total of 81 identified microRNA families, 116 potential target genes were predicted for 39 families and 11 targets were predicted for 4 among the 17 identified novel microRNAs. For understanding better the functions of microRNAs, target genes were analyzed by Gene Ontology and their pathways illustrated by KEGG pathway analyses. The presence of microRNAs identified in jute was validated by stem-loop RT-PCR followed by end point PCR and qPCR for randomly selected 20 known and novel microRNAs. This study exhaustively identifies microRNAs and their target genes in jute which will ultimately pave the way for understanding their role in this crop and other crops.

  19. Multiomics in Grape Berry Skin Revealed Specific Induction of the Stilbene Synthetic Pathway by Ultraviolet-C Irradiation1

    Science.gov (United States)

    Suzuki, Mami; Nakabayashi, Ryo; Ogata, Yoshiyuki; Sakurai, Nozomu; Tokimatsu, Toshiaki; Goto, Susumu; Suzuki, Makoto; Jasinski, Michal; Martinoia, Enrico; Otagaki, Shungo; Matsumoto, Shogo; Saito, Kazuki; Shiratake, Katsuhiro

    2015-01-01

    Grape (Vitis vinifera) accumulates various polyphenolic compounds, which protect against environmental stresses, including ultraviolet-C (UV-C) light and pathogens. In this study, we looked at the transcriptome and metabolome in grape berry skin after UV-C irradiation, which demonstrated the effectiveness of omics approaches to clarify important traits of grape. We performed transcriptome analysis using a genome-wide microarray, which revealed 238 genes up-regulated more than 5-fold by UV-C light. Enrichment analysis of Gene Ontology terms showed that genes encoding stilbene synthase, a key enzyme for resveratrol synthesis, were enriched in the up-regulated genes. We performed metabolome analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry, and 2,012 metabolite peaks, including unidentified peaks, were detected. Principal component analysis using the peaks showed that only one metabolite peak, identified as resveratrol, was highly induced by UV-C light. We updated the metabolic pathway map of grape in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and in the KaPPA-View 4 KEGG system, then projected the transcriptome and metabolome data on a metabolic pathway map. The map showed specific induction of the resveratrol synthetic pathway by UV-C light. Our results showed that multiomics is a powerful tool to elucidate the accumulation mechanisms of secondary metabolites, and updated systems, such as KEGG and KaPPA-View 4 KEGG for grape, can support such studies. PMID:25761715

  20. Congener-specific accumulation and trophic transfer of polychlorinated biphenyls in spider crab food webs revealed by stable isotope analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bodin, N. [IFREMER, DCN-BE, Technopole Brest-Iroise, Pointe du Diable, 29280 Plouzane (France); LPTC-UMR 5472 CNRS, Universite de Bordeaux 1, 351 cours de la Liberation, 33400 Talence (France)], E-mail: bodin.nathalie@caramail.com; Le Loc' h, F. [IRD, UR 070 RAP, Centre de Recherche Halieutique, Avenue Jean Monnet, B.P. 171, 34203 Sete Cedex (France); Caisey, X.; Le Guellec, A.-M.; Abarnou, A.; Loizeau, V. [IFREMER, DCN-BE, Technopole Brest-Iroise, Pointe du Diable, 29280 Plouzane (France); Latrouite, D. [IFREMER, DCB-STH, Technopole Brest-Iroise, Pointe du Diable, 29280 Plouzane (France)

    2008-01-15

    Polychlorobiphenyls (PCB) and stable isotopes ({delta}{sup 15}N and {delta}{sup 13}C) were analyzed in the spider crab (Maja brachydactyla) food web from the Iroise Sea (Western Brittany) and the Seine Bay (Eastern English Channel). PCB concentrations were all significantly higher in organisms from the Seine Bay than those from the Iroise Sea. PCB patterns were strongly related to the feeding mode of the species, and increased influence of higher chlorinated congeners was highlighted with trophic position of the organisms. PCB concentrations (lipid normalized) were significantly related to the isotopically derived trophic level (TL) in spider crab food webs. The highest trophic magnification factors (TMFs) were calculated for the congeners with 2,4,5-substitution, and were lower in the Seine Bay compared to the Iroise Sea. The confrontation of PCB and TL data also revealed biotransformation capacity of decapod crustaceans for specific congeners based on structure-activity relations. - The influence of feeding mode and trophic position on the fate of PCBs in spider crab food webs is discussed by using a stable isotopic approach.

  1. Comprehensive analysis of ultrasonic vocalizations in a mouse model of fragile X syndrome reveals limited, call type specific deficits.

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    Snigdha Roy

    Full Text Available Fragile X syndrome (FXS is a well-recognized form of inherited mental retardation, caused by a mutation in the fragile X mental retardation 1 (Fmr1 gene. The gene is located on the long arm of the X chromosome and encodes fragile X mental retardation protein (FMRP. Absence of FMRP in fragile X patients as well as in Fmr1 knockout (KO mice results, among other changes, in abnormal dendritic spine formation and altered synaptic plasticity in the neocortex and hippocampus. Clinical features of FXS include cognitive impairment, anxiety, abnormal social interaction, mental retardation, motor coordination and speech articulation deficits. Mouse pups generate ultrasonic vocalizations (USVs when isolated from their mothers. Whether those social ultrasonic vocalizations are deficient in mouse models of FXS is unknown. Here we compared isolation-induced USVs generated by pups of Fmr1-KO mice with those of their wild type (WT littermates. Though the total number of calls was not significantly different between genotypes, a detailed analysis of 10 different categories of calls revealed that loss of Fmr1 expression in mice causes limited and call-type specific deficits in ultrasonic vocalization: the carrier frequency of flat calls was higher, the percentage of downward calls was lower and that the frequency range of complex calls was wider in Fmr1-KO mice compared to their WT littermates.

  2. Regional specificity in deltamethrin induced cytochrome P450 expression in rat brain

    International Nuclear Information System (INIS)

    Yadav, Sanjay; Johri, Ashu; Dhawan, Alok; Seth, Prahlad K.; Parmar, Devendra

    2006-01-01

    Oral administration of deltamethrin (5 mg/kg x 7 or 15 or 21 days) was found to produce a time-dependent increase in the mRNA expression of xenobiotic metabolizing cytochrome P450 1A1 (CYP1A1), 1A2 and CYP2B1, 2B2 isoenzymes in rat brain. RT-PCR studies further showed that increase in the mRNA expression of these CYP isoenzymes observed after 21 days of exposure was region specific. Hippocampus exhibited maximum increase in the mRNA expression of CYP1A1, which was followed by pons-medulla, cerebellum and hypothalamus. The mRNA expression of CYP2B1 also exhibited maximum increase in the hypothalamus and hippocampus followed by almost similar increase in midbrain and cerebellum. In contrast, mRNA expression of CYP1A2 and CYP2B2, the constitutive isoenzymes exhibited relatively higher increase in pons-medulla, cerebellum and frontal cortex. Immunoblotting studies carried out with polyclonal antibody raised against rat liver CYP1A1/1A2 or CYP2B1/2B2 isoenzymes also showed increase in immunoreactivity comigrating with CYP1A1/1A2 or 2B1/2B2 in the microsomal fractions isolated from hippocampus, hypothalamus and cerebellum of rat treated with deltamethrin. Though the exact relationship of the xenobiotic metabolizing CYPs with the physiological function of the brain is yet to be clearly understood, the increase in the mRNA expression of the CYPs in the brain regions that regulate specific brain functions affected by deltamethrin have further indicated that modulation of these CYPs could be associated with the various endogenous functions of the brain

  3. Region-specific reduction in brain volume in young adults with perinatal hypoxic-ischaemic encephalopathy.

    Science.gov (United States)

    Bregant, Tina; Rados, Milan; Vasung, Lana; Derganc, Metka; Evans, Alan C; Neubauer, David; Kostovic, Ivica

    2013-11-01

    A severe form of perinatal hypoxic-ischaemic encephalopathy (HIE) carries a high risk of perinatal death and severe neurological sequelae while in mild HIE only discrete cognitive disorders may occur. To compare total brain volumes and region-specific cortical measurements between young adults with mild-moderate perinatal HIE and a healthy control group of the same age. MR imaging was performed in a cohort of 14 young adults (9 males, 5 females) with a history of mild or moderate perinatal HIE. The control group consisted of healthy participants, matched with HIE group by age and gender. Volumetric analysis was done after the processing of MR images using a fully automated CIVET pipeline. We measured gyrification indexes, total brain volume, volume of grey and white matter, and of cerebrospinal fluid. We also measured volume, thickness and area of the cerebral cortex in the parietal, occipital, frontal, and temporal lobe, and of the isthmus cinguli, parahippocampal and cingulated gyrus, and insula. The HIE patient group showed smaller absolute volumetric data. Statistically significant (p right hemisphere, of cortical areas in the right temporal lobe and parahippocampal gyrus, of cortical volumes in the right temporal lobe and of cortical thickness in the right isthmus of the cingulate gyrus were found. Comparison between the healthy group and the HIE group of the same gender showed statistically significant changes in the male HIE patients, where a significant reduction was found in whole brain volume; left parietal, bilateral temporal, and right parahippocampal gyrus cortical areas; and bilateral temporal lobe cortical volume. Our analysis of total brain volumes and region-specific corticometric parameters suggests that mild-moderate forms of perinatal HIE lead to reductions in whole brain volumes. In the study reductions were most pronounced in temporal lobe and parahippocampal gyrus. Copyright © 2013 European Paediatric Neurology Society. All rights reserved.

  4. Oxytocin Reduces Cocaine Cued Fos Activation in a Regionally Specific Manner

    Science.gov (United States)

    Leong, Kah-Chung; Freeman, Linnea R; Berini, Carole R; Ghee, Shannon M; See, Ronald E

    2017-01-01

    Abstract Background Oxytocin may be a possible treatment for multiple neuropsychiatric disorders, including cocaine addiction. Little is known about the site-specific effects of oxytocin on various drug addiction-related brain regions. Furthermore, sexually dimorphic effects of oxytocin on neural function in the addiction circuit have not been established. Here, we studied Fos expression following cocaine-cued reinstatement in both male and female rats. Methods Male and female rats underwent self-administration, extinction, and reinstatement tests. On test days, rats were given oxytocin or vehicle, and lever pressing was measured in response to conditioned cocaine cues. Rats were perfused and Fos staining measured in the central amygdala, medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus. Fos/oxytocin double labeling occurred in the paraventricular nucleus of the hypothalamus. Results Rats reinstated to cocaine cues relative to extinction responding and oxytocin reduced cocaine seeking. Oxytocin combined with contingent cue presentations increased Fos+ oxytocin cell bodies within the paraventricular nucleus of the hypothalamus relative to vehicle. Fos expression robustly increased in the central amygdala following oxytocin administration. Oxytocin reversed cue-induced Fos expression in the medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus. Central oxytocin infusion also attenuated reinstated cocaine seeking. Conclusions Oxytocin decreased reinstated cocaine seeking, increased Fos activation in the paraventricular nucleus of the hypothalamus and central amygdala, but normalized cue-induced Fos activation in the medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus, thereby demonstrating regionally specific activation patterns. No sex differences were seen for the effects of oxytocin on cocaine seeking and Fos activation, indicating that oxytocin acts on similar central neural circuits critical to

  5. Fault specific GIS based seismic hazard maps for the Attica region, Greece

    Science.gov (United States)

    Deligiannakis, G.; Papanikolaou, I. D.; Roberts, G.

    2018-04-01

    Traditional seismic hazard assessment methods are based on the historical seismic records for the calculation of an annual probability of exceedance for a particular ground motion level. A new fault-specific seismic hazard assessment method is presented, in order to address problems related to the incompleteness and the inhomogeneity of the historical records and to obtain higher spatial resolution of hazard. This method is applied to the region of Attica, which is the most densely populated area in Greece, as nearly half of the country's population lives in Athens and its surrounding suburbs, in the Greater Athens area. The methodology is based on a database of 24 active faults that could cause damage to Attica in case of seismic rupture. This database provides information about the faults slip rates, lengths and expected magnitudes. The final output of the method is four fault-specific seismic hazard maps, showing the recurrence of expected intensities for each locality. These maps offer a high spatial resolution, as they consider the surface geology. Despite the fact that almost half of the Attica region lies on the lowest seismic risk zone according to the official seismic hazard zonation of Greece, different localities have repeatedly experienced strong ground motions during the last 15 kyrs. Moreover, the maximum recurrence for each intensity occurs in different localities across Attica. Highest recurrence for intensity VII (151-156 times over 15 kyrs, or up to a 96 year return period) is observed in the central part of the Athens basin. The maximum intensity VIII recurrence (115 times over 15 kyrs, or up to a 130 year return period) is observed in the western part of Attica, while the maximum intensity IX (73-77/15 kyrs, or a 195 year return period) and X (25-29/15 kyrs, or a 517 year return period) recurrences are observed near the South Alkyonides fault system, which dominates the strong ground motions hazard in the western part of the Attica mainland.

  6. Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making.

    Science.gov (United States)

    Clarke, Hannah F; Horst, Nicole K; Roberts, Angela C

    2015-03-31

    Dysregulation of the orbitofrontal and ventrolateral prefrontal cortices is implicated in anxiety and mood disorders, but the specific contributions of each region are unknown, including how they gate the impact of threat on decision making. To address this, the effects of GABAergic inactivation of these regions were studied in marmoset monkeys performing an instrumental approach-avoidance decision-making task that is sensitive to changes in anxiety. Inactivation of either region induced a negative bias away from punishment that could be ameliorated with anxiolytic treatment. However, whereas the effects of ventrolateral prefrontal cortex inactivation on punishment avoidance were seen immediately, those of orbitofrontal cortex inactivation were delayed and their expression was dependent upon an amygdala-anterior hippocampal circuit. We propose that these negative biases result from deficits in attentional control and punishment prediction, respectively, and that they provide the basis for understanding how distinct regional prefrontal dysregulation contributes to the heterogeneity of anxiety disorders with implications for cognitive-behavioral treatment strategies.

  7. Complete avian malaria parasite genomes reveal features associated with lineage-specific evolution in birds and mammals

    Science.gov (United States)

    Böhme, Ulrike; Otto, Thomas D.; Cotton, James A.; Steinbiss, Sascha; Sanders, Mandy; Oyola, Samuel O.; Nicot, Antoine; Gandon, Sylvain; Patra, Kailash P.; Herd, Colin; Bushell, Ellen; Modrzynska, Katarzyna K.; Billker, Oliver; Vinetz, Joseph M.; Rivero, Ana; Newbold, Chris I.; Berriman, Matthew

    2018-01-01

    Avian malaria parasites are prevalent around the world and infect a wide diversity of bird species. Here, we report the sequencing and analysis of high-quality draft genome sequences for two avian malaria species, Plasmodium relictum and Plasmodium gallinaceum. We identify 50 genes that are specific to avian malaria, located in an otherwise conserved core of the genome that shares gene synteny with all other sequenced malaria genomes. Phylogenetic analysis suggests that the avian malaria species form an outgroup to the mammalian Plasmodium species, and using amino acid divergence between species, we estimate the avian- and mammalian-infective lineages diverged in the order of 10 million years ago. Consistent with their phylogenetic position, we identify orthologs of genes that had previously appeared to be restricted to the clades of parasites containing Plasmodium falciparum and Plasmodium vivax, the species with the greatest impact on human health. From these orthologs, we explore differential diversifying selection across the genus and show that the avian lineage is remarkable in the extent to which invasion-related genes are evolving. The subtelomeres of the P. relictum and P. gallinaceum genomes contain several novel gene families, including an expanded surf multigene family. We also identify an expansion of reticulocyte binding protein homologs in P. relictum, and within these proteins, we detect distinct regions that are specific to nonhuman primate, humans, rodent, and avian hosts. For the first time in the Plasmodium lineage, we find evidence of transposable elements, including several hundred fragments of LTR-retrotransposons in both species and an apparently complete LTR-retrotransposon in the genome of P. gallinaceum. PMID:29500236

  8. Continuous High Frequency Activity: A peculiar SEEG pattern related to specific brain regions

    Science.gov (United States)

    Melani, Federico; Zelmann, Rina; Mari, Francesco; Gotman, Jean

    2015-01-01

    Objective While visually marking the high frequency oscillations in the stereo-EEG of epileptic patients, we observed a continuous/semicontinuous activity in the ripple band (80–250 Hz), which we defined continuous High Frequency Activity (HFA). We aim to analyze in all brain regions the occurrence and significance of this particular pattern. Methods Twenty patients implanted in mesial temporal and neocortical areas were studied. One minute of slow-wave sleep was reviewed. The background was classified as continuous/semicontinuous, irregular, or sporadic based on the duration of the fast oscillations. Each channel was classified as inside/outside the seizure onset zone (SOZ) or a lesion. Results The continuous/semicontinuous HFA occurred in 54 of the 790 channels analyzed, with a clearly higher prevalence in hippocampus and occipital lobe. No correlation was found with the SOZ or lesions. In the occipital lobe the continuous/semicontinuous HFA was present independently of whether eyes were open or closed. Conclusions We describe what appears to be a new physiological High Frequency Activity, independent of epileptogenicity, present almost exclusively in the hippocampus and occipital cortex but independent of the alpha rhythm. Significance The continuous HFA may be an intrinsic characteristic of specific brain regions, reflecting a particular type of physiological neuronal activity. PMID:23768436

  9. The length of a lantibiotic hinge region has profound influence on antimicrobial activity and host specificity

    Directory of Open Access Journals (Sweden)

    Liang eZhou

    2015-01-01

    Full Text Available Lantibiotics are ribosomally synthesized (methyllanthionine containing peptides which can efficiently inhibit the growth of Gram-positive bacteria. As lantibiotics kill bacteria efficiently and resistance to them is difficult to be obtained, they have the potential to be used in many applications, e.g. in pharmaceutical industry or food industry. Nisin can inhibit the growth of Gram-positive bacteria by binding to lipid II and by making pores in their membrane. The C-terminal part of nisin is known to play an important role during translocation over the membrane and forming pore complexes. However, as the thickness of bacterial membranes varies between different species and environmental conditions, this property could have an influence on the pore forming activity of nisin. To investigate this, the so-called hinge region of nisin (residues NMK was engineered to vary from one to six amino acid residues and specific activity against different indicators was compared. Antimicrobial activity in liquid culture assays showed that wild type nisin is most active, while truncation of the hinge region dramatically reduced the activity of the peptide. However, one or two amino acids extensions showed only slightly reduced activity against most indicator strains. Notably, some variants (+2, +1, -1, -2 exhibited higher antimicrobial activity than nisin in agar well diffusion assays against Lactococcus lactis MG1363, Listeria monocytogenes, Enterococcus faecalis VE14089, Bacillus sporothermodurans IC4 and Bacillus cereus 4153 at certain temperatures.

  10. Modeling road traffic fatalities in India: Smeed's law, time invariance and regional specificity

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    Raj V. Ponnaluri

    2012-07-01

    Full Text Available Mathematical formulations linking road traffic fatalities to vehicle ownership, regional population, and economic growth continue to be developed against the backdrop of Smeed and Andreassen models. Though a few attempts were made, Smeed's law has not been fully tested in India. Using the 1991–2009 panel data from all states, this work (a developed the generalized Smeed and Andreassen models; (b evaluated if traffic fatalities were impacted by structural changes; and (c examined if – in relation to the generalized model – the individual (time and regional models are more relevant for application. Seven models (Smeed: original, generalized, time-variant, state-variant; and Andreassen: generalized, time-variant, state-variant were developed and tested for fit with the actual data. Results showed that the per vehicle fatality rate closely resembled Smeed's formulation. Chow-test yielded a significant F-stat, suggesting that the models for four pre-defined time-blocks are structurally different from the 19-year generalized model. The counterclockwise rotation of the log-linear form also suggested lower fatality rates. While the new government policies, reduced vehicle operating speeds, better healthcare, and improved vehicle technology could be the factors, further research is required to understand the reasons for fatality rate reductions. The intercept and gradients of the time-series models showed high stability and varied only slightly in comparison to the 19-year generalized models, thus suggesting that the latter are pragmatic for application. Regional formulations, however, indicate that they may be more relevant for studying trends and tendencies. This research illustrates the robustness of Smeed's law, and provides evidence for time-invariance but state-specificity.

  11. Region-specific proteolysis differentially regulates type 1 inositol 1,4,5-trisphosphate receptor activity.

    Science.gov (United States)

    Wang, Liwei; Wagner, Larry E; Alzayady, Kamil J; Yule, David I

    2017-07-14

    The inositol 1,4,5 trisphosphate receptor (IP 3 R) is an intracellular Ca 2+ release channel expressed predominately on the membranes of the endoplasmic reticulum. IP 3 R1 can be cleaved by caspase or calpain into at least two receptor fragments. However, the functional consequences of receptor fragmentation are poorly understood. Our previous work has demonstrated that IP 3 R1 channels, formed following either enzymatic fragmentation or expression of the corresponding complementary polypeptide chains, retain tetrameric architecture and are still activated by IP 3 binding despite the loss of peptide continuity. In this study, we demonstrate that region-specific receptor fragmentation modifies channel regulation. Specifically, the agonist-evoked temporal Ca 2+ release profile and protein kinase A modulation of Ca 2+ release are markedly altered. Moreover, we also demonstrate that activation of fragmented IP 3 R1 can result in a distinct functional outcome. Our work suggests that proteolysis of IP 3 R1 may represent a novel form of modulation of IP 3 R1 channel function and increases the repertoire of Ca 2+ signals achievable through this channel. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Specific Chemical and Genetic Markers Revealed a Thousands-Year Presence of Toxic Nodularia spumigena in the Baltic Sea.

    Science.gov (United States)

    Cegłowska, Marta; Toruńska-Sitarz, Anna; Kowalewska, Grażyna; Mazur-Marzec, Hanna

    2018-04-04

    In the Baltic Sea, diazotrophic cyanobacteria have been present for thousands of years, over the whole brackish water phase of the ecosystem. However, our knowledge about the species composition of the cyanobacterial community is limited to the last several decades. In the current study, the presence of species-specific chemical and genetic markers in deep sediments were analyzed to increase the existing knowledge on the history of toxic Nodularia spumigena blooms in the Baltic Sea. As chemical markers, three cyclic nonribosomal peptides were applied: the hepatotoxic nodularin, which in the sea was detected solely in N. spumigena , and two anabaenopeptins (AP827 and AP883a) characteristic of two different chemotypes of this species. From the same sediment samples, DNA was isolated and the gene involved in biosynthesis of nodularin, as well as the phycocyanin intergenic spacer region (PC-IGS), were amplified. The results of chemical and genetic analyses proved for the first time the thousands-year presence of toxic N. spumigena in the Baltic Sea. They also indicated that through all this time, the same two sub-populations of the species co-existed.

  13. Global mapping of cell type-specific open chromatin by FAIRE-seq reveals the regulatory role of the NFI family in adipocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Hironori Waki

    2011-10-01

    Full Text Available Identification of regulatory elements within the genome is crucial for understanding the mechanisms that govern cell type-specific gene expression. We generated genome-wide maps of open chromatin sites in 3T3-L1 adipocytes (on day 0 and day 8 of differentiation and NIH-3T3 fibroblasts using formaldehyde-assisted isolation of regulatory elements coupled with high-throughput sequencing (FAIRE-seq. FAIRE peaks at the promoter were associated with active transcription and histone modifications of H3K4me3 and H3K27ac. Non-promoter FAIRE peaks were characterized by H3K4me1+/me3-, the signature of enhancers, and were largely located in distal regions. The non-promoter FAIRE peaks showed dynamic change during differentiation, while the promoter FAIRE peaks were relatively constant. Functionally, the adipocyte- and preadipocyte-specific non-promoter FAIRE peaks were, respectively, associated with genes up-regulated and down-regulated by differentiation. Genes highly up-regulated during differentiation were associated with multiple clustered adipocyte-specific FAIRE peaks. Among the adipocyte-specific FAIRE peaks, 45.3% and 11.7% overlapped binding sites for, respectively, PPARγ and C/EBPα, the master regulators of adipocyte differentiation. Computational motif analyses of the adipocyte-specific FAIRE peaks revealed enrichment of a binding motif for nuclear family I (NFI transcription factors. Indeed, ChIP assay showed that NFI occupy the adipocyte-specific FAIRE peaks and/or the PPARγ binding sites near PPARγ, C/EBPα, and aP2 genes. Overexpression of NFIA in 3T3-L1 cells resulted in robust induction of these genes and lipid droplet formation without differentiation stimulus. Overexpression of dominant-negative NFIA or siRNA-mediated knockdown of NFIA or NFIB significantly suppressed both induction of genes and lipid accumulation during differentiation, suggesting a physiological function of these factors in the adipogenic program. Together, our

  14. Pan-cancer stratification of solid human epithelial tumors and cancer cell lines reveals commonalities and tissue-specific features of the CpG island methylator phenotype.

    Science.gov (United States)

    Sánchez-Vega, Francisco; Gotea, Valer; Margolin, Gennady; Elnitski, Laura

    2015-01-01

    The term CpG island methylator phenotype (CIMP) has been used to describe widespread DNA hypermethylation at CpG-rich genomic regions affecting clinically distinct subsets of cancer patients. Even though there have been numerous studies of CIMP in individual cancer types, a uniform analysis across tissues is still lacking. We analyze genome-wide patterns of CpG island hypermethylation in 5,253 solid epithelial tumors from 15 cancer types from TCGA and 23 cancer cell lines from ENCODE. We identify differentially methylated loci that define CIMP+ and CIMP- samples, and we use unsupervised clustering to provide a robust molecular stratification of tumor methylomes for 12 cancer types and all cancer cell lines. With a minimal set of 89 discriminative loci, we demonstrate accurate pan-cancer separation of the 12 CIMP+/- subpopulations, based on their average levels of methylation. Tumor samples in different CIMP subclasses show distinctive correlations with gene expression profiles and recurrence of somatic mutations, copy number variations, and epigenetic silencing. Enrichment analyses indicate shared canonical pathways and upstream regulators for CIMP-targeted regions across cancer types. Furthermore, genomic alterations showing consistent associations with CIMP+/- status include genes involved in DNA repair, chromatin remodeling genes, and several histone methyltransferases. Associations of CIMP status with specific clinical features, including overall survival in several cancer types, highlight the importance of the CIMP+/- designation for individual tumor evaluation and personalized medicine. We present a comprehensive computational study of CIMP that reveals pan-cancer commonalities and tissue-specific differences underlying concurrent hypermethylation of CpG islands across tumors. Our stratification of solid tumors and cancer cell lines based on CIMP status is data-driven and agnostic to tumor type by design, which protects against known biases that have hindered

  15. Retroviral vectors encoding ADA regulatory locus control region provide enhanced T-cell-specific transgene expression.

    Science.gov (United States)

    Trinh, Alice T; Ball, Bret G; Weber, Erin; Gallaher, Timothy K; Gluzman-Poltorak, Zoya; Anderson, French; Basile, Lena A

    2009-12-30

    Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone. A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection. Vectors that contained the ADA LCR were preferentially expressed in T-cell lines. Further improvements

  16. Retroviral vectors encoding ADA regulatory locus control region provide enhanced T-cell-specific transgene expression

    Science.gov (United States)

    2009-01-01

    Background Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone. Methods A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection. Results Vectors that contained the ADA LCR were preferentially expressed in T

  17. Molecular Dynamics Simulations of the STAS Domains of Rat Prestin and Human Pendrin Reveal Conformational Motions in Conserved Flexible Regions

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    Alok K. Sharma

    2014-02-01

    domain in solution structure may be more dynamic than rat prestin STAS. Regions of prestin and pendrin identified by RMS fluctuation data as exhibiting larger atomic fluctuations corresponded to nominal GDP-binding regions of the aligned Rv1739c STAS domain of M. tuberculosis. Conclusions: MD simulations of mammalian STAS domains reveal substantial predicted conformational heterogeneity. These predicted conformational dynamics serve to supplement the reported crystal structure of the rat prestin STAS domain, and extend our understanding of the roles of STAS domains in SLC26 anion transporter function.

