Reduced arctic tundra productivity linked with landform and climate change interactions.

PubMed

Lara, Mark J; Nitze, Ingmar; Grosse, Guido; Martin, Philip; McGuire, A David

2018-02-05

Arctic tundra ecosystems have experienced unprecedented change associated with climate warming over recent decades. Across the Pan-Arctic, vegetation productivity and surface greenness have trended positively over the period of satellite observation. However, since 2011 these trends have slowed considerably, showing signs of browning in many regions. It is unclear what factors are driving this change and which regions/landforms will be most sensitive to future browning. Here we provide evidence linking decadal patterns in arctic greening and browning with regional climate change and local permafrost-driven landscape heterogeneity. We analyzed the spatial variability of decadal-scale trends in surface greenness across the Arctic Coastal Plain of northern Alaska (~60,000 km²) using the Landsat archive (1999-2014), in combination with novel 30 m classifications of polygonal tundra and regional watersheds, finding landscape heterogeneity and regional climate change to be the most important factors controlling historical greenness trends. Browning was linked to increased temperature and precipitation, with the exception of young landforms (developed following lake drainage), which will likely continue to green. Spatiotemporal model forecasting suggests carbon uptake potential to be reduced in response to warmer and/or wetter climatic conditions, potentially increasing the net loss of carbon to the atmosphere, at a greater degree than previously expected.

Short Communication: An apospory-specific genomic region is conserved between Buffelgrass (Cenchrus ciliaris L.) and Pennisetum squamulatum Fresen.

PubMed

Roche; Cong; Chen; Hanna; Gustine; Sherwood; Ozias-Akins

1999-07-01

Twelve molecular markers linked to pseudogamous apospory, a form of gametophytic apomixis, were previously isolated from Pennisetum squamulatum Fresen. No recombination between these markers was found in a segregating population of 397 individuals (Ozias-Akins et al. 1998, Proc. Natl Acad. Sci. USA, 95, 5127-5132). The objective of the present study was to test if these markers were also linked to the aposporous mode of reproduction in two small segregating populations of Cenchrus ciliaris (= Pennisetum ciliare (L.)Link), another apomictic grass species. Among 12 markers (sequence characterized amplified regions, SCARs), six were scored as dominant markers between aposporous and sexual C. ciliaris genotypes (presence/absence, respectively). Five were always linked to apospory and one showed a low level of recombination in 84 progenies. Restriction fragment length polymorphisms (RFLPs) were observed between sexual and apomictic phenotypes for three of the six remaining SCARs from P. squamulatum when used as probes. No recombination was observed in the F1 progenies. Preliminary data from megabase DNA analysis and sequencing in both species indicate that an apospory-specific genomic region (ASGR) is highly conserved between the two species. Although C. ciliaris has a smaller genome size to P. squamulatum, a higher copy number for markers linked to apospory found in the former may impair the progress of positional cloning of gene(s) for apomixis in this species.

Immunoglobulin Heavy Chain Variable Region and Major Histocompatibility Region Genes Are Linked to Induced Graves' Disease in Females From Two Very Large Families of Recombinant Inbred Mice

PubMed Central

Aliesky, Holly; Banuelos, Bianca; Magana, Jessica; Williams, Robert W.; Rapoport, Basil

2014-01-01

Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism can be induced by immunizing mice with adenovirus expressing the human TSHR A-subunit. Prior analysis of induced Graves' disease in small families of recombinant inbred (RI) female mice demonstrated strong genetic control but did not resolve trait loci for TSHR antibodies or elevated serum T4. We investigated the genetic basis for induced Graves' disease in female mice of two large RI families and combined data with earlier findings to provide phenotypes for 178 genotypes. TSHR antibodies measured by inhibition of TSH binding to its receptor were highly significantly linked in the BXD set to the major histocompatibility region (chromosome 17), consistent with observations in 3 other RI families. In the LXS family, we detected linkage between T4 levels after TSHR-adenovirus immunization and the Ig heavy chain variable region (Igvh, chromosome 12). This observation is a key finding because components of the antigen binding region of Igs determine antibody specificity and have been previously linked to induced thyroid-stimulating antibodies. Data from the LXS family provide the first evidence in mice of a direct link between induced hyperthyroidism and Igvh genes. A role for major histocompatibility genes has now been established for genetic susceptibility to Graves' disease in both humans and mice. Future studies using arrays incorporating variation in the complex human Ig gene locus will be necessary to determine whether Igvh genes are also linked to Graves' disease in humans. PMID:25051451

Microsatellite signature of ecological selection for salt tolerance in a wild sunflower hybrid species, Helianthus paradoxus

PubMed Central

EDELIST, CÉCILE; LEXER, CHRISTIAN; DILLMANN, CHRISTINE; SICARD, DELPHINE; RIESEBERG, LOREN H.

2008-01-01

The hybrid sunflower species Helianthus paradoxus inhabits sporadic salt marshes in New Mexico and southwest Texas, USA, whereas its parental species, Helianthus annuus and Helianthus petiolaris, are salt sensitive. Previous studies identified three genomic regions — survivorship quantitative trait loci (QTLs) — that were under strong selection in experimental hybrids transplanted into the natural habitat of H. paradoxus. Here we ask whether these same genomic regions experienced significant selection during the origin and evolution of the natural hybrid, H. paradoxus. This was accomplished by comparing the variability of microsatellites linked to the three survivorship QTLs with those from genomic regions that were neutral in the experimental hybrids. As predicted if one or more selective sweeps had occurred in these regions, microsatellites linked to the survivorship QTLs exhibited a significant reduction in diversity in populations of the natural hybrid species. In contrast, no difference in diversity levels was observed between the two microsatellite classes in parental populations. PMID:17107488

Matching mammographic regions in mediolateral oblique and cranio caudal views: a probabilistic approach

NASA Astrophysics Data System (ADS)

Samulski, Maurice; Karssemeijer, Nico

2008-03-01

Most of the current CAD systems detect suspicious mass regions independently in single views. In this paper we present a method to match corresponding regions in mediolateral oblique (MLO) and craniocaudal (CC) mammographic views of the breast. For every possible combination of mass regions in the MLO view and CC view, a number of features are computed, such as the difference in distance of a region to the nipple, a texture similarity measure, the gray scale correlation and the likelihood of malignancy of both regions computed by single-view analysis. In previous research, Linear Discriminant Analysis was used to discriminate between correct and incorrect links. In this paper we investigate if the performance can be improved by employing a statistical method in which four classes are distinguished. These four classes are defined by the combinations of view (MLO/CC) and pathology (TP/FP) labels. We use distance-weighted k-Nearest Neighbor density estimation to estimate the likelihood of a region combination. Next, a correspondence score is calculated as the likelihood that the region combination is a TP-TP link. The method was tested on 412 cases with a malignant lesion visible in at least one of the views. In 82.4% of the cases a correct link could be established between the TP detections in both views. In future work, we will use the framework presented here to develop a context dependent region matching scheme, which takes the number and likelihood of possible alternatives into account. It is expected that more accurate determination of matching probabilities will lead to improved CAD performance.

Hemisphere Rule in Active Regions with Different Properties

NASA Astrophysics Data System (ADS)

Liu, Y.; Xiong, X.

2017-12-01

Magnetic twist in solar active regions has been found to have a hemispheric preferencein sign (hemisphere rule): negative in the northern hemisphere and positive in the southern.The strength of the preference reported in previous studies ranges greatly, from 58% to 82%.In this presentation, we will show an investigation that examines this hemispheric preference bystudying active regions in Solar Cycle 24 using the vector magnetic field data taken by the Helioseismicand Magnetic Imager (HMI). While in general the strength of the hemisphere preference is wellwithin the range reported by the previous studies, it differs substantially in different groupsof active regions that possess different properties in magnetic helicity: the group with theopposite signs of magnetic twist and writhe has a much stronger preference strength than thegroup with the same signs. This difference becomes even more significant in emerging activeregions. We place here a discussion on possible links between origin of magnetic twist, hemispherepreference, and emergence and evolution of active regions.

Brain Oscillatory Activity during Spatial Navigation: Theta and Gamma Activity Link Medial Temporal and Parietal Regions

ERIC Educational Resources Information Center

White, David J.; Congedo, Marco; Ciorciari, Joseph; Silberstein, Richard B.

2012-01-01

Brain oscillatory correlates of spatial navigation were investigated using blind source separation (BSS) and standardized low resolution electromagnetic tomography (sLORETA) analyses of 62-channel EEG recordings. Twenty-five participants were instructed to navigate to distinct landmark buildings in a previously learned virtual reality town…

Identification of rare recombinants leads to tightly linked markers for nematode resistance in peanut

USDA-ARS?s Scientific Manuscript database

Strong host resistance to root-knot nematode (RKN; Meloidogyne arenaria) introgressed from a wild diploid species to cultivated peanut was previously shown to be located on a large chromosomal region of linkage group A09. Little to no recombination in mapping populations has hindered fine mapping o...

Variation in the link between parental divorce and children's health disadvantage in low and high divorce settings.

PubMed

Smith-Greenaway, Emily; Clark, Shelley

2017-12-01

Like in other world regions, children with divorced parents in sub-Saharan Africa experience significant heath disadvantages relative to their peers with married parents. Preliminary evidence suggests this disadvantage may not be uniform across the subcontinent's diverse settings. Research from other world regions shows that the childhood health consequences of divorce vary across different contexts. Specifically, we hypothesize that the childhood disadvantages associated with divorce are more severe in regions of sub-Saharan Africa where divorce is rare, and less so where divorce is a more common family experience. Using Demographic and Health Survey data from 290 subnational regions within 31 sub-Saharan African countries, multilevel models document the previously shown link between having a divorced mother and child morbidity and mortality. The study results further demonstrate that the childhood health disadvantage is accentuated in subnational African regions where fewer women are divorced and muted in areas where more women are divorced. The findings demonstrate that the broader context can powerfully moderate childhood health inequalities traditionally thought of as operating at the family or individual level.

Deciphering Late-Pleistocence landscape evolution: linking proxies by combining pedo-stratigraphy and luminescence dating

NASA Astrophysics Data System (ADS)

Kreutzer, Sebastian; Meszner, Sascha; Faust, Dominik; Fuchs, Markus

2014-05-01

Interpreting former landscape evolution asks for understanding the processes that sculpt such landforms by means of deciphering complex systems. For reconstructing terrestrial Quaternary environments based on loess archives this might be considered, at least, as a three step process: (1) Identifying valuable records in appropriate morphological positions in a previously defined research area, (2) analysing the profiles by field work and laboratory methods and finally (3) linking the previously considered pseudo-isolated systems to set up a comprehensive picture. Especially the first and the last step might bring some pitfalls, as it is tempting to specify single records as pseudo-isolated, closed systems. They might be, with regard to their preservation in their specific morphological position, but in fact they are part of a complex, open system. Between 2008 and 2013, Late-Pleistocene loess archives in Saxony have been intensively investigated by field and laboratory methods. Linking pedo- and luminescence dating based chronostratigraphies, a composite profile for the entire Saxonian Loess Region has been established. With this, at least, two-fold approach we tried to avoid misinterpretations that might appear when focussing on one standard profile in an open morphological system. Our contribution focuses on this multi-proxy approach to decipher the Late-Pleistocene landscape evolution in the Saxonian Loess Region. Highlighting the challenges and advantages of combining different methods, we believe that (1) this multi-proxy approach is without alternative, (2) the combination of different profiles may simplify the more complex reality, but it may be a useful generalisation to understand and reveal the stratigraphical significance of the landscape evolution in this region.

Management of Ciguatoxin Risk in Eastern Australia

PubMed Central

Farrell, Hazel; Murray, Shauna A.; Zammit, Anthony; Edwards, Alan W.

2017-01-01

Between 2014 and 2016, five cases of ciguatera fish poisoning (CFP), involving twenty four individuals, were linked to Spanish Mackerel (Scomberomorus commerson) caught in the coastal waters of the state of New South Wales (NSW) on the east coast of Australia. Previously, documented cases of CFP in NSW were few, and primarily linked to fish imported from other regions. Since 2015, thirteen individuals were affected across four additional CFP cases in NSW, linked to fish imported from tropical locations. The apparent increase in CFP in NSW from locally sourced catch, combined with the risk of CFP from imported fish, has highlighted several considerations that should be incorporated into risk management strategies to minimize CFP exposure for seafood consumers. PMID:29135913

Prefrontal and medial temporal contributions to episodic memory-based reasoning.

PubMed

Suzuki, Chisato; Tsukiura, Takashi; Mochizuki-Kawai, Hiroko; Shigemune, Yayoi; Iijima, Toshio

2009-03-01

Episodic memory retrieval and reasoning are fundamental psychological components of our daily lives. Although previous studies have investigated the brain regions associated with these processes separately, the neural mechanisms of reasoning based on episodic memory retrieval are largely unknown. Here, we investigated the neural correlates underlying episodic memory-based reasoning using functional magnetic resonance imaging (fMRI). During fMRI scanning, subjects performed three tasks: reasoning, episodic memory retrieval, and episodic memory-based reasoning. We identified dissociable activations related to reasoning, episodic memory retrieval, and linking processes between the two. Regions related to reasoning were identified in the left ventral prefrontal cortices (PFC), and those related to episodic memory retrieval were found in the right medial temporal lobe (MTL) regions. In addition, activations predominant in the linking process between the two were found in the left dorsal and right ventral PFC. These findings suggest that episodic memory-based reasoning is composed of at least three processes, i.e., reasoning, episodic memory retrieval, and linking processes between the two, and that activation of both the PFC and MTL is crucial in episodic memory-based reasoning. These findings are the first to demonstrate that PFC and MTL regions contribute differentially to each process in episodic memory-based reasoning.

Functional connectivity associated with social networks in older adults: A resting-state fMRI study.

PubMed

Pillemer, Sarah; Holtzer, Roee; Blumen, Helena M

2017-06-01

Poor social networks and decreased levels of social support are associated with worse mood, health, and cognition in younger and older adults. Yet, we know very little about the brain substrates associated with social networks and social support, particularly in older adults. This study examined functional brain substrates associated with social networks using the Social Network Index (SNI) and resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI data from 28 non-demented older adults were analyzed with independent components analyses. As expected, four established resting-state networks-previously linked to motor, vision, speech, and other language functions-correlated with the quality (SNI-1: total number of high-contact roles of a respondent) and quantity (SNI-2: total number of individuals in a respondent's social network) of social networks: a sensorimotor, a visual, a vestibular/insular, and a left frontoparietal network. Moreover, SNI-1 was associated with greater functional connectivity in the lateral prefrontal regions of the left frontoparietal network, while SNI-2 was associated with greater functional connectivity in the medial prefrontal regions of this network. Thus, lateral prefrontal regions may be particularly linked to the quality of social networks while medial prefrontal regions may be particularly linked to the quantity of social networks.

Size and Content of the Sex-Determining Region of the Y Chromosome in Dioecious Mercurialis annua, a Plant with Homomorphic Sex Chromosomes.

PubMed

Veltsos, Paris; Cossard, Guillaume; Beaudoing, Emmanuel; Beydon, Genséric; Savova Bianchi, Dessislava; Roux, Camille; C González-Martínez, Santiago; R Pannell, John

2018-05-29

Dioecious plants vary in whether their sex chromosomes are heteromorphic or homomorphic, but even homomorphic sex chromosomes may show divergence between homologues in the non-recombining, sex-determining region (SDR). Very little is known about the SDR of these species, which might represent particularly early stages of sex-chromosome evolution. Here, we assess the size and content of the SDR of the diploid dioecious herb Mercurialis annua , a species with homomorphic sex chromosomes and mild Y-chromosome degeneration. We used RNA sequencing (RNAseq) to identify new Y-linked markers for M. annua. Twelve of 24 transcripts showing male-specific expression in a previous experiment could be amplified by polymerase chain reaction (PCR) only from males, and are thus likely to be Y-linked. Analysis of genome-capture data from multiple populations of M. annua pointed to an additional six male-limited (and thus Y-linked) sequences. We used these markers to identify and sequence 17 sex-linked bacterial artificial chromosomes (BACs), which form 11 groups of non-overlapping sequences, covering a total sequence length of about 1.5 Mb. Content analysis of this region suggests that it is enriched for repeats, has low gene density, and contains few candidate sex-determining genes. The BACs map to a subset of the sex-linked region of the genetic map, which we estimate to be at least 14.5 Mb. This is substantially larger than estimates for other dioecious plants with homomorphic sex chromosomes, both in absolute terms and relative to their genome sizes. Our data provide a rare, high-resolution view of the homomorphic Y chromosome of a dioecious plant.

Stress and Coping: Latino Youth Coming of Age in a New Latino Destination

ERIC Educational Resources Information Center

Brietzke, Maria; Perreira, Krista

2017-01-01

Previous research has linked stress to adverse mental health outcomes among Latino adolescents living in the United States. The mechanism through which this process operates continues to be explored, especially in regions of the country where Latin American immigrants and their children have only recently begun to migrate. Our study aimed to…

The Norrie disease gene maps to a 150 kb region on chromosome Xp11.3.

PubMed

Sims, K B; Lebo, R V; Benson, G; Shalish, C; Schuback, D; Chen, Z Y; Bruns, G; Craig, I W; Golbus, M S; Breakefield, X O

1992-05-01

Norrie disease is a human X-linked recessive disorder of unknown etiology characterized by congenital blindness, sensory neural deafness and mental retardation. This disease gene was previously linked to the DXS7 (L1.28) locus and the MAO genes in band Xp11.3. We report here fine physical mapping of the obligate region containing the Norrie disease gene (NDP) defined by a recombination and by the smallest submicroscopic chromosomal deletion associated with Norrie disease identified to date. Analysis, using in addition two overlapping YAC clones from this region, allowed orientation of the MAOA and MAOB genes in a 5'-3'-3'-5' configuration. A recombination event between a (GT)n polymorphism in intron 2 of the MAOB gene and the NDP locus, in a family previously reported to have a recombination between DXS7 and NDP, delineates a flanking marker telomeric to this disease gene. An anonymous DNA probe, dc12, present in one of the YACs and in a patient with a submicroscopic deletion which includes MAOA and MAOB but not L1.28, serves as a flanking marker centromeric to the disease gene. An Alu-PCR fragment from the right arm of the MAO YAC (YMAO.AluR) is not deleted in this patient and also delineates the centromeric extent of the obligate disease region. The apparent order of these loci is telomere ... DXS7-MAOA-MAOB-NDP-dc12-YMAO.AluR ... centromere. Together these data define the obligate region containing the NDP gene to a chromosomal segment less than 150 kb.

DTI-measured white matter abnormalities in adolescents with Conduct Disorder

PubMed Central

Haney-Caron, Emily; Caprihan, Arvind; Stevens, Michael C.

2013-01-01

Emerging research suggests that antisocial behavior in youth is linked to abnormal brain white matter microstructure, but the extent of such anatomical connectivity abnormalities remain largely untested because previous Conduct Disorder (CD) studies typically have selectively focused on specific frontotemporal tracts. This study aimed to replicate and extend previous frontotemporal diffusion tensor imaging (DTI) findings to determine whether noncomorbid CD adolescents have white matter microstructural abnormalities in major white matter tracts across the whole brain. Seventeen CD-diagnosed adolescents recruited from the community were compared to a group of 24 non-CD youth which did not differ in average age (12–18) or gender proportion. Tract-based spatial statistics (TBSS) fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) measurements were compared between groups using FSL nonparametric two-sample t test, clusterwise whole-brain corrected, p<.05. CD FA and AD deficits were widespread, but unrelated to gender, verbal ability, or CD age of onset. CD adolescents had significantly lower FA and AD values in frontal lobe and temporal lobe regions, including frontal lobe anterior/superior corona radiata, and inferior longitudinal and fronto-occpital fasciculi passing through the temporal lobe. The magnitude of several CD FA deficits was associated with number of CD symptoms. Because AD, but not RD, differed between study groups, abnormalities of axonal microstructure in CD rather than myelination are suggested. This study provides evidence that adolescent antisocial disorder is linked to abnormal white matter microstructure in more than just the uncinate fasciulcus as identified in previous DTI studies, or frontotemporal brain structures as suggested by functional neuroimaging studies. Instead, neurobiological risk specific to antisociality in adolescence is linked to microstructural abnormality in numerous long-range white matter connections among many diverse different brain regions. PMID:24139595

Academic health sciences library Website navigation: an analysis of forty-one Websites and their navigation tools.

PubMed

Brower, Stewart M

2004-10-01

The analysis included forty-one academic health sciences library (HSL) Websites as captured in the first two weeks of January 2001. Home pages and persistent navigational tools (PNTs) were analyzed for layout, technology, and links, and other general site metrics were taken. Websites were selected based on rank in the National Network of Libraries of Medicine, with regional and resource libraries given preference on the basis that these libraries are recognized as leaders in their regions and would be the most reasonable source of standards for best practice. A three-page evaluation tool was developed based on previous similar studies. All forty-one sites were evaluated in four specific areas: library general information, Website aids and tools, library services, and electronic resources. Metrics taken for electronic resources included orientation of bibliographic databases alphabetically by title or by subject area and with links to specifically named databases. Based on the results, a formula for determining obligatory links was developed, listing items that should appear on all academic HSL Web home pages and PNTs. These obligatory links demonstrate a series of best practices that may be followed in the design and construction of academic HSL Websites.

Genetic analysis of eight loci tightly linked to neurofibromatosis 1

PubMed Central

Stephens, Karen; Green, Philip; Riccardi, Vincent M.; Ng, Siu; Rising, Marcia; Barker, David; Darby, John K.; Falls, Kathleen M.; Collins, Francis S.; Willard, Huntington F.; Donis-Keller, Helen

1989-01-01

The genetic locus for neurofibromatosis 1 (NF1) has recently been mapped to the pericentromeric region of chromosome 17. We have genotyped eight previously identified RFLP probes on 50 NF1 families to determine the placement of the NF1 locus relative to the RFLP loci. Thirty-eight recombination events in the pericentromeric region were identified, eight involving crossovers between NF1 and loci on either chromosomal arm. Multipoint linkage analysis resulted in the unique placement of six loci at odds >100:1 in the order of pter–A10-41–EW301–NF1–EW207–CRI-L581–CRI-L946–qter. Owing to insufficient crossovers, three loci–D17Z1, EW206, and EW203–could not be uniquely localized. In this region female recombination rates were significantly higher than those of males. These data were part of a joint study aimed at the localization of both NF1 and tightly linked pericentromeric markers for chromosome 17. PMID:2491775

Reversible Information Flow across the Medial Temporal Lobe: The Hippocampus Links Cortical Modules during Memory Retrieval

PubMed Central

Cooper, Elisa; Henson, Richard N.

2013-01-01

A simple cue can be sufficient to elicit vivid recollection of a past episode. Theoretical models suggest that upon perceiving such a cue, disparate episodic elements held in neocortex are retrieved through hippocampal pattern completion. We tested this fundamental assumption by applying functional magnetic resonance imaging (fMRI) while objects or scenes were used to cue participants' recall of previously paired scenes or objects, respectively. We first demonstrate functional segregation within the medial temporal lobe (MTL), showing domain specificity in perirhinal and parahippocampal cortices (for object-processing vs scene-processing, respectively), but domain generality in the hippocampus (retrieval of both stimulus types). Critically, using fMRI latency analysis and dynamic causal modeling, we go on to demonstrate functional integration between these MTL regions during successful memory retrieval, with reversible signal flow from the cue region to the target region via the hippocampus. This supports the claim that the human hippocampus provides the vital associative link that integrates information held in different parts of cortex. PMID:23986252

TSPO Expression and Brain Structure in the Psychosis Spectrum.

PubMed

Hafizi, Sina; Guma, Elisa; Koppel, Alex; Da Silva, Tania; Kiang, Michael; Houle, Sylvain; Wilson, Alan A; Rusjan, Pablo M; Chakravarty, M Mallar; Mizrahi, Romina

2018-06-12

Psychosis is associated with abnormal structural changes in the brain including decreased regional brain volumes and abnormal brain morphology. However, the underlying causes of these structural abnormalities are less understood. The immune system, including microglial activation, has been implicated in the pathophysiology of psychosis. Although previous studies have suggested a connection between peripheral proinflammatory cytokines and structural brain abnormalities in schizophrenia, no in-vivo studies have investigated whether microglial activation is also linked to brain structure alterations previously observed in schizophrenia and its putative prodrome. In this study, we investigated the link between mitochondrial 18kDa translocator protein (TSPO) and structural brain characteristics (i.e. regional brain volume, cortical thickness, and hippocampal shape) in key brain regions such as dorsolateral prefrontal cortex and hippocampus of a large group of participants (N = 90) including individuals at clinical high risk (CHR) for psychosis, first-episode psychosis (mostly antipsychotic naïve) patients, and healthy volunteers. The participants underwent structural brain MRI scan and [ 18 F]FEPPA positron emission tomography (PET) targeting TSPO. A significant [ 18 F]FEPPA binding-by-group interaction was observed in morphological measures across the left hippocampus. In first-episode psychosis, we observed associations between [ 18 F]FEPPA V T (total volume of distribution) and outward and inward morphological alterations, respectively, in the dorsal and ventro-medial portions of the left hippocampus. These associations were not significant in CHR or healthy volunteers. There was no association between [ 18 F]FEPPA V T and other structural brain characteristics. Our findings suggest a link between TSPO expression and alterations in hippocampal morphology in first-episode psychosis. Copyright © 2018. Published by Elsevier Inc.

Proteasome, transporter associated with antigen processing, and class I genes in the nurse shark Ginglymostoma cirratum: evidence for a stable class I region and MHC haplotype lineages.

PubMed

Ohta, Yuko; McKinney, E Churchill; Criscitiello, Michael F; Flajnik, Martin F

2002-01-15

Cartilaginous fish (e.g., sharks) are derived from the oldest vertebrate ancestor having an adaptive immune system, and thus are key models for examining MHC evolution. Previously, family studies in two shark species showed that classical class I (UAA) and class II genes are genetically linked. In this study, we show that proteasome genes LMP2 and LMP7, shark-specific LMP7-like, and the TAP1/2 genes are linked to class I/II. Functional LMP7 and LMP7-like genes, as well as multiple LMP2 genes or gene fragments, are found only in some sharks, suggesting that different sets of peptides might be generated depending upon inherited MHC haplotypes. Cosmid clones bearing the MHC-linked classical class I genes were isolated and shown to contain proteasome gene fragments. A non-MHC-linked LMP7 gene also was identified on another cosmid, but only two exons of this gene were detected, closely linked to a class I pseudogene (UAA-NC2); this region probably resulted from a recent duplication and translocation from the functional MHC. Tight linkage of proteasome and class I genes, in comparison with gene organizations of other vertebrates, suggests a primordial MHC organization. Another nonclassical class I gene (UAA-NC1) was detected that is linked neither to MHC nor to UAA-NC2; its high level of sequence similarity to UAA suggests that UAA-NC1 also was recently derived from UAA and translocated from MHC. These data further support the principle of a primordial class I region with few class I genes. Finally, multiple paternities in one family were demonstrated, with potential segregation distortions.

X-linked infantile spinal muscular atrophy: clinical definition and molecular mapping.

PubMed

Dressman, Devin; Ahearn, Mary Ellen; Yariz, Kemal O; Basterrecha, Hugo; Martínez, Francisco; Palau, Francesc; Barmada, M Michael; Clark, Robin Dawn; Meindl, Alfons; Wirth, Brunhilde; Hoffman, Eric P; Baumbach-Reardon, Lisa

2007-01-01

X-linked infantile spinal-muscular atrophy (XL-SMA) is a rare disorder, which presents with the clinical characteristics of hypotonia, areflexia, and multiple congenital contractures (arthrogryposis) associated with loss of anterior horn cells and death in infancy. We have previously reported a single family with XL-SMA that mapped to Xp11.3-q11.2. Here we report further clinical description of XL-SMA plus an additional seven unrelated (XL-SMA) families from North America and Europe that show linkage data consistent with the same region. We first investigated linkage to the candidate disease gene region using microsatellite repeat markers. We further saturated the candidate disease gene region using polymorphic microsatellite repeat markers and single nucleotide polymorphisms in an effort to narrow the critical region. Two-point and multipoint linkage analysis was performed using the Allegro software package. Linkage analysis of all XL-SMA families displayed linkage consistent with the original XL-SMA region. The addition of new families and new markers has narrowed the disease gene interval for a XL-SMA locus between SNP FLJ22843 near marker DXS 8080 and SNP ARHGEF9 which is near DXS7132 (Xp11.3-Xq11.1).

Local Use-Dependent Sleep in Wakefulness Links Performance Errors to Learning

PubMed Central

Quercia, Angelica; Zappasodi, Filippo; Committeri, Giorgia; Ferrara, Michele

2018-01-01

Sleep and wakefulness are no longer to be considered as discrete states. During wakefulness brain regions can enter a sleep-like state (off-periods) in response to a prolonged period of activity (local use-dependent sleep). Similarly, during nonREM sleep the slow-wave activity, the hallmark of sleep plasticity, increases locally in brain regions previously involved in a learning task. Recent studies have demonstrated that behavioral performance may be impaired by off-periods in wake in task-related regions. However, the relation between off-periods in wake, related performance errors and learning is still untested in humans. Here, by employing high density electroencephalographic (hd-EEG) recordings, we investigated local use-dependent sleep in wake, asking participants to repeat continuously two intensive spatial navigation tasks. Critically, one task relied on previous map learning (Wayfinding) while the other did not (Control). Behaviorally awake participants, who were not sleep deprived, showed progressive increments of delta activity only during the learning-based spatial navigation task. As shown by source localization, delta activity was mainly localized in the left parietal and bilateral frontal cortices, all regions known to be engaged in spatial navigation tasks. Moreover, during the Wayfinding task, these increments of delta power were specifically associated with errors, whose probability of occurrence was significantly higher compared to the Control task. Unlike the Wayfinding task, during the Control task neither delta activity nor the number of errors increased progressively. Furthermore, during the Wayfinding task, both the number and the amplitude of individual delta waves, as indexes of neuronal silence in wake (off-periods), were significantly higher during errors than hits. Finally, a path analysis linked the use of the spatial navigation circuits undergone to learning plasticity to off periods in wake. In conclusion, local sleep regulation in wakefulness, associated with performance failures, could be functionally linked to learning-related cortical plasticity. PMID:29666574

Failure to find a chromosome 18 pericentric linkage in families with schizophrenia

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

De Lisi, L.E.; Shields, G.; Lehner, T.

1995-12-18

A recent report of a possible linkage of bipolar affective disorder to a pericentric region of chromosome 18 initiated the present investigation to search for a similar linkage in 32 families with schizophrenia. The results of a study using 5 markers mapped to this region show negative lod scores and only weak evidence for any linkage by nonparametric analyses. If the previously reported finding is a true positive linkage for bipolar disorder, then either it is unlikely to be related to the genetics of schizophrenia, or the proportion of families linked to this region is small. 12 refs., 4 tabs.

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

May, M.; Schwartz, C.; Huston, S.

The Opitz GBBB syndrome (OS) is characterized in part by widely spaced inner ocular canthi and hypospadias. Recently, linkage analysis showed that the gene for the X-linked form to be located in an 18 cM region spanning Xp22. We have now conducted linkage analysis in a family previously published as having the BBB syndrome and found tight linkage to DXS7104 (Z = 3.3, {theta} = 0.0). Our data narrows the candidate region to 4 cM and should facilitate the identification and characterization of one of the genes involved in midline development. 21 refs., 1 fig., 1 tab.

Optical imaging of the rat brain suggests a previously missing link between top-down and bottom-up nervous system function

PubMed Central

Greenfield, Susan A.; Badin, Antoine-Scott; Ferrati, Giovanni; Devonshire, Ian M.

2017-01-01

Abstract. Optical imaging with voltage-sensitive dyes enables the visualization of extensive yet highly transient coalitions of neurons (assemblies) operating throughout the brain on a subsecond time scale. We suggest that operating at the mesoscale level of brain organization, neuronal assemblies may provide a functional link between “bottom-up” cellular mechanisms and “top-down” cognitive ones within anatomically defined regions. We demonstrate in ex vivo rat brain slices how varying spatiotemporal dynamics of assemblies reveal differences not previously appreciated between: different stages of development in cortical versus subcortical brain areas, different sensory modalities (hearing versus vision), different classes of psychoactive drugs (anesthetics versus analgesics), different effects of anesthesia linked to hyperbaric conditions and, in vivo, depths of anesthesia. The strategy of voltage-sensitive dye imaging is therefore as powerful as it is versatile and as such can now be applied to the evaluation of neurochemical signaling systems and the screening of related new drugs, as well as to mathematical modeling and, eventually, even theories of consciousness. PMID:28573153

Optical imaging of the rat brain suggests a previously missing link between top-down and bottom-up nervous system function.

PubMed

Greenfield, Susan A; Badin, Antoine-Scott; Ferrati, Giovanni; Devonshire, Ian M

2017-07-01

Optical imaging with voltage-sensitive dyes enables the visualization of extensive yet highly transient coalitions of neurons (assemblies) operating throughout the brain on a subsecond time scale. We suggest that operating at the mesoscale level of brain organization, neuronal assemblies may provide a functional link between "bottom-up" cellular mechanisms and "top-down" cognitive ones within anatomically defined regions. We demonstrate in ex vivo rat brain slices how varying spatiotemporal dynamics of assemblies reveal differences not previously appreciated between: different stages of development in cortical versus subcortical brain areas, different sensory modalities (hearing versus vision), different classes of psychoactive drugs (anesthetics versus analgesics), different effects of anesthesia linked to hyperbaric conditions and, in vivo , depths of anesthesia. The strategy of voltage-sensitive dye imaging is therefore as powerful as it is versatile and as such can now be applied to the evaluation of neurochemical signaling systems and the screening of related new drugs, as well as to mathematical modeling and, eventually, even theories of consciousness.

Diversity and Distribution Patterns in High Southern Latitude Sponges

PubMed Central

Downey, Rachel V.; Griffiths, Huw J.; Linse, Katrin; Janussen, Dorte

2012-01-01

Sponges play a key role in Antarctic marine benthic community structure and dynamics and are often a dominant component of many Southern Ocean benthic communities. Understanding the drivers of sponge distribution in Antarctica enables us to understand many of general benthic biodiversity patterns in the region. The sponges of the Antarctic and neighbouring oceanographic regions were assessed for species richness and biogeographic patterns using over 8,800 distribution records. Species-rich regions include the Antarctic Peninsula, South Shetland Islands, South Georgia, Eastern Weddell Sea, Kerguelen Plateau, Falkland Islands and north New Zealand. Sampling intensity varied greatly within the study area, with sampling hotspots found at the Antarctic Peninsula, South Georgia, north New Zealand and Tierra del Fuego, with limited sampling in the Bellingshausen and Amundsen seas in the Southern Ocean. In contrast to previous studies we found that eurybathy and circumpolar distributions are important but not dominant characteristics in Antarctic sponges. Overall Antarctic sponge species endemism is ∼43%, with a higher level for the class Hexactinellida (68%). Endemism levels are lower than previous estimates, but still indicate the importance of the Polar Front in isolating the Southern Ocean fauna. Nineteen distinct sponge distribution patterns were found, ranging from regional endemics to cosmopolitan species. A single, distinct Antarctic demosponge fauna is found to encompass all areas within the Polar Front, and the sub-Antarctic regions of the Kerguelen Plateau and Macquarie Island. Biogeographical analyses indicate stronger faunal links between Antarctica and South America, with little evidence of links between Antarctica and South Africa, Southern Australia or New Zealand. We conclude that the biogeographic and species distribution patterns observed are largely driven by the Antarctic Circumpolar Current and the timing of past continent connectivity. PMID:22911840

Controlling self-sustained spiking activity by adding or removing one network link

NASA Astrophysics Data System (ADS)

Xu, Kesheng; Huang, Wenwen; Li, Baowen; Dhamala, Mukesh; Liu, Zonghua

2013-06-01

Being able to control the neuronal spiking activity in specific brain regions is central to a treatment scheme in several brain disorders such as epileptic seizures, mental depression, and Parkinson's diseases. Here, we present an approach for controlling self-sustained oscillations by adding or removing one directed network link in coupled neuronal oscillators, in contrast to previous approaches of adding stimuli or noise. We find that such networks can exhibit a variety of activity patterns such as on-off switch, sustained spikes, and short-term spikes. We derive the condition for a specific link to be the controller of the on-off effect. A qualitative analysis is provided to facilitate the understanding of the mechanism for spiking activity by adding one link. Our findings represent the first report on generating spike activity with the addition of only one directed link to a network and provide a deeper understanding of the microscopic roots of self-sustained spiking.

A Complex Genetic Basis to X-Linked Hybrid Male Sterility Between Two Species of House Mice

PubMed Central

Good, Jeffrey M.; Dean, Matthew D.; Nachman, Michael W.

2008-01-01

The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome. PMID:18689897

A complex genetic basis to X-linked hybrid male sterility between two species of house mice.

PubMed

Good, Jeffrey M; Dean, Matthew D; Nachman, Michael W

2008-08-01

The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome.

Academic health sciences library Website navigation: an analysis of forty-one Websites and their navigation tools

PubMed Central

Brower, Stewart M.

2004-01-01

Background: The analysis included forty-one academic health sciences library (HSL) Websites as captured in the first two weeks of January 2001. Home pages and persistent navigational tools (PNTs) were analyzed for layout, technology, and links, and other general site metrics were taken. Methods: Websites were selected based on rank in the National Network of Libraries of Medicine, with regional and resource libraries given preference on the basis that these libraries are recognized as leaders in their regions and would be the most reasonable source of standards for best practice. A three-page evaluation tool was developed based on previous similar studies. All forty-one sites were evaluated in four specific areas: library general information, Website aids and tools, library services, and electronic resources. Metrics taken for electronic resources included orientation of bibliographic databases alphabetically by title or by subject area and with links to specifically named databases. Results: Based on the results, a formula for determining obligatory links was developed, listing items that should appear on all academic HSL Web home pages and PNTs. Conclusions: These obligatory links demonstrate a series of best practices that may be followed in the design and construction of academic HSL Websites. PMID:15494756

Effects of Aging on the Neural Correlates of Successful Item and Source Memory Encoding

PubMed Central

Dennis, Nancy A.; Hayes, Scott M.; Prince, Steven E.; Madden, David J.; Huettel, Scott A.; Cabeza, Roberto

2009-01-01

To investigate the neural basis of age-related source memory (SM) deficits, young and older adults were scanned with fMRI while encoding faces, scenes, and face-scene pairs. Successful encoding activity was identified by comparing encoding activity for subsequently remembered versus forgotten items or pairs. Age deficits in successful encoding activity in hippocampal and prefrontal regions were more pronounced for SM (pairs) compared to item memory (faces and scenes). Age-related reductions were also found in regions specialized in processing faces (fusiform face area) and scenes (parahippocampal place area), but these reductions were similar for item and SM. Functional connectivity between the hippocampus and the rest of the brain was also affected by aging; whereas connections with posterior cortices were weaker in older adults, connections with anterior cortices including prefrontal regions were stronger in older adults. Taken together, the results provide a link between SM deficits in older adults and reduced recruitment of hippocampal and prefrontal regions during encoding. The functional connectivity findings are consistent with a posterior-anterior shift with aging (PASA), previously reported in several cognitive domains and linked to functional compensation. PMID:18605869

Memory Accumulation Mechanisms in Human Cortex Are Independent of Motor Intentions

PubMed Central

Tosoni, Annalisa; Mignogna, Valeria; McAvoy, Mark P.; Shulman, Gordon L.; Corbetta, Maurizio; Romani, Gian Luca

2014-01-01

Previous studies on perceptual decision-making have often emphasized a tight link between decisions and motor intentions. Human decisions, however, also depend on memories or experiences that are not closely tied to specific motor responses. Recent neuroimaging findings have suggested that, during episodic retrieval, parietal activity reflects the accumulation of evidence for memory decisions. It is currently unknown, however, whether these evidence accumulation signals are functionally linked to signals for motor intentions coded in frontoparietal regions and whether activity in the putative memory accumulator tracks the amount of evidence for only previous experience, as reflected in “old” reports, or for both old and new decisions, as reflected in the accuracy of memory judgments. Here, human participants used saccadic-eye and hand-pointing movements to report recognition judgments on pictures defined by different degrees of evidence for old or new decisions. A set of cortical regions, including the middle intraparietal sulcus, showed a monotonic variation of the fMRI BOLD signal that scaled with perceived memory strength (older > newer), compatible with an asymmetrical memory accumulator. Another set, including the hippocampus and the angular gyrus, showed a nonmonotonic response profile tracking memory accuracy (higher > lower evidence), compatible with a symmetrical accumulator. In contrast, eye and hand effector-specific regions in frontoparietal cortex tracked motor intentions but were not modulated by the amount of evidence for the effector outcome. We conclude that item recognition decisions are supported by a combination of symmetrical and asymmetrical accumulation signals largely segregated from motor intentions. PMID:24828652

Mapping the Rust Resistant Loci MXC3 and MER in P. trichocarpa and Assessing the Intermarker Linkage Disequilibrium in MXC3 Region

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

Yin, Tongming; Difazio, Stephen P.; Gunter, Lee E

In an attempt to elucidate the molecular mechanisms of Melampsora rust resistance in Populus trichocarpa, we have mapped two resistance loci, MXC3 and MER, and intensively characterized the flanking genomic sequence for the MXC3 locus and the level of linkage disequilibrium (LD) in natural populations. We used an interspecific backcross pedigree and a genetic map that was highly saturated with AFLP and SSR markers, and assembled shotgun-sequence data in the region containing markers linked to MXC3. The two loci were mapped to different linkage groups. Linkage disequilibrium for MXC3 was confined to two closely linked regions spanning 34 and 16more » kb, respectively. The MXC3 region also contained six disease-resistance candidate genes. The MER and MXC3 loci are clearly distinct, and may have different mechanisms of resistance, as different classes of putative resistance genes were present near each locus. The suppressed recombination previously observed in the MXC3 region was possibly caused by extensive hemizygous rearrangements confined to the original parent tree. The relatively low observed LD may facilitate association studies using candidate genes for rust resistance, but will probably inhibit marker-aided selection.« less

The kinematics of central-southern Turkey and northwest Syria revisited

NASA Astrophysics Data System (ADS)

Seyrek, Ali; Demir, Tuncer; Westaway, Rob; Guillou, Hervé; Scaillet, Stéphane; White, Tom S.; Bridgland, David R.

2014-03-01

Central-southern Turkey, NW Syria, and adjacent offshore areas in the NE Mediterranean region form the boundary zone between the Turkish, African and Arabian plates. A great deal of new information has emerged in recent years regarding senses and rates of active crustal deformation in this region, but this material has not hitherto been well integrated, so the interpretations of key localities by different teams remain contradictory. We have reviewed and synthesised this evidence, combining it with new investigations targeted at key areas of uncertainty. This work has led to the inference of previously unrecognised active faults and has clarified the roles of other structures within the framework of plate motions provided by GPS studies. Roughly one third of the relative motion between the Turkish and Arabian plates is accommodated on the Misis-Kyrenia Fault Zone, which links to the study region from the Kyrenia mountain range of northern Cyprus. Much of this motion passes NNE then eastward around the northern limit of the Amanos Mountains, as previously thought, but some of it splays northeastward to link into newly-recognised normal faulting within the Amanos Mountains. The remaining two thirds of the relative motion is accommodated along the Karasu Valley; some of this component steps leftward across the Amik Basin before passing southward onto the northern Dead Sea Fault Zone (DSFZ) but much of it continues southwestward, past the city of Antakya, then into offshore structures, ultimately linking to the subduction zone bounding the Turkish and African plates to the southwest of Cyprus. However, some of this offshore motion continues southward, west of the Syrian coast, before linking onshore into the southern DSFZ; this component of the relative motion is indeed the main reason why the slip rate on the northern DSFZ, measured geodetically, is so much lower than that on its southern counterpart. In some parts of this region, notably in the Karasu Valley, it is now clear how the expected relative plate motion has been accommodated on active faults during much of the Quaternary: rather than constant slip rates on individual faults, quite complex changes in the partitioning of this motion on timescales of hundreds of thousands of years are indicated. However, in other parts of the region it remains unclear whether additional major active faults remain unrecognised or whether significant relative motions are accommodated by distributed deformation or on the many smaller-scale structures present.

A new three-locus model for rootstock-induced dwarfing in apple revealed by genetic mapping of root bark percentage

PubMed Central

Harrison, Nicola; Harrison, Richard J.; Barber-Perez, Nuria; Cascant-Lopez, Emma; Cobo-Medina, Magdalena; Lipska, Marzena; Conde-Ruíz, Rebeca; Brain, Philip; Gregory, Peter J.; Fernández-Fernández, Felicidad

2016-01-01

Rootstock-induced dwarfing of apple scions revolutionized global apple production during the twentieth century, leading to the development of modern intensive orchards. A high root bark percentage (the percentage of the whole root area constituted by root cortex) has previously been associated with rootstock-induced dwarfing in apple. In this study, the root bark percentage was measured in a full-sib family of ungrafted apple rootstocks and found to be under the control of three loci. Two quantitative trait loci (QTLs) for root bark percentage were found to co-localize to the same genomic regions on chromosome 5 and chromosome 11 previously identified as controlling dwarfing, Dw1 and Dw2, respectively. A third QTL was identified on chromosome 13 in a region that has not been previously associated with dwarfing. The development of closely linked sequence-tagged site markers improved the resolution of allelic classes, thereby allowing the detection of dominance and epistatic interactions between loci, with high root bark percentage only occurring in specific allelic combinations. In addition, we report a significant negative correlation between root bark percentage and stem diameter (an indicator of tree vigour), measured on a clonally propagated grafted subset of the mapping population. The demonstrated link between root bark percentage and rootstock-induced dwarfing of the scion leads us to propose a three-locus model that is able to explain levels of dwarfing from the dwarf ‘M.27’ to the semi-invigorating rootstock ‘M.116’. Moreover, we suggest that the QTL on chromosome 13 (Rb3) might be analogous to a third dwarfing QTL, Dw3, which has not previously been identified. PMID:26826217

An fMRI investigation of responses to peer rejection in adolescents with autism spectrum disorders.

PubMed

Masten, Carrie L; Colich, Natalie L; Rudie, Jeffrey D; Bookheimer, Susan Y; Eisenberger, Naomi I; Dapretto, Mirella

2011-07-01

Peer rejection is particularly pervasive among adolescents with autism spectrum disorders (ASD). However, how adolescents with ASD differ from typically developing adolescents in their responses to peer rejection is poorly understood. The goal of the current investigation was to examine neural responses to peer exclusion among adolescents with ASD compared to typically developing adolescents. Nineteen adolescents with ASD and 17 typically developing controls underwent fMRI as they were ostensibly excluded by peers during an online game called Cyberball. Afterwards, participants reported their distress about the exclusion. Compared to typically developing adolescents, those with ASD displayed less activity in regions previously linked with the distressing aspect of peer exclusion, including the subgenual anterior cingulate and anterior insula, as well as less activity in regions previously linked with the regulation of distress responses during peer exclusion, including the ventrolateral prefrontal cortex and ventral striatum. Interestingly, however, both groups self-reported equivalent levels of distress. This suggests that adolescents with ASD may engage in differential processing of social experiences at the neural level, but be equally aware of, and concerned about, peer rejection. Overall, these findings contribute new insights about how this population may differentially experience negative social events in their daily lives.

An fMRI investigation of responses to peer rejection in adolescents with autism spectrum disorders

PubMed Central

Masten, Carrie L.; Colich, Natalie L.; Rudie, Jeffrey D.; Bookheimer, Susan Y.; Eisenberger, Naomi I.; Dapretto, Mirella

2011-01-01

Peer rejection is particularly pervasive among adolescents with autism spectrum disorders (ASD). However, how adolescents with ASD differ from typically developing adolescents in their responses to peer rejection is poorly understood. The goal of the current investigation was to examine neural responses to peer exclusion among adolescents with ASD compared to typically developing adolescents. Nineteen adolescents with ASD and 17 typically developing controls underwent fMRI as they were ostensibly excluded by peers during an online game called Cyberball. Afterwards, participants reported their distress about the exclusion. Compared to typically developing adolescents, those with ASD displayed less activity in regions previously linked with the distressing aspect of peer exclusion, including the subgenual anterior cingulate and anterior insula, as well as less activity in regions previously linked with the regulation of distress responses during peer exclusion, including the ventrolateral prefrontal cortex and ventral striatum. Interestingly, however, both groups self-reported equivalent levels of distress. This suggests that adolescents with ASD may engage in differential processing of social experiences at the neural level, but be equally aware of, and concerned about, peer rejection. Overall, these findings contribute new insights about how this population may differentially experience negative social events in their daily lives. PMID:22318914

Genotypic analysis of X-linked retinoschisis in Western Australia.

PubMed

Lamey, Tina; Laurin, Sarina; Chelva, Enid; De Roach, John

2010-01-01

X-linked Retinoschisis is a leading cause of juvenile macular degeneration. Four Western Australian families affected by X-Linked Retinoschisis were analysed using DNA and clinical information from the Australian Inherited Retinal Disease (IRD) Register and DNA Bank. By direct sequencing of the RS1 gene, three genetic variants were identified; 52+1G > T, 289T > G and 416delA. 289T > G has not been previously reported and is likely to cause a substitution of a membrane binding residue (W92G) in the functional discoidin domain. All clinically diagnosed individuals showed typical electronegative ERGs. The 52+1G > T obligate carrier also recorded a bilaterally abnormal rod ERG and mildly abnormal photopic responses. mfERG trace arrays showed reduced response densities in the paramacular region extending futher temporally for each eye.

Intelligence is associated with the modular structure of intrinsic brain networks.

PubMed

Hilger, Kirsten; Ekman, Matthias; Fiebach, Christian J; Basten, Ulrike

2017-11-22

General intelligence is a psychological construct that captures in a single metric the overall level of behavioural and cognitive performance in an individual. While previous research has attempted to localise intelligence in circumscribed brain regions, more recent work focuses on functional interactions between regions. However, even though brain networks are characterised by substantial modularity, it is unclear whether and how the brain's modular organisation is associated with general intelligence. Modelling subject-specific brain network graphs from functional MRI resting-state data (N = 309), we found that intelligence was not associated with global modularity features (e.g., number or size of modules) or the whole-brain proportions of different node types (e.g., connector hubs or provincial hubs). In contrast, we observed characteristic associations between intelligence and node-specific measures of within- and between-module connectivity, particularly in frontal and parietal brain regions that have previously been linked to intelligence. We propose that the connectivity profile of these regions may shape intelligence-relevant aspects of information processing. Our data demonstrate that not only region-specific differences in brain structure and function, but also the network-topological embedding of fronto-parietal as well as other cortical and subcortical brain regions is related to individual differences in higher cognitive abilities, i.e., intelligence.

Influences of Moisture Regimes and Functional Plant Types on Nutrient Cycling in Permafrost Regions

NASA Astrophysics Data System (ADS)

McCaully, R. E.; Arendt, C. A.; Newman, B. D.; Heikoop, J. M.; Wilson, C. J.; Sevanto, S.; Wales, N. A.; Wullschleger, S.

2017-12-01

In the permafrost-dominated Arctic, climatic feedbacks exist between permafrost, soil moisture, functional plant type and presence of nutrients. Functional plant types present within the Arctic regulate and respond to changes in hydrologic regimes and nutrient cycling. Specifically, alders are a member of the birch family that use root nodules to fix nitrogen, which is a limiting nutrient strongly linked to fertilizing Arctic ecosystems. Previous investigations in the Seward Peninsula, AK show elevated presence of nitrate within and downslope of alder patches in degraded permafrost systems, with concentrations an order of magnitude greater than that of nitrate measured above these patches. Further observations within these degraded permafrost systems are crucial to assess whether alders are drivers of, or merely respond to, nitrate fluxes. In addition to vegetative feedbacks with nitrate supply, previous studies have also linked low moisture content to high nitrate production. Within discontinuous permafrost regions, the absence of permafrost creates well-drained regions with unsaturated soils whereas the presence of permafrost limits vertical drainage of soil-pore water creating elevated soil moisture content, which likely corresponds to lower nitrate concentrations. We investigate these feedbacks further in the Seward Peninsula, AK, through research supported by the United States Department of Energy Next Generation Ecosystem Experiment (NGEE) - Arctic. Using soil moisture and thaw depth as proxies to determine the extent of permafrost degradation, we identify areas of discontinuous permafrost over a heterogeneous landscape and collect co-located soilwater chemistry samples to highlight the complex relationships that exist between alder patches, soil moisture regimes, the presence of permafrost and available nitrate supply. Understanding the role of nitrogen in degrading permafrost systems, in the context of both vegetation present and soil moisture, is crucial to understand the impacts of a warming climate on biogeochemical cycling in permafrost regions.

The Application of an Emerging Technique for Protein–Protein Interaction Interface Mapping: The Combination of Photo-Initiated Cross-Linking Protein Nanoprobes with Mass Spectrometry

PubMed Central

Ptáčková, Renata; Ječmen, Tomáš; Novák, Petr; Hudeček, Jiří; Stiborová, Marie; Šulc, Miroslav

2014-01-01

Protein–protein interaction was investigated using a protein nanoprobe capable of photo-initiated cross-linking in combination with high-resolution and tandem mass spectrometry. This emerging experimental approach introduces photo-analogs of amino acids within a protein sequence during its recombinant expression, preserves native protein structure and is suitable for mapping the contact between two proteins. The contact surface regions involved in the well-characterized interaction between two molecules of human 14-3-3ζ regulatory protein were used as a model. The employed photo-initiated cross-linking techniques extend the number of residues shown to be within interaction distance in the contact surface of the 14-3-3ζ dimer (Gln8–Met78). The results of this study are in agreement with our previously published data from molecular dynamic calculations based on high-resolution chemical cross-linking data and Hydrogen/Deuterium exchange mass spectrometry. The observed contact is also in accord with the 14-3-3ζ X-ray crystal structure (PDB 3dhr). The results of the present work are relevant to the structural biology of transient interaction in the 14-3-3ζ protein, and demonstrate the ability of the chosen methodology (the combination of photo-initiated cross-linking protein nanoprobes and mass spectrometry analysis) to map the protein-protein interface or regions with a flexible structure. PMID:24865487

Brain structure correlates of emotion-based rash impulsivity

PubMed Central

Muhlert, N.; Lawrence, A.D.

2015-01-01

Negative urgency (the tendency to engage in rash, ill-considered action in response to intense negative emotions), is a personality trait that has been linked to problematic involvement in several risky and impulsive behaviours, and to various forms of disinhibitory psychopathology, but its neurobiological correlates are poorly understood. Here, we explored whether inter-individual variation in levels of trait negative urgency was associated with inter-individual variation in regional grey matter volumes. Using voxel-based morphometry (VBM) in a sample (n = 152) of healthy participants, we found that smaller volumes of the dorsomedial prefrontal cortex and right temporal pole, regions previously linked to emotion appraisal, emotion regulation and emotion-based decision-making, were associated with higher levels of trait negative urgency. When controlling for other impulsivity linked personality traits (sensation seeking, lack of planning/perseverance) and negative emotionality per se (neuroticism), these associations remained, and an additional relationship was found between higher levels of trait negative urgency and smaller volumes of the left ventral striatum. This latter finding mirrors recent VBM findings in an animal model of impulsivity. Our findings offer novel insight into the brain structure correlates of one key source of inter-individual differences in impulsivity. PMID:25957991

Transfer function of radio over fiber multimode fiber optic links considering third-order dispersion.

PubMed

Capmany, J; Gasulla, Ivana

2007-08-20

Although a considerable number of multimode fiber (MMF) links operate in a wavelength region around 850 nm where chromatic dispersion of a given modal group mu is described adequately by the second derivative beta(mu) (2) of the propagation constant beta(mu)(omega), there is also an increasing interest in MMF links transmitting in the second spectral window (@1300nm) where this second derivative vanishes being thus necessary to consider the third derivative beta(mu) (3) in the evaluation of the transfer function of the multimode fiber link. We present in this paper, for the first time to our knowledge, an analytical model for the transfer function of a multimode fiber (MMF) optic link taken into account the impact of third-order dispersion. The model extends the operation of a previously reported one for second-order dispersion. Our results show that the performance of broadband radio over fiber transmission through middle-reach distances can be improved by working at the minimum-dispersion wavelength as long as low-linewidth lasers are employed.

Fluorescent sensor for mercury

DOEpatents

Wang, Zidong [Urbana, IL; Lee, Jung Heon [Evanston, IL; Lu, Yi [Champaign, IL

2011-11-22

The present invention provides a sensor for detecting mercury, comprising: a first polynucleotide, comprising a first region, and a second region, a second polynucleotide, a third polynucleotide, a fluorophore, and a quencher, wherein the third polynucleotide is optionally linked to the second region; the fluorophore is linked to the first polynucleotide and the quencher is linked to the second polynucleotide, or the fluorophore is linked to the second polynucleotide and the quencher is linked to the first polynucleotide; the first region and the second region hybridize to the second polynucleotide; and the second region binds to the third polynucleotide in the presence of Hg.sup.2+ ions.

Aspects of oceanic forcing of drought over Southwest Asia and the United States

NASA Astrophysics Data System (ADS)

Hoell, Andrew

An exceptionally severe drought affected much of the Northern Hemisphere mid-latitudes during 1998 -- 2002, with maxima over Southwest Asia and the United States. Previous research has suggested that the oceans played an important role in the hemispheric drought, with oceanic links to tropical Indo-west Pacific Ocean convection highlighted as important for Southwest Asia, and several additional ocean regions suggested as important for the United States. Here, the regional and hemispheric circulation response to tropical Indo-west Pacific Ocean convection is examined for both Southwest Asia and the United States, and the relative importance of individual sea surface temperature areas are explored for United States precipitation. For Southwest Asia, the regional thermodynamic forcing of precipitation and the Northern Hemisphere circulation are related to the leading pattern of Indian Ocean precipitation and its intraseasonal and interannual contributions. Both intraseasonal and interannual timescales are associated with baroclinic Gill-Matsuno-like circulation responses extending over southern Asia, but the interannual component also has a strong equivalent-barotropic circulation. A stationary barotropic Rossby wave extending over North America is associated with interannual tropical Indo-west Pacific Ocean convection and is supported by barotropic ray tracing. For United States regions, historical SST and precipitation links are identified for 1948 -- 1997, and the importance of these links are assessed during the 1998 -- 2002 drought using a linear regression model. The reconstructed precipitation has good correspondence for the Southwest and Southeast United States, but is not able to reproduce precipitation variability over the Northwest and Central United States, especially Texas.

On Known Unknowns: Fluency and the Neural Mechanisms of Illusory Truth

PubMed Central

Wang, Wei-Chun; Brashier, Nadia M.; Wing, Erik A.; Marsh, Elizabeth J.; Cabeza, Roberto

2016-01-01

The “illusory truth” effect refers to the phenomenon whereby repetition of a statement increases its likelihood of being judged true. This phenomenon has important implications for how we come to believe oft-repeated information that may be misleading or unknown. Behavioral evidence indicates that fluency or the subjective ease experienced while processing a statement underlies this effect. This suggests that illusory truth should be mediated by brain regions previously linked to fluency, such as the perirhinal cortex (PRC). To investigate this possibility, we scanned participants with fMRI while they rated the truth of unknown statements, half of which were presented earlier (i.e., repeated). The only brain region that showed an interaction between repetition and ratings of perceived truth was PRC, where activity increased with truth ratings for repeated, but not for new, statements. This finding supports the hypothesis that illusory truth is mediated by a fluency mechanism and further strengthens the link between PRC and fluency. PMID:26765947

Remote Linkages to Anomalous Winter Atmospheric Ridging over the Northeastern Pacific

NASA Technical Reports Server (NTRS)

Swain, Daniel L.; Singh, Deepti; Horton, Daniel E.; Mankin, Justin S.; Ballard, Tristan C.; Diffenbaugh, Noah S.

2017-01-01

Severe drought in California between 2013 and 2016 has been linked to the multiyear persistence of anomalously high atmospheric pressure over the northeastern Pacific Ocean, which deflected the Pacific storm track northward and suppressed regional precipitation during California's winter 'rainy season.' Multiple hypotheses have emerged regarding why this high pressure ridge near the west coast of North America was so resilient-including unusual sea surface temperature patterns in the Pacific Ocean, reductions in Arctic sea ice, random atmospheric variability, or some combination thereof. Here we explore relationships between previously documented atmospheric conditions over the North Pacific and several potential remote oceanic and cryospheric influences using both observational data and a large ensemble of climate model simulations. Our results suggest that persistent wintertime atmospheric ridging similar to that implicated in California's 2013-2016 drought can at least partially be linked to unusual Pacific sea surface temperatures, and that Pacific Ocean conditions may offer some degree of cool-season foresight in this region despite the presence of substantial internal variability.

Remote Linkages to Anomalous Winter Atmospheric Ridging Over the Northeastern Pacific

NASA Astrophysics Data System (ADS)

Swain, Daniel L.; Singh, Deepti; Horton, Daniel E.; Mankin, Justin S.; Ballard, Tristan C.; Diffenbaugh, Noah S.

2017-11-01

Severe drought in California between 2013 and 2016 has been linked to the multiyear persistence of anomalously high atmospheric pressure over the northeastern Pacific Ocean, which deflected the Pacific storm track northward and suppressed regional precipitation during California's winter "rainy season." Multiple hypotheses have emerged regarding why this high pressure ridge near the west coast of North America was so resilient—including unusual sea surface temperature patterns in the Pacific Ocean, reductions in Arctic sea ice, random atmospheric variability, or some combination thereof. Here we explore relationships between previously documented atmospheric conditions over the North Pacific and several potential remote oceanic and cryospheric influences using both observational data and a large ensemble of climate model simulations. Our results suggest that persistent wintertime atmospheric ridging similar to that implicated in California's 2013-2016 drought can at least partially be linked to unusual Pacific sea surface temperatures and that Pacific Ocean conditions may offer some degree of cool-season foresight in this region despite the presence of substantial internal variability.

The GENCODE exome: sequencing the complete human exome

PubMed Central

Coffey, Alison J; Kokocinski, Felix; Calafato, Maria S; Scott, Carol E; Palta, Priit; Drury, Eleanor; Joyce, Christopher J; LeProust, Emily M; Harrow, Jen; Hunt, Sarah; Lehesjoki, Anna-Elina; Turner, Daniel J; Hubbard, Tim J; Palotie, Aarno

2011-01-01

Sequencing the coding regions, the exome, of the human genome is one of the major current strategies to identify low frequency and rare variants associated with human disease traits. So far, the most widely used commercial exome capture reagents have mainly targeted the consensus coding sequence (CCDS) database. We report the design of an extended set of targets for capturing the complete human exome, based on annotation from the GENCODE consortium. The extended set covers an additional 5594 genes and 10.3 Mb compared with the current CCDS-based sets. The additional regions include potential disease genes previously inaccessible to exome resequencing studies, such as 43 genes linked to ion channel activity and 70 genes linked to protein kinase activity. In total, the new GENCODE exome set developed here covers 47.9 Mb and performed well in sequence capture experiments. In the sample set used in this study, we identified over 5000 SNP variants more in the GENCODE exome target (24%) than in the CCDS-based exome sequencing. PMID:21364695

In situ SIMS U-Pb dating of hydrothermal rutile: reliable age for the Zhesang Carlin-type gold deposit in the golden triangle region, SW China

NASA Astrophysics Data System (ADS)

Pi, Qiaohui; Hu, Ruizhong; Xiong, Bin; Li, Qiuli; Zhong, Richen

2017-12-01

The contiguous region between Guangxi, Guizhou, and Yunnan, commonly referred to as the Golden Triangle region in SW China, hosts many Carlin-type gold deposits. Previously, the ages of the gold mineralization in this region have not been well constrained due to the lack of suitable minerals for radiometric dating. This paper reports the first SIMS U-Pb age of hydrothermal rutile crystals for the Zhesang Carlin-type gold deposit in the region. The hydrothermal U-bearing rutile associated with gold-bearing sulfides in the deposit yields an U-Pb age of 213.6 ± 5.4 Ma, which is within the range of the previously reported arsenopyrite Re-Os isochron ages (204 ± 19 to 235 ± 33 Ma) for three other Carlin-type gold deposits in the region. Our new and more precise rutile U-Pb age confirms that the gold mineralization was contemporaneous with the Triassic W-Sn mineralization and associated granitic magmatism in the surrounding regions. Based on the temporal correlation, we postulate that coeval granitic plutons may be present at greater depths in the Golden Triangle region and that the formation of the Carlin-type gold deposits is probably linked to the coeval granitic magmatism in the region. This study clearly demonstrates that in situ rutile U-Pb dating is a robust tool for the geochronogical study of hydrothermal deposits that contain hydrothermal rutile.

Genome-wide association for milk production and female fertility traits in Canadian dairy Holstein cattle.

PubMed

Nayeri, Shadi; Sargolzaei, Mehdi; Abo-Ismail, Mohammed K; May, Natalie; Miller, Stephen P; Schenkel, Flavio; Moore, Stephen S; Stothard, Paul

2016-06-10

Genome-wide association studies (GWAS) are a powerful tool for detecting genomic regions explaining variation in phenotype. The objectives of the present study were to identify or refine the positions of genomic regions affecting milk production, milk components and fertility traits in Canadian Holstein cattle, and to use these positions to identify genes and pathways that may influence these traits. Several QTL regions were detected for milk production (MILK), fat production (FAT), protein production (PROT) and fat and protein deviation (FATD, PROTD respectively). The identified QTL regions for production traits (including milk production) support previous findings and some overlap with genes with known relevant biological functions identified in earlier studies such as DGAT1 and CPSF1. A significant region on chromosome 21 overlapping with the gene FAM181A and not previous linked to fertility in dairy cattle was identified for the calving to first service interval and days open. A functional enrichment analysis of the GWAS results yielded GO terms consistent with the specific phenotypes tested, for example GO terms GO:0007595 (lactation) and GO:0043627 (response to estrogen) for milk production (MILK), GO:0051057 (positive regulation of small GTPase mediated signal transduction) for fat production (FAT), GO:0040019 (positive regulation of embryonic development) for first service to calving interval (CTFS) and GO:0043268 (positive regulation of potassium ion transport) for days open (DO). In other cases the connection between the enriched GO terms and the traits were less clear, for example GO:0003279 (cardiac septum development) for FAT and GO:0030903 (notochord development) for DO trait. The chromosomal regions and enriched pathways identified in this study confirm several previous findings and highlight new regions and pathways that may contribute to variation in production or fertility traits in dairy cattle.

Neurotensin inversely modulates maternal aggression

PubMed Central

Gammie, Stephen C.; D’Anna, Kimberly L.; Gerstein, Hilary; Stevenson, Sharon A.

2008-01-01

Neurotensin (NT) is a versatile neuropeptide involved in analgesia, hypothermia, and schizophrenia. Although NT is released from and acts upon brain regions involved in social behaviors, it has not been linked to a social behavior. We previously selected mice for high maternal aggression (maternal defense), an important social behavior that protects offspring, and found significantly lower NT expression in the CNS of highly protective females. Our current study directly tested NT’s role in maternal defense. Intracerebroventricular (icv) injections of NT significantly impaired defense in terms of time aggressive and number of attacks at all doses tested (0.05, 0.1, 1.0, and 3.0 μg). Other maternal behaviors, including pup retrieval, were unaltered following NT injections (0.05 μg) relative to vehicle, suggesting specificity of NT action on defense. Further, icv injections of the NT receptor 1 (NT1) antagonist, SR 48692 (30 μg), significantly elevated maternal aggression in terms of time aggressive and attack number. To understand where NT may regulate aggression, we examined Fos following injection of either 0.1 μg NT or vehicle. 13 of 26 brain regions examined exhibited significant Fos increases with NT, including regions expressing NT1 and previously implicated in maternal aggression, such as lateral septum, bed nucleus of stria terminalis, paraventricular nucleus, and central amygdala. Together, our results indicate that NT inversely regulates maternal aggression and provide the first direct evidence that lowering of NT signaling can be a mechanism for maternal aggression. To our knowledge, this is the first study to directly link NT to a social behavior. PMID:19118604

Creative Activities in Music--A Genome-Wide Linkage Analysis.

PubMed

Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

2016-01-01

Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose a common genetic background for music-related creative behaviour and musical abilities at chromosome 4.

Active superconducting devices formed of thin films

DOEpatents

Martens, Jon S.; Beyer, James B.; Nordman, James E.; Hohenwarter, Gert K. G.

1991-05-28

Active superconducting devices are formed of thin films of superconductor which include a main conduction channel which has an active weak link region. The weak link region is composed of an array of links of thin film superconductor spaced from one another by voids and selected in size and thickness such that magnetic flux can propagate across the weak link region when it is superconducting. Magnetic flux applied to the weak link region will propagate across the array of links causing localized loss of superconductivity in the links and changing the effective resistance across the links. The magnetic flux can be applied from a control line formed of a superconducting film deposited coplanar with the main conduction channel and weak link region on a substrate. The devices can be formed of any type to superconductor but are particularly well suited to the high temperature superconductors since the devices can be entirely formed from coplanar films with no overlying regions. The devices can be utilized for a variety of electrical components, including switching circuits, amplifiers, oscillators and modulators, and are well suited to microwave frequency applications.

Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity.

PubMed

Smit, Dirk J A; Wright, Margaret J; Meyers, Jacquelyn L; Martin, Nicholas G; Ho, Yvonne Y W; Malone, Stephen M; Zhang, Jian; Burwell, Scott J; Chorlian, David B; de Geus, Eco J C; Denys, Damiaan; Hansell, Narelle K; Hottenga, Jouke-Jan; McGue, Matt; van Beijsterveldt, Catharina E M; Jahanshad, Neda; Thompson, Paul M; Whelan, Christopher D; Medland, Sarah E; Porjesz, Bernice; Lacono, William G; Boomsma, Dorret I

2018-06-26

Oscillatory activity is crucial for information processing in the brain, and has a long history as a biomarker for psychopathology. Variation in oscillatory activity is highly heritable, but current understanding of specific genetic influences remains limited. We performed the largest genome-wide association study to date of oscillatory power during eyes-closed resting electroencephalogram (EEG) across a range of frequencies (delta 1-3.75 Hz, theta 4-7.75 Hz, alpha 8-12.75 Hz, and beta 13-30 Hz) in 8,425 subjects. Additionally, we performed KGG positional gene-based analysis and brain-expression analyses. GABRA2-a known genetic marker for alcohol use disorder and epilepsy-significantly affected beta power, consistent with the known relation between GABA A interneuron activity and beta oscillations. Tissue-specific SNP-based imputation of gene-expression levels based on the GTEx database revealed that hippocampal GABRA2 expression may mediate this effect. Twenty-four genes at 3p21.1 were significant for alpha power (FDR q < .05). SNPs in this region were linked to expression of GLYCTK in hippocampal tissue, and GNL3 and ITIH4 in the frontal cortex-genes that were previously implicated in schizophrenia and bipolar disorder. In sum, we identified several novel genetic variants associated with oscillatory brain activity; furthermore, we replicated and advanced understanding of previously known genes associated with psychopathology (i.e., schizophrenia and alcohol use disorders). Importantly, these psychopathological liability genes affect brain functioning, linking the genes' expression to specific cortical/subcortical brain regions. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Links between phytoplankton dynamics and shell growth of Arctica islandica on the Faroe Shelf

NASA Astrophysics Data System (ADS)

Bonitz, Fabian Georg Wulf; Andersson, Carin; Trofimova, Tamara; Hátún, Hjálmar

2018-03-01

The phytoplankton dynamics on the Faroe Shelf are strongly connected to higher trophic levels, and their inter-annual variability has great importance for many organisms, including the principal fish stocks. Hence, information on the marked phytoplankton variability is scientifically and economically valuable. We show here that the shell growth variability in Arctica islandica shells has the potential to identify periods of increased and decreased phytoplankton concentrations on the Faroe Shelf and in the wider Faroese region in previous centuries. The growth of A. islandica has often been linked to changes in phytoplankton concentrations, i.e., food availability. By cross-matching life-collected and sub-fossil A. islandica shells from two separate locations on the Faroe Shelf, we have built a master chronology, which reaches back to the 17th century. This master chronology correlates well with a Primary Production index for the Faroe Shelf (r = 0.65; p < 0.01) and average April-June chlorophyll a concentrations in the central part of the shelf (r = 0.74; p < 0.01). A link is also identified between the shell growth and phytoplankton concentrations over the wider Faroese Channel Region, as represented in the Continuous Plankton Recorder surveys, especially for the months June-September (r = 0.39; p < 0.01). In addition, an inverse relationship is observed between the master chronology and on-shelf water temperatures from June-September (r = - 0.29; p < 0.01), which is likely associated with a previously reported inverse relationship between temperatures and the on-shelf primary production. An analysis of the δ18O in the shells shows that the main growing season of the shells presumably occurs during the spring and summer months, which concurs with the main spring bloom.

Alcohol use among Hispanic college students along the US/Mexico border.

PubMed

Montoya, Jared A; Wittenburg, David; Martinez, Vanessa

2016-11-01

The trend of alcohol use among college students has been shown to vary by ethnicity and has been linked to acculturation among Hispanics. Consistent findings indicate that males consume alcohol more frequently and in greater quantities compared to females. This study investigated the drinking habits of Hispanic college students living in the border region of South Texas. The study evaluated the influence of acculturation on alcohol consumption among Hispanic males and females. Two hundred and ninety-six Hispanic students participated in this study. The participants reported their drinking behaviors over the past 30 days and completed a measure of acculturation. Fifty-nine percent of the participants reported consuming alcohol in the past 30 days with more males than females reporting alcohol consumption. Logistic regression analysis indicated that age and gender, and not acculturation or enculturation, predicted drinking in the last 30 days. Among drinkers, the regression analyses indicated that gender and lower levels of Anglo orientation were linked to increased alcohol consumption, suggesting that Hispanics who were less oriented toward the Anglo culture consumed more alcohol than those more oriented toward the Anglo culture. Among drinkers, males and females did not differ in frequency or binge drinking, but males consumed more alcohol than females. Previous research indicates that greater acculturation is linked to greater consumption of alcohol; however, we found it to be associated with less consumption. The findings regarding gender represent some consistencies with previous research but there are some inconsistencies as well. These results suggest that less acculturated Hispanic male college students residing in the border region may be at a higher risk of alcohol abuse than Hispanic female students and more acculturated male students.

A Review of Aeromagnetic Anomalies in the Sawatch Range, Central Colorado

USGS Publications Warehouse

Bankey, Viki

2010-01-01

This report contains digital data and image files of aeromagnetic anomalies in the Sawatch Range of central Colorado. The primary product is a data layer of polygons with linked data records that summarize previous interpretations of aeromagnetic anomalies in this region. None of these data files and images are new; rather, they are presented in updated formats that are intended to be used as input to geographic information systems, standard graphics software, or map-plotting packages.

Aerosols cause intraseasonal short-term suppression of Indian monsoon rainfall.

PubMed

Dave, Prashant; Bhushan, Mani; Venkataraman, Chandra

2017-12-11

Aerosol abundance over South Asia during the summer monsoon season, includes dust and sea-salt, as well as, anthropogenic pollution particles. Using observations during 2000-2009, here we uncover repeated short-term rainfall suppression caused by coincident aerosols, acting through atmospheric stabilization, reduction in convection and increased moisture divergence, leading to the aggravation of monsoon break conditions. In high aerosol-low rainfall regions extending across India, both in deficient and normal monsoon years, enhancements in aerosols levels, estimated as aerosol optical depth and absorbing aerosol index, acted to suppress daily rainfall anomaly, several times in a season, with lags of a few days. A higher frequency of prolonged rainfall breaks, longer than seven days, occurred in these regions. Previous studies point to monsoon rainfall weakening linked to an asymmetric inter-hemispheric energy balance change attributed to aerosols, and short-term rainfall enhancement from radiative effects of aerosols. In contrast, this study uncovers intraseasonal short-term rainfall suppression, from coincident aerosol forcing over the monsoon region, leading to aggravation of monsoon break spells. Prolonged and intense breaks in the monsoon in India are associated with rainfall deficits, which have been linked to reduced food grain production in the latter half of the twentieth century.

Hot air and Congress

NASA Astrophysics Data System (ADS)

Balco, Greg

Bruce Doe's article, “A Potomac Perspective on the Growing Global Greenhouse” (Eos, January 5, 1999), contained the provocative suggestion that temperature in the Washington, D.C., region might be causally linked to congressional attention to the topics of greenhouse warming and global climate change, as well as federal funding for research into these topics. This assertion is particularly interesting in light of recent archaeological and paleoclimatic studies that suggest a link between large-scale regional climate change and major events in ancient civilizations. For example, the collapses of the Akkadian Empire, the Minoan civilization in Crete, the Old Kingdom of Egypt, and the Mayan civilization in Mexico appear to coincide with major regional climate changes, suggesting that climatic factors might be more important than previously proposed sociopolitical ones in explaining the history of these cultures (see, for example, K. Wright's article, “Empires in the Dust,” in Discover, March 1998).If a connection between climate and politics could be demonstrated in our own society, it might shed light on these past events. However, Doe did not further explore this possibility, presumably because of the lack of an appropriate quantitative measurement of legislative activity that could be compared to the temperature record.

Structural variants in genes associated with human Williams-Beuren syndrome underlie stereotypical hypersociability in domestic dogs.

PubMed

vonHoldt, Bridgett M; Shuldiner, Emily; Koch, Ilana Janowitz; Kartzinel, Rebecca Y; Hogan, Andrew; Brubaker, Lauren; Wanser, Shelby; Stahler, Daniel; Wynne, Clive D L; Ostrander, Elaine A; Sinsheimer, Janet S; Udell, Monique A R

2017-07-01

Although considerable progress has been made in understanding the genetic basis of morphologic traits (for example, body size and coat color) in dogs and wolves, the genetic basis of their behavioral divergence is poorly understood. An integrative approach using both behavioral and genetic data is required to understand the molecular underpinnings of the various behavioral characteristics associated with domestication. We analyze a 5-Mb genomic region on chromosome 6 previously found to be under positive selection in domestic dog breeds. Deletion of this region in humans is linked to Williams-Beuren syndrome (WBS), a multisystem congenital disorder characterized by hypersocial behavior. We associate quantitative data on behavioral phenotypes symptomatic of WBS in humans with structural changes in the WBS locus in dogs. We find that hypersociability, a central feature of WBS, is also a core element of domestication that distinguishes dogs from wolves. We provide evidence that structural variants in GTF2I and GTF2IRD1 , genes previously implicated in the behavioral phenotype of patients with WBS and contained within the WBS locus, contribute to extreme sociability in dogs. This finding suggests that there are commonalities in the genetic architecture of WBS and canine tameness and that directional selection may have targeted a unique set of linked behavioral genes of large phenotypic effect, allowing for rapid behavioral divergence of dogs and wolves, facilitating coexistence with humans.

Transient coupling relationships of the Holocene Australian monsoon

NASA Astrophysics Data System (ADS)

McRobie, F. H.; Stemler, T.; Wyrwoll, K.-H.

2015-08-01

The northwest Australian summer monsoon owes a notable degree of its interannual variability to interactions with other regional monsoon systems. Therefore, changes in the nature of these relationships may contribute to variability in monsoon strength over longer time scales. Previous attempts to evaluate how proxy records from the Indonesian-Australian monsoon region correspond to other records from the Indian and East Asian monsoon regions, as well as to El Niño-related proxy records, have been qualitative, relying on 'curve-fitting' methods. Here, we seek a quantitative approach for identifying coupling relationships between paleoclimate proxy records, employing statistical techniques to compute the interdependence of two paleoclimate time series. We verify the use of complex networks to identify coupling relationships between modern climate indices. This method is then extended to a set of paleoclimate proxy records from the Asian, Australasian and South American regions spanning the past 9000 years. The resulting networks demonstrate the existence of coupling relationships between regional monsoon systems on millennial time scales, but also highlight the transient nature of teleconnections during this period. In the context of the northwest Australian summer monsoon, we recognise a shift in coupling relationships from strong interhemispheric links with East Asian and ITCZ-related proxy records in the mid-Holocene to significantly weaker coupling in the later Holocene. Although the identified links cannot explain the underlying physical processes leading to coupling between regional monsoon systems, this method provides a step towards understanding the role that changes in teleconnections play in millennial-to orbital-scale climate variability.

Electrophoretic variation in low molecular weight lens crystallins from inbred strains of rats.

PubMed

Donner, M E; Skow, L C; Kunz, H W; Gill, T J

1985-10-01

Analysis of rat lens soluble proteins by analytical isoelectric focusing detected two inherited electrophoretic differences in low molecular weight (LM) crystallins from inbred strains of rats (Rattus norvegicus). The polymorphic lens crystallins were shown to be similar to a genetically variant LM crystallin, LEN-1, previously described in mice (Mus musculus) and encoded on chromosome 1, at a locus linked to Pep-3 (dipeptidase). Linkage analysis demonstrated that the rat crystallin locus was loosely linked to Pep-3 at a recombination distance of 38 +/- 4.5 U. These data suggest the conservation of a large chromosomal region during the evolution of Rodentia and support the hypothesis that the gamma-crystallins are evolving more rapidly than alpha- or beta-crystallins.

Identification of extreme precipitation threat across midlatitude regions based on short-wave circulations

NASA Astrophysics Data System (ADS)

Wang, Shih-Yu; Davies, Robert E.; Gillies, Robert R.

2013-10-01

most severe thunderstorms, producing extreme precipitation, occur over subtropical and midlatitude regions. Atmospheric conditions conducive to organized, intense thunderstorms commonly involve the coupling of a low-level jet (LLJ) with a synoptic short wave. The midlatitude synoptic activity is frequently modulated by the circumglobal teleconnection (CGT), in which meridional gradients of the jet stream act as a guide for short Rossby waves. Previous research has linked extreme precipitation events with either the CGT or the LLJ but has not linked the two circulation features together. In this study, a circulation-based index was developed by combining (a) the degree of the CGT and LLJ coupling, (b) the extent to which this CGT-LLJ coupling connects to regional precipitation and (c) the spatial correspondence with the CGT (short wave) trending pattern over the recent 32 years (1979-2010). Four modern-era global reanalyses, in conjunction with four gridded precipitation data sets, were utilized to minimize spurious trends. The results are suggestive of a link between the CGT/LLJ trends and several recent extreme precipitation events, including those leading to the 2008 Midwest flood in U.S., the 2011 tornado outbreaks in southeastern U.S., the 2010 Queensland flood in northeastern Australia, and to the opposite side the 2012 central U.S. drought. Moreover, an analysis of three Coupled Model Intercomparison Project Phase 5 models from the historical experiments points to the role of greenhouse gases in forming the CGT trends during the warm season.

Memory retrieval and the parietal cortex: a review of evidence from a dual-process perspective.

PubMed

Vilberg, Kaia L; Rugg, Michael D

2008-01-01

Although regions of the parietal cortex have been consistently implicated in episodic memory retrieval, the functional roles of these regions remain poorly understood. The present review presents a meta-analysis of findings from event-related fMRI studies reporting the loci of retrieval effects associated with familiarity- and recollection-related recognition judgments. The results of this analysis support previous suggestions that retrieval-related activity in lateral parietal cortex dissociates between superior regions, where activity likely reflects the task relevance of different classes of recognition test items, and more inferior regions where retrieval-related activity appears closely linked to successful recollection. It is proposed that inferior lateral parietal cortex forms part of a neural network supporting the 'episodic buffer' [Baddeley, A. D. (2000). The episodic buffer: A new component of working memory? Trends in Cognitive Sciences, 4, 417-423].

Air pollution or global warming: Attribution of extreme precipitation changes in eastern China—Comments on "Trends of extreme precipitation in Eastern China and their possible causes"

NASA Astrophysics Data System (ADS)

Wang, Yuan

2015-10-01

The recent study "Trends of Extreme Precipitation in Eastern China and Their Possible Causes" attributed the observed decrease/increase of light/heavy precipitation in eastern China to global warming rather than the regional aerosol effects. However, there exist compelling evidence from previous long-term observations and numerical modeling studies, suggesting that anthropogenic pollution is closely linked to the recent changes in precipitation intensity because of considerably modulated cloud physical properties by aerosols in eastern China. Clearly, a quantitative assessment of the aerosol and greenhouse effects on the regional scale is required to identify the primary cause for the extreme precipitation changes.

Endogenous opioidergic dysregulation of pain in fibromyalgia: a PET and fMRI study.

PubMed

Schrepf, Andrew; Harper, Daniel E; Harte, Steven E; Wang, Heng; Ichesco, Eric; Hampson, Johnson P; Zubieta, Jon-Kar; Clauw, Daniel J; Harris, Richard E

2016-10-01

Endogenous opioid system dysfunction potentially contributes to chronic pain in fibromyalgia (FM), but it is unknown if this dysfunction is related to established neurobiological markers of hyperalgesia. We previously reported that µ-opioid receptor (MOR) availability was reduced in patients with FM as compared with healthy controls in several pain-processing brain regions. In the present study, we compared pain-evoked functional magnetic resonance imaging with endogenous MOR binding and clinical pain ratings in female opioid-naive patients with FM (n = 18) using whole-brain analyses and regions of interest from our previous research. Within antinociceptive brain regions, including the dorsolateral prefrontal cortex (r = 0.81, P < 0.001) and multiple regions of the anterior cingulate cortex (all r > 0.67; all P < 0.02), reduced MOR availability was associated with decreased pain-evoked neural activity. Additionally, reduced MOR availability was associated with lower brain activation in the nucleus accumbens (r = 0.47, P = 0.050). In many of these regions, pain-evoked activity and MOR binding potential were also associated with lower clinical affective pain ratings. These findings are the first to link endogenous opioid system tone to regional pain-evoked brain activity in a clinical pain population. Our data suggest that dysregulation of the endogenous opioid system in FM could lead to less excitation in antinociceptive brain regions by incoming noxious stimulation, resulting in the hyperalgesia and allodynia commonly observed in this population. We propose a conceptual model of affective pain dysregulation in FM.

fMRI evidence of equivalent neural suppression by repetition and prior knowledge.

PubMed

Poppenk, J; McIntosh, A R; Moscovitch, M

2016-09-01

Stimulus repetition speeds behavioral responding (behavioral priming) and is accompanied by suppressed neural responses (repetition suppression; RS) that have been observed up to three days after initial exposure. While some proposals have suggested the two phenomena are linked, behavioral priming has been observed many years after initial exposure, whereas RS is widely considered a transitory phenomenon. This raises the question: what is the true upper limit of RS persistence? To answer this question, we scanned healthy, English-native adults with fMRI as they viewed novel (Asian) proverbs, recently repeated (Asian) proverbs, and previously known (English) proverbs that were matched on various dimensions. We then estimated RS by comparing repeated or previously known proverbs against novel ones. Multivariate analyses linked previously known and repeated proverbs with statistically indistinguishable RS in a broad visual-linguistic network. In each suppressed region, prior knowledge and repetition also induced a common shift in functional connectivity, further underscoring the similarity of the RS phenomenon induced by these conditions. By contrast, activated regions readily distinguished prior knowledge and repetition conditions in a manner consistent with engagement of semantic and episodic memory systems, respectively. Our results illustrate that regardless of whether RS is understood in terms of its magnitude, spatial extent or functional connectivity profile, typical RS effects can be elicited even under conditions where recently triggered biological processes or episodic memory are unlikely to play a prominent role. These results provide important new evidence that RS (of the kind observed after an interval of at least several minutes) reflects the facilitation of perceptual and comprehension processes by any type of information retrieved from long-term memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aberrant methylation of miR-34b is associated with long-term shiftwork: a potential mechanism for increased breast cancer susceptibility.

PubMed

Liu, Ran; Jacobs, Daniel I; Hansen, Johnni; Fu, Alan; Stevens, Richard G; Zhu, Yong

2015-02-01

Although the evidence linking exposure to light at night (LAN) and breast cancer risk continues to accumulate, the molecular mechanisms driving this association remain to be fully elucidated. We have previously suggested that long-term exposure to LAN through shiftwork may result in dysregulated patterns of methylation genome-wide. In this study, we investigate the link between miR-34b, a miRNA suggested to be an important tumor suppressor, and shiftwork-related breast cancer. Methylation states in the miR-34b promoter region were previously compared between 10 female long-term shiftworkers and 10 folate intake- and age-matched female dayworkers participating in the Danish "Diet, Cancer and Health" prospective cohort study. In order to further explore the functional role of miR-34b in breast tumorigenesis, a genome-wide expression microarray was carried out in miR-34b-overexpressed MCF-7 breast cancer cells and the identified transcripts were further analyzed for network and functional interrelatedness using Ingenuity Pathway Analysis software. We observed a 49.1 % increase in miR-34b promoter methylation among shiftworkers at a CpG site in this region (p = 0.016). Transfection of the miR-34b mimic in an MCF-7 breast cancer cell line induced differential expression of 230 transcripts that are involved in the interferon-mediated antiviral response as well as apoptotic and antiproliferative gene networks. Together, our results suggest that long-term shiftwork may increase the risk of breast cancer via methylation-based suppression of miR-34b and a consequent reduction in immunomediated anti-tumor capacity and support our previous findings that LAN may induce epigenetic alteration of cancer-relevant microRNAs.

ALS-linked mutant SOD1 proteins promote Aβ aggregates in ALS through direct interaction with Aβ.

PubMed

Jang, Ja-Young; Cho, Hyungmin; Park, Hye-Yoon; Rhim, Hyangshuk; Kang, Seongman

2017-11-04

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of motor neurons. Aggregation of ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) is a hallmark of a subset of familial ALS (fALS). Recently, intracellular amyloid-β (Aβ) is detected in motor neurons of both sporadic and familial ALS. We have previously shown that intracellular Aβ specifically interacts with G93A, an ALS-linked SOD1 mutant. However, little is known about the pathological and biological effect of this interaction in neurons. In this study, we have demonstrated that the Aβ-binding region is exposed on the SOD1 surface through the conformational changes due to misfolding of SOD1. Interestingly, we found that the intracellular aggregation of Aβ is enhanced through the direct interaction of Aβ with the Aβ-binding region exposed to misfolded SOD1. Ultimately, increased Aβ aggregation by this interaction promotes neuronal cell death. Consistent with this result, Aβ aggregates was three-fold higher in the brains of G93A transgenic mice than those of non Tg. Our study provides the first direct evidence that Aβ, an AD-linked factor, is associated to the pathogenesis of ALS and provides molecular clues to understand common aggregation mechanisms in the pathogenesis of neurodegenerative diseases. Furthermore, it will provide new insights into the development of therapeutic approaches for ALS. Copyright © 2017 Elsevier Inc. All rights reserved.

When three is not some: on the pragmatics of numerals.

PubMed

Shetreet, Einat; Chierchia, Gennaro; Gaab, Nadine

2014-04-01

Both numerals and quantifiers (like some) have more than one possible interpretation (i.e., weak and strong interpretations). Some studies have found similar behavior for numerals and quantifiers, whereas others have shown critical differences. It is, therefore, debated whether they are processed in the same way. A previous fMRI investigation showed that the left inferior frontal gyrus is linked to the computation of the strong interpretation of quantifiers (derived by a scalar implicature) and that the left middle frontal gyrus and the medial frontal gyrus are linked to processing the mismatch between the strong interpretation of quantifiers and the context in which they are presented. In the current study, we attempted to characterize the similarities and differences between numbers and quantifiers by examining brain activation patterns related to the processing of numerals in these brain regions. When numbers were presented in a mismatch context (i.e., where their strong interpretation did not match the context), they elicited brain activations similar to those previously observed with quantifiers in the same context type. Conversely, in a match context (i.e., where both interpretations of the scalar item matched the context), numbers elicited a different activation pattern than the one observed with quantifiers: Left inferior frontal gyrus activations in response to the match condition showed decrease for numbers (but not for quantifiers). Our results support previous findings suggesting that, although they share some features, numbers and quantifiers are processed differently. We discuss our results in light of various theoretical approaches linked to the representation of numerals.

Segregating polymorphisms of FOXP2 are associated with measures of inner speech, speech fluency and strength of handedness in a healthy population.

PubMed

Crespi, Bernard; Read, Silven; Hurd, Peter

2017-10-01

We genotyped a healthy population for three haplotype-tagging FOXP2 SNPs, and tested for associations of these SNPs with strength of handedness and questionnaire-based metrics of inner speech characteristics (ISP) and speech fluency (FLU), as derived from the Schizotypal Personality Questionnaire-BR. Levels of mixed-handedness were positively correlated with ISP and FLU, supporting prior work on these two domains. Genotype for rs7799109, a SNP previously linked with lateralization of left frontal regions underlying language, was associated with degree of mixed handedness and with scores for ISP and FLU phenotypes. Genotype of rs1456031, which has previously been linked with auditory hallucinations, was also associated with ISP phenotypes. These results provide evidence that FOXP2 SNPs influence aspects of human inner speech and fluency that are related to lateralized phenotypes, and suggest that the evolution of human language, as mediated by the adaptive evolution of FOXP2, involved features of inner speech. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigation of low energy space plasma

NASA Technical Reports Server (NTRS)

Comfort, R. H.; Horwitz, J. L.

1986-01-01

A statistical study of 1982 data for occurrences of equatorially trapped plasma has been extended. The previous survey, which utilized only the MSFC summary fiche, has been supplemented with the GSFC summary fiche, which has had the effect of substantially improving the late 1982 coverage. It was found that in the post midnight region (1 - 3 LT), the trapped plasma is limited to + or - 5 degrees magnetic latitude, while in the early afternoon (13-15 LT), latitude ranges as high as + or 30 degrees are found. This survey has provided a link to earlier ATS-6 and ISEE studies of pancake distributions. Although the most energetic, and most anisotopic plasmas are trapped within a few degrees of the equator, the results of these equatorial interactions extend substantially along the magnetic field line in the afternoon and dusk region and these high latitude extensions were previously studied by the Huntsville group. Results of this study were incorporated into a revision of the equatorial ion paper, which has been resubmitted and accepted for publication.

Real time mitigation of atmospheric turbulence in long distance imaging using the lucky region fusion algorithm with FPGA and GPU hardware acceleration

NASA Astrophysics Data System (ADS)

Jackson, Christopher Robert

"Lucky-region" fusion (LRF) is a synthetic imaging technique that has proven successful in enhancing the quality of images distorted by atmospheric turbulence. The LRF algorithm selects sharp regions of an image obtained from a series of short exposure frames, and fuses the sharp regions into a final, improved image. In previous research, the LRF algorithm had been implemented on a PC using the C programming language. However, the PC did not have sufficient sequential processing power to handle real-time extraction, processing and reduction required when the LRF algorithm was applied to real-time video from fast, high-resolution image sensors. This thesis describes two hardware implementations of the LRF algorithm to achieve real-time image processing. The first was created with a VIRTEX-7 field programmable gate array (FPGA). The other developed using the graphics processing unit (GPU) of a NVIDIA GeForce GTX 690 video card. The novelty in the FPGA approach is the creation of a "black box" LRF video processing system with a general camera link input, a user controller interface, and a camera link video output. We also describe a custom hardware simulation environment we have built to test the FPGA LRF implementation. The advantage of the GPU approach is significantly improved development time, integration of image stabilization into the system, and comparable atmospheric turbulence mitigation.

Patient Dashboard: the use of a colour-coded computerised clinical reminder in Whanganui regional general practices.

PubMed

McMenamin, John; Nicholson, Rick; Leech, Ken

2011-12-01

Clinical reminders have been shown to help general practice achieve an increase in some preventive care items, especially if they identify a patient's eligibility for the target item, prompt clinicians at the right time, provide a fast link to management tools and facilitate clinical recording. WRPHO has introduced the Patient Dashboard clinical reminder and monitored its impact on health targets. This paper reports the impact of a computerised colour-coded clinical reminder on achieving agreed health targets in Whanganui regional practices. Patient Dashboard was developed from previous versions in Auckland and Northland and provided to Whanganui regional practices with Primary Health Organisation (PHO) support. The Dashboard was linked with existing and new clinical management tools which automatically updated clinical records. Data from practices was pooled by Whanganui Regional Primary Health Organisation and target achievement rates reported over 15 months. Over the initial 15 months of Patient Dashboard use, recording of smoking status increased from 74% to 82% and of alcohol use from 15% to 47%. Screening for diabetes increased from 62% to 74%, cardiovascular risk assessment from 20% to 43%, cervical screening from 71% to 79%, and breast screening from 60% to 80%. Patient Dashboard was associated with increased performance indicators both for those targets which were part of a PHO programme and for targets without additional support.

Delineation by fluorescence in situ hybridization of a single hemizygous chromosomal region associated with aposporous embryo sac formation in Pennisetum squamulatum and Cenchrus ciliaris.

PubMed Central

Goel, Shailendra; Chen, Zhenbang; Conner, Joann A; Akiyama, Yukio; Hanna, Wayne W; Ozias-Akins, Peggy

2003-01-01

Apomixis is a means of asexual reproduction by which plants produce embryos without meiosis and fertilization; thus the embryo is of clonal, maternal origin. We previously reported molecular markers showing no recombination with the trait for aposporous embryo sac development in Pennisetum squamulatum and Cenchrus ciliaris, and the collective single-dose alleles defined an apospory-specific genomic region (ASGR). Fluorescence in situ hybridization (FISH) was used to confirm that the ASGR is a hemizygous genomic region and to determine its chromosomal position with respect to rDNA loci and centromere repeats. We also documented chromosome transmission from P. squamulatum in several backcrosses (BCs) with P. glaucum using genomic in situ hybridization (GISH). One to three complete P. squamulatum chromosomes were detected in BC(6), but only one of the three hybridized with the ASGR-linked markers. In P. squamulatum and in all BCs examined, the apospory-linked markers were located in the distal region of the short arm of a single chromosome. All alien chromosomes behaved as univalents during meiosis and segregated randomly in BC(3) and later BC generations, but presence of the ASGR-carrier chromosome alone was sufficient to confer apospory. FISH results support our hypotheses that hemizygosity, proximity to centromeric sequences, and chromosome structure may all play a role in low recombination in the ASGR. PMID:12663545

Salicylate-Induced Auditory Perceptual Disorders and Plastic Changes in Nonclassical Auditory Centers in Rats

PubMed Central

Chen, Guang-Di; Radziwon, Kelly E.; Manohar, Senthilvelan

2014-01-01

Previous studies have shown that sodium salicylate (SS) activates not only central auditory structures, but also nonauditory regions associated with emotion and memory. To identify electrophysiological changes in the nonauditory regions, we recorded sound-evoked local field potentials and multiunit discharges from the striatum, amygdala, hippocampus, and cingulate cortex after SS-treatment. The SS-treatment produced behavioral evidence of tinnitus and hyperacusis. Physiologically, the treatment significantly enhanced sound-evoked neural activity in the striatum, amygdala, and hippocampus, but not in the cingulate. The enhanced sound evoked response could be linked to the hyperacusis-like behavior. Further analysis showed that the enhancement of sound-evoked activity occurred predominantly at the midfrequencies, likely reflecting shifts of neurons towards the midfrequency range after SS-treatment as observed in our previous studies in the auditory cortex and amygdala. The increased number of midfrequency neurons would lead to a relative higher number of total spontaneous discharges in the midfrequency region, even though the mean discharge rate of each neuron may not increase. The tonotopical overactivity in the midfrequency region in quiet may potentially lead to tonal sensation of midfrequency (the tinnitus). The neural changes in the amygdala and hippocampus may also contribute to the negative effect that patients associate with their tinnitus. PMID:24891959

Parietal cortex mediates perceptual Gestalt grouping independent of stimulus size.

PubMed

Grassi, Pablo R; Zaretskaya, Natalia; Bartels, Andreas

2016-06-01

The integration of local moving elements into a unified gestalt percept has previously been linked to the posterior parietal cortex. There are two possible interpretations for the lack of involvement of other occipital regions. The first is that parietal cortex is indeed uniquely functionally specialized to perform grouping. Another possibility is that other visual regions can perform grouping as well, but that the large spatial separation of the local elements used previously exceeded their neurons' receptive field (RF) sizes, preventing their involvement. In this study we distinguished between these two alternatives. We measured whole-brain activity using fMRI in response to a bistable motion illusion that induced mutually exclusive percepts of either an illusory global Gestalt or of local elements. The stimulus was presented in two sizes, a large version known to activate IPS only, and a version sufficiently small to fit into the RFs of mid-level dorsal regions such as V5/MT. We found that none of the separately localized motion regions apart from parietal cortex showed a preference for global Gestalt perception, even for the smaller version of the stimulus. This outcome suggests that grouping-by-motion is mediated by a specialized size-invariant mechanism with parietal cortex as its anatomical substrate. Copyright © 2016 Elsevier Inc. All rights reserved.

Mutational analysis of the Wolfram syndrome gene in two families with chromosome 4p-linked bipolar affective disorder.

PubMed

Evans, K L; Lawson, D; Meitinger, T; Blackwood, D H; Porteous, D J

2000-04-03

Bipolar affective disorder (BPAD) is a complex disease with a significant genetic component. Heterozygous carriers of Wolfram syndrome (WFS) are at increased risk of psychiatric illness. A gene for WFS (WFS1) has recently been cloned and mapped to chromosome 4p, in the general region we previously reported as showing linkage to BPAD. Here we present sequence analysis of the WFS1 coding sequence in five affected individuals from two chromosome 4p-linked families. This resulted in the identification of six polymorphisms, two of which are predicted to change the amino acid sequence of the WFS1 protein, however none of the changes segregated with disease status. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:158-160, 2000. Copyright 2000 Wiley-Liss, Inc.

Mood-dependent integration in discourse comprehension: happy and sad moods affect consistency processing via different brain networks.

PubMed

Egidi, Giovanna; Caramazza, Alfonso

2014-12-01

According to recent research on language comprehension, the semantic features of a text are not the only determinants of whether incoming information is understood as consistent. Listeners' pre-existing affective states play a crucial role as well. The current fMRI experiment examines the effects of happy and sad moods during comprehension of consistent and inconsistent story endings, focusing on brain regions previously linked to two integration processes: inconsistency detection, evident in stronger responses to inconsistent endings, and fluent processing (accumulation), evident in stronger responses to consistent endings. The analysis evaluated whether differences in the BOLD response for consistent and inconsistent story endings correlated with self-reported mood scores after a mood induction procedure. Mood strongly affected regions previously associated with inconsistency detection. Happy mood increased sensitivity to inconsistency in regions specific for inconsistency detection (e.g., left IFG, left STS), whereas sad mood increased sensitivity to inconsistency in regions less specific for language processing (e.g., right med FG, right SFG). Mood affected more weakly regions involved in accumulation of information. These results show that mood can influence activity in areas mediating well-defined language processes, and highlight that integration is the result of context-dependent mechanisms. The finding that language comprehension can involve different networks depending on people's mood highlights the brain's ability to reorganize its functions. Copyright © 2014 Elsevier Inc. All rights reserved.

Seismo-Tectonics of the 2014 Chiang Rai, Thailand, Earthquake Sequence

NASA Astrophysics Data System (ADS)

Furlong, K. P.; Pananont, P.; Herman, M. W.; Waldhauser, F.; Pornsopin, P.; Warnitchai, P.; Kosuwan, S.

2016-12-01

On 5 May 2014, a Mw 6.2 strike-slip earthquake struck in the Mae Lao region of Chiang Rai province in Thailand. This earthquake occurred in a region of known faults, but identified as relatively low earthquake hazard, and caused substantial damage and injuries. Detailed field reconnaissance and deployment of a dense, temporary seismometer network allowed details of the damage and its relationship to seismicity to be analyzed. The aftershock sequence associated with this mainshock occurs on two well-defined trends, reflecting the two potential fault planes in earthquake focal mechanisms for the mainshock and the majority of the aftershocks. The damage area was relatively large for an event of this magnitude, but primarily occurs within the primary rupture (aftershock) region or along regional rivers with soils susceptible to liquefaction of other ground failure. Stress modeling combined with the time-series and pattern of aftershock activity lead us to propose that the initial mainshock rupture continued slightly onto its conjugate faults near its northern termination, helping to trigger the distinct pattern of two discrete, conjugate trends of aftershock activity that mirror the kinematics of the mainshock fault mechanism. Although this earthquake occurred in a region of known faults, it cannot be directly linked to a previously mapped structure. This coupled with the substantial damage from the event indicates that there is potentially a higher earthquake hazard in northern and central Thailand than previously recognized.

Frontopolar cortex and decision-making efficiency: comparing brain activity of experts with different professional background during an exploration-exploitation task.

PubMed

Laureiro-Martínez, Daniella; Canessa, Nicola; Brusoni, Stefano; Zollo, Maurizio; Hare, Todd; Alemanno, Federica; Cappa, Stefano F

2013-01-01

An optimal balance between efficient exploitation of available resources and creative exploration of alternatives is critical for adaptation and survival. Previous studies associated these behavioral drives with, respectively, the dopaminergic mesocorticolimbic system and frontopolar-intraparietal networks. We study the activation of these systems in two age and gender-matched groups of experienced decision-makers differing in prior professional background, with the aim to understand the neural bases of individual differences in decision-making efficiency (performance divided by response time). We compare brain activity of entrepreneurs (who currently manage the organization they founded based on their venture idea) and managers (who are constantly involved in making strategic decisions but have no venture experience) engaged in a gambling-task assessing exploitative vs. explorative decision-making. Compared with managers, entrepreneurs showed higher decision-making efficiency, and a stronger activation in regions of frontopolar cortex (FPC) previously associated with explorative choice. Moreover, activity across a network of regions previously linked to explore/exploit tradeoffs explained individual differences in choice efficiency. These results suggest new avenues for the study of individual differences in the neural antecedents of efficient decision-making.

Frontopolar cortex and decision-making efficiency: comparing brain activity of experts with different professional background during an exploration-exploitation task

PubMed Central

Laureiro-Martínez, Daniella; Canessa, Nicola; Brusoni, Stefano; Zollo, Maurizio; Hare, Todd; Alemanno, Federica; Cappa, Stefano F.

2014-01-01

An optimal balance between efficient exploitation of available resources and creative exploration of alternatives is critical for adaptation and survival. Previous studies associated these behavioral drives with, respectively, the dopaminergic mesocorticolimbic system and frontopolar-intraparietal networks. We study the activation of these systems in two age and gender-matched groups of experienced decision-makers differing in prior professional background, with the aim to understand the neural bases of individual differences in decision-making efficiency (performance divided by response time). We compare brain activity of entrepreneurs (who currently manage the organization they founded based on their venture idea) and managers (who are constantly involved in making strategic decisions but have no venture experience) engaged in a gambling-task assessing exploitative vs. explorative decision-making. Compared with managers, entrepreneurs showed higher decision-making efficiency, and a stronger activation in regions of frontopolar cortex (FPC) previously associated with explorative choice. Moreover, activity across a network of regions previously linked to explore/exploit tradeoffs explained individual differences in choice efficiency. These results suggest new avenues for the study of individual differences in the neural antecedents of efficient decision-making. PMID:24478664

Monoamine oxidase deficiency in males with an X chromosome deletion.

PubMed

Sims, K B; de la Chapelle, A; Norio, R; Sankila, E M; Hsu, Y P; Rinehart, W B; Corey, T J; Ozelius, L; Powell, J F; Bruns, G

1989-01-01

Mapping of the human MAOA gene to chromosomal region Xp21-p11 prompted our study of two affected males in a family previously reported to have Norrie disease resulting from a submicroscopic deletion in this chromosomal region. In this investigation we demonstrate in these cousins deletion of the MAOA gene, undetectable levels of MAO-A and MAO-B activities in their fibroblasts and platelets, respectively, loss of mRNA for MAO-A in fibroblasts, and substantial alterations in urinary catecholamine metabolites. The present study documents that a marked deficiency of MAO activity is compatible with life and that genes for MAO-A and MAO-B are near each other in this Xp chromosomal region. Some of the clinical features of these MAO deletion patients may help to identify X-linked MAO deficiency diseases in humans.

Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

PubMed

Lotta, Luca A; Gulati, Pawan; Day, Felix R; Payne, Felicity; Ongen, Halit; van de Bunt, Martijn; Gaulton, Kyle J; Eicher, John D; Sharp, Stephen J; Luan, Jian'an; De Lucia Rolfe, Emanuella; Stewart, Isobel D; Wheeler, Eleanor; Willems, Sara M; Adams, Claire; Yaghootkar, Hanieh; Forouhi, Nita G; Khaw, Kay-Tee; Johnson, Andrew D; Semple, Robert K; Frayling, Timothy; Perry, John R B; Dermitzakis, Emmanouil; McCarthy, Mark I; Barroso, Inês; Wareham, Nicholas J; Savage, David B; Langenberg, Claudia; O'Rahilly, Stephen; Scott, Robert A

2017-01-01

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

Intelligence moderates neural responses to monetary reward and punishment.

PubMed

Hawes, Daniel R; DeYoung, Colin G; Gray, Jeremy R; Rustichini, Aldo

2014-05-01

The relations between intelligence (IQ) and neural responses to monetary gains and losses were investigated in a simple decision task. In 94 healthy adults, typical responses of striatal blood oxygen level-dependent (BOLD) signal after monetary reward and punishment were weaker for subjects with higher IQ. IQ-moderated differential responses to gains and losses were also found for regions in the medial prefrontal cortex, posterior cingulate cortex, and left inferior frontal cortex. These regions have previously been identified with the subjective utility of monetary outcomes. Analysis of subjects' behavior revealed a correlation between IQ and the extent to which choices were related to experienced decision outcomes in preceding trials. Specifically, higher IQ predicted behavior to be more strongly correlated with an extended period of previously experienced decision outcomes, whereas lower IQ predicted behavior to be correlated exclusively to the most recent decision outcomes. We link these behavioral and imaging findings to a theoretical model capable of describing a role for intelligence during the evaluation of rewards generated by unknown probabilistic processes. Our results demonstrate neural differences in how people of different intelligence respond to experienced monetary rewards and punishments. Our theoretical discussion offers a functional description for how these individual differences may be linked to choice behavior. Together, our results and model support the hypothesis that observed correlations between intelligence and preferences may be rooted in the way decision outcomes are experienced ex post, rather than deriving exclusively from how choices are evaluated ex ante.

Brain structures in the sciences and humanities.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Sassa, Yuko; Kawashima, Ryuta

2015-11-01

The areas of academic interest (sciences or humanities) and area of study have been known to be associated with a number of factors associated with autistic traits. However, despite the vast amount of literature on the psychological and physiological characteristics associated with faculty membership, brain structural characteristics associated with faculty membership have never been investigated directly. In this study, we used voxel-based morphometry to investigate differences in regional gray matter volume (rGMV)/regional white matter volume (rWMV) between science and humanities students to test our hypotheses that brain structures previously robustly shown to be altered in autistic subjects are related to differences in faculty membership. We examined 312 science students (225 males and 87 females) and 179 humanities students (105 males and 74 females). Whole-brain analyses of covariance revealed that after controlling for age, sex, and total intracranial volume, the science students had significantly larger rGMV in an anatomical cluster around the medial prefrontal cortex and the frontopolar area, whereas the humanities students had significantly larger rWMV in an anatomical cluster mainly concentrated around the right hippocampus. These anatomical structures have been linked to autism in previous studies and may mediate cognitive functions that characterize differences in faculty membership. The present results may support the ideas that autistic traits and characteristics of the science students compared with the humanities students share certain characteristics from neuroimaging perspectives. This study improves our understanding of differences in faculty membership which is the link among cognition, biological factors, disorders, and education (academia).

Streptococcus gordonii DL1 adhesin SspB V-region mediates coaggregation via receptor polysaccharide of Actinomyces oris T14V.

PubMed

Back, C R; Douglas, S K; Emerson, J E; Nobbs, A H; Jenkinson, H F

2015-10-01

Streptococcus gordonii SspA and SspB proteins, members of the antigen I/II (AgI/II) family of Streptococcus adhesins, mediate adherence to cysteine-rich scavenger glycoprotein gp340 and cells of other oral microbial species. In this article we investigated further the mechanism of coaggregation between S. gordonii DL1 and Actinomyces oris T14V. Previous mutational analysis of S. gordonii suggested that SspB was necessary for coaggregation with A. oris T14V. We have confirmed this by showing that Lactococcus lactis surrogate host cells expressing SspB coaggregated with A. oris T14V and PK606 cells, while L. lactis cells expressing SspA did not. Coaggregation occurred independently of expression of A. oris type 1 (FimP) or type 2 (FimA) fimbriae. Polysaccharide was prepared from cells of A. oris T14V and found to contain 1,4-, 4,6- and 3,4-linked glucose, 1,4-linked mannose, and 2,4-linked galactose residues. When immobilized onto plastic wells this polysaccharide supported binding of L. lactis expressing SspB, but not binding of L. lactis expressing other AgI/II family proteins. Purified recombinant NAVP region of SspB, comprising amino acid (aa) residues 41-847, bound A. oris polysaccharide but the C-domain (932-1470 aa residues) did not. A site-directed deletion of 29 aa residues (Δ691-718) close to the predicted binding cleft within the SspB V-region ablated binding of the NAVP region to polysaccharide. These results infer that the V-region head of SspB recognizes an actinomyces polysaccharide ligand, so further characterizing a lectin-like coaggregation mechanism occurring between two important primary colonizers. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of Genetic Variants Linking Protein C and Lipoprotein Metabolism: The ARIC Study (Atherosclerosis Risk in Communities).

PubMed

Pankow, James S; Tang, Weihong; Pankratz, Nathan; Guan, Weihua; Weng, Lu-Chen; Cushman, Mary; Boerwinkle, Eric; Folsom, Aaron R

2017-03-01

Previous studies have identified common genetic variants in 4 chromosomal regions that together account for 14% to 15% of the variance in circulating levels of protein C. To further characterize the genetic architecture of protein C, we obtained denser coverage at some loci, extended investigation of protein C to low-frequency and rare variants, and searched for new associations in genes known to influence protein C. Genetic associations with protein C antigen level were evaluated in ≤10 778 European and 3190 black participants aged 45 to 64 years. Analyses included >26 million autosomal variants available after imputation to the 1000 Genomes reference panel along with additional low-frequency and rare variants directly genotyped using the Illumina ITMAT-Broad-CARe chip and Illumina HumanExome BeadChip. Genome-wide significant associations ( P <5×10 -8 ) were found for common variants in the GCKR , PROC , BAZ1B , and PROCR-EDEM2 regions in whites and PROC and PROCR-EDEM2 regions in blacks, confirming earlier findings. In a novel finding, the low-density lipoprotein cholesterol-lowering allele of rs12740374, located in the CELSR2-PSRC1-SORT1 region, was associated with lower protein C level in both whites and blacks, reaching genome-wide significance in a meta-analysis combining results from both groups ( P =1.4×10 -9 ). To further investigate a possible link between lipid metabolism and protein C level, we conducted Mendelian randomization analyses using 185 lipid-related genetic variants as instrumental variables. The results indicated that triglycerides, and possibly low-density lipoprotein cholesterol, influence protein C levels. Discovery of variants influencing circulating protein C levels in the CELSR2-PSRC1-SORT1 region may indicate a novel genetic link between lipoprotein metabolism and hemostasis. © 2017 American Heart Association, Inc.

Neural predictors of chocolate intake following chocolate exposure.

PubMed

Frankort, Astrid; Roefs, Anne; Siep, Nicolette; Roebroeck, Alard; Havermans, Remco; Jansen, Anita

2015-04-01

Previous studies have shown that one's brain response to high-calorie food cues can predict long-term weight gain or weight loss. The neural correlates that predict food intake in the short term have, however, hardly been investigated. This study examined which brain regions' activation predicts chocolate intake after participants had been either exposed to real chocolate or to control stimuli during approximately one hour, with interruptions for fMRI measurements. Further we investigated whether the variance in chocolate intake could be better explained by activated brain regions than by self-reported craving. In total, five brain regions correlated with subsequent chocolate intake. The activation of two reward regions (the right caudate and the left frontopolar cortex) correlated positively with intake in the exposure group. The activation of two regions associated with cognitive control (the left dorsolateral and left mid-dorsolateral PFC) correlated negatively with intake in the control group. When the regression analysis was conducted with the exposure and the control group together, an additional region's activation (the right anterior PFC) correlated positively with chocolate intake. In all analyses, the intake variance explained by neural correlates was above and beyond the variance explained by self-reported craving. These results are in line with neuroimaging research showing that brain responses are a better predictor of subsequent intake than self-reported craving. Therefore, our findings might provide for a missing link by associating brain activation, previously shown to predict weight change, with short-term intake. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genotype-phenotype characterization in 13 individuals with chromosome Xp11.22 duplications.

PubMed

Grams, Sarah E; Argiropoulos, Bob; Lines, Matthew; Chakraborty, Pranesh; Mcgowan-Jordan, Jean; Geraghty, Michael T; Tsang, Marilyn; Eswara, Marthand; Tezcan, Kamer; Adams, Kelly L; Linck, Leesa; Himes, Patricia; Kostiner, Dana; Zand, Dina J; Stalker, Heather; Driscoll, Daniel J; Huang, Taosheng; Rosenfeld, Jill A; Li, Xu; Chen, Emily

2016-04-01

We report 13 new individuals with duplications in Xp11.22-p11.23. The index family has one male and two female members in three generations with mild-severe intellectual disability (ID), speech delay, dysmorphic features, early puberty, constipation, and/or hand and foot abnormalities. Affected individuals were found to have two small duplications in Xp11.22 at nucleotide position (hg19) 50,112,063-50,456,458 bp (distal) and 53,160,114-53,713,154 bp (proximal). Collectively, these two regions include 14 RefSeq genes, prompting collection of a larger cohort of patients, in an attempt to delineate critical genes associated with the observed phenotype. In total, we have collected data on nine individuals with duplications overlapping the distal duplication region containing SHROOM4 and DGKK and eight individuals overlapping the proximal region including HUWE1. Duplications of HUWE1 have been previously associated with non-syndromic ID. Our data, with previously published reports, suggest that duplications involving SHROOM4 and DGKK may represent a new syndromic X-linked ID critical region associated with mild to severe ID, speech delay +/- dysarthria, attention deficit disorder, precocious puberty, constipation, and motor delay. We frequently observed foot abnormalities, 5th finger clinodactyly, tapering fingers, constipation, and exercise intolerance in patients with duplications of these two genes. Regarding duplications including the proximal region, our observations agree with previous studies, which have found associations with intellectual disability. In addition, expressive language delay, failure to thrive, motor delay, and 5th finger clinodactyly were also frequently observed in patients with the proximal duplication. © 2015 Wiley Periodicals, Inc.

Molecular evidence that the genes for dioecism and monoecism in Spinacia oleracea L. are located at different loci in a chromosomal region

PubMed Central

Yamamoto, K; Oda, Y; Haseda, A; Fujito, S; Mikami, T; Onodera, Y

2014-01-01

Spinach (Spinacia oleracea L.) is widely known to be dioecious. However, monoecious plants can also occur in this species. Sex expression in dioecious spinach plants is controlled by a single gene pair termed X and Y. Our previous study showed that a single, incompletely dominant gene, which controls the monoecious condition in spinach line 03–336, should be allelic or linked to X/Y. Here, we developed 19 AFLP markers closely linked to the monoecious gene. The AFLP markers were mapped to a 38.2-cM chromosomal region that included the monoecious gene, which is bracketed between flanking markers with a distance of 7.1 cM. The four AFLP markers developed in our studies were converted into sequence-characterized amplified region (SCAR) markers, which are linked to both the monoecious gene and Y and are common to both populations segregating for the genes. Linkage analysis using the SCAR markers suggested that the monoecious gene (M) and Y are located in different intervals, between different marker pairs. Analysis of populations segregating for both M and Y also directly demonstrates linkage of the genes at a distance of ∼12 cM. The data presented in this study may be useful for breeding dioecious and highly male monoecious lines utilized as the pollen parents for hybrid seed production, as well as for studies of the evolutionary history of sexual systems in this species, and can provide a molecular basis for positional cloning of the sex-determining genes. PMID:24169648

Genotyping by sequencing resolves shallow population structure to inform conservation of Chinook salmon (Oncorhynchus tshawytscha)

PubMed Central

Larson, Wesley A; Seeb, Lisa W; Everett, Meredith V; Waples, Ryan K; Templin, William D; Seeb, James E

2014-01-01

Recent advances in population genomics have made it possible to detect previously unidentified structure, obtain more accurate estimates of demographic parameters, and explore adaptive divergence, potentially revolutionizing the way genetic data are used to manage wild populations. Here, we identified 10 944 single-nucleotide polymorphisms using restriction-site-associated DNA (RAD) sequencing to explore population structure, demography, and adaptive divergence in five populations of Chinook salmon (Oncorhynchus tshawytscha) from western Alaska. Patterns of population structure were similar to those of past studies, but our ability to assign individuals back to their region of origin was greatly improved (>90% accuracy for all populations). We also calculated effective size with and without removing physically linked loci identified from a linkage map, a novel method for nonmodel organisms. Estimates of effective size were generally above 1000 and were biased downward when physically linked loci were not removed. Outlier tests based on genetic differentiation identified 733 loci and three genomic regions under putative selection. These markers and genomic regions are excellent candidates for future research and can be used to create high-resolution panels for genetic monitoring and population assignment. This work demonstrates the utility of genomic data to inform conservation in highly exploited species with shallow population structure. PMID:24665338

Words in Context: The Effects of Length, Frequency, and Predictability on Brain Responses During Natural Reading

PubMed Central

Schuster, Sarah; Hawelka, Stefan; Hutzler, Florian; Kronbichler, Martin; Richlan, Fabio

2016-01-01

Word length, frequency, and predictability count among the most influential variables during reading. Their effects are well-documented in eye movement studies, but pertinent evidence from neuroimaging primarily stem from single-word presentations. We investigated the effects of these variables during reading of whole sentences with simultaneous eye-tracking and functional magnetic resonance imaging (fixation-related fMRI). Increasing word length was associated with increasing activation in occipital areas linked to visual analysis. Additionally, length elicited a U-shaped modulation (i.e., least activation for medium-length words) within a brain stem region presumably linked to eye movement control. These effects, however, were diminished when accounting for multiple fixation cases. Increasing frequency was associated with decreasing activation within left inferior frontal, superior parietal, and occipito-temporal regions. The function of the latter region—hosting the putative visual word form area—was originally considered as limited to sublexical processing. An exploratory analysis revealed that increasing predictability was associated with decreasing activation within middle temporal and inferior frontal regions previously implicated in memory access and unification. The findings are discussed with regard to their correspondence with findings from single-word presentations and with regard to neurocognitive models of visual word recognition, semantic processing, and eye movement control during reading. PMID:27365297

Himalayan uplift shaped biomes in Miocene temperate Asia: evidence from leguminous Caragana.

PubMed

Zhang, Ming-Li; Xiang, Xiao-Guo; Xue, Juan-Juan; Sanderson, Stewart C; Fritsch, Peter W

2016-11-09

Caragana, with distinctive variation in leaf and rachis characters, exhibits three centers of geographic distribution, i.e., Central Asia, the Qinghai-Tibetan Plateau (QTP), and East Asia, corresponding to distinct biomes. Because Caragana species are often ecologically dominant components of the vegetation in these regions, it is regarded as a key taxon for the study of floristic evolution in the dry regions of temperate Asia. Based on an expanded data set of taxa and gene regions from those previously generated, we employed molecular clock and biogeographical analyses to infer the evolutionary history of Caragana and link it to floristic patterns, paleovegetation, and paleoclimate. Results indicate that Caragana is of arid origin from the Junggar steppe. Diversification of crown group Caragana, dated to the early Miocene ca. 18 Ma and onwards, can be linked to the Himalayan Motion stage of QTP uplift. Diversification of the major clades in the genus corresponding to taxonomic sections and morphological variation is inferred to have been driven by the uplift, as well as Asian interior aridification and East Asian monsoon formation, in the middle to late Miocene ca. 12~6 Ma. These findings demonstrate a synchronous evolution among floristics, vegetation and climate change in arid Central Asia, cold arid alpine QTP, and mesophytic East Asia.

Patterns of hippocampal-neocortical interactions in the retrieval of episodic autobiographical memories across the entire life-span of aged adults

PubMed Central

Viard, Armelle; Lebreton, Karine; Chételat, Gaël; Desgranges, Béatrice; Landeau, Brigitte; Young, Alan; De La Sayette, Vincent; Eustache, Francis; Piolino, Pascale

2010-01-01

We previously demonstrated that Episodic Autobiographical Memories (EAMs) rely on a network of brain regions comprising the medial temporal lobe (MTL) and distributed neocortical regions regardless of their remoteness. The findings supported the model of memory consolidation which proposes a permanent role of MTL during EAM retrieval (Multiple-Trace Theory or MTT) rather than a temporary role (standard model). Our present aim was to expand the results by examining the interactions between the MTL and neocortical regions (or MTL-neocortical links) during EAM retrieval with varying retention intervals. We used an experimental paradigm specially designed to engage aged participants in the recollection of EAMs, extracted from five different time-periods, covering their whole life-span, in order to examine correlations between activation in the MTL and neocortical regions. The nature of the memories was checked at debriefing by means of behavioral measures to control the degree of episodicity and properties of memories. Targeted correlational analyses carried out on the MTL, frontal, lateral temporal and posterior regions revealed strong links between the MTL and neocortex during the retrieval of both recent and remote EAMs, challenging the standard model of memory consolidation and supporting MTT instead. Further confirmation was given by results showing that activation in the left and right hippocampi significantly correlated during the retrieval of both recent and remote memories. Correlations among extra-MTL neocortical regions also emerged for all time-periods, confirming the critical role of the prefrontal, temporal (lateral temporal cortex and temporal pole), precuneus and posterior cingulate regions in EAM retrieval. Overall, this paper emphasizes the role of a bilateral network of MTL and neocortical areas whose activation correlate during the recollection of rich phenomenological recent and remote EAMs. PMID:19338022

Novel and recurrent NDP gene mutations in familial cases of Norrie disease and X-linked exudative vitreoretinopathy.

PubMed

Pelcastre, Erika L; Villanueva-Mendoza, Cristina; Zenteno, Juan C

2010-05-01

To present the results of molecular analysis of the NDP gene in Mexican families with Norrie disease (ND) and X-linked familial exudative vitreoretinopathy (XL-FEVR). Two unrelated families with ND and two with XL-FEVR were studied. Clinical diagnosis was suspected on the basis of a complete ophthalmologic examination. Molecular methods included DNA isolation from peripheral blood leucocytes, polymerase chain reaction amplification and direct nucleotide sequencing analysis of the complete coding region and exon-intron junctions of NDP. Haplotype analysis using NDP-linked microsatellites markers was performed in both ND families. A novel Norrin missense mutation, p.Arg41Thr, was identified in two apparently unrelated families with ND. Haplotype analysis demonstrated that affected males in these two families shared the same ND-linked haplotype, suggesting a common origin for this novel mutation. The previously reported p.Arg121Trp and p.Arg121Gln Norrin mutations were identified in the two families with XL-FEVR. Our results expand the mutational spectrum in ND. This is the first report of ND resulting from mutation at arginine position 41 of Norrin. Interestingly, mutations at the same residue but resulting in a different missense change were previously described in subjects with XL-FEVR (p.Arg41Lys) or persistent fetal vasculature syndrome (p.Arg41Ser), indicating that the novel p.Arg41Thr change causes a more severe retinal phenotype. Preliminary data suggest a founder effect for the ND p.Arg41Thr mutation in these two Mexican families.

Rickettsia parkeri Rickettsiosis, Arizona, USA.

PubMed

Herrick, Kristen L; Pena, Sandra A; Yaglom, Hayley D; Layton, Brent J; Moors, Amanda; Loftis, Amanda D; Condit, Marah E; Singleton, Joseph; Kato, Cecilia Y; Denison, Amy M; Ng, Dianna; Mertins, James W; Paddock, Christopher D

2016-05-01

In the United States, all previously reported cases of Rickettsia parkeri rickettsiosis have been linked to transmission by the Gulf Coast tick (Amblyomma maculatum). Here we describe 1 confirmed and 1 probable case of R. parkeri rickettsiosis acquired in a mountainous region of southern Arizona, well beyond the recognized geographic range of A. maculatum ticks. The likely vector for these 2 infections was identified as the Amblyomma triste tick, a Neotropical species only recently recognized in the United States. Identification of R. parkeri rickettsiosis in southern Arizona demonstrates a need for local ecologic and epidemiologic assessments to better understand geographic distribution and define public health risk. Education and outreach aimed at persons recreating or working in this region of southern Arizona would improve awareness and promote prevention of tickborne rickettsioses.

Creative Activities in Music – A Genome-Wide Linkage Analysis

PubMed Central

Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

2016-01-01

Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose a common genetic background for music-related creative behaviour and musical abilities at chromosome 4. PMID:26909693

Linking North American Summer Ozone Pollution Episodes to Subseasonal Atmospheric Variability

NASA Astrophysics Data System (ADS)

White, E. C.; Watt-Meyer, O.; Kushner, P. J.; Jones, D. B. A.

2017-12-01

Ozone concentrations in the planetary boundary layer (PBL) are positively correlated with surface air temperature due to shared influences including incident solar radiation and PBL stagnancy, as well as the temperature-sensitive emission of ozone precursor compounds. While previous studies have linked heat waves in North America to modes of subseasonal atmospheric variability, such analyses have not been applied to summertime ozone pollution episodes. This study investigates a possible link between subseasonal atmospheric variability in reanalysis data and summertime ozone pollution episodes identified in almost thirty years of in-situ measurements from the Air Quality System (AQS) network in the United States. AQS stations are grouped into regions likely to experience simultaneous extreme ozone concentrations using statistical clustering methods. Composite meteorological patterns are calculated for ozone episodes in each of these regions. The same analysis is applied to heat waves identified in AQS temperature records for comparison. Local meteorological features during typical ozone episodes include extreme temperatures and reduced cloud cover related to anomalous synoptic-scale anticyclonic circulation aloft. These anticyclonic anomalies are typically embedded in wave trains extending from the North Pacific to North Atlantic. Spectral analysis of these wave trains reveals that low-frequency standing waves play a prominent role. These long-lived circulation patterns may provide a means to increase air quality prediction lead-times and to estimate the frequency of ozone pollution episodes under climate change.

A rare duplication on chromosome 16p11.2 is identified in patients with psychosis in Alzheimer's disease.

PubMed

Zheng, Xiaojing; Demirci, F Yesim; Barmada, M Michael; Richardson, Gale A; Lopez, Oscar L; Sweet, Robert A; Kamboh, M Ilyas; Feingold, Eleanor

2014-01-01

Epidemiological and genetic studies suggest that schizophrenia and autism may share genetic links. Besides common single nucleotide polymorphisms, recent data suggest that some rare copy number variants (CNVs) are risk factors for both disorders. Because we have previously found that schizophrenia and psychosis in Alzheimer's disease (AD+P) share some genetic risk, we investigated whether CNVs reported in schizophrenia and autism are also linked to AD+P. We searched for CNVs associated with AD+P in 7 recurrent CNV regions that have been previously identified across autism and schizophrenia, using the Illumina HumanOmni1-Quad BeadChip. A chromosome 16p11.2 duplication CNV (chr16: 29,554,843-30,105,652) was identified in 2 of 440 AD+P subjects, but not in 136 AD subjects without psychosis, or in 593 AD subjects with intermediate psychosis status, or in 855 non-AD individuals. The frequency of this duplication CNV in AD+P (0.46%) was similar to that reported previously in schizophrenia (0.46%). This duplication CNV was further validated using the NanoString nCounter CNV Custom CodeSets. The 16p11.2 duplication has been associated with developmental delay, intellectual disability, behavioral problems, autism, schizophrenia (SCZ), and bipolar disorder. These two AD+P patients had no personal of, nor any identified family history of, SCZ, bipolar disorder and autism. To the best of our knowledge, our case report is the first suggestion that 16p11.2 duplication is also linked to AD+P. Although rare, this CNV may have an important role in the development of psychosis.

Structure of a Complete Mediator-RNA Polymerase II Pre-Initiation Complex.

PubMed

Robinson, Philip J; Trnka, Michael J; Bushnell, David A; Davis, Ralph E; Mattei, Pierre-Jean; Burlingame, Alma L; Kornberg, Roger D

2016-09-08

A complete, 52-protein, 2.5 million dalton, Mediator-RNA polymerase II pre-initiation complex (Med-PIC) was assembled and analyzed by cryo-electron microscopy and by chemical cross-linking and mass spectrometry. The resulting complete Med-PIC structure reveals two components of functional significance, absent from previous structures, a protein kinase complex and the Mediator-activator interaction region. It thereby shows how the kinase and its target, the C-terminal domain of the polymerase, control Med-PIC interaction and transcription. Copyright © 2016 Elsevier Inc. All rights reserved.

Dual control active superconductive devices

DOEpatents

Martens, Jon S.; Beyer, James B.; Nordman, James E.; Hohenwarter, Gert K. G.

1993-07-20

A superconducting active device has dual control inputs and is constructed such that the output of the device is effectively a linear mix of the two input signals. The device is formed of a film of superconducting material on a substrate and has two main conduction channels, each of which includes a weak link region. A first control line extends adjacent to the weak link region in the first channel and a second control line extends adjacent to the weak link region in the second channel. The current flowing from the first channel flows through an internal control line which is also adjacent to the weak link region of the second channel. The weak link regions comprise small links of superconductor, separated by voids, through which the current flows in each channel. Current passed through the control lines causes magnetic flux vortices which propagate across the weak link regions and control the resistance of these regions. The output of the device taken across the input to the main channels and the output of the second main channel and the internal control line will constitute essentially a linear mix of the two input signals imposed on the two control lines. The device is especially suited to microwave applications since it has very low input capacitance, and is well suited to being formed of high temperature superconducting materials since all of the structures may be formed coplanar with one another on a substrate.

A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy.

PubMed

Chen, Z Y; Battinelli, E M; Fielder, A; Bundey, S; Sims, K; Breakefield, X O; Craig, I W

1993-10-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by an abnormality of the peripheral retina. Both autosomal dominant (adFEVR) and X-linked (XLFEVR) forms have been described, but the biochemical defect(s) underlying the symptoms are unknown. Molecular analysis of the Norrie gene locus (NDP) in a four generation FEVR family (shown previously to exhibit linkage to the X-chromosome markers DXS228 and MAOA (Xp11.4-p11.3)) reveals a missense mutation in the highly conserved region of the NDP gene, which caused a neutral amino acid substitution (Leu124Phe), was detected in all of the affected males, but not in the unaffected family members, nor in normal controls. The observations suggest that phenotypes of both XLFEVR and Norrie disease can result from mutations in the same gene.

Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity

PubMed Central

2010-01-01

Background Previous reports have shown that peptides derived from the apolipoprotein E receptor binding region and the amphipathic α-helical domains of apolipoprotein AI have broad anti-infective activity and antiviral activity respectively. Lipoproteins and viruses share a similar cell biological niche, being of overlapping size and displaying similar interactions with mammalian cells and receptors, which may have led to other antiviral sequences arising within apolipoproteins, in addition to those previously reported. We therefore designed a series of peptides based around either apolipoprotein receptor binding regions, or amphipathic α-helical domains, and tested these for antiviral and antibacterial activity. Results Of the nineteen new peptides tested, seven showed some anti-infective activity, with two of these being derived from two apolipoproteins not previously used to derive anti-infective sequences. Apolipoprotein J (151-170) - based on a predicted amphipathic alpha-helical domain from apolipoprotein J - had measurable anti-HSV1 activity, as did apolipoprotein B (3359-3367) dp (apoBdp), the latter being derived from the LDL receptor binding domain B of apolipoprotein B. The more active peptide - apoBdp - showed similarity to the previously reported apoE derived anti-infective peptide, and further modification of the apoBdp sequence to align the charge distribution more closely to that of apoEdp or to introduce aromatic residues resulted in increased breadth and potency of activity. The most active peptide of this type showed similar potent anti-HIV activity, comparable to that we previously reported for the apoE derived peptide apoEdpL-W. Conclusions These data suggest that further antimicrobial peptides may be obtained using human apolipoprotein sequences, selecting regions with either amphipathic α-helical structure, or those linked to receptor-binding regions. The finding that an amphipathic α-helical region of apolipoprotein J has antiviral activity comparable with that for the previously reported apolipoprotein AI derived peptide 18A, suggests that full-length apolipoprotein J may also have such activity, as has been reported for full-length apolipoprotein AI. Although the strength of the anti-infective activity of the sequences identified was limited, this could be increased substantially by developing related mutant peptides. Indeed the apolipoprotein B-derived peptide mutants uncovered by the present study may have utility as HIV therapeutics or microbicides. PMID:20298574

Phylogenetic Analysis of Enterovirus 71 Strains Isolated during Linked Epidemics in Malaysia, Singapore, and Western Australia

PubMed Central

McMinn, Peter; Lindsay, Katie; Perera, David; Chan, Hung Ming; Chan, Kwai Peng; Cardosa, Mary Jane

2001-01-01

Enterovirus 71 (EV71) is a frequent cause of hand, foot, and mouth disease (HFMD) epidemics associated with severe neurological sequelae in a small proportion of cases. There has been a significant increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997. Recent HFMD epidemics in this region have been associated with a severe form of brainstem encephalitis associated with pulmonary edema and high case fatality rates. In this study, we show that four genetic lineages of EV71 have been prevalent in the Asia-Pacific region since 1997, including two previously undescribed genogroups (B3 and B4). Furthermore, we show that viruses belonging to genogroups B3 and B4 have circulated endemically in Southeast Asia during this period and have been the primary cause of several large HFMD or encephalitis epidemics in Malaysia, Singapore, and Western Australia. PMID:11462047

Nance-Horan syndrome: linkage analysis in 4 families refines localization in Xp22.31-p22.13 region.