  18. A novel system for tracking social preference dynamics in mice reveals sex- and strain-specific characteristics.

    Science.gov (United States)

    Netser, Shai; Haskal, Shani; Magalnik, Hen; Wagner, Shlomo

    2017-01-01

    Deciphering the biological mechanisms underlying social behavior in animal models requires standard behavioral paradigms that can be unbiasedly employed in an observer- and laboratory-independent manner. During the past decade, the three-chamber test has become such a standard paradigm used to evaluate social preference (sociability) and social novelty preference in mice. This test suffers from several caveats, including its reliance on spatial navigation skills and negligence of behavioral dynamics. Here, we present a novel experimental apparatus and an automated analysis system which offer an alternative to the three-chamber test while solving the aforementioned caveats. The custom-made apparatus is simple for production, and the analysis system is publically available as an open-source software, enabling its free use. We used this system to compare the dynamics of social behavior during the social preference and social novelty preference tests between male and female C57BL/6J mice. We found that in both tests, male mice keep their preference towards one of the stimuli for longer periods than females. We then employed our system to define several new parameters of social behavioral dynamics in mice and revealed that social preference behavior is segregated in time into two distinct phases. An early exploration phase, characterized by high rate of transitions between stimuli and short bouts of stimulus investigation, is followed by an interaction phase with low transition rate and prolonged interactions, mainly with the preferred stimulus. Finally, we compared the dynamics of social behavior between C57BL/6J and BTBR male mice, the latter of which are considered as asocial strain serving as a model for autism spectrum disorder. We found that BTBR mice ( n  = 8) showed a specific deficit in transition from the exploration phase to the interaction phase in the social preference test, suggesting a reduced tendency towards social interaction. We successfully

  19. Comparative Genomics of Methanopyrus sp. SNP6 and KOL6 Revealing Genomic Regions of Plasticity Implicated in Extremely Thermophilic Profiles

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    Zhiliang Yu

    2017-07-01

    Full Text Available Methanopyrus spp. are usually isolated from harsh niches, such as high osmotic pressure and extreme temperature. However, the molecular mechanisms for their environmental adaption are poorly understood. Archaeal species is commonly considered as primitive organism. The evolutional placement of archaea is a fundamental and intriguing scientific question. We sequenced the genomes of Methanopyrus strains SNP6 and KOL6 isolated from the Atlantic and Iceland, respectively. Comparative genomic analysis revealed genetic diversity and instability implicated in niche adaption, including a number of transporter- and integrase/transposase-related genes. Pan-genome analysis also defined the gene pool of Methanopyrus spp., in addition of ~120-Kb genomic region of plasticity impacting cognate genomic architecture. We believe that Methanopyrus genomics could facilitate efficient investigation/recognition of archaeal phylogenetic diverse patterns, as well as improve understanding of biological roles and significance of these versatile microbes.

  20. CRISPR/Cas9 cleavages in budding yeast reveal templated insertions and strand-specific insertion/deletion profiles.

    Science.gov (United States)

    Lemos, Brenda R; Kaplan, Adam C; Bae, Ji Eun; Ferrazzoli, Alexander E; Kuo, James; Anand, Ranjith P; Waterman, David P; Haber, James E

    2018-02-27

    Harnessing CRISPR-Cas9 technology provides an unprecedented ability to modify genomic loci via DNA double-strand break (DSB) induction and repair. We analyzed nonhomologous end-joining (NHEJ) repair induced by Cas9 in budding yeast and found that the orientation of binding of Cas9 and its guide RNA (gRNA) profoundly influences the pattern of insertion/deletions (indels) at the site of cleavage. A common indel created by Cas9 is a 1-bp (+1) insertion that appears to result from Cas9 creating a 1-nt 5' overhang that is filled in by a DNA polymerase and ligated. The origin of +1 insertions was investigated by using two gRNAs with PAM sequences located on opposite DNA strands but designed to cleave the same sequence. These templated +1 insertions are dependent on the X-family DNA polymerase, Pol4. Deleting Pol4 also eliminated +2 and +3 insertions, which are biased toward homonucleotide insertions. Using inverted PAM sequences, we also found significant differences in overall NHEJ efficiency and repair profiles, suggesting that the binding of the Cas9:gRNA complex influences subsequent NHEJ processing. As with events induced by the site-specific HO endonuclease, CRISPR-Cas9-mediated NHEJ repair depends on the Ku heterodimer and DNA ligase 4. Cas9 events are highly dependent on the Mre11-Rad50-Xrs2 complex, independent of Mre11's nuclease activity. Inspection of the outcomes of a large number of Cas9 cleavage events in mammalian cells reveals a similar templated origin of +1 insertions in human cells, but also a significant frequency of similarly templated +2 insertions.

  1. Some ethylene biosynthesis and AP2/ERF genes reveal a specific pattern of expression during somatic embryogenesis in Hevea brasiliensis

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    Piyatrakul Piyanuch

    2012-12-01

    Full Text Available Abstract Background Ethylene production and signalling play an important role in somatic embryogenesis, especially for species that are recalcitrant in in vitro culture. The AP2/ERF superfamily has been identified and classified in Hevea brasiliensis. This superfamily includes the ERFs involved in response to ethylene. The relative transcript abundance of ethylene biosynthesis genes and of AP2/ERF genes was analysed during somatic embryogenesis for callus lines with different regeneration potential, in order to identify genes regulated during that process. Results The analysis of relative transcript abundance was carried out by real-time RT-PCR for 142 genes. The transcripts of ERFs from group I, VII and VIII were abundant at all stages of the somatic embryogenesis process. Forty genetic expression markers for callus regeneration capacity were identified. Fourteen markers were found for proliferating calli and 35 markers for calli at the end of the embryogenesis induction phase. Sixteen markers discriminated between normal and abnormal embryos and, lastly, there were 36 markers of conversion into plantlets. A phylogenetic analysis comparing the sequences of the AP2 domains of Hevea and Arabidopsis genes enabled us to predict the function of 13 expression marker genes. Conclusions This first characterization of the AP2/ERF superfamily in Hevea revealed dramatic regulation of the expression of AP2/ERF genes during the somatic embryogenesis process. The gene expression markers of proliferating callus capacity to regenerate plants by somatic embryogenesis should make it possible to predict callus lines suitable to be used for multiplication. Further functional characterization of these markers opens up prospects for discovering specific AP2/ERF functions in the Hevea species for which somatic embryogenesis is difficult.

  2. Comparative analyses of population-scale phenomic data in electronic medical records reveal race-specific disease networks

    Science.gov (United States)

    Glicksberg, Benjamin S.; Li, Li; Badgeley, Marcus A.; Shameer, Khader; Kosoy, Roman; Beckmann, Noam D.; Pho, Nam; Hakenberg, Jörg; Ma, Meng; Ayers, Kristin L.; Hoffman, Gabriel E.; Dan Li, Shuyu; Schadt, Eric E.; Patel, Chirag J.; Chen, Rong; Dudley, Joel T.

    2016-01-01

    Motivation: Underrepresentation of racial groups represents an important challenge and major gap in phenomics research. Most of the current human phenomics research is based primarily on European populations; hence it is an important challenge to expand it to consider other population groups. One approach is to utilize data from EMR databases that contain patient data from diverse demographics and ancestries. The implications of this racial underrepresentation of data can be profound regarding effects on the healthcare delivery and actionability. To the best of our knowledge, our work is the first attempt to perform comparative, population-scale analyses of disease networks across three different populations, namely Caucasian (EA), African American (AA) and Hispanic/Latino (HL). Results: We compared susceptibility profiles and temporal connectivity patterns for 1988 diseases and 37 282 disease pairs represented in a clinical population of 1 025 573 patients. Accordingly, we revealed appreciable differences in disease susceptibility, temporal patterns, network structure and underlying disease connections between EA, AA and HL populations. We found 2158 significantly comorbid diseases for the EA cohort, 3265 for AA and 672 for HL. We further outlined key disease pair associations unique to each population as well as categorical enrichments of these pairs. Finally, we identified 51 key ‘hub’ diseases that are the focal points in the race-centric networks and of particular clinical importance. Incorporating race-specific disease comorbidity patterns will produce a more accurate and complete picture of the disease landscape overall and could support more precise understanding of disease relationships and patient management towards improved clinical outcomes. Contacts: rong.chen@mssm.edu or joel.dudley@mssm.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307606

  3. Comparative analyses of population-scale phenomic data in electronic medical records reveal race-specific disease networks.

    Science.gov (United States)

    Glicksberg, Benjamin S; Li, Li; Badgeley, Marcus A; Shameer, Khader; Kosoy, Roman; Beckmann, Noam D; Pho, Nam; Hakenberg, Jörg; Ma, Meng; Ayers, Kristin L; Hoffman, Gabriel E; Dan Li, Shuyu; Schadt, Eric E; Patel, Chirag J; Chen, Rong; Dudley, Joel T

    2016-06-15

    Underrepresentation of racial groups represents an important challenge and major gap in phenomics research. Most of the current human phenomics research is based primarily on European populations; hence it is an important challenge to expand it to consider other population groups. One approach is to utilize data from EMR databases that contain patient data from diverse demographics and ancestries. The implications of this racial underrepresentation of data can be profound regarding effects on the healthcare delivery and actionability. To the best of our knowledge, our work is the first attempt to perform comparative, population-scale analyses of disease networks across three different populations, namely Caucasian (EA), African American (AA) and Hispanic/Latino (HL). We compared susceptibility profiles and temporal connectivity patterns for 1988 diseases and 37 282 disease pairs represented in a clinical population of 1 025 573 patients. Accordingly, we revealed appreciable differences in disease susceptibility, temporal patterns, network structure and underlying disease connections between EA, AA and HL populations. We found 2158 significantly comorbid diseases for the EA cohort, 3265 for AA and 672 for HL. We further outlined key disease pair associations unique to each population as well as categorical enrichments of these pairs. Finally, we identified 51 key 'hub' diseases that are the focal points in the race-centric networks and of particular clinical importance. Incorporating race-specific disease comorbidity patterns will produce a more accurate and complete picture of the disease landscape overall and could support more precise understanding of disease relationships and patient management towards improved clinical outcomes. rong.chen@mssm.edu or joel.dudley@mssm.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  4. SU-F-I-12: Region-Specific Dictionary Learning for Low-Dose X-Ray CT Reconstruction

    International Nuclear Information System (INIS)

    Xu, Q; Han, H; Xing, L

    2016-01-01

    Purpose: Dictionary learning based method has attracted more and more attentions in low-dose CT due to the superior performance on suppressing noise and preserving structural details. Considering the structures and noise vary from region to region in one imaging object, we propose a region-specific dictionary learning method to improve the low-dose CT reconstruction. Methods: A set of normal-dose images was used for dictionary learning. Segmentations were performed on these images, so that the training patch sets corresponding to different regions can be extracted out. After that, region-specific dictionaries were learned from these training sets. For the low-dose CT reconstruction, a conventional reconstruction, such as filtered back-projection (FBP), was performed firstly, and then segmentation was followed to segment the image into different regions. Sparsity constraints of each region based on its dictionary were used as regularization terms. The regularization parameters were selected adaptively according to different regions. A low-dose human thorax dataset was used to evaluate the proposed method. The single dictionary based method was performed for comparison. Results: Since the lung region is very different from the other part of thorax, two dictionaries corresponding to lung region and the rest part of thorax respectively were learned to better express the structural details and avoid artifacts. With only one dictionary some artifact appeared in the body region caused by the spot atoms corresponding to the structures in the lung region. And also some structure in the lung regions cannot be recovered well by only one dictionary. The quantitative indices of the result by the proposed method were also improved a little compared to the single dictionary based method. Conclusion: Region-specific dictionary can make the dictionary more adaptive to different region characteristics, which is much desirable for enhancing the performance of dictionary learning

  5. SU-F-I-12: Region-Specific Dictionary Learning for Low-Dose X-Ray CT Reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Q; Han, H; Xing, L [Stanford University School of Medicine, Stanford, CA (United States)

    2016-06-15

    Purpose: Dictionary learning based method has attracted more and more attentions in low-dose CT due to the superior performance on suppressing noise and preserving structural details. Considering the structures and noise vary from region to region in one imaging object, we propose a region-specific dictionary learning method to improve the low-dose CT reconstruction. Methods: A set of normal-dose images was used for dictionary learning. Segmentations were performed on these images, so that the training patch sets corresponding to different regions can be extracted out. After that, region-specific dictionaries were learned from these training sets. For the low-dose CT reconstruction, a conventional reconstruction, such as filtered back-projection (FBP), was performed firstly, and then segmentation was followed to segment the image into different regions. Sparsity constraints of each region based on its dictionary were used as regularization terms. The regularization parameters were selected adaptively according to different regions. A low-dose human thorax dataset was used to evaluate the proposed method. The single dictionary based method was performed for comparison. Results: Since the lung region is very different from the other part of thorax, two dictionaries corresponding to lung region and the rest part of thorax respectively were learned to better express the structural details and avoid artifacts. With only one dictionary some artifact appeared in the body region caused by the spot atoms corresponding to the structures in the lung region. And also some structure in the lung regions cannot be recovered well by only one dictionary. The quantitative indices of the result by the proposed method were also improved a little compared to the single dictionary based method. Conclusion: Region-specific dictionary can make the dictionary more adaptive to different region characteristics, which is much desirable for enhancing the performance of dictionary learning

  6. Crystal structures of the F and pSLT plasmid TraJ N-terminal regions reveal similar homodimeric PAS folds with functional interchangeability

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jun; Wu, Ruiying; Adkins, Joshua N.; Joachimiak, Andrzej; Glover, Mark

    2014-09-16

    In the F-family of conjugative plasmids, TraJ is an essential transcriptional activator of the tra operon that encodes most of the proteins required for conjugation. Here we report for the first time the X-ray crystal structures of the TraJ N-terminal regions from the prototypic F plasmid (TraJF11-130) and from the Salmonella virulence plasmid pSLT (TraJpSLT 1-128). Both proteins form similar homodimeric Per-ARNT-Sim (PAS) fold structures. Mutational analysis reveals that the observed dimeric interface is critical for TraJF transcriptional activation, indicating that dimerization of TraJ is required for its in vivo function. An artificial ligand (oxidized dithiothreitol) occupies a cavity in the TraJF dimer interface, while a smaller cavity in corresponding region of the TraJpSLT structure lacks a ligand. Gas chromatography/mass spectrometry-electron ionization analysis of dithiothreitol-free TraJF suggests indole may be the natural TraJ ligand; however, disruption of the indole biosynthetic pathway does not affect TraJF function. Heterologous PAS domains from pSLT and R100 TraJ can functionally replace the TraJF PAS domain, suggesting that TraJ allelic specificity is mediated by the region C-terminal to the PAS domain.

  7. Genomic Resources of Three Pulsatilla Species Reveal Evolutionary Hotspots, Species-Specific Sites and Variable Plastid Structure in the Family Ranunculaceae.

    Science.gov (United States)

    Szczecińska, Monika; Sawicki, Jakub

    2015-09-15

    The European continent is presently colonized by nine species of the genus Pulsatilla, five of which are encountered only in mountainous regions of southwest and south-central Europe. The remaining four species inhabit lowlands in the north-central and eastern parts of the continent. Most plants of the genus Pulsatilla are rare and endangered, which is why most research efforts focused on their biology, ecology and hybridization. The objective of this study was to develop genomic resources, including complete plastid genomes and nuclear rRNA clusters, for three sympatric Pulsatilla species that are most commonly found in Central Europe. The results will supply valuable information about genetic variation, which can be used in the process of designing primers for population studies and conservation genetics research. The complete plastid genomes together with the nuclear rRNA cluster can serve as a useful tool in hybridization studies. Six complete plastid genomes and nuclear rRNA clusters were sequenced from three species of Pulsatilla using the Illumina sequencing technology. Four junctions between single copy regions and inverted repeats and junctions between the identified locally-collinear blocks (LCB) were confirmed by Sanger sequencing. Pulsatilla genomes of 120 unique genes had a total length of approximately 161-162 kb, and 21 were duplicated in the inverted repeats (IR) region. Comparative plastid genomes of newly-sequenced Pulsatilla and the previously-identified plastomes of Aconitum and Ranunculus species belonging to the family Ranunculaceae revealed several variations in the structure of the genome, but the gene content remained constant. The nuclear rRNA cluster (18S-ITS1-5.8S-ITS2-26S) of studied Pulsatilla species is 5795 bp long. Among five analyzed regions of the rRNA cluster, only Internal Transcribed Spacer 2 (ITS2) enabled the molecular delimitation of closely-related Pulsatilla patens and Pulsatilla vernalis. The determination of complete

  8. Strand-specific RNA-seq reveals widespread occurrence of novel cis-natural antisense transcripts in rice

    Directory of Open Access Journals (Sweden)

    Lu Tingting

    2012-12-01

    Full Text Available Abstract Background Cis-natural antisense transcripts (cis-NATs are RNAs transcribed from the antisense strand of a gene locus, and are complementary to the RNA transcribed from the sense strand. Common techniques including microarray approach and analysis of transcriptome databases are the major ways to globally identify cis-NATs in various eukaryotic organisms. Genome-wide in silico analysis has identified a large number of cis-NATs that may generate endogenous short interfering RNAs (nat-siRNAs, which participate in important biogenesis mechanisms for transcriptional and post-transcriptional regulation in rice. However, the transcriptomes are yet to be deeply sequenced to comprehensively investigate cis-NATs. Results We applied high-throughput strand-specific complementary DNA sequencing technology (ssRNA-seq to deeply sequence mRNA for assessing sense and antisense transcripts that were derived under salt, drought and cold stresses, and normal conditions, in the model plant rice (Oryza sativa. Combined with RAP-DB genome annotation (the Rice Annotation Project Database build-5 data set, 76,013 transcripts corresponding to 45,844 unique gene loci were assembled, in which 4873 gene loci were newly identified. Of 3819 putative rice cis-NATs, 2292 were detected as expressed and giving rise to small RNAs from their overlapping regions through integrated analysis of ssRNA-seq data and small RNA data. Among them, 503 cis-NATs seemed to be associated with specific conditions. The deep sequence data from isolated epidermal cells of rice seedlings further showed that 54.0% of cis-NATs were expressed simultaneously in a population of homogenous cells. Nearly 9.7% of rice transcripts were involved in one-to-one or many-to-many cis-NATs formation. Furthermore, only 17.4-34.7% of 223 many-to-many cis-NAT groups were all expressed and generated nat-siRNAs, indicating that only some cis-NAT groups may be involved in complex regulatory networks. Conclusions

  9. Microarray Analysis of Copy Number Variants on the Human Y Chromosome Reveals Novel and Frequent Duplications Overrepresented in Specific Haplogroups.

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    Martin M Johansson

    Full Text Available The human Y chromosome is almost always excluded from genome-wide investigations of copy number variants (CNVs due to its highly repetitive structure. This chromosome should not be forgotten, not only for its well-known relevance in male fertility, but also for its involvement in clinical phenotypes such as cancers, heart failure and sex specific effects on brain and behaviour.We analysed Y chromosome data from Affymetrix 6.0 SNP arrays and found that the signal intensities for most of 8179 SNP/CN probes in the male specific region (MSY discriminated between a male, background signals in a female and an isodicentric male containing a large deletion of the q-arm and a duplication of the p-arm of the Y chromosome. Therefore, this SNP/CN platform is suitable for identification of gain and loss of Y chromosome sequences. In a set of 1718 males, we found 25 different CNV patterns, many of which are novel. We confirmed some of these variants by PCR or qPCR. The total frequency of individuals with CNVs was 14.7%, including 9.5% with duplications, 4.5% with deletions and 0.7% exhibiting both. Hence, a novel observation is that the frequency of duplications was more than twice the frequency of deletions. Another striking result was that 10 of the 25 detected variants were significantly overrepresented in one or more haplogroups, demonstrating the importance to control for haplogroups in genome-wide investigations to avoid stratification. NO-M214(xM175 individuals presented the highest percentage (95% of CNVs. If they were not counted, 12.4% of the rest included CNVs, and the difference between duplications (8.9% and deletions (2.8% was even larger.Our results demonstrate that currently available genome-wide SNP platforms can be used to identify duplications and deletions in the human Y chromosome. Future association studies of the full spectrum of Y chromosome variants will demonstrate the potential involvement of gain or loss of Y chromosome sequence in

  10. Genomic library screening for viruses from the human dental plaque revealed pathogen-specific lytic phage sequences.

    Science.gov (United States)

    Al-Jarbou, Ahmed Nasser

    2012-01-01

    Bacterial pathogenesis presents an astounding arsenal of virulence factors that allow them to conquer many different niches throughout the course of infection. Principally fascinating is the fact that some bacterial species are able to induce different diseases by expression of different combinations of virulence factors. Nevertheless, studies aiming at screening for the presence of bacteriophages in humans have been limited. Such screening procedures would eventually lead to identification of phage-encoded properties that impart increased bacterial fitness and/or virulence in a particular niche, and hence, would potentially be used to reverse the course of bacterial infections. As the human oral cavity represents a rich and dynamic ecosystem for several upper respiratory tract pathogens. However, little is known about virus diversity in human dental plaque which is an important reservoir. We applied the culture-independent approach to characterize virus diversity in human dental plaque making a library from a virus DNA fraction amplified using a multiple displacement method and sequenced 80 clones. The resulting sequence showed 44% significant identities to GenBank databases by TBLASTX analysis. TBLAST homology comparisons showed that 66% was viral; 18% eukarya; 10% bacterial; 6% mobile elements. These sequences were sorted into 6 contigs and 45 single sequences in which 4 contigs and a single sequence showed significant identity to a small region of a putative prophage in the Corynebacterium diphtheria genome. These findings interestingly highlight the uniqueness of over half of the sequences, whilst the dominance of a pathogen-specific prophage sequences imply their role in virulence.

  11. Microbial Metabolism in Soil at Subzero Temperatures: Adaptation Mechanisms Revealed by Position-Specific 13C Labeling

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    Ezekiel K. Bore

    2017-05-01

    Full Text Available Although biogeochemical models designed to simulate carbon (C and nitrogen (N dynamics in high-latitude ecosystems incorporate extracellular parameters, molecular and biochemical adaptations of microorganisms to freezing remain unclear. This knowledge gap hampers estimations of the C balance and ecosystem feedback in high-latitude regions. To analyze microbial metabolism at subzero temperatures, soils were incubated with isotopomers of position-specifically 13C-labeled glucose at three temperatures: +5 (control, -5, and -20°C. 13C was quantified in CO2, bulk soil, microbial biomass, and dissolved organic carbon (DOC after 1, 3, and 10 days and also after 30 days for samples at -20°C. Compared to +5°C, CO2 decreased 3- and 10-fold at -5 and -20°C, respectively. High 13C recovery in CO2 from the C-1 position indicates dominance of the pentose phosphate pathway at +5°C. In contrast, increased oxidation of the C-4 position at subzero temperatures implies a switch to glycolysis. A threefold higher 13C recovery in microbial biomass at -5 than +5°C points to synthesis of intracellular compounds such as glycerol and ethanol in response to freezing. Less than 0.4% of 13C was recovered in DOC after 1 day, demonstrating complete glucose uptake by microorganisms even at -20°C. Consequently, we attribute the fivefold higher extracellular 13C in soil than in microbial biomass to secreted antifreeze compounds. This suggests that with decreasing temperature, intracellular antifreeze protection is complemented by extracellular mechanisms to avoid cellular damage by crystallizing water. The knowledge of sustained metabolism at subzero temperatures will not only be useful for modeling global C dynamics in ecosystems with periodically or permanently frozen soils, but will also be important in understanding and controlling the adaptive mechanisms of food spoilage organisms.

  12. Seedling transplants reveal species-specific responses of high-elevation tropical treeline trees to climate change.

    Science.gov (United States)

    Rehm, Evan M; Feeley, Kenneth J

    2016-08-01

    The elevations at which tropical treelines occur are believed to represent the point where low mean temperatures limit the growth of upright woody trees. Consequently, tropical treelines are predicted to shift to higher elevations with global warming. However, treelines throughout the tropics have remained stationary despite increasing global mean temperatures. The goal of the study reported here was to build a more comprehensive understanding of the effects of mean temperature, low-temperature extremes, shading, and their interactions on seedling survival at tropical treelines. We conducted a seedling transplant study using three dominant canopy-forming treeline species in the southern tropical Andes. We found species-specific differences and contrasting responses in seedling survival to changes in mean temperature. The most abundant naturally occurring species at the seedling stage outside the treeline, Weinmannia fagaroides, showed a negative relationship between the survival of transplanted seedlings and mean temperature, the opposite of a priori expectations. Conversely, Clethra cuneata showed increased survival at higher mean temperatures, but survival also increased with higher absolute low temperatures and the presence of shade. Finally, the survival of Gynoxys nitida seedlings was insensitive to temperature but increased under shade. These findings show that multiple factors can determine the upper distributional limit of species forming the current tropical treeline. As such, predictions of future local and regional tropical treeline shifts may need to consider several factors beyond changes in mean temperature. If the treeline remains stationary and cloud forests are unable to expand into higher elevations, there may be severe species loss in this biodiversity hotspot.

  13. Phylogenomic analysis of vertebrate thrombospondins reveals fish-specific paralogues, ancestral gene relationships and a tetrapod innovation

    Directory of Open Access Journals (Sweden)

    Adams Josephine C

    2006-04-01

    Full Text Available Abstract Background Thrombospondins (TSPs are evolutionarily-conserved, extracellular, calcium-binding glycoproteins with important roles in cell-extracellular matrix interactions, angiogenesis, synaptogenesis and connective tissue organisation. Five TSPs, designated TSP-1 through TSP-5, are encoded in the human genome. All but one have known roles in acquired or inherited human diseases. To further understand the roles of TSPs in human physiology and pathology, it would be advantageous to extend the repertoire of relevant vertebrate models. In general the zebrafish is proving an excellent model organism for vertebrate biology, therefore we set out to evaluate the status of TSPs in zebrafish and two species of pufferfish. Results We identified by bioinformatics that three fish species encode larger numbers of TSPs than vertebrates, yet all these sequences group as homologues of TSP-1 to -4. By phylogenomic analysis of neighboring genes, we uncovered that, in fish, a TSP-4-like sequence is encoded from the gene corresponding to the tetrapod TSP-5 gene. Thus, all TSP genes show conservation of synteny between fish and tetrapods. In the human genome, the TSP-1, TSP-3, TSP-4 and TSP-5 genes lie within paralogous regions that provide insight into the ancestral genomic context of vertebrate TSPs. Conclusion A new model for TSP evolution in vertebrates is presented. The TSP-5 protein sequence has evolved rapidly from a TSP-4-like sequence as an innovation in the tetrapod lineage. TSP biology in fish is complicated by the presence of additional lineage- and species-specific TSP paralogues. These novel results give deeper insight into the evolution of TSPs in vertebrates and open new directions for understanding the physiological and pathological roles of TSP-4 and TSP-5 in humans.

  14. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR).

    Science.gov (United States)

    Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J; Laclette, Juan P; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

    2015-05-19

    Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest.

  15. Region-specific role for Pten in maintenance of epithelial phenotype and integrity

    Science.gov (United States)

    Flodby, Per; Sunohara, Mitsuhiro; Castillo, Dan R.; McConnell, Alicia M.; Krishnaveni, Manda S.; Banfalvi, Agnes; Li, Min; Stripp, Barry; Zhou, Beiyun; Crandall, Edward D.; Minoo, Parviz

    2017-01-01

    Previous studies have demonstrated resistance to naphthalene-induced injury in proximal airways of mice with lung epithelial-specific deletion of the tumor-suppressor gene Pten, attributed to increased proliferation of airway progenitors. We tested effects of Pten loss following bleomycin injury, a model typically used to study distal lung epithelial injury, in conditional PtenSFTPC-cre knockout mice. Pten-deficient airway epithelium exhibited marked hyperplasia, particularly in small bronchioles and at bronchoalveolar duct junctions, with reduced E-cadherin and β-catenin expression between cells toward the luminal aspect of the hyperplastic epithelium. Bronchiolar epithelial and alveolar epithelial type II (AT2) cells in PtenSFTPC-cre mice showed decreased expression of epithelial markers and increased expression of mesenchymal markers, suggesting at least partial epithelial-mesenchymal transition at baseline. Surprisingly, and in contrast to previous studies, mutant mice were exquisitely sensitive to bleomycin, manifesting rapid weight loss, respiratory distress, increased early mortality (by day 5), and reduced dynamic lung compliance. This was accompanied by sloughing of the hyperplastic airway epithelium with occlusion of small bronchioles by cellular debris, without evidence of increased parenchymal lung injury. Increased airway epithelial cell apoptosis due to loss of antioxidant defenses, reflected by decreased expression of superoxide dismutase 3, in combination with deficient intercellular adhesion, likely predisposed to airway sloughing in knockout mice. These findings demonstrate an important role for Pten in maintenance of airway epithelial phenotype integrity and indicate that responses to Pten deletion in respiratory epithelium following acute lung injury are highly context-dependent and region-specific. PMID:27864284

  16. Physical Environmental Correlates of Domain-Specific Sedentary Behaviours across Five European Regions (the SPOTLIGHT Project).

    Science.gov (United States)

    Compernolle, Sofie; De Cocker, Katrien; Roda, Célina; Oppert, Jean-Michel; Mackenbach, Joreintje D; Lakerveld, Jeroen; Glonti, Ketevan; Bardos, Helga; Rutter, Harry; Cardon, Greet; De Bourdeaudhuij, Ilse

    2016-01-01

    The relation between neighbourhood environmental factors and domain-specific sedentary behaviours among adults remains unclear. This study firstly aims to examine the association of perceived and objectively measured neighbourhood safety, aesthetics, destinations and functionality with transport-related, work-related and leisure-time sedentary behaviour. Secondly, the study aims to assess whether these associations are moderated by age, gender or educational level. In 60 randomly sampled neighbourhoods from 5 urban regions in Europe (Ghent and suburbs, Paris and inner suburbs, Budapest and suburbs, the Randstad, and Greater London), a virtual audit with Google Street View was performed to assess environmental characteristics. A total of 5,205 adult inhabitants of these neighbourhoods reported socio-demographic characteristics, sedentary behaviours, and neighbourhood perceptions in an online survey. Generalized linear mixed models were conducted to examine associations between physical environmental neighbourhood factors and sedentary behaviours. Interaction terms were added to test the moderating role of individual-level socio-demographic variables. Lower levels of leisure-time sedentary behaviour (i.e. all leisure activities except television viewing and computer use) were observed among adults who perceived greater numbers of destinations such as supermarkets, recreational facilities, or restaurants in their neighbourhood, and among adults who lived in a neighbourhood with more objectively measured aesthetic features, such as trees, water areas or public parks. Lower levels of work-related sedentary behaviour were observed among adults who perceived less aesthetic features in their neighbourhood, and among adults who lived in a neighbourhood with less objectively measured destinations. Both age, gender and educational level moderated the associations between neighbourhood environmental factors and sedentary behaviours. Preliminary evidence was found for

  17. Physical Environmental Correlates of Domain-Specific Sedentary Behaviours across Five European Regions (the SPOTLIGHT Project.