PubMed

Toutain, A; Ronce, N; Dessay, B; Robb, L; Francannet, C; Le Merrer, M; Briard, M L; Kaplan, J; Moraine, C

1997-02-01

Nance-Horan syndrome (NHS) is an X-linked disease characterized by severe congenital cataract with microcornea, distinctive dental findings, evocative facial features and mental impairment in some cases. Previous linkage studies have placed the NHS gene in a large region from DXS143 (Xp22.31) to DXS451 (Xp22.13). To refine this localization further, we have performed linkage analysis in four families. As the maximum expected Lod score is reached in each family for several markers in the Xp22.31-p22.13 region and linkage to the rest of the X chromosome can be excluded, our study shows that NHS is a genetically homogeneous condition. An overall maximum two-point Lod score of 9.36 (theta = 0.00) is obtained with two closely linked markers taken together. DXS207 and DXS1053 in Xp22.2. Recombinant haplotypes indicate that the NHS gene lies between DXS85 and DXS1226. Multipoint analysis yield a maximum Lod score of 9.45 with the support interval spanning a 15-cM region that includes DXS16 and DXS1229/365. The deletion map of the Xp22.3-Xp21.3 region suggests that the phenotypic variability of NHS is not related to gross rearrangement of sequences of varying size but rather to allelic mutations in a single gene, presumably located proximal to DXS16 and distal to DXS1226. Comparison with the map position of the mouse Xcat mutation supports the location of the NHS gene between the GRPR and PDHA1 genes in Xp22.2.

Statistical Study in the mid-altitude cusp region: wave and particle data comparison using a normalized cusp crossing duration

NASA Astrophysics Data System (ADS)

Grison, B.; Escoubet, C. P.; Pitout, F.; Cornilleau-Wehrlin, N.; Dandouras, I.; Lucek, E.

2009-04-01

In the mid altitude cusp region the DC magnetic field presents a diamagnetic cavity due to intense ion earthward flux coming from the magnetosheath. A strong ultra low frequency (ULF) magnetic activity is also commonly observed in this region. Most of the mid altitude cusp statistical studies have focused on the location of the cusp and its dependence and response to solar wind, interplanetary magnetic field, dipole tilt angle parameters. In our study we use the database build by Pitout et al. (2006) in order to study the link of wave power in the ULF range (0.35-10Hz) measured by STAFF SC instrument with the ion plasma properties as measured by CIS (and CODIF) instrument as well as the diamagnetic cavity in the mid-altitude cusp region with FGM data. To compare the different crossings we don`t use the cusp position and dynamics but we use a normalized cusp crossing duration that permits to easily average the properties over a large number of crossings. As usual in the cusp, it is particularly relevant to sort the crossings by the corresponding interplanetary magnetic field (IMF) orientation in order to analyse the results. In particular we try to find out what is the most relevant parameter to link the strong wave activity with. The global statistic confirms previous single case observations that have noticed a simultaneity between ion injections and wave activity enhancements. We will also present results concerning other ion parameters and the diamagnetic cavity observed in the mid altitude cusp region.

Condition-dependent functional connectivity: syntax networks in bilinguals

PubMed Central

Dodel, Silke; Golestani, Narly; Pallier, Christophe; ElKouby, Vincent; Le Bihan, Denis; Poline, Jean-Baptiste

2005-01-01

This paper introduces a method to study the variation of brain functional connectivity networks with respect to experimental conditions in fMRI data. It is related to the psychophysiological interaction technique introduced by Friston et al. and extends to networks of correlation modulation (CM networks). Extended networks containing several dozens of nodes are determined in which the links correspond to consistent correlation modulation across subjects. In addition, we assess inter-subject variability and determine networks in which the condition-dependent functional interactions can be explained by a subject-dependent variable. We applied the technique to data from a study on syntactical production in bilinguals and analysed functional interactions differentially across tasks (word reading or sentence production) and across languages. We find an extended network of consistent functional interaction modulation across tasks, whereas the network comparing languages shows fewer links. Interestingly, there is evidence for a specific network in which the differences in functional interaction across subjects can be explained by differences in the subjects' syntactical proficiency. Specifically, we find that regions, including ones that have previously been shown to be involved in syntax and in language production, such as the left inferior frontal gyrus, putamen, insula, precentral gyrus, as well as the supplementary motor area, are more functionally linked during sentence production in the second, compared with the first, language in syntactically more proficient bilinguals than in syntactically less proficient ones. Our approach extends conventional activation analyses to the notion of networks, emphasizing functional interactions between regions independently of whether or not they are activated. On the one hand, it gives rise to testable hypotheses and allows an interpretation of the results in terms of the previous literature, and on the other hand, it provides a basis for studying the structure of functional interactions as a whole, and hence represents a further step towards the notion of large-scale networks in functional imaging. PMID:16087437

Refined mapping and YAC contig construction of the X-linked cleft palate and ankyloglossia locus (CPX) including the proximal X-Y homology breakpoint within Xq21.3

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

Forbes, S.A.; Brennan, L.; Richardson, M.

1996-01-01

The gene for X-linked cleft palate (CPX) has previously been mapped in an Icelandic kindred between the unordered proximal markers DXS1002/DXS349/DXS95 and the distal marker DXYS1X, which maps to the proximal end of the X-Y homology region in Xq21.3. Using six sequence-tagged sites (STSs) within the region, a total of 91 yeast artificial chromosome (YAC) clones were isolated and overlapped in a single contig that spans approximately 3.1 Mb between DXS1002 and DXYS1X. The order of microsatellite and STS markers in this was established as DXS1002-DXS1168-DXS349-DXS95-DXS364-DXS1196-DXS472-DXS1217-DXYS1X. A long-range restriction map of this region was created using eight nonchimeric, overlapping YACmore » clones. Analysis of newly positioned polymorphic markers in recombinant individuals from the Icelandic family has enabled us to identify DXS1196 and DXS1217 as the flanking markers for CPX. The maximum physical distance containing the CPX gene has been estimated to be 2.0 Mb, which is spanned by a minimum set of five nonchimeric YAC clones. In addition, YAC end clone and STS analyses have pinpointed the location of the proximal boundary of the X-Y homology region within the map. 40 refs., 2 figs., 2 tabs.« less

Connectivity and functional profiling of abnormal brain structures in pedophilia

PubMed Central

Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

2015-01-01

Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

The development of a modified human IFN-alpha2b linked to the Fc portion of human IgG1 as a novel potential therapeutic for the treatment of hepatitis C virus infection.

PubMed

Jones, Tim D; Hanlon, Marian; Smith, Beverley J; Heise, Charles T; Nayee, Prakash D; Sanders, Deborah A; Hamilton, Anita; Sweet, Clive; Unitt, Esther; Alexander, Graeme; Lo, Kin-Ming; Gillies, Stephen D; Carr, Frank J; Baker, Matthew P

2004-09-01

Interferon-alpha (IFN-alpha), in conjunction with ribavirin, is the current standard for the treatment of chronic hepatitis C virus (HCV) infection. This treatment requires frequent dosing, with a significant risk of the development of anti-IFN-alpha neutralizing antibodies that correlates with lack of efficacy or relapse. We have developed an IFN-alpha linked to the Fc region of human IgG1 for improved half-life and less frequent dosing. We have also identified, using a human T cell proliferation assay, three regions of IFN-alpha2b that are potentially immunogenic, and a variant containing a total of six mutations within these regions was made. This variant was made as a fusion to Fc either with or without a flexible linker between the fusion partners. Both configurations of the variant were less active than native IFN-alpha alone, although the variant containing the flexible linker had in vitro antiviral activity within the range of other modified IFN-alphas currently in clinical use. Peptides spanning the modified regions were tested in T cell proliferation assays and found to be less immunogenic than native controls when using peripheral blood mononuclear cells (PBMCs) from both healthy individuals and HCV-infected patients who had been treated previously with IFN-alpha2b. Copyright Mary Ann Liebert, Inc.

Connectivity and functional profiling of abnormal brain structures in pedophilia.

PubMed

Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

2015-06-01

Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. © 2015 Wiley Periodicals, Inc.

Regional endothermy as a trigger for gigantism in some extinct macropredatory sharks

PubMed Central

2017-01-01

Otodontids include some of the largest macropredatory sharks that ever lived, the most extreme case being Otodus (Megaselachus) megalodon. The reasons underlying their gigantism, distribution patterns and extinction have been classically linked with climatic factors and the evolution, radiation and migrations of cetaceans during the Paleogene. However, most of these previous proposals are based on the idea of otodontids as ectothermic sharks regardless of the ecological, energetic and body size constraints that this implies. Interestingly, a few recent studies have suggested the possible existence of endothermy in these sharks thus opening the door to a series of new interpretations. Accordingly, this work proposes that regional endothermy was present in otodontids and some closely related taxa (cretoxyrhinids), playing an important role in the evolution of gigantism and in allowing an active mode of live. The existence of regional endothermy in these groups is supported here by three different approaches including isotopic-based approximations, swimming speed inferences and the application of a novel methodology for assessing energetic budget and cost of swimming in extinct taxa. In addition, this finding has wider implications. It calls into question some previous paleotemperature estimates based partially on these taxa, suggests that the existing hypothesis about the evolution of regional endothermy in fishes requires modification, and provides key evidence for understanding the evolution of gigantism in active macropredators. PMID:28938002

The effect of the eye's surface topography on the total irradiance of ultraviolet radiation on the inner canthus.

PubMed

Birt, Benjamin; Cowling, Ian; Coyne, Steve; Michael, Greg

2007-04-02

Basal cell carcinoma is the most commonly occurring skin cancer in sub tropical climates. The link between ultraviolet radiation (UVR) and basal cell carcinomas (BCC) is strong. Numerous studies have investigated the spatial distribution of BCCs over the head and neck region and the relative UVR dose, with little or no correlation found between the UVR dose and occurrence rates. This is particularly noted in the inner canthus region. The inner canthus' field of view is restricted by the eye brow ridge, eye orbit and the cheek bone. Yet, the occurrence rate here of BCC's when compared to other regions that are more directly exposed to the environment is significantly higher. A possible causal effect for the increase in occurrence rate in this region is the focussed reflection of UVR from the tear film surface associated with the eye not previously considered in earlier studies. This paper investigates the potential for the surface topography of the eye to reflect focussed radiation towards the inner canthus using a ray tracing programme where the analysis is conducted at a cellular level. Defined hot spots, or striations, of increased irradiation were evidenced across the surface of the inner canthus. This increase in irradiation was not observed with macroscopic detectors which also possibly explain why this increased dose has not previously been detected during environmental measurements with large detectors on manikins or humans.

Regional endothermy as a trigger for gigantism in some extinct macropredatory sharks.

PubMed

Ferrón, Humberto G

2017-01-01

Otodontids include some of the largest macropredatory sharks that ever lived, the most extreme case being Otodus (Megaselachus) megalodon. The reasons underlying their gigantism, distribution patterns and extinction have been classically linked with climatic factors and the evolution, radiation and migrations of cetaceans during the Paleogene. However, most of these previous proposals are based on the idea of otodontids as ectothermic sharks regardless of the ecological, energetic and body size constraints that this implies. Interestingly, a few recent studies have suggested the possible existence of endothermy in these sharks thus opening the door to a series of new interpretations. Accordingly, this work proposes that regional endothermy was present in otodontids and some closely related taxa (cretoxyrhinids), playing an important role in the evolution of gigantism and in allowing an active mode of live. The existence of regional endothermy in these groups is supported here by three different approaches including isotopic-based approximations, swimming speed inferences and the application of a novel methodology for assessing energetic budget and cost of swimming in extinct taxa. In addition, this finding has wider implications. It calls into question some previous paleotemperature estimates based partially on these taxa, suggests that the existing hypothesis about the evolution of regional endothermy in fishes requires modification, and provides key evidence for understanding the evolution of gigantism in active macropredators.

Human Nonsyndromic Hereditary Deafness DFNA17 Is Due to a Mutation in Nonmuscle Myosin MYH9

PubMed Central

Lalwani, Anil K.; Goldstein, Jayne A.; Kelley, Michael J.; Luxford, William; Castelein, Caley M.; Mhatre, Anand N.

2000-01-01

The authors had previously mapped a new locus—DFNA17, for nonsyndromic hereditary hearing impairment—to chromosome 22q12.2-q13.3. DFNA17 spans a 17- to 23-cM region, and MYH9, a nonmuscle–myosin heavy-chain gene, is located within the linked region. Because of the importance of myosins in hearing, MYH9 was tested as a candidate gene for DFNA17. Expression of MYH9 in the rat cochlea was confirmed using reverse transcriptase–PCR and immunohistochemistry. MYH9 was immunolocalized in the organ of Corti, the subcentral region of the spiral ligament, and the Reissner membrane. Sequence analysis of MYH9 in a family with DFNA17 identified, at nucleotide 2114, a G→A transposition that cosegregated with the inherited autosomal dominant hearing impairment. This missense mutation changes codon 705 from an invariant arginine (R) to histidine (H), R705H, within a highly conserved SH1 linker region. Previous studies have shown that modification of amino acid residues within the SH1 helix causes dysfunction of the ATPase activity of the motor domain in myosin II. Both the precise role of MYH9 in the cochlea and the mechanism by which the R705H mutation leads to the DFNA17 phenotype (progressive hearing impairment and cochleosaccular degeneration) remain to be elucidated. PMID:11023810

Application of a fast sorting algorithm to the assignment of mass spectrometric cross-linking data.

PubMed

Petrotchenko, Evgeniy V; Borchers, Christoph H

2014-09-01

Cross-linking combined with MS involves enzymatic digestion of cross-linked proteins and identifying cross-linked peptides. Assignment of cross-linked peptide masses requires a search of all possible binary combinations of peptides from the cross-linked proteins' sequences, which becomes impractical with increasing complexity of the protein system and/or if digestion enzyme specificity is relaxed. Here, we describe the application of a fast sorting algorithm to search large sequence databases for cross-linked peptide assignments based on mass. This same algorithm has been used previously for assigning disulfide-bridged peptides (Choi et al., ), but has not previously been applied to cross-linking studies. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Individual- and regional-level determinants of human papillomavirus (HPV) vaccine refusal: the Ontario Grade 8 HPV vaccine cohort study.

PubMed

Remes, Olivia; Smith, Leah M; Alvarado-Llano, Beatriz E; Colley, Lindsey; Lévesque, Linda E

2014-10-08

Studies on the determinants of human papillomavirus (HPV) vaccine use have generally focused on individual-level characteristics, despite the potentially important influence of regional-level characteristics. Therefore, we undertook a population-based, retrospective cohort study to identify individual- and regional-level determinants of HPV vaccine refusal (non-receipt) in Ontario's (Canada) Grade 8 HPV Immunization Program. Ontario's administrative health and immunization databases were used to identify girls eligible for free HPV vaccination in 2007-2011 and to ascertain individual-level characteristics of cohort members (socio-demographics, vaccination history, health care utilization, medical history). The social and material characteristics of the girl's region (health unit) were derived from the 2006 Canadian Census. Generalized estimating equations (binomial distribution, logit link) were used to estimate the population-average effects of individual- and regional-level characteristics on HPV vaccine refusal. Our cohort consisted of 144,047 girls, 49.3% of whom refused HPV vaccination. Factors associated with refusal included a previous diagnosis of Down's syndrome (OR = 1.37, 95% CI 1.16-1.63) or autism (OR = 1.60, 95% CI 1.34-1.90), few physician visits (OR = 1.45, 95% CI 1.35-1.55), and previous refusal of mandatory (OR = 2.23, 95% CI 2.07-2.40) and optional (OR = 3.96, 95% CI 3.87-4.05) vaccines. Refusal was highest among the lowest and highest income levels. Finally, a previous diagnosis of obesity and living in an area of high deprivation were associated with lower refusal (OR = 0.87, 95% CI 0.83-0.92 and OR = 0.82 95%, CI 0.79-0.86, respectively). Studies on HPV vaccine determinants should consider regional-level factors. Efforts to increase HPV vaccine acceptance should include vulnerable populations (such as girls of low income) and girls with limited contact with the healthcare system.

Stimulus and response conflict processing during perceptual decision making.

PubMed

Wendelken, Carter; Ditterich, Jochen; Bunge, Silvia A; Carter, Cameron S

2009-12-01

Encoding and dealing with conflicting information is essential for successful decision making in a complex environment. In the present fMRI study, stimulus conflict and response conflict are contrasted in the context of a perceptual decision-making dot-motion discrimination task. Stimulus conflict was manipulated by varying dot-motion coherence along task-relevant and task-irrelevant dimensions. Response conflict was manipulated by varying whether or not competing stimulus dimensions provided evidence for the same or different responses. The right inferior frontal gyrus was involved specifically in the resolution of stimulus conflict, whereas the dorsal anterior cingulate cortex was shown to be sensitive to response conflict. Additionally, two regions that have been linked to perceptual decision making with dot-motion stimuli in monkey physiology studies were differentially engaged by stimulus conflict and response conflict. The middle temporal area, previously linked to processing of motion, was strongly affected by the presence of stimulus conflict. On the other hand, the superior parietal lobe, previously associated with accumulation of evidence for a response, was affected by the presence of response conflict. These results shed light on the neural mechanisms that support decision making in the presence of conflict, a cognitive operation fundamental to both basic survival and high-level cognition.

Testicular expressed genes are missing in familial X-Linked Kallmann syndrome due to two large different deletions in daughter's X chromosomes.

PubMed

Hershkovitz, Eli; Loewenthal, Neta; Peretz, Asaf; Parvari, Ruti

2008-01-01

X-linked Kallmann syndrome (KS) is caused mainly by point mutations, in the KAL1 gene. Large deletions >1 Mb are rare events in the human population and commonly result in contiguous gene syndromes. A search for the mutation causing KS carried out on two pairs of first-degree cousins of 2 sisters. Two different apparently independent deletions were found. The deleted sequences encompass the KAL1 gene and four known additional genes exclusively expressed in testis. Two of these genes belong to the FAM9 gene family, which shares some homology with the SCYP3 gene, previously implicated in azoospermia. One of the events causing the deletion may have been mediated by an L1 transposition, the other by a non-homologous end joining. Such non-homologous recombinations have not yet been reported in the KAL genomic region and thus this area may be more prone to deletions than previously expected. This is the first report on genetic characterization of KS with a deletion of solely testis-expressed genes. The absence of these genes may have unfavorable implications for the patients regarding future fertility. (c) 2008 S. Karger AG, Basel

Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders.

PubMed

Kos, Claire; van Tol, Marie-José; Marsman, Jan-Bernard C; Knegtering, Henderikus; Aleman, André

2016-10-01

Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar across different pathological conditions. The purpose of this systematic review was to provide an extensive overview of the neuroimaging literature on apathy including studies of various patient populations, and evaluate whether the current state of affairs suggest disorder specific or shared neural correlates of apathy. Results suggest that abnormalities within fronto-striatal circuits are most consistently associated with apathy across the different pathological conditions. Of note, abnormalities within the inferior parietal cortex were also linked to apathy, a region previously not included in neuroanatomical models of apathy. The variance in brain regions implicated in apathy may suggest that different routes towards apathy are possible. Future research should investigate possible alterations in different processes underlying goal-directed behavior, ranging from intention and goal-selection to action planning and execution. Copyright © 2016. Published by Elsevier Ltd.

Depth dependant element analysis of PbMg1/3Nb2/3O3 using muonic x-rays

NASA Astrophysics Data System (ADS)

Brown, K. L.; Stockdale, C. P. J.; Luo, H.; Zhao, X.; Li, J.-F.; Viehland, D.; Xu, G.; Gehring, P. M.; Ishida, K.; Hillier, A. D.; Stock, C.

2018-03-01

The relaxor PbMg1/3Nb2/3O3 (PMN) has received attention due to its potential applications as a piezoelectric when doped with PbTiO3 (PT). Previous results have found that there are two phases existing in the system, one linked to the near-surface regions of the sample, the other in the bulk. However, the exact origin of these two phases is unclear. In this paper, depth dependant analysis results from negative muon implantation experiments are presented. It is shown that the Pb content is constant throughout all depths probed in the sample, but the Mg and Nb content changes in the near-surface region below 100 μm. At an implantation depth of 60 μm, it is found that there is a 25% increase in Mg content, with a simultaneous 5% decrease in Nb content in order to maintain charge neutrality. These results show that the previously observed skin effects in PMN are due to a change in concentration and unit cell.

Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy

PubMed Central

Landsverk, Megan L.; Ruzzo, Elizabeth K.; Mefford, Heather C.; Buysse, Karen; Buchan, Jillian G.; Eichler, Evan E.; Petty, Elizabeth M.; Peterson, Esther A.; Knutzen, Dana M.; Barnett, Karen; Farlow, Martin R.; Caress, Judy; Parry, Gareth J.; Quan, Dianna; Gardner, Kathy L.; Hong, Ming; Simmons, Zachary; Bird, Thomas D.; Chance, Phillip F.; Hannibal, Mark C.

2009-01-01

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder associated with recurrent episodes of focal neuropathy primarily affecting the brachial plexus. Point mutations in the SEPT9 gene have been previously identified as the molecular basis of HNA in some pedigrees. However in many families, including those from North America demonstrating a genetic founder haplotype, no sequence mutations have been detected. We report an intragenic 38 Kb SEPT9 duplication that is linked to HNA in 12 North American families that share the common founder haplotype. Analysis of the breakpoints showed that the duplication is identical in all pedigrees, and molecular analysis revealed that the duplication includes the 645 bp exon in which previous HNA mutations were found. The SEPT9 transcript variants that span this duplication contain two in-frame repeats of this exon, and immunoblotting demonstrates larger molecular weight SEPT9 protein isoforms. This exon also encodes for a majority of the SEPT9 N-terminal proline rich region suggesting that this region plays a role in the pathogenesis of HNA. PMID:19139049

Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy.

PubMed

Landsverk, Megan L; Ruzzo, Elizabeth K; Mefford, Heather C; Buysse, Karen; Buchan, Jillian G; Eichler, Evan E; Petty, Elizabeth M; Peterson, Esther A; Knutzen, Dana M; Barnett, Karen; Farlow, Martin R; Caress, Judy; Parry, Gareth J; Quan, Dianna; Gardner, Kathy L; Hong, Ming; Simmons, Zachary; Bird, Thomas D; Chance, Phillip F; Hannibal, Mark C

2009-04-01

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder associated with recurrent episodes of focal neuropathy primarily affecting the brachial plexus. Point mutations in the SEPT9 gene have been previously identified as the molecular basis of HNA in some pedigrees. However in many families, including those from North America demonstrating a genetic founder haplotype, no sequence mutations have been detected. We report an intragenic 38 Kb SEPT9 duplication that is linked to HNA in 12 North American families that share the common founder haplotype. Analysis of the breakpoints showed that the duplication is identical in all pedigrees, and molecular analysis revealed that the duplication includes the 645 bp exon in which previous HNA mutations were found. The SEPT9 transcript variants that span this duplication contain two in-frame repeats of this exon, and immunoblotting demonstrates larger molecular weight SEPT9 protein isoforms. This exon also encodes for a majority of the SEPT9 N-terminal proline rich region suggesting that this region plays a role in the pathogenesis of HNA.

Extreme Precipitation and Beach Closures in the Great Lakes Region: Evaluating Risk among the Elderly

PubMed Central

Bush, Kathleen F.; Fossani, Cheryl L.; Li, Shi; Mukherjee, Bhramar; Gronlund, Carina J.; O’Neill, Marie S.

2014-01-01

As a result of climate change, extreme precipitation events are expected to increase in frequency and intensity. Runoff from these extreme events poses threats to water quality and human health. We investigated the impact of extreme precipitation and beach closings on the risk of gastrointestinal illness (GI)-related hospital admissions among individuals 65 and older in 12 Great Lakes cities from 2000 to 2006. Poisson regression models were fit in each city, controlling for temperature and long-term time trends. City-specific estimates were combined to form an overall regional risk estimate. Approximately 40,000 GI-related hospital admissions and over 100 beach closure days were recorded from May through September during the study period. Extreme precipitation (≥90th percentile) occurring the previous day (lag 1) is significantly associated with beach closures in 8 of the 12 cities (p < 0.05). However, no association was observed between beach closures and GI-related hospital admissions. These results support previous work linking extreme precipitation to compromised recreational water quality. PMID:24534768

Oceanic influence on seasonal malaria outbreaks over Senegal and Sahel. Predictability using S4CAST model

NASA Astrophysics Data System (ADS)

Diouf, Ibrahima; Deme, Abdoulaye; Rodriguez-Fonseca, Belen; Suárez-Moreno, Roberto; Cisse, Moustapha; Ndione, Jacques-André; Thierno Gaye, Amadou

2014-05-01

Senegal and, in general, West African regions are affected by important outbreaks of diseases with destructive consequences for human population, livestock and country's economy. The vector-borne diseases such as mainly malaria, Rift Valley Fever and dengue are affected by the interanual to decadal variability of climate. Analysis of the spatial and temporal variability of climate parameters and associated oceanic patterns is important in order to assess the climate impact on malaria transmission. In this study, the approach developed to study the malaria-climate link is predefined by the QWeCI project (Quantifying Weather and Climate Impacts on Health in Developing Countries). Preliminary observations and simulations results over Senegal Ferlo region, confirm that the risk of malaria transmission is mainly linked to climate parameters such as rainfall, temperature and relative humidity; and a lag of one to two months between the maximum of malaria and the maximum of climate parameters as rainfall is observed. As climate variables are able to be predicted from oceanic SST variability in remote regions, this study explores seasonal predictability of malaria incidence outbreaks from previous sea surface temperatures conditions in different ocean basins. We have found causal or coincident relationship between El Niño and malaria parameters by coupling LMM UNILIV malaria model and S4CAST statistiscal model with the aim of predicting the malaria parameters with more than 6 months in advance. In particular, El Niño is linked to an important decrease of the number of mosquitoes and the malaria incidence. Results from this research, after assessing the seasonal malaria parameters, are expected to be useful for decision makers to better access to climate forecasts and application on health in the framework of rolling back malaria transmission.

The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis.

PubMed

Heinz, Franz X; Stiasny, Karin

2017-03-01

Zika virus was discovered ∼70 years ago in Uganda and maintained a low profile as a human disease agent in Africa and Asia. Only recently has it caused explosive outbreaks in previously unaffected regions, first in Oceania and then in the Americas since 2015. Of special concern is the newly identified link between congenital malformations (especially microcephaly) and Zika virus infections during pregnancy. At present, it is unclear whether Zika virus changed its pathogenicity or whether the huge number of infections allowed the recognition of a previously cryptic pathogenic property. The purpose of this review is to discuss recent data on the molecular antigenic structure of Zika virus in the context of antibody-mediated neutralization and antibody-dependent enhancement (ADE) of infection, a phenomenon that has been implicated in the development of severe disease caused by the related dengue viruses. Emphasis is given to epitopes of antibodies that potently neutralize Zika virus and also to epitopes that provide antigenic links to other important human-pathogenic flaviviruses such as dengue, yellow fever, West Nile, Japanese encephalitis, and tick-borne encephalitis viruses. The antigenic cross talk between Zika and dengue viruses appears to be of special importance, since they cocirculate in many regions of endemicity and sequential infections are likely to occur frequently. New insights into the molecular antigenic structure of Zika virus and flaviviruses in general have provided the foundation for great progress made in developing Zika virus vaccines and antibodies for passive immunization. Copyright © 2017 American Society for Microbiology.

The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis

PubMed Central

Stiasny, Karin

2017-01-01

SUMMARY Zika virus was discovered ∼70 years ago in Uganda and maintained a low profile as a human disease agent in Africa and Asia. Only recently has it caused explosive outbreaks in previously unaffected regions, first in Oceania and then in the Americas since 2015. Of special concern is the newly identified link between congenital malformations (especially microcephaly) and Zika virus infections during pregnancy. At present, it is unclear whether Zika virus changed its pathogenicity or whether the huge number of infections allowed the recognition of a previously cryptic pathogenic property. The purpose of this review is to discuss recent data on the molecular antigenic structure of Zika virus in the context of antibody-mediated neutralization and antibody-dependent enhancement (ADE) of infection, a phenomenon that has been implicated in the development of severe disease caused by the related dengue viruses. Emphasis is given to epitopes of antibodies that potently neutralize Zika virus and also to epitopes that provide antigenic links to other important human-pathogenic flaviviruses such as dengue, yellow fever, West Nile, Japanese encephalitis, and tick-borne encephalitis viruses. The antigenic cross talk between Zika and dengue viruses appears to be of special importance, since they cocirculate in many regions of endemicity and sequential infections are likely to occur frequently. New insights into the molecular antigenic structure of Zika virus and flaviviruses in general have provided the foundation for great progress made in developing Zika virus vaccines and antibodies for passive immunization. PMID:28179396

Molecular interactions between photosystem I and ferredoxin: an integrated energy frustration and experimental model

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

Cashman, Derek J.; Zhu, Tuo; Simmerman, Richard F.

2014-08-01

The stromal domain (PsaC, PsaD, and PsaE) of photosystem I (PSI) reduces transiently bound ferredoxin (Fd) or flavodoxin. Experimental structures exist for all of these protein partners individually, but no experimental structure of the PSI/Fd or PSI/flavodoxin complexes is presently available. Molecular models of Fd docked onto the stromal domain of the cyanobacterial PSI site are constructed here utilizing X-ray and NMR structures of PSI and Fd, respectively. Moreover, predictions of potential protein-protein interaction regions are based on experimental site-directed mutagenesis and cross-linking studies to guide rigid body docking calculations of Fd into PSI, complemented by energy landscape theory tomore » bring together regions of high energetic frustration on each of the interacting proteins. Results identify two regions of high localized frustration on the surface of Fd that contain negatively charged Asp and Glu residues. Our study predicts that these regions interact predominantly with regions of high localized frustration on the PsaC, PsaD, and PsaE chains of PSI, which include several residues predicted by previous experimental studies.« less

Differences in genetic and environmental influences on the human cerebral cortex associated with development during childhood and adolescence.

PubMed

Lenroot, Rhoshel K; Schmitt, James E; Ordaz, Sarah J; Wallace, Gregory L; Neale, Michael C; Lerch, Jason P; Kendler, Kenneth S; Evans, Alan C; Giedd, Jay N

2009-01-01

In this report, we present the first regional quantitative analysis of age-related differences in the heritability of cortical thickness using anatomic MRI with a large pediatric sample of twins, twin siblings, and singletons (n = 600, mean age 11.1 years, range 5-19). Regions of primary sensory and motor cortex, which develop earlier, both phylogenetically and ontologically, show relatively greater genetic effects earlier in childhood. Later developing regions within the dorsal prefrontal cortex and temporal lobes conversely show increasingly prominent genetic effects with maturation. The observation that regions associated with complex cognitive processes such as language, tool use, and executive function are more heritable in adolescents than children is consistent with previous studies showing that IQ becomes increasingly heritable with maturity(Plomin et al. 1997: Psychol Sci 8:442-447). These results suggest that both the specific cortical region and the age of the population should be taken into account when using cortical thickness as an intermediate phenotype to link genes, environment, and behavior. (c) 2007 Wiley-Liss, Inc.

N-linked glycosylation of cortical N-methyl-D-aspartate and kainate receptor subunits in schizophrenia.

PubMed

Tucholski, Janusz; Simmons, Micah S; Pinner, Anita L; McMillan, Laurence D; Haroutunian, Vahram; Meador-Woodruff, James H

2013-08-21

Dysfunctional glutamate neurotransmission has been implicated in the pathophysiology of schizophrenia. Abnormal expressions in schizophrenia of ionotropic glutamate receptors (iGluRs) and the proteins that regulate their trafficking have been found to be region and subunit specific in brain, suggesting that abnormal trafficking of iGluRs may contribute toward altered glutamatergic neurotransmission. The post-translational modification N-glycosylation of iGluR subunits can be used as a proxy for their intracellular localization. Receptor complexes assemble in the lumen of the endoplasmic reticulum, where N-glycosylation begins with the addition of N-linked oligomannose glycans, and is subsequently trimmed and replaced by more elaborate glycans while trafficking through the Golgi apparatus. Previously, we found abnormalities in N-glycosylation of the GluR2 AMPA receptor subunit in schizophrenia. Here, we investigated N-glycosylation of N-methyl-D-aspartate and kainate (KA) receptor subunits in the dorsolateral prefrontal cortex from patients with schizophrenia and a comparison group. We used enzymatic deglycosylation with two glycosidases: endoglycosidase H (Endo H), which removes immature high mannose-containing sugars, and peptide-N-glycosidase F (PNGase F), which removes all N-linked sugars. The NR1, NR2A, NR2B, GluR6, and KA2 subunits were all sensitive to treatment with Endo H and PNGase F. The GluR6 KA receptor subunit was significantly more sensitive to Endo H-mediated deglycosylation in schizophrenia, suggesting a larger molecular mass of N-linked high mannose and/or hybrid sugars on GluR6. This finding, taken with our previous work, suggests that a cellular mechanism underlying abnormal glutamate neurotransmission in schizophrenia may involve abnormal trafficking of both AMPA and KA receptors.

High-resolution mapping of the x-linked hypohidrotic ectodermal dysplasia (EDA) locus

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

Zonana, J.; Jones, M.; Litt, M.

1992-11-01

The X-linked hypohidrotic ectodermal dysplasia (EDA) locus has been previously localized to the subchromosomal region Xq11-q21.1. The authors have extended previous linkage studies and analyzed linkage between the EDA locus and 10 marker loci, including five new loci, in 41 families. Four of the marker loci showed no recombination with the EDA locus, and six other loci were also linked to the EDA locus with recombination fractions of .009-.075. Multipoint analysis gave support to the placement of the PGK1P1 locus proximal to the EDA locus and the DXS453 and PGK1 loci distal to EDA. Further ordering of the loci couldmore » be inferred from a human-rodent somatic cell hybrid derived from an affected female with EDA and an X;9 translocation and from studies of an affected male with EDA and a submicroscopic deletion. Three of the proximal marker loci, which showed no recombination with the EDA locus, when used in combination, were informative in 92% of females. The closely linked flanking polymorphic loci DXS339 and DXS453 had heterozygosites of 72% and 76%, respectively, and when used jointly, they were doubly informative in 52% of females. The human DXS732 locus was defined by a conserved mouse probe pcos169E/4 (DXCrc169 locus) that consegregates with the mouse tabby (Ta) locus, a potential homologue to the EDA locus. The absence of recombination between EDA and the DXSA732 locus lends support to the hypothesis that the DXCrc169 locus in the mouse and the DXS732 locus in humans may contain candidate sequences for the Ta and EDA genes, respectively. 36 refs., 1 fig., 5 tabs.« less

Wide band fiber-optic communications

NASA Technical Reports Server (NTRS)

Bates, Harry E.

1993-01-01

A number of optical communication lines are now in use at the Kennedy Space Center (KSC) for the transmission of voice, computer data and video signals. At the present time most of these channels utilize a single carrier wavelength centered near 1300 nm. As a result of previous work the bandwidth capacity of a number of these channels is being increased by transmitting another signal in the 1550 nm region on the same fiber. This is accomplished by means of wavelength division multiplexing (WDM). It is therefore important to understand the bandwidth properties of the installed fiber plant. This work developed new procedures for measuring the bandwidth of fibers in both the 1300nm and 1550nm region. In addition, a preliminary study of fiber links terminating in the Engineering Development Laboratory was completed.

The proteolytic processing site of the precursor of lysyl oxidase.

PubMed Central

Cronshaw, A D; Fothergill-Gilmore, L A; Hulmes, D J

1995-01-01

The precise cleavage site of the N-terminal propeptide region of the precursor of lysyl oxidase has not yet been established, due to N-terminal blocking of the mature protein. Using a combination of peptide fragmentation, amino acid sequencing, time-of-flight m.s. and partial chemical unblocking procedures, it is shown that the mature form of lysyl oxidase begins at residue Asp-169 of the precursor protein (numbered according to the human sequence). The cleavage site is 28 residues to the C-terminal side of the site previously suggested on the basis of apparant molecular mass by SDS/PAGE, with the consequence that the two putative, N-linked glycosylation sites and the position of the Arg/Gln sequence polymorphism are now all in the precursor region. PMID:7864821

Linkage analysis of quantitative refraction and refractive errors in the Beaver Dam Eye Study.

PubMed

Klein, Alison P; Duggal, Priya; Lee, Kristine E; Cheng, Ching-Yu; Klein, Ronald; Bailey-Wilson, Joan E; Klein, Barbara E K

2011-07-13

Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed. Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed. Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 × 10(-4)), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 × 10(-3) and 1.48 × 10(-3), respectively) and to 7p15 of refraction (empiric P = 9.43 × 10(-4)). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 × 10(-3)), a region previously linked to high myopia. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11.

High-resolution meiotic and physical mapping of the Best vitelliform macular dystrophy (VMD2) locus to pericentromeric chromosome 11

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

Weber, B.H.F.; Vogt, G.; Stoehr, H.

1994-12-01

Best vitelliform macular dystrophy (VMD2) has previously been linked to several microsatellite markers from chromosome 11. Subsequently, additional genetic studies have refined the Best disease region to a 3.7-cM interval flanked by markers at D11S903 and PYGM. To further narrow the interval containing the Best disease gene and to obtain an estimate of the physical size of the minimal candidate region, we used a combination of high-resolution PCR hybrid mapping and analysis of recombinant Best disease chromosomes. We identified six markers from within the D11S903-PYGM interval that show no recombination with the defective gene in three multigeneration Best disease pedigrees.more » Our hybrid panel localizes these markers on either side of the centromere on chromosome 11. The closest markers flanking the disease gene are at D11S986 in band p12-11.22 on the short arm and at D11S480 in band q13.2-13.3 on the proximal long arm. This study demonstrates that the physical size of the Best disease region is exceedingly larger than previously estimated from the genetic data, because of the proximity of the defective gene to the centromere of chromosome 11.« less

Risky Adaptation: The Effect of Temperature Extremes on HIV Prevalence

NASA Astrophysics Data System (ADS)

Baker, R.

2016-12-01

Previous work has linked rainfall shock to an increase in HIV prevalence in Sub-Saharan Africa. In this paper we take advantage of repeated waves of the Demographic and Health Survey (DHS) and a new high resolution climate dataset for the African continent to test the non-linear relationship between temperature and HIV. We find a strong and significant relationship between recent high temperatures and increases in HIV prevalence in a region. We then test the effect of temperature on risk factors that may contribute to this increase. High temperatures are linked to an increase in sexual violence, number of partners and a decrease in condom usage - all of which may contribute to the uptake in HIV rate. This paper contributes to the literature on adaptation from two standpoints. First, we suggest that some behavioral changes that are classed as adaptations, in the sense that they allow for consumption smoothing in the face of extreme temperatures, may carry unexpected risks to the individuals involved. Second, we find preliminary evidence that the relationship between temperature and these risky behaviors is diminished in regions prone to higher temperatures, suggesting some adaptation is possible in the long run.

Prediction of the aggregation propensity of proteins from the primary sequence: aggregation properties of proteomes.

PubMed

Castillo, Virginia; Graña-Montes, Ricardo; Sabate, Raimon; Ventura, Salvador

2011-06-01

In the cell, protein folding into stable globular conformations is in competition with aggregation into non-functional and usually toxic structures, since the biophysical properties that promote folding also tend to favor intermolecular contacts, leading to the formation of β-sheet-enriched insoluble assemblies. The formation of protein deposits is linked to at least 20 different human disorders, ranging from dementia to diabetes. Furthermore, protein deposition inside cells represents a major obstacle for the biotechnological production of polypeptides. Importantly, the aggregation behavior of polypeptides appears to be strongly influenced by the intrinsic properties encoded in their sequences and specifically by the presence of selective short regions with high aggregation propensity. This allows computational methods to be used to analyze the aggregation properties of proteins without the previous requirement for structural information. Applications range from the identification of individual amyloidogenic regions in disease-linked polypeptides to the analysis of the aggregation properties of complete proteomes. Herein, we review these theoretical approaches and illustrate how they have become important and useful tools in understanding the molecular mechanisms underlying protein aggregation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synaptic Modifications in the Medial Prefrontal Cortex in Susceptibility and Resilience to Stress

PubMed Central

Wang, Minghui; Perova, Zinaida; Arenkiel, Benjamin R.

2014-01-01

When facing stress, most individuals are resilient whereas others are prone to developing mood disorders. The brain mechanisms underlying such divergent behavioral responses remain unclear. Here we used the learned helplessness procedure in mice to examine the role of the medial prefrontal cortex (mPFC), a brain region highly implicated in both clinical and animal models of depression, in adaptive and maladaptive behavioral responses to stress. We found that uncontrollable and inescapable stress induced behavioral state-dependent changes in the excitatory synapses onto a subset of mPFC neurons: those that were activated during behavioral responses as indicated by their expression of the activity reporter c-Fos. Whereas synaptic potentiation was linked to learned helplessness, a depression-like behavior, synaptic weakening, was associated with resilience to stress. Notably, enhancing the activity of mPFC neurons using a chemical–genetic method was sufficient to convert the resilient behavior into helplessness. Our results provide direct evidence that mPFC dysfunction is linked to maladaptive behavioral responses to stress, and suggest that enhanced excitatory synaptic drive onto mPFC neurons may underlie the previously reported hyperactivity of this brain region in depression. PMID:24872553

A SPECT study of language and brain reorganization three years after pediatric brain injury.

PubMed

Chiu Wong, Stephanie B; Chapman, Sandra B; Cook, Lois G; Anand, Raksha; Gamino, Jacquelyn F; Devous, Michael D

2006-01-01

Using single photon emission computed tomography (SPECT), we investigated brain plasticity in children 3 years after sustaining a severe traumatic brain injury (TBI). First, we assessed brain perfusion patterns (i.e., the extent of brain blood flow to regions of the brain) at rest in eight children who suffered severe TBI as compared to perfusion patterns in eight normally developing children. Second, we examined differences in perfusion between children with severe TBI who showed good versus poor recovery in complex discourse skills. Specifically, the children were asked to produce and abstract core meaning for two stories in the form of a lesson. Inconsistent with our predictions, children with severe TBI showed areas of increased perfusion as compared to normally developing controls. Adult studies have shown the reverse pattern with TBI associated with reduced perfusion. With regard to the second aim and consistent with previously identified brain-discourse relations, we found a strong positive association between perfusion in right frontal regions and discourse abstraction abilities, with higher perfusion linked to better discourse outcomes and lower perfusion linked to poorer discourse outcomes. Furthermore, brain-discourse patterns of increased perfusion in left frontal regions were associated with lower discourse abstraction ability. The results are discussed in terms of how brain changes may represent adaptive and maladaptive plasticity. The findings offer direction for future studies of brain plasticity in response to neurocognitive treatments.

UFD4 lacking the proteasome-binding region catalyses ubiquitination but is impaired in proteolysis.

PubMed

Xie, Youming; Varshavsky, Alexander

2002-12-01

The ubiquitin system recognizes degradation signals of protein substrates through E3-E2 ubiquitin ligases, which produce a substrate-linked multi-ubiquitin chain. Ubiquitinated substrates are degraded by the 26S proteasome, which consists of the 20S protease and two 19S particles. We previously showed that UBR1 and UFD4, two E3 ligases of the yeast Saccharomyces cerevisiae, interact with specific proteasomal subunits. Here we advance this analysis for UFD4 and show that it interacts with RPT4 and RPT6, two subunits of the 19S particle. The 201-residue amino-terminal region of UFD4 is essential for its binding to RPT4 and RPT6. UFD4(DeltaN), which lacks this N-terminal region, adds ubiquitin to test substrates with apparently wild-type activity, but is impaired in conferring short half-lives on these substrates. We propose that interaction of a targeted substrate with the 26S proteasome involves contacts of specific proteasomal subunits with the substrate-bound ubiquitin ligase, with the substrate-linked multi-ubiquitin chain and with the substrate itself. This multiple-site binding may function to slow down dissociation of the substrate from the proteasome and to facilitate the unfolding of substrate through ATP-dependent movements of the chaperone subunits of the 19S particle.

Domain-general signals in the cingulo-opercular network for visuospatial attention and episodic memory

PubMed Central

Sestieri, Carlo; Corbetta, Maurizio; Spadone, Sara; Romani, Gian Luca; Shulman, Gordon L.

2014-01-01

We investigated the functional properties of a previously described cingulo-opercular network (CON) putatively involved in cognitive control. Analyses of common fMRI task-evoked activity during perceptual and episodic memory search tasks that differently recruited the dorsal attention (DAN) and default mode network (DMN) established the generality of this network. Regions within the CON (anterior insula/frontal operculum and anterior cingulate/presupplementary cortex) displayed sustained signals during extended periods in which participants searched for behaviourally relevant information in a dynamically changing environment or from episodic memory in the absence of sensory stimulation. The CON was activated during all phases of both tasks, which involved trial initiation, target detection, decision and response, indicating its consistent involvement in a broad range of cognitive processes. Functional connectivity analyses showed that the CON flexibly linked with the DAN or DMN regions during perceptual or memory search, respectively. Aside from the CON, only a limited number of regions, including the lateral prefrontal cortex, showed evidence of domain-general, sustained activity, although in some cases the common activations may have reflected the functional-anatomical variability of domain-specific regions rather than a true domain-generality. These additional regions also showed task-dependent functional connectivity with the DMN and DAN, suggesting that this feature is not a specific marker of cognitive control. Finally, multivariate clustering analyses separated the CON from other fronto-parietal regions previously associated with cognitive control, indicating a unique fingerprint. We conclude that the CON’s functional properties and interactions with other brain regions support a broad role in cognition, consistent with its characterization as a task-control network. PMID:24144246

Analysis of ligand-receptor cross-linked fragments by mass spectrometry

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

Son, C.D.; Sargsyan, H.; Hurst, Gregory

G-protein coupled receptors (GPCRs) are a class of integral membrane receptor proteins that are characterized by a signature seven-transmembrane (7-TM) configuration. The a-factor receptor (Ste2p) from Saccharomyces cerevisiae is a GPCR that, upon binding of a peptide ligand, transduces a signal to initiate a cascade of events leading to the mating of haploid yeast cells. This study summarizes the application of affinity purification and of matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) experiments using biotinylated photoactivatable a-factor analogs. Affinity purification and enrichment of biotinylated peptides by monomeric avidin beads resulted in mass spectrometric detection of specific signals corresponding to crosslinked fragments ofmore » Ste2p. Data obtained from cyanogen bromide (CNBr) fragments of receptor cross-linked to an a-factor analog with the photoaffinity group p-benzoyl-L-phenylalanine on position 1 were in agreement with the previous results reported by our laboratory suggesting the cross-linking between position 1 of a-factor and a region of Ste2p covering residues 251 294.« less

A reappraisal of the age, origin and structural setting of sulphide mineralisation in the UK North Pennines Orefield

NASA Astrophysics Data System (ADS)

Holdsworth, Bob; Dempsey, Eddie; Selby, David; Le Cornu, Chris; Young, Brian

2015-04-01

The North Pennines Orefield (NPO) is centred on the Alston block, a structural high of fractured Carboniferous sedimentary rocks that unconformably overlie a Devonian age (ca. 399 Ma) granite pluton buried at shallow depths (<0.5 km). The orefield has long been considered to be a classic example of a Mississippi Valley Type (MVT) deposit where the source of the metals and sulphur are derived by hydrothermal leaching of the host sedimentary (carbonate-rich) rocks. The vein-hosted part of the orefield consists of linked systems of shear and tensile fractures with a variety of regionally recognised orientations (ESE-WNW Quarter Point, NE-SW, NW-SE Cross Veins). These are associated with lead (galena), iron (pyrite, pyrrhotite, marcasite), copper (chalcopyrite), zinc (sphalerite), fluorite, barite and quartz mineralization. New Rhenium-Osmium (Re-Os) isotope geochemical analysis of the vein-hosted pyrite mineralization suggests that: (i) the metalliferous ores of the NPO formed ca. 294Ma (earliest Permian); and (ii) that they carry an initial Os ratio indicative of a mantle source similar to that indicated by the initial Os ratio of the Whin Sill dolerite suite (emplacement ages ca. 297-294 Ma). New field observations and stress inversion analyses show that at least two regional deformation events are recognised in the Carboniferous host rocks of the NPO. A initial phase of Late Carboniferous ('Variscan') N-S compression pre-dates mineralisation and leads to formation of the NW-SE fractures, initiation of the Burtreeford Disturbance as a N-S fault and compressional reactivation of the previously extensional E-W Lunedale Fault. A later phase of dextral transtension (NNE-SSW extension, ESE-WNW compression) leads to the formation of the ESE-WNW and NE-SW veins, together with compressional reactivation of the Burtreeford Disturbance and Lunedale Fault. Field and microstructural analyses show that the transtensional deformation is synchronous with the main phases of NPO mineralisation and also with emplacement of the Whin Sill and associated intrusions. We conclude that: (i) the main phase of NPO mineralization occurred synchronously with regional dextral transtension during the earliest Permian; (ii) that mineralization is genetically linked to a mantle source and (iii) that the genesis of the NPO is closely linked to that of the broadly penecontemporaneous Whin Sill and associated intrusions in northern England. Our new findings are consistent with structural histories recognised in adjacent regions (e.g. Dent-Pennine Fault systems; Northumberland Basin) and point to a major regional phase of mantle-sourced mineralization, igneous intrusion and transtensional deformation in the early Permian. Previous models suggesting that the NPO is a classic example of a MVT mineral deposit or that the mineralizing fluids are related to the influx of Mesozoic brines are largely incorrect.

Mutational Survey of the PHEX Gene in Patients with X-linked Hypophosphatemic Rickets

PubMed Central

Ichikawa, Shoji; Traxler, Elizabeth A.; Estwick, Selina A.; Curry, Leah R.; Johnson, Michelle L.; Sorenson, Andrea H.; Imel, Erik A.; Econs, Michael J.

2008-01-01

X-linked hypophosphatemic rickets (XLH) is a dominantly inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. XLH is caused by inactivating mutations in PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). In this study, we sequenced the PHEX gene in subjects from 26 kindreds who were clinically diagnosed with XLH. Sequencing revealed 18 different mutations, of which thirteen have not been reported previously. In addition to deletions, splice site mutations, and missense and nonsense mutations, a rare point mutation in the 3’-untranslated region (3’-UTR) was identified as a novel cause of XLH. In summary, we identified a wide spectrum of mutations in the PHEX gene. Our data, in accord with those of others, indicate that there is no single predominant PHEX mutation responsible for XLH. PMID:18625346

The cosmic spiderweb: equivalence of cosmic, architectural and origami tessellations.

PubMed

Neyrinck, Mark C; Hidding, Johan; Konstantatou, Marina; van de Weygaert, Rien

2018-04-01

For over 20 years, the term 'cosmic web' has guided our understanding of the large-scale arrangement of matter in the cosmos, accurately evoking the concept of a network of galaxies linked by filaments. But the physical correspondence between the cosmic web and structural engineering or textile 'spiderwebs' is even deeper than previously known, and also extends to origami tessellations. Here, we explain that in a good structure-formation approximation known as the adhesion model, threads of the cosmic web form a spiderweb, i.e. can be strung up to be entirely in tension. The correspondence is exact if nodes sampling voids are included, and if structure is excluded within collapsed regions (walls, filaments and haloes), where dark-matter multistreaming and baryonic physics affect the structure. We also suggest how concepts arising from this link might be used to test cosmological models: for example, to test for large-scale anisotropy and rotational flows in the cosmos.

The cosmic spiderweb: equivalence of cosmic, architectural and origami tessellations

NASA Astrophysics Data System (ADS)

Neyrinck, Mark C.; Hidding, Johan; Konstantatou, Marina; van de Weygaert, Rien

2018-04-01

For over 20 years, the term `cosmic web' has guided our understanding of the large-scale arrangement of matter in the cosmos, accurately evoking the concept of a network of galaxies linked by filaments. But the physical correspondence between the cosmic web and structural engineering or textile `spiderwebs' is even deeper than previously known, and also extends to origami tessellations. Here, we explain that in a good structure-formation approximation known as the adhesion model, threads of the cosmic web form a spiderweb, i.e. can be strung up to be entirely in tension. The correspondence is exact if nodes sampling voids are included, and if structure is excluded within collapsed regions (walls, filaments and haloes), where dark-matter multistreaming and baryonic physics affect the structure. We also suggest how concepts arising from this link might be used to test cosmological models: for example, to test for large-scale anisotropy and rotational flows in the cosmos.

Intragenic SNP haplotypes associated with 84dup18 mutation in TNFRSF11A in four FEO pedigrees suggest three independent origins for this mutation.

PubMed

Elahi, Elahe; Shafaghati, Yousef; Asadi, Sareh; Absalan, Farnaz; Goodarzi, Hani; Gharaii, Nava; Karimi-Nejad, Mohammad Hassan; Shahram, Farhad; Hughes, Anne E

2007-01-01

Familial expansile osteolysis (FEO) is a rare disorder causing bone dysplasia. The clinical features of FEO include early-onset hearing loss, tooth destruction, and progressive lytic expansion within limb bones causing pain, fracture, and deformity. An 18-bp duplication in the first exon of the TNFRSF11A gene encoding RANK has been previously identified in four FEO pedigrees. Despite having the identical mutation, phenotypic variations among affected individuals of the same and different pedigrees were noted. Another 18-bp duplication, one base proximal to the duplication previously reported, was subsequently found in two unrelated FEO patients. Finally, mutations overlapping with the mutations found in the FEO pedigrees have been found in ESH and early-onset PDB pedigrees. An Iranian FEO pedigree that contains six affected individuals dispersed in three generations has previously been introduced; here, the clinical features of the proband are reported in greater detail, and the genetic defect of the pedigree is presented. Direct sequencing of the entire coding region and upstream and downstream noncoding regions of TNFRSF11A in her DNA revealed the same 18-bp duplication mutation as previously found in the four FEO pedigrees. Additionally, eight sequence variations as compared to the TNFRSF11A reference sequence were identified, and a haplotype linked to the mutation based on these variations was defined. Although the mutation in the Iranian and four of the previously described FEO pedigrees was the same, haplotypes based on the intragenic SNPs suggest that the mutations do not share a common descent.

Oxytocin and Vasopressin Receptor Gene Variation as a Proximate Base for Inter- and Intraspecific Behavioral Differences in Bonobos and Chimpanzees

PubMed Central

Staes, Nicky; Stevens, Jeroen M. G.; Helsen, Philippe; Hillyer, Mia; Korody, Marisa; Eens, Marcel

2014-01-01

Recent literature has revealed the importance of variation in neuropeptide receptor gene sequences in the regulation of behavioral phenotypic variation. Here we focus on polymorphisms in the oxytocin receptor gene (OXTR) and vasopressin receptor gene 1a (Avpr1a) in chimpanzees and bonobos. In humans, a single nucleotide polymorphism (SNP) in the third intron of OXTR (rs53576 SNP (A/G)) is linked with social behavior, with the risk allele (A) carriers showing reduced levels of empathy and prosociality. Bonobos and chimpanzees differ in these same traits, therefore we hypothesized that these differences might be reflected in variation at the rs53576 position. We sequenced a 320 bp region surrounding rs53576 but found no indications of this SNP in the genus Pan. However, we identified previously unreported SNP variation in the chimpanzee OXTR sequence that differs from both humans and bonobos. Humans and bonobos have previously been shown to have a more similar 5′ promoter region of Avpr1a when compared to chimpanzees, who are polymorphic for the deletion of ∼360 bp in this region (+/− DupB) which includes a microsatellite (RS3). RS3 has been linked with variation in levels of social bonding, potentially explaining part of the interspecies behavioral differences found in bonobos, chimpanzees and humans. To date, results for bonobos have been based on small sample sizes. Our results confirmed that there is no DupB deletion in bonobos with a sample size comprising approximately 90% of the captive founder population, whereas in chimpanzees the deletion of DupB had the highest frequency. Because of the higher frequency of DupB alleles in our bonobo population, we suggest that the presence of this microsatellite may partly reflect documented differences in levels of sociability found in bonobos and chimpanzees. PMID:25405348

A specific insertion of a solo-LTR characterizes the Y-chromosome of Bryonia dioica (Cucurbitaceae).

PubMed

Oyama, Ryan K; Silber, Martina V; Renner, Susanne S

2010-06-14

Relatively few species of flowering plants are dioecious and even fewer are known to have sex chromosomes. Current theory posits that homomorphic sex chromosomes, such as found in Bryonia dioica (Cucurbitaceae), offer insight into the early stages in the evolution of sex chromosomes from autosomes. Little is known about these early steps, but an accumulation of transposable element sequences has been observed on the Y-chromosomes of some species with heteromorphic sex chromosomes. Recombination, by which transposable elements are removed, is suppressed on at least part of the emerging Y-chromosome, and this may explain the correlation between the emergence of sex chromosomes and transposable element enrichment. We sequenced 2321 bp of the Y-chromosome in Bryonia dioica that flank a male-linked marker, BdY1, reported previously. Within this region, which should be suppressed for recombination, we observed a solo-LTR nested in a Copia-like transposable element. We also found other, presumably paralogous, solo-LTRs in a consensus sequence of the underlying Copia-like transposable element. Given that solo-LTRs arise via recombination events, it is noteworthy that we find one in a genomic region where recombination should be suppressed. Although the solo-LTR could have arisen before recombination was suppressed, creating the male-linked marker BdY1, our previous study on B. dioica suggested that BdY1 may not lie in the recombination-suppressed region of the Y-chromosome in all populations. Presence of a solo-LTR near BdY1 therefore fits with the observed correlation between retrotransposon accumulation and the suppression of recombination early in the evolution of sex chromosomes. These findings further suggest that the homomorphic sex chromosomes of B. dioica, the first organism for which genetic XY sex-determination was inferred, are evolutionarily young and offer reference information for comparative studies of other plant sex chromosomes.

Wing patterning gene redefines the mimetic history of Heliconius butterflies.

PubMed

Hines, Heather M; Counterman, Brian A; Papa, Riccardo; Albuquerque de Moura, Priscila; Cardoso, Marcio Z; Linares, Mauricio; Mallet, James; Reed, Robert D; Jiggins, Chris D; Kronforst, Marcus R; McMillan, W Owen

2011-12-06

The mimetic butterflies Heliconius erato and Heliconius melpomene have undergone parallel radiations to form a near-identical patchwork of over 20 different wing-pattern races across the Neotropics. Previous molecular phylogenetic work on these radiations has suggested that similar but geographically disjunct color patterns arose multiple times independently in each species. The neutral markers used in these studies, however, can move freely across color pattern boundaries, and therefore might not represent the history of the adaptive traits as accurately as markers linked to color pattern genes. To assess the evolutionary histories across different loci, we compared relationships among races within H. erato and within H. melpomene using a series of unlinked genes, genes linked to color pattern loci, and optix, a gene recently shown to control red color-pattern variation. We found that although unlinked genes partition populations by geographic region, optix had a different history, structuring lineages by red color patterns and supporting a single origin of red-rayed patterns within each species. Genes closely linked (80-250 kb) to optix exhibited only weak associations with color pattern. This study empirically demonstrates the necessity of examining phenotype-determining genomic regions to understand the history of adaptive change in rapidly radiating lineages. With these refined relationships, we resolve a long-standing debate about the origins of the races within each species, supporting the hypothesis that the red-rayed Amazonian pattern evolved recently and expanded, causing disjunctions of more ancestral patterns.

Links between white matter microstructure and cortisol reactivity to stress in early childhood: evidence for moderation by parenting.

PubMed

Sheikh, Haroon I; Joanisse, Marc F; Mackrell, Sarah M; Kryski, Katie R; Smith, Heather J; Singh, Shiva M; Hayden, Elizabeth P

2014-01-01

Activity of the hypothalamic-pituitary-adrenal axis (measured via cortisol reactivity) may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls' cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at age 3. White matter integrity was assessed by calculating fractional anisotropy (FA) of diffusion-weighted magnetic resonance imaging scans. Parenting styles were measured via a standardized parent-child interaction task. Significant associations were found between FA in white matter regions adjacent to the left thalamus, the right anterior cingulate cortex, and the right superior frontal gyrus (all ps < .001). Further, positive early caregiving moderated the effect of high cortisol reactivity on white matter FA (all ps ≤ .05), with high stress reactive girls who received greater parent positive affect showing white matter structure more similar to that of low stress reactive girls. Results show associations between white matter integrity of various limbic regions of the brain and early cortisol reactivity to stress and provide preliminary support for the notion that parenting may moderate associations.

Improvement of the Measure of the Network Survival Rate and its Application to a Japanese Business Relations Network

NASA Astrophysics Data System (ADS)

Kawamoto, Hirokazu; Takayasu, Hideki; Takayasu, Misako

We analyze the typical characteristics of the percolation transition of a large-scale complex network, a Japanese business relation network consisting of approximately 600,000 nodes and 4,000,000 links. By utilizing percolation characteristics, we revise the definition of network survival rate that we previously proposed. The new network survival rate has a strong correlation with the old one. The calculation cost is also much smaller and the number of trials decreases from 100,000 to 1,000. Finally, we discuss the identification of robust and fragile regions using this index.

Ala397Asp mutation of myosin VIIA gene segregating in a Spanish family with type-Ib Usher syndrome.

PubMed

Espinós, C; Millán, J M; Sánchez, F; Beneyto, M; Nájera, C

1998-06-01

In the current study, 12 Spanish families affected by type-I Usher syndrome, that was previously linked to chromosome 11q, were screened for the presence of mutations in the N-terminal coding portion of the motor domain of the myosin VIIA gene by single-strand conformation polymorphism analysis of the first 14 exons. A mutation (Ala397Asp) segregating with the disease was identified, and several polymorphisms were also detected. It is presumed that the other USHIB mutations in these families could be located in the unscreened regions of the gene.

Sialic acid catabolism and transport gene clusters are lineage specific in Vibrio vulnificus.

PubMed

Lubin, Jean-Bernard; Kingston, Joseph J; Chowdhury, Nityananda; Boyd, E Fidelma

2012-05-01

Sialic or nonulosonic acids are nine-carbon alpha ketosugars that are present in all vertebrate mucous membranes. Among bacteria, the ability to catabolize sialic acid as a carbon source is present mainly in pathogenic and commensal species of animals. Previously, it was shown that several Vibrio species carry homologues of the genes required for sialic acid transport and catabolism, which are genetically linked. In Vibrio cholerae on chromosome I, these genes are carried on the Vibrio pathogenicity island-2 region, which is confined to pathogenic isolates. We found that among the three sequenced Vibrio vulnificus clinical strains, these genes are present on chromosome II and are not associated with a pathogenicity island. To determine whether the sialic acid transport (SAT) and catabolism (SAC) region is universally present within V. vulnificus, we examined 67 natural isolates whose phylogenetic relationships are known. We found that the region was present predominantly among lineage I of V. vulnificus, which is comprised mainly of clinical isolates. We demonstrate that the isolates that contain this region can catabolize sialic acid as a sole carbon source. Two putative transporters are genetically linked to the region in V. vulnificus, the tripartite ATP-independent periplasmic (TRAP) transporter SiaPQM and a component of an ATP-binding cassette (ABC) transporter. We constructed an in-frame deletion mutation in siaM, a component of the TRAP transporter, and demonstrate that this transporter is essential for sialic acid uptake in this species. Expression analysis of the SAT and SAC genes indicates that sialic acid is an inducer of expression. Overall, our study demonstrates that the ability to catabolize and transport sialic acid is predominately lineage specific in V. vulnificus and that the TRAP transporter is essential for sialic acid uptake.

Deficiency mapping of quantitative trait loci affecting longevity in Drosophila melanogaster.

PubMed Central

Pasyukova, E G; Vieira, C; Mackay, T F

2000-01-01

In a previous study, sex-specific quantitative trait loci (QTL) affecting adult longevity were mapped by linkage to polymorphic roo transposable element markers, in a population of recombinant inbred lines derived from the Oregon and 2b strains of Drosophila melanogaster. Two life span QTL were each located on chromosomes 2 and 3, within sections 33E-46C and 65D-85F on the cytological map, respectively. We used quantitative deficiency complementation mapping to further resolve the locations of life span QTL within these regions. The Oregon and 2b strains were each crossed to 47 deficiencies spanning cytological regions 32F-44E and 64C-76B, and quantitative failure of the QTL alleles to complement the deficiencies was assessed. We initially detected a minimum of five and four QTL in the chromosome 2 and 3 regions, respectively, illustrating that multiple linked factors contribute to each QTL detected by recombination mapping. The QTL locations inferred from deficiency mapping did not generally correspond to those of candidate genes affecting oxidative and thermal stress or glucose metabolism. The chromosome 2 QTL in the 35B-E region was further resolved to a minimum of three tightly linked QTL, containing six genetically defined loci, 24 genes, and predicted genes that are positional candidates corresponding to life span QTL. This region was also associated with quantitative variation in life span in a sample of 10 genotypes collected from nature. Quantitative deficiency complementation is an efficient method for fine-scale QTL mapping in Drosophila and can be further improved by controlling the background genotype of the strains to be tested. PMID:11063689

Rain rate intensity model for communication link design across the Indian region

NASA Astrophysics Data System (ADS)

Kilaru, Aravind; Kotamraju, Sarat K.; Avlonitis, Nicholas; Sri Kavya, K. Ch.

2016-07-01

A study on rain statistical parameters such as one minute rain intensity, possible number of minute occurrences with respective percentage of time in a year has been evaluated for the purpose of communication link design at Ka, Q, V bands as well as at Free-Space Optical communication links (FSO). To understand possible outage period of a communication links due to rainfall and to investigate rainfall pattern, Automatic Weather Station (AWS) rainfall data is analysed due its ample presence across India. The climates of the examined AWS regions vary from desert to cold climate, heavy rainfall to variable rainfall regions, cyclone effective regions, mountain and coastal regions. In this way a complete and unbiased picture of the rainfall statistics for Indian region is evaluated. The analysed AWS data gives insight into yearly accumulated rainfall, maximum hourly accumulated rainfall, mean hourly accumulated rainfall, number of rainy days and number of rainy hours from 668 AWS locations. Using probability density function the one minute rainfall measurements at KL University is integrated with AWS measurements for estimating number of rain occurrences in terms of one minute rain intensity for annual rainfall accumulated between 100 mm and 5000 mm to give an insight into possible one minute accumulation pattern in an hour for comprehensive analysis of rainfall influence on a communication link for design engineers. So that low availability communications links at higher frequencies can be transformed into a reliable and economically feasible communication links for implementing High Throughput Services (HTS).

Recombination changes at the boundaries of fully and partially sex-linked regions between closely related Silene species pairs

PubMed Central

Campos, J L; Qiu, S; Guirao-Rico, S; Bergero, R; Charlesworth, D

2017-01-01

The establishment of a region of suppressed recombination is a critical change during sex chromosome evolution, leading to such properties as Y (and W) chromosome genetic degeneration, accumulation of repetitive sequences and heteromorphism. Although chromosome inversions can cause large regions to have suppressed recombination, and inversions are sometimes involved in sex chromosome evolution, gradual expansion of the non-recombining region could potentially sometimes occur. We here test whether closer linkage has recently evolved between the sex-determining region and several genes that are partially sex-linked in Silene latifolia, using Silene dioica, a closely related dioecious plants whose XY sex chromosome system is inherited from a common ancestor. The S. latifolia pseudoautosomal region (PAR) includes several genes extremely closely linked to the fully Y-linked region. These genes were added to an ancestral PAR of the sex chromosome pair in two distinct events probably involving translocations of autosomal genome regions causing multiple genes to become partially sex-linked. Close linkage with the PAR boundary must have evolved since these additions, because some genes added in both events now show almost complete sex linkage in S. latifolia. We compared diversity patterns of five such S. latifolia PAR boundary genes with their orthologues in S. dioica, including all three regions of the PAR (one gene that was in the ancestral PAR and two from each of the added regions). The results suggest recent recombination suppression in S. latifolia, since its split from S. dioica. PMID:27827389

Comparative Physical Mapping of the Apospory-Specific Genomic Region in Two Apomictic Grasses: Pennisetum squamulatum and Cenchrus ciliaris

PubMed Central

Goel, Shailendra; Chen, Zhenbang; Akiyama, Yukio; Conner, Joann A.; Basu, Manojit; Gualtieri, Gustavo; Hanna, Wayne W.; Ozias-Akins, Peggy

2006-01-01

In gametophytic apomicts of the aposporous type, each cell of the embryo sac is genetically identical to somatic cells of the ovule because they are products of mitosis, not of meiosis. The egg of the aposporous embryo sac follows parthenogenetic development into an embryo; therefore, uniform progeny result even from heterozygous plants, a trait that would be valuable for many crop species. Attempts to introgress apomixis from wild relatives into major crops through traditional breeding have been hindered by low or no recombination within the chromosomal region governing this trait (the apospory-specific genomic region or ASGR). The lack of recombination also has been a major obstacle to positional cloning of key genes. To further delineate and characterize the nonrecombinant ASGR, we have identified eight new ASGR-linked, AFLP-based molecular markers, only one of which showed recombination with the trait for aposporous embryo sac development. Bacterial artificial chromosome (BAC) clones identified with the ASGR-linked AFLPs or previously mapped markers, when mapped by fluorescence in situ hybridization in Pennisetum squamulatum and Cenchrus ciliaris, showed almost complete macrosynteny between the two apomictic grasses throughout the ASGR, although with an inverted order. A BAC identified with the recombinant AFLP marker mapped most proximal to the centromere of the ASGR-carrier chromosome in P. squamulatum but was not located on the ASGR-carrier chromosome in C. ciliaris. Exceptional regions where synteny was disrupted probably are nonessential for expression of the aposporous trait. The ASGR appears to be maintained as a haplotype even though its position in the genome can be variable. PMID:16547108

Semidirect Dynamical and Radiative Impact of North African Dust Transport on Lower Tropospheric Clouds over the Subtropical North Atlantic in CESM 1.0

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

DeFlorio, Mike; Ghan, Steven J.; Singh, Balwinder

This study uses a century length pre-industrial climate simulation by the Community Earth System Model (CESM 1.0) to explore statistical relationships between dust, clouds and atmospheric circulation, and to suggest a dynamical, rather than microphysical, mechanism linking subtropical North Atlantic lower tropospheric cloud cover with North African dust transport. The length of the run allows us to account for interannual variability of dust emissions and transport downstream of North Africa in the model. CESM’s mean climatology and probability distribution of aerosol optical depth in this region agrees well with available AERONET observations. In addition, CESM shows strong seasonal cycles ofmore » dust burden and lower tropospheric cloud fraction, with maximum values occurring during boreal summer, when a strong correlation between these two variables exists downstream of North Africa over the subtropical North Atlantic. Calculations of Estimated Inversion Strength (EIS) and composites of EIS on high and low downstream North Africa dust months during boreal summer reveal that dust is likely increasing inversion strength over this region due to both solar absorption and reflection. We find no evidence for a microphysical link between dust and lower tropospheric clouds in this region. These results yield new insight over an extensive period of time into the complex relationship between North African dust and lower tropospheric clouds over the open ocean, which has previously been hindered by spatiotemporal constraints of observations. Our findings lay a framework for future analyses using sub-monthly data over regions with different underlying dynamics.« less

Neotectonic inversion of the Hindu Kush-Pamir mountain region

USGS Publications Warehouse

Ruleman, C.A.