    Directory of Open Access Journals (Sweden)

    Sofie Compernolle

    Full Text Available The relation between neighbourhood environmental factors and domain-specific sedentary behaviours among adults remains unclear. This study firstly aims to examine the association of perceived and objectively measured neighbourhood safety, aesthetics, destinations and functionality with transport-related, work-related and leisure-time sedentary behaviour. Secondly, the study aims to assess whether these associations are moderated by age, gender or educational level.In 60 randomly sampled neighbourhoods from 5 urban regions in Europe (Ghent and suburbs, Paris and inner suburbs, Budapest and suburbs, the Randstad, and Greater London, a virtual audit with Google Street View was performed to assess environmental characteristics. A total of 5,205 adult inhabitants of these neighbourhoods reported socio-demographic characteristics, sedentary behaviours, and neighbourhood perceptions in an online survey. Generalized linear mixed models were conducted to examine associations between physical environmental neighbourhood factors and sedentary behaviours. Interaction terms were added to test the moderating role of individual-level socio-demographic variables.Lower levels of leisure-time sedentary behaviour (i.e. all leisure activities except television viewing and computer use were observed among adults who perceived greater numbers of destinations such as supermarkets, recreational facilities, or restaurants in their neighbourhood, and among adults who lived in a neighbourhood with more objectively measured aesthetic features, such as trees, water areas or public parks. Lower levels of work-related sedentary behaviour were observed among adults who perceived less aesthetic features in their neighbourhood, and among adults who lived in a neighbourhood with less objectively measured destinations. Both age, gender and educational level moderated the associations between neighbourhood environmental factors and sedentary behaviours.Preliminary evidence was

  18. Regional specific mean expiratory gas flow from Slmsub(Kr) equilibrium inhalation data

    International Nuclear Information System (INIS)

    Hamilton, D.; Causer, D.A.; McIntosh, J.A.; Godfrey, K.R.

    1985-01-01

    A new method of analysing the data available from routine sup(81m) Kr equilibrium inhalation investigations has been developed. The data for analysis are acquired from a gamma camera in the form of a sequential series of images from which multiple breath activity-time curves are generated for eight regions in the lung. The method is based on a description of the behaviour of the radioactive gas in the lung using a mathematical model. Values of specific mean expiratory gas flow, that is mean expiratory gas flow per unit lung volume, are calculated from the application of the model to the expiratory phase only only of a single breath activity-time curve which is generated from the multiple breath activity-time curve using post-acquisition gating. This method overcomes the problem of non-uniform inspiratory concentration of tracer gas experienced in previously reported techniques of analysing inhalation data obtained using poorly soluble radioactive gases. The model is shown, in simulation studies, to be an adequate description of the behaviour of radioactive gas in the lung and the analysis technique is shown, in clinical studies, to be both reproducible and sensitive to disease state. (orig.)

  19. System/subsystem specifications for the Worldwide Port System (WPS) Regional Integrated Cargo Database (ICDB)

    Energy Technology Data Exchange (ETDEWEB)

    Rollow, J.P.; Shipe, P.C.; Truett, L.F. [Oak Ridge National Lab., TN (United States); Faby, E.Z.; Fluker, J.; Grubb, J.; Hancock, B.R. [Univ. of Tennessee, Knoxville, TN (United States); Ferguson, R.A. [Science Applications International Corp., Oak Ridge, TN (United States)

    1995-11-20

    A system is being developed by the Military Traffic Management Command (MTMC) to provide data integration and worldwide management and tracking of surface cargo movements. The Integrated Cargo Database (ICDB) will be a data repository for the WPS terminal-level system, will be a primary source of queries and cargo traffic reports, will receive data from and provide data to other MTMC and non-MTMC systems, will provide capabilities for processing Advance Transportation Control and Movement Documents (ATCMDs), and will process and distribute manifests. This System/Subsystem Specifications for the Worldwide Port System Regional ICDB documents the system/subsystem functions, provides details of the system/subsystem analysis in order to provide a communication link between developers and operational personnel, and identifies interfaces with other systems and subsystems. It must be noted that this report is being produced near the end of the initial development phase of ICDB, while formal software testing is being done. Following the initial implementation of the ICDB system, maintenance contractors will be in charge of making changes and enhancing software modules. Formal testing and user reviews may indicate the need for additional software units or changes to existing ones. This report describes the software units that are components of this ICDB system as of August 1995.

  20. Subject-specific regional measures of water diffusion are associated with impairment in chronic spinal cord injury.

    Science.gov (United States)

    Choe, Ann S; Sadowsky, Cristina L; Smith, Seth A; van Zijl, Peter C M; Pekar, James J; Belegu, Visar

    2017-08-01

    We aimed to identify non-invasive imaging parameters that can serve as biomarkers for the integrity of the spinal cord, which is paramount to neurological function. Diffusion tensor imaging (DTI) indices are sensitive to axonal and myelin damage, and have strong potential to serve as such biomarkers. However, averaging DTI indices over large regions of interest (ROIs), a common approach to analyzing the images of injured spinal cord, leads to loss of subject-specific information. We investigated if DTI-tractography-driven, subject-specific demarcation approach can yield measures that are more specific to impairment. In 18 individuals with chronic spinal cord injury (SCI), subject-specific demarcation of the injury region was performed using DTI tractography, which yielded three regions relative to injury (RRI; regions superior to, at, and below injury epicenter). DTI indices averaged over each RRI were correlated with measures of residual motor and sensory function, obtained using the International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI). Total ISNCSCI score (ISNCSCI-tot; sum of ISNCSCI motor and sensory scores) was significantly (p injury epicenter (IRRI), the degree of which exceeded that of those measured from the entire cervical cord-suggesting contribution from Wallerian degeneration. DTI tractography-driven, subject-specific injury demarcation approach provided measures that were more specific to impairment. Notably, DTI indices obtained from the IRRI region showed the highest specificity to impairment, demonstrating their strong potential as biomarkers for the SCI severity.

  1. Improving cluster-based methods for investigating potential for insect pest species establishment: region-specific risk factors

    Directory of Open Access Journals (Sweden)

    Michael J. Watts

    2011-09-01

    Full Text Available Existing cluster-based methods for investigating insect species assemblages or profiles of a region to indicate the risk of new insect pest invasion have a major limitation in that they assign the same species risk factors to each region in a cluster. Clearly regions assigned to the same cluster have different degrees of similarity with respect to their species profile or assemblage. This study addresses this concern by applying weighting factors to the cluster elements used to calculate regional risk factors, thereby producing region-specific risk factors. Using a database of the global distribution of crop insect pest species, we found that we were able to produce highly differentiated region-specific risk factors for insect pests. We did this by weighting cluster elements by their Euclidean distance from the target region. Using this approach meant that risk weightings were derived that were more realistic, as they were specific to the pest profile or species assemblage of each region. This weighting method provides an improved tool for estimating the potential invasion risk posed by exotic species given that they have an opportunity to establish in a target region.

  2. DNA clasping by mycobacterial HU: the C-terminal region of HupB mediates increased specificity of DNA binding.

    Directory of Open Access Journals (Sweden)

    Sandeep Kumar

    Full Text Available BACKGROUND: HU a small, basic, histone like protein is a major component of the bacterial nucleoid. E. coli has two subunits of HU coded by hupA and hupB genes whereas Mycobacterium tuberculosis (Mtb has only one subunit of HU coded by ORF Rv2986c (hupB gene. One noticeable feature regarding Mtb HupB, based on sequence alignment of HU orthologs from different bacteria, was that HupB(Mtb bears at its C-terminal end, a highly basic extension and this prompted an examination of its role in Mtb HupB function. METHODOLOGY/PRINCIPAL FINDINGS: With this objective two clones of Mtb HupB were generated; one expressing full length HupB protein (HupB(Mtb and another which expresses only the N terminal region (first 95 amino acid of hupB (HupB(MtbN. Gel retardation assays revealed that HupB(MtbN is almost like E. coli HU (heat stable nucleoid protein in terms of its DNA binding, with a binding constant (K(d for linear dsDNA greater than 1000 nM, a value comparable to that obtained for the HUalphaalpha and HUalphabeta forms. However CTR (C-terminal Region of HupB(Mtb imparts greater specificity in DNA binding. HupB(Mtb protein binds more strongly to supercoiled plasmid DNA than to linear DNA, also this binding is very stable as it provides DNase I protection even up to 5 minutes. Similar results were obtained when the abilities of both proteins to mediate protection against DNA strand cleavage by hydroxyl radicals generated by the Fenton's reaction, were compared. It was also observed that both the proteins have DNA binding preference for A:T rich DNA which may occur at the regulatory regions of ORFs and the oriC region of Mtb. CONCLUSIONS/SIGNIFICANCE: These data thus point that HupB(Mtb may participate in chromosome organization in-vivo, it may also play a passive, possibly an architectural role.

  3. Polyphyletic Nature of Salmonella enterica Serotype Derby and Lineage-Specific Host-Association Revealed by Genome-Wide Analysis

    Science.gov (United States)

    Sévellec, Yann; Vignaud, Marie-Léone; Granier, Sophie A.; Lailler, Renaud; Feurer, Carole; Le Hello, Simon; Mistou, Michel-Yves; Cadel-Six, Sabrina

    2018-01-01

    In France, Salmonella Derby is one of the most prevalent serotypes in pork and poultry meat. Since 2006, it has ranked among the 10 most frequent Salmonella serotypes isolated in humans. In previous publications, Salmonella Derby isolates have been characterized by pulsed field gel electrophoresis (PFGE) and antimicrobial resistance (AMR) profiles revealing the existence of different pulsotypes and AMR phenotypic groups. However, these results suffer from the low discriminatory power of these typing methods. In the present study, we built a collection of 140 strains of S. Derby collected in France from 2014 to 2015 representative of the pork and poultry food sectors. The whole collection was characterized using whole genome sequencing (WGS), providing a significant contribution to the knowledge of this underrepresented serotype, with few genomes available in public databases. The genetic diversity of the S. Derby strains was analyzed by single-nucleotide polymorphism (SNP). We also investigated AMR by both genome and phenotype, the main Salmonella pathogenicity island (SPI) and the fimH gene sequences. Our results show that this S. Derby collection is spread across four different lineages genetically distant by an average of 15k SNPs. These lineages correspond to four multilocus sequence typing (MLST) types (ST39, ST40, ST71, and ST682), which were found to be associated with specific animal hosts: pork and poultry. While the ST71 and ST682 strains are pansusceptible, ST40 isolates are characterized by the multidrug resistant profile STR-SSS-TET. Considering virulence determinants, only ST39 and ST40 present the SPI-23, which has previously been associated with pork enterocyte invasion. Furthermore, the pork ST682 isolates were found to carry mutations in the fimH sequence that could participate in the host tropism of this group. Our phylogenetic analysis demonstrates the polyphyletic nature of the Salmonella serotype Derby and provides an opportunity to identify

  4. A Role of Endogenous Progesterone in Stroke Cerebroprotection Revealed by the Neural-Specific Deletion of Its Intracellular Receptors.

    Science.gov (United States)

    Zhu, Xiaoyan; Fréchou, Magalie; Liere, Philippe; Zhang, Shaodong; Pianos, Antoine; Fernandez, Neïké; Denier, Christian; Mattern, Claudia; Schumacher, Michael; Guennoun, Rachida

    2017-11-08

    Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult. Here, we used steroid profiling by gas chromatography-tandem mass spectrometry (GC-MS/MS) for exploring adaptive and sex-specific changes in brain levels of progesterone and its metabolites after MCAO. We show that, in the male mouse brain, progesterone is mainly metabolized via 5α-reduction leading to 5α-dihydroprogesterone (5α-DHP), also a progesterone receptor (PR) agonist ligand in neural cells, then to 3α,5α-tetrahydroprogesterone (3α,5α-THP). In the female mouse brain, levels of 5α-DHP and 3α,5α-THP are lower and levels of 20α-DHP are higher than in males. After MCAO, levels of progesterone and 5α-DHP are upregulated rapidly to pregnancy-like levels in the male but not in the female brain. To assess whether endogenous progesterone and 5α-DHP contribute to the resistance of neural cells to ischemic damage, we inactivated PR selectively in the CNS. Deletion of PR in the brain reduced its resistance to MCAO, resulting in increased infarct volumes and neurological deficits in both sexes. Importantly, endogenous PR ligands continue to protect the brain of aging mice. These results uncover the unexpected importance of endogenous progesterone and its metabolites in cerebroprotection. They also reveal that the female reproductive hormone progesterone is an endogenous cerebroprotective neurosteroid in both sexes. SIGNIFICANCE STATEMENT The brain responds to injury with protective signaling and has a remarkable capacity to protect itself. We show here that, in response to ischemic stroke, levels of progesterone and its neuroactive metabolite 5α-dihydroprogesterone are upregulated rapidly in the male mouse brain but not in the

  5. Polyphyletic Nature of Salmonella enterica Serotype Derby and Lineage-Specific Host-Association Revealed by Genome-Wide Analysis

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    Yann Sévellec

    2018-05-01

    Full Text Available In France, Salmonella Derby is one of the most prevalent serotypes in pork and poultry meat. Since 2006, it has ranked among the 10 most frequent Salmonella serotypes isolated in humans. In previous publications, Salmonella Derby isolates have been characterized by pulsed field gel electrophoresis (PFGE and antimicrobial resistance (AMR profiles revealing the existence of different pulsotypes and AMR phenotypic groups. However, these results suffer from the low discriminatory power of these typing methods. In the present study, we built a collection of 140 strains of S. Derby collected in France from 2014 to 2015 representative of the pork and poultry food sectors. The whole collection was characterized using whole genome sequencing (WGS, providing a significant contribution to the knowledge of this underrepresented serotype, with few genomes available in public databases. The genetic diversity of the S. Derby strains was analyzed by single-nucleotide polymorphism (SNP. We also investigated AMR by both genome and phenotype, the main Salmonella pathogenicity island (SPI and the fimH gene sequences. Our results show that this S. Derby collection is spread across four different lineages genetically distant by an average of 15k SNPs. These lineages correspond to four multilocus sequence typing (MLST types (ST39, ST40, ST71, and ST682, which were found to be associated with specific animal hosts: pork and poultry. While the ST71 and ST682 strains are pansusceptible, ST40 isolates are characterized by the multidrug resistant profile STR-SSS-TET. Considering virulence determinants, only ST39 and ST40 present the SPI-23, which has previously been associated with pork enterocyte invasion. Furthermore, the pork ST682 isolates were found to carry mutations in the fimH sequence that could participate in the host tropism of this group. Our phylogenetic analysis demonstrates the polyphyletic nature of the Salmonella serotype Derby and provides an opportunity

  6. Cognitive neuropsychological and regional cerebral blood flow study of a Japanese-English bilingual girl with specific language impairment (SLI).

    Science.gov (United States)

    Uno, Akira; Wydell, Taeko N; Kato, Motoichiro; Itoh, Kanae; Yoshino, Fumihiro

    2009-02-01

    We report here on an investigation into the possible factors which might have contributed to language impairment (LI) in EM, a 14-year-old Japanese-English bilingual girl. EM was born in the UK to Japanese parents with no other siblings, and used English to communicate with all other people except for her parents. A delay in her English language development was identified at primary school in the UK, which was attributed to her bilingualism. The deficiency in her English language skills persisted into her adolescence despite more than adequate educational opportunities (including additional language support). At the start of her secondary education, language ability/literacy attainment tests were conducted in both English and Japanese, and the results suggested specific language impairment (SLI) in both languages. Further, her brain Single Photon Emission Computed Tomography (SPECT) revealed significantly lower Regional Cerebral Blood Flow(rCBF) in the left temporo-parietal area, which is also similar to the area of dysfunction often found among Japanese individuals with SLI.

  7. Kinematics and hydrodynamics analysis of swimming anurans reveals striking inter-specific differences in the mechanism for producing thrust.

    Science.gov (United States)

    Richards, Christopher T

    2010-02-15

    This study aimed to compare the swimming kinematics and hydrodynamics within and among aquatic and semi-aquatic/terrestrial frogs. High-speed video was used to obtain kinematics of the leg joints and feet as animals swam freely across their natural range of speeds. Blade element analysis was then used to model the hydrodynamic thrust as a function of foot kinematics. Two purely aquatic frogs, Xenopus laevis and Hymenochirus boettgeri, were compared with two semi-aquatic/terrestrial frogs, Rana pipiens and Bufo americanus. The four species performed similarly. Among swimming strokes, peak stroke velocity ranged from 3.3+/-1.1 to 20.9+/-2.5, from 6.8+/-2.1 to 28.6+/-3.7 and from 4.9+/-0.5 to 20.9+/-4.1 body lengths per second (BL s(-1)) in X. laevis, H. boettgeri and R. pipiens, respectively (means +/- s.d.; N=4 frogs for each). B. americanus swam much more slowly at 3.1+/-0.3 to 7.0+/-2.0 BL s(-1) (N=3 frogs). Time-varying joint kinematics patterns were superficially similar among species. Because foot kinematics result from the cumulative motion of joints proximal to the feet, small differences in time-varying joint kinematics among species resulted in species-specific foot kinematics (therefore hydrodynamics) patterns. To obtain a simple measure of the hydrodynamically useful motion of the foot, this study uses 'effective foot velocity' (EFV): a measure of the component of foot velocity along the axis of swimming. Resolving EFV into translational and rotational components allows predictions of species-specific propulsion strategies. Additionally, a novel kinematic analysis is presented here that enables the partitioning of translational and rotational foot velocity into velocity components contributed by extension at each individual limb joint. Data from the kinematics analysis show that R. pipiens and B. americanus translated their feet faster than their body moved forward, resulting in positive net translational EFV. Conversely, translational EFV was slower than

  8. Quantitative analysis of DNA methylation at all human imprinted regions reveals preservation of epigenetic stability in adult somatic tissue

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    Woodfine Kathryn

    2011-01-01

    Full Text Available Abstract Background Genes subject to genomic imprinting are mono-allelically expressed in a parent-of-origin dependent manner. Each imprinted locus has at least one differentially methylated region (DMR which has allele specific DNA methylation and contributes to imprinted gene expression. Once DMRs are established, they are potentially able to withstand normal genome reprogramming events that occur during cell differentiation and germ-line DMRs are stably maintained throughout development. These DMRs, in addition to being either maternally or paternally methylated, have differences in whether methylation was acquired in the germ-line or post fertilization and are present in a variety of genomic locations with different Cytosine-phosphate guanine (CpG densities and CTCF binding capacities. We therefore examined the stability of maintenance of DNA methylation imprints and determined the normal baseline DNA methylation levels in several adult tissues for all imprinted genes. In order to do this, we first developed and validated 50 highly specific, quantitative DNA methylation pyrosequencing assays for the known DMRs associated with human imprinted genes. Results Remarkable stability of the DNA methylation imprint was observed in all germ-line DMRs and paternally methylated somatic DMRs (which maintained average methylation levels of between 35% - 65% in all somatic tissues, independent of gene expression. Maternally methylated somatic DMRs were found to have more variation with tissue specific methylation patterns. Most DMRs, however, showed some intra-individual variability for DNA methylation levels in peripheral blood, suggesting that more than one DMR needs to be examined in order to get an overall impression of the epigenetic stability in a tissue. The plasticity of DNA methylation at imprinted genes was examined in a panel of normal and cancer cell lines. All cell lines showed changes in DNA methylation, especially at the paternal germ

  9. Transcriptomic analysis reveals the gene expression profile that specifically responds to IBA during adventitious rooting in mung bean seedlings.

    Science.gov (United States)

    Li, Shi-Weng; Shi, Rui-Fang; Leng, Yan; Zhou, Yuan

    2016-01-12

    Auxin plays a critical role in inducing adventitious rooting in many plants. Indole-3-butyric acid (IBA) is the most widely employed auxin for adventitious rooting. However, the molecular mechanisms by which auxin regulate the process of adventitious rooting are less well known. The RNA-Seq data analysis indicated that IBA treatment greatly increased the amount of clean reads and the amount of expressed unigenes by 24.29 % and 27.42 % and by 4.3 % and 5.04 % at two time points, respectively, and significantly increased the numbers of unigenes numbered with RPKM = 10-100 and RPKM = 500-1000 by 13.04 % and 3.12 % and by 24.66 % and 108.2 % at two time points, respectively. Gene Ontology (GO) enrichment analysis indicated that the enrichment of down-regulated GOs was 2.87-fold higher than that of up-regulated GOs at stage 1, suggesting that IBA significantly down-regulated gene expression at 6 h. The GO functional category indicated that IBA significantly up- or down-regulated processes associated with auxin signaling, ribosome assembly and protein synthesis, photosynthesis, oxidoreductase activity and extracellular region, secondary cell wall biogenesis, and the cell wall during the development process. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated that ribosome biogenesis, plant hormone signal transduction, pentose and glucuronate interconversions, photosynthesis, phenylpropanoid biosynthesis, sesquiterpenoid and triterpenoid biosynthesis, ribosome, cutin, flavonoid biosynthesis, and phenylalanine metabolism were the pathways most highly regulated by IBA. A total of 6369 differentially expressed (2-fold change > 2) unigenes (DEGs) with 3693 (58 %) that were up-regulated and 2676 (42 %) down-regulated, 5433 unigenes with 2208 (40.6 %) that were up-regulated and 3225 (59.4 %) down-regulated, and 7664 unigenes with 3187 (41.6 %) that were up-regulated and 4477 (58.4 %) down-regulated were detected at stage 1

  10. THE FORMATION OF ENVIRONMENTAL AND ECONOMIC POLICY IN UKRAINE: REGIONAL SPECIFICITY

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    Volodymyr Korol’

    2016-03-01

    state in ore mining areas and industrial urban agglomerations, ensuring its sustainable improvement and ecologically balanced condition; - execution of environmentally sound assessments of population specific provision by different types of natural resources, including life-supporting; - improving the economic levers of environmental control. Ukraine is one of the countries whose development largely depends on balancing the use of available natural resource base, primarily life-supporting (land, water, mineral and raw material.  Research and analysis confirm that, despite the inherited problems of development, Ukraine has its  own opportunities of problems solving, especially through the effective using of all kinds natural resources. Assuming that the industrial structure is the core national economy, its dynamics, natural and  resource input, the priority objective is the improvement of industry structure in the direction of  increasing its technology and providing benefits to those sectors and industries that produce the final ecologically not capacious and environmentally friendly products. This is a problem of great strategic goal, to which the public policy must focus. Thus, the most active level of ecological and economic systems is regional one, as the region (area is also the governance subject, at this level environmental problems of society are emerging, the requirements for the production greening and environmental management are nominated. The region combines specific area points of productive forces distribution, polluting enterprises and natural resources using enterprises, which are parts of its economic structure. The structure and scale of regional production determine the character and volume of pollution, the intensity of the impact on the environment. Thus, the development of the national economy requires considering for at least three factors: first, the natural resource potential of the national territory, which in Ukraine, as in each country

  11. Charcoal records reveal past occurrences of disturbances in the forests of the Kisangani region, Democratic Republic of the Congo

    Science.gov (United States)

    Tshibamba Mukendi, John; Hubau, Wannes; Ntahobavuka, Honorine; Boyemba Bosela, Faustin; De Cannière, Charles; Beeckman, Hans

    2014-05-01

    Past disturbances have modified local density, structure and floristic composition of Central African rainforests. As such, these perturbations represent a driving force for forest dynamics and they were presumably at the origin of present-day forest mosaics. One of the most prominent disturbances within the forest is fire, leaving behind charcoal as a witness of past forest dynamics. Quantification and identification of ancient charcoal fragments found in soil layers (= pedoanthracology) allows a detailed reconstruction of forest history, including the possible occurrence of past perturbations. The primary objective of this study is to present palaeoenvironmental evidence for the existence of past disturbances in the forests of the Kisangani region (Democratic Republic of the Congo) using a pedoanthracological approach. We quantified and identified charcoal fragments from pedoanthracological excavations in the Yangambi, Yoko, Masako and Kole forest regions. Charcoal sampling was conducted in pit intervals of 10 cm, whereby pottery fragments were also registered and quantified. Floristic identifications were conducted using former protocols based on wood anatomy, which is largely preserved after charcoalification. 14 excavations were conducted and charcoal was found in most pit intervals. Specifically, 52 out of 56 sampled intervals from the Yangambi forest contained charcoal, along with 47 pit intervals from the Yoko forest reserve, 34 pit intervals from the Masako forest and 16 from the Kole forest. Highest specific anthracomasses were recorded in Yoko (167 mg charcoal per kg soil), followed by Yangambi (133 mg/kg), Masako (71,89 mg/kg) and finally Kole (42,4 mg/kg). Charcoal identifications point at a manifest presence of the family of Fabaceae (Caesalpinioideae). This family is characteristic for the tropical humid rainforest. The presence of charcoal fragments from these taxa, associated with pottery sherds on different depths within the profiles, suggests

  12. Mucosal immunization with PLGA-microencapsulated DNA primes a SIV-specific CTL response revealed by boosting with cognate recombinant modified vaccinia virus Ankara

    International Nuclear Information System (INIS)

    Sharpe, Sally; Hanke, Tomas; Tinsley-Bown, Anne; Dennis, Mike; Dowall, Stuart; McMichael, Andrew; Cranage, Martin

    2003-01-01

    Systemically administered DNA encoding a recombinant human immunodeficiency virus (HIV) derived immunogen effectively primes a cytotoxic T lymphocyte (CTL) response in macaques. In this further pilot study we have evaluated mucosal delivery of DNA as an alternative priming strategy. Plasmid DNA, pTH.HW, encoding a multi-CTL epitope gene, was incorporated into poly(D,L-lactic-co-glycolic acid) microparticles of less than 10 μm in diameter. Five intrarectal immunizations failed to stimulate a circulating vaccine-specific CTL response in 2 Mamu-A*01 + rhesus macaques. However, 1 week after intradermal immunization with a cognate modified vaccinia virus Ankara vaccine MVA.HW, CTL responses were detected in both animals that persisted until analysis postmortem, 12 weeks after the final boost. In contrast, a weaker and less durable response was seen in an animal vaccinated with the MVA construct alone. Analysis of lymphoid tissues revealed a disseminated CTL response in peripheral and regional lymph nodes but not the spleen of both mucosally primed animals

  13. Chromosome region-specific libraries for human genome analysis. Final progress report, 1 March 1991--28 February 1994

    Energy Technology Data Exchange (ETDEWEB)

    Kao, F.T.

    1994-04-01

    The objectives of this grant proposal include (1) development of a chromosome microdissection and PCR-mediated microcloning technology, (2) application of this microtechnology to the construction of region-specific libraries for human genome analysis. During this grant period, the authors have successfully developed this microtechnology and have applied it to the construction of microdissection libraries for the following chromosome regions: a whole chromosome 21 (21E), 2 region-specific libraries for the long arm of chromosome 2, 2q35-q37 (2Q1) and 2q33-q35 (2Q2), and 4 region-specific libraries for the entire short arm of chromosome 2, 2p23-p25 (2P1), 2p21-p23 (2P2), 2p14-p16 (wP3) and 2p11-p13 (2P4). In addition, 20--40 unique sequence microclones have been isolated and characterized for genomic studies. These region-specific libraries and the single-copy microclones from the library have been used as valuable resources for (1) isolating microsatellite probes in linkage analysis to further refine the disease locus; (2) isolating corresponding clones with large inserts, e.g. YAC, BAC, P1, cosmid and phage, to facilitate construction of contigs for high resolution physical mapping; and (3) isolating region-specific cDNA clones for use as candidate genes. These libraries are being deposited in the American Type Culture Collection (ATCC) for general distribution.

  14. Region-specific sensitivity of anemophilous pollen deposition to temperature and precipitation.

    Directory of Open Access Journals (Sweden)

    Timme H Donders

    Full Text Available Understanding relations between climate and pollen production is important for several societal and ecological challenges, importantly pollen forecasting for pollinosis treatment, forensic studies, global change biology, and high-resolution palaeoecological studies of past vegetation and climate fluctuations. For these purposes, we investigate the role of climate variables on annual-scale variations in pollen influx, test the regional consistency of observed patterns, and evaluate the potential to reconstruct high-frequency signals from sediment archives. A 43-year pollen-trap record from the Netherlands is used to investigate relations between annual pollen influx, climate variables (monthly and seasonal temperature and precipitation values, and the North Atlantic Oscillation climate index. Spearman rank correlation analysis shows that specifically in Alnus, Betula, Corylus, Fraxinus, Quercus and Plantago both temperature in the year prior to (T-1, as well as in the growing season (T, are highly significant factors (TApril rs between 0.30 [P<0.05[ and 0.58 [P<0.0001]; TJuli-1 rs between 0.32 [P<0.05[ and 0.56 [P<0.0001] in the annual pollen influx of wind-pollinated plants. Total annual pollen prediction models based on multiple climate variables yield R2 between 0.38 and 0.62 (P<0.0001. The effect of precipitation is minimal. A second trapping station in the SE Netherlands, shows consistent trends and annual variability, suggesting the climate factors are regionally relevant. Summer temperature is thought to influence the formation of reproductive structures, while temperature during the flowering season influences pollen release. This study provides a first predictive model for seasonal pollen forecasting, and also aides forensic studies. Furthermore, variations in pollen accumulation rates from a sub-fossil peat deposit are comparable with the pollen trap data. This suggests that high frequency variability pollen records from natural

  15. Brain region-specific altered expression and association of mitochondria-related genes in autism.

    Science.gov (United States)

    Anitha, Ayyappan; Nakamura, Kazuhiko; Thanseem, Ismail; Yamada, Kazuo; Iwayama, Yoshimi; Toyota, Tomoko; Matsuzaki, Hideo; Miyachi, Taishi; Yamada, Satoru; Tsujii, Masatsugu; Tsuchiya, Kenji J; Matsumoto, Kaori; Iwata, Yasuhide; Suzuki, Katsuaki; Ichikawa, Hironobu; Sugiyama, Toshiro; Yoshikawa, Takeo; Mori, Norio

    2012-11-01

    Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions. For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct (∆∆Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism. Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of DNAJC19, DNM1L, LRPPRC

  16. Brain region-specific altered expression and association of mitochondria-related genes in autism

    Directory of Open Access Journals (Sweden)

    Anitha Ayyappan

    2012-11-01

    Full Text Available Abstract Background Mitochondrial dysfunction (MtD has been observed in approximately five percent of children with autism spectrum disorders (ASD. MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA. Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions. Methods For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG, motor cortex (MC and thalamus (THL from autism patients (n=8 and controls (n=10 were obtained from the Autism Tissue Program (Princeton, NJ, USA. Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct (∆∆Ct method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism. Results Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2, neurofilament, light polypeptide (NEFL and solute carrier family 25, member 27 (SLC25A27 showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066 and SLC25A27 (P = 0.046; Z-score 1.990 showed genetic association with autism in Caucasian and Japanese samples, respectively. The

  17. RNA expression in a cartilaginous fish cell line reveals ancient 3′ noncoding regions highly conserved in vertebrates

    Science.gov (United States)

    Forest, David; Nishikawa, Ryuhei; Kobayashi, Hiroshi; Parton, Angela; Bayne, Christopher J.; Barnes, David W.

    2007-01-01

    We have established a cartilaginous fish cell line [Squalus acanthias embryo cell line (SAE)], a mesenchymal stem cell line derived from the embryo of an elasmobranch, the spiny dogfish shark S. acanthias. Elasmobranchs (sharks and rays) first appeared >400 million years ago, and existing species provide useful models for comparative vertebrate cell biology, physiology, and genomics. Comparative vertebrate genomics among evolutionarily distant organisms can provide sequence conservation information that facilitates identification of critical coding and noncoding regions. Although these genomic analyses are informative, experimental verification of functions of genomic sequences depends heavily on cell culture approaches. Using ESTs defining mRNAs derived from the SAE cell line, we identified lengthy and highly conserved gene-specific nucleotide sequences in the noncoding 3′ UTRs of eight genes involved in the regulation of cell growth and proliferation. Conserved noncoding 3′ mRNA regions detected by using the shark nucleotide sequences as a starting point were found in a range of other vertebrate orders, including bony fish, birds, amphibians, and mammals. Nucleotide identity of shark and human in these regions was remarkably well conserved. Our results indicate that highly conserved gene sequences dating from the appearance of jawed vertebrates and representing potential cis-regulatory elements can be identified through the use of cartilaginous fish as a baseline. Because the expression of genes in the SAE cell line was prerequisite for their identification, this cartilaginous fish culture system also provides a physiologically valid tool to test functional hypotheses on the role of these ancient conserved sequences in comparative cell biology. PMID:17227856

  18. Geochronology of Zircon in Eclogite Reveals Imbrication of the Ultrahigh-Pressure Western Gneiss Region of Norway.

    Science.gov (United States)

    Young, D. J.; Kylander-Clark, A. R.; Root, D. B.

    2014-12-01

    Eclogite provides the only record of kinematic events at the deepest levels of orogens. Integrating the U-Pb geochronology and trace element chemistry of zircon in eclogite reveals the most complete view of the PTt history, yet low concentrations of uranium and zirconium and drier compositions that hinder zircon growth at peak conditions render it a challenging rocktype for this approach. The iconic Western Gneiss Region (WGR) in Norway is one of the largest terranes of deeply subducted continental rocks in the world, and contains many indicators of ultrahigh-pressure metamorphic conditions (P>2.8 GPa) that developed during the Siluro-Devonian Caledonian Orogeny. A metamorphic transition from amphibolite-facies to ultrahigh-pressure eclogite facies broadly coincides with a km-scale shear zone that underlies the majority of the WGR. A critical unknown is the timing of movement on this feature, which emplaced allochthonous units above the Baltica basement, but might also have accommodated late-orogenic exhumation of the WGR from mantle depths. We carried out laser ablation split-stream ICPMS (LASS) and selected multigrain TIMS analyses of zircons from eleven eclogites across the southern WGR, of which eight are located within or above the shear zone. LASS spots on polished grains mostly yield weakly discordant Proterozoic intrusive ages, and often minimal indication of a Caledonian (U)HP metamorphic overprint. Direct ablation into unpolished zircon reveals thin rims of Caledonian age in some cases. Overall, the dataset shows that all samples began zircon growth at approximately the same time (ca. 430-420 Ma). Eclogite from lower levels of the shear zone does not contain any dates younger than ca. 410 Ma, however, while eclogite from higher levels continued growth until ca. 400 Ma. We interpret this to result from thrusting of the WGR above cooler basement after 410 Ma, terminating new zircon crystallization within the shear zone but allowing limited further growth in

  19. Substituent-specific antibody against glucuronoxylan reveals close association of glucuronic acid and acetyl substituents and distinct labeling patterns in tree species

    DEFF Research Database (Denmark)

    Koutaniemi, Sanna; Guillon, Fabienne; Tranquet, Olivier

    2012-01-01

    Immunolabeling can be used to locate plant cell wall carbohydrates or other components to specific cell types or to specific regions of the wall. Some antibodies against xylans exist; however, many partly react with the xylan backbone and thus provide limited information on the type of substituen...

  20. THE SPECIFICS OF NATIONAL REGIONAL DEVELOPMENT STRATEGY OF THE REPUBLIC OF MOLDOVA

    Directory of Open Access Journals (Sweden)

    Tatiana M. TOFAN

    2014-11-01

    Full Text Available The experience in the Republic of Moldova during 2010-2014 period to implement the National Strategy of Regional Development, has demonstrated the need to develop monitoring and evaluation methodology of these strategy, and put accent on the development of regional statistics, on the indicators of projects, regions and the national level, on the development of methodology for assessing the impact of the projects, to ensure the dissemination of results in monitoring and evaluation by placing the information on the website of the Ministry of Regional Development and Construction and Regional Development Agencies in periodic newsletters. To ensure transparency in monitoring and evaluation in the implementation of regional development policy confirms the responsibility of actors involved in the area, condition the right to take effective measures to correct the activities which do not correspond to the policy and provides the opportunity to examine the dynamics of the processes of socio-economic development of the regions.

  1. Oceanic, Latitudinal, and Sex-Specific Variation in Demography of a Tropical Deepwater Snapper across the Indo-Pacific Region

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    Ashley J. Williams

    2017-12-01

    Full Text Available Deepwater tropical fisheries provide an important source of income and protein to Pacific and Indian Ocean coastal communities who are highly dependent on fish for food security. The development of quantitative assessments and management strategies for these deepwater fisheries has been hindered by insufficient biological and fisheries data. We examine the age-specific demography of the pygmy ruby snapper Etelis carbunculus, an important target species in tropical deepwater fisheries, across 90° of longitude and 20° of latitude in the Pacific and Indian Oceans. Our results show that growth of E. carbunculus varies significantly between oceans and sexes and across latitudes in both oceans. Estimates of natural and fishing mortality were similar between oceans, but higher for females than males in both oceans. Evidence of greater fishing pressure on females than males is likely due to the larger size-at-age of females compared to males, assuming that selectivity of the fishing gear is related directly to fish size. Sex ratios were significantly female biased in both oceans despite this species being gonochoristic, and maturity schedules were similar between sexes in the Pacific Ocean. This species exhibits a protracted spawning season from mid-spring to autumn (i.e., October to May in the Pacific Ocean. These results represent the first estimates of age-specific demographic parameters for E. carbunculus, and provide the foundation for the development of the first species-specific assessment models and harvest strategies for the species. Future stock assessment models for E. carbunculus should consider sex-specific demographic parameters and spatial variation in demography. Our results reveal substantial differences in biology between E. carbunculus and the giant ruby snapper E. sp., a cryptic congeneric species, and thus contribute to greater clarity in managing fisheries that are dependent on these two species. Furthermore, the improved

  2. The Geographic Distribution of Saccharomyces cerevisiae Isolates within three Italian Neighboring Winemaking Regions Reveals Strong Differences in Yeast Abundance, Genetic Diversity and Industrial Strain Dissemination

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    Alessia Viel

    2017-08-01

    Full Text Available In recent years the interest for natural fermentations has been re-evaluated in terms of increasing the wine terroir and managing more sustainable winemaking practices. Therefore, the level of yeast genetic variability and the abundance of Saccharomyces cerevisiae native populations in vineyard are becoming more and more crucial at both ecological and technological level. Among the factors that can influence the strain diversity, the commercial starter release that accidentally occur in the environment around the winery, has to be considered. In this study we led a wide scale investigation of S. cerevisiae genetic diversity and population structure in the vineyards of three neighboring winemaking regions of Protected Appellation of Origin, in North-East of Italy. Combining mtDNA RFLP and microsatellite markers analyses we evaluated 634 grape samples collected over 3 years. We could detect major differences in the presence of S. cerevisiae yeasts, according to the winemaking region. The population structures revealed specificities of yeast microbiota at vineyard scale, with a relative Appellation of Origin area homogeneity, and transition zones suggesting a geographic differentiation. Surprisingly, we found a widespread industrial yeast dissemination that was very high in the areas where the native yeast abundance was low. Although geographical distance is a key element involved in strain distribution, the high presence of industrial strains in vineyard reduced the differences between populations. This finding indicates that industrial yeast diffusion it is a real emergency and their presence strongly interferes with the natural yeast microbiota.

  3. Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013

    DEFF Research Database (Denmark)

    Peterson, Carrie Beth

    2015-01-01

    BACKGROUND: Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries...... between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. METHODS: We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey...... informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini...

  4. Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013

    DEFF Research Database (Denmark)

    Moesgaard Iburg, Kim

    2015-01-01

    Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries...... between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey...... informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini...

  5. Monitoring of seismic events from a specific source region using a single regional array: A case study

    Science.gov (United States)

    Gibbons, S. J.; Kværna, T.; Ringdal, F.

    2005-07-01

    In the monitoring of earthquakes and nuclear explosions using a sparse worldwide network of seismic stations, it is frequently necessary to make reliable location estimates using a single seismic array. It is also desirable to screen out routine industrial explosions automatically in order that analyst resources are not wasted upon detections which can, with a high level of confidence, be associated with such a source. The Kovdor mine on the Kola Peninsula of NW Russia is the site of frequent industrial blasts which are well recorded by the ARCES regional seismic array at a distance of approximately 300 km. We describe here an automatic procedure for identifying signals which are likely to result from blasts at the Kovdor mine and, wherever possible, for obtaining single array locations for such events. Carefully calibrated processing parameters were chosen using measurements from confirmed events at the mine over a one-year period for which the operators supplied Ground Truth information. Phase arrival times are estimated using an autoregressive method and slowness and azimuth are estimated using broadband f{-} k analysis in fixed frequency bands and time-windows fixed relative to the initial P-onset time. We demonstrate the improvement to slowness estimates resulting from the use of fixed frequency bands. Events can be located using a single array if, in addition to the P-phase, at least one secondary phase is found with both an acceptable slowness estimate and valid onset-time estimate. We evaluate the on-line system over a twelve month period; every event known to have occured at the mine is detected by the process and 32 out of 53 confirmed events were located automatically. The remaining events were classified as “very likely” Kovdor events and were subsequently located by an analyst. The false alarm rate is low; only 84 very likely Kovdor events were identified during the whole of 2003 and none of these were subsequently located at a large distance from

  6. Cortical pitch regions in humans respond primarily to resolved harmonics and are located in specific tonotopic regions of anterior auditory cortex.

    Science.gov (United States)

    Norman-Haignere, Sam; Kanwisher, Nancy; McDermott, Josh H

    2013-12-11

    Pitch is a defining perceptual property of many real-world sounds, including music and speech. Classically, theories of pitch perception have differentiated between temporal and spectral cues. These cues are rendered distinct by the frequency resolution of the ear, such that some frequencies produce "resolved" peaks of excitation in the cochlea, whereas others are "unresolved," providing a pitch cue only via their temporal fluctuations. Despite longstanding interest, the neural structures that process pitch, and their relationship to these cues, have remained controversial. Here, using fMRI in humans, we report the following: (1) consistent with previous reports, all subjects exhibited pitch-sensitive cortical regions that responded substantially more to harmonic tones than frequency-matched noise; (2) the response of these regions was mainly driven by spectrally resolved harmonics, although they also exhibited a weak but consistent response to unresolved harmonics relative to noise; (3) the response of pitch-sensitive regions to a parametric manipulation of resolvability tracked psychophysical discrimination thresholds for the same stimuli; and (4) pitch-sensitive regions were localized to specific tonotopic regions of anterior auditory cortex, extending from a low-frequency region of primary auditory cortex into a more anterior and less frequency-selective region of nonprimary auditory cortex. These results demonstrate that cortical pitch responses are located in a stereotyped region of anterior auditory cortex and are predominantly driven by resolved frequency components in a way that mirrors behavior.

  7. Age- and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — Differences in various mitochondrial bioenergetics parameters in different brain regions in different age groups. This dataset is associated with the following...

  8. Process- and Domain-Specificity in Regions Engaged for Face Processing: An fMRI Study of Perceptual Differentiation

    Science.gov (United States)

    Collins, Heather R.; Zhu, Xun; Bhatt, Ramesh S.; Clark, Jonathan D.; Joseph, Jane E.

    2015-01-01

    The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. The present study parametrically varied demands on featural, first-order configural or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing) or reflected generalized perceptual differentiation (i.e. differentiation that crosses category and processing type boundaries). Regions of interest were identified in a separate localizer run or with a similarity regressor in the face-matching runs. The predominant principle accounting for fMRI signal modulation in most regions was generalized perceptual differentiation. Nearly all regions showed perceptual differentiation for both faces and houses for more than one processing type, even if the region was identified as face-preferential in the localizer run. Consistent with process-specificity, some regions showed perceptual differentiation for first-order processing of faces and houses (right fusiform face area and occipito-temporal cortex, and right lateral occipital complex), but not for featural or second-order processing. Somewhat consistent with domain-specificity, the right inferior frontal gyrus showed perceptual differentiation only for faces in the featural matching task. The present findings demonstrate that the majority of regions involved in perceptual differentiation of faces are also involved in differentiation of other visually homogenous categories. PMID:22849402

  9. Mechanism of selective VEGF-A binding by neuropilin-1 reveals a basis for specific ligand inhibition.

    Directory of Open Access Journals (Sweden)

    Matthew W Parker

    Full Text Available Neuropilin (Nrp receptors function as essential cell surface receptors for the Vascular Endothelial Growth Factor (VEGF family of proangiogenic cytokines and the semaphorin 3 (Sema3 family of axon guidance molecules. There are two Nrp homologues, Nrp1 and Nrp2, which bind to both overlapping and distinct members of the VEGF and Sema3 family of molecules. Nrp1 specifically binds the VEGF-A(164/5 isoform, which is essential for developmental angiogenesis. We demonstrate that VEGF-A specific binding is governed by Nrp1 residues in the b1 coagulation factor domain surrounding the invariant Nrp C-terminal arginine binding pocket. Further, we show that Sema3F does not display the Nrp-specific binding to the b1 domain seen with VEGF-A. Engineered soluble Nrp receptor fragments that selectively sequester ligands from the active signaling complex are an attractive modality for selectively blocking the angiogenic and chemorepulsive functions of Nrp ligands. Utilizing the information on Nrp ligand binding specificity, we demonstrate Nrp constructs that specifically sequester Sema3 in the presence of VEGF-A. This establishes that unique mechanisms are used by Nrp receptors to mediate specific ligand binding and that these differences can be exploited to engineer soluble Nrp receptors with specificity for Sema3.

  10. Biophysical Studies on BEX3, the p75NTR-Associated Cell Death Executor, Reveal a High-Order Oligomer with Partially Folded Regions.

    Directory of Open Access Journals (Sweden)

    Katia M S Cabral

    Full Text Available BEX3 (Brain Expressed X-linked protein 3 is a member of a mammal-specific placental protein family. Several studies have found the BEX proteins to be associated with neurodegeneration, the cell cycle and cancer. BEX3 has been predicted to be intrinsically disordered and also to represent an intracellular hub for cell signaling. The pro-apoptotic activity of BEX3 in association with a number of additional proteins has been widely supported; however, to the best of our knowledge, very limited data are available on the conformation of any of the members of the BEX family. In this study, we structurally characterized BEX3 using biophysical experimental data. Small angle X-ray scattering and atomic force microscopy revealed that BEX3 forms a specific higher-order oligomer that is consistent with a globular molecule. Solution nuclear magnetic resonance, partial proteinase K digestion, circular dichroism spectroscopy, and fluorescence techniques that were performed on the recombinant protein indicated that the structure of BEX3 is composed of approximately 31% α-helix and 20% β-strand, contains partially folded regions near the N- and C-termini, and a core which is proteolysis-resistant around residues 55-120. The self-oligomerization of BEX3 has been previously reported in cell culture and is consistent with our in vitro data.

  11. Biophysical Studies on BEX3, the p75NTR-Associated Cell Death Executor, Reveal a High-Order Oligomer with Partially Folded Regions.

    Science.gov (United States)

    Cabral, Katia M S; Raymundo, Diana P; Silva, Viviane S; Sampaio, Laura A G; Johanson, Laizes; Hill, Luis Fernando; Almeida, Fabio C L; Cordeiro, Yraima; Almeida, Marcius S

    2015-01-01

    BEX3 (Brain Expressed X-linked protein 3) is a member of a mammal-specific placental protein family. Several studies have found the BEX proteins to be associated with neurodegeneration, the cell cycle and cancer. BEX3 has been predicted to be intrinsically disordered and also to represent an intracellular hub for cell signaling. The pro-apoptotic activity of BEX3 in association with a number of additional proteins has been widely supported; however, to the best of our knowledge, very limited data are available on the conformation of any of the members of the BEX family. In this study, we structurally characterized BEX3 using biophysical experimental data. Small angle X-ray scattering and atomic force microscopy revealed that BEX3 forms a specific higher-order oligomer that is consistent with a globular molecule. Solution nuclear magnetic resonance, partial proteinase K digestion, circular dichroism spectroscopy, and fluorescence techniques that were performed on the recombinant protein indicated that the structure of BEX3 is composed of approximately 31% α-helix and 20% β-strand, contains partially folded regions near the N- and C-termini, and a core which is proteolysis-resistant around residues 55-120. The self-oligomerization of BEX3 has been previously reported in cell culture and is consistent with our in vitro data.

  12. Positron Emission Tomography Imaging Reveals Auditory and Frontal Cortical Regions Involved with Speech Perception and Loudness Adaptation.

    Directory of Open Access Journals (Sweden)

    Georg Berding

    Full Text Available Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation. The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus.

  13. Positron Emission Tomography Imaging Reveals Auditory and Frontal Cortical Regions Involved with Speech Perception and Loudness Adaptation.

    Science.gov (United States)

    Berding, Georg; Wilke, Florian; Rode, Thilo; Haense, Cathleen; Joseph, Gert; Meyer, Geerd J; Mamach, Martin; Lenarz, Minoo; Geworski, Lilli; Bengel, Frank M; Lenarz, Thomas; Lim, Hubert H

    2015-01-01

    Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation). The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET) in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus.

  14. Brain Region-Specific Activity Patterns after Recent or Remote Memory Retrieval of Auditory Conditioned Fear

    Science.gov (United States)

    Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

    2012-01-01

    Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or…

  15. A comparative antibody analysis of Pannexin1 expression in four rat brain regions reveals varying subcellular localizations

    Directory of Open Access Journals (Sweden)

    Angela C Cone

    2013-02-01

    Full Text Available Pannexin1 (Panx1 channels release cytosolic ATP in response to signaling pathways. Panx1 is highly expressed in the central nervous system. We used four antibodies with different Panx1 anti-peptide epitopes to analyze four regions of rat brain. These antibodies labeled the same bands in Western blots and had highly similar patterns of immunofluorescence in tissue culture cells expressing Panx1, but Western blots of brain lysates from Panx1 knockout and control mice showed different banding patterns. Localizations of Panx1 in brain slices were generated using automated wide-field mosaic confocal microscopy for imaging large regions of interest while retaining maximum resolution for examining cell populations and compartments. We compared Panx1 expression over the cerebellum, hippocampus with adjacent cortex, thalamus and olfactory bulb. While Panx1 localizes to the same neuronal cell types, subcellular localizations differ. Two antibodies with epitopes against the intracellular loop and one against the carboxy terminus preferentially labeled cell bodies, while an antibody raised against an N-terminal peptide highlighted neuronal processes more than cell bodies. These labeling patterns may be a reflection of different cellular and subcellular localizations of full-length and/or modified Panx1 channels where each antibody is highlighting unique or differentially accessible Panx1 populations. However, we cannot rule out that one or more of these antibodies have specificity issues. All data associated with experiments from these four antibodies are presented in a manner that allows them to be compared and our claims thoroughly evaluated, rather than eliminating results that were questionable. Each antibody is given a unique identifier through the NIF Antibody Registry that can be used to track usage of individual antibodies across papers and all image and metadata are made available in the public repository, the Cell Centered Database, for on

  16. Mutational analysis of the hypervariable region of hepatitis e virus reveals its involvement in the efficiency of viral RNA replication.

    Science.gov (United States)

    Pudupakam, R S; Kenney, Scott P; Córdoba, Laura; Huang, Yao-Wei; Dryman, Barbara A; Leroith, Tanya; Pierson, F William; Meng, Xiang-Jin

    2011-10-01

    The RNA genome of the hepatitis E virus (HEV) contains a hypervariable region (HVR) in ORF1 that tolerates small deletions with respect to infectivity. To further investigate the role of the HVR in HEV replication, we constructed a panel of mutants with overlapping deletions in the N-terminal, central, and C-terminal regions of the HVR by using a genotype 1 human HEV luciferase replicon and analyzed the effects of deletions on viral RNA replication in Huh7 cells. We found that the replication levels of the HVR deletion mutants were markedly reduced in Huh7 cells, suggesting a role of the HVR in viral replication efficiency. To further verify the results, we constructed HVR deletion mutants by using a genetically divergent, nonmammalian avian HEV, and similar effects on viral replication efficiency were observed when the avian HEV mutants were tested in LMH cells. Furthermore, the impact of complete HVR deletion on virus infectivity was tested in chickens, using an avian HEV mutant with a complete HVR deletion. Although the deletion mutant was still replication competent in LMH cells, the complete HVR deletion resulted in a loss of avian HEV infectivity in chickens. Since the HVR exhibits extensive variations in sequence and length among different HEV genotypes, we further examined the interchangeability of HVRs and demonstrated that HVR sequences are functionally exchangeable between HEV genotypes with regard to viral replication and infectivity in vitro, although genotype-specific HVR differences in replication efficiency were observed. The results showed that although the HVR tolerates small deletions with regard to infectivity, it may interact with viral and host factors to modulate the efficiency of HEV replication.

  17. Magnitude and extent of land subsidence in central Mexico revealed by regional InSAR ALOS time-series survey

    Science.gov (United States)

    Chaussard, E.; Wdowinski, S.; Amelung, F.; Cabral-Cano, E.

    2013-05-01

    Massive groundwater extraction is very common in Mexico and is well known to result in land subsidence. However, most surveys dedicated to land subsidence focus on one single city, mainly Mexico City, and thus fail to provide a comprehensive picture of the problem. Here we use a space-based radar remote sensing technique, known as Interferometric Synthetic Aperture Radar (InSAR) to detect land subsidence in the entire central Mexico area. We used data from the Japanese satellite ALOS, processed over 600 SAR images acquired between 2007-2011 and produced over 3000 interferograms to cover and area of 200,000 km2 in central Mexico. We identify land subsidence in twenty-one areas, including seventeen cities, namely from east to west, Puebla, Mexico city, Toluca de Lerdo, Queretaro, San Luis de la Paz, south of San Luis de la Paz, Celaya, south of Villa de Reyes, San Luis Potosi, west of Villa de Arista, Morelia, Salamanca, Irapuato, Silao, Leon, Aguascalientes, north of Aguascalientes, Zamora de Hidalgo, Guadalajara, Ahuacatlan, and Tepic. Subsidence rates of 30 cm/yr are observed in Mexico City, while in the other locations typical rates of 5-10 cm/yr are noticed. Regional surveys of this type are necessary for the development of hazard mitigation plans and efficient use of ground-based monitoring. We additionally correlate subsidence with land use, surface geology, and faults distribution and suggest that groundwater extraction for agricultural, urban, and industrial uses are the main causes of land subsidence. We also reveal that the limits of the subsiding areas often correlate with existing faults, motion on these faults being driven by water extraction rather than by tectonic activity. In all the subsiding locations we observe high ground velocity gradients emphasizing the significant risks associated with land subsidence in central Mexico. Averaged 2007-2011 ground velocity map from ALOS InSAR time-series in central Mexico, revealing land subsidence in 21

  18. EU COHESION POLICY NEEDS DIFFERENTIATED POLICY MIX ADEQUATE TO SPECIFICS OF ECONOMIC REGIONS

    Directory of Open Access Journals (Sweden)

    Gheorghe ZAMAN

    2008-06-01

    Full Text Available The 2007-2013 programming period of the EU focuses on economic and social cohesion via three fundamental objectives: convergence – competitiveness and employment – European territorial co-operation. The horizontal dimension of cohesion policy refers to diminishing the regional disparities and solidarity with the lagging regions’ population. Considering the big regional disparities in the New Member States (NMS as well as the gap between their GDP per capita at national level and the EU average, these countries are the main beneficiary of the EU financial allocations, especially via convergence objective. However, two interrelated questions are entailed by this issue. One of them refers to the capacity of these countries to absorb effectively the EU funds. The other one concentrates on the impact of the absorbed EU funds, in other words to the qualitative aspects of the absorption capacity. Our paper discusses these aspects mainly from the viewpoint of regional disparities in the NMS, proposing a typology of their regions based on the main regional growth characteristics. The implications of the structural assistance on regional disparities are also addressed, taking into consideration economic and social criteria and requirements at EU, national, regional and local levels.

  19. Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate

    Science.gov (United States)

    Mangold, Elisabeth; Böhmer, Anne C.; Ishorst, Nina; Hoebel, Ann-Kathrin; Gültepe, Pinar; Schuenke, Hannah; Klamt, Johanna; Hofmann, Andrea; Gölz, Lina; Raff, Ruth; Tessmann, Peter; Nowak, Stefanie; Reutter, Heiko; Hemprich, Alexander; Kreusch, Thomas; Kramer, Franz-Josef; Braumann, Bert; Reich, Rudolf; Schmidt, Gül; Jäger, Andreas; Reiter, Rudolf; Brosch, Sibylle; Stavusis, Janis; Ishida, Miho; Seselgyte, Rimante; Moore, Gudrun E.; Nöthen, Markus M.; Borck, Guntram; Aldhorae, Khalid A.; Lace, Baiba; Stanier, Philip; Knapp, Michael; Ludwig, Kerstin U.