2011-01-01

The Hindu Kush-Pamir region of southern Asia is one of Earth's most rapidly deforming regions and it is poorly understood. This study develops a kinematic model based on active faulting in this part of the Trans-Himalayan orogenic belt. Previous studies have described north-verging thrust faults and some strike-slip faults, reflected in the northward-convex geomorphologic and structural grain of the Pamir Mountains. However, this structural analysis suggests that contemporary tectonics are changing the style of deformation from north-verging thrusts formed during the initial contraction of the Himalayan orogeny to south-verging thrusts and a series of northwest-trending, dextral strike-slip faults in the modern transpressional regime. These northwest-trending fault zones are linked to the major right-lateral Karakoram fault, located to the east, as synthetic, conjugate shears that form a right-stepping en echelon pattern. Northwest-trending lineaments with dextral displacements extend continuously westward across the Hindu Kush-Pamir region indicating a pattern of systematic shearing of multiple blocks to the northwest as the deformation effects from Indian plate collision expands to the north-northwest. Locally, east-northeast- and northwest-trending faults display sinistral and dextral displacement, respectively, yielding conjugate shear pairs developed in a northwest-southeast compressional stress field. Geodetic measurements and focal mechanisms from historical seismicity support these surficial, tectono-morphic observations. The conjugate shear pairs may be structurally linked subsidiary faults and co-seismically slip during single large magnitude (> M7) earthquakes that occur on major south-verging thrust faults. This kinematic model provides a potential context for prehistoric, historic, and future patterns of faulting and earthquakes.

The UL5 and UL52 subunits of the herpes simplex virus type 1 helicase-primase subcomplex exhibit a complex interdependence for DNA binding.

PubMed

Biswas, N; Weller, S K

2001-05-18

Herpes simplex virus type 1 encodes a heterotrimeric helicase-primase complex composed of the products of the UL5, UL52, and UL8 genes. The UL5 protein contains seven motifs found in all members of helicase Superfamily 1 (SF1), and the UL52 protein contains several conserved motifs found in primases; however, the contributions of each subunit to the biochemical activities of the subcomplex are not clear. In this work, the DNA binding properties of wild type and mutant subcomplexes were examined using single-stranded, duplex, and forked substrates. A gel mobility shift assay indicated that the UL5-UL52 subcomplex binds more efficiently to the forked substrate than to either single strand or duplex DNA. Although nucleotides are not absolutely required for DNA binding, ADP stimulated the binding of UL5-UL52 to single strand DNA whereas ATP, ADP, and adenosine 5'-O-(thiotriphosphate) stimulated the binding to a forked substrate. We have previously shown that both subunits contact single-stranded DNA in a photocross-linking assay (Biswas, N., and Weller, S. K. (1999) J. Biol. Chem. 274, 8068-8076). In this study, photocross-linking assays with forked substrates indicate that the UL5 and UL52 subunits contact the forked substrates at different positions, UL52 at the single-stranded DNA tail and UL5 near the junction between single-stranded and double-stranded DNA. Neither subunit was able to cross-link a forked substrate when 5-iododeoxyuridine was located within the duplex portion. Photocross-linking experiments with subcomplexes containing mutant versions of UL5 and wild type UL52 indicated that the integrity of the ATP binding region is important for DNA binding of both subunits. These results support our previous proposal that UL5 and UL52 exhibit a complex interdependence for DNA binding (Biswas, N., and Weller, S. K. (1999) J. Biol. Chem. 274, 8068-8076) and indicate that the UL52 subunit may play a more active role in helicase activity than had previously been thought.

Association of enhanced limbic response to threat with decreased cortical facial recognition memory response in schizophrenia

PubMed Central

Satterthwaite, Theodore D.; Wolf, Daniel H.; Loughead, James; Ruparel, Kosha; Valdez, Jeffrey N.; Siegel, Steven J.; Kohler, Christian G.; Gur, Raquel E.; Gur, Ruben C.

2014-01-01

Objective Recognition memory of faces is impaired in patients with schizophrenia, as is the neural processing of threat-related signals, but how these deficits interact to produce symptoms is unclear. Here we used an affective face recognition paradigm to examine possible interactions between cognitive and affective neural systems in schizophrenia. Methods fMRI (3T) BOLD response was examined in 21 controls and 16 patients during a two-choice recognition task using images of human faces. Each target face had previously been displayed with a threatening or non-threatening affect, but here were displayed with neutral affect. Responses to successful recognition and for the effect of previously threatening vs. non-threatening affect were evaluated, and correlations with total BPRS examined. Functional connectivity analyses examined the relationship between activation in the amygdala and cortical regions involved in recognition memory. Results Patients performed the task more slowly than controls. Controls recruited the expected cortical regions to a greater degree than patients, and patients with more severe symptoms demonstrated proportionally less recruitment. Increased symptoms were also correlated with augmented amygdala and orbitofrontal cortex response to threatening faces. Controls exhibited a negative correlation between activity in the amygdala and cortical regions involved in cognition, while patients showed a weakening of that relationship. Conclusions Increased symptoms were related to an enhanced threat response in limbic regions and a diminished recognition memory response in cortical regions, supporting a link between two brain systems often examined in isolation. This finding suggests that abnormal processing of threat-related signals in the environment may exacerbate cognitive impairment in schizophrenia. PMID:20194482

Arctic Sea Ice Export Through Fram Strait and Atmospheric Planetary Waves

NASA Technical Reports Server (NTRS)

Cavalieri, Donald J.; Koblinsky, Chester (Technical Monitor)

2001-01-01

A link is found between the variability of Arctic sea ice export through Ram Strait and the phase of the longest atmospheric planetary wave (zonal wave 1) in SLP for the period 1958-1997. Previous studies have identified a link between From Strait ice export and the North Atlantic Oscillation (NAO), but this link has been described as unstable because of a lack of consistency over time scales longer than the last two decades. Inconsistent and low correlations are also found between From Strait ice export and the Arctic Oscillation (AD) index. This paper shows that the phase of zonal wave 1 explains 60% - 70% of the simulated From Strait ice export variance over the Goodyear period 1958 - 1997. Unlike the NAB and AD links, these high variances are consistent for both the first and second halves of the Goodyear period. This consistency is attributed to the sensitivity of the wave I phase at high latitudes to the presence of secondary low pressure systems in the Barents Sea that serve to drive sea ice southward through From Strait. These results provide further evidence that the phase of zonal wave 1 in SLP at high latitudes drives regional as well as hemispheric low frequency Arctic Ocean and sea ice variability.

Cambrian Sauk transgression in the Grand Canyon region redefined by detrital zircons

NASA Astrophysics Data System (ADS)

Karlstrom, Karl; Hagadorn, James; Gehrels, George; Matthews, William; Schmitz, Mark; Madronich, Lauren; Mulder, Jacob; Pecha, Mark; Giesler, Dominique; Crossey, Laura

2018-06-01

The Sauk transgression was one of the most dramatic global marine transgressions in Earth history. It is recorded by deposition of predominantly Cambrian non-marine to shallow marine sheet sandstones unconformably above basement rocks far into the interiors of many continents. Here we use dating of detrital zircons sampled from above and below the Great Unconformity in the Grand Canyon region to bracket the timing of the Sauk transgression at this classic location. We find that the Sixtymile Formation, long considered a Precambrian unit beneath the Great Unconformity, has maximum depositional ages that get younger up-section from 527 to 509 million years old. The unit contains angular unconformities and soft-sediment deformation that record a previously unknown period of intracratonic faulting and epeirogeny spanning four Cambrian stages. The overlying Tapeats Sandstone has youngest detrital zircon ages of 505 to 501 million years old. When linked to calibrated trilobite zone ages of greater than 500 million years old, these age constraints show that the marine transgression across a greater than 300-km-wide cratonic region took place during an interval 505 to 500 million years ago—more recently and more rapidly than previously thought. We redefine this onlap as the main Sauk transgression in the region. Mechanisms for this rapid flooding of the continent include thermal subsidence following the final breakup of Rodinia, combined with abrupt global eustatic changes driven by climate and/or mantle buoyancy modifications.

U14 small nucleolar RNA makes multiple contacts with the pre-ribosomal RNA.

PubMed

Morrissey, J P; Tollervey, D

1997-06-01

The small nucleolar RNA (snoRNA) U14 has two regions of extended primary sequence complementarity to the 18S rRNA. The 3' region (domain B) shows the consensus structure for the methylation guide class of snoRNAs, whereas base-pairing between the 5' region (domain A) and the 18S rRNA sequence is required for the formation of functional ribosomes. Between domains A and B lies another essential region (domain Y). Here we report that yeast U14 can be cross-linked in vivo to the pre-rRNA; cross-linking is detected exclusively with the 35S primary transcript. Many nucleotides in U14 that lie outside of domains A and B are cross-linked to the pre-rRNA; in particular the essential domain Y region is cross-linked at several sites. U14 is, therefore, in far more extensive contact with the pre-rRNA than predicted from simple base-pairing models. Moreover, U14 can be cross-linked to other small RNA species. The functional interactions made by U14 during ribosome synthesis are likely to be very complex.

Structure of the Repulsive Guidance Molecule (RGM)—Neogenin Signaling Hub

PubMed Central

Bell, Christian H.; Bishop, Benjamin; Tang, Chenxiang; Gilbert, Robert J.C.; Aricescu, A. Radu; Pasterkamp, R. Jeroen; Siebold, Christian

2016-01-01

Repulsive guidance molecule family members (RGMs) control fundamental and diverse cellular processes, including motility and adhesion, immune cell regulation, and systemic iron metabolism. However, it is not known how RGMs initiate signaling through their common cell-surface receptor, neogenin (NEO1). Here, we present crystal structures of the NEO1 RGM-binding region and its complex with human RGMB (also called dragon). The RGMB structure reveals a previously unknown protein fold and a functionally important autocatalytic cleavage mechanism and provides a framework to explain numerous disease-linked mutations in RGMs. In the complex, two RGMB ectodomains conformationally stabilize the juxtamembrane regions of two NEO1 receptors in a pH-dependent manner. We demonstrate that all RGM-NEO1 complexes share this architecture, which therefore represents the core of multiple signaling pathways. PMID:23744777

Transcription map of Xq27: candidates for several X-linked diseases.

PubMed

Zucchi, I; Jones, J; Affer, M; Montagna, C; Redolfi, E; Susani, L; Vezzoni, P; Parvari, R; Schlessinger, D; Whyte, M P; Mumm, S

1999-04-15

Human Xq27 contains candidate regions for several disorders, yet is predicted to be a gene-poor cytogenetic band. We have developed a transcription map for the entire cytogenetic band to facilitate the identification of the relatively small number of expected candidate genes. Two approaches were taken to identify genes: (1) a group of 64 unique STSs that were generated during the physical mapping of the region were used in RT-PCR with RNA from human adult and fetal brain and (2) ESTs that have been broadly mapped to this region of the chromosome were finely mapped using a high-resolution yeast artificial chromosome contig. This combined approach identified four distinct regions of transcriptional activity within the Xq27 band. Among them is a region at the centromeric boundary that contains candidate regions for several rare developmental disorders (X-linked recessive hypoparathyroidism, thoracoabdominal syndrome, albinism-deafness syndrome, and Borjeson-Forssman-Lehman syndrome). Two transcriptionally active regions were identified in the center of Xq27 and include candidate regions for X-linked mental retardation syndrome 6, X-linked progressive cone dystrophy, X-linked retinitis pigmentosa 24, and a prostate cancer susceptibility locus. The fourth region of transcriptional activity encompasses the FMR1 (FRAXA) and FMR2 (FRAXE) genes. The analysis thus suggests clustered transcription in Xq27 and provides candidates for several heritable disorders for which the causative genes have not yet been found. Copyright 1999 Academic Press.

Pre-configured polyhedron based protection against multi-link failures in optical mesh networks.

PubMed

Huang, Shanguo; Guo, Bingli; Li, Xin; Zhang, Jie; Zhao, Yongli; Gu, Wanyi

2014-02-10

This paper focuses on random multi-link failures protection in optical mesh networks, instead of single, the dual or sequential failures of previous studies. Spare resource efficiency and failure robustness are major concerns in link protection strategy designing and a k-regular and k-edge connected structure is proved to be one of the optimal solutions for link protection network. Based on this, a novel pre-configured polyhedron based protection structure is proposed, and it could provide protection for both simultaneous and sequential random link failures with improved spare resource efficiency. Its performance is evaluated in terms of spare resource consumption, recovery rate and average recovery path length, as well as compared with ring based and subgraph protection under probabilistic link failure scenarios. Results show the proposed novel link protection approach has better performance than previous works.

Fine mapping QTL for drought resistance traits in rice (Oryza sativa L.) using bulk segregant analysis.

PubMed

Salunkhe, Arvindkumar Shivaji; Poornima, R; Prince, K Silvas Jebakumar; Kanagaraj, P; Sheeba, J Annie; Amudha, K; Suji, K K; Senthil, A; Babu, R Chandra

2011-09-01

Drought stress is a major limitation to rice (Oryza sativa L.) yields and its stability, especially in rainfed conditions. Developing rice cultivars with inherent capacity to withstand drought stress would improve rainfed rice production. Mapping quantitative trait loci (QTLs) linked to drought resistance traits will help to develop rice cultivars suitable for water-limited environments through molecular marker-assisted selection (MAS) strategy. However, QTL mapping is usually carried out by genotyping large number of progenies, which is labour-intensive, time-consuming and cost-ineffective. Bulk segregant analysis (BSA) serves as an affordable strategy for mapping large effect QTLs by genotyping only the extreme phenotypes instead of the entire mapping population. We have previously mapped a QTL linked to leaf rolling and leaf drying in recombinant inbred (RI) lines derived from two locally adapted indica rice ecotypes viz., IR20/Nootripathu using BSA. Fine mapping the QTL will facilitate its application in MAS. BSA was done by bulking DNA of 10 drought-resistant and 12 drought-sensitive RI lines. Out of 343 rice microsatellites markers genotyped, RM8085 co-segregated among the RI lines constituting the respective bulks. RM8085 was mapped in the middle of the QTL region on chromosome 1 previously identified in these RI lines thus reducing the QTL interval from 7.9 to 3.8 cM. Further, the study showed that the region, RM212-RM302-RM8085-RM3825 on chromosome 1, harbours large effect QTLs for drought-resistance traits across several genetic backgrounds in rice. Thus, the QTL may be useful for drought resistance improvement in rice through MAS and map-based cloning.

Genes located in a chromosomal inversion are correlated with territorial song in white-throated sparrows.

PubMed

Zinzow-Kramer, W M; Horton, B M; McKee, C D; Michaud, J M; Tharp, G K; Thomas, J W; Tuttle, E M; Yi, S; Maney, D L

2015-11-01

The genome of the white-throated sparrow (Zonotrichia albicollis) contains an inversion polymorphism on chromosome 2 that is linked to predictable variation in a suite of phenotypic traits including plumage color, aggression and parental behavior. Differences in gene expression between the two color morphs, which represent the two common inversion genotypes (ZAL2/ZAL2 and ZAL2/ZAL2(m) ), may therefore advance our understanding of the molecular underpinnings of these phenotypes. To identify genes that are differentially expressed between the two morphs and correlated with behavior, we quantified gene expression and terrirorial aggression, including song, in a population of free-living white-throated sparrows. We analyzed gene expression in two brain regions, the medial amygdala (MeA) and hypothalamus. Both regions are part of a 'social behavior network', which is rich in steroid hormone receptors and previously linked with territorial behavior. Using weighted gene co-expression network analyses, we identified modules of genes that were correlated with both morph and singing behavior. The majority of these genes were located within the inversion, showing the profound effect of the inversion on the expression of genes captured by the rearrangement. These modules were enriched with genes related to retinoic acid signaling and basic cellular functioning. In the MeA, the most prominent pathways were those related to steroid hormone receptor activity. Within these pathways, the only gene encoding such a receptor was ESR1 (estrogen receptor 1), a gene previously shown to predict song rate in this species. The set of candidate genes we identified may mediate the effects of a chromosomal inversion on territorial behavior. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Modeling a linkage between blood transcriptional expression and activity in brain regions to infer the phenotype of schizophrenia patients.

PubMed

Ibrahim, El Chérif; Guillemot, Vincent; Comte, Magali; Tenenhaus, Arthur; Zendjidjian, Xavier Yves; Cancel, Aida; Belzeaux, Raoul; Sauvanaud, Florence; Blin, Olivier; Frouin, Vincent; Fakra, Eric

2017-09-07

Hundreds of genetic loci participate to schizophrenia liability. It is also known that impaired cerebral connectivity is directly related to the cognitive and affective disturbances in schizophrenia. How genetic susceptibility and brain neural networks interact to specify a pathological phenotype in schizophrenia remains elusive. Imaging genetics, highlighting brain variations, has proven effective to establish links between vulnerability loci and associated clinical traits. As previous imaging genetics works in schizophrenia have essentially focused on structural DNA variants, these findings could be blurred by epigenetic mechanisms taking place during gene expression. We explored the meaningful links between genetic data from peripheral blood tissues on one hand, and regional brain reactivity to emotion task assayed by blood oxygen level-dependent functional magnetic resonance imaging on the other hand, in schizophrenia patients and matched healthy volunteers. We applied Sparse Generalized Canonical Correlation Analysis to identify joint signals between two blocks of variables: (i) the transcriptional expression of 33 candidate genes, and (ii) the blood oxygen level-dependent activity in 16 region of interest. Results suggested that peripheral transcriptional expression is related to brain imaging variations through a sequential pathway, ending with the schizophrenia phenotype. Generalization of such an approach to larger data sets should thus help in outlining the pathways involved in psychiatric illnesses such as schizophrenia. SEARCHING FOR LINKS TO AID DIAGNOSIS: Researchers explore links between the expression of genes associated with schizophrenia in blood cells and variations in brain activity during emotion processing. El Chérif Ibrahim and Eric Fakra at Aix-Marseille Université, France, and colleagues have developed a method to relate the expression levels of 33 schizophrenia susceptibility genes in blood cells and functional magnetic resonance imaging (fMRI) data obtained as individuals carry out a task that triggers emotional responses. Although they found no significant differences in the expression of genes between the 26 patients with schizophrenia and 26 healthy controls they examined, variations in activity in the superior temporal gyrus were strongly linked to schizophrenia-associated gene expression and presence of disease. Similar analyses of larger data sets will shed further light on the relationship between peripheral molecular changes and disease-related behaviors and ultimately, aid the diagnosis of neuropsychiatric disease.

Design and characterization of an engineered gp41 protein from human immunodeficiency virus-1 as a tool for drug discovery

NASA Astrophysics Data System (ADS)

Stewart, Kent D.; Steffy, Kevin; Harris, Kevin; Harlan, John E.; Stoll, Vincent S.; Huth, Jeffrey R.; Walter, Karl A.; Gramling-Evans, Emily; Mendoza, Renaldo R.; Severin, Jean M.; Richardson, Paul L.; Barrett, Leo W.; Matayoshi, Edmund D.; Swift, Kerry M.; Betz, Stephen F.; Muchmore, Steve W.; Kempf, Dale J.; Molla, Akhter

2007-01-01

Two new proteins of approximately 70 amino acids in length, corresponding to an unnaturally-linked N- and C-helix of the ectodomain of the gp41 protein from the human immunodeficiency virus (HIV) type 1, were designed and characterized. A designed tripeptide links the C-terminus of the C-helix with the N-terminus of the N-helix in a circular permutation so that the C-helix precedes the N-helix in sequence. In addition to the artificial peptide linkage, the C-helix is truncated at its N-terminus to expose a region of the N-helix known as the "Trp-Trp-Ile" binding pocket. Sedimentation, crystallographic, and nuclear magnetic resonance studies confirmed that the protein had the desired trimeric structure with an unoccupied binding site. Spectroscopic and centrifugation studies demonstrated that the engineered protein had ligand binding characteristics similar to previously reported constructs. Unlike previous constructs which expose additional, shallow, non-conserved, and undesired binding pockets, only the single deep and conserved Trp-Trp-Ile pocket is exposed in the proteins of this study. This engineered version of gp41 protein will be potentially useful in research programs aimed at discovery of new drugs for therapy of HIV-infection in humans.

(De-)accentuation and the process of information status: evidence from event-related brain potentials.

PubMed

Baumann, Stefan; Schumacher, Petra B

2012-09-01

The paper reports on a perception experiment in German that investigated the neuro-cognitive processing of information structural concepts and their prosodic marking using event-related brain potentials (ERPs). Experimental conditions controlled the information status (given vs. new) of referring and non-referring target expressions (nouns vs. adjectives) and were elicited via context sentences, which did not - unlike most previous ERP studies in the field--trigger an explicit focus expectation. Target utterances displayed prosodic realizations of the critical words which differed in accent position and accent type. Electrophysiological results showed an effect of information status, maximally distributed over posterior sites, displaying a biphasic N400--Late Positivity pattern for new information. We claim that this pattern reflects increased processing demands associated with new information, with the N400 indicating enhanced costs from linking information with the previous discourse and the Late Positivity indicating the listener's effort to update his/her discourse model. The prosodic manipulation registered more pronounced effects over anterior regions and revealed an enhanced negativity followed by a Late Positivity for deaccentuation, probably also reflecting costs from discourse linking and updating respectively. The data further lend indirect support for the idea that givenness applies not only to referents but also to non-referential expressions ('lexical givenness').

Poverty determinants of acute respiratory infections among Mapuche indigenous peoples in Chile's Ninth Region of Araucania, using GIS and spatial statistics to identify health disparities

PubMed Central

Rojas, Flavio

2007-01-01

Background This research concerns Araucanía, often called the Ninth Region, the poorest region of Chile where inequalities are most extreme. Araucanía hasn't enjoyed the economic success Chile achieved when the country returned to democracy in 1990. The Ninth Region also has the largest ethnic Mapuche population, located in rural areas and attached to small agricultural properties. Written and oral histories of diseases have been the most frequently used methods to explore the links between an ancestral population's perception of health conditions and their deprived environments. With census data and hospital records, it is now possible to incorporate statistical data about the links between poverty and disease among ethnic communities and compare results with non-Mapuche population. Data sources Hospital discharge records from Health Services North N = 24,126 patients, year 2003, and 7 hospitals), Health Services South (N = 81,780 patients and 25 hospitals); CAS-2/Family records (N = 527,539 individuals, 439 neighborhoods, 32 Comunas). Methods Given the over-dispersion of data and the clustered nature of observations, we used the global Moran's I and General G Gettis-Ord procedures to test spatial dependence. These tests confirmed the clusters of disease and the need to use spatial regression within a General Linear Mixed Model perspective. Results Health outcomes indicate significantly higher morbidity rates for the Mapuche compared to non-Mapuche in both age groups < 5 and 15–44, respectively; for the groups 70–79 and 80 + years of age, this trend is reversed. Mortality rates, however, are higher among Mapuches than non-Mapuches for the entire Ninth Region and for all age groups. Mortality caused by respiratory infections is higher among Mapuches than non-Mapuches in all age-groups. A major finding is the link between poverty and respiratory infections. Conclusion Poverty is significantly associated with respiratory infections in the population of Chile's Ninth Region. High deprivation areas are associated with poverty, and poverty is a predictor of respiratory infections. Mapuches are at higher risk of deaths caused by respiratory infections in all age groups. Exponential and spherical spatial correlation models were tested to estimate the previous association and were compared with non-spatial Poisson, concluding that significant spatial variability was present in the data. PMID:17605804

Poverty determinants of acute respiratory infections among Mapuche indigenous peoples in Chile's Ninth Region of Araucania, using GIS and spatial statistics to identify health disparities.

PubMed

Rojas, Flavio

2007-07-02

This research concerns Araucanía, often called the Ninth Region, the poorest region of Chile where inequalities are most extreme. Araucanía hasn't enjoyed the economic success Chile achieved when the country returned to democracy in 1990. The Ninth Region also has the largest ethnic Mapuche population, located in rural areas and attached to small agricultural properties. Written and oral histories of diseases have been the most frequently used methods to explore the links between an ancestral population's perception of health conditions and their deprived environments. With census data and hospital records, it is now possible to incorporate statistical data about the links between poverty and disease among ethnic communities and compare results with non-Mapuche population. Hospital discharge records from Health Services North N = 24,126 patients, year 2003, and 7 hospitals), Health Services South (N = 81,780 patients and 25 hospitals); CAS-2/Family records (N = 527,539 individuals, 439 neighborhoods, 32 Comunas). Given the over-dispersion of data and the clustered nature of observations, we used the global Moran's I and General G Gettis-Ord procedures to test spatial dependence. These tests confirmed the clusters of disease and the need to use spatial regression within a General Linear Mixed Model perspective. Health outcomes indicate significantly higher morbidity rates for the Mapuche compared to non-Mapuche in both age groups < 5 and 15-44, respectively; for the groups 70-79 and 80 + years of age, this trend is reversed. Mortality rates, however, are higher among Mapuches than non-Mapuches for the entire Ninth Region and for all age groups. Mortality caused by respiratory infections is higher among Mapuches than non-Mapuches in all age-groups. A major finding is the link between poverty and respiratory infections. Poverty is significantly associated with respiratory infections in the population of Chile's Ninth Region. High deprivation areas are associated with poverty, and poverty is a predictor of respiratory infections. Mapuches are at higher risk of deaths caused by respiratory infections in all age groups. Exponential and spherical spatial correlation models were tested to estimate the previous association and were compared with non-spatial Poisson, concluding that significant spatial variability was present in the data.

An edge-centric perspective on the human connectome: link communities in the brain.

PubMed

de Reus, Marcel A; Saenger, Victor M; Kahn, René S; van den Heuvel, Martijn P

2014-10-05

Brain function depends on efficient processing and integration of information within a complex network of neural interactions, known as the connectome. An important aspect of connectome architecture is the existence of community structure, providing an anatomical basis for the occurrence of functional specialization. Typically, communities are defined as groups of densely connected network nodes, representing clusters of brain regions. Looking at the connectome from a different perspective, instead focusing on the interconnecting links or edges, we find that the white matter pathways between brain regions also exhibit community structure. Eleven link communities were identified: five spanning through the midline fissure, three through the left hemisphere and three through the right hemisphere. We show that these link communities are consistently identifiable and investigate the network characteristics of their underlying white matter pathways. Furthermore, examination of the relationship between link communities and brain regions revealed that the majority of brain regions participate in multiple link communities. In particular, the highly connected and central hub regions showed a rich level of community participation, supporting the notion that these hubs play a pivotal role as confluence zones in which neural information from different domains merges. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Auditory Selective Attention to Speech Modulates Activity in the Visual Word Form Area

PubMed Central

Yoncheva, Yuliya N.; Zevin, Jason D.; Maurer, Urs

2010-01-01

Selective attention to speech versus nonspeech signals in complex auditory input could produce top-down modulation of cortical regions previously linked to perception of spoken, and even visual, words. To isolate such top-down attentional effects, we contrasted 2 equally challenging active listening tasks, performed on the same complex auditory stimuli (words overlaid with a series of 3 tones). Instructions required selectively attending to either the speech signals (in service of rhyme judgment) or the melodic signals (tone-triplet matching). Selective attention to speech, relative to attention to melody, was associated with blood oxygenation level–dependent (BOLD) increases during functional magnetic resonance imaging (fMRI) in left inferior frontal gyrus, temporal regions, and the visual word form area (VWFA). Further investigation of the activity in visual regions revealed overall deactivation relative to baseline rest for both attention conditions. Topographic analysis demonstrated that while attending to melody drove deactivation equivalently across all fusiform regions of interest examined, attending to speech produced a regionally specific modulation: deactivation of all fusiform regions, except the VWFA. Results indicate that selective attention to speech can topographically tune extrastriate cortex, leading to increased activity in VWFA relative to surrounding regions, in line with the well-established connectivity between areas related to spoken and visual word perception in skilled readers. PMID:19571269

Corruption and use of antibiotics in regions of Europe.

PubMed

Rönnerstrand, Björn; Lapuente, Victor

2017-03-01

The aim of this article is to investigate the association between corruption and antibiotic use at sub-national level. We explore the correlation between, on the one hand, two measures of corruption (prevalence of corruption in the health sector and prevalence of bribes in the society) at regional level from the European Quality of Government Index; and, on the other, the consumption of antibiotics in those European regions from a 2009 Special Euro Barometer. In a multivariate regression model, we control for potential confounders: purchasing power of standardized regional gross domestic product, inhabitants per medical doctor and age-standardized all-cause mortality rates. We find that there is a strong positive association between both measures of corruption (i.e. in the health sector, and in the society at large) and antibiotics use; and that this association is robust to the introduction of the control variables. These results support previous findings in the literature linking corruption to higher antibiotic use at cross-national level. We show that corruption does seem to account for some of the remarkable between-region variation in antibiotic consumption in Europe. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Evolved developmental homeostasis disturbed in LB1 from Flores, Indonesia, denotes Down syndrome and not diagnostic traits of the invalid species Homo floresiensis

NASA Astrophysics Data System (ADS)

Henneberg, Maciej; Eckhardt, Robert B.; Chavanaves, Sakdapong; Hsü, Kenneth J.

2014-08-01

Human skeletons from Liang Bua Cave, Flores, Indonesia, are coeval with only Homo sapiens populations worldwide and no other previously known hominins. We report here for the first time to our knowledge the occipitofrontal circumference of specimen LB1. This datum makes it possible to link the 430-mL endocranial volume of LB1 reported by us previously, later confirmed independently by other investigators, not only with other human skeletal samples past and present but also with a large body of clinical data routinely collected on patients with developmental disorders. Our analyses show that the brain size of LB1 is in the range predicted for an individual with Down syndrome (DS) in a normal small-bodied population from the geographic region that includes Flores. Among additional diagnostic signs of DS and other skeletal dysplasiae are abnormally short femora combined with disproportionate flat feet. Liang Bua Cave femora, known only for LB1, match interlimb proportions for DS. Predictions based on corrected LB1 femur lengths show a stature normal for other H. sapiens populations in the region.

Novel regulation of Smad3 oligomerization and DNA binding by its linker domain.

PubMed

Vasilaki, Eleftheria; Siderakis, Manos; Papakosta, Paraskevi; Skourti-Stathaki, Konstantina; Mavridou, Sofia; Kardassis, Dimitris

2009-09-08

Smad proteins are key effectors of the transforming growth factor beta (TGFbeta) signaling pathway in mammalian cells. Smads are composed of two highly structured and conserved domains called Mad homology 1 (MH1) and 2 (MH2), which are linked together by a nonconserved linker region. The recent identification of phosphorylation sites and binding sites for ubiquitin ligases in the linker regions of TGFbeta and bone morphogenetic protein (BMP) receptor-regulated Smads suggested that the linker may contribute to the regulation of Smad function by facilitating cross-talks with other signaling pathways. In the present study, we have generated and characterized novel Smad3 mutants bearing individual substitutions of conserved and nonconserved amino acid residues within a previously described transcriptionally active linker fragment. Our analysis showed that the conserved linker amino acids glutamine 222 and proline 229 play important roles in Smad functions such as homo- and hetero-oligomerization, nuclear accumulation in response to TGFbeta stimulation, and DNA binding. Furthermore, a Smad3 mutant bearing a substitution of the nonconserved amino acid asparagine 218 to alanine displayed enhanced transactivation potential relative to wild type Smad3. Finally, Smad3 P229A inhibited TGFbeta signaling when overexpressed in mammalian cells. In conclusion, our data are in line with previous studies supporting an important regulatory role of the linker region of Smads in their function as key transducers of TGFbeta signaling.

Evaluating the economic damages of transport disruptions using a transnational and interregional input-output model for Japan, China, and South Korea

NASA Astrophysics Data System (ADS)

Irimoto, Hiroshi; Shibusawa, Hiroyuki; Miyata, Yuzuru

2017-10-01

Damage to transportation networks as a result of natural disasters can lead to economic losses due to lost trade along those links in addition to the costs of damage to the infrastructure itself. This study evaluates the economic damages of transport disruptions such as highways, tunnels, bridges, and ports using a transnational and interregional Input-Output Model that divides the world into 23 regions: 9 regions in Japan, 7 regions in China, and 4 regions in Korea, Taiwan, ASEAN5, and the USA to allow us to focus on Japan's regional and international links. In our simulation, economic ripple effects of both international and interregional transport disruptions are measured by changes in the trade coefficients in the input-output model. The simulation showed that, in the case of regional links in Japan, a transport disruption in the Kanmon Straits causes the most damage to our targeted world, resulting in economic damage of approximately 36.3 billion. In the case of international links among Japan, China, and Korea, damage to the link between Kanto in Japan and Huabei in China causes economic losses of approximately 31.1 billion. Our result highlights the importance of disaster prevention in the Kanmon Straits, Kanto, and Huabei to help ensure economic resilience.

Caribbean coral growth influenced by anthropogenic aerosol emissions

NASA Astrophysics Data System (ADS)

Kwiatkowski, Lester; Cox, Peter M.; Economou, Theo; Halloran, Paul R.; Mumby, Peter J.; Booth, Ben B. B.; Carilli, Jessica; Guzman, Hector M.

2013-05-01

Coral growth rates are highly dependent on environmental variables such as sea surface temperature and solar irradiance. Multi-decadal variability in coral growth rates has been documented throughout the Caribbean over the past 150-200 years, and linked to variations in Atlantic sea surface temperatures. Multi-decadal variability in sea surface temperatures in the North Atlantic, in turn, has been linked to volcanic and anthropogenic aerosol forcing. Here, we examine the drivers of changes in coral growth rates in the western Caribbean between 1880 and 2000, using previously published coral growth chronologies from two sites in the region, and a numerical model. Changes in coral growth rates over this period coincided with variations in sea surface temperature and incoming short-wave radiation. Our model simulations show that variations in the concentration of anthropogenic aerosols caused variations in sea surface temperature and incoming radiation in the second half of the twentieth century. Before this, variations in volcanic aerosols may have played a more important role. With the exception of extreme mass bleaching events, we suggest that neither climate change from greenhouse-gas emissions nor ocean acidification is necessarily the driver of multi-decadal variations in growth rates at some Caribbean locations. Rather, the cause may be regional climate change due to volcanic and anthropogenic aerosol emissions.

Communicative versus strategic rationality: Habermas theory of communicative action and the social brain.

PubMed

Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael; Denke, Claudia

2013-01-01

In the philosophical theory of communicative action, rationality refers to interpersonal communication rather than to a knowing subject. Thus, a social view of rationality is suggested. The theory differentiates between two kinds of rationality, the emancipative communicative and the strategic or instrumental reasoning. Using experimental designs in an fMRI setting, recent studies explored similar questions of reasoning in the social world and linked them with a neural network including prefrontal and parietal brain regions. Here, we employed an fMRI approach to highlight brain areas associated with strategic and communicative reasoning according to the theory of communicative action. Participants were asked to assess different social scenarios with respect to communicative or strategic rationality. We found a network of brain areas including temporal pole, precuneus, and STS more activated when participants performed communicative reasoning compared with strategic thinking and a control condition. These brain regions have been previously linked to moral sensitivity. In contrast, strategic rationality compared with communicative reasoning and control was associated with less activation in areas known to be related to moral sensitivity, emotional processing, and language control. The results suggest that strategic reasoning is associated with reduced social and emotional cognitions and may use different language related networks. Thus, the results demonstrate experimental support for the assumptions of the theory of communicative action.

GARP is regulated by miRNAs and controls latent TGF-β1 production by human regulatory T cells.

PubMed

Gauthy, Emilie; Cuende, Julia; Stockis, Julie; Huygens, Caroline; Lethé, Bernard; Collet, Jean-François; Bommer, Guido; Coulie, Pierre G; Lucas, Sophie

2013-01-01

GARP is a transmembrane protein present on stimulated human regulatory T lymphocytes (Tregs), but not on other T lymphocytes (Th cells). It presents the latent form of TGF-β1 on the Treg surface. We report here that GARP favors the cleavage of the pro-TGF-β1 precursor and increases the amount of secreted latent TGF-β1. Stimulated Tregs, which naturally express GARP, and Th cells transfected with GARP secrete a previously unknown form of latent TGF-β1 that is disulfide-linked to GARP. These GARP/TGF-β1 complexes are possibly shed from the T cell surface. Secretion of GARP/TGF-β1 complexes was not observed with transfected 293 cells and may thus be restricted to the T cell lineage. We conclude that in stimulated human Tregs, GARP not only displays latent TGF-β1 at the cell surface, but also increases its secretion by forming soluble disulfide-linked complexes. Moreover, we identified six microRNAs (miRNAs) that are expressed at lower levels in Treg than in Th clones and that target a short region of the GARP 3' UTR. In transfected Th cells, the presence of this region decreased GARP levels, cleavage of pro-TGF-β1, and secretion of latent TGF-β1.

Integrating mRNA and Protein Sequencing Enables the Detection and Quantitative Profiling of Natural Protein Sequence Variants of Populus trichocarpa.

PubMed

Abraham, Paul E; Wang, Xiaojing; Ranjan, Priya; Nookaew, Intawat; Zhang, Bing; Tuskan, Gerald A; Hettich, Robert L

2015-12-04

Next-generation sequencing has transformed the ability to link genotypes to phenotypes and facilitates the dissection of genetic contribution to complex traits. However, it is challenging to link genetic variants with the perturbed functional effects on proteins encoded by such genes. Here we show how RNA sequencing can be exploited to construct genotype-specific protein sequence databases to assess natural variation in proteins, providing information about the molecular toolbox driving cellular processes. For this study, we used two natural genotypes selected from a recent genome-wide association study of Populus trichocarpa, an obligate outcrosser with tremendous phenotypic variation across the natural population. This strategy allowed us to comprehensively catalogue proteins containing single amino acid polymorphisms (SAAPs), as well as insertions and deletions. We profiled the frequency of 128 types of naturally occurring amino acid substitutions, including both expected (neutral) and unexpected (non-neutral) SAAPs, with a subset occurring in regions of the genome having strong polymorphism patterns consistent with recent positive and/or divergent selection. By zeroing in on the molecular signatures of these important regions that might have previously been uncharacterized, we now provide a high-resolution molecular inventory that should improve accessibility and subsequent identification of natural protein variants in future genotype-to-phenotype studies.

Convergent evolution in the genetic basis of Müllerian mimicry in heliconius butterflies.

PubMed

Baxter, Simon W; Papa, Riccardo; Chamberlain, Nicola; Humphray, Sean J; Joron, Mathieu; Morrison, Clay; ffrench-Constant, Richard H; McMillan, W Owen; Jiggins, Chris D

2008-11-01

The neotropical butterflies Heliconius melpomene and H. erato are Müllerian mimics that display the same warningly colored wing patterns in local populations, yet pattern diversity between geographic regions. Linkage mapping has previously shown convergent red wing phenotypes in these species are controlled by loci on homologous chromosomes. Here, AFLP bulk segregant analysis using H. melpomene crosses identified genetic markers tightly linked to two red wing-patterning loci. These markers were used to screen a H. melpomene BAC library and a tile path was assembled spanning one locus completely and part of the second. Concurrently, a similar strategy was used to identify a BAC clone tightly linked to the locus controlling the mimetic red wing phenotypes in H. erato. A methionine rich storage protein (MRSP) gene was identified within this BAC clone, and comparative genetic mapping shows red wing color loci are in homologous regions of the genome of H. erato and H. melpomene. Subtle differences in these convergent phenotypes imply they evolved independently using somewhat different developmental routes, but are nonetheless regulated by the same switch locus. Genetic mapping of MRSP in a third related species, the "tiger" patterned H. numata, has no association with wing patterning and shows no evidence for genomic translocation of wing-patterning loci.

The Cell Cycle Regulator CCDC6 Is a Key Target of RNA-Binding Protein EWS

PubMed Central

Duggimpudi, Sujitha; Larsson, Erik; Nabhani, Schafiq; Borkhardt, Arndt; Hoell, Jessica I

2015-01-01

Genetic translocation of EWSR1 to ETS transcription factor coding region is considered as primary cause for Ewing sarcoma. Previous studies focused on the biology of chimeric transcription factors formed due to this translocation. However, the physiological consequences of heterozygous EWSR1 loss in these tumors have largely remained elusive. Previously, we have identified various mRNAs bound to EWS using PAR-CLIP. In this study, we demonstrate CCDC6, a known cell cycle regulator protein, as a novel target regulated by EWS. siRNA mediated down regulation of EWS caused an elevated apoptosis in cells in a CCDC6-dependant manner. This effect was rescued upon re-expression of CCDC6. This study provides evidence for a novel functional link through which wild-type EWS operates in a target-dependant manner in Ewing sarcoma. PMID:25751255

Serotonin transporter genotype (5-HTTLPR) and electrocortical responses indicating the sensitivity to negative emotional cues.

PubMed

Papousek, Ilona; Reiser, Eva M; Schulter, Günter; Fink, Andreas; Holmes, Emily A; Niederstätter, Harald; Nagl, Simone; Parson, Walther; Weiss, Elisabeth M

2013-12-01

Growing literature indicates that emotional reactivity and regulation are strongly linked to genetic modulation of serotonergic neurotransmission. However, until now, most studies have focused on the relationship between genotypic markers, in particular the serotonin transporter-linked polymorphic region (5-HTTLPR), and neural structures using MRI. The current study aimed to bridge the gap between the relevant MRI literature on the effects of the 5-HTTLPR genotype and the research tradition focusing on transient lateralized changes of electrocortical activity in the prefrontal cortex using electroencephalography (EEG). Lateral shifts of EEG alpha asymmetry in response to an aversive film consisting of scenes of real injury and death were assessed in healthy participants (n = 165). To evaluate the specificity of the 5-HTTLPR effect, participants were also tested for the COMT Val158Met polymorphism which is linked to dopamine inactivation. While viewing the film, individuals homozygous for the 5-HTTLPR short allele displayed a clear lateral shift of dorsolateral frontal activity to the right, which was virtually absent in participants carrying the long allele. The heightened electrocortical response to the aversive stimulation and its direction indicates a greater propensity of s/s homozygotes to experience withdrawal oriented affect in response to negative emotion cues in the environment. Moreover, together with previous research the findings support the notion of a link between the serotonergic system and self-regulation related to avoidance motivation, and a link between the dopaminergic system and self-regulation related to approach motivation.

In situ spectroscopic study of the plastic deformation of amorphous silicon under nonhydrostatic conditions induced by indentation

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

Gerbig, Yvonne B.; Michaels, C. A.; Bradby, Jodie E.

Indentation-induced plastic deformation of amorphous silicon (a-Si) thin films was studied by in situ Raman imaging of the deformed contact region of an indented sample, employing a Raman spectroscopy-enhanced instrumented indentation technique (IIT). The occurrence and evolving spatial distribution of changes in the a-Si structure caused by processes, such as polyamorphization and crystallization, induced by indentation loading were observed. Furthermore, the obtained experimental results are linked with previously published work on the plastic deformation of a-Si under hydrostatic compression and shear deformation to establish a model for the deformation behavior of a-Si under indentation loading.

In situ spectroscopic study of the plastic deformation of amorphous silicon under nonhydrostatic conditions induced by indentation

DOE PAGES

Gerbig, Yvonne B.; Michaels, C. A.; Bradby, Jodie E.; ...

2015-12-17

Indentation-induced plastic deformation of amorphous silicon (a-Si) thin films was studied by in situ Raman imaging of the deformed contact region of an indented sample, employing a Raman spectroscopy-enhanced instrumented indentation technique (IIT). The occurrence and evolving spatial distribution of changes in the a-Si structure caused by processes, such as polyamorphization and crystallization, induced by indentation loading were observed. Furthermore, the obtained experimental results are linked with previously published work on the plastic deformation of a-Si under hydrostatic compression and shear deformation to establish a model for the deformation behavior of a-Si under indentation loading.

Association of enhanced limbic response to threat with decreased cortical facial recognition memory response in schizophrenia.

PubMed

Satterthwaite, Theodore D; Wolf, Daniel H; Loughead, James; Ruparel, Kosha; Valdez, Jeffrey N; Siegel, Steven J; Kohler, Christian G; Gur, Raquel E; Gur, Ruben C

2010-04-01

Recognition memory of faces is impaired in patients with schizophrenia, as is the neural processing of threat-related signals, but how these deficits interact to produce symptoms is unclear. The authors used an affective face recognition paradigm to examine possible interactions between cognitive and affective neural systems in schizophrenia. Blood-oxygen-level-dependent response was examined by means of functional magnetic resonance imaging (3 Tesla) in healthy comparison subjects (N=21) and in patients with schizophrenia (N=12) or schizoaffective disorder, depressed type (N=4), during a two-choice recognition task that used images of human faces. Each target face, previously displayed with a threatening or nonthreatening affect, was displayed with neutral affect. Responses to successful recognition and responses to the effect of previously threatening versus nonthreatening affect were evaluated, and correlations with symptom severity (total Brief Psychiatric Rating Scale score) were examined. Functional connectivity analyses examined the relationship between activation in the amygdala and cortical regions involved in recognition memory. Patients performed the task more slowly than healthy comparison subjects. Comparison subjects recruited the expected cortical regions to a greater degree than patients, and patients with more severe symptoms demonstrated proportionally less recruitment. Increased symptoms were also correlated with augmented amygdala and orbitofrontal cortex response to threatening faces. Comparison subjects exhibited a negative correlation between activity in the amygdala and cortical regions involved in cognition, while patients showed weakening of this relationship. Increased symptoms were related to an enhanced threat response in limbic regions and a diminished recognition memory response in cortical regions, supporting a link between these two brain systems that are often examined in isolation. This finding suggests that abnormal processing of threat-related signals in the environment may exacerbate cognitive impairment in schizophrenia.

The Oncoprotein Tax Binds the SRC-1-Interacting Domain of CBP/p300 To Mediate Transcriptional Activation

PubMed Central

Scoggin, Kirsten E. S.; Ulloa, Aida; Nyborg, Jennifer K.

2001-01-01

Oncogenesis associated with human T-cell leukemia virus (HTLV) infection is directly linked to the virally encoded transcription factor Tax. To activate HTLV-1 transcription Tax interacts with the cellular protein CREB and the pleiotropic coactivators CBP and p300. While extensively studied, the molecular mechanisms of Tax transcription function and coactivator utilization are not fully understood. Previous studies have focused on Tax binding to the KIX domain of CBP, as this was believed to be the key step in recruiting the coactivator to the HTLV-1 promoter. In this study, we identify a carboxy-terminal region of CBP (and p300) that strongly interacts with Tax and mediates Tax transcription function. Through deletion mutagenesis, we identify amino acids 2003 to 2212 of CBP, which we call carboxy-terminal region 2 (CR2), as the minimal region for Tax interaction. Interestingly, this domain corresponds to the steroid receptor coactivator 1 (SRC-1)-interacting domain of CBP. We show that a double point mutant targeted to one of the putative α-helical motifs in this domain significantly compromises the interaction with Tax. We also characterize the region of Tax responsible for interaction with CR2 and show that the previously identified transactivation domain of Tax (amino acids 312 to 319) participates in CR2 binding. This region of Tax corresponds to a consensus amphipathic helix, and single point mutations targeted to amino acids on the face of this helix abolish interaction with CR2 and dramatically reduce Tax transcription function. Finally, we demonstrate that Tax and SRC-1 bind to CR2 in a mutually exclusive fashion. Together, these studies identify a novel Tax-interacting site on CBP/p300 and extend our understanding of the molecular mechanism of Tax transactivation. PMID:11463834

Characterizing commercial oil palm expansion in Latin America: land use change and trade

NASA Astrophysics Data System (ADS)

Furumo, Paul Richard; Aide, T. Mitchell

2017-02-01

Commodity crop expansion has increased with the globalization of production systems and consumer demand, linking distant socio-ecological systems. Oil palm plantations are expanding in the tropics to satisfy growing oilseed and biofuel markets, and much of this expansion has caused extensive deforestation, especially in Asia. In Latin America, palm oil output has doubled since 2001, and the majority of expansion seems to be occurring on non-forested lands. We used MODIS satellite imagery (250 m resolution) to map current oil palm plantations in Latin America and determined prior land use and land cover (LULC) using high-resolution images in Google Earth. In addition, we compiled trade data to determine where Latin American palm oil flows, in order to better understand the underlying drivers of expansion in the region. Based on a sample of 342 032 ha of oil palm plantations across Latin America, we found that 79% replaced previously intervened lands (e.g. pastures, croplands, bananas), primarily cattle pastures (56%). The remaining 21% came from areas that were classified as woody vegetation (e.g. forests), most notably in the Amazon and the Petén region in northern Guatemala. Latin America is a net exporter of palm oil but the majority of palm oil exports (70%) stayed within the region, with Mexico importing about half. Growth of the oil palm sector may be driven by global factors, but environmental and economic outcomes vary between regions (i.e. Asia and Latin America), within regions (i.e. Colombia and Peru), and within single countries (i.e. Guatemala), suggesting that local conditions are influential. The present trend of oil palm expanding onto previously cleared lands, guided by roundtable certifications programs, provides an opportunity for more sustainable development of the oil palm sector in Latin America.

[Positioning of mRNA 3' of the a site bound codon on the human 80S ribosome].

PubMed

Molotkov, M V; Graĭfer, D M; Demeshkina, N A; Repkova, M N; Ven'iaminova, A G; Karpova, G G

2005-01-01

Short mRNA analogues carrying a UUU triplet at the 5'-termini and a perfluorophenylazide group at either the N7 atom of the guanosine or the C5 atom of the uridine 3' of the triplet were applied to study positioning of mRNA 3' of the A site codon. Complexes of 80S ribosomes with the mRNA analogues were obtained in the presence of tRNAPhe that directed UUU codon to the P site and consequently provided placement of the nucleotide with cross-linker in positions +9 or +12 with respect to the first nucleotide of the P site bound codon. Both types mRNA analogues cross-linked to the 18S rRNA and 40S proteins under mild UV-irradiation. Cross-linking patterns in the complexes where modified nucleotides of the mRNA analogues were in position +7 were analyzed for comparison (cross-linking to the 18S rRNA in such complexes has been studied previously). The efficiency of cross-linking to the ribosomal components depended on the nature of the modified nucleotide in the mRNA analogue and its position on the ribosome, extent of cross-linking to the 18S rRNA being decreased drastically when the modified nucleotide was moved from position +7 to position +12. The nucleotides of 18S rRNA cross-linked to mRNA analogues were determined. Modified nucleotides in positions +9 and +12 cross-linked to the invariant dinucleotide A1824/A1825 and to variable A1823 in the 3'-minidomain of 18S rRNA as well as to protein S15. The same ribosomal components have been found earlier to cross-link to modified mRNA nucleotides in positions from +4 to +7. Besides, all mRNA analogues cross-linked to the invariant nucleotide c1698 in the 3'-minidomain and to and the conserved region 605-620 closing helix 18 in the 5'-domain.

Learning Temporal Statistics for Sensory Predictions in Aging.

PubMed

Luft, Caroline Di Bernardi; Baker, Rosalind; Goldstone, Aimee; Zhang, Yang; Kourtzi, Zoe

2016-03-01

Predicting future events based on previous knowledge about the environment is critical for successful everyday interactions. Here, we ask which brain regions support our ability to predict the future based on implicit knowledge about the past in young and older age. Combining behavioral and fMRI measurements, we test whether training on structured temporal sequences improves the ability to predict upcoming sensory events; we then compare brain regions involved in learning predictive structures between young and older adults. Our behavioral results demonstrate that exposure to temporal sequences without feedback facilitates the ability of young and older adults to predict the orientation of an upcoming stimulus. Our fMRI results provide evidence for the involvement of corticostriatal regions in learning predictive structures in both young and older learners. In particular, we showed learning-dependent fMRI responses for structured sequences in frontoparietal regions and the striatum (putamen) for young adults. However, for older adults, learning-dependent activations were observed mainly in subcortical (putamen, thalamus) regions but were weaker in frontoparietal regions. Significant correlations of learning-dependent behavioral and fMRI changes in these regions suggest a strong link between brain activations and behavioral improvement rather than general overactivation. Thus, our findings suggest that predicting future events based on knowledge of temporal statistics engages brain regions involved in implicit learning in both young and older adults.

Climatic controls on the isotopic composition and availability of soil nitrogen in mountainous tropical forests

NASA Astrophysics Data System (ADS)

Weintraub, S. R.; Cole, R. J.; Schmitt, C. G.; All, J.

2014-12-01

Tropical forests in mountainous regions are often assumed to be nitrogen (N) limited, yet N dynamics across rugged terrain can be complex due to gradients in climate and topography. Elucidating patterns of N availability and loss across such gradients is necessary to predict and manage tropical forest response to environmental changes such as increasing N deposition and rising temperatures. However, such data is currently lacking, particularly in remote locations that are of high conservation value. To address this gap, a research expedition organized by the American Climber Science Program recently made a coast-to-coast journey across a remote region of Costa Rica, travelling over the Cordillera Talamanca and through La Amistad International Park. Numerous biological, chemical and hydrologic measurements were made en-route across montane to premontane wet tropical forests, spanning nearly 2,000 m in elevation and 200 km. Surface soil samples collected at regular intervals along this transect illuminate environmental drivers of N dynamics across the region. The dataset reveals strong links between soil natural abundance N isotopic composition (δ15N) and elevation and temperature parameters, and weaker links to precipitation and topography. This is in general agreement with global scale observations, but divergence from some previously published works is apparent and will be discussed. δ15N mass balance models suggest that N isotope patterns reflect differences in forms of N loss and the relative importance of fractionating and non-fractionating pathways. When combined with data on several other edaphic properties, especially C:N stoichiometry, the results points toward notable variation in soil N availability and N constraints across the transect. This study illustrates large, but predictable, variation in key N cycle traits across the premontane to montane wet tropical forest transition. These findings have management-relevant implications for tropical regions.

Cross-sectional interview study of fertility, pregnancy, and urogenital schistosomiasis in coastal Kenya: Documented treatment in childhood is associated with reduced odds of subfertility among adult women

PubMed Central

Miller-Fellows, Sarah C.; Howard, Laura; Kramer, Rebekah; Hildebrand, Vanessa; Furin, Jennifer; Mutuku, Francis M.; Mukoko, Dunstan; Ivy, Julianne A.

2017-01-01

Background Previous research has documented an increased risk of subfertility in areas of sub-Saharan Africa, as well as an ecological association between urogenital schistosomiasis prevalence and decreased fertility. This pilot project examined reproductive patterns and the potential effects of childhood urogenital Schistosoma haematobium infection and individual treatment experience on adult subfertility among women who were long-term residents in an S. haematobium-endemic region of coastal Kenya. Methodology/Principal findings We analyzed findings from 162 in-depth interviews with women of childbearing age in a rural, coastal community, linking them, if possible, to their individual treatment records from previous multi-year longitudinal studies of parasitic infections. Reproductive histories indicated a much local higher local rate of subfertility (44%) than worldwide averages (8–12%). Although, due to the very high regional prevalence of schistosomiasis, a clear relationship could not be demonstrated between a history of S. haematobium infection and adult subfertility, among a convenience sub-sample of 61 women who had received documented treatment during previous interventional trials, a significant association was found between age at first anti-schistosomal treatment and later fertility in adulthood, with those women treated before age 21 significantly less likely to have subfertility (P = 0.001). Conclusions/Significance The high subfertility rate documented in this pilot study suggests the importance of programs to prevent and treat pelvic infections in their early stages to preclude reproductive tract damage. The available documented treatment data also suggest that early anti-schistosomal treatment may prevent the fertility-damaging effects of urogenital schistosomiasis, and lend support for programs that provide universal treatment of children in S. haematobium-endemic regions. PMID:29176778

Cross-sectional interview study of fertility, pregnancy, and urogenital schistosomiasis in coastal Kenya: Documented treatment in childhood is associated with reduced odds of subfertility among adult women.

PubMed

Miller-Fellows, Sarah C; Howard, Laura; Kramer, Rebekah; Hildebrand, Vanessa; Furin, Jennifer; Mutuku, Francis M; Mukoko, Dunstan; Ivy, Julianne A; King, Charles H

2017-11-01

Previous research has documented an increased risk of subfertility in areas of sub-Saharan Africa, as well as an ecological association between urogenital schistosomiasis prevalence and decreased fertility. This pilot project examined reproductive patterns and the potential effects of childhood urogenital Schistosoma haematobium infection and individual treatment experience on adult subfertility among women who were long-term residents in an S. haematobium-endemic region of coastal Kenya. We analyzed findings from 162 in-depth interviews with women of childbearing age in a rural, coastal community, linking them, if possible, to their individual treatment records from previous multi-year longitudinal studies of parasitic infections. Reproductive histories indicated a much local higher local rate of subfertility (44%) than worldwide averages (8-12%). Although, due to the very high regional prevalence of schistosomiasis, a clear relationship could not be demonstrated between a history of S. haematobium infection and adult subfertility, among a convenience sub-sample of 61 women who had received documented treatment during previous interventional trials, a significant association was found between age at first anti-schistosomal treatment and later fertility in adulthood, with those women treated before age 21 significantly less likely to have subfertility (P = 0.001). The high subfertility rate documented in this pilot study suggests the importance of programs to prevent and treat pelvic infections in their early stages to preclude reproductive tract damage. The available documented treatment data also suggest that early anti-schistosomal treatment may prevent the fertility-damaging effects of urogenital schistosomiasis, and lend support for programs that provide universal treatment of children in S. haematobium-endemic regions.

Mental retardation in a boy with an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1: Implication for the MRX locus

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

Muroya, Koji; Ogata, Tsutomu; Natsuo, Nobutake

Although genotype-phenotype correlations in male patients with various types of nullisomy for Xp22.3 have assigned a locus for X-linked mental retardation (MRX) to an approximately 3-Mb region between DXS31 and STS, the precise location has not been determined. In this paper, we describe a 14 7/12 year old Japanese boy with mental retardation and an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1, and compare the deletion map with that of previously reported three familial male patients with low-normal intelligence and a similar interstitial deletion at Xp22.3. The results suggest that the MRX gene is further localized to themore » roughly 1.5-Mb region between DXS1060 and DXS1139. 31 refs., 4 figs.« less

Historic and contemporary contamination in the marine environment of Kuwait: An overview.

PubMed

Al-Sarawi, Hanan A; Jha, Awadhesh N; Al-Sarawi, Mohammad A; Lyons, Brett P

2015-11-30

The rapid expansion of industry, along with previous pollution events linked to conflicts in the region, have led to a variety of contaminants being inadvertently or deliberately discharged into Kuwait's marine environment. These include polycyclic aromatic hydrocarbons (PAHs) and trace metals, from the petrochemical industry, and contaminated brine from the region's desalination industries. The present paper has reviewed over 60 studies that have reported the levels of contaminants, including PAHs, metals and polychlorinated biphenyls (PCBs) present in seawater, sediment and representative marine organisms. Most of the reviewed literature confirmed that while Kuwait's marine environment has been subjected to a wide array of pollution events, the actual levels of contamination remains relatively low. However, sediment contamination hotspots associated with point sources of industrial contamination, such as originating from the Shuaiba industrial area, do exist at a number of locations around the coast. Copyright © 2015 Elsevier Ltd. All rights reserved.

In Vitro Evolution of the Human Immunodeficiency Virus Type 1 Gag-Protease Region and Maintenance of Reverse Transcriptase Resistance following Prolonged Drug Exposure†

PubMed Central

La Seta Catamancio, Simona; De Pasquale, Maria Pia; Citterio, Paola; Kurtagic, Semir; Galli, Massimo; Rusconi, Stefano

2001-01-01

We studied the human immunodeficiency virus type 1 phenotypic and genotypic profiles of a dual drug-resistant isolate (isolate 14aPost-DR) selected for zidovudine (ZDV) and lamivudine (3TC) resistance and then cultured in the presence of 3TC and a protease inhibitor: indinavir (IDV), ritonavir, or KNI-272. The IDV-treated virus was highly resistant to 3TC, ZDV, and IDV and accumulated protease mutations at positions M46I and V82F. A change from alanine to valine was observed in 4 of 10 clones in the P2 position of the p7-p1 Gag-protease cleavage site, linked to position M46I in the dominant viral quasispecies. Previous 3TC resistance did not impair the development of additional mutations in the protease and Gag-protease cleavage regions. PMID:11230439

Observations of a high-excitation transition of SO in galactic H II regions

NASA Astrophysics Data System (ADS)

Watt, G. D.; Millar, T. J.; White, G. J.; Harten, R. H.

1986-02-01

High-excitation observations of the 56-45 transition of SO at 251 GHz have been made. The central four arcminutes of the Orion-KL region have been mapped and a survey of 6 other galactic sources has been performed. Detailed chemical kinetic models have been utilised to investigate the chemistry of sulphur in view of recent estimates of sulphur depletion and the possibility of a gas phase carbon to oxygen ratio greater than 1. The authors find a link between the SO/SO2 and C/O ratios and that their data are consistent with the high C I abundance detected in the Orion ridge component. In the plateau source the enhanced abundances of SO and SO2 may be caused by a molecular outflow from an oxygen-rich star. In addition a previously undetected methanol line and an unidentified line appear in the Orion data.

Locking the Elbow: Improved Antibody Fab Fragments as Chaperones for Structure Determination.

PubMed

Bailey, Lucas J; Sheehy, Kimberly M; Dominik, Pawel K; Liang, Wenguang G; Rui, Huan; Clark, Michael; Jaskolowski, Mateusz; Kim, Yejoon; Deneka, Dawid; Tang, Wei-Jen; Kossiakoff, Anthony A

2018-02-02

Antibody Fab fragments have been exploited with significant success to facilitate the structure determination of challenging macromolecules as crystallization chaperones and as molecular fiducial marks for single particle cryo-electron microscopy approaches. However, the inherent flexibility of the "elbow" regions, which link the constant and variable domains of the Fab, can introduce disorder and thus diminish their effectiveness. We have developed a phage display engineering strategy to generate synthetic Fab variants that significantly reduces elbow flexibility, while maintaining their high affinity and stability. This strategy was validated using previously recalcitrant Fab-antigen complexes where introduction of an engineered elbow region enhanced crystallization and diffraction resolution. Furthermore, incorporation of the mutations appears to be generally portable to other synthetic antibodies and may serve as a universal strategy to enhance the success rates of Fabs as structure determination chaperones. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sublethal Dosage of Imidacloprid Reduces the Microglomerular Density of Honey Bee Mushroom Bodies

PubMed Central

Peng, Yi-Chan; Yang, En-Cheng

2016-01-01

The dramatic loss of honey bees is a major concern worldwide. Previous studies have indicated that neonicotinoid insecticides cause behavioural abnormalities and have proven that exposure to sublethal doses of imidacloprid during the larval stage decreases the olfactory learning ability of adults. The present study shows the effect of sublethal doses of imidacloprid on the neural development of the honey bee brain by immunolabelling synaptic units in the calyces of mushroom bodies. We found that the density of the synaptic units in the region of the calyces, which are responsible for olfactory and visual functions, decreased after being exposed to a sublethal dose of imidacloprid. This not only links a decrease in olfactory learning ability to abnormal neural connectivity but also provides evidence that imidacloprid damages the development of the nervous system in regions responsible for both olfaction and vision during the larval stage of the honey bee. PMID:26757950

Accommodation of structural rearrangements in the huntingtin-interacting protein 1 coiled-coil domain.

PubMed

Wilbur, Jeremy D; Hwang, Peter K; Brodsky, Frances M; Fletterick, Robert J

2010-03-01

Huntingtin-interacting protein 1 (HIP1) is an important link between the actin cytoskeleton and clathrin-mediated endocytosis machinery. HIP1 has also been implicated in the pathogenesis of Huntington's disease. The binding of HIP1 to actin is regulated through an interaction with clathrin light chain. Clathrin light chain binds to a flexible coiled-coil domain in HIP1 and induces a compact state that is refractory to actin binding. To understand the mechanism of this conformational regulation, a high-resolution crystal structure of a stable fragment from the HIP1 coiled-coil domain was determined. The flexibility of the HIP1 coiled-coil region was evident from its variation from a previously determined structure of a similar region. A hydrogen-bond network and changes in coiled-coil monomer interaction suggest that the HIP1 coiled-coil domain is uniquely suited to allow conformational flexibility.

Effects of Link Annotations on Search Performance in Layered and Unlayered Hierarchically Organized Information Spaces.

ERIC Educational Resources Information Center

Fraser, Landon; Locatis, Craig

2001-01-01

Investigated the effects of link annotations on high school user search performance in Web hypertext environments having deep (layered) and shallow link structures. Results confirmed previous research that shallow link structures are better than deep (layered) link structures, and also showed that annotations had virtually no effect on search…

Common chromosomal fragile sites (CFS) may be involved in normal and traumatic cognitive stress memory consolidation and altered nervous system immunity.

PubMed

Gericke, G S

2010-05-01

Previous reports of specific patterns of increased fragility at common chromosomal fragile sites (CFS) found in association with certain neurobehavioural disorders did not attract attention at the time due to a shift towards molecular approaches to delineate neuropsychiatric disorder candidate genes. Links with miRNA, altered methylation and the origin of copy number variation indicate that CFS region characteristics may be part of chromatinomic mechanisms that are increasingly linked with neuroplasticity and memory. Current reports of large-scale double-stranded DNA breaks in differentiating neurons and evidence of ongoing DNA demethylation of specific gene promoters in adult hippocampus may shed new light on the dynamic epigenetic changes that are increasingly appreciated as contributing to long-term memory consolidation. The expression of immune recombination activating genes in key stress-induced memory regions suggests the adoption by the brain of this ancient pattern recognition and memory system to establish a structural basis for long-term memory through controlled chromosomal breakage at highly specific genomic regions. It is furthermore considered that these mechanisms for management of epigenetic information related to stress memory could be linked, in some instances, with the transfer of the somatically acquired information to the germline. Here, rearranged sequences can be subjected to further selection and possible eventual retrotranscription to become part of the more stable coding machinery if proven to be crucial for survival and reproduction. While linkage of cognitive memory with stress and fear circuitry and memory establishment through structural DNA modification is proposed as a normal process, inappropriate activation of immune-like genomic rearrangement processes through traumatic stress memory may have the potential to lead to undesirable activation of neuro-inflammatory processes. These theories could have a significant impact on the interpretation of risks posed by heredity and the environment and the search for neuropsychiatric candidate genes.

Electromobility Shift Assay Reveals Evidence in Favor of Allele-Specific Binding of RUNX1 to the 5' Hypersensitive Site 4-Locus Control Region.

PubMed

Dehghani, Hossein; Ghobakhloo, Sepideh; Neishabury, Maryam

2016-08-01

In our previous studies on the Iranian β-thalassemia (β-thal) patients, we identified an association between the severity of the β-thal phenotype and the polymorphic palindromic site at the 5' hypersensitive site 4-locus control region (5'HS4-LCR) of the β-globin gene cluster. Furthermore, a linkage disequilibrium was observed between this region and XmnI-HBG2 in the patient population. Based on this data, it was suggested that the well-recognized phenotype-ameliorating role assigned to positive XmnI could be associated with its linked elements in the LCR. To investigate the functional significance of polymorphisms at the 5'HS4-LCR, we studied its influence on binding of transcription factors. Web-based predictions of transcription factor binding revealed a binding site for runt-related transcription factor 1 (RUNX1), when the allele at the center of the palindrome (TGGGG(A/G)CCCCA) was A but not when it was G. Furthermore, electromobility shift assay (EMSA) presented evidence in support of allele-specific binding of RUNX1 to 5'HS4. Considering that RUNX1 is a well-known regulator of hematopoiesis, these preliminary data suggest the importance of further studies to confirm this interaction and consequently investigate its functional and phenotypical relevance. These studies could help us to understand the molecular mechanism behind the phenotype modifying role of the 5'HS4-LCR polymorphic palindromic region (rs16912979), which has been observed in previous studies.

[The consumption of alcohol, tobacco and drugs in adolescents].

PubMed

Martínez Alvarez, J; García González, J; Domingo Gutiérrez, M; Machín Fernández, A J

1996-10-31

To find how much alcohol, tobacco and drugs adolescents consume and identify some linked socio-family variables. A crossover and descriptive study, with randomised sampling stratified by classrooms. Secondary schools in the town of Lugo. 805 students of both sexes from the secondary schools. We used a self-filled anonymous semiclosed questionnaire. 34.6% habitually consumed alcohol, of whom 43.3% had got drunk at least once in the previous 6 months and 7.1% on more than 13 occasions. 25.7% were habitual smokers. 12.3% had consumed cannabis; 10.1% tranquilisers; 7.5% amphetamines; 4.6% sleeping pills; 2.1% cocaine; 1.9% LSD; 1.5% heroin. Variables linked to consumption were: age, repeating the school year, considering him/herself a bad student, fighting, consumption by both parents, not doing sports, having more money and not having a good relationship with parents. Adolescent alcohol, tobacco and drug consumption is high and similar to other regions of Spain. Prevention strategies are needed, in the family, at school and in the media.

Transitional fossil earwigs--a missing link in Dermaptera evolution.

PubMed

Zhao, Jingxia; Zhao, Yunyun; Shih, Chungkun; Ren, Dong; Wang, Yongjie

2010-11-10

The Dermaptera belongs to a group of winged insects of uncertain relationship within Polyneoptera, which has expanded anal region and adds numerous anal veins in the hind wing. Evolutional history and origin of Dermaptera have been in contention. In this paper, we report two new fossil earwigs in a new family of Bellodermatidae fam. nov. The fossils were collected from the Jiulongshan Formation (Middle Jurassic) in Inner Mongolia, northeast China. This new family, characterized by an unexpected combination of primitive and derived characters, is bridging the missing link between suborders of Archidermaptera and Eodermaptera. Phylogenetic analyses support the new family to be a new clade at the base of previously defined Eodermaptera and to be a stem group of (Eodermaptera+Neodermaptera). Evolutional history and origin of Dermaptera have been in contention, with dramatically different viewpoints by contemporary authors. It is suggested that the oldest Dermaptera might possibly be traced back to the Late Triassic-Early Jurassic and they had divided into Archidermaptera and (Eodermaptera+Neodermaptera) in the Middle Jurassic.

Decoding the regulatory landscape of melanoma reveals TEADS as regulators of the invasive cell state

PubMed Central

Verfaillie, Annelien; Imrichova, Hana; Atak, Zeynep Kalender; Dewaele, Michael; Rambow, Florian; Hulselmans, Gert; Christiaens, Valerie; Svetlichnyy, Dmitry; Luciani, Flavie; Van den Mooter, Laura; Claerhout, Sofie; Fiers, Mark; Journe, Fabrice; Ghanem, Ghanem-Elias; Herrmann, Carl; Halder, Georg; Marine, Jean-Christophe; Aerts, Stein

2015-01-01

Transcriptional reprogramming of proliferative melanoma cells into a phenotypically distinct invasive cell subpopulation is a critical event at the origin of metastatic spreading. Here we generate transcriptome, open chromatin and histone modification maps of melanoma cultures; and integrate this data with existing transcriptome and DNA methylation profiles from tumour biopsies to gain insight into the mechanisms underlying this key reprogramming event. This shows thousands of genomic regulatory regions underlying the proliferative and invasive states, identifying SOX10/MITF and AP-1/TEAD as regulators, respectively. Knockdown of TEADs shows a previously unrecognized role in the invasive gene network and establishes a causative link between these transcription factors, cell invasion and sensitivity to MAPK inhibitors. Using regulatory landscapes and in silico analysis, we show that transcriptional reprogramming underlies the distinct cellular states present in melanoma. Furthermore, it reveals an essential role for the TEADs, linking it to clinically relevant mechanisms such as invasion and resistance. PMID:25865119

The cosmic spiderweb: equivalence of cosmic, architectural and origami tessellations

PubMed Central

Hidding, Johan; Konstantatou, Marina; van de Weygaert, Rien

2018-01-01

For over 20 years, the term ‘cosmic web’ has guided our understanding of the large-scale arrangement of matter in the cosmos, accurately evoking the concept of a network of galaxies linked by filaments. But the physical correspondence between the cosmic web and structural engineering or textile ‘spiderwebs’ is even deeper than previously known, and also extends to origami tessellations. Here, we explain that in a good structure-formation approximation known as the adhesion model, threads of the cosmic web form a spiderweb, i.e. can be strung up to be entirely in tension. The correspondence is exact if nodes sampling voids are included, and if structure is excluded within collapsed regions (walls, filaments and haloes), where dark-matter multistreaming and baryonic physics affect the structure. We also suggest how concepts arising from this link might be used to test cosmological models: for example, to test for large-scale anisotropy and rotational flows in the cosmos. PMID:29765637

The Juberg-Marsidi syndrome maps to the proximal long arm of the X chromosome (Xq12-q21)

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

Saugier-Veber, P.; Abadie, V.; Turleau, C.

Juberg-Marsidi syndrome (McKusick 309590) is a rare X-linked recessive condition characterized by severe mental retardation, growth failure, sensorineural deafness, and microgenitalism. Here the authors report on the genetic mapping of the Juberg-Marsidi gene to the proximal long arm of the X chromosome (Xq12-q21) by linkage to probe pRX214H1 at the DXS441 locus (Z = 3.24 at [theta] = .00). Multipoint linkage analysis placed the Juberg-Marsidi gene within the interval defined by the DXS159 and the DXYS1X loci in the Xq12-q21 region. These data provide evidence for the genetic distinction between Juberg-Marsidi syndrome and several other X-linked mental retardation syndromes thatmore » have hypogonadism and hypogenitalism and that have been localized previously. Finally, the mapping of the Juberg-Marsidi gene is of potential interest for reliable genetic counseling of at-risk women. 25 refs., 2 figs., 3 tabs.« less

Linkage Analysis of Quantitative Refraction and Refractive Errors in the Beaver Dam Eye Study

PubMed Central

Duggal, Priya; Lee, Kristine E.; Cheng, Ching-Yu; Klein, Ronald; Bailey-Wilson, Joan E.; Klein, Barbara E. K.

2011-01-01

Purpose. Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed. Methods. Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed. Results. Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 × 10−4), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 × 10−3 and 1.48 × 10−3, respectively) and to 7p15 of refraction (empiric P = 9.43 × 10−4). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 × 10−3), a region previously linked to high myopia. Conclusions. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11. PMID:21571680

Study of spacecraft direct readout meteorological systems

NASA Technical Reports Server (NTRS)

Bartlett, R.; Elam, W.; Hoedemaker, R.

1973-01-01

Characteristics are defined of the next generation direct readout meteorological satellite system with particular application to Tiros N. Both space and ground systems are included. The recommended space system is composed of four geosynchronous satellites and two low altitude satellites in sun-synchronous orbit. The goesynchronous satellites transmit to direct readout ground stations via a shared S-band link, relayed FOFAX satellite cloud cover pictures (visible and infrared) and weather charts (WEFAX). Basic sensor data is transmitted to regional Data Utilization Stations via the same S-band link. Basic sensor data consists of 0.5 n.m. sub-point resolution data in the 0.55 - 0.7 micron spectral region, and 4.0 n.m. resolution data in the 10.5 - 12.6 micron spectral region. The two low altitude satellites in sun-synchronous orbit provide data to direct readout ground stations via a 137 MHz link, a 400 Mhz link, and an S-band link.

Recruitment of the cross-linked opsonic receptor CD32A (FcγRIIA) to high-density detergent-resistant membrane domains in human neutrophils

PubMed Central

2004-01-01

We have previously shown that CD32A (or FcγRIIA), one of the main opsonin receptors, was rapidly insolubilized and degraded in intact neutrophils after its cross-linking. In view of these experimental difficulties, the early signalling steps in response to CD32A activation were studied in purified plasma membranes of neutrophils. After CD32A cross-linking in these fractions, the tyrosine phosphorylation of two major substrates, the receptor itself and the tyrosine kinase Syk, was observed. Phosphorylation of these two proteins was observed only in the presence of orthovanadate, indicating the presence, in the membranes, of one or more tyrosine phosphatases that maintain CD32A dephosphorylation. The tyrosine phosphorylation of these two proteins was inhibited by the Src kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2). The ligation of CD32A led to its recruitment to a previously uncharacterized subset of high-density flotillin-1-positive DRMs (detergent-resistant membranes). The changes in the solubility properties of CD32A were observed in the absence of added ATP; therefore, they were probably not secondary to the tyrosine phosphorylation of the receptor, rather they preceded it. Src kinases as well as Syk were constitutively present in DRMs of high and low density and no evident changes in their distribution were detected after cross-linking of CD32A. Pretreatment of plasma membranes with methyl-β-cyclodextrin did not inhibit the recruitment of CD32A to DRMs, although it led to the loss of the Src kinase Lyn from these fractions. In addition, methyl-β-cyclodextrin inhibited the tyrosine phosphorylation of CD32A and Syk induced by cross-linking of CD32A. This membrane model allowed us to observe a movement of CD32A from detergent-soluble regions of the membranes to DRMs, where it joined Src kinases and Syk and became tyrosine-phosphorylated. PMID:15130090

Copy number variation of two separate regulatory regions upstream of SOX9 causes isolated 46,XY or 46,XX disorder of sex development.

PubMed

Kim, Gwang-Jin; Sock, Elisabeth; Buchberger, Astrid; Just, Walter; Denzer, Friederike; Hoepffner, Wolfgang; German, James; Cole, Trevor; Mann, Jillian; Seguin, John H; Zipf, William; Costigan, Colm; Schmiady, Hardi; Rostásy, Moritz; Kramer, Mildred; Kaltenbach, Simon; Rösler, Bernd; Georg, Ina; Troppmann, Elke; Teichmann, Anne-Christin; Salfelder, Anika; Widholz, Sebastian A; Wieacker, Peter; Hiort, Olaf; Camerino, Giovanna; Radi, Orietta; Wegner, Michael; Arnold, Hans-Henning; Scherer, Gerd

2015-04-01

SOX9 mutations cause the skeletal malformation syndrome campomelic dysplasia in combination with XY sex reversal. Studies in mice indicate that SOX9 acts as a testis-inducing transcription factor downstream of SRY, triggering Sertoli cell and testis differentiation. An SRY-dependent testis-specific enhancer for Sox9 has been identified only in mice. A previous study has implicated copy number variations (CNVs) of a 78 kb region 517-595 kb upstream of SOX9 in the aetiology of both 46,XY and 46,XX disorders of sex development (DSD). We wanted to better define this region for both disorders. By CNV analysis, we identified SOX9 upstream duplications in three cases of SRY-negative 46,XX DSD, which together with previously reported duplications define a 68 kb region, 516-584 kb upstream of SOX9, designated XXSR (XX sex reversal region). More importantly, we identified heterozygous deletions in four families with SRY-positive 46,XY DSD without skeletal phenotype, which define a 32.5 kb interval 607.1-639.6 kb upstream of SOX9, designated XY sex reversal region (XYSR). To localise the suspected testis-specific enhancer, XYSR subfragments were tested in cell transfection and transgenic experiments. While transgenic experiments remained inconclusive, a 1.9 kb SRY-responsive subfragment drove expression specifically in Sertoli-like cells. Our results indicate that isolated 46,XY and 46,XX DSD can be assigned to two separate regulatory regions, XYSR and XXSR, far upstream of SOX9. The 1.9 kb SRY-responsive subfragment from the XYSR might constitute the core of the Sertoli-cell enhancer of human SOX9, representing the so far missing link in the genetic cascade of male sex determination. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Gastric Glycoform of MUC5AC Is a Biomarker of Mucinous Cysts of the Pancreas

PubMed Central

Sinha, Jessica; Cao, Zheng; Dai, Jianliang; Tang, Huiyuan; Partyka, Katie; Hostetter, Galen; Simeone, Diane M.; Feng, Ziding; Allen, Peter J.; Brand, Randall E.; Haab, Brian B.

2016-01-01

Molecular indicators to specify the risk posed by a pancreatic cyst would benefit patients. Previously we showed that most cancer-precursor cysts, termed mucinous cysts, produce abnormal glycoforms of the proteins MUC5AC and endorepellin. Here we sought to validate the glycoforms as a biomarker of mucinous cysts and to specify the oligosaccharide linkages that characterize MUC5AC. We hypothesized that mucinous cysts secrete MUC5AC displaying terminal N-acetylglucosamine (GlcNAc) in either alpha or beta linkage. We used antibody-lectin sandwich assays to detect glycoforms of MUC5AC and endorepellin in cyst fluid samples from three independent cohorts of 49, 32, and 66 patients, and we used monoclonal antibodies to test for terminal, alpha-linked GlcNAc and the enzyme that produces it. A biomarker panel comprising the previously-identified glycoforms of MUC5AC and endorepellin gave 96%, 96%, and 87% accuracy for identifying mucinous cysts in the three cohorts with an average sensitivity of 92% and an average specificity of 94%. Glycan analysis showed that MUC5AC produced by a subset of mucinous cysts displays terminal alpha-GlcNAc, a motif expressed in stomach glands. The alpha-linked glycoform of MUC5AC was unique to intraductal papillary mucinous neoplasms (IPMN), whereas terminal beta-linked GlcNAc was increased in both IPMNs and mucinous cystic neoplasms (MCN). The enzyme that synthesizes alpha-GlcNAc, A4GNT, was expressed in the epithelia of mucinous cysts that expressed alpha-GlcNAc, especially in regions with high-grade dysplasia. Thus IPMNs secrete a gastric glycoform of MUC5AC that displays terminal alpha-GlcNAc, and the combined alpha-GlcNAc and beta-GlcNAc glycoforms form an accurate biomarker of mucinous cysts. PMID:27992432

Genome-Wide Association Study Identifies Loci for Salt Tolerance during Germination in Autotetraploid Alfalfa (Medicago sativa L.) Using Genotyping-by-Sequencing

PubMed Central

Yu, Long-Xi; Liu, Xinchun; Boge, William; Liu, Xiang-Ping

2016-01-01

Salinity is one of major abiotic stresses limiting alfalfa (Medicago sativa L.) production in the arid and semi-arid regions in US and other counties. In this study, we used a diverse panel of alfalfa accessions previously described by Zhang et al. (2015) to identify molecular markers associated with salt tolerance during germination using genome-wide association study (GWAS) and genotyping-by-sequencing (GBS). Phenotyping was done by germinating alfalfa seeds under different levels of salt stress. Phenotypic data of adjusted germination rates and SNP markers generated by GBS were used for marker-trait association. Thirty six markers were significantly associated with salt tolerance in at least one level of salt treatments. Alignment of sequence tags to the Medicago truncatula genome revealed genetic locations of the markers on all chromosomes except chromosome 3. Most significant markers were found on chromosomes 1, 2, and 4. BLAST search using the flanking sequences of significant markers identified 14 putative candidate genes linked to 23 significant markers. Most of them were repeatedly identified in two or three salt treatments. Several loci identified in the present study had similar genetic locations to the reported QTL associated with salt tolerance in M. truncatula. A locus identified on chromosome 6 by this study overlapped with that by drought in our previous study. To our knowledge, this is the first report on mapping loci associated with salt tolerance during germination in autotetraploid alfalfa. Further investigation on these loci and their linked genes would provide insight into understanding molecular mechanisms by which salt and drought stresses affect alfalfa growth. Functional markers closely linked to the resistance loci would be useful for MAS to improve alfalfa cultivars with enhanced resistance to drought and salt stresses. PMID:27446182

Novel Missense Mutation A789V in IQSEC2 Underlies X-Linked Intellectual Disability in the MRX78 Family

PubMed Central

Kalscheuer, Vera M.; James, Victoria M.; Himelright, Miranda L.; Long, Philip; Oegema, Renske; Jensen, Corinna; Bienek, Melanie; Hu, Hao; Haas, Stefan A.; Topf, Maya; Hoogeboom, A. Jeannette M.; Harvey, Kirsten; Walikonis, Randall; Harvey, Robert J.

2016-01-01

Disease gene discovery in neurodevelopmental disorders, including X-linked intellectual disability (XLID) has recently been accelerated by next-generation DNA sequencing approaches. To date, more than 100 human X chromosome genes involved in neuronal signaling pathways and networks implicated in cognitive function have been identified. Despite these advances, the mutations underlying disease in a large number of XLID families remained unresolved. We report the resolution of MRX78, a large family with six affected males and seven affected females, showing X-linked inheritance. Although a previous linkage study had mapped the locus to the short arm of chromosome X (Xp11.4-p11.23), this region contained too many candidate genes to be analyzed using conventional approaches. However, our X-chromosome exome resequencing, bioinformatics analysis and inheritance testing revealed a missense mutation (c.C2366T, p.A789V) in IQSEC2, encoding a neuronal GDP-GTP exchange factor for Arf family GTPases (ArfGEF) previously implicated in XLID. Molecular modeling of IQSEC2 revealed that the A789V substitution results in the insertion of a larger side-chain into a hydrophobic pocket in the catalytic Sec7 domain of IQSEC2. The A789V change is predicted to result in numerous clashes with adjacent amino acids and disruption of local folding of the Sec7 domain. Consistent with this finding, functional assays revealed that recombinant IQSEC2A789V was not able to catalyze GDP-GTP exchange on Arf6 as efficiently as wild-type IQSEC2. Taken together, these results strongly suggest that the A789V mutation in IQSEC2 is the underlying cause of XLID in the MRX78 family. PMID:26793055

Genes That Escape X-Inactivation in Humans Have High Intraspecific Variability in Expression, Are Associated with Mental Impairment but Are Not Slow Evolving

PubMed Central

Zhang, Yuchao; Castillo-Morales, Atahualpa; Jiang, Min; Zhu, Yufei; Hu, Landian; Urrutia, Araxi O.; Kong, Xiangyin; Hurst, Laurence D.

2013-01-01

In female mammals most X-linked genes are subject to X-inactivation. However, in humans some X-linked genes escape silencing, these escapees being candidates for the phenotypic aberrations seen in polyX karyotypes. These escape genes have been reported to be under stronger purifying selection than other X-linked genes. Although it is known that escape from X-inactivation is much more common in humans than in mice, systematic assays of escape in humans have to date employed only interspecies somatic cell hybrids. Here we provide the first systematic next-generation sequencing analysis of escape in a human cell line. We analyzed RNA and genotype sequencing data obtained from B lymphocyte cell lines derived from Europeans (CEU) and Yorubans (YRI). By replicated detection of heterozygosis in the transcriptome, we identified 114 escaping genes, including 76 not previously known to be escapees. The newly described escape genes cluster on the X chromosome in the same chromosomal regions as the previously known escapees. There is an excess of escaping genes associated with mental retardation, consistent with this being a common phenotype of polyX phenotypes. We find both differences between populations and between individuals in the propensity to escape. Indeed, we provide the first evidence for there being both hyper- and hypo-escapee females in the human population, consistent with the highly variable phenotypic presentation of polyX karyotypes. Considering also prior data, we reclassify genes as being always, never, and sometimes escape genes. We fail to replicate the prior claim that genes that escape X-inactivation are under stronger purifying selection than others. PMID:24023392

Genome-Wide Association Study Identifies Loci for Salt Tolerance during Germination in Autotetraploid Alfalfa (Medicago sativa L.) Using Genotyping-by-Sequencing.

PubMed

Yu, Long-Xi; Liu, Xinchun; Boge, William; Liu, Xiang-Ping

2016-01-01

Salinity is one of major abiotic stresses limiting alfalfa (Medicago sativa L.) production in the arid and semi-arid regions in US and other counties. In this study, we used a diverse panel of alfalfa accessions previously described by Zhang et al. (2015) to identify molecular markers associated with salt tolerance during germination using genome-wide association study (GWAS) and genotyping-by-sequencing (GBS). Phenotyping was done by germinating alfalfa seeds under different levels of salt stress. Phenotypic data of adjusted germination rates and SNP markers generated by GBS were used for marker-trait association. Thirty six markers were significantly associated with salt tolerance in at least one level of salt treatments. Alignment of sequence tags to the Medicago truncatula genome revealed genetic locations of the markers on all chromosomes except chromosome 3. Most significant markers were found on chromosomes 1, 2, and 4. BLAST search using the flanking sequences of significant markers identified 14 putative candidate genes linked to 23 significant markers. Most of them were repeatedly identified in two or three salt treatments. Several loci identified in the present study had similar genetic locations to the reported QTL associated with salt tolerance in M. truncatula. A locus identified on chromosome 6 by this study overlapped with that by drought in our previous study. To our knowledge, this is the first report on mapping loci associated with salt tolerance during germination in autotetraploid alfalfa. Further investigation on these loci and their linked genes would provide insight into understanding molecular mechanisms by which salt and drought stresses affect alfalfa growth. Functional markers closely linked to the resistance loci would be useful for MAS to improve alfalfa cultivars with enhanced resistance to drought and salt stresses.

Genome-wide Association Study of Dermatomyositis Reveals Genetic Overlap with other Autoimmune Disorders

PubMed Central

Miller, Frederick W.; Cooper, Robert G.; Vencovsky, Jiri; Rider, Lisa G.; Danko, Katalin; Wedderburn, Lucy R.; Lundberg, Ingrid E.; Pachman, Lauren M.; Reed, Ann M.; Ytterberg, Steven R.; Padyukov, Leonid; Selva-O’Callaghan, Albert; Radstake, Timothy; Isenberg, David A.; Chinoy, Hector; Ollier, William E. R.; O’Hanlon, Terrance P.; Peng, Bo; Lee, Annette; Lamb, Janine A.; Chen, Wei; Amos, Christopher I.; Gregersen, Peter K.

2014-01-01

Objective To identify new genetic associations with juvenile and adult dermatomyositis (DM). Methods We performed a genome-wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1178) and controls (n = 4724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM. Results Compared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS-level significance (P < 5x10−8) at 80 genotyped SNPs. An analysis of 141 non-MHC SNPs previously associated with autoimmune diseases showed that three SNPs linked with three genes were associated with DM, with a false discovery rate (FDR) < 0.05. These genes were phospholipase C like 1 (PLCL1, rs6738825, FDR=0.00089), B lymphoid tyrosine kinase (BLK, rs2736340, FDR=0.00031), and chemokine (C-C motif) ligand 21 (CCL21, rs951005, FDR=0.0076). None of these genes was previously reported to be associated with DM. Conclusion Our findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non-MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches. PMID:23983088

Sex differences in brain activation to emotional stimuli: a meta-analysis of neuroimaging studies.

PubMed

Stevens, Jennifer S; Hamann, Stephan

2012-06-01

Substantial sex differences in emotional responses and perception have been reported in previous psychological and psychophysiological studies. For example, women have been found to respond more strongly to negative emotional stimuli, a sex difference that has been linked to an increased risk of depression and anxiety disorders. The extent to which such sex differences are reflected in corresponding differences in regional brain activation remains a largely unresolved issue, however, in part because relatively few neuroimaging studies have addressed this issue. Here, by conducting a quantitative meta-analysis of neuroimaging studies, we were able to substantially increase statistical power to detect sex differences relative to prior studies, by combining emotion studies which explicitly examined sex differences with the much larger number of studies that examined only women or men. We used an activation likelihood estimation approach to characterize sex differences in the likelihood of regional brain activation elicited by emotional stimuli relative to non-emotional stimuli. We examined sex differences separately for negative and positive emotions, in addition to examining all emotions combined. Sex differences varied markedly between negative and positive emotion studies. The majority of sex differences favoring women were observed for negative emotion, whereas the majority of the sex differences favoring men were observed for positive emotion. This valence-specificity was particularly evident for the amygdala. For negative emotion, women exhibited greater activation than men in the left amygdala, as well as in other regions including the left thalamus, hypothalamus, mammillary bodies, left caudate, and medial prefrontal cortex. In contrast, for positive emotion, men exhibited greater activation than women in the left amygdala, as well as greater activation in other regions including the bilateral inferior frontal gyrus and right fusiform gyrus. These meta-analysis findings indicate that the amygdala, a key region for emotion processing, exhibits valence-dependent sex differences in activation to emotional stimuli. The greater left amygdala response to negative emotion for women accords with previous reports that women respond more strongly to negative emotional stimuli, as well as with hypothesized links between increased neurobiological reactivity to negative emotion and increased prevalence of depression and anxiety disorders in women. The finding of greater left amygdala activation for positive emotional stimuli in men suggests that greater amygdala responses reported previously for men for specific types of positive stimuli may also extend to positive stimuli more generally. In summary, this study extends efforts to characterize sex differences in brain activation during emotion processing by providing the largest and most comprehensive quantitative meta-analysis to date, and for the first time examining sex differences as a function of positive vs. negative emotional valence. The current findings highlight the importance of considering sex as a potential factor modulating emotional processing and its underlying neural mechanisms, and more broadly, the need to consider individual differences in understanding the neurobiology of emotion. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fellow travellers: a concordance of colonization patterns between mice and men in the North Atlantic region.

PubMed

Jones, E P; Skirnisson, K; McGovern, T H; Gilbert, M T P; Willerslev, E; Searle, J B

2012-03-19

House mice (Mus musculus) are commensals of humans and therefore their phylogeography can reflect human colonization and settlement patterns. Previous studies have linked the distribution of house mouse mitochondrial (mt) DNA clades to areas formerly occupied by the Norwegian Vikings in Norway and the British Isles. Norwegian Viking activity also extended further westwards in the North Atlantic with the settlement of Iceland, short-lived colonies in Greenland and a fleeting colony in Newfoundland in 1000 AD. Here we investigate whether house mouse mtDNA sequences reflect human history in these other regions as well. House mice samples from Iceland, whether from archaeological Viking Age material or from modern-day specimens, had an identical mtDNA haplotype to the clade previously linked with Norwegian Vikings. From mtDNA and microsatellite data, the modern-day Icelandic mice also share the low genetic diversity shown by their human hosts on Iceland. Viking Age mice from Greenland had an mtDNA haplotype deriving from the Icelandic haplotype, but the modern-day Greenlandic mice belong to an entirely different mtDNA clade. We found no genetic association between modern Newfoundland mice and the Icelandic/ancient Greenlandic mice (no ancient Newfoundland mice were available). The modern day Icelandic and Newfoundland mice belong to the subspecies M. m. domesticus, the Greenlandic mice to M. m. musculus. In the North Atlantic region, human settlement history over a thousand years is reflected remarkably by the mtDNA phylogeny of house mice. In Iceland, the mtDNA data show the arrival and continuity of the house mouse population to the present day, while in Greenland the data suggest the arrival, subsequent extinction and recolonization of house mice--in both places mirroring the history of the European human host populations. If house mice arrived in Newfoundland with the Viking settlers at all, then, like the humans, their presence was also fleeting and left no genetic trace. The continuity of mtDNA haplotype in Iceland over 1000 years illustrates that mtDNA can retain the signature of the ancestral house mouse founders. We also show that, in terms of genetic variability, house mouse populations may also track their host human populations.

Inherited crustal features and tectonic blocks of the Transantarctic Mountains: An aeromagnetic perspective (Victoria Land, Antarctica)

NASA Astrophysics Data System (ADS)

Ferraccioli, F.; Bozzo, E.

1999-11-01

Aeromagnetic images covering a sector of the Transantarctic Mountains in Victoria Land as well as the adjacent Ross Sea are used to study possible relationships between tectonic blocks along the Cenozoic and Mesozoic West Antarctic rift shoulder and prerift features inherited mainly from the Paleozoic terranes involved in the Ross Orogen. The segmentation between the Prince Albert Mountains block and the Deep Freeze Range-Terra Nova Bay region is related to an inherited NW to NNW ice-covered boundary, which we name the "central Victoria Land boundary." It is interpreted to be the unexposed, southern continuation of the Ross age back arc Exiles thrust system recognized at the Pacific coast. The regional magnetic high to the west of the central Victoria Land boundary is attributed to Ross age calc-alkaline back arc intrusives forming the in-board Wilson "Terrane," thus shifting the previously interpreted Precambrian "shield" at least 100 km farther to the west. The high-frequency anomalies of the Prince Albert Mountains and beneath the Polar Plateau show that this region was extensively effected by Jurassic tholeiitic magmatism; NE to NNE trending magnetic lineations within this pattern could reflect Cretaceous and/or Cenozoic faulting. The western and eastern edges of the Deep Freeze Range block, which flanks the Mesozoic Rennick Graben, are marked by two NW magnetic lineaments following the Priestley and Campbell Faults. The Campbell Fault is interpreted to be the reactivated Wilson thrust fault zone and is the site of a major isotopic discontinuity in the basement. To the east of the Campbell Fault, much higher amplitude magnetic anomalies reveal mafic-ultramafic intrusives associated with the alkaline Meander Intrusive Group (Eocene-Miocene). These intrusives are likely genetically linked to the highly uplifted Southern Cross Mountains block. The NW-SE trends crossing the previously recognized ENE trending Polar 3 Anomaly offshore of the Southern Cross Mountains are probably linked to Cenozoic reactivation of the Paleozoic Wilson-Bowers suture zone as proposed from recent seismic interpretations. The ENE trend of the anomaly may also be structural, and if so, it could reflect an inherited fault zone of the cratonal margin.

Folding, But Not Surface Area Expansion, Is Associated with Cellular Morphological Maturation in the Fetal Cerebral Cortex

PubMed Central

Studholme, Colin; Frias, Antonio E.

2017-01-01

Altered macroscopic anatomical characteristics of the cerebral cortex have been identified in individuals affected by various neurodevelopmental disorders. However, the cellular developmental mechanisms that give rise to these abnormalities are not understood. Previously, advances in image reconstruction of diffusion magnetic resonance imaging (MRI) have made possible high-resolution in utero measurements of water diffusion anisotropy in the fetal brain. Here, diffusion anisotropy within the developing fetal cerebral cortex is longitudinally characterized in the rhesus macaque, focusing on gestation day (G85) through G135 of the 165 d term. Additionally, for subsets of animals characterized at G90 and G135, immunohistochemical staining was performed, and 3D structure tensor analyses were used to identify the cellular processes that most closely parallel changes in water diffusion anisotropy with cerebral cortical maturation. Strong correlations were found between maturation of dendritic arbors on the cellular level and the loss of diffusion anisotropy with cortical development. In turn, diffusion anisotropy changes were strongly associated both regionally and temporally with cortical folding. Notably, the regional and temporal dependence of diffusion anisotropy and folding were distinct from the patterns observed for cerebral cortical surface area expansion. These findings strengthen the link proposed in previous studies between cellular-level changes in dendrite morphology and noninvasive diffusion MRI measurements of the developing cerebral cortex and support the possibility that, in gyroencephalic species, structural differentiation within the cortex is coupled to the formation of gyri and sulci. SIGNIFICANCE STATEMENT Abnormal brain morphology has been found in populations with neurodevelopmental disorders. However, the mechanisms linking cellular level and macroscopic maturation are poorly understood, even in normal brains. This study contributes new understanding to this subject using serial in utero MRI measurements of rhesus macaque fetuses, from which macroscopic and cellular information can be derived. We found that morphological differentiation of dendrites was strongly associated both regionally and temporally with folding of the cerebral cortex. Interestingly, parallel associations were not observed with cortical surface area expansion. These findings support the possibility that perturbed morphological differentiation of cells within the cortex may underlie abnormal macroscopic characteristics of individuals affected by neurodevelopmental disorders. PMID:28069920

A GIS-based decision support system for regional eco-security assessment and its application on the Tibetan Plateau.

PubMed

Xiaodan, Wang; Xianghao, Zhong; Pan, Gao

2010-10-01

Regional eco-security assessment is an intricate, challenging task. In previous studies, the integration of eco-environmental models and geographical information systems (GIS) usually takes two approaches: loose coupling and tight coupling. However, the present study used a full coupling approach to develop a GIS-based regional eco-security assessment decision support system (ESDSS). This was achieved by merging the pressure-state-response (PSR) model and the analytic hierarchy process (AHP) into ArcGIS 9 as a dynamic link library (DLL) using ArcObjects in ArcGIS and Visual Basic for Applications. Such an approach makes it easy to capitalize on the GIS visualization and spatial analysis functions, thereby significantly supporting the dynamic estimation of regional eco-security. A case study is presented for the Tibetan Plateau, known as the world's "third pole" after the Arctic and Antarctic. Results verified the usefulness and feasibility of the developed method. As a useful tool, the ESDSS can also help local managers to make scientifically-based and effective decisions about Tibetan eco-environmental protection and land use. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Fathering and Mothering in the Family System: Linking Marital Hostility and Aggression in Adopted Toddlers

ERIC Educational Resources Information Center

Stover, Carla Smith; Connell, Christian M.; Leve, Leslie D.; Neiderhiser, Jenae M.; Shaw, Daniel S.; Scaramella, Laura V.; Conger, Rand; Reiss, David

2012-01-01

Background: Previous studies have linked marital conflict, parenting, and externalizing problems in early childhood. However, these studies have not examined whether genes account for these links nor have they examined whether contextual factors such as parental personality or financial distress might account for links between marital conflict and…

A Brain Network Processing the Age of Faces

PubMed Central

Homola, György A.; Jbabdi, Saad; Beckmann, Christian F.; Bartsch, Andreas J.

2012-01-01

Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships. PMID:23185334

Mapping land water and energy balance relations through conditional sampling of remote sensing estimates of atmospheric forcing and surface states

NASA Astrophysics Data System (ADS)

Farhadi, Leila; Entekhabi, Dara; Salvucci, Guido

2016-04-01

In this study, we develop and apply a mapping estimation capability for key unknown parameters that link the surface water and energy balance equations. The method is applied to the Gourma region in West Africa. The accuracy of the estimation method at point scale was previously examined using flux tower data. In this study, the capability is scaled to be applicable with remotely sensed data products and hence allow mapping. Parameters of the system are estimated through a process that links atmospheric forcing (precipitation and incident radiation), surface states, and unknown parameters. Based on conditional averaging of land surface temperature and moisture states, respectively, a single objective function is posed that measures moisture and temperature-dependent errors solely in terms of observed forcings and surface states. This objective function is minimized with respect to parameters to identify evapotranspiration and drainage models and estimate water and energy balance flux components. The uncertainty of the estimated parameters (and associated statistical confidence limits) is obtained through the inverse of Hessian of the objective function, which is an approximation of the covariance matrix. This calibration-free method is applied to the mesoscale region of Gourma in West Africa using multiplatform remote sensing data. The retrievals are verified against tower-flux field site data and physiographic characteristics of the region. The focus is to find the functional form of the evaporative fraction dependence on soil moisture, a key closure function for surface and subsurface heat and moisture dynamics, using remote sensing data.

Navigation To and From a Page: Which Links Get Clicked From Where

EPA Pesticide Factsheets

Use Google Analytics navigation summary data to find out what page users most frequently click your Contact Us link from (Previous Page Path), or which links on your homepage are popular or unpopular (Next Page Path).

Microsatellite-based fine mapping of the Van der Woude syndrome locus to an interval of 4.1 cM between D1S245 and D1S414

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

Sander, A.; Schmelzle, R.; Murray, J.C.

1995-01-01

Van der Woude syndrome (VWS) is an autosomal dominant craniofacial disorder characterized by lip pits, clefting of the primary or secondary palate, and hypodontia. The gene has been localized, by RFLP-based linkage studies, to region 1q32-41 between D1S65-REN and D1S65-TGFB2. In this study we report the linkage analysis of 15 VWS families, using 18 microsatellite markers. Multipoint linkage analysis places the gene, with significant odds of 2,344:1, in a 4.1-cM interval flanked by D1S245 and D1S414. Two-point linkage analysis demonstrates close linkage of VWS with D1S205 (lod score [Z] = 24.41 at {theta} = .00) and with D1S491 (Z =more » 21.23 at {theta} = .00). The results revise the previous assignment of the VWS locus and show in an integrated map of the region 1q32-42 that the VWS gene resides more distally than previously suggested. When information about heterozygosity of the closely linked marker D1S491 in the affected members of the VWS family with a microdeletion is taken into account, the VWS critical region can be further narrowed, to the 3.6-cM interval between D1S491 and D1S414. 38 refs., 3 figs., 2 tabs.« less

Linking Climate to Incidence of Zoonotic Cutaneous Leishmaniasis (L. major) in Pre-Saharan North Africa

NASA Technical Reports Server (NTRS)

Bounoua, Lahouari; Kahime, Kholoud; Houti, Leila; Blakey, Tara; Ebi, Kristie L.; Zhang, Ping; Imhoff, Marc L.; Thome, Kurtis J.; Dudek, Claire; Sahabi, Salah A.;

Genetic and physical map of the von Recklinghausen neurofibromatosis (NF1) region on chromosome 17

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

Yagle, M.K.; Parruti, G.; Xu, W.

The von Recklinghausen neurofibromatosis 1 (NF1) locus has been previously assigned to the proximal long arm of chromosome 17, and two NF1 patients have been identified who have constitutional balanced translocations involving 17q11.2. The authors have constructed a cosmid library from a chromosome-mediated gene transfectant, KLT8, that contains approximately 10% of chromosome 17, including 17q11.2. Cosmids isolated from this library have been mapped across a panel of somatic cell hybrids, including the hybrids from the two patients, and have been localized to seven small regions of proximal 17q. They have 5 cosmids that map directly above the two NF1 translocations,more » and 11 cosmids that map directly below. Of these, 2 cosmids in each region are linked to the disease locus and 3 of these cosmids show no recombination. One distal cosmid, 2B/B35, detects the two NF1 translocations by pulsed-field gel analysis and has been used to produce a long-range restriction map that covers the translocations.« less

Modeling Climate-Water Impacts on Electricity Sector Capacity Expansion: Preprint

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

Cohen, S. M.; Macknick, J.; Averyt, K.

2014-05-01

Climate change has the potential to exacerbate water availability concerns for thermal power plant cooling, which is responsible for 41% of U.S. water withdrawals. This analysis describes an initial link between climate, water, and electricity systems using the National Renewable Energy Laboratory (NREL) Regional Energy Deployment System (ReEDS) electricity system capacity expansion model. Average surface water projections from Coupled Model Intercomparison Project 3 (CMIP3) data are applied to surface water rights available to new generating capacity in ReEDS, and electric sector growth is compared with and without climate-influenced water rights. The mean climate projection has only a small impact onmore » national or regional capacity growth and water use because most regions have sufficient unappropriated or previously retired water rights to offset climate impacts. Climate impacts are notable in southwestern states that purchase fewer water rights and obtain a greater share from wastewater and other higher-cost water resources. The electric sector climate impacts demonstrated herein establish a methodology to be later exercised with more extreme climate scenarios and a more rigorous representation of legal and physical water availability.« less

The neural basis of responsibility attribution in decision-making.

PubMed

Li, Peng; Shen, Yue; Sui, Xue; Chen, Changming; Feng, Tingyong; Li, Hong; Holroyd, Clay

2013-01-01

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent's emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context.

The Neural Basis of Responsibility Attribution in Decision-Making

PubMed Central

Li, Peng; Shen, Yue; Sui, Xue; Chen, Changming; Feng, Tingyong; Li, Hong; Holroyd, Clay

2013-01-01

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent’s emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context. PMID:24224053

Intrinsically-disordered N-termini in human parechovirus 1 capsid proteins bind encapsidated RNA.

PubMed

Shakeel, Shabih; Evans, James D; Hazelbaker, Mark; Kao, C Cheng; Vaughan, Robert C; Butcher, Sarah J

2018-04-11

Human parechoviruses (HPeV) are picornaviruses with a highly-ordered RNA genome contained within icosahedrally-symmetric capsids. Ordered RNA structures have recently been shown to interact with capsid proteins VP1 and VP3 and facilitate virus assembly in HPeV1. Using an assay that combines reversible cross-linking, RNA affinity purification and peptide mass fingerprinting (RCAP), we mapped the RNA-interacting regions of the capsid proteins from the whole HPeV1 virion in solution. The intrinsically-disordered N-termini of capsid proteins VP1 and VP3, and unexpectedly, VP0, were identified to interact with RNA. Comparing these results to those obtained using recombinantly-expressed VP0 and VP1 confirmed the virion binding regions, and revealed unique RNA binding regions in the isolated VP0 not previously observed in the crystal structure of HPeV1. We used RNA fluorescence anisotropy to confirm the RNA-binding competency of each of the capsid proteins' N-termini. These findings suggests that dynamic interactions between the viral RNA and the capsid proteins modulate virus assembly, and suggest a novel role for VP0.

The carboxyl-terminal region is a determinant for the intracellular behavior of the chorionic gonadotropin beta subunit: effects on the processing of the Asn-linked oligosaccharides.

PubMed

Muyan, M; Boime, I

1998-05-01

The placental hormone human CG (hCG) consists of two noncovalently linked alpha- and beta-subunits similar to the other glycoprotein hormones LH, FSH, and TSH. These heterodimers share a common alpha subunit but differ in their structurally distinct beta subunits. The CGbeta subunit is distinguished among the beta subunits by the presence of a C-terminal extension with four serine-linked oligosaccharides (carboxyl terminal peptide or CTP). In previous studies we observed that deleting this sequence decreased assembly of the truncated CGbeta subunit (CGbeta114) with the alpha-subunit and increased the heterogeneity of the secreted forms of the uncombined subunit synthesized in transfected Chinese hamster ovary (CHO) cells. The latter result was attributed to alterations in the processing of the two N-linked oligosaccharides. To examine at what step this heterogeneity occurs, the CGbeta and CGbeta114 genes were transfected into wild-type and mutant CHO cell lines that are defective in the late steps of the N-linked carbohydrate-processing pathway. We show here that removal of the CTP alters the processing of the core mannosyl unit of the subunit to complex forms at both glycosylation sites and that the oligosaccharides contain polylactosamine. Although it has been presumed that there is little intramolecular interaction between the CTP and the proximal domains of the subunit, our data suggest that the CTP sequence participates in the folding of the newly synthesized subunit, which is manifest by the posttranslational changes observed here.

Relationship between auditory thresholds, central spontaneous activity and hair cell loss after acoustic trauma

PubMed Central

Mulders, W.H.A.M.; Ding, D.; Salvi, R.; Robertson, D.

2011-01-01

Acoustic trauma caused by exposure to a very loud sound increases spontaneous activity in central auditory structures such as the inferior colliculus. This hyperactivity has been suggested as a neural substrate for tinnitus, a phantom hearing sensation. In previous studies we have described a tentative link between the frequency region of hearing impairment and the corresponding tonotopic regions in the inferior colliculus showing hyperactivity. In this study we further investigated the relationship between cochlear compound action potential threshold loss, cochlear outer and inner hair cell loss and central hyperactivity in inferior colliculus of guinea pigs. Two weeks after a 10 kHz pure tone acoustic trauma, a tight relationship was demonstrated between the frequency region of compound action potential threshold loss and frequency regions in the inferior colliculus showing hyperactivity. Extending the duration of the acoustic trauma from 1 to 2 h did not result in significant increases in final cochlear threshold loss, but did result in a further increase of spontaneous firing rates in the inferior colliculus. Interestingly, hair cell loss was not present in the frequency regions where elevated cochlear thresholds and central hyperactivity were measured, suggesting that subtle changes in hair cell or primary afferent neural function are sufficient for central hyperactivity to be triggered and maintained. PMID:21491427

A case report of two male siblings with autism and duplication of Xq13-q21, a region including three genes predisposing for autism.

PubMed

Wentz, Elisabet; Vujic, Mihailo; Kärrstedt, Ewa-Lotta; Erlandsson, Anna; Gillberg, Christopher

2014-05-01

Autism spectrum disorder, severe behaviour problems and duplication of the Xq12 to Xq13 region have recently been described in three male relatives. To describe the psychiatric comorbidity and dysmorphic features, including craniosynostosis, of two male siblings with autism and duplication of the Xq13 to Xq21 region, and attempt to narrow down the number of duplicated genes proposed to be leading to global developmental delay and autism. We performed DNA sequencing of certain exons of the TWIST1 gene, the FGFR2 gene and the FGFR3 gene. We also performed microarray analysis of the DNA. In addition to autism, the two male siblings exhibited severe learning disability, self-injurious behaviour, temper tantrums and hyperactivity, and had no communicative language. Chromosomal analyses were normal. Neither of the two siblings showed mutations of the sequenced exons known to produce craniosynostosis. The microarray analysis detected an extra copy of a region on the long arm of chromosome X, chromosome band Xq13.1-q21.1. Comparison of our two cases with previously described patients allowed us to identify three genes predisposing for autism in the duplicated chromosomal region. Sagittal craniosynostosis is also a new finding linked to the duplication.

Parasitism drives host genome evolution: Insights from the Pasteuria ramosa-Daphnia magna system.

PubMed

Bourgeois, Yann; Roulin, Anne C; Müller, Kristina; Ebert, Dieter

2017-04-01

Because parasitism is thought to play a major role in shaping host genomes, it has been predicted that genomic regions associated with resistance to parasites should stand out in genome scans, revealing signals of selection above the genomic background. To test whether parasitism is indeed such a major factor in host evolution and to better understand host-parasite interaction at the molecular level, we studied genome-wide polymorphisms in 97 genotypes of the planktonic crustacean Daphnia magna originating from three localities across Europe. Daphnia magna is known to coevolve with the bacterial pathogen Pasteuria ramosa for which host genotypes (clonal lines) are either resistant or susceptible. Using association mapping, we identified two genomic regions involved in resistance to P. ramosa, one of which was already known from a previous QTL analysis. We then performed a naïve genome scan to test for signatures of positive selection and found that the two regions identified with the association mapping further stood out as outliers. Several other regions with evidence for selection were also found, but no link between these regions and phenotypic variation could be established. Our results are consistent with the hypothesis that parasitism is driving host genome evolution. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Webinar Presentation: Linking Regional Aerosol Emission Changes with Multiple Impact Measures through Direct and Cloud-Related Forcing Estimates

EPA Pesticide Factsheets

This presentation, Linking Regional Aerosol Emission Changes with Multiple Impact Measures through Direct and Cloud-Related Forcing Estimates, was given at the STAR Black Carbon 2016 Webinar Series: Accounting for Impact, Emissions, and Uncertainty.

Social media use in German visceral surgeons: a cross-sectional study of a national cohort.

PubMed

Boßelmann, C M; Griffiths, B; Gallagher, H J; Matzel, K E; Brady, R R W

2018-02-01

Engagement in social media is increasing. Medical professionals have been adapting LinkedIn, a professional networking site, and Twitter, a microblogging service, for a number of uses. This development has been described for a number of medical specialties, but there remains a paucity of European data. A study was undertaken to measure the engagement and activity of German visceral surgeons on social media platforms. Visceral surgeons were identified from 15 regional Associations of Statutory Health Insurance Physicians (Kassenärztliche Vereinigungen) opt-in registers. A manual search was subsequently performed across key professional social media platforms. The presence of a profile and key markers of use were recorded. In total, 575 visceral surgeons were identified. 523 (93%) were men. 183 (31%) surgeons engaged in professional social media. 22 (3.8%) used Twitter, producing a mean of 16.43 tweets with a mean of 7.57 followers. 137 (24%) surgeons had a profile on LinkedIn with a mean of 46.36 connections. Female surgeons were less connected on LinkedIn (P < 0.005). 60 (10%) used Xing, with a mean of 27.95 connections. There were no significant differences in use of social media between surgeons from Eastern and Western Germany (P = 0.262) or male and female surgeons (P = 0.399). German visceral surgeons are less engaged and less active on social media than previously examined cohorts. Loco-regional, cultural, demographic and regulatory matters may have a significant influence on uptake. If this surgical cohort wishes to have a wider international presence then education on the potential benefits of these tools may be needed. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

Oscillations and trends of river discharge in the southern Central Andes and linkages with climate variability

NASA Astrophysics Data System (ADS)

Castino, Fabiana; Bookhagen, Bodo; Strecker, Manfred R.

2017-12-01

This study analyzes the discharge variability of small to medium drainage basins (102-104 km2) in the southern Central Andes of NW Argentina. The Hilbert-Huang Transform (HHT) was applied to evaluate non-stationary oscillatory modes of variability and trends, based on four time series of monthly-normalized discharge anomaly between 1940 and 2015. Statistically significant trends reveal increasing discharge during the past decades and document an intensification of the hydrological cycle during this period. An Ensemble Empirical Mode Decomposition (EEMD) analysis revealed that discharge variability in this region can be best described by five quasi-periodic statistically significant oscillatory modes, with mean periods varying from 1 to ∼20 y. Moreover, we show that discharge variability is most likely linked to the phases of the Pacific Decadal Oscillation (PDO) at multi-decadal timescales (∼20 y) and, to a lesser degree, to the Tropical South Atlantic SST anomaly (TSA) variability at shorter timescales (∼2-5 y). Previous studies highlighted a rapid increase in discharge in the southern Central Andes during the 1970s, inferred to have been associated with the global 1976-77 climate shift. Our results suggest that the rapid discharge increase in the NW Argentine Andes coincides with the periodic enhancement of discharge, which is mainly linked to a negative to positive transition of the PDO phase and TSA variability associated with a long-term increasing trend. We therefore suggest that variations in discharge in this region are largely driven by both natural variability and the effects of global climate change. We furthermore posit that the links between atmospheric and hydrologic processes result from a combination of forcings that operate on different spatiotemporal scales.

Childhood adversity is linked to differential brain volumes in adolescents with alcohol use disorder: a voxel-based morphometry study.

PubMed

Brooks, Samantha J; Dalvie, Shareefa; Cuzen, Natalie L; Cardenas, Valerie; Fein, George; Stein, Dan J

2014-06-01

Previous neuroimaging studies link both alcohol use disorder (AUD) and early adversity to neurobiological differences in the adult brain. However, the association between AUD and childhood adversity and effects on the developing adolescent brain are less clear, due in part to the confound of psychiatric comorbidity. Here we examine early life adversity and its association with brain volume in a unique sample of 116 South African adolescents (aged 12-16) with AUD but without psychiatric comorbidity. Participants were 58 adolescents with DSM-IV alcohol dependence and with no other psychiatric comorbidities, and 58 age-, gender- and protocol-matched light/non-drinking controls (HC). Assessments included the Childhood Trauma Questionnaire (CTQ). MR images were acquired on a 3T Siemens Magnetom Allegra scanner. Volumes of global and regional structures were estimated using SPM8 Voxel Based Morphometry (VBM), with analysis of covariance (ANCOVA) and regression analyses. In whole brain ANCOVA analyses, a main effect of group when examining the AUD effect after covarying out CTQ was observed on brain volume in bilateral superior temporal gyrus. Subsequent regression analyses to examine how childhood trauma scores are linked to brain volumes in the total cohort revealed a negative correlation in the left hippocampus and right precentral gyrus. Furthermore, bilateral (but most significantly left) hippocampal volume was negatively associated with sub-scores on the CTQ in the total cohort. These findings support our view that some alterations found in brain volumes in studies of adolescent AUD may reflect the impact of confounding factors such as psychiatric comorbidity rather than the effects of alcohol per se. In particular, early life adversity may influence the developing adolescent brain in specific brain regions, such as the hippocampus.

Dissecting the genetic heterogeneity of myopia susceptibility in an Ashkenazi Jewish population using ordered subset analysis

PubMed Central

Simpson, Claire L.; Wojciechowski, Robert; Ibay, Grace; Stambolian, Dwight

2011-01-01

Purpose Despite many years of research, most of the genetic factors contributing to myopia development remain unknown. Genetic studies have pointed to a strong inherited component, but although many candidate regions have been implicated, few genes have been positively identified. Methods We have previously reported 2 genomewide linkage scans in a population of 63 highly aggregated Ashkenazi Jewish families that identified a locus on chromosome 22. Here we used ordered subset analysis (OSA), conditioned on non-parametric linkage to chromosome 22 to detect other chromosomal regions which had evidence of linkage to myopia in subsets of the families, but not the overall sample. Results Strong evidence of linkage to a 19-cM linkage interval with a peak OSA nonparametric allele-sharing logarithm-of-odds (LOD) score of 3.14 on 20p12-q11.1 (ΔLOD=2.39, empirical p=0.029) was identified in a subset of 20 families that also exhibited strong evidence of linkage to chromosome 22. One other locus also presented with suggestive LOD scores >2.0 on chromosome 11p14-q14 and one locus on chromosome 6q22-q24 had an OSA LOD score=1.76 (ΔLOD=1.65, empirical p=0.02). Conclusions The chromosome 6 and 20 loci are entirely novel and appear linked in a subset of families whose myopia is known to be linked to chromosome 22. The chromosome 11 locus overlaps with the known Myopia-7 (MYP7, OMIM 609256) locus. Using ordered subset analysis allows us to find additional loci linked to myopia in subsets of families, and underlines the complex genetic heterogeneity of myopia even in highly aggregated families and genetically isolated populations such as the Ashkenazi Jews. PMID:21738393

A Study of Cross-linked Regions of Poly(Vinyl Alcohol) Gels by Small-Angle Neutron Scattering

NASA Astrophysics Data System (ADS)

Lawrence, Mathias B.; Desa, J. A. E.; Aswal, V. K.

2011-07-01

A poly(vinyl alcohol)-borax cross-linked hydrogel has been studied by Small Angle Neutron Scattering as a function of borax concentration in the wave-vector transfer (Q) range of 0.017 Å-1 to 0.36 Å-1. It is found that as the concentration of borax increases, so does the intensity of scattering in this range. Beyond a borax concentration of 2 mg/ml, the increase in cross-linked PVA chains leads to cross-linked units larger than 150 Å as evidenced by a reduction in intensity in the lower Q region.

Trench motion-controlled slab morphology and stress variations: Implications for the isolated 2015 Bonin Islands deep earthquake

NASA Astrophysics Data System (ADS)

Yang, Ting; Gurnis, Michael; Zhan, Zhongwen

2017-07-01

The subducted old and cold Pacific Plate beneath the young Philippine Sea Plate at the Izu-Bonin trench over the Cenozoic hosts regional deep earthquakes. We investigate slab morphology and stress regimes under different trench motion histories with mantle convection models. Viscosity, temperature, and deviatoric stress are inherently heterogeneous within the slab, which we link to the occurrence of isolated earthquakes. Models expand on previous suggestions that observed slab morphology variations along the Izu-Bonin subduction zone, exhibited as shallow slab dip angles in the north and steeper dip angles in the south, are mainly due to variations in the rate of trench retreat from the north (where it is fast) to the south (where it is slow). Geodynamic models consistent with the regional plate tectonics, including oceanic plate age, plate convergence rate, and trench motion history, reproduce the seismologically observed principal stress direction and slab morphology. We suggest that the isolated 680 km deep, 30 May 2015 Mw 7.9 Bonin Islands earthquake, which lies east of the well-defined Benioff zone and has its principal compressional stress direction oriented toward the tip of the previously defined Benioff zone, can be explained by Pacific slab buckling in response to the slow trench retreat.

Diurnal feeding behavior of the American Eel Anguilla rostrata

USGS Publications Warehouse

Engman, Augustin C.; Fischer, Jesse R.; Kwak, Thomas J.; Walter, Michael J.

2017-01-01

Despite potential to structure ecosystem food webs through top-down effects, the trophic interactions of the American Eel Anguilla rostrata remain largely understudied. All previous research on the trophic ecology of American Eel in inland aquatic ecosystems has been conducted in temperate continental regions of the species' range. These studies have led to a paradigm that American Eel is a nocturnally active benthic predator, which most commonly consumes benthic invertebrates. Tropical island streams and rivers have habitats and communities that are distinct from temperate counterparts, but comprise a large portion of the adult habitat in the American Eel's range. We documented a previously undescribed diurnal feeding behavior by American Eel in a Caribbean river and demonstrate that this behavior, and a shift toward more frequent daytime feeding, is linked to periodic mass migrations of postlarvae of amphidromous fish taxa, including the Sicydiine goby Sicydiumspp. Our findings indicate that periodic mass migrations of amphidromous postlarvae could function as a potentially important food source for American Eel in tropical regions of its distribution, despite the intermittence of availability. Furthermore, this suggests that the American Eel plays an important role in the structure of tropical lotic food webs through top-down effects that are potentially augmented by instream barriers.

The neural components of empathy: predicting daily prosocial behavior.

PubMed

Morelli, Sylvia A; Rameson, Lian T; Lieberman, Matthew D

2014-01-01

Previous neuroimaging studies on empathy have not clearly identified neural systems that support the three components of empathy: affective congruence, perspective-taking, and prosocial motivation. These limitations stem from a focus on a single emotion per study, minimal variation in amount of social context provided, and lack of prosocial motivation assessment. In the current investigation, 32 participants completed a functional magnetic resonance imaging session assessing empathic responses to individuals experiencing painful, anxious, and happy events that varied in valence and amount of social context provided. They also completed a 14-day experience sampling survey that assessed real-world helping behaviors. The results demonstrate that empathy for positive and negative emotions selectively activates regions associated with positive and negative affect, respectively. In addition, the mirror system was more active during empathy for context-independent events (pain), whereas the mentalizing system was more active during empathy for context-dependent events (anxiety, happiness). Finally, the septal area, previously linked to prosocial motivation, was the only region that was commonly activated across empathy for pain, anxiety, and happiness. Septal activity during each of these empathic experiences was predictive of daily helping. These findings suggest that empathy has multiple input pathways, produces affect-congruent activations, and results in septally mediated prosocial motivation.

Inferences on the evolutionary history of the Drosophila americana polymorphic X/4 fusion from patterns of polymorphism at the X-linked paralytic and elav genes.

PubMed Central

Vieira, Cristina P; Coelho, Paula A; Vieira, Jorge

2003-01-01

In Drosophila there is limited evidence on the nature of evolutionary forces affecting chromosomal arrangements other than inversions. The study of the X/4 fusion polymorphism of Drosophila americana is thus of interest. Polymorphism patterns at the paralytic (para) gene, located at the base of the X chromosome, suggest that there is suppressed crossing over in this region between fusion and nonfusion chromosomes but not within fusion and nonfusion chromosomes. These data are thus compatible with previous claims that within fusion chromosomes the amino acid clines found at fused1 (also located at the base of the X chromosome) are likely maintained by local selection. The para data set also suggests a young age of the X/4 fusion. Polymorphism data on para and elav (located at the middle region of the X chromosome) suggest that there is no population structure other than that caused by the X/4 fusion itself. These findings are therefore compatible with previous claims that selection maintains the strong association observed between the methionine/threonine variants at fused1 and the status of the X chromosome as fused or unfused to the fourth chromosome. PMID:12930752

The neural components of empathy: Predicting daily prosocial behavior

PubMed Central

Rameson, Lian T.; Lieberman, Matthew D.

2014-01-01

Previous neuroimaging studies on empathy have not clearly identified neural systems that support the three components of empathy: affective congruence, perspective-taking, and prosocial motivation. These limitations stem from a focus on a single emotion per study, minimal variation in amount of social context provided, and lack of prosocial motivation assessment. In the current investigation, 32 participants completed a functional magnetic resonance imaging session assessing empathic responses to individuals experiencing painful, anxious, and happy events that varied in valence and amount of social context provided. They also completed a 14-day experience sampling survey that assessed real-world helping behaviors. The results demonstrate that empathy for positive and negative emotions selectively activates regions associated with positive and negative affect, respectively. In addition, the mirror system was more active during empathy for context-independent events (pain), whereas the mentalizing system was more active during empathy for context-dependent events (anxiety, happiness). Finally, the septal area, previously linked to prosocial motivation, was the only region that was commonly activated across empathy for pain, anxiety, and happiness. Septal activity during each of these empathic experiences was predictive of daily helping. These findings suggest that empathy has multiple input pathways, produces affect-congruent activations, and results in septally mediated prosocial motivation. PMID:22887480

Sternoclavicular Arthritis as a Clinical Presentation for Lyme Disease.

PubMed

Ramgopal, Sriram; Rosenkranz, Margalit; Nowalk, Andrew J; Zuckerbraun, Noel S

2018-04-01

Lyme disease is caused by Borrelia burgdorferi and can lead to dermatologic, neurologic, cardiac, and musculoskeletal manifestations. The arthritis of Lyme disease is typically monoarticular, with the knee being most commonly involved. Lyme arthritis of small joints has not previously been well described. We report 3 children who presented with sternoclavicular joint swelling and who were found to have Lyme disease based on enzyme-linked immunosorbent assay and Western blot. This description of sternoclavicular Lyme arthritis highlights the importance of considering Lyme disease in the differential and diagnostic workup of new onset, small joint arthritis in patients presenting from or with travel to Lyme endemic regions. Copyright © 2018 by the American Academy of Pediatrics.

Critical region within 22q11.2 linked to higher rate of autism spectrum disorder.

PubMed

Clements, Caitlin C; Wenger, Tara L; Zoltowski, Alisa R; Bertollo, Jennifer R; Miller, Judith S; de Marchena, Ashley B; Mitteer, Lauren M; Carey, John C; Yerys, Benjamin E; Zackai, Elaine H; Emanuel, Beverly S; McDonald-McGinn, Donna M; Schultz, Robert T

2017-01-01

Previous studies have reported no clear critical region for medical comorbidities in children with deletions or duplications of 22q11.2. The purpose of this study was to evaluate whether individuals with small nested deletions or duplications of the LCR-A to B region of 22q11.2 show an elevated rate of autism spectrum disorder (ASD) compared to individuals with deletions or duplications that do not include this region. We recruited 46 patients with nested deletions ( n  = 33) or duplications ( n  = 13) of 22q11.2, including LCR-A to B ( n del  = 11), LCR-A to C ( n del  = 4), LCR-B to D ( n del  = 14; n dup  = 8), LCR-C to D ( n del  = 4; n dup  = 2), and smaller nested regions ( n  = 3). Parent questionnaire, record review, and, for a subset, in-person evaluation were used for ASD diagnostic classification. Rates of ASD in individuals with involvement of LCR-B to LCR-D were compared with Fisher's exact test to LCR-A to LCR-B for deletions, and to a previously published sample of LCR-A to LCR-D for duplications. The rates of medical comorbidities and psychiatric diagnoses were determined from questionnaires and chart review. We also report group mean differences on psychiatric questionnaires. Individuals with deletions involving LCR-A to B showed a 39-44% rate of ASD compared to 0% in individuals whose deletions did not involve LCR-A to B. We observed similar rates of medical comorbidities in individuals with involvement of LCR-A to B and LCR-B to D for both duplications and deletions, consistent with prior studies. Children with nested deletions of 22q11.2 may be at greater risk for autism spectrum disorder if the region includes LCR-A to LCR-B. Replication is needed.

Neural Correlates of Attitude Change Following Positive and Negative Advertisements

PubMed Central

Kato, Junko; Ide, Hiroko; Kabashima, Ikuo; Kadota, Hiroshi; Takano, Kouji; Kansaku, Kenji

2009-01-01

Understanding changes in attitudes towards others is critical to understanding human behaviour. Neuropolitical studies have found that the activation of emotion-related areas in the brain is linked to resilient political preferences, and neuroeconomic research has analysed the neural correlates of social preferences that favour or oppose consideration of intrinsic rewards. This study aims to identify the neural correlates in the prefrontal cortices of changes in political attitudes toward others that are linked to social cognition. Functional magnetic resonance imaging (fMRI) experiments have presented videos from previous electoral campaigns and television commercials for major cola brands and then used the subjects' self-rated affinity toward political candidates as behavioural indicators. After viewing negative campaign videos, subjects showing stronger fMRI activation in the dorsolateral prefrontal cortex lowered their ratings of the candidate they originally supported more than did those with smaller fMRI signal changes in the same region. Subjects showing stronger activation in the medial prefrontal cortex tended to increase their ratings more than did those with less activation. The same regions were not activated by viewing negative advertisements for cola. Correlations between the self-rated values and the neural signal changes underscore the metric representation of observed decisions (i.e., whether to support or not) in the brain. This indicates that neurometric analysis may contribute to the exploration of the neural correlates of daily social behaviour. PMID:19503749

Cenozoic motion between East and West Antarctica

PubMed

Cande; Stock; Muller; Ishihara

2000-03-09

The West Antarctic rift system is the result of late Mesozoic and Cenozoic extension between East and West Antarctica, and represents one of the largest active continental rift systems on Earth. But the timing and magnitude of the plate motions leading to the development of this rift system remain poorly known, because of a lack of magnetic anomaly and fracture zone constraints on seafloor spreading. Here we report on magnetic data, gravity data and swath bathymetry collected in several areas of the south Tasman Sea and northern Ross Sea. These results enable us to calculate mid-Cenozoic rotation parameters for East and West Antarctica. These rotations show that there was roughly 180 km of separation in the western Ross Sea embayment in Eocene and Oligocene time. This episode of extension provides a tectonic setting for several significant Cenozoic tectonic events in the Ross Sea embayment including the uplift of the Transantarctic Mountains and the deposition of large thicknesses of Oligocene sediments. Inclusion of this East-West Antarctic motion in the plate circuit linking the Australia, Antarctic and Pacific plates removes a puzzling gap between the Lord Howe rise and Campbell plateau found in previous early Tertiary reconstructions of the New Zealand region. Determination of this East-West Antarctic motion also resolves a long standing controversy regarding the contribution of deformation in this region to the global plate circuit linking the Pacific to the rest of the world.

The Effects of Both Recent and Long-Term Selection and Genetic Drift Are Readily Evident in North American Barley Breeding Populations

PubMed Central

Poets, Ana M.; Mohammadi, Mohsen; Seth, Kiran; Wang, Hongyun; Kono, Thomas J. Y.; Fang, Zhou; Muehlbauer, Gary J.; Smith, Kevin P.; Morrell, Peter L.

2015-01-01

Barley was introduced to North America ∼400 yr ago but adaptation to modern production environments is more recent. Comparisons of allele frequencies among growth habits and spike (inflorescence) types in North America indicate that significant genetic differentiation has accumulated in a relatively short evolutionary time span. Allele frequency differentiation is greatest among barley with two-row vs. six-row spikes, followed by spring vs. winter growth habit. Large changes in allele frequency among breeding programs suggest a major contribution of genetic drift and linked selection on genetic variation. Despite this, comparisons of 3613 modern North American cultivated barley breeding lines that differ for spike-type and growth habit permit the discovery of 142 single nucleotide polymorphism (SNP) outliers putatively linked to targets of selection. For example, SNPs within the Cbf4, Ppd-H1, and Vrn-H1 loci, which have previously been associated with agronomically adaptive phenotypes, are identified as outliers. Analysis of extended haplotype sharing identifies genomic regions shared within and among breeding populations, suggestive of a number of genomic regions subject to recent selection. Finally, we are able to identify recent bouts of gene flow between breeding populations that could point to the sharing of agronomically adaptive variation. These results are supported by pedigrees and breeders’ understanding of germplasm sharing. PMID:26715093

Spatial and temporal variation of Cenozoic surface elevation in the Great Basin and Sierra Nevada

USGS Publications Warehouse

Horton, T.W.; Sjostrom, D.J.; Abruzzese, M.J.; Poage, M.A.; Waldbauer, J.R.; Hren, M.; Wooden, J.; Chamberlain, C.P.

2004-01-01

The surface uplift of mountain belts caused by tectonism plays an important role in determining the long-term climate evolution of the Earth. However, the general lack of information on the paleotopography of mountain belts limits our ability to identify the links and feedbacks between topography, tectonics, and climate change on geologic time-scales. Here, we present a ??18O and ??D record of authigenic minerals for the northern Great Basin that captures the timing and magnitude of regional surface uplift and subsidence events in the western United States during the Cenozoic. Authigenic calcite, smectite, and chert ??18O values suggest the northern Great Basin region experienced ???2km of surface uplift between the middle Eocene and early Oligocene followed by ???1 to 2km of surface subsidence in the southern Great Basin and/or Sierra Nevada since the middle Miocene. These data when combined with previously published work show that the surface uplift history varied in both space and time. Surface uplift migrated from north to south with high elevations in southern British Columbia and northeastern Washington in the middle Eocene and development of surface uplift in north and central Nevada in the Oligocene. This pattern of north to south surface uplift is similar to the timing of magmatism in the western Cordillera, a result that supports tectonic models linking magamtism with removal of mantle lithosphere and/or a subducting slab.