    2016-01-01

    Nonsyndromic cleft lip with/without cleft palate (nsCL/P) and nonsyndromic cleft palate only (nsCPO) are the most frequent subphenotypes of orofacial clefts. A common syndromic form of orofacial clefting is Van der Woude syndrome (VWS) where individuals have CL/P or CPO, often but not always associated with lower lip pits. Recently, ∼5% of VWS-affected individuals were identified with mutations in the grainy head-like 3 gene (GRHL3). To investigate GRHL3 in nonsyndromic clefting, we sequenced its coding region in 576 Europeans with nsCL/P and 96 with nsCPO. Most strikingly, nsCPO-affected individuals had a higher minor allele frequency for rs41268753 (0.099) than control subjects (0.049; p = 1.24 × 10−2). This association was replicated in nsCPO/control cohorts from Latvia, Yemen, and the UK (pcombined = 2.63 × 10−5; ORallelic = 2.46 [95% CI 1.6–3.7]) and reached genome-wide significance in combination with imputed data from a GWAS in nsCPO triads (p = 2.73 × 10−9). Notably, rs41268753 is not associated with nsCL/P (p = 0.45). rs41268753 encodes the highly conserved p.Thr454Met (c.1361C>T) (GERP = 5.3), which prediction programs denote as deleterious, has a CADD score of 29.6, and increases protein binding capacity in silico. Sequencing also revealed four novel truncating GRHL3 mutations including two that were de novo in four families, where all nine individuals harboring mutations had nsCPO. This is important for genetic counseling: given that VWS is rare compared to nsCPO, our data suggest that dominant GRHL3 mutations are more likely to cause nonsyndromic than syndromic CPO. Thus, with rare dominant mutations and a common risk variant in the coding region, we have identified an important contribution for GRHL3 in nsCPO. PMID:27018475

  20. Process and domain specificity in regions engaged for face processing: an fMRI study of perceptual differentiation.

    Science.gov (United States)

    Collins, Heather R; Zhu, Xun; Bhatt, Ramesh S; Clark, Jonathan D; Joseph, Jane E

    2012-12-01

    The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. This study parametrically varied demands on featural, first-order configural, or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing), or reflected generalized perceptual differentiation (i.e., differentiation that crosses category and processing type boundaries). ROIs were identified in a separate localizer run or with a similarity regressor in the face-matching runs. The predominant principle accounting for fMRI signal modulation in most regions was generalized perceptual differentiation. Nearly all regions showed perceptual differentiation for both faces and houses for more than one processing type, even if the region was identified as face-preferential in the localizer run. Consistent with process specificity, some regions showed perceptual differentiation for first-order processing of faces and houses (right fusiform face area and occipito-temporal cortex and right lateral occipital complex), but not for featural or second-order processing. Somewhat consistent with domain specificity, the right inferior frontal gyrus showed perceptual differentiation only for faces in the featural matching task. The present findings demonstrate that the majority of regions involved in perceptual differentiation of faces are also involved in differentiation of other visually homogenous categories.

  1. Improvement of tool support of the spatial approach to regional planning: problems, specifics, trends

    Directory of Open Access Journals (Sweden)

    Nataliya Gennadievna Yushkova

    2015-01-01

    Full Text Available The emerging imperatives of innovation economic development in Russia determine the content of conceptual and institutional constraints to the development of regional economic systems (RES. They consider the regional planning system as a leading priority in its inseparable unity with modern public administration tasks. However, the practice of development of long-term plans in the RF subjects proves that the innovation challenges of economic policy are not reflected properly in them or they are significantly distorted. The following reasons reduce the effectiveness of modernization processes in the RF subjects and hamper the appropriate reaction of RES on their impact: the lack of coordination between socio-economic and spatial regional plans, the imbalance of interaction between state authorities engaged in long-term planning, the lack of real prerequisites for the implementation of innovation initiatives in the regions. Systematization and analysis of long-term plans make it possible to substantiate the consistency of the spatial approach to regional planning expressed in the dominance of the transformational function that synchronizes the configuration and parameters of RES, and to establish ways to integrate spatial components in the system of regional planning through optimization of its tool support. The change in the content of the instrumentation support is based on the synthesis of the predominant basic characteristics of the existing tools used in isolated subsystems of regional planning of socio-economic and territorial development. The study has established a system of tool support for regional planning that adapts to the changes in both internal and external factors in the development of RES. Three main groups of tools: organizing, regulating, and coordinating are defined by their typing in accordance with the groups of management functions. The article proposes the modeling of combinations of tools that are subordinated to the

  2. Antiviral activity of Small interfering RNAs: Specificity testing using heterologous virus reveals interferon-related effects overlooked by conventional mismatch controls

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Lorenzen, Niels; Pedersen, Finn Skou

    2006-01-01

    to the viral glycoprotein gene of the target-virus efficiently inhibited viral multiplication in infected cell cultures, while two of three corresponding mismatched siRNAs did not have this effect. This suggested specific interference, but similar results were obtained when the same siRNAs were tested against...... a heterologous virus. Further analyses revealed that the siRNAs induced a non-target-specific anti-viral effect correlating with upregulation of the interferon induced Mx gene....

  3. Transcriptome analysis reveals regional and temporal differences in mucosal immune system development in the small intestine of neonatal calves.

    Science.gov (United States)

    Liang, Guanxiang; Malmuthuge, Nilusha; Bao, Hua; Stothard, Paul; Griebel, Philip J; Guan, Le Luo

    2016-08-11

    Postnatal development of the mammalian mucosal immune system is crucial for responding to the rapid colonization by commensal bacteria and possible exposure to pathogens. This study analyzed expression patterns for mRNAs and their relationship with microRNAs (miRNAs) in the bovine small intestine during the critical neonatal period (0 to 42 days). This analysis revealed molecular mechanisms regulating the postnatal development of the intestinal mucosal immune system. Small intestine samples (jejunum and ileum) were collected from newborn male, Holstein calves immediately post-partum (n = 3) and at 7 (n = 5), 21 (n = 5), and 42 (n = 5) days of age and the transcriptomes were profiled using RNA-Seq. When analyzing all time points collectively, greater expression of genes encoding the complement functional pathway, as well as lower expression of genes encoding Toll-like receptors and NOD-like receptors were observed in the jejunum when compared to the ileum. In addition, significant changes in the expression of immune-related genes were detected within the first week post-partum in both jejunum and ileum. For example, increased expression of genes encoding tight junction proteins (claudin 1, claudin 4 and occludin), an antimicrobial peptide (Regenerating Islet-Derived 3-γ), NOD-like receptors (NACHT, LRR and PYD domain-containing protein 3), regulatory T cell marker (forkhead box P3), and both anti-inflammatory (interleukin 10) and pro-inflammatory (interleukin 8) cytokines was observed throughout the small intestine of 7-day-old calves when compared to newborn calves. Moreover, the expression of mucosal immune-related genes were either positively or negatively correlated with total bacterial population depending on both intestinal region and age. The integrated analysis of miRNAs and mRNAs supported the conclusion that miRNAs may regulate temporal changes in the expression of genes encoding tight junction proteins (miR-335), cytokines (miR-335) and

  4. Two negative cis-regulatory regions involved in fruit-specific promoter activity from watermelon (Citrullus vulgaris S.).

    Science.gov (United States)

    Yin, Tao; Wu, Hanying; Zhang, Shanglong; Lu, Hongyu; Zhang, Lingxiao; Xu, Yong; Chen, Daming; Liu, Jingmei

    2009-01-01

    A 1.8 kb 5'-flanking region of the large subunit of ADP-glucose pyrophosphorylase, isolated from watermelon (Citrullus vulgaris S.), has fruit-specific promoter activity in transgenic tomato plants. Two negative regulatory regions, from -986 to -959 and from -472 to -424, were identified in this promoter region by fine deletion analyses. Removal of both regions led to constitutive expression in epidermal cells. Gain-of-function experiments showed that these two regions were sufficient to inhibit RFP (red fluorescent protein) expression in transformed epidermal cells when fused to the cauliflower mosaic virus (CaMV) 35S minimal promoter. Gel mobility shift experiments demonstrated the presence of leaf nuclear factors that interact with these two elements. A TCCAAAA motif was identified in these two regions, as well as one in the reverse orientation, which was confirmed to be a novel specific cis-element. A quantitative beta-glucuronidase (GUS) activity assay of stable transgenic tomato plants showed that the activities of chimeric promoters harbouring only one of the two cis-elements, or both, were approximately 10-fold higher in fruits than in leaves. These data confirm that the TCCAAAA motif functions as a fruit-specific element by inhibiting gene expression in leaves.

  5. Secondary structure of the rRNA ITS2 region reveals key evolutionary patterns in acroporid corals.

    Science.gov (United States)

    Coleman, Annette W; van Oppen, Madeleine J H

    2008-10-01

    This study investigates the ribosomal RNA transcript secondary structure in corals as confirmed by compensatory base changes in Isopora/Acropora species. These species are unique versus all other corals in the absence of a eukaryote-wide conserved structural component, the helix III in internal transcriber spacer (ITS) 2, and their variability in the 5.8S-LSU helix basal to ITS2, a helix with pairings identical among all other scleractinian corals. Furthermore, Isopora/Acropora individuals display at least two, and as many as three, ITS sequence isotypes in their genome which appear to be capable of function. From consideration of the conserved elements in ITS2 and flanking regions, it appears that there are three major groups within the IsoporaAcropora lineage: the Isopora + Acropora "longi" group, the large group including Caribbean Acropora + the Acropora "carib" types plus the bulk of the Indo-Pacific Acropora species, and the remaining enigmatic "pseudo" group found in the Pacific. Interbreeding is possible among Caribbean A. palmata and A. cervicornis and among some species of Indo-Pacific Acropora. Recombinant ITS sequences are obvious among these latter, such that morphology (as represented by species name) does not correlate with common ITS sequence. The combination of characters revealed by RNA secondary structure analyses suggests a recent past/current history of interbreeding among the Indo-Pacific Acropora species and a shared ancestry of some of these with the Caribbean Acropora. The unusual absence of helix III of ITS2 of Isopora/Acropora species may have some causative role in the equally unusual instability in the 5.8S-LSU helix basal to ITS2 of this species complex.

  6. Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes

    DEFF Research Database (Denmark)

    Winther, Thilde Nordmann; Jacobsen, Kari Stougaard; Mirza, Aashiq Hussain

    2014-01-01

    Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role...... in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes. Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children...... with chronic hepatitis B (CHB) and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBe...

  7. Developing regionally specific grazing practices to promote production, profitability, and environmental quality

    Science.gov (United States)

    Rangelands are valued for their capacity to provide diverse suites of ecosystem services, from food production to carbon storage to biological diversity. Although rangelands worldwide share common characteristics, differences among biogeographic regions result in differences in the types of opportun...

  8. Genomic Resources of Three Pulsatilla Species Reveal Evolutionary Hotspots, Species-Specific Sites and Variable Plastid Structure in the Family Ranunculaceae

    Directory of Open Access Journals (Sweden)

    Monika Szczecińska

    2015-09-01

    Full Text Available Background: The European continent is presently colonized by nine species of the genus Pulsatilla, five of which are encountered only in mountainous regions of southwest and south-central Europe. The remaining four species inhabit lowlands in the north-central and eastern parts of the continent. Most plants of the genus Pulsatilla are rare and endangered, which is why most research efforts focused on their biology, ecology and hybridization. The objective of this study was to develop genomic resources, including complete plastid genomes and nuclear rRNA clusters, for three sympatric Pulsatilla species that are most commonly found in Central Europe. The results will supply valuable information about genetic variation, which can be used in the process of designing primers for population studies and conservation genetics research. The complete plastid genomes together with the nuclear rRNA cluster can serve as a useful tool in hybridization studies. Methodology/principal findings: Six complete plastid genomes and nuclear rRNA clusters were sequenced from three species of Pulsatilla using the Illumina sequencing technology. Four junctions between single copy regions and inverted repeats and junctions between the identified locally-collinear blocks (LCB were confirmed by Sanger sequencing. Pulsatilla genomes of 120 unique genes had a total length of approximately 161–162 kb, and 21 were duplicated in the inverted repeats (IR region. Comparative plastid genomes of newly-sequenced Pulsatilla and the previously-identified plastomes of Aconitum and Ranunculus species belonging to the family Ranunculaceae revealed several variations in the structure of the genome, but the gene content remained constant. The nuclear rRNA cluster (18S-ITS1-5.8S-ITS2-26S of studied Pulsatilla species is 5795 bp long. Among five analyzed regions of the rRNA cluster, only Internal Transcribed Spacer 2 (ITS2 enabled the molecular delimitation of closely-related Pulsatilla

  9. Evidence for gene-specific rather than transcription rate-dependent histone H3 exchange in yeast coding regions.

    Science.gov (United States)

    Gat-Viks, Irit; Vingron, Martin

    2009-02-01

    In eukaryotic organisms, histones are dynamically exchanged independently of DNA replication. Recent reports show that different coding regions differ in their amount of replication-independent histone H3 exchange. The current paradigm is that this histone exchange variability among coding regions is a consequence of transcription rate. Here we put forward the idea that this variability might be also modulated in a gene-specific manner independently of transcription rate. To that end, we study transcription rate-independent replication-independent coding region histone H3 exchange. We term such events relative exchange. Our genome-wide analysis shows conclusively that in yeast, relative exchange is a novel consistent feature of coding regions. Outside of replication, each coding region has a characteristic pattern of histone H3 exchange that is either higher or lower than what was expected by its RNAPII transcription rate alone. Histone H3 exchange in coding regions might be a way to add or remove certain histone modifications that are important for transcription elongation. Therefore, our results that gene-specific coding region histone H3 exchange is decoupled from transcription rate might hint at a new epigenetic mechanism of transcription regulation.

  10. A remote arene-binding site on prostate specific membrane antigen revealed by antibody-recruiting small molecules

    Czech Academy of Sciences Publication Activity Database

    Zhang, A.X.; Murelli, R.P.; Bařinka, Cyril; Michel, J.; Cocleaza, A.; Jorgensen, W.L.; Lubkowski, J.; Spiegel, D.A.

    2010-01-01

    Roč. 132, č. 36 (2010), s. 12711-12716 ISSN 0002-7863 Institutional research plan: CEZ:AV0Z50520701 Keywords : Prostate -specific membrane antigen * antibody recruiting molecules * Structure-activity relationship Subject RIV: CE - Biochemistry Impact factor: 9.019, year: 2010

  11. miRNA-target chimeras reveal miRNA 3'-end pairing as a major determinant of Argonaute target specificity

    DEFF Research Database (Denmark)

    Moore, Michael J; Scheel, Troels K H; Luna, Joseph M

    2015-01-01

    microRNAs (miRNAs) act as sequence-specific guides for Argonaute (AGO) proteins, which mediate posttranscriptional silencing of target messenger RNAs. Despite their importance in many biological processes, rules governing AGO-miRNA targeting are only partially understood. Here we report a modifie...

  12. Combining substrate specificity analysis with support vector classifiers reveals feruloyl esterase as a phylogenetically informative protein group

    DEFF Research Database (Denmark)

    Olivares Hernandez, Roberto; Sunner, Hampus; Frisvad, Jens Christian

    2010-01-01

    Background Our understanding of how fungi evolved to develop a variety of ecological niches, is limited but of fundamental biological importance. Specifically, the evolution of enzymes affects how well species can adapt to new environmental conditions. Feruloyl esterases (FAEs) are enzymes able...

  13. Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: a randomized cross-over study.

    Science.gov (United States)

    Windischberger, Christian; Lanzenberger, Rupert; Holik, Alexander; Spindelegger, Christoph; Stein, Patrycja; Moser, Ulrike; Gerstl, Florian; Fink, Martin; Moser, Ewald; Kasper, Siegfried

    2010-01-15

    Area-specific and stimulation-dependent changes of human brain activation by selective serotonin reuptake inhibitors (SSRI) are an important issue for improved understanding of treatment mechanisms, given the frequent prescription of these drugs in depression and anxiety disorders. The aim of this neuroimaging study was to investigate differences in BOLD-signal caused by administration of the SSRIs escitalopram and citalopram using pharmacological functional magnetic resonance imaging (pharmaco-fMRI). Eighteen healthy subjects participated in a placebo-controlled, randomized, double-blind study in cross-over repeated measures design. Each volunteer performed facial emotional discrimination and a sensorimotor control paradigm during three scanning sessions. Citalopram (20 mg/d), escitalopram (10 mg/d) and placebo were administered for 10 days each with a drug-free period of at least 21 days. Significant pharmacological effects on BOLD-signal were found in the amygdala, medial frontal gyrus, parahippocampal, fusiform and middle temporal gyri. Post-hoc t-tests revealed decreased BOLD-signal in the right amygdala and left parahippocampal gyrus in both pharmacological conditions, compared to placebo. Escitalopram, compared to citalopram, induced a decrease of BOLD-signal in the medial frontal gyrus and an increase in the right fusiform and left parahippocampal gyri. Drug effects were concentrated in brain regions with dense serotonergic projections. Both escitalopram and citalopram attenuated BOLD-signal in the amygdala and parahippocampal cortex to emotionally significant stimuli compared to control stimuli. We believe that reduced reactivity in the medial frontal gyrus found for escitalopram compared to citalopram administration might explain the response differences between study drugs as demonstrated in previous clinical trials.

  14. Region-Specific Defects of Respiratory Capacities in the Ndufs4(KO Mouse Brain.

    Directory of Open Access Journals (Sweden)

    Ernst-Bernhard Kayser

    Full Text Available Lack of NDUFS4, a subunit of mitochondrial complex I (NADH:ubiquinone oxidoreductase, causes Leigh syndrome (LS, a progressive encephalomyopathy. Knocking out Ndufs4, either systemically or in brain only, elicits LS in mice. In patients as well as in KO mice distinct regions of the brain degenerate while surrounding tissue survives despite systemic complex I dysfunction. For the understanding of disease etiology and ultimately for the development of rationale treatments for LS, it appears important to uncover the mechanisms that govern focal neurodegeneration.Here we used the Ndufs4(KO mouse to investigate whether regional and temporal differences in respiratory capacity of the brain could be correlated with neurodegeneration. In the KO the respiratory capacity of synaptosomes from the degeneration prone regions olfactory bulb, brainstem and cerebellum was significantly decreased. The difference was measurable even before the onset of neurological symptoms. Furthermore, neither compensating nor exacerbating changes in glycolytic capacity of the synaptosomes were found. By contrast, the KO retained near normal levels of synaptosomal respiration in the degeneration-resistant/resilient "rest" of the brain. We also investigated non-synaptic mitochondria. The KO expectedly had diminished capacity for oxidative phosphorylation (state 3 respiration with complex I dependent substrate combinations pyruvate/malate and glutamate/malate but surprisingly had normal activity with α-ketoglutarate/malate. No correlation between oxidative phosphorylation (pyruvate/malate driven state 3 respiration and neurodegeneration was found: Notably, state 3 remained constant in the KO while in controls it tended to increase with time leading to significant differences between the genotypes in older mice in both vulnerable and resilient brain regions. Neither regional ROS damage, measured as HNE-modified protein, nor regional complex I stability, assessed by blue native

  15. Matrix factorization reveals aging-specific co-expression gene modules in the fat and muscle tissues in nonhuman primates

    Science.gov (United States)

    Wang, Yongcui; Zhao, Weiling; Zhou, Xiaobo

    2016-10-01

    Accurate identification of coherent transcriptional modules (subnetworks) in adipose and muscle tissues is important for revealing the related mechanisms and co-regulated pathways involved in the development of aging-related diseases. Here, we proposed a systematically computational approach, called ICEGM, to Identify the Co-Expression Gene Modules through a novel mathematical framework of Higher-Order Generalized Singular Value Decomposition (HO-GSVD). ICEGM was applied on the adipose, and heart and skeletal muscle tissues in old and young female African green vervet monkeys. The genes associated with the development of inflammation, cardiovascular and skeletal disorder diseases, and cancer were revealed by the ICEGM. Meanwhile, genes in the ICEGM modules were also enriched in the adipocytes, smooth muscle cells, cardiac myocytes, and immune cells. Comprehensive disease annotation and canonical pathway analysis indicated that immune cells, adipocytes, cardiomyocytes, and smooth muscle cells played a synergistic role in cardiac and physical functions in the aged monkeys by regulation of the biological processes associated with metabolism, inflammation, and atherosclerosis. In conclusion, the ICEGM provides an efficiently systematic framework for decoding the co-expression gene modules in multiple tissues. Analysis of genes in the ICEGM module yielded important insights on the cooperative role of multiple tissues in the development of diseases.

  16. Specification and evaluation of a regional PACS in the SaxTeleMed project

    Science.gov (United States)

    Lemke, Heinz U.; Niederlag, W.; Heuser, H.

    2002-05-01

    During the early development phase of PACS, its implementation was mainly a matter of the radiological department of a hospital. This is changing rapidly and PACS planning and realization is increasingly seen in the context of a hospital-wide approach. With a growth of networking amongst healthcare institutions and the growing relevance of teleradiological scenarios, new strategies must be followed which take not only local but also regional and global aspects of PACS into consideration. One such regional PACS project was initiated by the Ministry of Social Welfare of the Free State of Saxony in Germany. This 'reference model program for the digitization of imaging procedures and communication of images between hospitals in the free state of Saxony' (SaxTeleMed) covers seven regional projects distributed throughout Saxony. Each regional project is organized around so called lead hospitals, which network with other cooperating hospitals and medical practices. The regional reference projects are designed to be largely independent from one another. In some instances, however, a network connection between reference projects is also considered. Altogether, 39 hospitals and medical centers are involved in the model program. The aim of this program is to test the technical, organizational, legal and economic problems in the area of digitization and networking within the free State of Saxony. With the knowledge gained it is expected to improve future investment decisions in healthcare and above all to implement secure systems.

  17. Opsoclonus-induced occipital deactivation with a region-specific distribution

    NARCIS (Netherlands)

    de Jong, BM; van Weerden, TW; Haaxma, R

    The cerebral distribution of 2-[18F]fluoro 2-deoxy-D-glucose (FDG) uptake in a patient with opsoclonus was measured by positron emission tomography (PET) and subsequently compared with the distribution in ten normal subjects. Statistical parametric mapping (SPM) revealed a decreased occipital FDG

  18. Quantitative analysis of commensal Escherichia coli populations reveals host-specific enterotypes at the intra-species level

    OpenAIRE

    Smati, Mounira; Clermont, Olivier; Bleibtreu, Alexandre; Fourreau, Frédéric; David, Anthony; Daubié, Anne-Sophie; Hignard, Cécile; Loison, Odile; Picard, Bertrand; Denamur, Erick

    2015-01-01

    The primary habitat of the Escherichia coli species is the gut of warm-blooded vertebrates. The E. coli species is structured into four main phylogenetic groups A, B1, B2, and D. We estimated the relative proportions of these phylogroups in the feces of 137 wild and domesticated animals with various diets living in the Ile de France (Paris) region by real-time PCR. We distinguished three main clusters characterized by a particular abundance of two or more phylogroups within the E. coli animal...

  19. Structural and biochemical studies of a fluoroacetyl-CoA-specific thioesterase reveal a molecular basis for fluorine selectivity.

    Science.gov (United States)

    Weeks, Amy M; Coyle, Scott M; Jinek, Martin; Doudna, Jennifer A; Chang, Michelle C Y

    2010-11-02

    We have initiated a broad-based program aimed at understanding the molecular basis of fluorine specificity in enzymatic systems, and in this context, we report crystallographic and biochemical studies on a fluoroacetyl-coenzyme A (CoA) specific thioesterase (FlK) from Streptomyces cattleya. Our data establish that FlK is competent to protect its host from fluoroacetate toxicity in vivo and demonstrate a 10(6)-fold discrimination between fluoroacetyl-CoA (k(cat)/K(M) = 5 × 10⁷ M⁻¹ s⁻¹) and acetyl-CoA (k(cat)/K(M) = 30 M⁻¹ s⁻¹) based on a single fluorine substitution that originates from differences in both substrate reactivity and binding. We show that Thr 42, Glu 50, and His 76 are key catalytic residues and identify several factors that influence substrate selectivity. We propose that FlK minimizes interaction with the thioester carbonyl, leading to selection against acetyl-CoA binding that can be recovered in part by new C═O interactions in the T42S and T42C mutants. We hypothesize that the loss of these interactions is compensated by the entropic driving force for fluorinated substrate binding in a hydrophobic binding pocket created by a lid structure, containing Val 23, Leu 26, Phe 33, and Phe 36, that is not found in other structurally characterized members of this superfamily. We further suggest that water plays a critical role in fluorine specificity based on biochemical and structural studies focused on the unique Phe 36 "gate" residue, which functions to exclude water from the active site. Taken together, the findings from these studies offer molecular insights into organofluorine recognition and design of fluorine-specific enzymes.

  20. Stereospecific suppression of active site mutants by methylphosphonate substituted substrates reveals the stereochemical course of site-specific DNA recombination

    OpenAIRE

    Rowley, Paul A.; Kachroo, Aashiq H.; Ma, Chien-Hui; Maciaszek, Anna D.; Guga, Piotr; Jayaram, Makkuni

    2015-01-01

    Tyrosine site-specific recombinases, which promote one class of biologically important phosphoryl transfer reactions in DNA, exemplify active site mechanisms for stabilizing the phosphate transition state. A highly conserved arginine duo (Arg-I; Arg-II) of the recombinase active site plays a crucial role in this function. Cre and Flp recombinase mutants lacking either arginine can be rescued by compensatory charge neutralization of the scissile phosphate via methylphosphonate (MeP) modificati...

  1. Reconstructed ancestral enzymes reveal that negative selection drove the evolution of substrate specificity in ADP-dependent kinases.

    Science.gov (United States)

    Castro-Fernandez, Víctor; Herrera-Morande, Alejandra; Zamora, Ricardo; Merino, Felipe; Gonzalez-Ordenes, Felipe; Padilla-Salinas, Felipe; Pereira, Humberto M; Brandão-Neto, Jose; Garratt, Richard C; Guixe, Victoria

    2017-09-22

    One central goal in molecular evolution is to pinpoint the mechanisms and evolutionary forces that cause an enzyme to change its substrate specificity; however, these processes remain largely unexplored. Using the glycolytic ADP-dependent kinases of archaea, including the orders Thermococcales , Methanosarcinales , and Methanococcales , as a model and employing an approach involving paleoenzymology, evolutionary statistics, and protein structural analysis, we could track changes in substrate specificity during ADP-dependent kinase evolution along with the structural determinants of these changes. To do so, we studied five key resurrected ancestral enzymes as well as their extant counterparts. We found that a major shift in function from a bifunctional ancestor that could phosphorylate either glucose or fructose 6-phosphate (fructose-6-P) as a substrate to a fructose 6-P-specific enzyme was started by a single amino acid substitution resulting in negative selection with a ground-state mode against glucose and a subsequent 1,600-fold change in specificity of the ancestral protein. This change rendered the residual phosphorylation of glucose a promiscuous and physiologically irrelevant activity, highlighting how promiscuity may be an evolutionary vestige of ancestral enzyme activities, which have been eliminated over time. We also could reconstruct the evolutionary history of substrate utilization by using an evolutionary model of discrete binary characters, indicating that substrate uses can be discretely lost or acquired during enzyme evolution. These findings exemplify how negative selection and subtle enzyme changes can lead to major evolutionary shifts in function, which can subsequently generate important adaptive advantages, for example, in improving glycolytic efficiency in Thermococcales . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Cyclosporin A treatment of Leishmania donovani reveals stage-specific functions of cyclophilins in parasite proliferation and viability.

    Directory of Open Access Journals (Sweden)

    Wai-Lok Yau

    Full Text Available BACKGROUND: Cyclosporin A (CsA has important anti-microbial activity against parasites of the genus Leishmania, suggesting CsA-binding cyclophilins (CyPs as potential drug targets. However, no information is available on the genetic diversity of this important protein family, and the mechanisms underlying the cytotoxic effects of CsA on intracellular amastigotes are only poorly understood. Here, we performed a first genome-wide analysis of Leishmania CyPs and investigated the effects of CsA on host-free L. donovani amastigotes in order to elucidate the relevance of these parasite proteins for drug development. METHODOLOGY/PRINCIPAL FINDINGS: Multiple sequence alignment and cluster analysis identified 17 Leishmania CyPs with significant sequence differences to human CyPs, but with highly conserved functional residues implicated in PPIase function and CsA binding. CsA treatment of promastigotes resulted in a dose-dependent inhibition of cell growth with an IC50 between 15 and 20 microM as demonstrated by proliferation assay and cell cycle analysis. Scanning electron microscopy revealed striking morphological changes in CsA treated promastigotes reminiscent to developing amastigotes, suggesting a role for parasite CyPs in Leishmania differentiation. In contrast to promastigotes, CsA was highly toxic to amastigotes with an IC50 between 5 and 10 microM, revealing for the first time a direct lethal effect of CsA on the pathogenic mammalian stage linked to parasite thermotolerance, independent from host CyPs. Structural modeling, enrichment of CsA-binding proteins from parasite extracts by FPLC, and PPIase activity assays revealed direct interaction of the inhibitor with LmaCyP40, a bifunctional cyclophilin with potential co-chaperone function. CONCLUSIONS/SIGNIFICANCE: The evolutionary expansion of the Leishmania CyP protein family and the toxicity of CsA on host-free amastigotes suggest important roles of PPIases in parasite biology and implicate

  3. [Specific features of surgical anatomy of the subhyoid region with special reference to tracheostomy].

    Science.gov (United States)

    Chernykh, A V; Mashkova, T A; Nerovnyĭ, A I; Maleev, Iu V

    2010-01-01

    Peculiarities of thyroid gland linear dimensions, volume, shape, and topographical features were investigated using the morphological material obtained from 426 human corpses of either gender with a view to using this information for planning and performing tracheostomy in residents of the Central Chernozem region, Russia. The study yielded new data on surgical anatomy of additional muscles of the subhyoid region, thyroid isthmus and pyramidal lobe. Rare and previously unknown variants of anatomical structure of the anterior cervical area are described that may play the role of risk factors of postoperative complications of tracheostomy. Relevant recommendations are provided for practicing otorhinolaryngologists.

  4. Region-Specific Involvement of Actin Rearrangement-Related Synaptic Structure Alterations in Conditioned Taste Aversion Memory

    Science.gov (United States)

    Bi, Ai-Ling; Wang, Yue; Li, Bo-Qin; Wang, Qian-Qian; Ma, Ling; Yu, Hui; Zhao, Ling; Chen, Zhe-Yu

    2010-01-01

    Actin rearrangement plays an essential role in learning and memory; however, the spatial and temporal regulation of actin dynamics in different phases of associative memory has not been fully understood. Here, using the conditioned taste aversion (CTA) paradigm, we investigated the region-specific involvement of actin rearrangement-related…

  5. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes

    NARCIS (Netherlands)

    Skaletsky, Helen; Kuroda-Kawaguchi, Tomoko; Minx, Patrick J.; Cordum, Holland S.; Hillier, LaDeana; Brown, Laura G.; Repping, Sjoerd; Pyntikova, Tatyana; Ali, Johar; Bieri, Tamberlyn; Chinwalla, Asif; Delehaunty, Andrew; Delehaunty, Kim; Du, Hui; Fewell, Ginger; Fulton, Lucinda; Fulton, Robert; Graves, Tina; Hou, Shun-Fang; Latrielle, Philip; Leonard, Shawn; Mardis, Elaine; Maupin, Rachel; McPherson, John; Miner, Tracie; Nash, William; Nguyen, Christine; Ozersky, Philip; Pepin, Kymberlie; Rock, Susan; Rohlfing, Tracy; Scott, Kelsi; Schultz, Brian; Strong, Cindy; Tin-Wollam, Aye; Yang, Shiaw-Pyng; Waterston, Robert H.; Wilson, Richard K.; Rozen, Steve; Page, David C.

    2003-01-01

    The male-specific region of the Y chromosome, the MSY, differentiates the sexes and comprises 95% of the chromosome's length. Here, we report that the MSY is a mosaic of heterochromatic sequences and three classes of euchromatic sequences: X-transposed, X-degenerate and ampliconic. These classes

  6. Revealing of endogenous Marinobufagin by an ultra-specific and sensitive UHPLC-MS/MS assay in pregnant women.

    Science.gov (United States)

    Lenaerts, Charline; Bond, Liz; Tuytten, Robin; Blankert, Bertrand

    2018-09-01

    Marinobufagenin (MBG) is a bufadienolide cardiac inotrope implicated in volume expansion-mediated hypertensive states including essential hypertension and preeclampsia (PE). Endogenous MBG is an inhibitor of the α1-isoform of Na + ,K + -ATPase with vasoconstrictive and cardiotonic properties, causing hypertension and natriuresis. Elevated endogenous MBG-like material levels have been described by immunoassays in salt-sensitive pregnant and preeclamptic rats as well as in preeclamptic human patients. The rise of endogenous MBG-like material appears prior the development of the main symptoms of PE, leading us to consider MBG as one of the potential biomarkers for PE. The weak specificity and the high variability of the published immunoassays gives no certification about endogenous MBG existence. This led us to set-up a highly specific and sensitive analytical method to detect MBG in plasma at low levels relying on liquid chromatography combined to mass spectrometry (UHPLC-MS/MS) with recording of 7 highly specific MRM transitions for MBG. Pure MBG standard used in the method development was obtained by purification from the Bufo marinus toad venom. d 3 -25-hydroxyvitamin D3 was used as internal standard. An increasing organic gradient with mobile phase A and B composed of 97:3 (v/v) H 2 O: MeOH and 50:45:5 (v/v/v) MeOH:IPA:H 2 O at pH 4.5 respectively was used on a Pursuit 3 PFP column (100 mm × 3 mm; 3 µm) to allow elution and separation of the plasmatic compounds. Chromatographic analyses of plasma samples were preceded by a precipitation of proteins pretreatment. The developed UHPLC-MS/MS assay has been applied to early-pregnant women plasma samples allowing us to investigate MBG plasma levels. Thanks to the high specificity of the assay we were able to authenticate and certify the presence of endogenous MBG in early-pregnant women plasma with the use of the 7 selected specific mass transitions. These pioneering preliminary results are giving a

  7. A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis.

    Science.gov (United States)

    Taroni, Jaclyn N; Greene, Casey S; Martyanov, Viktor; Wood, Tammara A; Christmann, Romy B; Farber, Harrison W; Lafyatis, Robert A; Denton, Christopher P; Hinchcliff, Monique E; Pioli, Patricia A; Mahoney, J Matthew; Whitfield, Michael L

    2017-03-23

    Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. Our results suggest that the innate immune

  8. The Variable Regions of Lactobacillus rhamnosus Genomes Reveal the Dynamic Evolution of Metabolic and Host-Adaptation Repertoires.

    Science.gov (United States)

    Ceapa, Corina; Davids, Mark; Ritari, Jarmo; Lambert, Jolanda; Wels, Michiel; Douillard, François P; Smokvina, Tamara; de Vos, Willem M; Knol, Jan; Kleerebezem, Michiel

    2016-07-02

    Lactobacillus rhamnosus is a diverse Gram-positive species with strains isolated from different ecological niches. Here, we report the genome sequence analysis of 40 diverse strains of L. rhamnosus and their genomic comparison, with a focus on the variable genome. Genomic comparison of 40 L. rhamnosus strains discriminated the conserved genes (core genome) and regions of plasticity involving frequent rearrangements and horizontal transfer (variome). The L. rhamnosus core genome encompasses 2,164 genes, out of 4,711 genes in total (the pan-genome). The accessory genome is dominated by genes encoding carbohydrate transport and metabolism, extracellular polysaccharides (EPS) biosynthesis, bacteriocin production, pili production, the cas system, and the associated clustered regularly interspaced short palindromic repeat (CRISPR) loci, and more than 100 transporter functions and mobile genetic elements like phages, plasmid genes, and transposons. A clade distribution based on amino acid differences between core (shared) proteins matched with the clade distribution obtained from the presence-absence of variable genes. The phylogenetic and variome tree overlap indicated that frequent events of gene acquisition and loss dominated the evolutionary segregation of the strains within this species, which is paralleled by evolutionary diversification of core gene functions. The CRISPR-Cas system could have contributed to this evolutionary segregation. Lactobacillus rhamnosus strains contain the genetic and metabolic machinery with strain-specific gene functions required to adapt to a large range of environments. A remarkable congruency of the evolutionary relatedness of the strains' core and variome functions, possibly favoring interspecies genetic exchanges, underlines the importance of gene-acquisition and loss within the L. rhamnosus strain diversification. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  9. Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.

    Science.gov (United States)

    Bolton, Helen; Graham, Sarah J L; Van der Aa, Niels; Kumar, Parveen; Theunis, Koen; Fernandez Gallardo, Elia; Voet, Thierry; Zernicka-Goetz, Magdalena

    2016-03-29

    Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.

  10. Rapid allopolyploid radiation of moonwort ferns (Botrychium; Ophioglossaceae) revealed by PacBio sequencing of homologous and homeologous nuclear regions.

    Science.gov (United States)

    Dauphin, Benjamin; Grant, Jason R; Farrar, Donald R; Rothfels, Carl J

    2018-03-01

    Polyploidy is a major speciation process in vascular plants, and is postulated to be particularly important in shaping the diversity of extant ferns. However, limitations in the availability of bi-parental markers for ferns have greatly limited phylogenetic investigation of polyploidy in this group. With a large number of allopolyploid species, the genus Botrychium is a classic example in ferns where recurrent polyploidy is postulated to have driven frequent speciation events. Here, we use PacBio sequencing and the PURC bioinformatics pipeline to capture all homeologous or allelic copies of four long (∼1 kb) low-copy nuclear regions from a sample of 45 specimens (25 diploids and 20 polyploids) representing 37 Botrychium taxa, and three outgroups. This sample includes most currently recognized Botrychium species in Europe and North America, and the majority of our specimens were genotyped with co-dominant nuclear allozymes to ensure species identification. We analyzed the sequence data using maximum likelihood (ML) and Bayesian inference (BI) concatenated-data ("gene tree") approaches to explore the relationships among Botrychium species. Finally, we estimated divergence times among Botrychium lineages and inferred the multi-labeled polyploid species tree showing the origins of the polyploid taxa, and their relationships to each other and to their diploid progenitors. We found strong support for the monophyly of the major lineages within Botrychium and identified most of the parental donors of the polyploids; these results largely corroborate earlier morphological and allozyme-based investigations. Each polyploid had at least two distinct homeologs, indicating that all sampled polyploids are likely allopolyploids (rather than autopolyploids). Our divergence-time analyses revealed that these allopolyploid lineages originated recently-within the last two million years-and thus that the genus has undergone a recent radiation, correlated with multiple independent

  11. Temporal Fluctuation in North East Baltic Sea Region Cattle Population Revealed by Mitochondrial and Y-Chromosomal DNA Analyses

    Science.gov (United States)

    Niemi, Marianna; Bläuer, Auli; Iso-Touru, Terhi; Harjula, Janne; Nyström Edmark, Veronica; Rannamäe, Eve; Lõugas, Lembi; Sajantila, Antti; Lidén, Kerstin; Taavitsainen, Jussi-Pekka

    2015-01-01

    Background Ancient DNA analysis offers a way to detect changes in populations over time. To date, most studies of ancient cattle have focused on their domestication in prehistory, while only a limited number of studies have analysed later periods. Conversely, the genetic structure of modern cattle populations is well known given the undertaking of several molecular and population genetic studies. Results Bones and teeth from ancient cattle populations from the North-East Baltic Sea region dated to the Prehistoric (Late Bronze and Iron Age, 5 samples), Medieval (14), and Post-Medieval (26) periods were investigated by sequencing 667 base pairs (bp) from the mitochondrial DNA (mtDNA) and 155 bp of intron 19 in the Y-chromosomal UTY gene. Comparison of maternal (mtDNA haplotypes) genetic diversity in ancient cattle (45 samples) with modern cattle populations in Europe and Asia (2094 samples) revealed 30 ancient mtDNA haplotypes, 24 of which were shared with modern breeds, while 6 were unique to the ancient samples. Of seven Y-chromosomal sequences determined from ancient samples, six were Y2 and one Y1 haplotype. Combined data including Swedish samples from the same periods (64 samples) was compared with the occurrence of Y-chromosomal haplotypes in modern cattle (1614 samples). Conclusions The diversity of haplogroups was highest in the Prehistoric samples, where many haplotypes were unique. The Medieval and Post-Medieval samples also show a high diversity with new haplotypes. Some of these haplotypes have become frequent in modern breeds in the Nordic Countries and North-Western Russia while other haplotypes have remained in only a few local breeds or seem to have been lost. A temporal shift in Y-chromosomal haplotypes from Y2 to Y1 was detected that corresponds with the appearance of new mtDNA haplotypes in the Medieval and Post-Medieval period. This suggests a replacement of the Prehistoric mtDNA and Y chromosomal haplotypes by new types of cattle. PMID:25992976

  12. Areas of distribution in Cyanobacteria; specificity of the cyanoprokaryotic microflora in the Mediterranean region

    Czech Academy of Sciences Publication Activity Database

    Komárek, Jiří

    2003-01-01

    Roč. 16, č. 1 (2003), s. 341-354 ISSN 1120-4060. [OPTIMA Meeting /10./. Palermo , 13.09.2001-19.09.2001] R&D Projects: GA AV ČR KSK6005114 Keywords : cyanobacteria * Mediterranean region Subject RIV: EF - Botanics

  13. Age-and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    Science.gov (United States)

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellu...

  14. Specificity of Atmosphere Correction of Satellite Ocean Color Data in Far-Eastern Region

    Science.gov (United States)

    Trusenkova, O.; Kachur, V.; Aleksanin, A. I.

    2016-02-01

    It was carried out an error analysis of satellite reflectance coefficients (Rrs) of MODIS/AQUA colour data for two atmospheric correction algorithms (NIR, MUMM) in the Far-Eastern region. Some sets of unique data of in situ and satellite measurements have been analysed. A set has some measurements with ASD spectroradiometer for each satellite pass. The measurement allocations were selected so the Chlorophyll-a concentration has high variability. Analysis of arbitrary set demonstrated that the main error component is systematic error, and it has simple relations on Rrs values. The reasons of such error behavior are considered. The most probable explanation of the large errors of oceanic color parameters in the Far-Eastern region is the ability of high concentrations of continental aerosol. A comparison of satellite and in situ measurements at AERONET stations of USA and South Korea regions has been made. It was shown that for NIR-correction of the atmosphere influence the error values in these two regions have differences up to 10 times for almost the same water turbidity and relatively good accuracy of computation of aerosol optical thickness. The study was supported by grant Russian Scientific Foundation No. 14-50-00034, by grant of Russian Foundation of Basic Research No.15-35-21032-mol-a-ved, and by Program of Basic Research "Far East" of Far Eastern Branch of Russian Academy of Sciences.

  15. Premature deaths attributed to source-specific BC emissions in six urban US regions

    International Nuclear Information System (INIS)

    Turner, Matthew D; Henze, Daven K; Capps, Shannon L; Hakami, Amir; Zhao, Shunliu; Resler, Jaroslav; Carmichael, Gregory R; Stanier, Charles O; Baek, Jaemeen; Sandu, Adrian; Russell, Armistead G; Nenes, Athanasios; Pinder, Rob W; Napelenok, Sergey L; Bash, Jesse O; Percell, Peter B; Chai, Tianfeng

    2015-01-01

    Recent studies have shown that exposure to particulate black carbon (BC) has significant adverse health effects and may be more detrimental to human health than exposure to PM 2.5 as a whole. Mobile source BC emission controls, mostly on diesel-burning vehicles, have successfully decreased mobile source BC emissions to less than half of what they were 30 years ago. Quantification of the benefits of previous emissions controls conveys the value of these regulatory actions and provides a method by which future control alternatives could be evaluated. In this study we use the adjoint of the Community Multiscale Air Quality (CMAQ) model to estimate highly-resolved spatial distributions of benefits related to emission reductions for six urban regions within the continental US. Emissions from outside each of the six chosen regions account for between 7% and 27% of the premature deaths attributed to exposure to BC within the region. While we estimate that nonroad mobile and onroad diesel emissions account for the largest number of premature deaths attributable to exposure to BC, onroad gasoline is shown to have more than double the benefit per unit emission relative to that of nonroad mobile and onroad diesel. Within the region encompassing New York City and Philadelphia, reductions in emissions from large industrial combustion sources that are not classified as EGUs (i.e., non-EGU) are estimated to have up to triple the benefits per unit emission relative to reductions to onroad diesel sectors, and provide similar benefits per unit emission to that of onroad gasoline emissions in the region. While onroad mobile emissions have been decreasing in the past 30 years and a majority of vehicle emission controls that regulate PM focus on diesel emissions, our analysis shows the most efficient target for stricter controls is actually onroad gasoline emissions. (letter)

  16. Comprehensive Analysis of CD8+-T-Cell Responses against Hepatitis C Virus Reveals Multiple Unpredicted Specificities

    OpenAIRE

    Lauer, Georg M.; Ouchi, Kei; Chung, Raymond T.; Nguyen, Tam N.; Day, Cheryl L.; Purkis, Deborah R.; Reiser, Markus; Kim, Arthur Y.; Lucas, Michaela; Klenerman, Paul; Walker, Bruce D.

    2002-01-01

    The hepatitis C virus (HCV)-specific CD8+-T-cell response is thought to play a critical role in HCV infection. Studies of these responses have largely relied on the analysis of a small number of previously described or predicted HCV epitopes, mostly restricted by HLA A2. In order to determine the actual breadth and magnitude of CD8+-T-cell responses in the context of diverse HLA class I alleles, we performed a comprehensive analysis of responses to all expressed HCV proteins. By using a panel...

  17. Analysis of an RNA-seq Strand-Specific Library from an East Timorese Cucumber Sample Reveals a Complete Cucurbit aphid-borne yellows virus Genome.

    Science.gov (United States)

    Maina, Solomon; Edwards, Owain R; de Almeida, Luis; Ximenes, Abel; Jones, Roger A C

    2017-05-11

    Analysis of an RNA-seq library from cucumber leaf RNA extracted from a fast technology for analysis of nucleic acids (FTA) card revealed the first complete genome of Cucurbit aphid-borne yellows virus (CABYV) from East Timor. We compare it with 35 complete CABYV genomes from other world regions. It most resembled the genome of the South Korean isolate HD118. Copyright © 2017 Maina et al.

  18. Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection.

    Science.gov (United States)

    Chung, Chee Yeun; Seo, Hyemyung; Sonntag, Kai Christian; Brooks, Andrew; Lin, Ling; Isacson, Ole

    2005-07-01

    Molecular differences between dopamine (DA) neurons may explain why the mesostriatal DA neurons in the A9 region preferentially degenerate in Parkinson's disease (PD) and toxic models, whereas the adjacent A10 region mesolimbic and mesocortical DA neurons are relatively spared. To characterize innate physiological differences between A9 and A10 DA neurons, we determined gene expression profiles in these neurons in the adult mouse by laser capture microdissection, microarray analysis and real-time PCR. We found 42 genes relatively elevated in A9 DA neurons, whereas 61 genes were elevated in A10 DA neurons [> 2-fold; false discovery rate (FDR) neurotoxic or protective biochemical pathways. Three A9-elevated molecules [G-protein coupled inwardly rectifying K channel 2 (GIRK2), adenine nucleotide translocator 2 (ANT-2) and the growth factor IGF-1] and three A10-elevated peptides (GRP, CGRP and PACAP) were further examined in both alpha-synuclein overexpressing PC12 (PC12-alphaSyn) cells and rat primary ventral mesencephalic (VM) cultures exposed to MPP+ neurotoxicity. GIRK2-positive DA neurons were more vulnerable to MPP+ toxicity and overexpression of GIRK2 increased the vulnerability of PC12-alphaSyn cells to the toxin. Blocking of ANT decreased vulnerability to MPP+ in both cell culture systems. Exposing cells to IGF-1, GRP and PACAP decreased vulnerability of both cell types to MPP+, whereas CGRP protected PC12-alphaSyn cells but not primary VM DA neurons. These results indicate that certain differentially expressed molecules in A9 and A10 DA neurons may play key roles in their relative vulnerability to toxins and PD.

  19. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Willing, B.; Halfvarson, J.; Dicksved, J.; Rosenquist, M.; Jarnerot, G.; Engstrand, L.; Tysk, C.; Jansson, J. K

    2008-08-15

    Large inter-individual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease. To reduce variations in exposure during establishment of the gut flora and influence of genotype, we studied the mucosaassociated microbiota of monozygotic twin pairs that were discordant (n=6) or concordant (n=4) for Crohn's disease. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing and quantitative real-time PCR. The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal Crohn's had a dramatically lower abundance (P<0.001) of Faecalibacterium prausnitzii and increased abundance (P<0.03) of Escherichia coli compared to healthy co-twins and those with Crohn's localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype. The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal Crohn's disease phenotype, distinct from colonic Crohn's disease and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of Crohn's and eventually customized treatment.

  20. Combinatorial Modulation of Signaling Pathways Reveals Cell-Type-Specific Requirements for Highly Efficient and Synchronous iPSC Reprogramming

    Directory of Open Access Journals (Sweden)

    Simon E. Vidal

    2014-10-01

    Full Text Available The differentiated state of somatic cells provides barriers for the derivation of induced pluripotent stem cells (iPSCs. To address why some cell types reprogram more readily than others, we studied the effect of combined modulation of cellular signaling pathways. Surprisingly, inhibition of transforming growth factor β (TGF-β together with activation of Wnt signaling in the presence of ascorbic acid allows >80% of murine fibroblasts to acquire pluripotency after 1 week of reprogramming factor expression. In contrast, hepatic and blood progenitors predominantly required only TGF-β inhibition or canonical Wnt activation, respectively, to reprogram at efficiencies approaching 100%. Strikingly, blood progenitors reactivated endogenous pluripotency loci in a highly synchronous manner, and we demonstrate that expression of specific chromatin-modifying enzymes and reduced TGF-β/mitogen-activated protein (MAP kinase activity are intrinsic properties associated with the unique reprogramming response of these cells. Our observations define cell-type-specific requirements for the rapid and synchronous reprogramming of somatic cells.

  1. Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer

    International Nuclear Information System (INIS)

    Kangaspeska, Sara; Hultsch, Susanne; Jaiswal, Alok; Edgren, Henrik; Mpindi, John-Patrick; Eldfors, Samuli; Brück, Oscar; Aittokallio, Tero; Kallioniemi, Olli

    2016-01-01

    The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns. The online version of this article (doi:10.1186/s12885-016-2452-5) contains supplementary material, which is available to authorized users

  2. Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer.

    Science.gov (United States)

    Kangaspeska, Sara; Hultsch, Susanne; Jaiswal, Alok; Edgren, Henrik; Mpindi, John-Patrick; Eldfors, Samuli; Brück, Oscar; Aittokallio, Tero; Kallioniemi, Olli

    2016-07-04

    The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns.

  3. Quantitative phosphoproteomic analysis reveals shared and specific targets of Arabidopsis MPK3, MPK4 and MPK6

    KAUST Repository

    Rayapuram, Naganand; Bigeard, Jean; Alhoraibi, Hanna Mohsen Abdulrab; Bonhomme, Ludovic; Hesse, Anne-Marie; Vinh, Joelle; Hirt, Heribert; Pflieger, Delphine

    2017-01-01

    In Arabidopsis, mitogen-activated protein kinases MPK3, MPK4 and MPK6 constitute essential relays for a variety of functions including cell division, development and innate immunity. While some substrates of MPK3, MPK4 and MPK6 have been identified, the picture is still far from complete. To identify substrates of these MAPKs likely involved in cell division, growth and development we compared the phosphoproteomes of wild-type and mpk3, mpk4 and mpk6. To study the function of these MAPKs in innate immunity, we analyzed their phosphoproteomes following microbe-associated molecular pattern (MAMP) treatment. Partially overlapping substrates were retrieved for all three MAPKs, showing target specificity to one, two or all three MAPKs in different biological processes. More precisely, our results illustrate the fact that the entity to be defined as a specific or a shared substrate for MAPKs is not a phosphoprotein but a particular (S/T)P phosphorylation site in a given protein. As a whole, 152 peptides were identified to be differentially phosphorylated in response to MAMP treatment and/or when compared between genotypes and 70 of them could be classified as putative MAPK targets. Biochemical analysis of a number of putative MAPK substrates by phosphorylation and interaction assays confirmed the global phosphoproteome approach. Our study also expands the set of MAPK substrates to involve other protein kinases, including calcium-dependent (CDPK) and sugar non-fermenting (SnRK) protein kinases.

  4. Quantitative phosphoproteomic analysis reveals shared and specific targets of Arabidopsis MPK3, MPK4 and MPK6

    KAUST Repository

    Rayapuram, Naganand

    2017-11-23

    In Arabidopsis, mitogen-activated protein kinases MPK3, MPK4 and MPK6 constitute essential relays for a variety of functions including cell division, development and innate immunity. While some substrates of MPK3, MPK4 and MPK6 have been identified, the picture is still far from complete. To identify substrates of these MAPKs likely involved in cell division, growth and development we compared the phosphoproteomes of wild-type and mpk3, mpk4 and mpk6. To study the function of these MAPKs in innate immunity, we analyzed their phosphoproteomes following microbe-associated molecular pattern (MAMP) treatment. Partially overlapping substrates were retrieved for all three MAPKs, showing target specificity to one, two or all three MAPKs in different biological processes. More precisely, our results illustrate the fact that the entity to be defined as a specific or a shared substrate for MAPKs is not a phosphoprotein but a particular (S/T)P phosphorylation site in a given protein. As a whole, 152 peptides were identified to be differentially phosphorylated in response to MAMP treatment and/or when compared between genotypes and 70 of them could be classified as putative MAPK targets. Biochemical analysis of a number of putative MAPK substrates by phosphorylation and interaction assays confirmed the global phosphoproteome approach. Our study also expands the set of MAPK substrates to involve other protein kinases, including calcium-dependent (CDPK) and sugar non-fermenting (SnRK) protein kinases.

  5. Structure-guided functional characterization of DUF1460 reveals a highly specific NlpC/P60 amidase family.

    Science.gov (United States)

    Xu, Qingping; Mengin-Lecreulx, Dominique; Patin, Delphine; Grant, Joanna C; Chiu, Hsiu-Ju; Jaroszewski, Lukasz; Knuth, Mark W; Godzik, Adam; Lesley, Scott A; Elsliger, Marc-André; Deacon, Ashley M; Wilson, Ian A

    2014-12-02

    GlcNAc-1,6-anhydro-MurNAc-tetrapeptide is a major peptidoglycan degradation intermediate and a cytotoxin. It is generated by lytic transglycosylases and further degraded and recycled by various enzymes. We have identified and characterized a highly specific N-acetylmuramoyl-L-alanine amidase (AmiA) from Bacteroides uniformis, a member of the DUF1460 protein family, that hydrolyzes GlcNAc-1,6-anhydro-MurNAc-peptide into disaccharide and stem peptide. The high-resolution apo structure at 1.15 Å resolution shows that AmiA is related to NlpC/P60 γ-D-Glu-meso-diaminopimelic acid amidases and shares a common catalytic core and cysteine peptidase-like active site. AmiA has evolved structural adaptations that reconfigure the substrate recognition site. The preferred substrates for AmiA were predicted in silico based on structural and bioinformatics data, and subsequently were characterized experimentally. Further crystal structures of AmiA in complexes with GlcNAc-1,6-anhydro-MurNAc and GlcNAc have enabled us to elucidate substrate recognition and specificity. DUF1460 is highly conserved in structure and defines another amidase family. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Diversity and strain specificity of plant cell wall degrading enzymes revealed by the draft genome of Ruminococcus flavefaciens FD-1.

    Directory of Open Access Journals (Sweden)

    Margret E Berg Miller

    Full Text Available BACKGROUND: Ruminococcus flavefaciens is a predominant cellulolytic rumen bacterium, which forms a multi-enzyme cellulosome complex that could play an integral role in the ability of this bacterium to degrade plant cell wall polysaccharides. Identifying the major enzyme types involved in plant cell wall degradation is essential for gaining a better understanding of the cellulolytic capabilities of this organism as well as highlighting potential enzymes for application in improvement of livestock nutrition and for conversion of cellulosic biomass to liquid fuels. METHODOLOGY/PRINCIPAL FINDINGS: The R. flavefaciens FD-1 genome was sequenced to 29x-coverage, based on pulsed-field gel electrophoresis estimates (4.4 Mb, and assembled into 119 contigs providing 4,576,399 bp of unique sequence. As much as 87.1% of the genome encodes ORFs, tRNA, rRNAs, or repeats. The GC content was calculated at 45%. A total of 4,339 ORFs was detected with an average gene length of 918 bp. The cellulosome model for R. flavefaciens was further refined by sequence analysis, with at least 225 dockerin-containing ORFs, including previously characterized cohesin-containing scaffoldin molecules. These dockerin-containing ORFs encode a variety of catalytic modules including glycoside hydrolases (GHs, polysaccharide lyases, and carbohydrate esterases. Additionally, 56 ORFs encode proteins that contain carbohydrate-binding modules (CBMs. Functional microarray analysis of the genome revealed that 56 of the cellulosome-associated ORFs were up-regulated, 14 were down-regulated, 135 were unaffected, when R. flavefaciens FD-1 was grown on cellulose versus cellobiose. Three multi-modular xylanases (ORF01222, ORF03896, and ORF01315 exhibited the highest levels of up-regulation. CONCLUSIONS/SIGNIFICANCE: The genomic evidence indicates that R. flavefaciens FD-1 has the largest known number of fiber-degrading enzymes likely to be arranged in a cellulosome architecture. Functional

  7. Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Chung Jae

    2009-06-01

    Full Text Available Abstract Background Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Although the precise mechanism(s underlying the development of platinum resistance in late-stage ovarian cancer patients currently remains unknown, CpG-island (CGI methylation, a phenomenon strongly associated with aberrant gene silencing and ovarian tumorigenesis, may contribute to this devastating condition. Methods To model the onset of drug resistance, and investigate DNA methylation and gene expression alterations associated with platinum resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation and mRNA expression microarray analyses. To identify chemoresistance-associated, biological pathways likely impacted by DNA methylation, promoter CGI methylation and mRNA expression profiles were integrated and subjected to pathway enrichment analysis. Results Promoter CGI methylation revealed a positive association (Spearman correlation of 0.99 between the total number of hypermethylated CGIs and GI50 values (i.e., increased drug resistance following successive cisplatin treatment cycles. In accord with that result, chemoresistance was reversible by DNA methylation inhibitors. Pathway enrichment analysis revealed hypermethylation-mediated repression of cell adhesion and tight junction pathways and hypomethylation-mediated activation of the cell growth-promoting pathways PI3K/Akt, TGF-beta, and cell cycle progression, which may contribute to the onset of chemoresistance in ovarian cancer cells. Conclusion Selective epigenetic disruption of distinct biological

  8. Compound-Specific Radiocarbon Dating Reveals the Age Distribution of Plant-Wax Biomarkers Exported to the Bengal Fan

    Science.gov (United States)

    Galy, V.; French, K. L.; Hein, C. J.; Haghipour, N.; Wacker, L.; Kudrass, H.; Eglinton, T. I.