Communicative versus Strategic Rationality: Habermas Theory of Communicative Action and the Social Brain

PubMed Central

Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael; Denke, Claudia

2013-01-01

In the philosophical theory of communicative action, rationality refers to interpersonal communication rather than to a knowing subject. Thus, a social view of rationality is suggested. The theory differentiates between two kinds of rationality, the emancipative communicative and the strategic or instrumental reasoning. Using experimental designs in an fMRI setting, recent studies explored similar questions of reasoning in the social world and linked them with a neural network including prefrontal and parietal brain regions. Here, we employed an fMRI approach to highlight brain areas associated with strategic and communicative reasoning according to the theory of communicative action. Participants were asked to assess different social scenarios with respect to communicative or strategic rationality. We found a network of brain areas including temporal pole, precuneus, and STS more activated when participants performed communicative reasoning compared with strategic thinking and a control condition. These brain regions have been previously linked to moral sensitivity. In contrast, strategic rationality compared with communicative reasoning and control was associated with less activation in areas known to be related to moral sensitivity, emotional processing, and language control. The results suggest that strategic reasoning is associated with reduced social and emotional cognitions and may use different language related networks. Thus, the results demonstrate experimental support for the assumptions of the theory of communicative action. PMID:23734238

The combination of direct and paired link graphs can boost repetitive genome assembly

PubMed Central

Shi, Wenyu; Ji, Peifeng

2017-01-01

Abstract Currently, most paired link based scaffolding algorithms intrinsically mask the sequences between two linked contigs and bypass their direct link information embedded in the original de Bruijn assembly graph. Such disadvantage substantially complicates the scaffolding process and leads to the inability of resolving repetitive contig assembly. Here we present a novel algorithm, inGAP-sf, for effectively generating high-quality and continuous scaffolds. inGAP-sf achieves this by using a new strategy based on the combination of direct link and paired link graphs, in which direct link is used to increase graph connectivity and to decrease graph complexity and paired link is employed to supervise the traversing process on the direct link graph. Such advantage greatly facilitates the assembly of short-repeat enriched regions. Moreover, a new comprehensive decision model is developed to eliminate the noise routes accompanying with the introduced direct link. Through extensive evaluations on both simulated and real datasets, we demonstrated that inGAP-sf outperforms most of the genome scaffolding algorithms by generating more accurate and continuous assembly, especially for short repetitive regions. PMID:27924003

Temporal context, preference, and resistance to change.

PubMed

Podlesnik, Christopher A; Jimenez-Gomez, Corina; Thrailkill, Eric A; Shahan, Timothy A

2011-09-01

According to behavioral momentum theory, preference and relative resistance to change in concurrent-chains schedules are correlated and reflect the relative conditioned value of discriminative stimuli. In the present study, we explore the generality of this relation by manipulating the temporal context within a concurrent-chains procedure through changes in the duration of the initial links. Consistent with previous findings, preference for a richer terminal link was less extreme with longer initial links across three experiments with pigeons. In Experiment 1, relative resistance to change and preference were related inversely when responding was disrupted with response-independent food presentations during initial links, replicating a previous finding with rats. However, more food was presented with longer initial links, confounding the disrupter and initial-link duration. In Experiment 2, presession feeding was used instead and eliminated the negative relation between relative resistance to change and preference, but relative resistance to change was not sensitive to relative terminal-link reinforcement rates. In Experiment 3, with more extreme relative terminal-link reinforcement rates, increasing initial-link duration similarly decreased preference and relative resistance to change for the richer terminal link. Thus, when conditions of disruption are equal and assessed under the appropriate reinforcement conditions, changes in temporal context impact relative resistance to change and preference similarly.

From memory to prospection: what are the overlapping and the distinct components between remembering and imagining?

PubMed Central

Zheng, Huimin; Luo, Jiayi; Yu, Rongjun

2014-01-01

Reflecting on past events and reflecting on future events are two fundamentally different processes, each traveling in the opposite direction of the other through conceptual time. But what we are able to imagine seems to be constrained by what we have previously experienced, suggesting a close link between memory and prospection. Recent theories suggest that recalling the past lies at the core of imagining and planning for the future. The existence of this link is supported by evidence gathered from neuroimaging, lesion, and developmental studies. Yet it is not clear exactly how the novel episodes people construct in their sense of the future develop out of their historical memories. There must be intermediary processes that utilize memory as a basis on which to generate future oriented thinking. Here, we review studies on goal-directed processing, associative learning, cognitive control, and creativity and link them with research on prospection. We suggest that memory cooperates with additional functions like goal-directed learning to construct and simulate novel events, especially self-referential events. The coupling between memory-related hippocampus and other brain regions may underlie such memory-based prospection. Abnormalities in this constructive process may contribute to mental disorders such as schizophrenia. PMID:25147532

Task-Based Core-Periphery Organization of Human Brain Dynamics

PubMed Central

Bassett, Danielle S.; Wymbs, Nicholas F.; Rombach, M. Puck; Porter, Mason A.; Mucha, Peter J.; Grafton, Scott T.

2013-01-01

As a person learns a new skill, distinct synapses, brain regions, and circuits are engaged and change over time. In this paper, we develop methods to examine patterns of correlated activity across a large set of brain regions. Our goal is to identify properties that enable robust learning of a motor skill. We measure brain activity during motor sequencing and characterize network properties based on coherent activity between brain regions. Using recently developed algorithms to detect time-evolving communities, we find that the complex reconfiguration patterns of the brain's putative functional modules that control learning can be described parsimoniously by the combined presence of a relatively stiff temporal core that is composed primarily of sensorimotor and visual regions whose connectivity changes little in time and a flexible temporal periphery that is composed primarily of multimodal association regions whose connectivity changes frequently. The separation between temporal core and periphery changes over the course of training and, importantly, is a good predictor of individual differences in learning success. The core of dynamically stiff regions exhibits dense connectivity, which is consistent with notions of core-periphery organization established previously in social networks. Our results demonstrate that core-periphery organization provides an insightful way to understand how putative functional modules are linked. This, in turn, enables the prediction of fundamental human capacities, including the production of complex goal-directed behavior. PMID:24086116

Surface expression of Eastern Mediterranean slab dynamics: Uplift at the SW margin of the Central Anatolian Plateau

NASA Astrophysics Data System (ADS)

Schildgen, T. F.; Cosentino, D.; Caruso, A.; Yildirim, C.; Echtler, H.; Strecker, M. R.

2011-12-01

The Central Anatolian plateau in Turkey borders one of the most complex tectonic regions on Earth, where collision of the Arabian plate with Eurasia in Eastern Anatolia transitions to a cryptic pattern of subduction of the African beneath the Eurasian plate, with concurrent westward extrusion of the Anatolian microplate. Topographic growth of the southern margin of the Central Anatolian plateau has proceeded in discrete stages that can be distinguished based on the outcrop pattern and ages of uplifted marine sediments. These marine units, together with older basement rocks and younger continental sedimentary fills, also record an evolving nature of crustal deformation and uplift patterns that can be used to test the viability of different uplift mechanisms that have contributed to generate the world's third-largest orogenic plateau. Late Miocene marine sediments outcrop along the SW plateau margin at 1.5 km elevation, while they blanket the S and SE margins at up to more than 2 km elevation. Our new biostratigraphic data limit the age of 1.5-km-high marine sediments along the SW plateau margin to < 7.17 Ma, while regional lithostratigraphic correlations imply that the age is < 6.7 Ma. After reconstructing the post-Late Miocene surface uplift pattern from elevations of uplifted marine sediments and geomorphic reference surfaces, it is clear that regional surface uplift reaches maximum values along the modern plateau margin, with the SW margin experiencing less cumulative uplift compared to the S and SE margins. Our structural measurements and inversion modeling of faults within the uplifted region agree with previous findings in surrounding regions, with early contraction followed by strike-slip and extensional deformation. Shallow earthquake focal mechanisms show that the extensional phase has continued to the present. Broad similarities in the onset of surface uplift (after 7 Ma) and a change in the kinematic evolution of the plateau margin (after 8 Ma) suggest that these phenomena may have been linked with a change in the tectonic stress field associated with the process(es) causing post-7 Ma surface uplift. The complex geometry of lithospheric slabs beneath the southern plateau margin, early Pliocene to recent alkaline volcanism, and the localized uplift pattern with accompanying tensional/transtensional stresses point toward slab tearing and localized heating at the base of the lithosphere as a probable mechanism for post-7 Ma uplift of the SW margin. Considering previous work in the region, slab break-off is more likely responsible for non-contractional uplift along the S and SE margins. Overall there appears to be an important link between slab dynamics and surface uplift across the whole southern margin of the Central Anatolian plateau.

Linking Orbital, Field, and Laboratory Analyses of Dolerites in the McMurdo Dry Valleys of Antarctica: Terrestrial Studies and Planetary Applications

NASA Astrophysics Data System (ADS)

Salvatore, M. R.; Mustard, J. F.; Head, J. W.; Marchant, D. R.; Wyatt, M. B.; Seeley, J.

2012-03-01

Primary igneous and secondary alteration signatures can be resolved using orbital spectroscopy over mafic regions of the McMurdo Dry Valleys. We assess the nature of these signatures and their link to surface stability and regional microclimates.

Sequence variation in the env gene of simian immunodeficiency virus recovered from immunized macaques is predominantly in the V1 region.

PubMed

Almond, N; Jenkins, A; Heath, A B; Kitchin, P

1993-05-01

Three cynomolgus macaques were immunized with recombinant envelope protein preparations derived from simian immunodeficiency virus (SIV). Although humoral and cellular responses were elicited by the immunization regime, all macaques became infected upon challenge with 10 MID50 of the 11/88 virus challenge stock of SIVmac251-32H. The polymerase chain reaction was used to amplify proviral SIV gp120 sequences present in the blood of both immunized and control macaques at 2 months post-infection. A comparison of the predominant sequences found in the region from V2 to V5 of gp120 failed to differentiate provirus recovered from either immunized or control animals. A detailed investigation of sequences obtained from the hypervariable V1 region identified a mixture of sequences in both immunized and control macaques. Some sequences were identical to those previously detected in the virus challenge stock, whereas others had not been detected previously. Phenogram analysis of the new V1 sequences found in immunized animals revealed that they were quite distinct from those from the virus challenge stock and that they included alterations to potential N-linked glycosylation sites. In contrast, new sequence variants recovered from the control animals were closely related to sequences from the virus challenge stock. The difference in diversity of new V1 sequences recovered from immunized and control macaques was highly significant (P < 0.001). Thus, the presence of pre-existing immune responses to SIV envelope protein is associated with greater genetic change in the V1 region of gp120. These data are discussed in relation to the epitopes of SIV gp120 that may confer protection from in vivo challenge.

The Neural Bases of Interoceptive Encoding and Recall in Healthy Adults and Adults With Depression.

PubMed

DeVille, Danielle C; Kerr, Kara L; Avery, Jason A; Burrows, Kaiping; Bodurka, Jerzy; Feinstein, Justin S; Khalsa, Sahib S; Paulus, Martin P; Simmons, W Kyle

2018-06-01

Theoretical models assert that the brain's interoceptive network links external stimuli with their interoceptive consequences, thereby supporting later recall of these associations to guide the selection of healthy behaviors. If these accounts are correct, previously reported interoceptive abnormalities in major depressive disorder (MDD) should lead to altered recall of associations between external stimuli and their interoceptive (somatic) consequences. To date, the processes underlying interoceptive recall have never been experimentally investigated. We designed and implemented the Interoceptive Encoding and Recall task to compare interoceptive and exteroceptive recall among subjects with MDD (n = 24) and healthy comparison subjects (n = 21). During the encoding phase, subjects learned to pair neutral visual cues (geometric shapes) with aversive interoceptive and exteroceptive stimuli. Later, while undergoing functional magnetic resonance imaging, subjects were prompted to recall the stimulus associated with each shape. Interoceptive recall, relative to exteroceptive recall, was associated with bilateral mid-to-posterior insula activation. Relative to the healthy control participants, participants with depression exhibited marked hypoactivation of the right dorsal mid-insula during interoceptive recall. In healthy control subjects, simply recalling a stimulus associated with a previous interoceptive challenge activated a key region in the brain's interoceptive network. Although previous research has linked MDD with aberrant processing of interoceptive stimuli, the current study is the first to demonstrate that individuals with MDD exhibit decreased insula activity while recalling interoceptive memories. It is possible that insula hypoactivation during interoceptive recall may affect the representation of prior interoceptive experiences in ways that contribute to depressive symptomology and the relationship between depression and systemic health. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

High-resolution SAR11 ecotype dynamics at the Bermuda Atlantic Time-series Study site by phylogenetic placement of pyrosequences

PubMed Central

Vergin, Kevin L; Beszteri, Bánk; Monier, Adam; Cameron Thrash, J; Temperton, Ben; Treusch, Alexander H; Kilpert, Fabian; Worden, Alexandra Z; Giovannoni, Stephen J

2013-01-01

Advances in next-generation sequencing technologies are providing longer nucleotide sequence reads that contain more information about phylogenetic relationships. We sought to use this information to understand the evolution and ecology of bacterioplankton at our long-term study site in the Western Sargasso Sea. A bioinformatics pipeline called PhyloAssigner was developed to align pyrosequencing reads to a reference multiple sequence alignment of 16S ribosomal RNA (rRNA) genes and assign them phylogenetic positions in a reference tree using a maximum likelihood algorithm. Here, we used this pipeline to investigate the ecologically important SAR11 clade of Alphaproteobacteria. A combined set of 2.7 million pyrosequencing reads from the 16S rRNA V1–V2 regions, representing 9 years at the Bermuda Atlantic Time-series Study (BATS) site, was quality checked and parsed into a comprehensive bacterial tree, yielding 929 036 Alphaproteobacteria reads. Phylogenetic structure within the SAR11 clade was linked to seasonally recurring spatiotemporal patterns. This analysis resolved four new SAR11 ecotypes in addition to five others that had been described previously at BATS. The data support a conclusion reached previously that the SAR11 clade diversified by subdivision of niche space in the ocean water column, but the new data reveal a more complex pattern in which deep branches of the clade diversified repeatedly across depth strata and seasonal regimes. The new data also revealed the presence of an unrecognized clade of Alphaproteobacteria, here named SMA-1 (Sargasso Mesopelagic Alphaproteobacteria, group 1), in the upper mesopelagic zone. The high-resolution phylogenetic analyses performed herein highlight significant, previously unknown, patterns of evolutionary diversification, within perhaps the most widely distributed heterotrophic marine bacterial clade, and strongly links to ecosystem regimes. PMID:23466704

High-resolution SAR11 ecotype dynamics at the Bermuda Atlantic Time-series Study site by phylogenetic placement of pyrosequences.

PubMed

Vergin, Kevin L; Beszteri, Bánk; Monier, Adam; Thrash, J Cameron; Temperton, Ben; Treusch, Alexander H; Kilpert, Fabian; Worden, Alexandra Z; Giovannoni, Stephen J

2013-07-01

Advances in next-generation sequencing technologies are providing longer nucleotide sequence reads that contain more information about phylogenetic relationships. We sought to use this information to understand the evolution and ecology of bacterioplankton at our long-term study site in the Western Sargasso Sea. A bioinformatics pipeline called PhyloAssigner was developed to align pyrosequencing reads to a reference multiple sequence alignment of 16S ribosomal RNA (rRNA) genes and assign them phylogenetic positions in a reference tree using a maximum likelihood algorithm. Here, we used this pipeline to investigate the ecologically important SAR11 clade of Alphaproteobacteria. A combined set of 2.7 million pyrosequencing reads from the 16S rRNA V1-V2 regions, representing 9 years at the Bermuda Atlantic Time-series Study (BATS) site, was quality checked and parsed into a comprehensive bacterial tree, yielding 929 036 Alphaproteobacteria reads. Phylogenetic structure within the SAR11 clade was linked to seasonally recurring spatiotemporal patterns. This analysis resolved four new SAR11 ecotypes in addition to five others that had been described previously at BATS. The data support a conclusion reached previously that the SAR11 clade diversified by subdivision of niche space in the ocean water column, but the new data reveal a more complex pattern in which deep branches of the clade diversified repeatedly across depth strata and seasonal regimes. The new data also revealed the presence of an unrecognized clade of Alphaproteobacteria, here named SMA-1 (Sargasso Mesopelagic Alphaproteobacteria, group 1), in the upper mesopelagic zone. The high-resolution phylogenetic analyses performed herein highlight significant, previously unknown, patterns of evolutionary diversification, within perhaps the most widely distributed heterotrophic marine bacterial clade, and strongly links to ecosystem regimes.

Ventromedial Frontal Cortex Is Critical for Guiding Attention to Reward-Predictive Visual Features in Humans.

PubMed

Vaidya, Avinash R; Fellows, Lesley K

2015-09-16

Adaptively interacting with our environment requires extracting information that will allow us to successfully predict reward. This can be a challenge, particularly when there are many candidate cues, and when rewards are probabilistic. Recent work has demonstrated that visual attention is allocated to stimulus features that have been associated with reward on previous trials. The ventromedial frontal lobe (VMF) has been implicated in learning in dynamic environments of this kind, but the mechanism by which this region influences this process is not clear. Here, we hypothesized that the VMF plays a critical role in guiding attention to reward-predictive stimulus features based on feedback. We tested the effects of VMF damage in human subjects on a visual search task in which subjects were primed to attend to task-irrelevant colors associated with different levels of reward, incidental to the search task. Consistent with previous work, we found that distractors had a greater influence on reaction time when they appeared in colors associated with high reward in the previous trial compared with colors associated with low reward in healthy control subjects and patients with prefrontal damage sparing the VMF. However, this reward modulation of attentional priming was absent in patients with VMF damage. Thus, an intact VMF is necessary for directing attention based on experience with cue-reward associations. We suggest that this region plays a role in selecting reward-predictive cues to facilitate future learning. There has been a swell of interest recently in the ventromedial frontal cortex (VMF), a brain region critical to associative learning. However, the underlying mechanism by which this region guides learning is not well understood. Here, we tested the effects of damage to this region in humans on a task in which rewards were linked incidentally to visual features, resulting in trial-by-trial attentional priming. Controls and subjects with prefrontal damage sparing the VMF showed normal reward priming, but VMF-damaged patients did not. This work sheds light on a potential mechanism through which this region influences behavior. We suggest that the VMF is necessary for directing attention to reward-predictive visual features based on feedback, facilitating future learning and decision-making. Copyright © 2015 the authors 0270-6474/15/3512813-11$15.00/0.

The Evolutionary Tempo of Sex Chromosome Degradation in Carica papaya.

PubMed

Wu, Meng; Moore, Richard C

2015-06-01

Genes on non-recombining heterogametic sex chromosomes may degrade over time through the irreversible accumulation of deleterious mutations. In papaya, the non-recombining male-specific region of the Y (MSY) consists of two evolutionary strata corresponding to chromosomal inversions occurring approximately 7.0 and 1.9 MYA. The step-wise recombination suppression between the papaya X and Y allows for a temporal examination of the degeneration progress of the young Y chromosome. Comparative evolutionary analyses of 55 X/Y gene pairs showed that Y-linked genes have more unfavorable substitutions than X-linked genes. However, this asymmetric evolutionary pattern is confined to the oldest stratum, and is only observed when recently evolved pseudogenes are included in the analysis, indicating a slow degeneration tempo of the papaya Y chromosome. Population genetic analyses of coding sequence variation of six Y-linked focal loci in the oldest evolutionary stratum detected an excess of nonsynonymous polymorphism and reduced codon bias relative to autosomal loci. However, this pattern was also observed for corresponding X-linked loci. Both the MSY and its corresponding X-specific region are pericentromeric where recombination has been shown to be greatly reduced. Like the MSY region, overall selective efficacy on the X-specific region may be reduced due to the interference of selective forces between highly linked loci, or the Hill-Robertson effect, that is accentuated in regions of low or suppressed recombination. Thus, a pattern of gene decay on the X-specific region may be explained by relaxed purifying selection and widespread genetic hitchhiking due to its pericentromeric location.

The Developmental Course of Illicit Substance Use from Age 12 to 22: Links with Depressive, Anxiety, and Behavior Disorders at Age 18

ERIC Educational Resources Information Center

Lansford, Jennifer E.; Erath, Stephen; Yu, Tianyi; Pettit, Gregory S.; Dodge, Kenneth A.; Bates, John E.

2008-01-01

Background: Previous theory and research suggest links between substance use and externalizing behavior problems, but links between substance use and internalizing problems are less clear. The present study sought to understand concurrent links among diagnoses of substance use disorders, internalizing disorders, and behavior disorders at age 18 as…

Outcome dependency alters the neural substrates of impression formation

PubMed Central

Ames, Daniel L.; Fiske, Susan T.

2015-01-01

How do people maintain consistent impressions of other people when other people are often inconsistent? The present research addresses this question by combining recent neuroscientific insights with ecologically meaningful behavioral methods. Participants formed impressions of real people whom they met in a personally involving situation. fMRI and supporting behavioral data revealed that outcome dependency (i.e., depending on another person for a desired outcome) alters previously identified neural dynamics of impression formation. Consistent with past research, a functional localizer identified a region of dorsomedial PFC previously linked to social impression formation. In the main task, this ROI revealed the predicted patterns of activity across outcome dependency conditions: greater BOLD response when information confirmed (vs. violated) social expectations if participants were outcome-independent and the reverse pattern if participants were outcome-dependent. We suggest that, although social perceivers often discount expectancy-disconfirming information as noise, being dependent on another person for a desired outcome focuses impression-formation processing on the most diagnostic information, rather than on the most tractable information. PMID:23850465

Detection, breakpoint identification and detailed characterisation of a CNV at the FRA16D site using SNP assays.

PubMed

Winchester, L; Newbury, D F; Monaco, A P; Ragoussis, J

2008-01-01

Copy Number Variants (CNV) and other submicroscopic structural changes are now recognised to be widespread across the human genome. We show that SNP data generated for association study can be utilised for the identification of deletion CNVs. During analysis of data for an SNP association study for Specific Language Impairment (SLI) a deletion was identified. SLI adversely affects the language development of children in the absence of any obvious cause. Previous studies have found linkage to a region on chromosome 16. The deletion was located in a known fragile site FRA16D in intron 5-6 of the WWOX gene (also known as FOR). Changes in the FRA16D site have been previously linked to cancer and are often characterised in cell lines. A long-range PCR assay was used to confirm the existence of the deletion. We also show the breakpoint identification and large-scale characterisation of this CNV in a normal human sample set. Copyright 2009 S. Karger AG, Basel.

The 2017 North Korea M6 seismic sequence: moment tensor, source time function, and aftershocks

NASA Astrophysics Data System (ADS)

Ni, S.; Zhan, Z.; Chu, R.; He, X.

2017-12-01

On September 3rd, 2017, an M6 seismic event occurred in North Korea, with location near previous nuclear test sites. The event features strong P waves and short period Rayleigh waves are observed in contrast to weak S waves, suggesting mostly explosion mechanism. We performed joint inversion for moment tensor and depth with both local and teleseismic waveforms, and find that the event is shallow with mostly isotropic yet substantial non-isotropic components. Deconvolution of seismic waveforms of this event with respect to previous nuclear test events shows clues of complexity in source time function. The event is followed by smaller earthquakes, as early as 8.5 minutes and lasted at least to October. The later events occurred in a compact region, and show clear S waves, suggesting double couple focal mechanism. Via analyzing Rayleigh wave spectrum, these smaller events are found to be shallow. Relative locations, difference in waveforms of the events are used to infer their possible links and generation mechanism.

Availability of Communications for the NATO Air Command and Control System in the Central Region and 5ATAF

DTIC Science & Technology

1991-10-01

Ground LINKI LISA (Note 1) LISA Environment Data LINK 3 (also supporting mission (single multi- Unks LINK 6 management, ontrol, functional LINK 7 status...LINK 7 status reports, C2RM, message MBDL and sensors) catalogue) ATDL-1 ATDL-1 (Note 2) LINK 11B (Note 3) LINKI 1B ACCS Ground- LINK 4 (interim Air

Identification of mildew resistance in wild and cultivated Central Asian grape germplasm

PubMed Central

2013-01-01

Background Cultivated grapevines, Vitis vinifera subsp. sativa, evolved from their wild relative, V. vinifera subsp. sylvestris. They were domesticated in Central Asia in the absence of the powdery mildew fungus, Erysiphe necator, which is thought to have originated in North America. However, powdery mildew resistance has previously been discovered in two Central Asian cultivars and in Chinese Vitis species. Results A set of 380 unique genotypes were evaluated with data generated from 34 simple sequence repeat (SSR) markers. The set included 306 V. vinifera cultivars, 40 accessions of V. vinifera subsp. sylvestris, and 34 accessions of Vitis species from northern Pakistan, Afghanistan and China. Based on the presence of four SSR alleles previously identified as linked to the powdery mildew resistance locus, Ren1, 10 new mildew resistant genotypes were identified in the test set: eight were V. vinifera cultivars and two were V. vinifera subsp. sylvestris based on flower and seed morphology. Sequence comparison of a 620 bp region that includes the Ren1-linked allele (143 bp) of the co-segregating SSR marker SC8-0071-014, revealed that the ten newly identified genotypes have sequences that are essentially identical to the previously identified mildew resistant V. vinifera cultivars: ‘Kishmish vatkana’ and ‘Karadzhandal’. Kinship analysis determined that three of the newly identified powdery mildew resistant accessions had a relationship with ‘Kishmish vatkana’ and ‘Karadzhandal’, and that six were not related to any other accession in this study set. Clustering procedures assigned accessions into three groups: 1) Chinese species; 2) a mixed group of cultivated and wild V. vinifera; and 3) table grape cultivars, including nine of the powdery mildew resistant accessions. Gene flow was detected among the groups. Conclusions This study provides evidence that powdery mildew resistance is present in V. vinifera subsp. sylvestris, the dioecious wild progenitor of the cultivated grape. Four first-degree parent progeny relationships were discovered among the hermaphroditic powdery mildew resistant cultivars, supporting the existence of intentional grape breeding efforts. Although several Chinese grape species are resistant to powdery mildew, no direct genetic link to the resistance found in V. vinifera could be established. PMID:24093598

X-linked hypophosphatemia attributable to pseudoexons of the PHEX gene.

PubMed

Christie, P T; Harding, B; Nesbit, M A; Whyte, M P; Thakker, R V

2001-08-01

X-linked hypophosphatemia is commonly caused by mutations of the coding region of PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). However, such PHEX mutations are not detected in approximately one third of X-linked hypophosphatemia patients who may harbor defects in the noncoding or intronic regions. We have therefore investigated 11 unrelated X-linked hypophosphatemia patients in whom coding region mutations had been excluded, for intronic mutations that may lead to mRNA splicing abnormalities, by the use of lymphoblastoid RNA and RT-PCRs. One X-linked hypophosphatemia patient was found to have 3 abnormally large transcripts, resulting from 51-bp, 100-bp, and 170-bp insertions, all of which would lead to missense peptides and premature termination codons. The origin of these transcripts was a mutation (g to t) at position +1268 of intron 7, which resulted in the occurrence of a high quality novel donor splice site (ggaagg to gtaagg). Splicing between this novel donor splice site and 3 preexisting, but normally silent, acceptor splice sites within intron 7 resulted in the occurrences of the 3 pseudoexons. This represents the first report of PHEX pseudoexons and reveals further the diversity of genetic abnormalities causing X-linked hypophosphatemia.

Linking results of key and supplementary comparisons of AC/DC voltage transfer references

NASA Astrophysics Data System (ADS)

Velychko, Oleh

2018-04-01

A regional key comparison (KC) COOMET.EM-K6.a and a supplementary comparison (SC) COOMET.EM-S1 of AC/DC voltage transfer references were conducted between participating laboratories from the Eurasian region. Measurements were made over the period 2004-2014. The results showed good agreement between all but one of the participating laboratories. The proposed procedure of linking results of key and SCs of regional metrology organization of AC/DC voltage transfer references is presented. Linking results is realized for COOMET.EM-K6.a and CCEM-K6.a KCs, and for COOMET.EM-K6.a KC and COOMET.EM-S1 SC.

The candidate histocompatibility locus of a Basal chordate encodes two highly polymorphic proteins.

PubMed

Nydam, Marie L; Netuschil, Nikolai; Sanders, Erin; Langenbacher, Adam; Lewis, Daniel D; Taketa, Daryl A; Marimuthu, Arumugapradeep; Gracey, Andrew Y; De Tomaso, Anthony W

2013-01-01

The basal chordate Botryllus schlosseri undergoes a natural transplantation reaction governed by a single, highly polymorphic locus called the fuhc. Our initial characterization of this locus suggested it encoded a single gene alternatively spliced into two transcripts: a 555 amino acid-secreted form containing the first half of the gene, and a full-length, 1008 amino acid transmembrane form, with polymorphisms throughout the ectodomain determining outcome. We have now found that the locus encodes two highly polymorphic genes which are separated by a 227 bp intergenic region: first, the secreted form as previously described, and a second gene encoding a 531 amino acid membrane-bound gene containing three extracellular immunoglobulin domains. While northern blotting revealed only these two mRNAs, both PCR and mRNA-seq detect a single capped and polyadenylated transcript that encodes processed forms of both genes linked by the intergenic region, as well as other transcripts in which exons of the two genes are spliced together. These results might suggest that the two genes are expressed as an operon, during which both genes are co-transcribed and then trans-spliced into two separate messages. This type of transcriptional regulation has been described in tunicates previously; however, the membrane-bound gene does not encode a typical Splice Leader (SL) sequence at the 5' terminus that usually accompanies trans-splicing. Thus, the presence of stable transcripts encoding both genes may suggest a novel mechanism of regulation, or conversely may be rare but stable transcripts in which the two mRNAs are linked due to a small amount of read-through by RNA polymerase. Both genes are highly polymorphic and co-expressed on tissues involved in histocompatibility. In addition, polymorphisms on both genes correlate with outcome, although we have found a case in which it appears that the secreted form may be major allorecognition determinant.

Unexpected Heterodivalent Recruitment of NOS1AP to nNOS Reveals Multiple Sites for Pharmacological Intervention in Neuronal Disease Models.

PubMed

Li, Li-Li; Melero-Fernandez de Mera, Raquel M; Chen, Jia; Ba, Wei; Kasri, Nael Nadif; Zhang, Mingjie; Courtney, Michael J

2015-05-13

The protein NOS1AP/CAPON mediates signaling from a protein complex of NMDA receptor, PSD95 and nNOS. The only stroke trial for neuroprotectants that showed benefit to patients targeted this ternary complex. NOS1AP/nNOS interaction regulates small GTPases, iron transport, p38MAPK-linked excitotoxicity, and anxiety. Moreover, the nos1ap gene is linked to disorders from schizophrenia, post-traumatic stress disorder, and autism to cardiovascular disorders and breast cancer. Understanding protein interactions required for NOS1AP function, therefore, has broad implications for numerous diseases. Here we show that the interaction of NOS1AP with nNOS differs radically from the classical PDZ docking assumed to be responsible. The NOS1AP PDZ motif does not bind nNOS as measured by multiple methods. In contrast, full-length NOS1AP forms an unusually stable interaction with nNOS. We mapped the discrepancy between full-length and C-terminal PDZ motif to a novel internal region we call the ExF motif. The C-terminal PDZ motif, although neither sufficient nor necessary for binding, nevertheless promotes the stability of the complex. It therefore potentially affects signal transduction and suggests that functional interaction of nNOS with NOS1AP might be targetable at two distinct sites. We demonstrate that excitotoxic pathways can be regulated, in cortical neuron and organotypic hippocampal slice cultures from rat, either by the previously described PDZ ligand TAT-GESV or by the ExF motif-bearing region of NOS1AP, even when lacking the critical PDZ residues as long as the ExF motif is intact and not mutated. This previously unrecognized heterodivalent interaction of nNOS with NOS1AP may therefore provide distinct opportunities for pharmacological intervention in NOS1AP-dependent signaling and excitotoxicity. Copyright © 2015 the authors 0270-6474/15/357349-16$15.00/0.

Discovery and introgression of the wild sunflower-derived novel downy mildew resistance gene Pl 19 in confection sunflower (Helianthus annuus L.).

PubMed

Zhang, Z W; Ma, G J; Zhao, J; Markell, S G; Qi, L L

2017-01-01

A new downy mildew resistance gene, Pl 19 , was identified from wild Helianthus annuus accession PI 435414, introduced to confection sunflower, and genetically mapped to linkage group 4 of the sunflower genome. Wild Helianthus annuus accession PI 435414 exhibited resistance to downy mildew, which is one of the most destructive diseases to sunflower production globally. Evaluation of the 140 BC 1 F 2:3 families derived from the cross of CMS CONFSCLB1 and PI 435414 against Plasmopara halstedii race 734 revealed that a single dominant gene controls downy mildew resistance in the population. Bulked segregant analysis conducted in the BC 1 F 2 population with 860 simple sequence repeat (SSR) markers indicated that the resistance derived from wild H. annuus was associated with SSR markers located on linkage group (LG) 4 of the sunflower genome. To map and tag this resistance locus, designated Pl 19 , 140 BC 1 F 2 individuals were used to construct a linkage map of the gene region. Two SSR markers, ORS963 and HT298, were linked to Pl 19 within a distance of 4.7 cM. After screening 27 additional single nucleotide polymorphism (SNP) markers previously mapped to this region, two flanking SNP markers, NSA_003564 and NSA_006089, were identified as surrounding the Pl 19 gene at a distance of 0.6 cM from each side. Genetic analysis indicated that Pl 19 is different from Pl 17 , which had previously been mapped to LG4, but is closely linked to Pl 17 . This new gene is highly effective against the most predominant and virulent races of P. halstedii currently identified in North America and is the first downy mildew resistance gene that has been transferred to confection sunflower. The selected resistant germplasm derived from homozygous BC 2 F 3 progeny provides a novel gene for use in confection sunflower breeding programs.

Regional and Local Glacial-Earthquake Patterns in Greenland

NASA Astrophysics Data System (ADS)

Olsen, K.; Nettles, M.

2016-12-01

Icebergs calved from marine-terminating glaciers currently account for up to half of the 400 Gt of ice lost annually from the Greenland ice sheet (Enderlin et al., 2014). When large capsizing icebergs ( 1 Gt of ice) calve, they produce elastic waves that propagate through the solid earth and are observed as teleseismically detectable MSW 5 glacial earthquakes (e.g., Ekström et al., 2003; Nettles & Ekström, 2010 Tsai & Ekström, 2007; Veitch & Nettles, 2012). The annual number of these events has increased dramatically over the past two decades. We analyze glacial earthquakes from 2011-2013, which expands the glacial-earthquake catalog by 50%. The number of glacial-earthquake solutions now available allows us to investigate regional patterns across Greenland and link earthquake characteristics to changes in ice dynamics at individual glaciers. During the years of our study Greenland's west coast dominated glacial-earthquake production. Kong Oscar Glacier, Upernavik Isstrøm, and Jakobshavn Isbræ all produced more glacial earthquakes during this time than in preceding years. We link patterns in glacial-earthquake production and cessation to the presence or absence of floating ice tongues at glaciers on both coasts of Greenland. The calving model predicts glacial-earthquake force azimuths oriented perpendicular to the calving front, and comparisons between seismic data and satellite imagery confirm this in most instances. At two glaciers we document force azimuths that have recently changed orientation and confirm that similar changes have occurred in the calving-front geometry. We also document glacial earthquakes at one previously quiescent glacier. Consistent with previous work, we model the glacial-earthquake force-time function as a boxcar with horizontal and vertical force components that vary synchronously. We investigate limitations of this approach and explore improvements that could lead to a more accurate representation of the glacial earthquake source.

Characterization and mapping of leaf rust resistance in four durum wheat cultivars.

PubMed

Kthiri, Dhouha; Loladze, Alexander; MacLachlan, P R; N'Diaye, Amidou; Walkowiak, Sean; Nilsen, Kirby; Dreisigacker, Susanne; Ammar, Karim; Pozniak, Curtis J

2018-01-01

Widening the genetic basis of leaf rust resistance is a primary objective of the global durum wheat breeding effort at the International Wheat and Maize Improvement Center (CIMMYT). Breeding programs in North America are following suit, especially after the emergence of new races of Puccinia triticina such as BBG/BP and BBBQD in Mexico and the United States, respectively. This study was conducted to characterize and map previously undescribed genes for leaf rust resistance in durum wheat and to develop reliable molecular markers for marker-assisted breeding. Four recombinant inbred line (RIL) mapping populations derived from the resistance sources Amria, Byblos, Geromtel_3 and Tunsyr_2, which were crossed to the susceptible line ATRED #2, were evaluated for their reaction to the Mexican race BBG/BP of P. triticina. Genetic analyses of host reactions indicated that leaf rust resistance in these genotypes was based on major seedling resistance genes. Allelism tests among resistant parents supported that Amria and Byblos carried allelic or closely linked genes. The resistance in Geromtel_3 and Tunsyr_2 also appeared to be allelic. Bulked segregant analysis using the Infinium iSelect 90K single nucleotide polymorphism (SNP) array identified two genomic regions for leaf rust resistance; one on chromosome 6BS for Geromtel_3 and Tunsyr_2 and the other on chromosome 7BL for Amria and Byblos. Polymorphic SNPs identified within these regions were converted to kompetitive allele-specific PCR (KASP) assays and used to genotype the RIL populations. KASP markers usw215 and usw218 were the closest to the resistance genes in Geromtel_3 and Tunsyr_2, while usw260 was closely linked to the resistance genes in Amria and Byblos. DNA sequences associated with these SNP markers were anchored to the wild emmer wheat (WEW) reference sequence, which identified several candidate resistance genes. The molecular markers reported herein will be useful to effectively pyramid these resistance genes with other previously marked genes into adapted, elite durum wheat genotypes.

Characterization and mapping of leaf rust resistance in four durum wheat cultivars

PubMed Central

Kthiri, Dhouha; Loladze, Alexander; MacLachlan, P. R.; N’Diaye, Amidou; Walkowiak, Sean; Nilsen, Kirby; Dreisigacker, Susanne; Ammar, Karim

2018-01-01

Widening the genetic basis of leaf rust resistance is a primary objective of the global durum wheat breeding effort at the International Wheat and Maize Improvement Center (CIMMYT). Breeding programs in North America are following suit, especially after the emergence of new races of Puccinia triticina such as BBG/BP and BBBQD in Mexico and the United States, respectively. This study was conducted to characterize and map previously undescribed genes for leaf rust resistance in durum wheat and to develop reliable molecular markers for marker-assisted breeding. Four recombinant inbred line (RIL) mapping populations derived from the resistance sources Amria, Byblos, Geromtel_3 and Tunsyr_2, which were crossed to the susceptible line ATRED #2, were evaluated for their reaction to the Mexican race BBG/BP of P. triticina. Genetic analyses of host reactions indicated that leaf rust resistance in these genotypes was based on major seedling resistance genes. Allelism tests among resistant parents supported that Amria and Byblos carried allelic or closely linked genes. The resistance in Geromtel_3 and Tunsyr_2 also appeared to be allelic. Bulked segregant analysis using the Infinium iSelect 90K single nucleotide polymorphism (SNP) array identified two genomic regions for leaf rust resistance; one on chromosome 6BS for Geromtel_3 and Tunsyr_2 and the other on chromosome 7BL for Amria and Byblos. Polymorphic SNPs identified within these regions were converted to kompetitive allele-specific PCR (KASP) assays and used to genotype the RIL populations. KASP markers usw215 and usw218 were the closest to the resistance genes in Geromtel_3 and Tunsyr_2, while usw260 was closely linked to the resistance genes in Amria and Byblos. DNA sequences associated with these SNP markers were anchored to the wild emmer wheat (WEW) reference sequence, which identified several candidate resistance genes. The molecular markers reported herein will be useful to effectively pyramid these resistance genes with other previously marked genes into adapted, elite durum wheat genotypes. PMID:29746580

Plant Sex Chromosomes.

PubMed

Charlesworth, Deborah

2016-04-29

Although individuals in most flowering plant species, and in many haploid plants, have both sex functions, dioecious species-in which individuals have either male or female functions only-are scattered across many taxonomic groups, and many species have genetic sex determination. Among these, some have visibly heteromorphic sex chromosomes, and molecular genetic studies are starting to uncover sex-linked markers in others, showing that they too have fully sex-linked regions that are either too small or are located in chromosomes that are too small to be cytologically detectable from lack of pairing, lack of visible crossovers, or accumulation of heterochromatin. Detailed study is revealing that, like animal sex chromosomes, plant sex-linked regions show evidence for accumulation of repetitive sequences and genetic degeneration. Estimating when recombination stopped confirms the view that many plants have young sex-linked regions, making plants of great interest for studying the timescale of these changes.

Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests.

PubMed

Tsai, Wen-Yang; Youn, Han Ha; Brites, Carlos; Tsai, Jih-Jin; Tyson, Jasmine; Pedroso, Celia; Drexler, Jan Felix; Stone, Mars; Simmons, Graham; Busch, Michael P; Lanteri, Marion; Stramer, Susan L; Balmaseda, Angel; Harris, Eva; Wang, Wei-Kung

2017-11-13

The explosive spread of Zika virus (ZIKV) and associated microcephaly present an urgent need for sensitive and specific serodiagnostic tests, particularly for pregnant women in dengue virus (DENV)-endemic regions. Recent reports of enhanced ZIKV replication by dengue-immune sera have raised concerns about the role of previous DENV infection on the risk and severity of microcephaly and other ZIKV complications. Enzyme-linked immunosorbent assays (ELISAs) based on ZIKV and DENV nonstructural protein 1 (NS1) were established to test acute, convalescent phase, and post-convalescent phase serum/plasma samples from reverse-transcription polymerase chain reaction-confirmed cases including 20 primary ZIKV, 25 ZIKV with previous DENV, 58 secondary DENV, and 16 primary DENV1 infections. ZIKV-NS1 immunoglobulin M (IgM) and immunoglobulin G (IgG) ELISAs combined can detect ZIKV infection with a sensitivity of 95% and specificity of 66.7%. The ZIKV-NS1 IgG cross-reactivity by samples from secondary DENV infection cases ranged from 66.7% to 28.1% (within 1 month to 1-2 years post-illness, respectively). Addition of DENV1-NS1 IgG ELISA can distinguish primary ZIKV infection; the ratio of absorbance of ZIKV-NS1 to DENV1-NS1 IgG ELISA can distinguish ZIKV with previous DENV and secondary DENV infections with a sensitivity of 87.5% and specificity of 81.3%. These findings were supported by analysis of sequential samples. An algorithm for ZIKV serodiagnosis based on 3 simple ELISAs is proposed to distinguish primary ZIKV, ZIKV with previous DENV, and secondary DENV infections; this could be applied to serodiagnosis for ZIKV, serosurveillance, and monitoring ZIKV infection during pregnancy to understand the epidemiology, pathogenesis, and complications of ZIKV in dengue-endemic regions. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Characterizations of 9p21 candidate genes in familial melanoma

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

Walker, G.J.; Flores, J.F.; Glendening, J.M.

We have previously collected and characterized 16 melanoma families for the inheritance of a familial melanoma predisposition gene on 9p21. Clear evidence for genetic linkage has been detected in 8 of these families with the 9p21 markers D9S126 and 1FNA, while linkage of the remaining families to this region is less certain. A candidate for the 9p21 familial melanoma gene, the cyclin kinase inhibitor gene p16 (also known as the multiple tumor suppressor 1 (MTS1) gene), has been recently indentified. Notably, a nonsense mutation within the p16 gene has been detected in the lymphoblastoid cell line DNA from a dysplasticmore » nevus syndrome (DNS), or familial melanoma, patient. The p16 gene is also known to be frequently deleted or mutated in a variety of tumor cell lines (including melanoma) and resides within a region that has been defined as harboring the 9p21 melanoma predisposition locus. This region is delineated on the distal side by the marker D9S736 (which resides just distal to the p16 gene) and extends in a proximal direction to the marker D9S171. Overall, the entire distance between these two loci is estimated at 3-5Mb. Preliminary analysis of our two largest 9p21-linked melanoma kindreds (by direct sequencing of PCR products) has not yet revealed mutations within the coding region of the p16 gene. Others have reported that 8/11 unrelated 9p21-linked melanoma families do not appear to carry p16 mutations; thus the possibility exists that p16 is not a melanoma susceptibility gene per se, although it appears to play some role in melanoma tumor progression. Our melanoma kindred DNAs are currently being analyzed by SSCP using primers that amplify exons of other candidate genes from the 9p21 region implicated in familial melanoma. These novel genes reside within a distinct critical region of homozygous loss in melanoma which is located >2 Mb from the p16 gene on 9p21.« less

Neuroimaging meta-analysis of cannabis use studies reveals convergent functional alterations in brain regions supporting cognitive control and reward processing.

PubMed

Yanes, Julio A; Riedel, Michael C; Ray, Kimberly L; Kirkland, Anna E; Bird, Ryan T; Boeving, Emily R; Reid, Meredith A; Gonzalez, Raul; Robinson, Jennifer L; Laird, Angela R; Sutherland, Matthew T

2018-03-01

Lagging behind rapid changes to state laws, societal views, and medical practice is the scientific investigation of cannabis's impact on the human brain. While several brain imaging studies have contributed important insight into neurobiological alterations linked with cannabis use, our understanding remains limited. Here, we sought to delineate those brain regions that consistently demonstrate functional alterations among cannabis users versus non-users across neuroimaging studies using the activation likelihood estimation meta-analysis framework. In ancillary analyses, we characterized task-related brain networks that co-activate with cannabis-affected regions using data archived in a large neuroimaging repository, and then determined which psychological processes may be disrupted via functional decoding techniques. When considering convergent alterations among users, decreased activation was observed in the anterior cingulate cortex, which co-activated with frontal, parietal, and limbic areas and was linked with cognitive control processes. Similarly, decreased activation was observed in the dorsolateral prefrontal cortex, which co-activated with frontal and occipital areas and linked with attention-related processes. Conversely, increased activation among users was observed in the striatum, which co-activated with frontal, parietal, and other limbic areas and linked with reward processing. These meta-analytic outcomes indicate that cannabis use is linked with differential, region-specific effects across the brain.

The Role of Neuronal Signaling in Controlling Cerebral Blood Flow

ERIC Educational Resources Information Center

Drake, Carrie T.; Iadecola, Costantino

2007-01-01

Well-regulated blood flow within the brain is vital to normal function. The brain's requirement for sufficient blood flow is ensured by a tight link between neural activity and blood flow. The link between regional synaptic activity and regional cerebral blood flow, termed functional hyperemia, is the basis for several modern imaging techniques…

DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states.

PubMed

White, Eric J; Emanuelsson, Olof; Scalzo, David; Royce, Thomas; Kosak, Steven; Oakeley, Edward J; Weissman, Sherman; Gerstein, Mark; Groudine, Mark; Snyder, Michael; Schübeler, Dirk

2004-12-21

Duplication of the genome during the S phase of the cell cycle does not occur simultaneously; rather, different sequences are replicated at different times. The replication timing of specific sequences can change during development; however, the determinants of this dynamic process are poorly understood. To gain insights into the contribution of developmental state, genomic sequence, and transcriptional activity to replication timing, we investigated the timing of DNA replication at high resolution along an entire human chromosome (chromosome 22) in two different cell types. The pattern of replication timing was correlated with respect to annotated genes, gene expression, novel transcribed regions of unknown function, sequence composition, and cytological features. We observed that chromosome 22 contains regions of early- and late-replicating domains of 100 kb to 2 Mb, many (but not all) of which are associated with previously described chromosomal bands. In both cell types, expressed sequences are replicated earlier than nontranscribed regions. However, several highly transcribed regions replicate late. Overall, the DNA replication-timing profiles of the two different cell types are remarkably similar, with only nine regions of difference observed. In one case, this difference reflects the differential expression of an annotated gene that resides in this region. Novel transcribed regions with low coding potential exhibit a strong propensity for early DNA replication. Although the cellular function of such transcripts is poorly understood, our results suggest that their activity is linked to the replication-timing program.

Development of a clinician reputation metric to identify appropriate problem-medication pairs in a crowdsourced knowledge base.

PubMed

McCoy, Allison B; Wright, Adam; Rogith, Deevakar; Fathiamini, Safa; Ottenbacher, Allison J; Sittig, Dean F

2014-04-01

Correlation of data within electronic health records is necessary for implementation of various clinical decision support functions, including patient summarization. A key type of correlation is linking medications to clinical problems; while some databases of problem-medication links are available, they are not robust and depend on problems and medications being encoded in particular terminologies. Crowdsourcing represents one approach to generating robust knowledge bases across a variety of terminologies, but more sophisticated approaches are necessary to improve accuracy and reduce manual data review requirements. We sought to develop and evaluate a clinician reputation metric to facilitate the identification of appropriate problem-medication pairs through crowdsourcing without requiring extensive manual review. We retrieved medications from our clinical data warehouse that had been prescribed and manually linked to one or more problems by clinicians during e-prescribing between June 1, 2010 and May 31, 2011. We identified measures likely to be associated with the percentage of accurate problem-medication links made by clinicians. Using logistic regression, we created a metric for identifying clinicians who had made greater than or equal to 95% appropriate links. We evaluated the accuracy of the approach by comparing links made by those physicians identified as having appropriate links to a previously manually validated subset of problem-medication pairs. Of 867 clinicians who asserted a total of 237,748 problem-medication links during the study period, 125 had a reputation metric that predicted the percentage of appropriate links greater than or equal to 95%. These clinicians asserted a total of 2464 linked problem-medication pairs (983 distinct pairs). Compared to a previously validated set of problem-medication pairs, the reputation metric achieved a specificity of 99.5% and marginally improved the sensitivity of previously described knowledge bases. A reputation metric may be a valuable measure for identifying high quality clinician-entered, crowdsourced data. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of a clinician reputation metric to identify appropriate problem-medication pairs in a crowdsourced knowledge base

PubMed Central

McCoy, Allison B.; Wright, Adam; Rogith, Deevakar; Fathiamini, Safa; Ottenbacher, Allison J.; Sittig, Dean F.

2014-01-01

Background Correlation of data within electronic health records is necessary for implementation of various clinical decision support functions, including patient summarization. A key type of correlation is linking medications to clinical problems; while some databases of problem-medication links are available, they are not robust and depend on problems and medications being encoded in particular terminologies. Crowdsourcing represents one approach to generating robust knowledge bases across a variety of terminologies, but more sophisticated approaches are necessary to improve accuracy and reduce manual data review requirements. Objective We sought to develop and evaluate a clinician reputation metric to facilitate the identification of appropriate problem-medication pairs through crowdsourcing without requiring extensive manual review. Approach We retrieved medications from our clinical data warehouse that had been prescribed and manually linked to one or more problems by clinicians during e-prescribing between June 1, 2010 and May 31, 2011. We identified measures likely to be associated with the percentage of accurate problem-medication links made by clinicians. Using logistic regression, we created a metric for identifying clinicians who had made greater than or equal to 95% appropriate links. We evaluated the accuracy of the approach by comparing links made by those physicians identified as having appropriate links to a previously manually validated subset of problem-medication pairs. Results Of 867 clinicians who asserted a total of 237,748 problem-medication links during the study period, 125 had a reputation metric that predicted the percentage of appropriate links greater than or equal to 95%. These clinicians asserted a total of 2464 linked problem-medication pairs (983 distinct pairs). Compared to a previously validated set of problem-medication pairs, the reputation metric achieved a specificity of 99.5% and marginally improved the sensitivity of previously described knowledge bases. Conclusion A reputation metric may be a valuable measure for identifying high quality clinician-entered, crowdsourced data. PMID:24321170

Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders.

PubMed

Miller, Frederick W; Cooper, Robert G; Vencovský, Jiří; Rider, Lisa G; Danko, Katalin; Wedderburn, Lucy R; Lundberg, Ingrid E; Pachman, Lauren M; Reed, Ann M; Ytterberg, Steven R; Padyukov, Leonid; Selva-O'Callaghan, Albert; Radstake, Timothy R D J; Isenberg, David A; Chinoy, Hector; Ollier, William E R; O'Hanlon, Terrance P; Peng, Bo; Lee, Annette; Lamb, Janine A; Chen, Wei; Amos, Christopher I; Gregersen, Peter K

2013-12-01

To identify new genetic associations with juvenile and adult dermatomyositis (DM). We performed a genome-wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1,178) and controls (n = 4,724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single-nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM. Compared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS-level significance (P < 5 × 10(-8)) at 80 genotyped SNPs. An analysis of 141 non-MHC SNPs previously associated with autoimmune diseases showed that 3 SNPs linked with 3 genes were associated with DM, with a false discovery rate (FDR) of <0.05. These genes were phospholipase C-like 1 (PLCL1; rs6738825, FDR = 0.00089), B lymphoid tyrosine kinase (BLK; rs2736340, FDR = 0.0031), and chemokine (C-C motif) ligand 21 (CCL21; rs951005, FDR = 0.0076). None of these genes was previously reported to be associated with DM. Our findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non-MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Precursory enhancement of EIA in the morning sector: Contribution from mid-latitude large earthquakes in the north-east Asian region

NASA Astrophysics Data System (ADS)

Ryu, Kwangsun; Oyama, Koh-Ichiro; Bankov, Ludmil; Chen, Chia-Hung; Devi, Minakshi; Liu, Huixin; Liu, Jann-Yenq

2016-01-01

To investigate whether the link between seismic activity and EIA (equatorial ionization anomaly) enhancement is valid for mid-latitude seismic activity, DEMETER observations around seven large earthquakes in the north-east Asian region were fully analyzed (M ⩾ 6.8). In addition, statistical analysis was performed for 35 large earthquakes (M ⩾ 6.0) that occurred during the DEMETER observation period. The results suggest that mid-latitude earthquakes do contribute to EIA enhancement, represented as normalized equatorial Ne , and that ionospheric change precedes seismic events, as has been reported in previous studies. According to statistical studies, the normalized equatorial density enhancement is sensitive and proportional to both the magnitude and the hypocenter depth of an earthquake. The mechanisms that can explain the contribution of mid-latitude seismic activity to EIA variation are briefly discussed based on current explanations of the geochemical and ionospheric processes involved in lithosphere-ionosphere interaction.

Comparative promoter analysis allows de novo identification of specialized cell junction-associated proteins.

PubMed

Cohen, Clemens D; Klingenhoff, Andreas; Boucherot, Anissa; Nitsche, Almut; Henger, Anna; Brunner, Bodo; Schmid, Holger; Merkle, Monika; Saleem, Moin A; Koller, Klaus-Peter; Werner, Thomas; Gröne, Hermann-Josef; Nelson, Peter J; Kretzler, Matthias

2006-04-11

Shared transcription factor binding sites that are conserved in distance and orientation help control the expression of gene products that act together in the same biological context. New bioinformatics approaches allow the rapid characterization of shared promoter structures and can be used to find novel interacting molecules. Here, these principles are demonstrated by using molecules linked to the unique functional unit of the glomerular slit diaphragm. An evolutionarily conserved promoter model was generated by comparative genomics in the proximal promoter regions of the slit diaphragm-associated molecule nephrin. Phylogenetic promoter fingerprints of known elements of the slit diaphragm complex identified the nephrin model in the promoter region of zonula occludens-1 (ZO-1). Genome-wide scans using this promoter model effectively predicted a previously unrecognized slit diaphragm molecule, cadherin-5. Nephrin, ZO-1, and cadherin-5 mRNA showed stringent coexpression across a diverse set of human glomerular diseases. Comparative promoter analysis can identify regulatory pathways at work in tissue homeostasis and disease processes.

BAPA Database: Linking landslide occurrence with rainfall in Asturias (Spain)

NASA Astrophysics Data System (ADS)

Valenzuela, Pablo; José Domínguez-Cuesta, María; Jiménez-Sánchez, Montserrat

2015-04-01

Asturias is a region in northern Spain with a temperate and humid climate. In this region, slope instability processes are very common and often cause economic losses and, sometimes, human victims. To prevent the geological risk involved, it is of great interest to predict landslide spatial and temporal occurrence. Some previous investigations have shown the importance of rainfall as a trigger factor. Despite the high incidence of these phenomena in Asturias, there are no databases of recent and actual landslides. The BAPA Project (Base de Datos de Argayos del Principado de Asturias - Principality of Asturias Landslide Database) aims to create an inventory of slope instabilities which have occurred between 1980 and 2015. The final goal is to study in detail the relationship between rainfall and slope instabilities in Asturias, establishing precipitation thresholds and soil moisture conditions necessary to instability triggering. This work presents the database progress showing its structure divided into various fields that essentially contain information related to spatial, temporal, geomorphological and damage data.

Combined copper/zinc attachment to prion protein

NASA Astrophysics Data System (ADS)

Hodak, Miroslav; Bernholc, Jerry

2013-03-01

Misfolding of prion protein (PrP) is responsible for diseases such as ``mad-cow disease'' in cattle and Creutzfeldt-Jacob in humans. Extensive experimental investigation has established that this protein strongly interacts with copper ions, and this ability has been linked to its still unknown function. Attachment of other metal ions (zinc, iron, manganese) have been demonstrated as well, but none of them could outcompete copper. Recent finding, however, indicates that at intermediate concentrations both copper and zinc ions can attach to the PrP at the octarepeat region, which contains high affinity metal binding sites. Based on this evidence, we have performed density functional theory simulations to investigate the combined Cu/Zn attachment. We consider all previously reported binding modes of copper at the octarepeat region and examine a possibility simultaneous Cu/Zn attachment. We find that this can indeed occur for only one of the known binding sites, when copper changes its coordination mode to allow for attachment of zinc ion. The implications of the simultaneous attachment on neural function remain to be explored.

Accommodation of structural rearrangements in the huntingtin-interacting protein 1 coiled-coil domain

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

Wilbur, Jeremy D., E-mail: jwilbur@msg.ucsf.edu; Hwang, Peter K.; Brodsky, Frances M.

2010-03-01

Variable packing interaction related to the conformational flexibility within the huntingtin-interacting protein 1 coiled coil domain. Huntingtin-interacting protein 1 (HIP1) is an important link between the actin cytoskeleton and clathrin-mediated endocytosis machinery. HIP1 has also been implicated in the pathogenesis of Huntington’s disease. The binding of HIP1 to actin is regulated through an interaction with clathrin light chain. Clathrin light chain binds to a flexible coiled-coil domain in HIP1 and induces a compact state that is refractory to actin binding. To understand the mechanism of this conformational regulation, a high-resolution crystal structure of a stable fragment from the HIP1 coiled-coilmore » domain was determined. The flexibility of the HIP1 coiled-coil region was evident from its variation from a previously determined structure of a similar region. A hydrogen-bond network and changes in coiled-coil monomer interaction suggest that the HIP1 coiled-coil domain is uniquely suited to allow conformational flexibility.« less

Introspective Minds: Using ALE Meta-Analyses to Study Commonalities in the Neural Correlates of Emotional Processing, Social & Unconstrained Cognition

PubMed Central

Schilbach, Leonhard; Bzdok, Danilo; Timmermans, Bert; Fox, Peter T.; Laird, Angela R.; Vogeley, Kai; Eickhoff, Simon B.

2012-01-01

Previous research suggests overlap between brain regions that show task-induced deactivations and those activated during the performance of social-cognitive tasks. Here, we present results of quantitative meta-analyses of neuroimaging studies, which confirm a statistical convergence in the neural correlates of social and resting state cognition. Based on the idea that both social and unconstrained cognition might be characterized by introspective processes, which are also thought to be highly relevant for emotional experiences, a third meta-analysis was performed investigating studies on emotional processing. By using conjunction analyses across all three sets of studies, we can demonstrate significant overlap of task-related signal change in dorso-medial prefrontal and medial parietal cortex, brain regions that have, indeed, recently been linked to introspective abilities. Our findings, therefore, provide evidence for the existence of a core neural network, which shows task-related signal change during socio-emotional tasks and during resting states. PMID:22319593

Discovery of a regioselectivity switch in nitrating P450s guided by molecular dynamics simulations and Markov models

NASA Astrophysics Data System (ADS)

Dodani, Sheel C.; Kiss, Gert; Cahn, Jackson K. B.; Su, Ye; Pande, Vijay S.; Arnold, Frances H.

2016-05-01

The dynamic motions of protein structural elements, particularly flexible loops, are intimately linked with diverse aspects of enzyme catalysis. Engineering of these loop regions can alter protein stability, substrate binding and even dramatically impact enzyme function. When these flexible regions are unresolvable structurally, computational reconstruction in combination with large-scale molecular dynamics simulations can be used to guide the engineering strategy. Here we present a collaborative approach that consists of both experiment and computation and led to the discovery of a single mutation in the F/G loop of the nitrating cytochrome P450 TxtE that simultaneously controls loop dynamics and completely shifts the enzyme's regioselectivity from the C4 to the C5 position of L-tryptophan. Furthermore, we find that this loop mutation is naturally present in a subset of homologous nitrating P450s and confirm that these uncharacterized enzymes exclusively produce 5-nitro-L-tryptophan, a previously unknown biosynthetic intermediate.

Tectonics and volcanism in central Mexico - A Landsat Thematic Mapper perspective

NASA Technical Reports Server (NTRS)

Johnson, C. A.; Harrison, C. G. A.

1989-01-01

Digitally enhanced Landsat Thematic Mapper (TM) images were used to map neotectonic deformation in central Mexico. This region has been studied for decades using a variety of geological and geophysical techniques, but synoptic mapping of neotectonic activity and major fault zones there, and an evaluation of their regional relationship to the character and location of volcanism were not previously possible until the application of synoptic, high resolution satellite imagery. Interpretation of the TM images shows that the tectonic deformation is closely linked in time and space to the dominantly calc-alkaline volcanics of the Mexican Volcanic Belt (MVB). The eruptive style and distribution of the volcanics is clearly related to the deformation resulting from relative motions of three large crustal blocks south of the MVB. Therefore, zones of weakness within the crust of central Mexico, which may be inherited from earlier episodes of deformation, are a principal factor controlling the oblique orientation of the MVB relative to the Acapulco Trench.

A complex dominance hierarchy is controlled by polymorphism of small RNAs and their targets.

PubMed

Yasuda, Shinsuke; Wada, Yuko; Kakizaki, Tomohiro; Tarutani, Yoshiaki; Miura-Uno, Eiko; Murase, Kohji; Fujii, Sota; Hioki, Tomoya; Shimoda, Taiki; Takada, Yoshinobu; Shiba, Hiroshi; Takasaki-Yasuda, Takeshi; Suzuki, Go; Watanabe, Masao; Takayama, Seiji

2016-12-22

In diploid organisms, phenotypic traits are often biased by effects known as Mendelian dominant-recessive interactions between inherited alleles. Phenotypic expression of SP11 alleles, which encodes the male determinants of self-incompatibility in Brassica rapa, is governed by a complex dominance hierarchy 1-3 . Here, we show that a single polymorphic 24 nucleotide small RNA, named SP11 methylation inducer 2 (Smi2), controls the linear dominance hierarchy of the four SP11 alleles (S 44 > S 60 > S 40 > S 29 ). In all dominant-recessive interactions, small RNA variants derived from the linked region of dominant SP11 alleles exhibited high sequence similarity to the promoter regions of recessive SP11 alleles and acted in trans to epigenetically silence their expression. Together with our previous study 4 , we propose a new model: sequence similarity between polymorphic small RNAs and their target regulates mono-allelic gene expression, which explains the entire five-phased linear dominance hierarchy of the SP11 phenotypic expression in Brassica.

Exploration of Functional Connectivity During Preferred Music Stimulation in Patients with Disorders of Consciousness

PubMed Central

Heine, Lizette; Castro, Maïté; Martial, Charlotte; Tillmann, Barbara; Laureys, Steven; Perrin, Fabien

2015-01-01

Preferred music is a highly emotional and salient stimulus, which has previously been shown to increase the probability of auditory cognitive event-related responses in patients with disorders of consciousness (DOC). To further investigate whether and how music modifies the functional connectivity of the brain in DOC, five patients were assessed with both a classical functional connectivity scan (control condition), and a scan while they were exposed to their preferred music (music condition). Seed-based functional connectivity (left or right primary auditory cortex), and mean network connectivity of three networks linked to conscious sound perception were assessed. The auditory network showed stronger functional connectivity with the left precentral gyrus and the left dorsolateral prefrontal cortex during music as compared to the control condition. Furthermore, functional connectivity of the external network was enhanced during the music condition in the temporo-parietal junction. Although caution should be taken due to small sample size, these results suggest that preferred music exposure might have effects on patients auditory network (implied in rhythm and music perception) and on cerebral regions linked to autobiographical memory. PMID:26617542

Phytoplankton growth balanced by clam and zooplankton grazing and net transport into the low-salinity zone of the San Francisco Estuary

USGS Publications Warehouse

Kimmerer, Wim J.; Thompson, Janet K.

2014-01-01

We estimated the influence of planktonic and benthic grazing on phytoplankton in the strongly tidal, river-dominated northern San Francisco Estuary using data from an intensive study of the low salinity foodweb in 2006–2008 supplemented with long-term monitoring data. A drop in chlorophyll concentration in 1987 had previously been linked to grazing by the introduced clam Potamocorbula amurensis, but numerous changes in the estuary may be linked to the continued low chlorophyll. We asked whether phytoplankton continued to be suppressed by grazing and what proportion of the grazing was by benthic bivalves. A mass balance of phytoplankton biomass included estimates of primary production and grazing by microzooplankton, mesozooplankton, and clams. Grazing persistently exceeded net phytoplankton growth especially for larger cells, and grazing by microzooplankton often exceeded that by clams. A subsidy of phytoplankton from other regions roughly balanced the excess of grazing over growth. Thus, the influence of bivalve grazing on phytoplankton biomass can be understood only in the context of limits on phytoplankton growth, total grazing, and transport.

Gene-based association study of genes linked to hippocampal sclerosis of aging neuropathology: GRN, TMEM106B, ABCC9, and KCNMB2

PubMed Central

Katsumata, Yuriko; Nelson, Peter T.; Ellingson, Sally R.; Fardo, David W.

2017-01-01

Hippocampal sclerosis of aging (HS-Aging) is a common neurodegenerative condition associated with dementia. To learn more about genetic risk of HS-Aging pathology, we tested gene-based associations of the GRN, TMEM106B, ABCC9, and KCNMB2 genes, which were reported to be associated with HS-Aging pathology in previous studies. Genetic data were obtained from the Alzheimer’s Disease Genetics Consortium (ADGC), linked to autopsy-derived neuropathological outcomes from the National Alzheimer’s Coordinating Center (NACC). Of the 3,251 subjects included in the study, 271 (8.3%) were identified as an HS-Aging case. The significant gene-based association between the ABCC9 gene and HS-Aging appeared to be driven by a region in which a significant haplotype-based association was found. We tested this haplotype as an expression Quantitative Trait Locus (eQTL) using two different public-access brain gene expression databases. The HS-Aging pathology protective ABCC9 haplotype was associated with decreased ABCC9 expression, indicating a possible toxic gain of function. PMID:28131462

Does degree of handedness in a group of right-handed individuals affect language comprehension?

PubMed

Newman, Sharlene; Malaia, Evie; Seo, Roy

2014-04-01

The impact of handedness on language processing has been studied extensively and the results indicate that there is a relationship between the two variables; however, the nature of the relationship is not at all clear. In the current study we explored degree of handedness (DH) opposed to direction in a group of right-handed individuals. fMRI was used to explore the impact of DH on the sentence comprehension network. The results revealed that during sentence comprehension activation in regions linked to semantic memory (e.g., anterior temporal cortex) were modulated by DH. Also, unexpectedly the precuneus/posterior cingulate gyrus which has been linked to episodic memory was also affected by DH. These results extend those reported previously by showing that the neural architecture that supports sentence comprehension is modulated by DH. More specifically, together the results presented here support the hypothesis proposed by Townsend, Carrithers, and Bever (2001) that DH interacts with the language system and impacts the strategy used during sentence comprehension. Copyright © 2014 Elsevier Inc. All rights reserved.

Preclinical Vaccine Study of Plasmodium vivax Circumsporozoite Protein Derived-Synthetic Polypeptides Formulated in Montanide ISA 720 and Montanide ISA 51 Adjuvants

PubMed Central

Arévalo-Herrera, Myriam; Vera, Omaira; Castellanos, Angélica; Céspedes, Nora; Soto, Liliana; Corradin, Giampietro; Herrera, Sócrates

2011-01-01

Plasmodium vivax circumsporozoite (CS) protein is a leading malaria vaccine candidate previously assessed in animals and humans. Here, combinations of three synthetic polypeptides corresponding to amino (N), central repeat (R), and carboxyl (C) regions of the CS protein formulated in Montanide ISA 720 or Montanide ISA 51 adjuvants were assessed for immunogenicity in rodents and primates. BALB/c mice and Aotus monkeys were divided into test and control groups and were immunized three times with doses of 50 and 100 μg of vaccine or placebo. Antigen-specific antimalarial antibodies were determined by enzyme-linked immunosorbent assay, immunofluorescent antibody test, and IFN-γ responses by enzyme-linked immunosorbent spot (ELIspot). Both vaccine formulations were highly immunogenic in both species. Mice developed better antibody responses against C and R polypeptides, whereas the N polypeptide was more immunogenic in monkeys. Anti-peptide antibodies remained detectable for several months and recognized native proteins on sporozoites. Differences between Montanide ISA 720 and Montanide ISA 51 formulations were not significant. PMID:21292874

Are transnational tobacco companies' market access strategies linked to economic development models? A case study of South Korea.

PubMed

Lee, Sungkyu; Holden, Chris; Lee, Kelley

2013-01-01

Transnational tobacco companies (TTCs) have used varied strategies to access previously closed markets. Using TTCs' efforts to enter the South Korean market from the late 1980s as a case study, this article asks whether there are common patterns in these strategies that relate to the broader economic development models adopted by targeted countries. An analytical review of the existing literature on TTCs' efforts to access emerging markets was conducted to develop hypotheses relating TTCs' strategies to countries' economic development models. A case study of Korea was then undertaken based on analysis of internal tobacco industry documents. Findings were consistent with the hypothesis that TTCs' strategies in Korea were linked to Korea's export-oriented economic development model and its hostile attitude towards foreign investment. A fuller understanding of TTCs' strategies for expansion globally can be derived by locating them within the economic development models of specific countries or regions. Of foremost importance is the need for governments to carefully balance economic and public health policies when considering liberalisation.

Looking beyond food aid to livelihoods, protection and partnerships: strategies for WFP in the Darfur states.

PubMed

Young, Helen

2007-03-01

The humanitarian crisis in Darfur remains extremely serious. The optimism that followed the signing of the Abuja Peace Accord was followed by a rapid deterioration in security on the ground in part associated with increasing factionalism in various rebel movements. This paper briefly reviews the evolution of the crisis, its impact on lives and livelihoods and the response by the World Food Programme (WFP) to June 2006. The major challenges and issues facing the food aid programme in the previous 18 months included: dealing with insecurity while maintaining or even extending programme outreach; the need to link protection with assistance more explicitly; and determining the wider impact of food aid programming on the processes and institutions linked with the conflict. The paper discusses the main strategic issues facing WFP in the future such as: integrating security and protection with needs assessments and operational decisions, broadening response strategies beyond food aid and bringing livelihoods to the fore, the need to review cost-efficiency, promoting partnerships and strengthening national and regional capacities.

Are transnational tobacco companies’ market access strategies linked to economic development models? A case study of South Korea

PubMed Central

Lee, Sungkyu; Holden, Chris; Lee, Kelley

2013-01-01

Transnational tobacco companies (TTCs) have used varied strategies to access previously closed markets. Using TTCs’ efforts to enter the South Korean market from the late 1980s as a case study, this article asks whether there are common patterns in these strategies that relate to the broader economic development models adopted by targeted countries. An analytical review of the existing literature on TTCs’ efforts to access emerging markets was conducted to develop hypotheses relating TTCs’ strategies to countries’ economic development models. A case study of Korea was then undertaken based on analysis of internal tobacco industry documents. Findings were consistent with the hypothesis that TTCs’ strategies in Korea were linked to Korea’s export-oriented economic development model and its hostile attitude toward foreign investment. A fuller understanding of TTCs’ strategies for expansion globally can be derived by locating them within the economic development models of specific countries or regions. Of foremost importance is the need for governments to carefully balance economic and public health policies when considering liberalisation. PMID:23327486

Association of trait emotional intelligence and individual fMRI-activation patterns during the perception of social signals from voice and face.

PubMed

Kreifelts, Benjamin; Ethofer, Thomas; Huberle, Elisabeth; Grodd, Wolfgang; Wildgruber, Dirk

2010-07-01

Multimodal integration of nonverbal social signals is essential for successful social interaction. Previous studies have implicated the posterior superior temporal sulcus (pSTS) in the perception of social signals such as nonverbal emotional signals as well as in social cognitive functions like mentalizing/theory of mind. In the present study, we evaluated the relationships between trait emotional intelligence (EI) and fMRI activation patterns in individual subjects during the multimodal perception of nonverbal emotional signals from voice and face. Trait EI was linked to hemodynamic responses in the right pSTS, an area which also exhibits a distinct sensitivity to human voices and faces. Within all other regions known to subserve the perceptual audiovisual integration of human social signals (i.e., amygdala, fusiform gyrus, thalamus), no such linked responses were observed. This functional difference in the network for the audiovisual perception of human social signals indicates a specific contribution of the pSTS as a possible interface between the perception of social information and social cognition. (c) 2009 Wiley-Liss, Inc.

SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington’s Disease Mice

PubMed Central

Tulino, Raffaella; Benjamin, Agnesska C.; Jolinon, Nelly; Smith, Donna L.; Chini, Eduardo N.; Carnemolla, Alisia; Bates, Gillian P.

2016-01-01

Huntington’s disease (HD) is a neurodegenerative disorder for which there are no disease-modifying treatments. SIRT1 is a NAD+-dependent protein deacetylase that is implicated in maintaining neuronal health during development, differentiation and ageing. Previous studies suggested that the modulation of SIRT1 activity is neuroprotective in HD mouse models, however, the mechanisms controlling SIRT1 activity are unknown. We have identified a striatum-specific phosphorylation-dependent regulatory mechanism of SIRT1 induction under normal physiological conditions, which is impaired in HD. We demonstrate that SIRT1 activity is down-regulated in the brains of two complementary HD mouse models, which correlated with altered SIRT1 phosphorylation levels. This SIRT1 impairment could not be rescued by the ablation of DBC1, a negative regulator of SIRT1, but was linked to changes in the sub-cellular distribution of AMPK-α1, a positive regulator of SIRT1 function. This work provides insights into the regulation of SIRT1 activity with the potential for the development of novel therapeutic strategies. PMID:26815359

[Autism and language: some molecular aspects].

PubMed

Benítez-Burraco, A

Autism is a cognitive disorder that includes among its distinguishing symptoms a deficit in the pragmatic component of language. Yet, it seems that there are certain subtypes where other deficiencies have been seen to affect the phonological, lexical, syntactical and morphological components of language. Linkage and association analyses aimed at identifying the genes that constitute causal or risk factors for the disorder have allowed researchers to identify certain loci that appear to be linked or associated to a statistically significant degree with autism endophenotypes of a linguistic nature. The target genes in this type of analysis play a number of different biological roles related with the development and functioning of the nervous system. On certain occasions, the loci thus identified coincide with others that had previously been linked to diverse language disorders (one paradigmatic case would be that of the chromosomal region 7q31 in relation to specific language disorder). This suggests that such disorders and autism might share a partially common genetic foundation that would account for the similarities observed between them at the phenotypic level.

Unbiased clustering estimation in the presence of missing observations

NASA Astrophysics Data System (ADS)

Bianchi, Davide; Percival, Will J.

2017-11-01

In order to be efficient, spectroscopic galaxy redshift surveys do not obtain redshifts for all galaxies in the population targeted. The missing galaxies are often clustered, commonly leading to a lower proportion of successful observations in dense regions. One example is the close-pair issue for SDSS spectroscopic galaxy surveys, which have a deficit of pairs of observed galaxies with angular separation closer than the hardware limit on placing neighbouring fibres. Spatially clustered missing observations will exist in the next generations of surveys. Various schemes have previously been suggested to mitigate these effects, but none works for all situations. We argue that the solution is to link the missing galaxies to those observed with statistically equivalent clustering properties, and that the best way to do this is to rerun the targeting algorithm, varying the angular position of the observations. Provided that every pair has a non-zero probability of being observed in one realization of the algorithm, then a pair-upweighting scheme linking targets to successful observations, can correct these issues. We present such a scheme, and demonstrate its validity using realizations of an idealized simple survey strategy.

How climate change threats water resource: the case of the Thau coastal lagoon (Mediterranean Sea, France)

NASA Astrophysics Data System (ADS)

La Jeunesse, Isabelle; Sellami, Haykel; Cirelli, Claudia

2014-05-01

The latest reports of the intergovernmental panel on climate change explained that the Mediterranean regions are especially vulnerable to the impacts of climate change. These latest are expected to have strong impacts on the management of water resources and on regional economies. The aim of this paper is to discuss impacts of climate changes on the Thau case study in relation to the evolution of water balance, water uses and adaptation to climate change. The Thau coastal lagoon is located in the Mediterranean coast in south of France in the Languedoc-Roussillon Region. Economic activities are diverse from shellfish farming, fertilizers industries to agriculture and tourism. However, tourism and shellfish farming are of major importance for local economy. If tourism is mainly turned to the Sea coast, shellfishes grow within the lagoon and rely on water quality. Previous studies have demonstrated the link between the coastal lagoon water quality and inputs of freshwater from the catchment. Thus, changes in rainfalls, runoff and water balance would not only affect water uses but also water quality. Climate changes projections are presented following the implementation of 4 downscaled climatic models. Impacts on water balance are modelled with SWAT (Soil Water Assessment Tool) for 2041-2070 compared to the 1971-2000 reference period. The decrease of precipitations and water balance will impact discharges and thus decrease the freshwater inputs to the coastal lagoon. A study of water uses conducted in interactions with stakeholders within the Thau area has permitted to assess both current and evolution of water uses. It has revealed local water resources are depleting while water demand is increasing and is planned to continue to increase in the really near future. To prevent water scarcity events, mainly due to the climate change context, the Regional authorities have connected the catchment to the Rhône river to import water. The conclusion of this study is while expected impacts of climate changes on the Thau system were expected to be linked to water balance depletion in the catchment, the main threats are now linked to the impact on water quality of the introduction of the Rhône river waters within the system. This study is conducted in the CLIMB EU-FP7 project (2010-2014).

Using in situ hybridization and PFGE Southern hybridization to detect translocation breakpoints in a BOR/TRPS patient cell line

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

Gu, J.Z.; Sapru, M.; Smith, D.

Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by ear malformations, cervical fistulae, hearing loss and renal abnormalities. We have integrated the Genethon YAC contig maps with additional markers in the chromosome 8q region genetically linked by a unique patient cell line. This cell line is from a patient who has both the branchio-oto-renal syndrome and tricho-rhino-phalangeal syndrome (TRPS). High resolution cytogenetics demonstrated a direct insertion of materials from 8q13.3q21.13 to 8q24.11. TRPS has been previously linked to deletions involving 8q24.11-q24.13. The rearrangement in this patient suggests that TRPS results from loss of gene function due to insertion atmore » the 8q24.11 breakpoint and the possible location for the BOR gene is at either of the two breakpoints of 8q13.3 and 8q21.13. We have constructed cosmid contigs in 8q24.11. In situ hybridization with cosmids mapped to these locations as probes has helped to narrow down the breakpoints. Combinations of cosmids on either side or overlapping the 8q24.11 breakpoint show split signals on one chromosome 8q arm due to insertion of the materials from the proximal region. Cosmids mapped to the TRPS deletion region have been used to hybridize to pulsed field gel genomic blots of DNA from the patient cell line and detected rearranged genomic fragments. Both in situ hybridization and genomic PFGE Southern blot will be used to precisely locate the breakpoints.« less

Xp11.22 deletions encompassing CENPVL1, CENPVL2, MAGED1 and GSPT2 as a cause of syndromic X-linked intellectual disability.

PubMed

Grau, Christina; Starkovich, Molly; Azamian, Mahshid S; Xia, Fan; Cheung, Sau Wai; Evans, Patricia; Henderson, Alex; Lalani, Seema R; Scott, Daryl A

2017-01-01

By searching a clinical database of over 60,000 individuals referred for array-based CNV analyses and online resources, we identified four males from three families with intellectual disability, developmental delay, hypotonia, joint hypermobility and relative macrocephaly who carried small, overlapping deletions of Xp11.22. The maximum region of overlap between their deletions spanned ~430 kb and included two pseudogenes, CENPVL1 and CENPVL2, whose functions are not known, and two protein coding genes-the G1 to S phase transition 2 gene (GSPT2) and the MAGE family member D1 gene (MAGED1). Deletions of this ~430 kb region have not been previously implicated in human disease. Duplications of GSPT2 have been documented in individuals with intellectual disability, but the phenotypic consequences of a loss of GSPT2 function have not been elucidated in humans or mouse models. Changes in MAGED1 have not been associated with intellectual disability in humans, but loss of MAGED1 function is associated with neurocognitive and neurobehavioral phenotypes in mice. In all cases, the Xp11.22 deletion was inherited from an unaffected mother. Studies performed on DNA from one of these mothers did not show evidence of skewed X-inactivation. These results suggest that deletions of an ~430 kb region on chromosome Xp11.22 that encompass CENPVL1, CENPVL2, GSPT2 and MAGED1 cause a distinct X-linked syndrome characterized by intellectual disability, developmental delay, hypotonia, joint hypermobility and relative macrocephaly. Loss of GSPT2 and/or MAGED1 function may contribute to the intellectual disability and developmental delay seen in males with these deletions.

Cospectral budget of turbulence explains the bulk properties of smooth pipe flow.

PubMed

Katul, Gabriel G; Manes, Costantino

2014-12-01

Connections between the wall-normal turbulent velocity spectrum E(ww)(k) at wave number k and the mean velocity profile (MVP) are explored in pressure-driven flows confined within smooth walls at moderate to high bulk Reynolds numbers (Re). These connections are derived via a cospectral budget for the longitudinal (u') and wall-normal (w') velocity fluctuations, which include a production term due to mean shear interacting with E(ww)(k), viscous effects, and a decorrelation between u' and w' by pressure-strain effects [=π(k)]. The π(k) is modeled using a conventional Rotta-like return-to-isotropy closure but adjusted to include the effects of isotropization of the production term. The resulting cospectral budget yields a generalization of a previously proposed "spectral link" between the MVP and the spectrum of turbulence. The proposed cospectral budget is also shown to reproduce the measured MVP across the pipe with changing Re including the MVP shapes in the buffer and wake regions. Because of the links between E(ww)(k) and the MVP, the effects of intermittency corrections to inertial subrange scales and the so-called spectral bottleneck reported as k approaches viscous dissipation eddy sizes (η) on the MVP shapes are investigated and shown to be of minor importance. Inclusion of a local Reynolds number correction to a parameter associated with the spectral exponential cutoff as kη→1 appears to be more significant to the MVP shape in the buffer region. While the bulk shape of the MVP is reasonably reproduced in all regions of the pipe, the solution to the cospectral budget systematically underestimates the negative curvature of the MVP within the buffer layer.

Atmospheric moisture transport: the bridge between ocean evaporation and Arctic ice melting

NASA Astrophysics Data System (ADS)

Gimeno, L.; Vázquez, M.; Nieto, R.; Trigo, R. M.

2015-09-01

Changes in the atmospheric moisture transport have been proposed as a vehicle for interpreting some of the most significant changes in the Arctic region. The increasing moisture over the Arctic during the last decades is not strongly associated with the evaporation that takes place within the Arctic area itself, despite the fact that the sea ice cover is decreasing. Such an increment is consistent and is more dependent on the transport of moisture from the extratropical regions to the Arctic that has increased in recent decades and is expected to increase within a warming climate. This increase could be due either to changes in circulation patterns which have altered the moisture sources, or to changes in the intensity of the moisture sources because of enhanced evaporation, or a combination of these two mechanisms. In this short communication we focus on the more objective assessment of the strong link between ocean evaporation trends and Arctic Sea ice melting. We will critically analyse several recent results suggesting links between moisture transport and the extent of sea ice in the Arctic, this being one of the most distinct indicators of continuous climate change both in the Arctic and on a global scale. To do this we will use a sophisticated Lagrangian approach to develop a more robust framework on some of these previous disconnecting results, using new information and insights. Results reached in this study stress the connection between two climate change indicators, namely an increase in evaporation over source regions (mainly the Mediterranean Sea, the North Atlantic Ocean and the North Pacific Ocean in the paths of the global western boundary currents and their extensions) and Arctic ice melting precursors.

Holocene tephrostratigraphy in high-latitude peatlands of the Southern Hemisphere: a link through time?

NASA Astrophysics Data System (ADS)

Roland, T. P.; Amesbury, M. J.; Charman, D.; De Vleeeschouwer, F.; Hodgson, D.; Hughes, P. D. M.; Mauquoy, D.; Piotrowska, N.; Royles, J.; van Bellen, S.; Vanneste, H.

2014-12-01

We present preliminary tephrostratigraphic data from south Patagonian peatlands and moss banks from the Antarctic Peninsula that provide greater chronological constraint to Holocene palaeoclimatic records and increase the potential for inter-regional correlation. Relative to the Northern Hemisphere, there is a paucity of high-resolution, robustly dated Holocene palaeoclimate records in the Southern Hemisphere, limiting our ability to validate climate models in this region and fully understand variation in the global climate system over time. In the absence of long-term instrumental data, multi-proxy (testate amoebae, plant macrofossils, δ13C, δ18O and δD) palaeoclimatic records from south Patagonian peatlands can provide valuable information about the long-term variability of the southern westerlies, a key component in determining the Southern Ocean's function as a sink or source of atmospheric carbon dioxide. Similarly, multi-proxy palaeoclimatic reconstructions from moss banks provide a unique terrestrial palaeoenvironmental archive from the Antarctic Peninsula, where records of past ecological change are rare and provide vital context for the recent, rapid biotic change recorded since the mid-20th century. Robust chronologies are imperative for the accurate examination of spatial and temporal patterns in Holocene climate variation. Previous work has confirmed the presence of discrete tephra horizons in south Patagonian peatlands and Antarctic Peninsula moss banks but the examination of distal, cryptotephras is currently underemployed as a geochronological tool. The chronological potential of these archives is considerable, given their high and largely continuous accumulation rates and suitability for 14C dating, presenting additional opportunities to refine the ages of major Holocene eruptions. Here, we present initial tephrostratigraphic results from both regions and explore the links between them.

Structural evolution of the Rio Grande rift: Synchronous exhumation of rift flanks from 20-10 Ma, embryonic core complexes, and fluid-enhanced Quaternary extension

NASA Astrophysics Data System (ADS)

Ricketts, Jason William

The Rio Grande rift in Colorado and New Mexico is one of the well-exposed and well-studied continental rifts in the world. Interest in the rift is driven not only by pure scientific intrigue, but also by a desire and a necessity to quantify earthquake hazards in New Mexico as well as to assess various water related issues throughout the state. These motivating topics have thus far led to the publication of two Geological Society of America Special Publication volumes in 1994 and 2013. This dissertation aims at building on the wealth of previous knowledge about the rift, and is composed of three separate chapters that focus on the structural evolution of the Rio Grande rift at several different time and spatial scales. At the largest scale, apatite (U-Th)/He thermochronologic data suggest synchronous extension along the entire length of the Rio Grande rift in Colorado and New Mexico from 20-10 Ma, which is important for understanding and evaluating possible driving mechanisms which are responsible for the rift. Previous tectonic and magmatic events in western North America were highly influential in the formation of the Rio Grande rift, and the new thermochronologic data suggest that its formation may have been closely linked to foundering and removal of the underlying Farallon Plate. A fundamental result of rift development at these scales is a concentration of strain is some regions of the rift. In these regions of maximum extension, fault networks display a geometry involving both high- and low-angle fault networks. These geometries are similar to the early stages in the development of metamorphic core complexes, and thus these regions in the rift link incipient extensional environments to highly extended terranes. At shorter time scales, heterogeneous strain accumulation may be governed in part by fluids in fault zones. As an example, along the western edge of the Albuquerque basin, travertine deposits are cut by extensional veins that record anomalously high strain rates during the Quaternary at this location. The fluids that precipitated the travertine and calcite in veins also contain a small component of deeply-derived fluids such that surface extension in this part of the rift is coupled with processes at deeper levels. Together, these studies suggest that removal of the Farallon slab beneath Colorado and New Mexico may have been a primary mechanism establishing extension in the Rio Grande rift, while continued extension is heterogeneous in time and space and provides an important link between surface processes and processes that operate at mid-crustal levels.

Representativeness of individual external doses estimated for one quarter of residents in the Fukushima Prefecture after the nuclear disaster: the Fukushima Health Management Survey.

PubMed

Ishikawa, Tetsuo; Takahashi, Hideto; Yasumura, Seiji; Ohtsuru, Akira; Sakai, Akira; Ohira, Tetsuya; Sakata, Ritsu; Ozasa, Kotaro; Akahane, Keiichi; Yonai, Shunsuke; Kurihara, Osamu; Kamiya, Kenji; Abe, Masafumi

2017-09-25

After the Fukushima Dai-ichi Nuclear Power Plant accident, the Fukushima Health Management Survey (FHMS) was launched. The Basic Survey, a component of FHMS, is a questionnaire used to survey residents across the Fukushima Prefecture about their behaviour in the first 4 months after the accident. The questionnaire findings are used to determine individual external doses by linking behaviour data to a computer programme with daily gamma ray dose rate maps, drawn after the accident. Through 30 June 2015, the response rate was only 27.2% (558 550 population), indicating that the findings might not be generalisable because of poor representativeness of the population. The objective of this study was to clarify if the data from the FHMS Basic Survey were representative of the entire population, by conducting a new survey to compare the external doses between non-respondents and respondents in the previous survey. A total of 5350 subjects were randomly selected from 7 local regions of Fukushima Prefecture. An interview survey was conducted with the non-respondents to the FHMS Basic Survey. A total of 990 responses were obtained from the previous non-responders by interview survey. For the regions Kempoku, Kenchu, Kennan, Aizu, Minami-Aizu, Soso, and Iwaki, differences in mean effective dose (95% confidence interval) in mSv between the non-responders and previous responders were 0.12 (0.01-0.23), -0.09 (-0.21-0.03), -0.06 (-0.18-0.07), 0.05 (-0.04-0.14), 0.01 (-0.01-0.02), 0.09 (0.01-0.17), 0.09 (0.00-0.17), respectively. The differences fall neither within the interval (-∞, -0.25) nor within the interval (0.25, ∞). These findings imply that mean effective doses between the previous and new respondents were not different, with a significantly indifferent region of 0.25 mSv according to equivalence tests. The present study indicates that the dose distribution obtained from about one-quarter of Fukushima residents represents the dose distribution for the entire Fukushima Prefecture.

Continuous EEG-fMRI in Pre-Surgical Evaluation of a Patient with Symptomatic Seizures: Bold Activation Linked to Interictal Epileptic Discharges Caused by Cavernoma.

PubMed

Avesani, M; Formaggio, E; Milanese, F; Baraldo, A; Gasparini, A; Cerini, R; Bongiovanni, L G; Pozzi Mucelli, R; Fiaschi, A; Manganotti, P

2008-04-07

We used continuous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) to identify the linkage between the "epileptogenic" and the "irritative" area in a patient with symptomatic epilepsy (cavernoma, previously diagnosed and surgically treated), i.e. a patient with a well known "epileptogenic area", and to increase the possibility of a non invasive pre-surgical evaluation of drug-resistant epilepsies. A compatible MRI system was used (EEG with 29 scalp electrodes and two electrodes for ECG and EMG) and signals were recorded with a 1.5 Tesla MRI scanner. After the recording session and MRI artifact removal, EEG data were analyzed offline and used as paradigms in fMRI study. Activation (EEG sequences with interictal slow-spiked-wave activity) and rest (sequences of normal EEG) conditions were compared to identify the potential resulting focal increase in BOLD signal and to consider if this is spatially linked to the interictal focus used as a paradigm and to the lesion. We noted an increase in the BOLD signal in the left neocortical temporal region, laterally and posteriorly to the poro-encephalic cavity (residual of cavernoma previously removed), that is around the "epileptogenic area". In our study "epileptogenic" and "irritative" areas were connected with each other. Combined EEG-fMRI may become routine in clinical practice for a better identification of an irritative and lesional focus in patients with symptomatic drug-resistant epilepsy.

Whole-genome sequencing of Atacama skeleton shows novel mutations linked with dysplasia

PubMed Central

Bhattacharya, Sanchita; Li, Jian; Sockell, Alexandra; Kan, Matthew J.; Bava, Felice A.; Chen, Shann-Ching; Ávila-Arcos, María C.; Ji, Xuhuai; Smith, Emery; Asadi, Narges B.; Lachman, Ralph S.; Lam, Hugo Y.K.; Bustamante, Carlos D.; Butte, Atul J.; Nolan, Garry P.

2018-01-01

Over a decade ago, the Atacama humanoid skeleton (Ata) was discovered in the Atacama region of Chile. The Ata specimen carried a strange phenotype—6-in stature, fewer than expected ribs, elongated cranium, and accelerated bone age—leading to speculation that this was a preserved nonhuman primate, human fetus harboring genetic mutations, or even an extraterrestrial. We previously reported that it was human by DNA analysis with an estimated bone age of about 6–8 yr at the time of demise. To determine the possible genetic drivers of the observed morphology, DNA from the specimen was subjected to whole-genome sequencing using the Illumina HiSeq platform with an average 11.5× coverage of 101-bp, paired-end reads. In total, 3,356,569 single nucleotide variations (SNVs) were found as compared to the human reference genome, 518,365 insertions and deletions (indels), and 1047 structural variations (SVs) were detected. Here, we present the detailed whole-genome analysis showing that Ata is a female of human origin, likely of Chilean descent, and its genome harbors mutations in genes (COL1A1, COL2A1, KMT2D, FLNB, ATR, TRIP11, PCNT) previously linked with diseases of small stature, rib anomalies, cranial malformations, premature joint fusion, and osteochondrodysplasia (also known as skeletal dysplasia). Together, these findings provide a molecular characterization of Ata's peculiar phenotype, which likely results from multiple known and novel putative gene mutations affecting bone development and ossification. PMID:29567674

Spatial-Operator Algebra For Flexible-Link Manipulators

NASA Technical Reports Server (NTRS)

Jain, Abhinandan; Rodriguez, Guillermo

1994-01-01

Method of computing dynamics of multiple-flexible-link robotic manipulators based on spatial-operator algebra, which originally applied to rigid-link manipulators. Aspects of spatial-operator-algebra approach described in several previous articles in NASA Tech Briefs-most recently "Robot Control Based on Spatial-Operator Algebra" (NPO-17918). In extension of spatial-operator algebra to manipulators with flexible links, each link represented by finite-element model: mass of flexible link apportioned among smaller, lumped-mass rigid bodies, coupling of motions expressed in terms of vibrational modes. This leads to operator expression for modal-mass matrix of link.

Examples of Linking Codes Within GeoFramework

NASA Astrophysics Data System (ADS)

Tan, E.; Choi, E.; Thoutireddy, P.; Aivazis, M.; Lavier, L.; Quenette, S.; Gurnis, M.

2003-12-01

Geological processes usually encompass a broad spectrum of length and time scales. Traditionally, a modeling code (solver) is written to solve a problem with specific length and time scales in mind. The utility of the solver beyond the designated purpose is usually limited. Furthermore, two distinct solvers, even if each can solve complementary parts of a new problem, are difficult to link together to solve the problem as a whole. For example, Lagrangian deformation model with visco-elastoplastic crust is used to study deformation near plate boundary. Ideally, the driving force of the deformation should be derived from underlying mantle convection, and it requires linking the Lagrangian deformation model with a Eulerian mantle convection model. As our understanding of geological processes evolves, the need of integrated modeling codes, which should reuse existing codes as much as possible, begins to surface. GeoFramework project addresses this need by developing a suite of reusable and re-combinable tools for the Earth science community. GeoFramework is based on and extends Pyre, a Python-based modeling framework, recently developed to link solid (Lagrangian) and fluid (Eulerian) models, as well as mesh generators, visualization packages, and databases, with one another for engineering applications. Under the framework, a solver is aware of the existence of other solvers and can interact with each other via exchanging information across adjacent boundary. A solver needs to conform a standard interface and provide its own implementation for exchanging boundary information. The framework also provides facilities to control the coordination between interacting solvers. We will show an example of linking two solvers within GeoFramework. CitcomS is a finite element code which solves for thermal convection within a 3D spherical shell. CitcomS can solve for problems either within a full spherical (global) domain or a restricted (regional) domain of a full sphere by using different meshers. We can embed a regional CitcomS solver within a global CitcomS solver. We not that linking instances of the same solver is conceptually equivalent to linking to different solvers. The global solver has a coarser grid and a longer stable time step than the regional solver. Therefore, a global-solver time step consists of several regional-solver time steps. The time-marching scheme is described below. First, the global solver is advanced one global-solver time step. Then, the regional solver is advanced for several regional-solver time steps until it catches up global solver. Within each regional-solver time step, the velocity field of the global solver is interpolated in time and then is imposed to the regional solver as boundary conditions. Finally, the temperature field of the regional solver is extrapolated in space and is fed back to the global. These two solvers are linked and synchronized by the time-marching scheme. An effort to embed a visco-elastoplastic representation of the crust within viscous mantle flow is underway.

Coexistence of minicircular and a highly rearranged mtDNA molecule suggests that recombination shapes mitochondrial genome organization.

PubMed

Mao, Meng; Austin, Andrew D; Johnson, Norman F; Dowton, Mark

2014-03-01

Recombination has been proposed as a possible mechanism to explain mitochondrial (mt) gene rearrangements, although the issue of whether mtDNA recombination occurs in animals has been controversial. In this study, we sequenced the entire mt genome of the megaspilid wasp Conostigmus sp., which possessed a highly rearranged mt genome. The sequence of the A+T-rich region contained a number of different types of repeats, similar to those reported previously in the nematode Meloidogyne javanica, in which recombination was discovered. In Conostigmus, we detected the end products of recombination: a range of minicircles. However, using isolated (cloned) fragments of the A+T-rich region, we established that some of these minicircles were found to be polymerase chain reaction (PCR) artifacts. It appears that regions with repeats are prone to PCR template switching or PCR jumping. Nevertheless, there is strong evidence that one minicircle is real, as amplification primers that straddle the putative breakpoint junction produce a single strong amplicon from genomic DNA but not from the cloned A+T-rich region. The results provide support for the direct link between recombination and mt gene rearrangement. Furthermore, we developed a model of recombination which is important for our understanding of mtDNA evolution.

Injury to the Premature Cerebellum: Outcome is Related to Remote Cortical Development

PubMed Central

Limperopoulos, Catherine; Chilingaryan, Gevorg; Sullivan, Nancy; Guizard, Nicolas; Robertson, Richard L.; du Plessis, Adré J.

2014-01-01

Cerebellar injury is an important complication of preterm birth with far-reaching neuropsychiatric sequelae. We have previously shown a significant association between isolated injury to the premature cerebellum and subsequent impairment of regional volumetric growth in the contralateral cerebrum. In the current study, we examine the relationship between these remote regional impairments of cerebral volumetric growth and domain-specific functional deficits in these children. In 40 ex-preterm infants with isolated cerebellar injury, we performed neurodevelopmental evaluations and quantitative magnetic resonance imaging (MRI) studies at a mean age of 34 months. We measured cortical gray matter volumes in 8 parcellated regions of each cerebral hemisphere, as well as right and left cerebellar volumes. We show highly significant associations between early signs of autism and dorsolateral prefrontal cortex volume (P < 0.001); gross motor scores and sensorimotor cortical volumes (P < 0.001); and cognitive and expressive language scores and premotor and mid-temporal cortical volumes (P < 0.001). By multivariate analyses, each unit increase in the corresponding regional cerebral volume was associated with lower odds of abnormal outcome score, adjusted for age at MRI and contralateral cerebellar volume. This is the first report linking secondary impairment of remote cerebral cortical growth and functional disabilities in survivors of prematurity-related cerebellar brain injury. PMID:23146968

Region-specific chromatin decondensation and micronucleus formation induced by 5-azacytidine in human TIG-7 cells.

PubMed

Satoh, T; Yamamoto, K; Miura, K F; Sofuni, T

2004-01-01

A human diploid lung fibroblast cell strain, TIG-7, has a heteromorphic chromosome 15 with an extra short arm carrying a homogeneously staining region (15p+hsr). We demonstrated previously that the 15p+hsr consists of an inactive and G+C-rich rDNA cluster characterized by fluorescence in situ hybridization (FISH) and various chromosome banding techniques. Thus, it was suggested that the region could contain highly methylated DNA. To observe methylation status on the target region directly under the microscope, we used a demethylating agent, 5-azacytidine (5-azaC), to induce decondensation of the chromatin containing methylated DNA. At 24 h after treatment with 0.5 microM 5-azaC, marked decondensation of the 15p+hsr was observed in almost all of the metaphases. Furthermore, we observed micronuclei, which were equivalent to the rDNA of the 15p+hsr demonstrated by FISH in the same preparation. In contrast, the DNA cross-linking agent mitomycin C (MMC) preferentially induced 15p+hsr-negative micronuclei. These findings indicated that chromatin decondensation and subsequent DNA strand breakage induced by the demethylating effect of 5-azaC led specifically to 15p+hsr-positive micronuclei. Copyright 2003 S. Karger AG, Basel

Analysis of the reptile CD1 genes: evolutionary implications.

PubMed

Yang, Zhi; Wang, Chunyan; Wang, Tao; Bai, Jianhui; Zhao, Yu; Liu, Xuhan; Ma, Qingwei; Wu, Xiaobing; Guo, Ying; Zhao, Yaofeng; Ren, Liming

2015-06-01

CD1, as the third family of antigen-presenting molecules, is previously only found in mammals and chickens, which suggests that the chicken and mammalian CD1 shared a common ancestral gene emerging at least 310 million years ago. Here, we describe CD1 genes in the green anole lizard and Crocodylia, demonstrating that CD1 is ubiquitous in mammals, birds, and reptiles. Although the reptilian CD1 protein structures are predicted to be similar to human CD1d and chicken CD1.1, CD1 isotypes are not found to be orthologous between mammals, birds, and reptiles according to phylogenetic analyses, suggesting an independent diversification of CD1 isotypes during the speciation of mammals, birds, and reptiles. In the green anole lizard, although the single CD1 locus and MHC I gene are located on the same chromosome, there is an approximately 10-Mb-long sequence in between, and interestingly, several genes flanking the CD1 locus belong to the MHC paralogous region on human chromosome 19. The CD1 genes in Crocodylia are located in two loci, respectively linked to the MHC region and MHC paralogous region (corresponding to the MHC paralogous region on chromosome 19). These results provide new insights for studying the origin and evolution of CD1.

Analysis of X chromosome genomic DNA sequence copy number variation associated with premature ovarian failure (POF)

PubMed Central

Quilter, C.R.; Karcanias, A.C.; Bagga, M.R.; Duncan, S.; Murray, A.; Conway, G.S.; Sargent, C.A.; Affara, N.A.

2013-01-01

BACKGROUND Premature ovarian failure (POF) is a heterogeneous disease defined as amenorrhoea for >6 months before age 40, with an FSH serum level >40 mIU/ml (menopausal levels). While there is a strong genetic association with POF, familial studies have also indicated that idiopathic POF may also be genetically linked. Conventional cytogenetic analyses have identified regions of the X chromosome that are strongly associated with ovarian function, as well as several POF candidate genes. Cryptic chromosome abnormalities that have been missed might be detected by array comparative genomic hybridization. METHODS In this study, samples from 42 idiopathic POF patients were subjected to a complete end-to-end X/Y chromosome tiling path array to achieve a detailed copy number variation (CNV) analysis of X chromosome involvement in POF. The arrays also contained a 1 Mb autosomal tiling path as a reference control. Quantitative PCR for selected genes contained within the CNVs was used to confirm the majority of the changes detected. The expression pattern of some of these genes in human tissue RNA was examined by reverse transcription (RT)–PCR. RESULTS A number of CNVs were identified on both Xp and Xq, with several being shared among the POF cases. Some CNVs fall within known polymorphic CNV regions, and others span previously identified POF candidate regions and genes. CONCLUSIONS The new data reported in this study reveal further discrete X chromosome intervals not previously associated with the disease and therefore implicate new clusters of candidate genes. Further studies will be required to elucidate their involvement in POF. PMID:20570974

Oncostatin M suppresses metastasis of lung adenocarcinoma by inhibiting SLUG expression through coordination of STATs and PIASs signalings.

PubMed

Pan, Chih-Ming; Wang, Mong-Lien; Chiou, Shih-Hwa; Chen, Hsiao-Yun; Wu, Cheng-Wen

2016-09-13

Oncostatin M (OSM) is linked with multiple biological responses including growth and differentiation. Previous reports showed inhibitory effects of OSM in tumor progression while others showed promoting effects. The dual role of OSM in the development of various cancers is still unclear. We previously described OSM-mediated SLUG suppression, leading to repressed metastasis of lung adenocarcinoma (LAC) cells. However, the underlying mechanism remains elusive. Here, we showed that OSM suppresses SLUG express in LAC cells through a STAT1-dependent transcriptional inhibition. Knockdown of STAT1 reversed the OSM-suppressed SLUG expression and rescued the OSM-mediated inhibition of cell proliferation, migration, and invasion in vitro, as well as pulmonary metastasis in vivo. STAT1 suppressed SLUG transcription through binding to its promoter region in response to OSM. Furthermore, PIAS4, a co-repressor of STAT, and HDAC1 were able to bind to STAT1 on SLUG promoter region, resulting in reduced H3K9 acetylation and suppressed SLUG expression upon OSM treatment. In contrast, PIAS3 bound to activated STAT3, another effector of OSM, in response to OSM and blocked the binding of STAT3 to SLUG promoter region, preventing STAT3-dependent activation of SLUG transcription. Our findings suggested that OSM suppresses SLUG expression and tumor metastasis of LAC through inducing the inhibitory effect of the STAT1-dependent pathway and suppressing the activating effect of STAT3-dependent signaling. These results can serve as a scientific basis for the potential therapeutic intervention of OSM in cancer cells.

Human Cytochrome P450 2E1 Mutations That Alter Mitochondrial Targeting Efficiency and Susceptibility to Ethanol-induced Toxicity in Cellular Models*

PubMed Central

Bansal, Seema; Anandatheerthavarada, Hindupur K.; Prabu, Govindaswamy K.; Milne, Ginger L.; Martin, Martha V.; Guengerich, F. Peter; Avadhani, Narayan G.

2013-01-01

Human polymorphisms in the 5′-upstream regulatory regions and also protein coding regions of cytochrome P450 2E1 (CYP2E1) are known to be associated with several diseases, including cancer and alcohol liver toxicity. In this study, we report novel mutations in the N-terminal protein targeting regions of CYP2E1 that markedly affect subcellular localization of the protein. Variant W23R/W30R protein (termed W23/30R) is preferentially targeted to mitochondria but very poorly to the endoplasmic reticulum, whereas the L32N protein is preferentially targeted to the endoplasmic reticulum and poorly to mitochondria. These results explain the physiological significance of bimodal CYP targeting to the endoplasmic reticulum and mitochondria previously described. COS-7 cells and HepG2 cells stably expressing W23/30R mutations showed markedly increased alcohol toxicity in terms of increased production of reactive oxygen species, respiratory dysfunction, and loss of cytochrome c oxidase subunits and activity. Stable cells expressing the L32N variant, on the other hand, were relatively less responsive to alcohol-induced toxicity and mitochondrial dysfunction. These results further support our previous data, based on mutational studies involving altered targeting, indicating that mitochondria-targeted CYP2E1 plays an important role in alcohol liver toxicity. The results also provide an interesting new link to genetic variations affecting subcellular distribution of CYP2E1 with alcohol-induced toxicity. PMID:23471973

The role of the Drosophila lateral horn in olfactory information processing and behavioral response.

PubMed

Schultzhaus, Janna N; Saleem, Sehresh; Iftikhar, Hina; Carney, Ginger E

2017-04-01

Animals must rapidly and accurately process environmental information to produce the correct behavioral responses. Reactions to previously encountered as well as to novel but biologically important stimuli are equally important, and one understudied region in the insect brain plays a role in processing both types of stimuli. The lateral horn is a higher order processing center that mainly processes olfactory information and is linked via olfactory projection neurons to another higher order learning center, the mushroom body. This review focuses on the lateral horn of Drosophila where most functional studies have been performed. We discuss connectivity between the primary olfactory center, the antennal lobe, and the lateral horn and mushroom body. We also present evidence for the lateral horn playing roles in innate behavioral responses by encoding biological valence to novel odor cues and in learned responses to previously encountered odors by modulating neural activity within the mushroom body. We describe how these processes contribute to acceptance or avoidance of appropriate or inappropriate mates and food, as well as the identification of predators. The lateral horn is a sexually dimorphic and plastic region of the brain that modulates other regions of the brain to ensure that insects produce rapid and effective behavioral responses to both novel and learned stimuli, yet multiple gaps exist in our knowledge of this important center. We anticipate that future studies on olfactory processing, learning, and innate behavioral responses will include the lateral horn in their examinations, leading to a more comprehensive understanding of olfactory information relay and resulting behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increased Risk of Death for Patients on the Waitlist for Liver Transplant Residing at Greater Distance From Specialized Liver Transplant Centers in the United States.

PubMed

Cicalese, Luca; Shirafkan, Ali; Jennings, Kristofer; Zorzi, Daria; Rastellini, Cristiana

2016-10-01

We have previously shown that patients listed for orthotopic liver transplantation (OLT) in United Network for Organ Sharing Region 4 (Texas and Oklahoma) have higher waitlist mortality rates when residing more than 30 miles from specialized liver transplant centers (LTC). Considering that findings might only be exclusive for this region with its peculiarities in terms of having the highest land surface extensions, lowest population densities, and largest rural populations. We investigated the entire OLT patient population in the United States to assess if our previous regional findings are nationally validated and if a rural, micropolitan, or metropolitan residence location affects outcome of waitlisted OLT patients in the nation. Patients waiting for OLT in the United States from 2002 to 2012 were stratified by distance from the patients' residence to LTC and by Rural Urban Commuting Area (RUCA) codes classification. Statistical analyses were performed to evaluate risk of mortality on the waitlist and the likelihood to receive an OLT using a Cox proportional hazards model and a generalized additive model with a logistic link. Survival time and probability of death while on the waitlist for OLT using distance to LTC showed significant increased risk with the distance (P = 0.001 and P < 0.0001, respectively). At the same time, using RUCA classification as the variable did not show significance (P = 0.14 and P = 0.73, respectively). Distance from an LTC is a risk factor of mortality on the waitlist for OLT, whereas RUCA classification is not a significant factor.

GOES West - Western Region WFO Satellite Imagery - Satellite Products and

Science.gov Websites

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A Simple Forecasting Model Linking Macroeconomic Policy to Industrial Employment Demand.

ERIC Educational Resources Information Center

Malley, James R.; Hady, Thomas F.

A study detailed further a model linking monetary and fiscal policy to industrial employment in metropolitan and nonmetropolitan areas of four United States regions. The model was used to simulate the impacts on area and regional employment of three events in the economy: changing real gross national product (GNP) via monetary policy, holding the…

Exclusion of RAI2 as the causative gene for Nance-Horan syndrome.

PubMed

Walpole, S M; Ronce, N; Grayson, C; Dessay, B; Yates, J R; Trump, D; Toutain, A

1999-05-01

Nance-Horan syndrome (NHS) is an X-linked condition characterised by congenital cataracts, microphthalmia and/or microcornea, unusual dental morphology, dysmorphic facial features, and developmental delay in some cases. Recent linkage studies have mapped the NHS disease gene to a 3.5-cM interval on Xp22.2 between DXS1053 and DXS443. We previously identified a human homologue of a mouse retinoic-acid-induced gene (RAI2) within the NHS critical flanking interval and have tested the gene as a candidate for Nance-Horan syndrome in nine NHS-affected families. Direct sequencing of the RAI2 gene and predicted promoter region has revealed no mutations in the families screened; RAI2 is therefore unlikely to be associated with NHS.

Meteorological interpretation of transient LOD changes

NASA Astrophysics Data System (ADS)

Masaki, Y.

2008-04-01

The Earth’s spin rate is mainly changed by zonal winds. For example, seasonal changes in global atmospheric circulation and episodic changes accompanied with El Nĩ os are clearly detected n in the Length-of-day (LOD). Sub-global to regional meteorological phenomena can also change the wind field, however, their effects on the LOD are uncertain because such LOD signals are expected to be subtle and transient. In our previous study (Masaki, 2006), we introduced atmospheric pressure gradients in the upper atmosphere in order to obtain a rough picture of the meteorological features that can change the LOD. In this presentation, we compare one-year LOD data with meteorological elements (winds, temperature, pressure, etc.) and make an attempt to link transient LOD changes with sub-global meteorological phenomena.

Differential regulation by ATP versus ADP further links CaMKII aggregation to ischemic conditions

PubMed Central

Vest, Rebekah S.; O’Leary, Heather; Bayer, K. Ulrich

2009-01-01

CaMKII, a major mediator of synaptic plasticity, forms extra-synaptic clusters under ischemic conditions. This study further supports self-aggregation of CaMKII holoenzymes as the underlying mechanism. Aggregation in vitro was promoted by mimicking ischemic conditions: low pH (6.8 or less), Ca2+ (and calmodulin), and low ATP and/or high ADP concentration. Mutational analysis showed that high ATP prevented aggregation by a mechanism involving T286 auto-phosphorylation, and indicated requirement for nucleotide binding but not auto-phosphorylation also for extra-synaptic clustering within neurons. These results clarify a previously apparent paradox in the nucleotide and phosphorylation requirement of aggregation, and support a mechanism that involves inter-holoenzyme T286-region/T-site interaction. PMID:19840793

The Aeronautical Data Link: Decision Framework for Architecture Analysis

NASA Technical Reports Server (NTRS)

Morris, A. Terry; Goode, Plesent W.

2003-01-01

A decision analytic approach that develops optimal data link architecture configuration and behavior to meet multiple conflicting objectives of concurrent and different airspace operations functions has previously been developed. The approach, premised on a formal taxonomic classification that correlates data link performance with operations requirements, information requirements, and implementing technologies, provides a coherent methodology for data link architectural analysis from top-down and bottom-up perspectives. This paper follows the previous research by providing more specific approaches for mapping and transitioning between the lower levels of the decision framework. The goal of the architectural analysis methodology is to assess the impact of specific architecture configurations and behaviors on the efficiency, capacity, and safety of operations. This necessarily involves understanding the various capabilities, system level performance issues and performance and interface concepts related to the conceptual purpose of the architecture and to the underlying data link technologies. Efficient and goal-directed data link architectural network configuration is conditioned on quantifying the risks and uncertainties associated with complex structural interface decisions. Deterministic and stochastic optimal design approaches will be discussed that maximize the effectiveness of architectural designs.

Using phylogenomics to understand the link between biogeographic origins and regional diversification in ratsnakes.

PubMed

Chen, Xin; Lemmon, Alan R; Lemmon, Emily Moriarty; Pyron, R Alexander; Burbrink, Frank T

2017-06-01

Globally distributed groups may show regionally distinct rates of diversification, where speciation is elevated given timing and sources of ecological opportunity. However, for most organisms, nearly complete sampling at genomic-data scales to reduce topological error in all regions is unattainable, thus hampering conclusions related to biogeographic origins and rates of diversification. We explore processes leading to the diversity of global ratsnakes and test several important hypotheses related to areas of origin and enhanced diversification upon colonizing new continents. We estimate species trees inferred from phylogenomic scale data (304 loci) while exploring several strategies that consider topological error from each individual gene tree. With a dated species tree, we examine taxonomy and test previous hypotheses that suggest the ratsnakes originated in the Old World (OW) and dispersed to New World (NW). Furthermore, we determine if dispersal to the NW represented a source of ecological opportunity, which should show elevated rates of species diversification. We show that ratsnakes originated in the OW during the mid-Oligocene and subsequently dispersed to the NW by the mid-Miocene; diversification was also elevated in a subclade of NW taxa. Finally, the optimal biogeographic region-dependent speciation model shows that the uptick in ratsnake diversification was associated with colonization of the NW. We consider several alternative explanations that account for regionally distinct diversification rates. Copyright © 2017 Elsevier Inc. All rights reserved.

[Utility of chromosome banding with ALU I enzyme for identifying methylated areas in breast cancer].

PubMed

Rojas-Atencio, Alicia; Yamarte, Leonard; Urdaneta, Karelis; Soto-Alvarez, Marisol; Alvarez Nava, Francisco; Cañizalez, Jenny; Quintero, Maribel; Atencio, Raquel; González, Richard

2012-12-01

Cancer is a group of disorders characterized by uncontrolled cell growth which is produced by two successive events: increased cell proliferation (tumor or neoplasia) and the invasive capacity of these cells (metastasis). DNA methylation is an epigenetic process which has been involved as an important pathogenic factor of cancer. DNA methylation participates in the regulation of gene expression, directly, by preventing the union of transcription factors, and indirectly, by promoting the "closed" structure of the chromatine. The objectives of this study were to identify hypermethyled chromosomal regions through the use of restriction Alu I endonuclease, and to relate cytogenetically these regions with tumor suppressive gene loci. Sixty peripheral blood samples of females with breast cancer were analyzed. Cell cultures were performed and cytogenetic spreads, previously digested with Alu I enzyme, were stained with Giemsa. Chromosomal centromeric and not centromeric regions were stained in 37% of cases. About 96% of stained hypermethyled chromosomal regions (1q, 2q, 6q) were linked with methylated genes associated with breast cancer. In addition, centromeric regions in chromosomes 3, 4, 8, 13, 14, 15 and 17, usually unstained, were found positive to digestion with Alu I enzime and Giemsa staining. We suggest the importance of this technique for the global visualization of the genome which can find methylated genes related to breast cancer, and thus lead to a specific therapy, and therefore a better therapeutic response.

A second locus for very-late-onset Alzheimer disease: a genome scan reveals linkage to 20p and epistasis between 20p and the amyloid precursor protein region.

PubMed

Olson, Jane M; Goddard, Katrina A B; Dudek, Doreen M

2002-07-01

We used a covariate-based linkage method to reanalyze genome scan data from affected sibships collected by the Alzheimer Disease (AD) Genetics Initiative of the National Institute of Mental Health. As reported in an earlier article, the amyloid-beta precursor protein (APP) region is strongly linked to affected sib pairs of the oldest current age (i.e., age either at last exam or at death) who lack E4 alleles at the apolipoprotein E (ApoE) locus. We now report that a region on 20p shows the same pattern. A model that includes current age and the number of E2 alleles as covariates gives a LOD score of 4.1. The signal on 20p is near the location of the gene coding for cystatin-C, previously shown to be associated with late-onset AD and to codeposit with APP in the brains of patients with AD. Two-locus analysis provides evidence of strong epistasis between 20p and the APP region, limited to the oldest age group and to those lacking ApoE4 alleles. We speculate that high-risk polymorphisms in both regions produce a biological interaction between these two proteins that increases susceptibility to a very-late-onset form of AD.

Meta-analysis of genome-wide scans for blood pressure in African American and Nigerian samples. The National Heart, Lung, and Blood Institute GeneLink Project.

PubMed

Rice, Treva; Cooper, Richard S; Wu, Xiaodong; Bouchard, Claude; Rankinen, Tuomo; Rao, D C; Jaquish, Cashell E; Fabsitz, Richard R; Province, Michael A

2006-03-01

In many genetic studies of complex traits, sample sizes are often too small to detect linkages of low-to-moderate effects. However, the combined linkage evidence across several studies can be synthesized using meta-analysis with the aim of providing more definitive support of linkage. In the current study using the National Heart, Lung, and Blood Institute (NHLBI) GeneLink Project, a meta-analysis based on a modification of Fisher's method of pooling P values was used to investigate linkage for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values across three studies involving African American and Nigerian families (HyperGEN, Health, Risk Factors, Exercise Training and Genetics [HERITAGE], and Genetics of Hypertension in Blacks). The meta results suggest two regions (2p and 7p) provide enhanced linkage evidence compared with the individual study results. The maximal meta Lod score of 2.9 on 2p14-p13.1 (64-78 cM) represented approximately 1-Lod unit increase over the respective individual study scores. This general region has been implicated previously involving primarily families of white ethnicity and provides confirmatory evidence that this QTL is common across ethnic groups. The second finding at 7p21.3-p15.3 (8-25 cM) provided a meta Lod of 3.5. Although region was implicated primarily in the Nigerian subjects the low-level but consistent support involving the African American families (individual Lod score of 1.0) suggests a novel QTL with respect to BP variation in individuals of black ethnicity. Follow-up studies involving positional cloning efforts of the combined families showing linkage evidence in these regions (particularly 2p) may be warranted to verify these findings and identify the genes and causative variants.

Sequestosome 1/p62 links familial ALS mutant SOD1 to LC3 via an ubiquitin-independent mechanism.

PubMed

Gal, Jozsef; Ström, Anna-Lena; Kwinter, David M; Kilty, Renée; Zhang, Jiayu; Shi, Ping; Fu, Weisi; Wooten, Marie W; Zhu, Haining

2009-11-01

The p62/sequestosome 1 protein has been identified as a component of pathological protein inclusions in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). P62 has also been implicated in autophagy, a process of mass degradation of intracellular proteins and organelles. Autophagy is a critical pathway for degrading misfolded and/or damaged proteins, including the copper-zinc superoxide dismutase (SOD1) mutants linked to familial ALS. We previously reported that p62 interacted with ALS mutants of SOD1 and that the ubiquitin-association domain of p62 was dispensable for the interaction. In this study, we identified two distinct regions of p62 that were essential to its binding to mutant SOD1: the N-terminal Phox and Bem1 (PB1) domain (residues 1-104) and a separate internal region (residues 178-224) termed here as SOD1 mutant interaction region (SMIR). The PB1 domain is required for appropriate oligomeric status of p62 and the SMIR is the actual region interacting with mutant SOD1. Within the SMIR, the conserved W184, H190 and positively charged R183, R186, K187, and K189 residues are critical to the p62-mutant SOD1 interaction as substitution of these residues with alanine resulted in significantly abolished binding. In addition, SMIR and the p62 sequence responsible for the interaction with LC3, a protein essential for autophagy activation, are independent of each other. In cells lacking p62, the existence of mutant SOD1 in acidic autolysosomes decreased, suggesting that p62 can function as an adaptor between mutant SOD1 and the autophagy machinery. This study provides a novel molecular mechanism by which mutant SOD1 can be recognized by p62 in an ubiquitin-independent fashion and targeted for the autophagy-lysosome degradation pathway.

Source Parameters from Full Moment Tensor Inversions of Potentially Induced Earthquakes in Western Canada

NASA Astrophysics Data System (ADS)

Wang, R.; Gu, Y. J.; Schultz, R.; Kim, A.; Chen, Y.

2015-12-01

During the past four years, the number of earthquakes with magnitudes greater than three has substantially increased in the southern section of Western Canada Sedimentary Basin (WCSB). While some of these events are likely associated with tectonic forces, especially along the foothills of the Canadian Rockies, a significant fraction occurred in previously quiescent regions and has been linked to waste water disposal or hydraulic fracturing. A proper assessment of the origin and source properties of these 'induced earthquakes' requires careful analyses and modeling of regional broadband data, which steadily improved during the past 8 years due to recent establishments of regional broadband seismic networks such as CRANE, RAVEN and TD. Several earthquakes, especially those close to fracking activities (e.g. Fox creek town, Alberta) are analyzed. Our preliminary full moment tensor inversion results show maximum horizontal compressional orientations (P-axis) along the northeast-southwest orientation, which agree with the regional stress directions from borehole breakout data and the P-axis of historical events. The decomposition of those moment tensors shows evidence of strike-slip mechanism with near vertical fault plane solutions, which are comparable to the focal mechanisms of injection induced earthquakes in Oklahoma. Minimal isotropic components have been observed, while a modest percentage of compensated-linear-vector-dipole (CLVD) components, which have been linked to fluid migraition, may be required to match the waveforms. To further evaluate the non-double-couple components, we compare the outcomes of full, deviatoric and pure double couple (DC) inversions using multiple frequency ranges and phases. Improved location and depth information from a novel grid search greatly assists the identification and classification of earthquakes in potential connection with fluid injection or extraction. Overall, a systematic comparison of the source attributes of intermediate-sized earthquakes present a new window into the nature of potentially induced earthquakes in the WCSB.

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

Kim, D.; Worster, T.; Boustany, R.M.

The neuronal lipofuscinoses (NCLs) are a group of disorders characterized by cognitive decline, blindness, seizures, and death. Pathologically, it is characterized by accumulation of lipofuscin deposits, generally in easily identifiable `curvilinear bodies`. It is inherited as an autosomal recessive disorder, with the exception of the adult onset form, which may be inherited as an autosomal dominant trait. The loci for the juvenile (CLN3), infantile (CLN1), and very recently, Finnish late-infantile (CLN5) NCLs have been mapped by genetic linkage analysis to chromosome 16p, 1p, and 13q, respectively. The classical late-infantile (LNCL) defect (CLN2) has not yet been mapped. Previous analysis withmore » tightly linked markers excluded CLN2 from the CLN1 and CLN3 regions. We have initiated a genome-wide screen for CLN2, taking advantage of the large collection of highly polymorphic markers that has been developed through the Human Genome Initiative. The high degree of heterozygosity of these markers makes it feasible to carry out successful linkage analysis in small nuclear families, such as found in LNCL. Our current collection of LNCL pedigrees includes 19 U.S. families and 11 Costa Rican families. Simulation studies have shown that we can detect linkage using a subset of 6 LNCL families, a 10 cM sieve, and a lod score criterion of 0.50 for follow-up. A linked region spanned by two markers has over a 95% chance of generating such a lod score, while an unlinked marker has less than a 5% chance of doing so. Follow-up will consist of genotyping the additional families and two additional markers in this region. To date, we have completed typing with 65 markers on chromosomes 1, 2, 9, 13, 16, 18, 19, 20, 21, and 22. The results of this analysis formally exclude about 25% of the human genome as the location of CLN2, including the region of chromosome 13 where CLN5 has been mapped. Updated results will be presented.« less

Friis Hills glacial history: an international collaboration to examine Miocene climate in Antarctica

NASA Astrophysics Data System (ADS)

Halberstadt, A. R. W.; Kowalewski, D. E.

2016-12-01

The Friis Hills, Antarctica (western McMurdo Dry Valleys) contain unique, well-preserved records of Miocene climate. These terrestrial deposits hold geomorphic clues for deciphering the glacial history in a region directly adjacent to the East Antarctic Ice Sheet. Stacked till sheets, interbedded with lake sediments and non-glacial deposits, reveal a complex history of ice flow and erosion throughout multiple glacial-interglacial cycles (Lewis and Ashworth, 2015). Fossiliferous beds containing Nothofagus, diatoms, algal cells, pollen, insects, and mosses provide past climatological constraints. The Friis Hills sustained multiple alpine glaciations as well as full ice-sheet development, recording glacial drainage reorganization and evidence of previous ice configurations that possibly overrode the Transantarctic Mountains (Lewis and Ashworth, 2015) exposing only scattered nunataks (i.e. a portion of Friis Hills). Lack of chronological control has previously hindered efforts to link the Friis Hills glacial history with regional context; a tephra deposit at the base of the glacial drifts currently provides a single age constraint within the drift deposits. To build upon previous studies, an international collaboration between the USAP, Antarctic New Zealand, and the Italian Antarctic community proposes to core a paleo-lake in the center of the Friis Hills in November 2016, thereby acquiring one of the oldest continuous sedimentological records within the McMurdo Dry Valleys. Here we report discoveries from this year's fieldwork, and reconstruct paleoenvironment at the periphery of the East Antarctic Ice Sheet for the mid-early Miocene, a critical time when marine isotopic records indicate dramatic ice fluctuations. Ash within the sediment core stratigraphy will provide a more robust chronology for the region, and will also suggest possible outcrop locations of corresponding ash deposits to pursue while in the field. We anticipate that the Friis Hills stratigraphy will have the necessary chronological control for correlation with offshore marine records from the Ross Embayment, including the ANDRILL project.

Polypharmacy and Polymorbidity in Older Adults in Brazil: a public health challenge

PubMed Central

Ramos, Luiz Roberto; Tavares, Noemia Urruth Leão; Bertoldi, Andréa Dâmaso; Farias, Mareni Rocha; Oliveira, Maria Auxiliadora; Luiza, Vera Lucia; Pizzol, Tatiane da Silva Dal; Arrais, Paulo Sérgio Dourado; Mengue, Sotero Serrate

2016-01-01

ABSTRACT OBJECTIVE To analyze variations in the prevalence of chronic use of medicines by older adults in Brazil according to its possible association with the most prevalent chronic diseases and demographic and health factors, and to identify risk factors for polypharmacy. METHODS A study based on data from the National Survey on Access, Use and Promotion of Rational Use of Medicines (PNAUM), a cross-sectional, population-based survey with probability sampling in Brazilian urban areas. The independent variable was the number of chronic-use medicines taken by older adults, linked to eight chronic diseases investigated. The intervening variables were gender, age group, marital status, level of education, socioeconomic status, Brazilian region, body mass index, smoking, self-perceived health, hospitalization in the previous year and having health insurance, besides the investigated chronic diseases. A multivariable analysis identified risk factors for polypharmacy. RESULTS Prevalence of at least one chronic-use medicines among older adults was 93.0%. Of the total number of older adults, 18.0% used at least five medications (polypharmacy). Polypharmacy was higher among the oldest individuals (20.0%), in the South region (25.0%), in those with poor self-perceived health (35.0%), in obese individuals (26.0%), in those with reported health insurance (23.0%) or hospitalization in the previous year (31.0%), and among those who reported any of the investigated diseases, particularly diabetes (36.0%) and heart diseases (43.0%). The variables remaining in the final risk model for polypharmacy were age, region, perceived health, health insurance, hospitalization in the previous year and all investigated diseases except stroke. CONCLUSIONS Older adults with specific diseases have risk factors for polypharmacy modifiable by actions aimed at the rational use of medicines. With the current population aging and successful drug access policy, the trend is an increase in drug use by older adults, which should feature as a priority in the planning agenda of the Brazilian Unified Health System (SUS). PMID:27982377

Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms.

PubMed

Johnson, Monica; Alsaleh, Nasser; Mendoza, Ryan P; Persaud, Indushekhar; Bauer, Alison K; Saba, Laura; Brown, Jared M

2018-01-01

Mast cells represent a crucial cell type in host defense; however, maladaptive responses are contributing factors in the pathogenesis of allergic diseases. Previous work in our laboratory has shown that exposure to silver nanoparticles (AgNPs) results in mast cell degranulation via a non-immunoglobulin E (IgE) mechanism. In this study, we utilized a systems biology approach to identify novel genetic factors playing a role in AgNP-induced mast cell degranulation compared to the classical activation by antigen-mediated FcεRI crosslinking. Mast cell degranulation was assessed in bone marrow-derived mast cells isolated from 23 strains of mice following exposure to AgNPs or FcεRI crosslinking with dinitrophenyl (DNP). Utilizing strain-dependent mast cell degranulation, an association mapping study identified 3 chromosomal regions that were significantly associated with mast cell degranulation by AgNP and one non-overlapping region associated with DNP-mediated degranulation. Two of the AgNP-associated regions correspond to genes previously reported to be associated with allergic disorders (Trac2 on chromosome 1 and Traf6 on chromosome 2) and an uncharacterized gene identified on chromosome 1 (Fam126b). In conjunction, RNA-sequencing performed on mast cells from the high and low responder strains revealed 3754 and 34 differentially expressed genes that were unique to DNP and AgNP exposures, respectively. Select candidate genes include Ptger4, a gene encoding a G-protein coupled receptor in addition to a multifunctional adaptor protein, Txnip, that may be driving mast cell degranulation by AgNP. Taken together, we identified novel genes that have not been previously shown to play a role in nanoparticle-mediated mast cell activation. With further functional evaluation in the future, these genes may be potential therapeutic targets in the treatment of non-IgE mediated mast cell-linked disorders.

Metabolic syndrome in Portugal: prevalence and implications for cardiovascular risk--results from the VALSIM Study.

PubMed

Fiuza, Manuela; Cortez-Dias, Nuno; Martins, Susana; Belo, Adriana

2008-12-01

The metabolic syndrome (MS) is a constellation of risk factors of metabolic origin that is associated with increased risk of type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). Several regional studies have been conducted to determine its prevalence, but they are insufficient to determine the situation nationally or to characterize overall cardiovascular risk in Portugal. To determine the prevalence of MS and each of its components in adult primary health care users in Portugal. The VALSIM Study, involving 719 general practitioners (GPs), was performed in a primary care setting, based on stratified distribution and proportional to the population density of each region of mainland Portugal and the islands of Madeira and the Azores. The first two adult patients scheduled for an appointment on a given day were invited to participate, irrespective of the reason for the consultation. After informed consent was obtained, a questionnaire on sociodemographic, clinical and laboratory data was completed by the GP. A previous diagnosis of coronary artery disease (CAD), stroke or DM was identified by the GP based on medical records. A diagnosis of MS was defined according to the NCEP ATP III criteria. Logistic regression multivariate analysis was used to assess the risk of MS according to age, body mass index (BMI), waist circumference (WC) and region of residence for each gender, and to determine the association of CAD, stroke and DM with gender, age, BMI, WC, blood pressure and previous diagnosis of hypertension (HT), fasting glucose and previous diagnosis of DM. The study included 16,856 individuals (mean age 58.1+/-15.1 years, 18-96 years; 61.62% women). The prevalence of MS adjusted for gender, age and size of region was 27.5% and showed regional variations, being highest in the Alentejo (30.99%) and lowest in the Algarve (24.42%). MS was more common among women and increased with age, BMI and WC. Independent protective factors were residence in the Algarve (odds ratio [OR]: 0.78; 95% confidence interval [CI] 0.66-0.92 p=0.002) or in Lisbon and Tagus Valley (OR: 0.83, 95% CI 0.77-0.91, p<0.001), while residence in the Northern (OR: 1.11; 95% CI 1.01-1.21, p=0.03) or Central regions (OR: 1.08; 95% CI 1.002-1.16, p=0.045) was an independent risk factor after correction for gender and age. MS was linked to increased prevalence of HT (OR: 3.88; 95% CI 3.61-4.18, p<0.001), and high blood pressure was the most frequent MS component, particularly in men (93.7%). MS was the most powerful factor associated with a diagnosis of DM, particularly in women (OR 7.23; 95% CI 6.22-8.40, p<0.001). Although there was a strong association between MS and CAD (OR: 1.16; 95% CI 1.01-1.34, p=0.043), the most potent risk factor associated with CVD was HT. The prevalence of MS in Portugal is high (27.5%) and is strongly linked to the occurrence of CVD, and in particular to DM. These results highlight the need to implement preventive strategies for reducing overall cardiovascular risk in the Portuguese population.

Understanding tree growth in response to moisture variability: Linking 32 years of satellite based soil moisture observations with tree rings

NASA Astrophysics Data System (ADS)

Albrecht, Franziska; Dorigo, Wouter; Gruber, Alexander; Wagner, Wolfgang; Kainz, Wolfgang

2014-05-01

Climate change induced drought variability impacts global forest ecosystems and forest carbon cycle dynamics. Physiological drought stress might even become an issue in regions generally not considered water-limited. The water balance at the soil surface is essential for forest growth. Soil moisture is a key driver linking precipitation and tree development. Tree ring based analyses are a potential approach to study the driving role of hydrological parameters for tree growth. However, at present two major research gaps are apparent: i) soil moisture records are hardly considered and ii) only a few studies are linking tree ring chronologies and satellite observations. Here we used tree ring chronologies obtained from the International Tree ring Data Bank (ITRDB) and remotely sensed soil moisture observations (ECV_SM) to analyze the moisture-tree growth relationship. The ECV_SM dataset, which is being distributed through ESA's Climate Change Initiative for soil moisture covers the period 1979 to 2010 at a spatial resolution of 0.25°. First analyses were performed for Mongolia, a country characterized by a continental arid climate. We extracted 13 tree ring chronologies suitable for our analysis from the ITRDB. Using monthly satellite based soil moisture observations we confirmed previous studies on the seasonality of soil moisture in Mongolia. Further, we investigated the relationship between tree growth (as reflected by tree ring width index) and remotely sensed soil moisture records by applying correlation analysis. In terms of correlation coefficient a strong response of tree growth to soil moisture conditions of current April to August was observed, confirming a strong linkage between tree growth and soil water storage. The highest correlation was found for current April (R=0.44), indicating that sufficient water supply is vital for trees at the beginning of the growing season. To verify these results, we related the chronologies to reanalysis precipitation and temperature datasets. Precipitation was important during both the current and previous growth season. Temperature showed the strongest correlation for previous (R=0.12) and current October (R=0.21). Hence, our results demonstrated that water supply is most likely limiting tree growth during the growing season, while temperature is determining its length. We are confident that long-term satellite based soil moisture observations can bridge spatial and temporal limitations that are inherent to in situ measurements, which are traditionally used for tree ring research. Our preliminary results are a foundation for further studies linking remotely sensed datasets and tree ring chronologies, an approach that has not been widely investigated among the scientific community.