    2017-12-01

    The stable isotope composition of leaf-wax compounds preserved in lacustrine and marine sediments has been widely used to reconstruct terrestrial paleo-environments. However, the timescales of plant-wax storage in continental reservoirs before riverine export are not well known, representing a key uncertainty in paleo-environment studies. We couple numerical models with bulk and leaf-wax fatty acid organic 13C and 14C signatures hosted in a high-deposition-rate sediment core from the Bengal shelf canyon in order to estimate storage timescales within the Ganges-Brahmaputra catchment area. The fatty acid 14C record reveals a muted nuclear weapons bomb spike, requiring that the Ganges-Brahmaputra river system exports a mixture of young and old (pre-aged) leaf-wax compounds. According to numerical simulations, 79-83% of the leaf-wax fatty acids in this core are sourced from continental reservoirs that store organic carbon on an average of 1000-1200 calendar years, while the remainder has an average age of 15 years. These results demonstrate that a majority of the leaf-wax compounds produced in the Ganges-Brahmaputra river basin was stored in soils, floodplains, and wetlands prior to its export to the Bengal Fan. We will discuss the implications of these findings for plant-wax based paleoenvironmental records.

  9. Gene-centric metagenomics of the fiber-adherent bovine rumen microbiome reveals forage specific glycoside hydrolases.

    Science.gov (United States)

    Brulc, Jennifer M; Antonopoulos, Dionysios A; Miller, Margret E Berg; Wilson, Melissa K; Yannarell, Anthony C; Dinsdale, Elizabeth A; Edwards, Robert E; Frank, Edward D; Emerson, Joanne B; Wacklin, Pirjo; Coutinho, Pedro M; Henrissat, Bernard; Nelson, Karen E; White, Bryan A

    2009-02-10

    The complex microbiome of the rumen functions as an effective system for the conversion of plant cell wall biomass to microbial protein, short chain fatty acids, and gases. As such, it provides a unique genetic resource for plant cell wall degrading microbial enzymes that could be used in the production of biofuels. The rumen and gastrointestinal tract harbor a dense and complex microbiome. To gain a greater understanding of the ecology and metabolic potential of this microbiome, we used comparative metagenomics (phylotype analysis and SEED subsystems-based annotations) to examine randomly sampled pyrosequence data from 3 fiber-adherent microbiomes and 1 pooled liquid sample (a mixture of the liquid microbiome fractions from the same bovine rumens). Even though the 3 animals were fed the same diet, the community structure, predicted phylotype, and metabolic potentials in the rumen were markedly different with respect to nutrient utilization. A comparison of the glycoside hydrolase and cellulosome functional genes revealed that in the rumen microbiome, initial colonization of fiber appears to be by organisms possessing enzymes that attack the easily available side chains of complex plant polysaccharides and not the more recalcitrant main chains, especially cellulose. Furthermore, when compared with the termite hindgut microbiome, there are fundamental differences in the glycoside hydrolase content that appear to be diet driven for either the bovine rumen (forages and legumes) or the termite hindgut (wood).

  10. Intra- and interspecific trait variations reveal functional relationships between specific leaf area and soil niche within a subtropical forest.

    Science.gov (United States)

    He, Dong; Chen, Yongfa; Zhao, Kangning; Cornelissen, J H C; Chu, Chengjin

    2018-02-03

    How functional traits vary with environmental conditions is of fundamental importance in trait-based community ecology. However, how intraspecific variability in functional traits is connected to species distribution is not well understood. This study investigated inter- and intraspecific variation of a key functional trait, i.e. specific leaf area (leaf area per unit dry mass; SLA), in relation to soil factors and tested if trait variation is more closely associated with specific environmental regimes for low-variability species than for high-variability species. In a subtropical evergreen forest plot (50 ha, southern China), 106 700 leaves from 5335 individuals of 207 woody species were intensively collected, with 30 individuals sampled for most species to ensure a sufficient sample size representative of intraspecific variability. Soil conditions for each plant were estimated by kriging from more than 1700 observational soil locations across the plot. Intra- and interspecific variation in SLA were separately related to environmental factors. Based on the species-specific variation of SLA, species were categorized into three groups: low-, intermediate- and high-intraspecific variability. Intraspecific habitat ranges and the strength of SLA-habitat relationships were compared among these three groups. Interspecific variation in SLA overrides the intraspecific variation (77 % vs. 8 %). Total soil nitrogen (TN, positively) and total organic carbon (TOC, negatively) are the most important explanatory factors for SLA variation at both intra- and interspecific levels. SLA, both within and between species, decreases with decreasing soil nitrogen availability. As predicted, species with low intraspecific variability in SLA have narrower habitat ranges with respect to soil TOC and TN and show a stronger SLA-habitat association than high-variability species. For woody plants low SLA is a phenotypic and probably adaptive response to nitrogen stress, which drives the

  11. Rhizobia Indigenous to the Okavango Region in Sub-Saharan Africa: Diversity, Adaptations, and Host Specificity

    OpenAIRE

    Grönemeyer, Jann L.; Kulkarni, Ajinkya; Berkelmann, Dirk; Hurek, Thomas; Reinhold-Hurek, Barbara

    2014-01-01

    The rhizobial community indigenous to the Okavango region has not yet been characterized. The isolation of indigenous rhizobia can provide a basis for the formulation of a rhizobial inoculant. Moreover, their identification and characterization contribute to the general understanding of species distribution and ecology. Isolates were obtained from nodules of local varieties of the pulses cowpea, Bambara groundnut, peanut, hyacinth bean, and common bean. Ninety-one of them were identified by B...

  12. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

    Science.gov (United States)

    2012-01-01

    Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. Methods RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. Results We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be

  13. A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance

    KAUST Repository

    Sheen, Patricia

    2017-10-11

    Tuberculosis (TB) is a major global health problem and drug resistance compromises the efforts to control this disease. Pyrazinamide (PZA) is an important drug used in both first and second line treatment regimes. However, its complete mechanism of action and resistance remains unclear.We genotyped and sequenced the complete genomes of 68 M. tuberculosis strains isolated from unrelated TB patients in Peru. No clustering pattern of the strains was verified based on spoligotyping. We analyzed the association between PZA resistance with non-synonymous mutations and specific genes. We found mutations in pncA and novel genes significantly associated with PZA resistance in strains without pncA mutations. These included genes related to transportation of metal ions, pH regulation and immune system evasion.These results suggest potential alternate mechanisms of PZA resistance that have not been found in other populations, supporting that the antibacterial activity of PZA may hit multiple targets.

  14. A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance

    KAUST Repository

    Sheen, Patricia; Requena, David; Gushiken, Eduardo; Gilman, Robert H.; Antiparra, Ricardo; Lucero, Bryan; Lizá rraga, Pilar; Cieza, Basilio; Roncal, Elisa; Grandjean, Louis; Pain, Arnab; McNerney, Ruth; Clark, Taane G.; Moore, David; Zimic, Mirko

    2017-01-01

    Tuberculosis (TB) is a major global health problem and drug resistance compromises the efforts to control this disease. Pyrazinamide (PZA) is an important drug used in both first and second line treatment regimes. However, its complete mechanism of action and resistance remains unclear.We genotyped and sequenced the complete genomes of 68 M. tuberculosis strains isolated from unrelated TB patients in Peru. No clustering pattern of the strains was verified based on spoligotyping. We analyzed the association between PZA resistance with non-synonymous mutations and specific genes. We found mutations in pncA and novel genes significantly associated with PZA resistance in strains without pncA mutations. These included genes related to transportation of metal ions, pH regulation and immune system evasion.These results suggest potential alternate mechanisms of PZA resistance that have not been found in other populations, supporting that the antibacterial activity of PZA may hit multiple targets.

  15. Bat Accelerated Regions Identify a Bat Forelimb Specific Enhancer in the HoxD Locus.

    Directory of Open Access Journals (Sweden)

    Betty M Booker

    2016-03-01

    Full Text Available The molecular events leading to the development of the bat wing remain largely unknown, and are thought to be caused, in part, by changes in gene expression during limb development. These expression changes could be instigated by variations in gene regulatory enhancers. Here, we used a comparative genomics approach to identify regions that evolved rapidly in the bat ancestor, but are highly conserved in other vertebrates. We discovered 166 bat accelerated regions (BARs that overlap H3K27ac and p300 ChIP-seq peaks in developing mouse limbs. Using a mouse enhancer assay, we show that five Myotis lucifugus BARs drive gene expression in the developing mouse limb, with the majority showing differential enhancer activity compared to the mouse orthologous BAR sequences. These include BAR116, which is located telomeric to the HoxD cluster and had robust forelimb expression for the M. lucifugus sequence and no activity for the mouse sequence at embryonic day 12.5. Developing limb expression analysis of Hoxd10-Hoxd13 in Miniopterus natalensis bats showed a high-forelimb weak-hindlimb expression for Hoxd10-Hoxd11, similar to the expression trend observed for M. lucifugus BAR116 in mice, suggesting that it could be involved in the regulation of the bat HoxD complex. Combined, our results highlight novel regulatory regions that could be instrumental for the morphological differences leading to the development of the bat wing.

  16. Region-specific expression of mitochondrial complex I genes during murine brain development.

    Directory of Open Access Journals (Sweden)

    Stefanie Wirtz

    Full Text Available Mutations in the nuclear encoded subunits of mitochondrial complex I (NADH:ubiquinone oxidoreductase may cause circumscribed cerebral lesions ranging from degeneration of the striatal and brainstem gray matter (Leigh syndrome to leukodystrophy. We hypothesized that such pattern of regional pathology might be due to local differences in the dependence on complex I function. Using in situ hybridization we investigated the relative expression of 33 nuclear encoded complex I subunits in different brain regions of the mouse at E11.5, E17.5, P1, P11, P28 and adult (12 weeks. With respect to timing and relative intensity of complex I gene expression we found a highly variant pattern in different regions during development. High average expression levels were detected in periods of intense neurogenesis. In cerebellar Purkinje and in hippocampal CA1/CA3 pyramidal neurons we found a second even higher peak during the period of synaptogenesis and maturation. The extraordinary dependence of these structures on complex I gene expression during synaptogenesis is in accord with our recent findings that gamma oscillations--known to be associated with higher cognitive functions of the mammalian brain--strongly depend on the complex I activity. However, with the exception of the mesencephalon, we detected only average complex I expression levels in the striatum and basal ganglia, which does not explain the exquisite vulnerability of these structures in mitochondrial disorders.

  17. Patient-specific metrics of invasiveness reveal significant prognostic benefit of resection in a predictable subset of gliomas.

    Directory of Open Access Journals (Sweden)

    Anne L Baldock

    Full Text Available Malignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas.In 243 patients presenting with contrast-enhancing gliomas, estimates of the relative invasiveness of each patient's tumor, in terms of the ratio of net proliferation rate of the glioma cells to their net dispersal rate, were derived by applying a patient-specific mathematical model to routine pretreatment MR imaging. The effect of varying degrees of extent of resection on overall survival was assessed for cohorts of patients grouped by tumor invasiveness.We demonstrate that patients with more diffuse tumors showed no survival benefit (P = 0.532 from gross total resection over subtotal/biopsy, while those with nodular (less diffuse tumors showed a significant benefit (P = 0.00142 with a striking median survival benefit of over eight months compared to sub-totally resected tumors in the same cohort (an 80% improvement in survival time for GTR only seen for nodular tumors.These results suggest that our patient-specific, model-based estimates of tumor invasiveness have clinical utility in surgical decision making. Quantification of relative invasiveness assessed from routinely obtained pre-operative imaging provides a practical predictor of the benefit of gross total resection.

  18. Genome-wide analysis of the expansin gene superfamily reveals grapevine-specific structural and functional characteristics.

    Directory of Open Access Journals (Sweden)

    Silvia Dal Santo

    Full Text Available BACKGROUND: Expansins are proteins that loosen plant cell walls in a pH-dependent manner, probably by increasing the relative movement among polymers thus causing irreversible expansion. The expansin superfamily (EXP comprises four distinct families: expansin A (EXPA, expansin B (EXPB, expansin-like A (EXLA and expansin-like B (EXLB. There is experimental evidence that EXPA and EXPB proteins are required for cell expansion and developmental processes involving cell wall modification, whereas the exact functions of EXLA and EXLB remain unclear. The complete grapevine (Vitis vinifera genome sequence has allowed the characterization of many gene families, but an exhaustive genome-wide analysis of expansin gene expression has not been attempted thus far. METHODOLOGY/PRINCIPAL FINDINGS: We identified 29 EXP superfamily genes in the grapevine genome, representing all four EXP families. Members of the same EXP family shared the same exon-intron structure, and phylogenetic analysis confirmed a closer relationship between EXP genes from woody species, i.e. grapevine and poplar (Populus trichocarpa, compared to those from Arabidopsis thaliana and rice (Oryza sativa. We also identified grapevine-specific duplication events involving the EXLB family. Global gene expression analysis confirmed a strong correlation among EXP genes expressed in mature and green/vegetative samples, respectively, as reported for other gene families in the recently-published grapevine gene expression atlas. We also observed the specific co-expression of EXLB genes in woody organs, and the involvement of certain grapevine EXP genes in berry development and post-harvest withering. CONCLUSION: Our comprehensive analysis of the grapevine EXP superfamily confirmed and extended current knowledge about the structural and functional characteristics of this gene family, and also identified properties that are currently unique to grapevine expansin genes. Our data provide a model for the

  19. Nucleus-specific expression in the multinuclear mushroom-forming fungus Agaricus bisporus reveals different nuclear regulatory programs.

    Science.gov (United States)

    Gehrmann, Thies; Pelkmans, Jordi F; Ohm, Robin A; Vos, Aurin M; Sonnenberg, Anton S M; Baars, Johan J P; Wösten, Han A B; Reinders, Marcel J T; Abeel, Thomas

    2018-04-24

    Many fungi are polykaryotic, containing multiple nuclei per cell. In the case of heterokaryons, there are different nuclear types within a single cell. It is unknown what the different nuclear types contribute in terms of mRNA expression levels in fungal heterokaryons. Each cell of the mushroom Agaricus bisporus contains two to 25 nuclei of two nuclear types originating from two parental strains. Using RNA-sequencing data, we assess the differential mRNA contribution of individual nuclear types and its functional impact. We studied differential expression between genes of the two nuclear types, P1 and P2, throughout mushroom development in various tissue types. P1 and P2 produced specific mRNA profiles that changed through mushroom development. Differential regulation occurred at the gene level, rather than at the locus, chromosomal, or nuclear level. P1 dominated mRNA production throughout development, and P2 showed more differentially up-regulated genes in important functional groups. In the vegetative mycelium, P2 up-regulated almost threefold more metabolism genes and carbohydrate active enzymes (cazymes) than P1, suggesting phenotypic differences in growth. We identified widespread transcriptomic variation between the nuclear types of A. bisporus Our method enables studying nucleus-specific expression, which likely influences the phenotype of a fungus in a polykaryotic stage. Our findings have a wider impact to better understand gene regulation in fungi in a heterokaryotic state. This work provides insight into the transcriptomic variation introduced by genomic nuclear separation. Copyright © 2018 the Author(s). Published by PNAS.

  20. Proteomic analysis reveals age-related changes in tendon matrix composition, with age- and injury-specific matrix fragmentation.

    Science.gov (United States)

    Peffers, Mandy J; Thorpe, Chavaunne T; Collins, John A; Eong, Robin; Wei, Timothy K J; Screen, Hazel R C; Clegg, Peter D

    2014-09-12

    Energy storing tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT), are highly prone to injury, the incidence of which increases with aging. The cellular and molecular mechanisms that result in increased injury in aged tendons are not well established but are thought to result in altered matrix turnover. However, little attempt has been made to fully characterize the tendon proteome nor determine how the abundance of specific tendon proteins changes with aging and/or injury. The aim of this study was, therefore, to assess the protein profile of normal SDFTs from young and old horses using label-free relative quantification to identify differentially abundant proteins and peptide fragments between age groups. The protein profile of injured SDFTs from young and old horses was also assessed. The results demonstrate distinct proteomic profiles in young and old tendon, with alterations in the levels of proteins involved in matrix organization and regulation of cell tension. Furthermore, we identified several new peptide fragments (neopeptides) present in aged tendons, suggesting that there are age-specific cleavage patterns within the SDFT. Proteomic profile also differed between young and old injured tendon, with a greater number of neopeptides identified in young injured tendon. This study has increased the knowledge of molecular events associated with tendon aging and injury, suggesting that maintenance and repair of tendon tissue may be reduced in aged individuals and may help to explain why the risk of injury increases with aging. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Vertebral heights and ratios are not only race-specific, but also gender- and region-specific: establishment of reference values for mainland Chinese.

    Science.gov (United States)

    Ning, Lei; Song, Li-Jiang; Fan, Shun-Wu; Zhao, Xing; Chen, Yi-Lei; Li, Zhao-Zhi; Hu, Zi-Ang

    2017-10-11

    This study established gender-specific reference values in mainland Chinese (MC) and is important for quantitative morphometry for diagnosis and epidemiological study of osteoporotic vertebral compressive fracture. Comparisons of reference values among different racial populations are then performed to demonstrate the MC-specific characteristic. Osteoporotic vertebral compressive fracture (OVCF) is a common complication of osteoporosis in the elder population. Clinical diagnosis and epidemiological study of OVCF often employ quantitative morphometry, which relies heavily on the comparison of patients' vertebral parameters to existing reference values derived from the normal population. Thus, reference values are crucial in clinical diagnosis. To our knowledge, this is the first study to establish reference values of the mainland Chinese (MC) for quantitative morphometry. Vertebral heights including anterior (Ha), middle (Hm), posterior (Hp) heights, and predicted posterior height (pp) from T4 to L5 were obtained; and ratios of Ha/Hp, Hm/Hp and Hp/pp. were calculated from 585 MC (both female and male) for establishing reference values and subsequent comparisons with other studies. Vertebral heights increased progressively from T4 to L3 but then decreased in L4 and L5. Both genders showed similar ratios of vertebral dimensions, but male vertebrae were statistically larger than those of female (P values for MC. Our results also indicated the necessity of establishing reference values that are not only race- and gender-specific, but also population- or region-specific for accurate quantitative morphometric assessment of OVCF.

  2. Regulatory regions in the rat lactase-phlorizin hydrolase gene that control cell-specific expression

    NARCIS (Netherlands)

    Verhave, Menno; Krasinski, Stephen D.; Christian, Sara I.; van Schaik, Sandrijn; van den Brink, Gijs R.; Doting, Edwina M. H.; Maas, Saskia M.; Wolthers, Katja C.; Grand, Richard J.; Montgomery, Robert K.

    2004-01-01

    OBJECTIVES: Lactase-phlorizin hydrolase (LPH) is an enterocyte-specific gene whose expression has been well-characterized, not only developmentally but also along the crypt-villus axis and along the length of the small bowel. Previous studies from the authors' laboratory have demonstrated that 2 kb

  3. Testing the Neoclassical Migration Model: Overall and Age-Group Specific Results for German Regions

    DEFF Research Database (Denmark)

    Mitze, Timo; Reinkowski, Janina

    as for age-group specific estimates. Thereby, the impact of labor market signals is tested to be of greatest magnitude for workforce relevant age-groups and especially young cohorts between 18 to 25 and 25 to 30 years. This latter result underlines the prominent role played by labor market conditions...

  4. EST-SSR marker revealed effective over biochemical and morphological scepticism towards identification of specific turmeric (Curcuma longa L.) cultivars.

    Science.gov (United States)

    Sahoo, Ambika; Jena, Sudipta; Kar, Basudeba; Sahoo, Suprava; Ray, Asit; Singh, Subhashree; Joshi, Raj Kumar; Acharya, Laxmikanta; Nayak, Sanghamitra

    2017-05-01

    Turmeric (Curcuma longa L., family Zingiberaceae) is one of the most economically important plants for its use in food, medicine, and cosmetic industries. Cultivar identification is a major constraint in turmeric, owing to high degree of morphological similarity that in turn, affects its commercialization. The present study addresses this constraint, using EST-SSR marker based, molecular identification of 8 elite cultivars and 88 accessions in turmeric. Fifty EST-SSR primers were screened against eight cultivars of turmeric (Suroma, Roma, Lakadong, Megha, Alleppey Supreme, Kedaram, Pratibha, and Suvarna); out of which 11 primers showed polymorphic banding pattern. The polymorphic information content (PIC) of these primers ranged from 0.13 to 0.48. However, only three SSR loci (CSSR 14, CSSR 15, and CSSR 18) gave reproducible unique banding pattern clearly distinguishing the cultivars 'Lakadong' and 'Suvarna' from other cultivars tested. These three unique SSR markers also proved to be effective in identification of 'Lakadong' cultivars when analysed with 88 accessions of turmeric collected from different agro-climatic regions. Furthermore, two identified cultivars (Lakadong and Suvarna) could also be precisely differentiated when analysed and based on phylogenetic tree, with other 94 genotypes of turmeric. The novel SSR markers can be used for identification and authentication of two commercially important turmeric cultivars 'Lakadong' and 'Suvarna'.

  5. Imaging mass spectrometry reveals fiber-specific distribution of acetylcarnitine and contraction-induced carnitine dynamics in rat skeletal muscles.

    Science.gov (United States)

    Furuichi, Yasuro; Goto-Inoue, Naoko; Manabe, Yasuko; Setou, Mitsutoshi; Masuda, Kazumi; Fujii, Nobuharu L

    2014-10-01

    Carnitine is well recognized as a key regulator of long-chain fatty acyl group translocation into the mitochondria. In addition, carnitine, as acetylcarnitine, acts as an acceptor of excess acetyl-CoA, a potent inhibitor of pyruvate dehydrogenase. Here, we provide a new methodology for accurate quantification of acetylcarnitine content and determination of its localization in skeletal muscles. We used matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to visualize acetylcarnitine distribution in rat skeletal muscles. MALDI-IMS and immunohistochemistry of serial cross-sections showed that acetylcarnitine was enriched in the slow-type muscle fibers. The concentration of ATP was lower in muscle regions with abundant acetylcarnitine, suggesting a relationship between acetylcarnitine and metabolic activity. Using our novel method, we detected an increase in acetylcarnitine content after muscle contraction. Importantly, this increase was not detected using traditional biochemical assays of homogenized muscles. We also demonstrated that acetylation of carnitine during muscle contraction was concomitant with glycogen depletion. Our methodology would be useful for the quantification of acetylcarnitine and its contraction-induced kinetics in skeletal muscles. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Monoclonal Antibodies Specific for STAT3β Reveal Its Contribution to Constitutive STAT3 Phosphorylation in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Uddalak Bharadwaj

    2014-09-01

    Full Text Available Since its discovery in mice and humans 19 years ago, the contribution of alternatively spliced Stat3, Stat3β, to the overall functions of Stat3 has been controversial. Tyrosine-phosphorylated (p Stat3β homodimers are more stable, bind DNA more avidly, are less susceptible to dephosphorylation, and exhibit distinct intracellular dynamics, most notably markedly prolonged nuclear retention, compared to pStat3α homodimers. Overexpression of one or the other isoform in cell lines demonstrated that Stat3β acted as a dominant-negative of Stat3α in transformation assays; however, studies with mouse strains deficient in one or the other isoform indicated distinct contributions of Stat3 isoforms to inflammation. Current immunological reagents cannot differentiate Stat3β proteins derived from alternative splicing vs. proteolytic cleavage of Stat3α. We developed monoclonal antibodies that recognize the 7 C-terminal amino acids unique to Stat3β (CT7 and do not cross-react with Stat3α. Immunoblotting studies revealed that levels of Stat3β protein, but not Stat3α, in breast cancer cell lines positively correlated with overall pStat3 levels, suggesting that Stat3β may contribute to constitutive Stat3 activation in this tumor system. The ability to unambiguously discriminate splice alternative Stat3β from proteolytic Stat3β and Stat3α will provide new insights into the contribution of Stat3β vs. Stat3α to oncogenesis, as well as other biological and pathological processes.

  7. Comparative analyses of six solanaceous transcriptomes reveal a high degree of sequence conservation and species-specific transcripts

    Directory of Open Access Journals (Sweden)

    Ouyang Shu

    2005-09-01

    Full Text Available Abstract Background The Solanaceae is a family of closely related species with diverse phenotypes that have been exploited for agronomic purposes. Previous studies involving a small number of genes suggested sequence conservation across the Solanaceae. The availability of large collections of Expressed Sequence Tags (ESTs for the Solanaceae now provides the opportunity to assess sequence conservation and divergence on a genomic scale. Results All available ESTs and Expressed Transcripts (ETs, 449,224 sequences for six Solanaceae species (potato, tomato, pepper, petunia, tobacco and Nicotiana benthamiana, were clustered and assembled into gene indices. Examination of gene ontologies revealed that the transcripts within the gene indices encode a similar suite of biological processes. Although the ESTs and ETs were derived from a variety of tissues, 55–81% of the sequences had significant similarity at the nucleotide level with sequences among the six species. Putative orthologs could be identified for 28–58% of the sequences. This high degree of sequence conservation was supported by expression profiling using heterologous hybridizations to potato cDNA arrays that showed similar expression patterns in mature leaves for all six solanaceous species. 16–19% of the transcripts within the six Solanaceae gene indices did not have matches among Solanaceae, Arabidopsis, rice or 21 other plant gene indices. Conclusion Results from this genome scale analysis confirmed a high level of sequence conservation at the nucleotide level of the coding sequence among Solanaceae. Additionally, the results indicated that part of the Solanaceae transcriptome is likely to be unique for each species.

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

    Directory of Open Access Journals (Sweden)

    Maria Jesus Iglesias

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

  9. Fruit metabolite networks in engineered and non-engineered tomato genotypes reveal fluidity in a hormone and agroecosystem specific manner.

    Science.gov (United States)

    Fatima, Tahira; Sobolev, Anatoly P; Teasdale, John R; Kramer, Matthew; Bunce, Jim; Handa, Avtar K; Mattoo, Autar K

    Metabolomics provides a view of endogenous metabolic patterns not only during plant growth, development and senescence but also in response to genetic events, environment and disease. The effects of the field environment on plant hormone-specific metabolite profiles are largely unknown. Few studies have analyzed useful phenotypes generated by introducing single or multiple gene events alongside the non-engineered wild type control at field scale to determine the robustness of the genetic trait and its modulation in the metabolome as a function of specific agroecosystem environments. We evaluated the influence of genetic background (high polyamine lines; low methyl jasmonate line; low ethylene line; and isogenic genotypes carrying double transgenic events) and environments (hairy vetch, rye, plastic black mulch and bare soil mulching systems) on the metabolomic profile of isogenic reverse genetic mutations and selected mulch based cropping systems in tomato fruit. Net photosynthesis and fruit yield were also determined. NMR spectroscopy was used for quantifying metabolites that are central to primary metabolism. We analyzed both the first moment (means) of metabolic response to genotypes and agroecosystems by traditional univariate/multivariate methods, and the second moment (covariances) of responses by creating networks that depicted changes in correlations of paired metabolites. This particular approach is novel and was necessary because our experimental material yielded highly variable metabolic responses that could not be easily understood using the traditional analytical approaches for first moment statistics. High endogenous spermidine and spermine content exhibited strong effects on amino acids, Krebs cycle intermediates and energy molecules (ADP + ATP) in ripening fruits of plants grown under different agroecosystem environments. The metabolic response to high polyamine genotypes was similar to the response to hairy vetch cover crop mulch; supported by

  10. Specific genomic regions are differentially affected by copy number alterations across distinct cancer types, in aggregated cytogenetic data.

    Science.gov (United States)

    Kumar, Nitin; Cai, Haoyang; von Mering, Christian; Baudis, Michael

    2012-01-01

    Regional genomic copy number alterations (CNA) are observed in the vast majority of cancers. Besides specifically targeting well-known, canonical oncogenes, CNAs may also play more subtle roles in terms of modulating genetic potential and broad gene expression patterns of developing tumors. Any significant differences in the overall CNA patterns between different cancer types may thus point towards specific biological mechanisms acting in those cancers. In addition, differences among CNA profiles may prove valuable for cancer classifications beyond existing annotation systems. We have analyzed molecular-cytogenetic data from 25579 tumors samples, which were classified into 160 cancer types according to the International Classification of Disease (ICD) coding system. When correcting for differences in the overall CNA frequencies between cancer types, related cancers were often found to cluster together according to similarities in their CNA profiles. Based on a randomization approach, distance measures from the cluster dendrograms were used to identify those specific genomic regions that contributed significantly to this signal. This approach identified 43 non-neutral genomic regions whose propensity for the occurrence of copy number alterations varied with the type of cancer at hand. Only a subset of these identified loci overlapped with previously implied, highly recurrent (hot-spot) cytogenetic imbalance regions. Thus, for many genomic regions, a simple null-hypothesis of independence between cancer type and relative copy number alteration frequency can be rejected. Since a subset of these regions display relatively low overall CNA frequencies, they may point towards second-tier genomic targets that are adaptively relevant but not necessarily essential for cancer development.

  11. Premature Aging Phenotype in Mice Lacking High-Affinity Nicotinic Receptors: Region-Specific Changes in Layer V Pyramidal Cell Morphology.

    Science.gov (United States)

    Konsolaki, Eleni; Skaliora, Irini

    2015-08-01

    The mechanisms by which aging leads to alterations in brain structure and cognitive deficits are unclear. Α deficient cholinergic system has been implicated as one of the main factors that could confer a heightened vulnerability to the aging process, and mice lacking high-affinity nicotinic receptors (β2(-/-)) have been proposed as an animal model of accelerated cognitive aging. To date, however, age-related changes in neuronal microanatomy have not been studied in these mice. In the present study, we examine the neuronal structure of yellow fluorescent protein (YFP(+)) layer V neurons in 2 cytoarchitectonically distinct cortical regions in wild-type (WT) and β2(-/-) animals. We find that (1) substantial morphological differences exist between YFP(+) cells of the anterior cingulate cortex (ACC) and primary visual cortex (V1), in both genotypes; (2) in WT animals, ACC cells are more susceptible to aging compared with cells in V1; and (3) β2 deletion is associated with a regionally and temporally specific increase in vulnerability to aging. ACC cells exhibit a prematurely aged phenotype already at 4-6 months, whereas V1 cells are spared in adulthood but strongly affected in old animals. Collectively, our data reveal region-specific synergistic effects of aging and genotype and suggest distinct vulnerabilities in V1 and ACC neurons. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Electron microscopy and three-dimensional reconstruction of native thin filaments reveal species-specific differences in regulatory strand densities

    Energy Technology Data Exchange (ETDEWEB)

    Cammarato, Anthony, E-mail: acammara@burnham.org [Department of Physiology and Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118 (United States); Craig, Roger [Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655 (United States); Lehman, William [Department of Physiology and Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118 (United States)

    2010-01-01

    Throughout the animal kingdom striated muscle contraction is regulated by the thin filament troponin-tropomyosin complex. Homologous regulatory components are shared among vertebrate and arthropod muscles; however, unique protein extensions and/or components characterize the latter. The Troponin T (TnT) isoforms of Drosophila indirect flight and tarantula femur muscle for example contain distinct C-terminal extensions and are {approx}20% larger overall than their vertebrate counterpart. Using electron microscopy and three-dimensional helical reconstruction of native Drosophila, tarantula and frog muscle thin filaments we have identified species-specific differences in tropomyosin regulatory strand densities. The strands on the arthropod thin filaments were significantly larger in diameter than those from vertebrates, although not significantly different from each other. These findings reflect differences in the regulatory troponin-tropomyosin complex, which are likely due to the larger TnT molecules aligning and extending along much of the tropomyosin strands' length. Such an arrangement potentially alters the physical properties of the regulatory strands and may help establish contractile characteristics unique to certain arthropod muscles.

  13. Specific interactions between arbuscular mycorrhizal fungi and plant growth-promoting bacteria--as revealed by different combinations

    Energy Technology Data Exchange (ETDEWEB)

    Jaderlund, Lotta; Arthurson, Veronica; Granhall, Ulf; Jansson, Janet K.

    2008-05-15

    The interactions between two plant growth promoting rhizobacteria (PGPR), Pseudomonas fluorescens SBW25 and Paenibacillus brasilensis PB177, two arbuscular mycorrhizal (AM) fungi (Glomus mosseae and G. intraradices) and one pathogenic fungus (Microdochium nivale) were investigated on winter wheat (Triticum aestivum cultivar Tarso) in a greenhouse trial. PB177, but not SBW25, had strong inhibitory effects on M. nivale in dual culture plate assays. The results from the greenhouse experiment show very specific interactions; e.g. the two AM fungi react differently when interacting with the same bacteria on plants. G. intraradices (single inoculation or together with SBW25) increased plant dry weight on M. nivale infested plants, suggesting that the pathogenic fungus is counteracted by G. intraradices, but PB177 inhibited this positive effect. This is an example of two completely different reactions between the same AM fungus and two species of bacteria, previously known to enhance plant growth and inhibit pathogens. When searching for plant growth promoting microorganisms it is therefore important to test for the most suitable combination of plant, bacteria and fungi in order to get satisfactory plant growth benefits.

  14. Cell-Type-Specific Circuit Connectivity of Hippocampal CA1 Revealed through Cre-Dependent Rabies Tracing

    Directory of Open Access Journals (Sweden)

    Yanjun Sun

    2014-04-01

    Full Text Available We developed and applied a Cre-dependent, genetically modified rabies-based tracing system to map direct synaptic connections to specific CA1 neuron types in the mouse hippocampus. We found common inputs to excitatory and inhibitory CA1 neurons from CA3, CA2, the entorhinal cortex (EC, the medial septum (MS, and, unexpectedly, the subiculum. Excitatory CA1 neurons receive inputs from both cholinergic and GABAergic MS neurons, whereas inhibitory neurons receive a great majority of inputs from GABAergic MS neurons. Both cell types also receive weaker input from glutamatergic MS neurons. Comparisons of inputs to CA1 PV+ interneurons versus SOM+ interneurons showed similar strengths of input from the subiculum, but PV+ interneurons received much stronger input than SOM+ neurons from CA3, the EC, and the MS. Thus, rabies tracing identifies hippocampal circuit connections and maps how the different input sources to CA1 are distributed with different strengths on each of its constituent cell types.

  15. Cognitive assessment of mice strains heterozygous for cell-adhesion genes reveals strain-specific alterations in timing.

    Science.gov (United States)

    Gallistel, C R; Tucci, Valter; Nolan, Patrick M; Schachner, Melitta; Jakovcevski, Igor; Kheifets, Aaron; Barboza, Luendro

    2014-03-05

    We used a fully automated system for the behavioural measurement of physiologically meaningful properties of basic mechanisms of cognition to test two strains of heterozygous mutant mice, Bfc (batface) and L1, and their wild-type littermate controls. Both of the target genes are involved in the establishment and maintenance of synapses. We find that the Bfc heterozygotes show reduced precision in their representation of interval duration, whereas the L1 heterozygotes show increased precision. These effects are functionally specific, because many other measures made on the same mice are unaffected, namely: the accuracy of matching temporal investment ratios to income ratios in a matching protocol, the rate of instrumental and classical conditioning, the latency to initiate a cued instrumental response, the trials on task and the impulsivity in a switch paradigm, the accuracy with which mice adjust timed switches to changes in the temporal constraints, the days to acquisition, and mean onset time and onset variability in the circadian anticipation of food availability.

  16. Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation.

    Science.gov (United States)

    De Cegli, Rossella; Iacobacci, Simona; Flore, Gemma; Gambardella, Gennaro; Mao, Lei; Cutillo, Luisa; Lauria, Mario; Klose, Joachim; Illingworth, Elizabeth; Banfi, Sandro; di Bernardo, Diego

    2013-01-01

    Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology 'reverse engineering' approaches. We 'reverse engineered' an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators of gene expression ('hubs'). We discovered that E130012A19Rik (E13), highly expressed in mouse ES cells as compared with differentiated cells, was a central 'hub' of the network. We demonstrated that E13 is a protein-coding gene implicated in regulating the commitment towards the different neuronal subtypes and glia cells. The overexpression and knock-down of E13 in ES cell lines, undergoing differentiation into neurons and glia cells, caused a strong up-regulation of the glutamatergic neurons marker Vglut2 and a strong down-regulation of the GABAergic neurons marker GAD65 and of the radial glia marker Blbp. We confirmed E13 expression in the cerebral cortex of adult mice and during development. By immuno-based affinity purification, we characterized protein partners of E13, involved in the Polycomb complex. Our results suggest a role of E13 in regulating the division between glutamatergic projection neurons and GABAergic interneurons and glia cells possibly by epigenetic-mediated transcriptional regulation.

  17. Regulators of Long-Term Memory Revealed by Mushroom Body-Specific Gene Expression Profiling in Drosophila melanogaster.

    Science.gov (United States)

    Widmer, Yves F; Bilican, Adem; Bruggmann, Rémy; Sprecher, Simon G

    2018-06-20

    Memory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short-term memory traces rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory formation. With Drosophila melanogaster as a model system we profiled transcriptomic changes in the mushroom body, a memory center in the fly brain, at distinct time intervals during appetitive olfactory long-term memory formation using the targeted DamID technique. We describe the gene expression profiles during these phases and tested 33 selected candidate genes for deficits in long-term memory formation using RNAi knockdown. We identified 10 genes that enhance or decrease memory when knocked-down in the mushroom body. For vajk-1 and hacd1 , the two strongest hits, we gained further support for their crucial role in appetitive learning and forgetting. These findings show that profiling gene expression changes in specific cell-types harboring memory traces provides a powerful entry point to identify new genes involved in learning and memory. The presented transcriptomic data may further be used as resource to study genes acting at different memory phases. Copyright © 2018, Genetics.

  18. Electron microscopy and three-dimensional reconstruction of native thin filaments reveal species-specific differences in regulatory strand densities

    International Nuclear Information System (INIS)

    Cammarato, Anthony; Craig, Roger; Lehman, William

    2010-01-01

    Throughout the animal kingdom striated muscle contraction is regulated by the thin filament troponin-tropomyosin complex. Homologous regulatory components are shared among vertebrate and arthropod muscles; however, unique protein extensions and/or components characterize the latter. The Troponin T (TnT) isoforms of Drosophila indirect flight and tarantula femur muscle for example contain distinct C-terminal extensions and are ∼20% larger overall than their vertebrate counterpart. Using electron microscopy and three-dimensional helical reconstruction of native Drosophila, tarantula and frog muscle thin filaments we have identified species-specific differences in tropomyosin regulatory strand densities. The strands on the arthropod thin filaments were significantly larger in diameter than those from vertebrates, although not significantly different from each other. These findings reflect differences in the regulatory troponin-tropomyosin complex, which are likely due to the larger TnT molecules aligning and extending along much of the tropomyosin strands' length. Such an arrangement potentially alters the physical properties of the regulatory strands and may help establish contractile characteristics unique to certain arthropod muscles.

  19. Systematic and quantitative comparison of digest efficiency and specificity reveals the impact of trypsin quality on MS-based proteomics.

    Science.gov (United States)

    Burkhart, Julia Maria; Schumbrutzki, Cornelia; Wortelkamp, Stefanie; Sickmann, Albert; Zahedi, René Peiman

    2012-02-02

    Trypsin is the most frequently used proteolytic enzyme in mass spectrometry-based proteomics. Beside its good availability, it also offers some major advantages such as an optimal average peptide length of ~14 amino acids, and typically the presence of at least two defined positive charges at the N-terminus as well as the C-terminal Arg/Lys, rendering tryptic peptides well suited for CID-based LC-MS/MS. Here, we conducted a systematic study of different types of commercially available trypsin in order to qualitatively and quantitatively compare cleavage specificity, efficiency as well as reproducibility and the potential impact on quantitation and proteome coverage. We present a straightforward strategy applied to complex digests of human platelets, comprising (1) digest controls using a monolithic column HPLC-setup, (2) SCX enrichment of semitryptic/nonspecific peptides, (3) targeted MRM analysis of corresponding full cleavage/missed cleavage peptide pairs as well as (4) LC-MS analyses of complete digests with a three-step data interpretation. Thus, differences in digest performance can be readily assessed, rendering these procedures extremely beneficial to quality control not only the trypsin of choice, but also to effectively compare as well as optimize different digestion conditions and to evaluate the reproducibility of a dedicated digest protocol for all kinds of quantitative proteome studies. Copyright © 2011 Elsevier B.V. All rights reserved.

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

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    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

  1. 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

  2. Deep sequencing of the Camellia sinensis transcriptome revealed candidate genes for major metabolic pathways of tea-specific compounds

    Energy Technology Data Exchange (ETDEWEB)

    Shi, CY; Yang, H; Wei, CL; Yu, O; Zhang, ZZ; Sun, J; Wan, XC

    2011-01-01

    Tea is one of the most popular non-alcoholic beverages worldwide. However, the tea plant, Camellia sinensis, is difficult to culture in vitro, to transform, and has a large genome, rendering little genomic information available. Recent advances in large-scale RNA sequencing (RNA-seq) provide a fast, cost-effective, and reliable approach to generate large expression datasets for functional genomic analysis, which is especially suitable for non-model species with un-sequenced genomes. Using high-throughput Illumina RNA-seq, the transcriptome from poly (A){sup +} RNA of C. sinensis was analyzed at an unprecedented depth (2.59 gigabase pairs). Approximate 34.5 million reads were obtained, trimmed, and assembled into 127,094 unigenes, with an average length of 355 bp and an N50 of 506 bp, which consisted of 788 contig clusters and 126,306 singletons. This number of unigenes was 10-fold higher than existing C. sinensis sequences deposited in GenBank (as of August 2010). Sequence similarity analyses against six public databases (Uniprot, NR and COGs at NCBI, Pfam, InterPro and KEGG) found 55,088 unigenes that could be annotated with gene descriptions, conserved protein domains, or gene ontology terms. Some of the unigenes were assigned to putative metabolic pathways. Targeted searches using these annotations identified the majority of genes associated with several primary metabolic pathways and natural product pathways that are important to tea quality, such as flavonoid, theanine and caffeine biosynthesis pathways. Novel candidate genes of these secondary pathways were discovered. Comparisons with four previously prepared cDNA libraries revealed that this transcriptome dataset has both a high degree of consistency with previous EST data and an approximate 20 times increase in coverage. Thirteen unigenes related to theanine and flavonoid synthesis were validated. Their expression patterns in different organs of the tea plant were analyzed by RT-PCR and quantitative real

  3. Deep sequencing of the Camellia sinensis transcriptome revealed candidate genes for major metabolic pathways of tea-specific compounds

    Directory of Open Access Journals (Sweden)

    Chen Qi

    2011-02-01

    Full Text Available Abstract Background Tea is one of the most popular non-alcoholic beverages worldwide. However, the tea plant, Camellia sinensis, is difficult to culture in vitro, to transform, and has a large genome, rendering little genomic information available. Recent advances in large-scale RNA sequencing (RNA-seq provide a fast, cost-effective, and reliable approach to generate large expression datasets for functional genomic analysis, which is especially suitable for non-model species with un-sequenced genomes. Results Using high-throughput Illumina RNA-seq, the transcriptome from poly (A+ RNA of C. sinensis was analyzed at an unprecedented depth (2.59 gigabase pairs. Approximate 34.5 million reads were obtained, trimmed, and assembled into 127,094 unigenes, with an average length of 355 bp and an N50 of 506 bp, which consisted of 788 contig clusters and 126,306 singletons. This number of unigenes was 10-fold higher than existing C. sinensis sequences deposited in GenBank (as of August 2010. Sequence similarity analyses against six public databases (Uniprot, NR and COGs at NCBI, Pfam, InterPro and KEGG found 55,088 unigenes that could be annotated with gene descriptions, conserved protein domains, or gene ontology terms. Some of the unigenes were assigned to putative metabolic pathways. Targeted searches using these annotations identified the majority of genes associated with several primary metabolic pathways and natural product pathways that are important to tea quality, such as flavonoid, theanine and caffeine biosynthesis pathways. Novel candidate genes of these secondary pathways were discovered. Comparisons with four previously prepared cDNA libraries revealed that this transcriptome dataset has both a high degree of consistency with previous EST data and an approximate 20 times increase in coverage. Thirteen unigenes related to theanine and flavonoid synthesis were validated. Their expression patterns in different organs of the tea plant were

  4. Fluid escape structures in the Graham Bank region (Sicily Channel, Central Mediterranean) revealing volcanic and neotectonic activity.

    Science.gov (United States)

    Spatola, Daniele; Pennino, Valentina; Basilone, Luca; Interbartolo, Francesco; Micallef, Aaron; Sulli, Attilio; Basilone, Walter

    2016-04-01

    morphometric analysis of these volcanoes has been conducted: they are up to about 115-160 m high and 500-1500 m wide. Most of them show very strongly inclined flanks with 30° of average slope. The SCV2 and SCV3 form the Graham Bank, 3.5X2.8 km wide, elongated in the NW-SE direction. At the top of SCV2 focused seepage plumes were observed in the entire water column, through the CHIRP data, where we calculated that they release, a volume of about 10950 m3 and 43960 m3of gases, respectively. In this work, we present the first results of a data collection that have got as main result the identification and mapping of the fluid escape structures revealing the relationship between the active tectonic with migration of fluids, to be used to assess the Submarine Geo-Hazard in the Sicily Channel. We identified two fluid escape fields whose genesis and evolution appear linked to the neotectonic and volcanic activities respectively, that represent the main controlling factors for the migration of fluid; considering the good correlation between pockmarks and the main identified fault systems. In conclusion, our results suggest that the degassing of fluids in this region is rooted at depth, and is mainly aligned with the NW-SE dip/strike slip fault systems, repeatedly reactivated, and linked to the volcanic activity.

  5. Optogenetic fMRI and electrophysiological identification of region-specific connectivity between the cerebellar cortex and forebrain.

    Science.gov (United States)

    Choe, Katrina Y; Sanchez, Carlos F; Harris, Neil G; Otis, Thomas S; Mathews, Paul J

    2018-06-01

    Complex animal behavior is produced by dynamic interactions between discrete regions of the brain. As such, defining functional connections between brain regions is critical in gaining a full understanding of how the brain generates behavior. Evidence suggests that discrete regions of the cerebellar cortex functionally project to the forebrain, mediating long-range communication potentially important in motor and non-motor behaviors. However, the connectivity map remains largely incomplete owing to the challenge of driving both reliable and selective output from the cerebellar cortex, as well as the need for methods to detect region specific activation across the entire forebrain. Here we utilize a paired optogenetic and fMRI (ofMRI) approach to elucidate the downstream forebrain regions modulated by activating a region of the cerebellum that induces stereotypical, ipsilateral forelimb movements. We demonstrate with ofMRI, that activating this forelimb motor region of the cerebellar cortex results in functional activation of a variety of forebrain and midbrain areas of the brain, including the hippocampus and primary motor, retrosplenial and anterior cingulate cortices. We further validate these findings using optogenetic stimulation paired with multi-electrode array recordings and post-hoc staining for molecular markers of activated neurons (i.e. c-Fos). Together, these findings demonstrate that a single discrete region of the cerebellar cortex is capable of influencing motor output and the activity of a number of downstream forebrain as well as midbrain regions thought to be involved in different aspects of behavior. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. GWAS signals across the HLA regions: revealing a clue for common etiology underlying infectious tumors and other immunity diseases

    Institute of Scientific and Technical Information of China (English)

    Yin Yao Shugart; Ying Wang; Wei-Hua Jia; Yi-Xin Zeng

    2011-01-01

    Increasing evidence suggests that multiple genes in the human leukocyte antigen (HLA) regions play an important role in development of cancers and immunity disorders. However, the biological mechanisms of the HLA associations are not well understood. We recently conducted a survey of all genome-wide association studies (GWAS) with significant findings in the HLA regions and concluded that diseases such as cancer and immune disorders are more likely to be associated with genetic variants located in the HLA regions than other diseases. This finding is suggestive for testing a hypothesis of a common etiology of infectious tumors and other immunity diseases.

  7. Music listening engages specific cortical regions within the temporal lobes: differences between musicians and non-musicians.

    Science.gov (United States)

    Angulo-Perkins, Arafat; Aubé, William; Peretz, Isabelle; Barrios, Fernando A; Armony, Jorge L; Concha, Luis

    2014-10-01

    Music and speech are two of the most relevant and common sounds in the human environment. Perceiving and processing these two complex acoustical signals rely on a hierarchical functional network distributed throughout several brain regions within and beyond the auditory cortices. Given their similarities, the neural bases for processing these two complex sounds overlap to a certain degree, but particular brain regions may show selectivity for one or the other acoustic category, which we aimed to identify. We examined 53 subjects (28 of them professional musicians) by functional magnetic resonance imaging (fMRI), using a paradigm designed to identify regions showing increased activity in response to different types of musical stimuli, compared to different types of complex sounds, such as speech and non-linguistic vocalizations. We found a region in the anterior portion of the superior temporal gyrus (aSTG) (planum polare) that showed preferential activity in response to musical stimuli and was present in all our subjects, regardless of musical training, and invariant across different musical instruments (violin, piano or synthetic piano). Our data show that this cortical region is preferentially involved in processing musical, as compared to other complex sounds, suggesting a functional role as a second-order relay, possibly integrating acoustic characteristics intrinsic to music (e.g., melody extraction). Moreover, we assessed whether musical experience modulates the response of cortical regions involved in music processing and found evidence of functional differences between musicians and non-musicians during music listening. In particular, bilateral activation of the planum polare was more prevalent, but not exclusive, in musicians than non-musicians, and activation of the right posterior portion of the superior temporal gyrus (planum temporale) differed between groups. Our results provide evidence of functional specialization for music processing in specific

  8. Metabolite Profiling and Transcript Analysis Reveal Specificities in the Response of a Berry Derived Cell Culture to Abiotic Stresses

    Directory of Open Access Journals (Sweden)

    Biruk eAyenew

    2015-09-01

    Full Text Available As climate changes, there is a need to understand the expected effects on viticulture. In nature, stresses exist in a combined manner, hampering the elucidation of the effect of individual cues on grape berry metabolism. Cell suspension culture originated from pea-size Gamy Red grape berry was used to harness metabolic response to high light (2500 µmol m-2s-1, high temperature (40 0C and their combination in comparison to 25 0C and 100 µmol m-2s-1 under controlled condition. When LC-MS and GC-MS based metabolite profiling was implemented and integrated with targeted RT-qPCR transcript analysis specific responses were observed to the different cues. High light enhanced polyphenol metabolism while high temperature and its combination with high light induced amino acid and organic acid metabolism with additional effect on polyphenols. The trend of increment in TCA cycle genes like ATCs, ACo1 and IDH in the combined treatment might support the observed increment in organic acids, GABA shunt, and their derivatives. The apparent phenylalanine reduction with polyphenol increment under high light suggests enhanced fueling of the precursor towards the downstream phenylpropanoid pathway. In the polyphenol metabolism, a differential pattern of expression of flavonoid 3’,5’ hydroxylase and flavonoid 3’ hydroxylase was observed under high light and combined cues which were accompanied by characteristic metabolite profiles. High temperature decreased glycosylated cyanidin and peonidin forms while the combined cues increased acetylated and coumarylated peonidin forms. Transcription factors regulating anthocyanin metabolism and their methylation, MYB, OMT, UFGT and DFR, were expressed differentially among the treatments, overall in agreement with the metabolite profiles. Taken together these data provide insights into the coordination of central and secondary metabolism in relation to multiple abiotic stresses.

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

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    Gallinger Steven

    2005-06-01

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

  10. Solute-specific patterns and drivers of urban stream chemistry revealed by long-term monitoring in Baltimore, Maryland

    Science.gov (United States)

    Reisinger, A. J.; Woytowitz, E.; Majcher, E.; Rosi, E. J.; Groffman, P.

    2017-12-01

    Urban streams receive a myriad of chemical inputs from the surrounding landscape due to altered lithology (asphalt, concrete), leaky sewage infrastructure, and other human activities (road salt, fertilizer, industrial wastes, wastewater effluent), potentially leading to multiple chemical stressors occurring simultaneously. To evaluate potential drivers of water chemistry change, we used approximately 20 years of weekly water chemistry monitoring data from streams in the Baltimore Ecosystem Study (BES) to quantify trends of annual loads and flow-weighted concentrations for multiple solutes of interest, including nitrate (NO3-), phosphate (PO43-), total nitrogen (TN), total phosphorus (TP), chloride (Cl-), and sulfate (SO42-) and subsequently examined various gray and green infrastructure characteristics at the watershed scale. For example, we quantified annual volume and duration of reported sanitary sewer overflows (SSO) and cumulative storage volume and area of various best management practices (BMPs). Site- and solute-specific trends differed, but across our monitoring network we found evidence for decreasing annual export for multiple solutes. Additionally, we found that changes in gray- and green-infrastructure characteristics were related to changes in water quality at our most downstream (most urban) monitoring site. For example, annual NO3- loads increased with longer cumulative SSO duration, whereas annual PO43- and TP loads decreased with a cumulative BMP area in the watershed. Further, we used same long-term water chemistry data and multivariate analyses to investigate whether urban streams have unique water chemistry fingerprints representing the multiple chemical stressors at a given site, which could provide insight into sources and impacts of water-quality impairment. These analyses and results illustrate the major role gray and green infrastructure play in influencing water quality in urban environments, and illustrate that focusing on a variety of

  11. A novel Zika virus mouse model reveals strain specific differences in virus pathogenesis and host inflammatory immune responses.

    Directory of Open Access Journals (Sweden)

    Shashank Tripathi

    2017-03-01

    Full Text Available Zika virus (ZIKV is a mosquito borne flavivirus, which was a neglected tropical pathogen until it emerged and spread across the Pacific Area and the Americas, causing large human outbreaks associated with fetal abnormalities and neurological disease in adults. The factors that contributed to the emergence, spread and change in pathogenesis of ZIKV are not understood. We previously reported that ZIKV evades cellular antiviral responses by targeting STAT2 for degradation in human cells. In this study, we demonstrate that Stat2-/- mice are highly susceptible to ZIKV infection, recapitulate virus spread to the central nervous system (CNS, gonads and other visceral organs, and display neurological symptoms. Further, we exploit this model to compare ZIKV pathogenesis caused by a panel of ZIKV strains of a range of spatiotemporal history of isolation and representing African and Asian lineages. We observed that African ZIKV strains induce short episodes of severe neurological symptoms followed by lethality. In comparison, Asian strains manifest prolonged signs of neuronal malfunctions, occasionally causing death of the Stat2-/- mice. African ZIKV strains induced higher levels of inflammatory cytokines and markers associated with cellular infiltration in the infected brain in mice, which may explain exacerbated pathogenesis in comparison to those of the Asian lineage. Interestingly, viral RNA levels in different organs did not correlate with the pathogenicity of the different strains. Taken together, we have established a new murine model that supports ZIKV infection and demonstrate its utility in highlighting intrinsic differences in the inflammatory response induced by different ZIKV strains leading to severity of disease. This study paves the way for the future interrogation of strain-specific changes in the ZIKV genome and their contribution to viral pathogenesis.

  12. Analysis of expression in the Anopheles gambiae developing testes reveals rapidly evolving lineage-specific genes in mosquitoes

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    Krzywinski Jaroslaw

    2009-07-01

    Full Text Available Abstract Background Male mosquitoes do not feed on blood and are not involved in delivery of pathogens to humans. Consequently, they are seldom the subjects of research, which results in a very poor understanding of their biology. To gain insights into male developmental processes we sought to identify genes transcribed exclusively in the reproductive tissues of male Anopheles gambiae pupae. Results Using a cDNA subtraction strategy, five male-specifically or highly male-biased expressed genes were isolated, four of which remain unannotated in the An. gambiae genome. Spatial and temporal expression patterns suggest that each of these genes is involved in the mid-late stages of spermatogenesis. Their sequences are rapidly evolving; however, two genes possess clear homologs in a wide range of taxa and one of these probably acts in a sperm motility control mechanism conserved in many organisms, including humans. The other three genes have no match to sequences from non-mosquito taxa, thus can be regarded as orphans. RNA in situ hybridization demonstrated that one of the orphans is transcribed in spermatids, which suggests its involvement in sperm maturation. Two other orphans have unknown functions. Expression analysis of orthologs of all five genes indicated that male-biased transcription was not conserved in the majority of cases in Aedes and Culex. Conclusion Discovery of testis-expressed orphan genes in mosquitoes opens new prospects for the development of innovative control methods. The orphan encoded proteins may represent unique targets of selective anti-mosquito sterilizing agents that will not affect non-target organisms.

  13. Analysis of expression in the Anopheles gambiae developing testes reveals rapidly evolving lineage-specific genes in mosquitoes.

    Science.gov (United States)

    Krzywinska, Elzbieta; Krzywinski, Jaroslaw

    2009-07-06

    Male mosquitoes do not feed on blood and are not involved in delivery of pathogens to humans. Consequently, they are seldom the subjects of research, which results in a very poor understanding of their biology. To gain insights into male developmental processes we sought to identify genes transcribed exclusively in the reproductive tissues of male Anopheles gambiae pupae. Using a cDNA subtraction strategy, five male-specifically or highly male-biased expressed genes were isolated, four of which remain unannotated in the An. gambiae genome. Spatial and temporal expression patterns suggest that each of these genes is involved in the mid-late stages of spermatogenesis. Their sequences are rapidly evolving; however, two genes possess clear homologs in a wide range of taxa and one of these probably acts in a sperm motility control mechanism conserved in many organisms, including humans. The other three genes have no match to sequences from non-mosquito taxa, thus can be regarded as orphans. RNA in situ hybridization demonstrated that one of the orphans is transcribed in spermatids, which suggests its involvement in sperm maturation. Two other orphans have unknown functions. Expression analysis of orthologs of all five genes indicated that male-biased transcription was not conserved in the majority of cases in Aedes and Culex. Discovery of testis-expressed orphan genes in mosquitoes opens new prospects for the development of innovative control methods. The orphan encoded proteins may represent unique targets of selective anti-mosquito sterilizing agents that will not affect non-target organisms.

  14. Grouping subjects based on conditioning criteria reveals differences in acquisition rates and in strength of conditioning-specific reflex modification.

    Science.gov (United States)

    Smith-Bell, Carrie A; Schreurs, Bernard G

    2017-11-01

    Averaging behavioral data such as the nictitating membrane response (NMR) across subjects can conceal important individual and group differences. Analyses were conducted of NMR data from rabbits that were grouped based on the point during NMR conditioning when subjects produced 8 conditioned responses (CR) in a set of 10 trials. This resulted in five groups (Early Day 1, Late Day 1, Early Day 2, Late Day 2, Early Day 3) in which group differences in CR acquisition rates were found. Percent (%) CRs were not found to increase monotonically and between-session differences in % CR were found. Conditioning-specific reflex modification (CRM) of the