83. Ventricular Enlargement and Progressive Reduction in Cortical Gray Matter Are Linked in Prodromal Youth Who Develop Psychosis

PubMed Central

Chung, Yoonho; Haut, Kristen; He, George; Van Erp, Theo; McEwen, Sarah; Addington, Jean; Bearden, Carrie; Cadenhead, Kristin; Cornblatt, Barbara; Mathalon, Daniel; McGlashan, Thomas; Perkins, Diana; Seidman, Larry; Tsuang, Ming; Walker, Elaine; Woods, Scott; Cannon, Tyrone

2017-01-01

Abstract Background: In a recent prospective longitudinal neuroimaging study, clinical high-risk (CHR) individuals who later developed full-blown psychosis showed an accelerated rate of gray matter thinning in superior and medial prefrontal cortex (PFC) and expansion of the ventricular system after applying a stringent correction for multiple comparisons. Although cortical and subcortical volume loss and enlarged ventricles are well characterized structural brain abnormalities among patients with schizophrenia, no prior study has evaluated whether these progressive changes of neuroanatomical indicators are linked in time prior to onset of psychosis. Therefore, we investigated the relationship between the changes in cortical gray matter thickness and ventricular volume using the longitudinal neuroimaging data from the North American Prodrome Longitudinal Study (NAPLS) at the whole-brain level. Methods: MRI structural data were acquired at baseline and 12-month follow-up, and follow-up scans for those who developed fully psychotic symptoms were assessed at the point of conversion. In total, 37 CHR cases who converted to psychosis, 230 CHR cases who did not convert (nonconverters), and 132 healthy comparison subjects had usable baseline and second time point scans. Imaging measures were first transformed to annualized rates of percent change (ARCH) in each cortical vertex. Interval is the time between BL and FU scans in years. Relationships between ARCH of total ventricle volume and ARCH of cortical gray matter values were tested vertex-wise using the general linear model. Among the subjects with BL and 12-FU data available, 125 CHR cases and 66 controls were followed to an additional third time point for a 24-month MRI assessment. For the purpose of testing the replicability of our main hypotheses, neuroanatomical ARCH measures between the 12 and 24 month follow-ups were also computed with a parallel set of statistical tests as described earlier. Results: The results showed that ventricular expansion is linked in time to progressive reduction of gray matter, rather than to structural changes in proximal subcortical regions, in a broadly distributed set of cortical regions among CHR youth, including superior, medial, lateral, and inferior PFC, superior temporal gyrus, and parietal cortices. In contrast, the healthy controls did not show the same pattern of associations. The main findings were further replicated using a third assessment wave of MRI scans in a subset of study participants who were followed for an additional year. Conclusion: In summary, expansion of the ventricular spaces is linked in time with an accelerated rate of widespread cortical thinning prior to psychosis onset. The cortical regions experiencing altered maturation during the psychosis prodrome may be more widespread than the regionally specific clusters that have been identified in previous case–control studies

Transcriptional activation of Mina by Sp1/3 factors.

PubMed

Lian, Shangli; Potula, Hari Hara S K; Pillai, Meenu R; Van Stry, Melanie; Koyanagi, Madoka; Chung, Linda; Watanabe, Makiko; Bix, Mark

2013-01-01

Mina is an epigenetic gene regulatory protein known to function in multiple physiological and pathological contexts, including pulmonary inflammation, cell proliferation, cancer and immunity. We showed previously that the level of Mina gene expression is subject to natural genetic variation linked to 21 SNPs occurring in the Mina 5' region. In order to explore the mechanisms regulating Mina gene expression, we set out to molecularly characterize the Mina promoter in the region encompassing these SNPs. We used three kinds of assays--reporter, gel shift and chromatin immunoprecipitation--to analyze a 2 kb genomic fragment spanning the upstream and intron 1 regions flanking exon 1. Here we discovered a pair of Mina promoters (P1 and P2) and a P1-specific enhancer element (E1). Pharmacologic inhibition and siRNA knockdown experiments suggested that Sp1/3 transcription factors trigger Mina expression through additive activity targeted to a cluster of four Sp1/3 binding sites forming the P1 promoter. These results set the stage for comprehensive analysis of Mina gene regulation from the context of tissue specificity, the impact of inherited genetic variation and the nature of upstream signaling pathways.

Transcriptional Activation of Mina by Sp1/3 Factors

PubMed Central

Lian, Shangli; Potula, Hari Hara S. K.; Pillai, Meenu R.; Van Stry, Melanie; Koyanagi, Madoka; Chung, Linda; Watanabe, Makiko; Bix, Mark

2013-01-01

Mina is an epigenetic gene regulatory protein known to function in multiple physiological and pathological contexts, including pulmonary inflammation, cell proliferation, cancer and immunity. We showed previously that the level of Mina gene expression is subject to natural genetic variation linked to 21 SNPs occurring in the Mina 5′ region [1]. In order to explore the mechanisms regulating Mina gene expression, we set out to molecularly characterize the Mina promoter in the region encompassing these SNPs. We used three kinds of assays – reporter, gel shift and chromatin immunoprecipitation – to analyze a 2 kb genomic fragment spanning the upstream and intron 1 regions flanking exon 1. Here we discovered a pair of Mina promoters (P1 and P2) and a P1-specific enhancer element (E1). Pharmacologic inhibition and siRNA knockdown experiments suggested that Sp1/3 transcription factors trigger Mina expression through additive activity targeted to a cluster of four Sp1/3 binding sites forming the P1 promoter. These results set the stage for comprehensive analysis of Mina gene regulation from the context of tissue specificity, the impact of inherited genetic variation and the nature of upstream signaling pathways. PMID:24324617

Atlantic SSTs control regime shifts in forest fire activity of Northern Scandinavia

PubMed Central

Drobyshev, Igor; Bergeron, Yves; Vernal, Anne de; Moberg, Anders; Ali, Adam A.; Niklasson, Mats

2016-01-01

Understanding the drivers of the boreal forest fire activity is challenging due to the complexity of the interactions driving fire regimes. We analyzed drivers of forest fire activity in Northern Scandinavia (above 60 N) by combining modern and proxy data over the Holocene. The results suggest that the cold climate in northern Scandinavia was generally characterized by dry conditions favourable to periods of regionally increased fire activity. We propose that the cold conditions over the northern North Atlantic, associated with low SSTs, expansion of sea ice cover, and the southward shift in the position of the subpolar gyre, redirect southward the precipitation over Scandinavia, associated with the westerlies. This dynamics strengthens high pressure systems over Scandinavia and results in increased regional fire activity. Our study reveals a previously undocumented teleconnection between large scale climate and ocean dynamics over the North Atlantic and regional boreal forest fire activity in Northern Scandinavia. Consistency of the pattern observed annually through millennium scales suggests that a strong link between Atlantic SST and fire activity on multiple temporal scales over the entire Holocene is relevant for understanding future fire activity across the European boreal zone. PMID:26940995

Collagen fibril surface displays a constellation of sites capable of promoting fibril assembly, stability, and hemostasis

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

Orgel, J.P.; Antipova, O.; Sagi, I.

Fibrillar collagens form the structural basis of organs and tissues including the vasculature, bone, and tendon. They are also dynamic, organizational scaffolds that present binding and recognition sites for ligands, cells, and platelets. We interpret recently published X-ray diffraction findings and use atomic force microscopy data to illustrate the significance of new insights into the functional organization of the collagen fibril. These data indicate that collagen's most crucial functional domains localize primarily to the overlap region, comprising a constellation of sites we call the 'master control region.' Moreover, the collagen's most exposed aspect contains its most stable part - themore » C-terminal region that controls collagen assembly, cross-linking, and blood clotting. Hidden beneath the fibril surface exists a constellation of 'cryptic' sequences poised to promote hemostasis and cell - collagen interactions in tissue injury and regeneration. These findings begin to address several important, and previously unresolved, questions: How functional domains are organized in the fibril, which domains are accessible, and which require proteolysis or structural trauma to become exposed? Here we speculate as to how collagen fibrillar organization impacts molecular processes relating to tissue growth, development, and repair.« less

Connections between the tropical Pacific Ocean, Arctic sea ice, and anomalous northeastern Pacific ridging

NASA Astrophysics Data System (ADS)

Swain, D. L.; Singh, D.; Horton, D. E.; Mankin, J. S.; Ballard, T.; Thomas, L. N.; Diffenbaugh, N. S.

2016-12-01

The ongoing and severe drought in California is linked to the multi-year persistence of anomalously strong ridging along the west coast of North America, which has deflected the Pacific storm track north of its climatological mean position. Recent work has shown that that highly amplified and strongly meridional atmospheric flow patterns in this region similar to the "Ridiculously Resilient Ridge" have become more common in recent decades. Previous investigations have suggested multiple possible contributors to this conspicuous atmospheric anomaly—including remote teleconnections to unusual tropical Pacific Ocean warmth and/or reduced Arctic sea ice, internal (natural) atmospheric variability, and anthropogenic forcing due to greenhouse gas emissions. Here, we explore observed relationships between mid-tropospheric atmospheric structure in this region and five hypothesized surface forcings: sea ice extent in the (1) Barents/Kara and (2) Beaufort/Chukchi regions, and sea surface temperatures in the (3) extratropical northeastern Pacific Ocean, (4) western tropical Pacific Ocean, and (5) eastern tropical Pacific Ocean. Using a predictive model based upon these observed relationships, we also investigate whether the failure of the powerful 2015-2016 El Niño event to bring above-average precipitation to California could have been predicted based upon these teleconnections.

Interaction of Zn(II)bleomycin-A2 and Zn(II)peplomycin with a DNA hairpin containing the 5'-GT-3' binding site in comparison with the 5'-GC-3' binding site studied by NMR spectroscopy.

PubMed

Follett, Shelby E; Ingersoll, Azure D; Murray, Sally A; Reilly, Teresa M; Lehmann, Teresa E

2017-10-01

Bleomycins are a group of glycopeptide antibiotics synthesized by Streptomyces verticillus that are widely used for the treatment of various neoplastic diseases. These antibiotics have the ability to chelate a metal center, mainly Fe(II), and cause site-specific DNA cleavage. Bleomycins are differentiated by their C-terminal regions. Although this antibiotic family is a successful course of treatment for some types of cancers, it is known to cause pulmonary fibrosis. Previous studies have identified that bleomycin-related pulmonary toxicity is linked to the C-terminal region of these drugs. This region has been shown to closely interact with DNA. We examined the binding of Zn(II)peplomycin and Zn(II)bleomycin-A 2 to a DNA hairpin of sequence 5'-CCAGTATTTTTACTGG-3', containing the binding site 5'-GT-3', and compared the results with those obtained from our studies of the same MBLMs bound to a DNA hairpin containing the binding site 5'-GC-3'. We provide evidence that the DNA base sequence has a strong impact in the final structure of the drug-target complex.

Atlantic SSTs control regime shifts in forest fire activity of Northern Scandinavia

NASA Astrophysics Data System (ADS)

Drobyshev, Igor; Bergeron, Yves; Vernal, Anne De; Moberg, Anders; Ali, Adam A.; Niklasson, Mats

2016-03-01

Understanding the drivers of the boreal forest fire activity is challenging due to the complexity of the interactions driving fire regimes. We analyzed drivers of forest fire activity in Northern Scandinavia (above 60 N) by combining modern and proxy data over the Holocene. The results suggest that the cold climate in northern Scandinavia was generally characterized by dry conditions favourable to periods of regionally increased fire activity. We propose that the cold conditions over the northern North Atlantic, associated with low SSTs, expansion of sea ice cover, and the southward shift in the position of the subpolar gyre, redirect southward the precipitation over Scandinavia, associated with the westerlies. This dynamics strengthens high pressure systems over Scandinavia and results in increased regional fire activity. Our study reveals a previously undocumented teleconnection between large scale climate and ocean dynamics over the North Atlantic and regional boreal forest fire activity in Northern Scandinavia. Consistency of the pattern observed annually through millennium scales suggests that a strong link between Atlantic SST and fire activity on multiple temporal scales over the entire Holocene is relevant for understanding future fire activity across the European boreal zone.

Atlantic SSTs control regime shifts in forest fire activity of Northern Scandinavia.

PubMed

Drobyshev, Igor; Bergeron, Yves; Vernal, Anne de; Moberg, Anders; Ali, Adam A; Niklasson, Mats

2016-03-04

Understanding the drivers of the boreal forest fire activity is challenging due to the complexity of the interactions driving fire regimes. We analyzed drivers of forest fire activity in Northern Scandinavia (above 60 N) by combining modern and proxy data over the Holocene. The results suggest that the cold climate in northern Scandinavia was generally characterized by dry conditions favourable to periods of regionally increased fire activity. We propose that the cold conditions over the northern North Atlantic, associated with low SSTs, expansion of sea ice cover, and the southward shift in the position of the subpolar gyre, redirect southward the precipitation over Scandinavia, associated with the westerlies. This dynamics strengthens high pressure systems over Scandinavia and results in increased regional fire activity. Our study reveals a previously undocumented teleconnection between large scale climate and ocean dynamics over the North Atlantic and regional boreal forest fire activity in Northern Scandinavia. Consistency of the pattern observed annually through millennium scales suggests that a strong link between Atlantic SST and fire activity on multiple temporal scales over the entire Holocene is relevant for understanding future fire activity across the European boreal zone.

Hubble Peers into the Storm

NASA Image and Video Library

2017-12-08

This shot from the NASA/ESA Hubble Space Telescope shows a maelstrom of glowing gas and dark dust within one of the Milky Way’s satellite galaxies, the Large Magellanic Cloud (LMC). This stormy scene shows a stellar nursery known as N159, an HII region over 150 light-years across. N159 contains many hot young stars. These stars are emitting intense ultraviolet light, which causes nearby hydrogen gas to glow, and torrential stellar winds, which are carving out ridges, arcs, and filaments from the surrounding material. At the heart of this cosmic cloud lies the Papillon Nebula, a butterfly-shaped region of nebulosity. This small, dense object is classified as a High-Excitation Blob, and is thought to be tightly linked to the early stages of massive star formation. N159 is located over 160,000 light-years away. It resides just south of the Tarantula Nebula (heic1402), another massive star-forming complex within the LMC. This image comes from Hubble’s Advanced Camera for Surveys. The region was previously imaged by Hubble’s Wide Field Planetary Camera 2, which also resolved the Papillon Nebula for the first time. Credit: ESA/Hubble & NASA

The biological basis of a universal constraint on color naming: cone contrasts and the two-way categorization of colors.

PubMed

Xiao, Youping; Kavanau, Christopher; Bertin, Lauren; Kaplan, Ehud

2011-01-01

Many studies have provided evidence for the existence of universal constraints on color categorization or naming in various languages, but the biological basis of these constraints is unknown. A recent study of the pattern of color categorization across numerous languages has suggested that these patterns tend to avoid straddling a region in color space at or near the border between the English composite categories of "warm" and "cool". This fault line in color space represents a fundamental constraint on color naming. Here we report that the two-way categorization along the fault line is correlated with the sign of the L- versus M-cone contrast of a stimulus color. Moreover, we found that the sign of the L-M cone contrast also accounted for the two-way clustering of the spatially distributed neural responses in small regions of the macaque primary visual cortex, visualized with optical imaging. These small regions correspond to the hue maps, where our previous study found a spatially organized representation of stimulus hue. Altogether, these results establish a direct link between a universal constraint on color naming and the cone-specific information that is represented in the primate early visual system.

Replication of long-bone length QTL in the F9-F10 LG,SM advanced intercross.

PubMed

Norgard, Elizabeth A; Jarvis, Joseph P; Roseman, Charles C; Maxwell, Taylor J; Kenney-Hunt, Jane P; Samocha, Kaitlin E; Pletscher, L Susan; Wang, Bing; Fawcett, Gloria L; Leatherwood, Christopher J; Wolf, Jason B; Cheverud, James M

2009-04-01

Quantitative trait locus (QTL) mapping techniques are frequently used to identify genomic regions associated with variation in phenotypes of interest. However, the F(2) intercross and congenic strain populations usually employed have limited genetic resolution resulting in relatively large confidence intervals that greatly inhibit functional confirmation of statistical results. Here we use the increased resolution of the combined F(9) and F(10) generations (n = 1455) of the LG,SM advanced intercross to fine-map previously identified QTL associated with the lengths of the humerus, ulna, femur, and tibia. We detected 81 QTL affecting long-bone lengths. Of these, 49 were previously identified in the combined F(2)-F(3) population of this intercross, while 32 represent novel contributors to trait variance. Pleiotropy analysis suggests that most QTL affect three to four long bones or serially homologous limb segments. We also identified 72 epistatic interactions involving 38 QTL and 88 novel regions. This analysis shows that using later generations of an advanced intercross greatly facilitates fine-mapping of confidence intervals, resolving three F(2)-F(3) QTL into multiple linked loci and narrowing confidence intervals of other loci, as well as allowing identification of additional QTL. Further characterization of the biological bases of these QTL will help provide a better understanding of the genetics of small variations in long-bone length.

Long-delayed bright dancing sprite with large Horizontal displacement from its parent flash

NASA Astrophysics Data System (ADS)

Yang, Jing; Lu, Gaopeng; Lee, Li-Jou; Feng, Guili

2015-07-01

We reported in this paper the observation of a very bright long-delayed dancing sprite with distinct horizontal displacement from its parent stroke. The dancing sprite lasted only 60 ms, and the morphology consisted of three fields with two slim dim sprite elements in the first two fields and a very bright large element in the third field, different from other observations where the dancing sprites usually contained multiple elements over a longer time interval, and the sprite shape and brightness in the video field are often similar to the previous fields. The bright sprite was displaced at least 38 km from its parent cloud-to-ground (CG) stroke and occurred over comparatively higher cloud top region. The parent flash of this compact dancing sprite was of positive polarity, with only one return stroke (approximately +24 kA) and obvious continuing current process, and the charge moment change of stroke was small (barely above the threshold for sprite production). All the sprite elements occurred during the continuing current stage, and the bright long-delayed sprite element induced a considerable current pulse. The dancing feature of this sprite may be linked to the electrical charge structure, dynamics and microphysics of parent storm, and the inferred development of parent CG flash was consistent with previous very high-frequency (VHF) observations of lightning in the same region.

Genome-Wide Association Mapping of Crown Rust Resistance in Oat Elite Germplasm.

PubMed

Klos, Kathy Esvelt; Yimer, Belayneh A; Babiker, Ebrahiem M; Beattie, Aaron D; Bonman, J Michael; Carson, Martin L; Chong, James; Harrison, Stephen A; Ibrahim, Amir M H; Kolb, Frederic L; McCartney, Curt A; McMullen, Michael; Fetch, Jennifer Mitchell; Mohammadi, Mohsen; Murphy, J Paul; Tinker, Nicholas A

2017-07-01

Oat crown rust, caused by f. sp. , is a major constraint to oat ( L.) production in many parts of the world. In this first comprehensive multienvironment genome-wide association map of oat crown rust, we used 2972 single-nucleotide polymorphisms (SNPs) genotyped on 631 oat lines for association mapping of quantitative trait loci (QTL). Seedling reaction to crown rust in these lines was assessed as infection type (IT) with each of 10 crown rust isolates. Adult plant reaction was assessed in the field in a total of 10 location-years as percentage severity (SV) and as infection reaction (IR) in a 0-to-1 scale. Overall, 29 SNPs on 12 linkage groups were predictive of crown rust reaction in at least one experiment at a genome-wide level of statistical significance. The QTL identified here include those in regions previously shown to be linked with seedling resistance genes , , , , , and and also with adult-plant resistance and adaptation-related QTL. In addition, QTL on linkage groups Mrg03, Mrg08, and Mrg23 were identified in regions not previously associated with crown rust resistance. Evaluation of marker genotypes in a set of crown rust differential lines supported as the identity of . The SNPs with rare alleles associated with lower disease scores may be suitable for use in marker-assisted selection of oat lines for crown rust resistance. Copyright © 2017 Crop Science Society of America.

Meta-connectomics: human brain network and connectivity meta-analyses.

PubMed

Crossley, N A; Fox, P T; Bullmore, E T

2016-04-01

Abnormal brain connectivity or network dysfunction has been suggested as a paradigm to understand several psychiatric disorders. We here review the use of novel meta-analytic approaches in neuroscience that go beyond a summary description of existing results by applying network analysis methods to previously published studies and/or publicly accessible databases. We define this strategy of combining connectivity with other brain characteristics as 'meta-connectomics'. For example, we show how network analysis of task-based neuroimaging studies has been used to infer functional co-activation from primary data on regional activations. This approach has been able to relate cognition to functional network topology, demonstrating that the brain is composed of cognitively specialized functional subnetworks or modules, linked by a rich club of cognitively generalized regions that mediate many inter-modular connections. Another major application of meta-connectomics has been efforts to link meta-analytic maps of disorder-related abnormalities or MRI 'lesions' to the complex topology of the normative connectome. This work has highlighted the general importance of network hubs as hotspots for concentration of cortical grey-matter deficits in schizophrenia, Alzheimer's disease and other disorders. Finally, we show how by incorporating cellular and transcriptional data on individual nodes with network models of the connectome, studies have begun to elucidate the microscopic mechanisms underpinning the macroscopic organization of whole-brain networks. We argue that meta-connectomics is an exciting field, providing robust and integrative insights into brain organization that will likely play an important future role in consolidating network models of psychiatric disorders.

Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another: confirmation of genetic heterogeneity.

PubMed Central

Lester, D H; Inglehearn, C F; Bashir, R; Ackford, H; Esakowitz, L; Jay, M; Bird, A C; Wright, A F; Papiha, S S; Bhattacharya, S S

1990-01-01

Recently Dryja and his co-workers observed a mutation in the 23d codon of the rhodopsin gene in a proportion of autosomal dominant retinitis pigmentosa (ADRP) patients. Linkage analysis with a rhodopsin-linked probe C17 (D3S47) was carried out in two large British ADRP families, one with diffuse-type (D-type) RP and the other with regional-type (R-type) RP. Significantly positive lod scores (lod score maximum [Zmax] = +5.58 at recombination fraction [theta] = .0) were obtained between C17 and our D-type ADRP family showing complete penetrance. Sequence and oligonucleotide analysis has, however, shown that no point mutation at the 23d codon exists in affected individuals in our complete-penetrance pedigree, indicating that another rhodopsin mutation is probably responsible for ADRP in this family. Significantly negative lod scores (Z less than -2 at theta = .045) were, however, obtained between C17 and our R-type family which showed incomplete penetrance. Previous results presented by this laboratory also showed no linkage between C17 and another large British R-type ADRP family with incomplete penetrance. This confirms genetic heterogeneity. Some types of ADRP are being caused by different mutations in the rhodopsin locus (3q21-24) or another tightly linked gene in this region, while other types of ADRP are the result of mutations elsewhere in the genome. Images Figure 2 Figure 3 Figure 4 PMID:2393026

Application of machine learning methods to describe the effects of conjugated equine estrogens therapy on region-specific brain volumes.

PubMed

Casanova, Ramon; Espeland, Mark A; Goveas, Joseph S; Davatzikos, Christos; Gaussoin, Sarah A; Maldjian, Joseph A; Brunner, Robert L; Kuller, Lewis H; Johnson, Karen C; Mysiw, W Jerry; Wagner, Benjamin; Resnick, Susan M

2011-05-01

Use of conjugated equine estrogens (CEE) has been linked to smaller regional brain volumes in women aged ≥65 years; however, it is unknown whether this results in a broad-based characteristic pattern of effects. Structural magnetic resonance imaging was used to assess regional volumes of normal tissue and ischemic lesions among 513 women who had been enrolled in a randomized clinical trial of CEE therapy for an average of 6.6 years, beginning at ages 65-80 years. A multivariate pattern analysis, based on a machine learning technique that combined Random Forest and logistic regression with L(1) penalty, was applied to identify patterns among regional volumes associated with therapy and whether patterns discriminate between treatment groups. The multivariate pattern analysis detected smaller regional volumes of normal tissue within the limbic and temporal lobes among women that had been assigned to CEE therapy. Mean decrements ranged as high as 7% in the left entorhinal cortex and 5% in the left perirhinal cortex, which exceeded the effect sizes reported previously in frontal lobe and hippocampus. Overall accuracy of classification based on these patterns, however, was projected to be only 54.5%. Prescription of CEE therapy for an average of 6.6 years is associated with lower regional brain volumes, but it does not induce a characteristic spatial pattern of changes in brain volumes of sufficient magnitude to discriminate users and nonusers. Copyright © 2011 Elsevier Inc. All rights reserved.

Application of machine learning methods to describe the effects of conjugated equine estrogens therapy on region-specific brain volumes

PubMed Central

Casanova, Ramon; Espeland, Mark A.; Goveas, Joseph S.; Davatzikos, Christos; Gaussoin, Sarah A.; Maldjian, Joseph A.; Brunner, Robert L.; Kuller, Lewis H.; Johnson, Karen C.; Mysiw, W. Jerry; Wagner, Benjamin; Resnick, Susan M.

2011-01-01

Use of conjugated equine estrogens (CEE) has been linked to smaller regional brain volumes in women aged ≥65 years, however it is unknown whether this results in a broad-based characteristic pattern of effects. Structural MRI was used to assess regional volumes of normal tissue and ischemic lesions among 513 women who had been enrolled in a randomized clinical trial of CEE therapy for an average of 6.6 years, beginning at ages 65-80 years. A multivariate pattern analysis, based on a machine learning technique that combined Random Forest and logistic regression with L1 penalty, was applied to identify patterns among regional volumes associated with therapy and whether patterns discriminate between treatment groups. The multivariate pattern analysis detected smaller regional volumes of normal tissue within the limbic and temporal lobes among women that had been assigned to CEE therapy. Mean decrements ranged as high as 7% in the left entorhinal cortex and 5% in the left perirhinal cortex, which exceeded the effect sizes reported previously in frontal lobe and hippocampus. Overall accuracy of classification based on these patterns, however, was projected to be only 54.5%. Prescription of CEE therapy for an average of 6.6 years is associated with lower regional brain volumes, but it does not induce a characteristic spatial pattern of changes in brain volumes of sufficient magnitude to discriminate users and non-users. PMID:21292420

Dengue virus infection in a French traveller to the hilly region of Nepal in 2015: a case report.

PubMed

Gupta, Birendra Prasad; Adhikari, Anurag; Rauniyar, Ramanuj; Kurmi, Roshan; Upadhya, Bishnu Prasad; Jha, Bimlesh Kumar; Pandey, Basudev; Das Manandhar, Krishna

2016-03-21

Dengue viral infections are known to pose a significant risk during travel to tropical regions, but it is surprising to find dengue transmission in the hilly region of Nepal, which is over 1800mtr above sea level. A 43-year-old Caucasian female traveler from France presented with fever and abdominal pain following a diarrheal illness while visiting the central hilly region of Nepal. Over the course of 9 days, she developed fever, body aches, and joint pain, with hemorrhagic manifestation. She was hospitalized in India and treated with supportive care, with daily monitoring of her platelets. An assessment by enzyme-linked immunosorbent assay showed that she was positive for dengue non-structural protein 1. Upon her return to France, dengue virus was confirmed by reverse transcriptase-polymerase chain reaction. The district where this dengue case was reported is in the hilly region of Nepal, neighboring the capital city Kathmandu. To the best of our knowledge, there has previously been no dengue cases reported from the district. This study is important because it aims to establish a potential region of dengue virus circulation not only in the tropics, but also in the subtropics as well, which in Nepal may exceed elevations of 1800mtr. This recent case report has raised alarm among concerned health personnel, researchers, and organizations that this infectious disease is now on the way to becoming established in a temperate climate.

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

Wolf-Chase, Grace; Arvidsson, Kim; Smutko, Michael, E-mail: gwolfchase@adlerplanetarium.org

We present the results of a narrow-band near-infrared imaging survey for Molecular Hydrogen emission-line Objects (MHOs) toward 26 regions containing high-mass protostellar candidates and massive molecular outflows. We have detected a total of 236 MHOs, 156 of which are new detections, in 22 out of the 26 regions. We use H{sub 2} 2.12 μ m/H{sub 2} 2.25 μ m flux ratios, together with morphology, to separate the signatures of fluorescence associated with photo-dissociation regions (PDRs) from shocks associated with outflows in order to identify the MHOs. PDRs have typical low flux ratios of ∼1.5–3, while the vast majority of MHOsmore » display flux ratios typical of C-type shocks (∼6–20). A few MHOs exhibit flux ratios consistent with expected values for J-type shocks (∼3–4), but these are located in regions that may be contaminated with fluorescent emission. Some previously reported MHOs have low flux ratios, and are likely parts of PDRs rather than shocks indicative of outflows. We identify a total of 36 outflows across the 22 target regions where MHOs were detected. In over half these regions, MHO arrangements and fluorescent structures trace features present in CO outflow maps, suggesting that the CO emission traces a combination of dynamical effects, which may include gas entrained in expanding PDRs as well as bipolar outflows. Where possible, we link MHO complexes to distinct outflows and identify candidate driving sources.« less

Unexplained Cases of Allergic Reactions Linked to Red Meat

MedlinePlus

... that starts after being bitten by a lone star tick may cause unexplained cases of recurrent anaphylaxis. ... after eating meat. Previous studies have linked lone star tick bites to this unusual food allergy. The ...

Linking regional stakeholder scenarios and shared socioeconomic pathways: Quantified West African food and climate futures in a global context.

PubMed

Palazzo, Amanda; Vervoort, Joost M; Mason-D'Croz, Daniel; Rutting, Lucas; Havlík, Petr; Islam, Shahnila; Bayala, Jules; Valin, Hugo; Kadi Kadi, Hamé Abdou; Thornton, Philip; Zougmore, Robert

2017-07-01

The climate change research community's shared socioeconomic pathways (SSPs) are a set of alternative global development scenarios focused on mitigation of and adaptation to climate change. To use these scenarios as a global context that is relevant for policy guidance at regional and national levels, they have to be connected to an exploration of drivers and challenges informed by regional expertise. In this paper, we present scenarios for West Africa developed by regional stakeholders and quantified using two global economic models, GLOBIOM and IMPACT, in interaction with stakeholder-generated narratives and scenario trends and SSP assumptions. We present this process as an example of linking comparable scenarios across levels to increase coherence with global contexts, while presenting insights about the future of agriculture and food security under a range of future drivers including climate change. In these scenarios, strong economic development increases food security and agricultural development. The latter increases crop and livestock productivity leading to an expansion of agricultural area within the region while reducing the land expansion burden elsewhere. In the context of a global economy, West Africa remains a large consumer and producer of a selection of commodities. However, the growth in population coupled with rising incomes leads to increases in the region's imports. For West Africa, climate change is projected to have negative effects on both crop yields and grassland productivity, and a lack of investment may exacerbate these effects. Linking multi-stakeholder regional scenarios to the global SSPs ensures scenarios that are regionally appropriate and useful for policy development as evidenced in the case study, while allowing for a critical link to global contexts.

Serotonin Transporter-Linked Polymorphic Region (5-HTTLPR) Genotype and Stressful Life Events Interact to Predict Preschool-Onset Depression: A Replication and Developmental Extension

ERIC Educational Resources Information Center

Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Tillman, Rebecca; Luby, Joan L.

2014-01-01

Background: Scientific enthusiasm about gene × environment interactions, spurred by the 5-HTTLPR (serotonin transporter-linked polymorphic region) × SLEs (stressful life events) interaction predicting depression, have recently been tempered by sober realizations of small effects and meta-analyses reaching opposing conclusions. These mixed findings…

Functional Overlap between Regions Involved in Speech Perception and in Monitoring One's Own Voice during Speech Production

ERIC Educational Resources Information Center

Zheng, Zane Z.; Munhall, Kevin G.; Johnsrude, Ingrid S.

2010-01-01

The fluency and the reliability of speech production suggest a mechanism that links motor commands and sensory feedback. Here, we examined the neural organization supporting such links by using fMRI to identify regions in which activity during speech production is modulated according to whether auditory feedback matches the predicted outcome or…

EPA Region 3 Quality Management Plans

EPA Pesticide Factsheets

Has links to resources that describe the Region's Quality Assurance Program, which is a collection of the Region's ongoing quality assurance (QA) policies, procedures, responsibilities and management systems.

Neural activity, neural connectivity, and the processing of emotionally valenced information in older adults: links with life satisfaction.

PubMed

Waldinger, Robert J; Kensinger, Elizabeth A; Schulz, Marc S

2011-09-01

This study examines whether differences in late-life well-being are linked to how older adults encode emotionally valenced information. Using fMRI with 39 older adults varying in life satisfaction, we examined how viewing positive and negative images would affect activation and connectivity of an emotion-processing network. Participants engaged most regions within this network more robustly for positive than for negative images, but within the PFC this effect was moderated by life satisfaction, with individuals higher in satisfaction showing lower levels of activity during the processing of positive images. Participants high in satisfaction showed stronger correlations among network regions-particularly between the amygdala and other emotion processing regions-when viewing positive, as compared with negative, images. Participants low in satisfaction showed no valence effect. Findings suggest that late-life satisfaction is linked with how emotion-processing regions are engaged and connected during processing of valenced information. This first demonstration of a link between neural recruitment and late-life well-being suggests that differences in neural network activation and connectivity may account for the preferential encoding of positive information seen in some older adults.

Neural Activity, Neural Connectivity, and the Processing of Emotionally-Valenced Information in Older Adults: Links with Life Satisfaction

PubMed Central

Waldinger, Robert J.; Kensinger, Elizabeth A.; Schulz, Marc S.

2013-01-01

This study examines whether differences in late-life well-being are linked to how older adults encode emotionally-valenced information. Using fMRI with 39 older adults varying in life satisfaction, we examined how viewing positive and negative images affected activation and connectivity of an emotion-processing network. Participants engaged most regions within this network more robustly for positive than for negative images, but within the PFC this effect was moderated by life satisfaction, with individuals higher in satisfaction showing lower levels of activity during the processing of positive images. Participants high in satisfaction showed stronger correlations among network regions – particularly between the amygdala and other emotion processing regions – when viewing positive as compared to negative images. Participants low in satisfaction showed no valence effect. Findings suggest that late-life satisfaction is linked with how emotion-processing regions are engaged and connected during processing of valenced information. This first demonstration of a link between neural recruitment and late-life well-being suggests that differences in neural network activation and connectivity may account for the preferential encoding of positive information seen in some older adults. PMID:21590504

An unusual birthmark case thought to be linked to a person who had previously died.

PubMed

Keil, H H; Tucker, J B

2000-12-01

The following case report describes a Burmese subject with an unusual birthmark and birth defects thought by local people to be linked to events surrounding the death of his mother's first husband. The nature of the link is explored, including how the assumption of a linkage could have led to subsequent events.

Longitudinal links between childhood peer acceptance and the neural correlates of sharing.

PubMed

Will, Geert-Jan; Crone, Eveline A; van Lier, Pol A C; Güroğlu, Berna

2018-01-01

Childhood peer acceptance is associated with high levels of prosocial behavior and advanced perspective taking skills. Yet, the neurobiological mechanisms underlying these associations have not been studied. This functional magnetic resonance imaging study examined the neural correlates of sharing decisions in a group of adolescents who had a stable accepted status (n = 27) and a group who had a chronic rejected status (n = 19) across six elementary school grades. Both groups of adolescents played three allocation games in which they could share money with strangers with varying costs and profits to them and the other person. Stably accepted adolescents were more likely to share their money with unknown others than chronically rejected adolescents when sharing was not costly. Neuroimaging analyses showed that stably accepted adolescents, compared to chronically rejected adolescents, exhibited higher levels of activation in the temporo-parietal junction, posterior superior temporal sulcus, temporal pole, pre-supplementary motor area, and anterior insula during costly sharing decisions. These findings demonstrate that stable peer acceptance across childhood is associated with heightened activity in brain regions previously linked to perspective taking and the detection of social norm violations during adolescence, and thereby provide insight into processes underlying the widely established links between peer acceptance and prosocial behavior. © 2016 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

Computational advances towards linking BOLD and behavior.

PubMed

Serences, John T; Saproo, Sameer

2012-03-01

Traditionally, fMRI studies have focused on analyzing the mean response amplitude within a cortical area. However, the mean response is blind to many important patterns of cortical modulation, which severely limits the formulation and evaluation of linking hypotheses between neural activity, BOLD responses, and behavior. More recently, multivariate pattern classification analysis (MVPA) has been applied to fMRI data to evaluate the information content of spatially distributed activation patterns. This approach has been remarkably successful at detecting the presence of specific information in targeted brain regions, and provides an extremely flexible means of extracting that information without a precise generative model for the underlying neural activity. However, this flexibility comes at a cost: since MVPA relies on pooling information across voxels that are selective for many different stimulus attributes, it is difficult to infer how specific sub-sets of tuned neurons are modulated by an experimental manipulation. In contrast, recently developed encoding models can produce more precise estimates of feature-selective tuning functions, and can support the creation of explicit linking hypotheses between neural activity and behavior. Although these encoding models depend on strong - and often untested - assumptions about the response properties of underlying neural generators, they also provide a unique opportunity to evaluate population-level computational theories of perception and cognition that have previously been difficult to assess using either single-unit recording or conventional neuroimaging techniques. Copyright © 2011. Published by Elsevier Ltd.

Fellow travellers: a concordance of colonization patterns between mice and men in the North Atlantic region

PubMed Central

2012-01-01

Background House mice (Mus musculus) are commensals of humans and therefore their phylogeography can reflect human colonization and settlement patterns. Previous studies have linked the distribution of house mouse mitochondrial (mt) DNA clades to areas formerly occupied by the Norwegian Vikings in Norway and the British Isles. Norwegian Viking activity also extended further westwards in the North Atlantic with the settlement of Iceland, short-lived colonies in Greenland and a fleeting colony in Newfoundland in 1000 AD. Here we investigate whether house mouse mtDNA sequences reflect human history in these other regions as well. Results House mice samples from Iceland, whether from archaeological Viking Age material or from modern-day specimens, had an identical mtDNA haplotype to the clade previously linked with Norwegian Vikings. From mtDNA and microsatellite data, the modern-day Icelandic mice also share the low genetic diversity shown by their human hosts on Iceland. Viking Age mice from Greenland had an mtDNA haplotype deriving from the Icelandic haplotype, but the modern-day Greenlandic mice belong to an entirely different mtDNA clade. We found no genetic association between modern Newfoundland mice and the Icelandic/ancient Greenlandic mice (no ancient Newfoundland mice were available). The modern day Icelandic and Newfoundland mice belong to the subspecies M. m. domesticus, the Greenlandic mice to M. m. musculus. Conclusions In the North Atlantic region, human settlement history over a thousand years is reflected remarkably by the mtDNA phylogeny of house mice. In Iceland, the mtDNA data show the arrival and continuity of the house mouse population to the present day, while in Greenland the data suggest the arrival, subsequent extinction and recolonization of house mice - in both places mirroring the history of the European human host populations. If house mice arrived in Newfoundland with the Viking settlers at all, then, like the humans, their presence was also fleeting and left no genetic trace. The continuity of mtDNA haplotype in Iceland over 1000 years illustrates that mtDNA can retain the signature of the ancestral house mouse founders. We also show that, in terms of genetic variability, house mouse populations may also track their host human populations. PMID:22429664

An evidential link prediction method and link predictability based on Shannon entropy

NASA Astrophysics Data System (ADS)

Yin, Likang; Zheng, Haoyang; Bian, Tian; Deng, Yong

2017-09-01

Predicting missing links is of both theoretical value and practical interest in network science. In this paper, we empirically investigate a new link prediction method base on similarity and compare nine well-known local similarity measures on nine real networks. Most of the previous studies focus on the accuracy, however, it is crucial to consider the link predictability as an initial property of networks itself. Hence, this paper has proposed a new link prediction approach called evidential measure (EM) based on Dempster-Shafer theory. Moreover, this paper proposed a new method to measure link predictability via local information and Shannon entropy.

Cross-linking of initiation factor IF3 to Escherichia coli 30S ribosomal subunit by trans-diamminedichloroplatinum(II): characterization of two cross-linking sites in 16S rRNA; a possible way of functioning for IF3.

PubMed Central

Ehresmann, C; Moine, H; Mougel, M; Dondon, J; Grunberg-Manago, M; Ebel, J P; Ehresmann, B

1986-01-01

The initiation factor IF3 is platinated with trans-diamminedichloroplatinum(II) and cross-linked to Escherichia coli 30S ribosomal subunit. Two cross-linking sites are unambiguously identified on the 16S rRNA: a major one, in the region 819-859 in the central domain, and a minor one, in the region 1506-1529 in the 3'-terminal domain. Specific features of these sequences together with their particular location within the 30S subunit lead us to postulate a role for IF3, that conciliates topographical and functional observations made so far. Images PMID:2425339

Linking knowledge and action through mental models of sustainable agriculture.

PubMed

Hoffman, Matthew; Lubell, Mark; Hillis, Vicken

2014-09-09

Linking knowledge to action requires understanding how decision-makers conceptualize sustainability. This paper empirically analyzes farmer "mental models" of sustainability from three winegrape-growing regions of California where local extension programs have focused on sustainable agriculture. The mental models are represented as networks where sustainability concepts are nodes, and links are established when a farmer mentions two concepts in their stated definition of sustainability. The results suggest that winegrape grower mental models of sustainability are hierarchically structured, relatively similar across regions, and strongly linked to participation in extension programs and adoption of sustainable farm practices. We discuss the implications of our findings for the debate over the meaning of sustainability, and the role of local extension programs in managing knowledge systems.

Linking knowledge and action through mental models of sustainable agriculture

PubMed Central

Hoffman, Matthew; Lubell, Mark; Hillis, Vicken

2014-01-01

Linking knowledge to action requires understanding how decision-makers conceptualize sustainability. This paper empirically analyzes farmer “mental models” of sustainability from three winegrape-growing regions of California where local extension programs have focused on sustainable agriculture. The mental models are represented as networks where sustainability concepts are nodes, and links are established when a farmer mentions two concepts in their stated definition of sustainability. The results suggest that winegrape grower mental models of sustainability are hierarchically structured, relatively similar across regions, and strongly linked to participation in extension programs and adoption of sustainable farm practices. We discuss the implications of our findings for the debate over the meaning of sustainability, and the role of local extension programs in managing knowledge systems. PMID:25157158

Insights on the SO2 Poisoning of Pt3Co/VC and Pt/VC Fuel Cell Catalysts

DTIC Science & Technology

2010-01-01

catalyst is performed at the cathode of proton exchange membrane fuel cells ( PEMFCs ) in order to link previously reported results at the elec- trode...stripping voltammetry and underpotential deposition (upd) of copper adatoms. Then the performance of PEMFC cathodes employing 30wt.% Pt3Co/VC and 50wt.% Pt/VC...proton exchange membrane fuel cells( PEMFCs )in order to link previously reported results at the elec- trode/solution interface to the FC environment. First

Sources of Sahelian-Sudan moisture: Insights from a moisture-tracing atmospheric model

NASA Astrophysics Data System (ADS)

Salih, Abubakr A. M.; Zhang, Qiong; Pausata, Francesco S. R.; Tjernström, Michael

2016-07-01

The summer rainfall across Sahelian-Sudan is one of the main sources of water for agriculture, human, and animal needs. However, the rainfall is characterized by large interannual variability, which has attracted extensive scientific efforts to understand it. This study attempts to identify the source regions that contribute to the Sahelian-Sudan moisture budget during July through September. We have used an atmospheric general circulation model with an embedded moisture-tracing module (Community Atmosphere Model version 3), forced by observed (1979-2013) sea-surface temperatures. The result suggests that about 40% of the moisture comes with the moisture flow associated with the seasonal migration of the Intertropical Convergence Zone (ITCZ) and originates from Guinea Coast, central Africa, and the Western Sahel. The Mediterranean Sea, Arabian Peninsula, and South Indian Ocean regions account for 10.2%, 8.1%, and 6.4%, respectively. Local evaporation and the rest of the globe supply the region with 20.3% and 13.2%, respectively. We also compared the result from this study to a previous analysis that used the Lagrangian model FLEXPART forced by ERA-Interim. The two approaches differ when comparing individual regions, but are in better agreement when neighboring regions of similar atmospheric flow features are grouped together. Interannual variability with the rainfall over the region is highly correlated with contributions from regions that are associated with the ITCZ movement, which is in turn linked to the Atlantic Multidecadal Oscillation. Our result is expected to provide insights for the effort on seasonal forecasting of the rainy season over Sahelian Sudan.

Hekate: Software Suite for the Mass Spectrometric Analysis and Three-Dimensional Visualization of Cross-Linked Protein Samples

PubMed Central

2013-01-01

Chemical cross-linking of proteins combined with mass spectrometry provides an attractive and novel method for the analysis of native protein structures and protein complexes. Analysis of the data however is complex. Only a small number of cross-linked peptides are produced during sample preparation and must be identified against a background of more abundant native peptides. To facilitate the search and identification of cross-linked peptides, we have developed a novel software suite, named Hekate. Hekate is a suite of tools that address the challenges involved in analyzing protein cross-linking experiments when combined with mass spectrometry. The software is an integrated pipeline for the automation of the data analysis workflow and provides a novel scoring system based on principles of linear peptide analysis. In addition, it provides a tool for the visualization of identified cross-links using three-dimensional models, which is particularly useful when combining chemical cross-linking with other structural techniques. Hekate was validated by the comparative analysis of cytochrome c (bovine heart) against previously reported data.1 Further validation was carried out on known structural elements of DNA polymerase III, the catalytic α-subunit of the Escherichia coli DNA replisome along with new insight into the previously uncharacterized C-terminal domain of the protein. PMID:24010795

Changes of cloudiness over tropical land during the past few decades and its link to global climate change

NASA Astrophysics Data System (ADS)

Arias, P.; Fu, R.; Li, W.

2007-12-01

Tropical forests play a key role in determining the global carbon-climate feedback in the 21st century. Changes in rainforest growth and mortality rates, especially in the deep and least perturbed forest areas, have been consistently observed across global tropics in recent years. Understanding the underlying causes of these changes, especially their links to the global climate change, is especially important in determining the future of the tropical rainforests in the 21st century. Previous studies have mostly focus on the potential influences from elevated atmospheric CO2 and increasing surface temperature. Because the rainforests in wet tropical region is often light limited, we explore whether cloudiness have changed, if so, whether it is consistent with that expected from changes in forest growth rate. We will report our observational analysis examining the trends in annual average shortwave (SW) downwelling radiation, total cloud cover, and cumulus cover over the tropical land regions and to link them with trends in convective available potencial energy (CAPE). ISCCP data and radiosonde records available from the Department of Atmospheric Sciences of the University of Wyoming (http://www.weather.uwyo.edu/upperair/sounding.html) are used to study the trends. The period for the trend analysis is 1984-2004 for the ISCCP data and 1980-2006 for the radiosondes. The results for the Amazon rainforest region suggest a decreasing trend in total cloud and convective cloud covers, which results in an increase in downwelling SW radiation at the surface. These changes of total and convective clouds are consistent with a trend of decreasing CAPE and an elevated Level of Free Convection (LFC) height, as obtained from the radiosondes. All the above mentioned trends are statistically significant based on the Mann-Kendall test with 95% of confidence. These results consistently suggest the downward surface solar radiation has been increasing since 1984, result from a decrease of convective and total cloudiness over the Southern Amazon basin, due to an increase of LFC and atmospheric thermodynamic stability. Such an increase of surface SW radiation probably has contributed to the increasing in growth rate for the forests in the Amazon forests. Currently, the same analysis is being applied using radiosonde data from the Comprehensive Aerological Reference Data Set (CARDS) over the Amazon and Congo basins and the Southeast Asia. Our objective is to identify changes in cloudiness over tropical land and identify its underlying causes, especially the link to changes in surface temperature and humidity.

Understanding moisture recycling for atmospheric river management in Amazonian communities

NASA Astrophysics Data System (ADS)

Weng, Wei; Luedeke, Matthias; Zemp, Delphine-Clara; Lakes, Tobia; Pradhan, Prajal; Kropp, Juergen

2017-04-01

The invisible atmospheric transports of moisture have recently attracted more research efforts into understanding their structures, processes involved and their function as an ecosystem service. Current attention has been focused on larger scale analysis such as studying global or continental level moisture recycling. Here we applied a water balance model to backtrack the flying river that sustains two local communities in the Colombian and Peruvian Amazon where vulnerable communities rely highly on the rainfall for agricultural practices. By utilising global precipitation (TRMM Multisatillite Precipitation Analysis; TMPA) and evapotranspiration products (Moderate Resolution Imaging Spectroradiometer MODIS, MOD16ET) as input data in the present modelling experiments to compensate the sparse ground observation data in these regions, the moisture recycling process targeting the two amazonian communities which has not yet been explored quantitatively has been shown. The TMPA was selected because of its proved comparativeness with observation data in its precipitation estimations over Amazon regions while the MOD16ET data was chosen for being validated by previous studies in the Amazon basin and for reported good performance. In average, 45.5 % of the precipitation occurring to Caquetá region in Colombia is of terrestrial origin from the South American continent while 48.2% of the total rainfall received by Peruvian Yurimaguas is also from the South American land sources. The spatial distribution of the precipitationsheds (defined previously as the upwind contribution of evapotranspiration to a specific location's precipitation) shows transboundary and transnational shares in the moisture contributors of the precipitation for both regions. An interesting reversed upstream-downstream roles can be observed when the upstream regions in traditional watershed thinking become downstream areas considering precipitationsheds and flying rivers. Strong seasonal variations are also detected by our results. Since undergoing rapid land cultivation expansion in the precipitationsheds of these study areas can potentially alter the moisture recycling process which sustains ecosystem and communities, the tele-connection linking the contributors and recipients presented in this study has highlighted that region-wise collaboration and communication will be essential for an adaptive Amazonia facing environmental change, especially in regards to its vulnerable communities.

Phase Diagrams of Three-Dimensional Anderson and Quantum Percolation Models Using Deep Three-Dimensional Convolutional Neural Network

NASA Astrophysics Data System (ADS)

Mano, Tomohiro; Ohtsuki, Tomi

2017-11-01

The three-dimensional Anderson model is a well-studied model of disordered electron systems that shows the delocalization-localization transition. As in our previous papers on two- and three-dimensional (2D, 3D) quantum phase transitions [J. Phys. Soc. Jpn. 85, 123706 (2016), 86, 044708 (2017)], we used an image recognition algorithm based on a multilayered convolutional neural network. However, in contrast to previous papers in which 2D image recognition was used, we applied 3D image recognition to analyze entire 3D wave functions. We show that a full phase diagram of the disorder-energy plane is obtained once the 3D convolutional neural network has been trained at the band center. We further demonstrate that the full phase diagram for 3D quantum bond and site percolations can be drawn by training the 3D Anderson model at the band center.

BETR North America: A regionally segmented multimedia contaminant fate model for North America

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

MacLeod, M.; Woodfine, D.G.; Mackay, D.

We present the Berkeley-Trent North American contaminant fate model (BETR North America), a regionally segmented multimedia contaminant fate model based on the fugacity concept. The model is built on a framework that links contaminant fate models of individual regions, and is generally applicable to large, spatially heterogeneous areas. The North American environment is modeled as 24 ecological regions, within each region contaminant fate is described using a 7 compartment multimedia fugacity model including a vertically segmented atmosphere, freshwater, freshwater sediment, soil, coastal water and vegetation compartments. Inter-regional transport of contaminants in the atmosphere, freshwater and coastal water is described usingmore » a database of hydrological and meteorological data compiled with Geographical Information Systems (GIS) techniques. Steady-state and dynamic solutions to the 168 mass balance equations that make up the linked model for North America are discussed, and an illustrative case study of toxaphene transport from the southern United States to the Great Lakes Basin is presented. Regionally segmented models such as BETR North America can provide a critical link between evaluative models of long-range transport potential and contaminant concentrations observed in remote regions. The continent-scale mass balance calculated by the model provides a sound basis for evaluating long-range transport potential of organic pollutants, and formulation of continent scale management and regulatory strategies for chemicals.« less

Development and evaluation of a crowdsourcing methodology for knowledge base construction: identifying relationships between clinical problems and medications

PubMed Central

Wright, Adam; Laxmisan, Archana; Ottosen, Madelene J; McCoy, Jacob A; Butten, David; Sittig, Dean F

2012-01-01

Objective We describe a novel, crowdsourcing method for generating a knowledge base of problem–medication pairs that takes advantage of manually asserted links between medications and problems. Methods Through iterative review, we developed metrics to estimate the appropriateness of manually entered problem–medication links for inclusion in a knowledge base that can be used to infer previously unasserted links between problems and medications. Results Clinicians manually linked 231 223 medications (55.30% of prescribed medications) to problems within the electronic health record, generating 41 203 distinct problem–medication pairs, although not all were accurate. We developed methods to evaluate the accuracy of the pairs, and after limiting the pairs to those meeting an estimated 95% appropriateness threshold, 11 166 pairs remained. The pairs in the knowledge base accounted for 183 127 total links asserted (76.47% of all links). Retrospective application of the knowledge base linked 68 316 medications not previously linked by a clinician to an indicated problem (36.53% of unlinked medications). Expert review of the combined knowledge base, including inferred and manually linked problem–medication pairs, found a sensitivity of 65.8% and a specificity of 97.9%. Conclusion Crowdsourcing is an effective, inexpensive method for generating a knowledge base of problem–medication pairs that is automatically mapped to local terminologies, up-to-date, and reflective of local prescribing practices and trends. PMID:22582202

Exact and Optimal Quantum Mechanics/Molecular Mechanics Boundaries.

PubMed

Sun, Qiming; Chan, Garnet Kin-Lic

2014-09-09

Motivated by recent work in density matrix embedding theory, we define exact link orbitals that capture all quantum mechanical (QM) effects across arbitrary quantum mechanics/molecular mechanics (QM/MM) boundaries. Exact link orbitals are rigorously defined from the full QM solution, and their number is equal to the number of orbitals in the primary QM region. Truncating the exact set yields a smaller set of link orbitals optimal with respect to reproducing the primary region density matrix. We use the optimal link orbitals to obtain insight into the limits of QM/MM boundary treatments. We further analyze the popular general hybrid orbital (GHO) QM/MM boundary across a test suite of molecules. We find that GHOs are often good proxies for the most important optimal link orbital, although there is little detailed correlation between the detailed GHO composition and optimal link orbital valence weights. The optimal theory shows that anions and cations cannot be described by a single link orbital. However, expanding to include the second most important optimal link orbital in the boundary recovers an accurate description. The second optimal link orbital takes the chemically intuitive form of a donor or acceptor orbital for charge redistribution, suggesting that optimal link orbitals can be used as interpretative tools for electron transfer. We further find that two optimal link orbitals are also sufficient for boundaries that cut across double bonds. Finally, we suggest how to construct "approximately" optimal link orbitals for practical QM/MM calculations.

Measurement of ring A-reduced progesterone metabolites by enzyme-linked immunoassay with colorimetric detection: baseline levels of six metabolites, including pregnanolone, in male rat plasma.

PubMed

Ocvirk, Rok; Franklin, Keith B J; Pearson Murphy, Beverley E

2009-02-01

The performance of an antiserum to progesterone and pregnane neurosteroids was assessed in two competitive assay setups: radioimmunoassay and enzyme-linked immunoassay with colorimetric detection, both with the same limit of detection of 2 pg. The enzyme-linked immunoassay was less labor-intensive and had better precision of measurement and was used to measure progesterone and six of its ring A-reduced metabolites in rat plasma. The measured levels of allopregnanolone and progesterone were in agreement with those reported previously when measured by gas chromatography/mass spectrometry and high-performance liquid chromatography coupled with radioimmunoassay and substantially lower than those previously measured by radioimmunoassay without chromatographic separation. Both isomers of dihydroprogesterone and all four isomers of pregnanolone were detected in rat plasma, indicating that progesterone is metabolized by reduction at the C5 and C3 position of the A ring, in both alpha and beta configurations. In addition to 5beta-dihydroprogesterone and isopregnanolone, which have not been previously detected in the rat, we found considerable amounts of pregnanolone, which is neuroactive, with similar potency to that of allopregnanolone but was previously thought not to be produced in rats.

Shifting species interactions in terrestrial dryland ecosystems under altered water availability and climate change

USGS Publications Warehouse

McCluney, Kevin E.; Belnap, Jayne; Collins, Scott L.; González, Angélica L.; Hagen, Elizabeth M.; Holland, J. Nathaniel; Kotler, Burt P.; Maestre, Fernando T.; Smith, Stanley D.; Wolf, Blair O.

2012-01-01

Species interactions play key roles in linking the responses of populations, communities, and ecosystems to environmental change. For instance, species interactions are an important determinant of the complexity of changes in trophic biomass with variation in resources. Water resources are a major driver of terrestrial ecology and climate change is expected to greatly alter the distribution of this critical resource. While previous studies have documented strong effects of global environmental change on species interactions in general, responses can vary from region to region. Dryland ecosystems occupy more than one-third of the Earth's land mass, are greatly affected by changes in water availability, and are predicted to be hotspots of climate change. Thus, it is imperative to understand the effects of environmental change on these globally significant ecosystems. Here, we review studies of the responses of population-level plant-plant, plant-herbivore, and predator-prey interactions to changes in water availability in dryland environments in order to develop new hypotheses and predictions to guide future research. To help explain patterns of interaction outcomes, we developed a conceptual model that views interaction outcomes as shifting between (1) competition and facilitation (plant-plant), (2) herbivory, neutralism, or mutualism (plant-herbivore), or (3) neutralism and predation (predator-prey), as water availability crosses physiological, behavioural, or population-density thresholds. We link our conceptual model to hypothetical scenarios of current and future water availability to make testable predictions about the influence of changes in water availability on species interactions. We also examine potential implications of our conceptual model for the relative importance of top-down effects and the linearity of patterns of change in trophic biomass with changes in water availability. Finally, we highlight key research needs and some possible broader impacts of our findings. Overall, we hope to stimulate and guide future research that links changes in water availability to patterns of species interactions and the dynamics of populations and communities in dryland ecosystems.

Environmental links to interannual variability in shellfish toxicity in Cobscook Bay and eastern Maine, a strongly tidally mixed coastal region

NASA Astrophysics Data System (ADS)

Horecka, Hannah M.; Thomas, Andrew C.; Weatherbee, Ryan A.

2014-05-01

The Gulf of Maine experiences annual closures of shellfish harvesting due to the accumulation of toxins produced by dinoflagellates of the genus Alexandrium. Factors controlling the timing, location, and magnitude of these events in eastern Maine remain poorly understood. Previous work identified possible linkages between interannual variability of oceanographic variables and shellfish toxicity along the western Maine coastline but no such linkages were evident along the eastern Maine coast in the vicinity of Cobscook Bay, where strong tidal mixing tends to reduce seasonal variability in oceanographic properties. Using 21 years (1985-2005) of shellfish toxicity data, interannual variability in two metrics of annual toxicity, maximum magnitude and total annual toxicity, from stations in the Cobscook Bay region are examined for relationships to a suite of available environmental variables. Consistent with earlier work, no (or only weak) correlations were found between toxicity and oceanographic variables, even those very proximate to the stations such as local sea surface temperature. Similarly no correlations were evident between toxicity and air temperature, precipitation or relative humidity. The data suggest possible connections to local river discharge, but plausible mechanisms are not obvious. Correlations between toxicity and two variables indicative of local meteorological conditions, dew point and atmospheric pressure, both suggest a link between increased toxicity in these eastern Maine stations and weather conditions characterized by clearer skies/drier air (or less stormy/humid conditions). As no correlation of opposite sign was evident between toxicity and local precipitation, one plausible link is through light availability and its positive impact on phytoplankton production in this persistently foggy section of coast. These preliminary findings point to both the value of maintaining long-term shellfish toxicity sampling and a need for inclusion of weather variability in future modeling studies aimed at development of a more mechanistic understanding of factors controlling interannual differences in eastern Gulf of Maine shellfish toxicity.

Novel opportunities for computational biology and sociology in drug discovery☆

PubMed Central

Yao, Lixia; Evans, James A.; Rzhetsky, Andrey

2013-01-01

Current drug discovery is impossible without sophisticated modeling and computation. In this review we outline previous advances in computational biology and, by tracing the steps involved in pharmaceutical development, explore a range of novel, high-value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery. These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use. Computation can also be used to model research teams and innovative regions and to estimate the value of academy–industry links for scientific and human benefit. Attention to these opportunities could promise punctuated advance and will complement the well-established computational work on which drug discovery currently relies. PMID:20349528

Chronic kidney disease of unknown aetiology and ground-water ionicity: study based on Sri Lanka.

PubMed

Dharma-Wardana, M W C; Amarasiri, Sarath L; Dharmawardene, Nande; Panabokke, C R

2015-04-01

High incidence of chronic kidney disease of unknown aetiology (CKDU) in Sri Lanka is shown to correlate with the presence of irrigation works and rivers that bring-in 'nonpoint source' fertilizer runoff from intensely agricultural regions. We review previous attempts to link CKDU with As, Cd and other standard toxins. Those studies (e.g. the WHO-sponsored study), while providing a wealth of data, are inconclusive in regard to aetiology. Here, we present new proposals based on increased ionicity of drinking water due to fertilizer runoff into the river system, redox processes in the soil and features of 'tank'-cascades and aquifers. The consequent chronic exposure to high ionicity in drinking water is proposed to debilitate the kidney via a Hofmeister-type (i.e. protein-denaturing) mechanism.

A partially folded structure of amyloid-beta(1-40) in an aqueous environment.

PubMed

Vivekanandan, Subramanian; Brender, Jeffrey R; Lee, Shirley Y; Ramamoorthy, Ayyalusamy

2011-07-29

Aggregation of the Aβ(1-40) peptide is linked to the development of extracellular plaques characteristic of Alzheimer's disease. While previous studies commonly show the Aβ(1-40) is largely unstructured in solution, we show that Aβ(1-40) can adopt a compact, partially folded structure. In this structure (PDB ID: 2LFM), the central hydrophobic region of the peptide forms a 3(10) helix from H13 to D23 and the N- and C-termini collapse against the helix due to the clustering of hydrophobic residues. Helical intermediates have been predicted to be crucial on-pathway intermediates in amyloid fibrillogenesis, and the structure presented here presents a new target for investigation of early events in Aβ(1-40) fibrillogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

El Niño suppresses Antarctic warming

NASA Astrophysics Data System (ADS)

Bertler, Nancy A. N.; Barrett, Peter J.; Mayewski, Paul A.; Fogt, Ryan L.; Kreutz, Karl J.; Shulmeister, James

2004-08-01

Here we present new isotope records derived from snow samples from the McMurdo Dry Valleys, Antarctica and re-analysis data of the European Centre for Medium-Range Weather Forecasts (ERA-40) to explain the connection between the warming of the Pacific sector of the Southern Ocean [Jacka and Budd, 1998; Jacobs et al., 2002] and the current cooling of the terrestrial Ross Sea region [Doran et al., 2002a]. Our analysis confirms previous findings that the warming is linked to the El Niño Southern Oscillation (ENSO) [Kwok and Comiso, 2002a, 2002b; Carleton, 2003; Ribera and Mann, 2003; Turner, 2004], and provides new evidence that the terrestrial cooling is caused by a simultaneous ENSO driven change in atmospheric circulation, sourced in the Amundsen Sea and West Antarctica.

Coherent transport structures in magnetized plasmas. I. Theory

NASA Astrophysics Data System (ADS)

Di Giannatale, G.; Falessi, M. V.; Grasso, D.; Pegoraro, F.; Schep, T. J.

2018-05-01

In a pair of linked articles (called Papers I and II, respectively), we apply the concept of Lagrangian Coherent Structures (LCSs) borrowed from the study of dynamical systems to magnetic field configurations in order to separate regions where field lines have a different kind of behaviour. In the present article, Paper I, after recalling the definition and the properties of the LCSs, we show how this conceptual framework can be applied to the study of particle transport in a magnetized plasma. Furthermore, we introduce a simplified model that allows us to consider explicitly the case where the magnetic configuration evolves in time on time scales comparable to the particle transit time through the configuration. In contrast with previous works on this topic, this analysis requires that a system that is aperiodic in time be investigated.

IMPAIRED VERBAL COMPREHENSION OF QUANTIFIERS IN CORTICOBASAL SYNDROME

PubMed Central

Troiani, Vanessa; Clark, Robin; Grossman, Murray

2011-01-01

Objective Patients with Corticobasal Syndrome (CBS) have atrophy in posterior parietal cortex. This region of atrophy has been previously linked with their quantifier comprehension difficulty, but previous studies used visual stimuli, making it difficult to account for potential visuospatial deficits in CBS patients. The current study evaluated comprehension of generalized quantifiers using strictly verbal materials. Method CBS patients, a brain-damaged control group (consisting of Alzheimer's Disease and frontotemporal dementia), and age-matched controls participated in this study. We assessed familiar temporal, spatial, and monetary domains of verbal knowledge comparatively. Judgment accuracy was only evaluated in statements for which patients demonstrated accurate factual knowledge about the target domain. Results We found that patients with CBS are significantly impaired in their ability to evaluate quantifiers compared to healthy seniors and a brain-damaged control group, even in this strictly visual task. This impairment was seen in the vast majority of individual CBS patients. Conclusions These findings offer additional evidence of quantifier impairment in CBS patients and emphasize that this impairment cannot be attributed to potential spatial processing impairments in patients with parietal disease. PMID:21381823

Polymorphism of the Tryptophan Hydroxylase 2 (TPH2) Gene Is Associated with Chimpanzee Neuroticism

PubMed Central

Morimura, Naruki; Udono, Toshifumi; Hayasaka, Ikuo; Humle, Tatyana; Murayama, Yuichi; Ito, Shin'ichi; Inoue-Murayama, Miho

2011-01-01

In the brain, serotonin production is controlled by tryptophan hydroxylase 2 (TPH2), a genotype. Previous studies found that mutations on the TPH2 locus in humans were associated with depression and studies of mice and studies of rhesus macaques have shown that the TPH2 locus was involved with aggressive behavior. We previously reported a functional single nucleotide polymorphism (SNP) in the form of an amino acid substitution, Q468R, in the chimpanzee TPH2 gene coding region. In the present study we tested whether this SNP was associated with neuroticism in captive and wild-born chimpanzees living in Japan and Guinea, respectively. Even after correcting for multiple tests (Bonferroni p = 0.05/6 = 0.008), Q468R was significantly related to higher neuroticism (β = 0.372, p = 0.005). This study is the first to identify a genotype linked to a personality trait in chimpanzees. In light of the prior studies on humans, mice, and rhesus macaques, these findings suggest that the relationship between neuroticism and TPH2 has deep phylogenetic roots. PMID:21765945

Caucasian Families Exhibit Significant Linkage of Myopia to Chromosome 11p.

PubMed

Musolf, Anthony M; Simpson, Claire L; Moiz, Bilal A; Long, Kyle A; Portas, Laura; Murgia, Federico; Ciner, Elise B; Stambolian, Dwight; Bailey-Wilson, Joan E

2017-07-01

Myopia is a common visual disorder caused by eye overgrowth, resulting in blurry vision. It affects one in four Americans, and its prevalence is increasing. The genetic mechanisms that underpin myopia are not completely understood. Here, we use genotype data and linkage analyses to identify high-risk genetic loci that are significantly linked to myopia. Individuals from 56 Caucasian families with a history of myopia were genotyped on an exome-based array, and the single nucleotide polymorphism (SNP) data were merged with microsatellite genotype data. Refractive error measures on the samples were converted into binary phenotypes consisting of affected, unaffected, or unknown myopia status. Parametric linkage analyses assuming an autosomal dominant model with 90% penetrance and 10% phenocopy rate were performed. Single variant two-point analyses yielded three significantly linked SNPs at 11p14.1 and 11p11.2; a further 45 SNPs at 11p were found to be suggestive. No other chromosome had any significant SNPs or more than seven suggestive linkages. Two of the significant SNPs were located in BBOX1-AS1 and one in the intergenic region between ORA47 and TRIM49B. Collapsed haplotype pattern two-point analysis and multipoint analyses also yielded multiple suggestively linked genes at 11p. Multipoint analysis also identified suggestive evidence of linkage on 20q13. We identified three genome-wide significant linked variants on 11p for myopia in Caucasians. Although the novel specific signals still need to be replicated, 11p is a promising region that has been identified by other linkage studies with a number of potentially interesting candidate genes. We hope that the identification of these regions on 11p as potential causal regions for myopia will lead to more focus on these regions and maybe possible replication of our specific linkage peaks in other studies. We further plan targeted sequencing on 11p for our most highly linked families to more clearly understand the source of the linkage in this region.

Epidemiological link of a major cholera outbreak in Greater Accra region of Ghana, 2014.

PubMed

Ohene-Adjei, Kennedy; Kenu, Ernest; Bandoh, Delia Akosua; Addo, Prince Nii Ossah; Noora, Charles Lwanga; Nortey, Priscillia; Afari, Edwin Andrew

2017-10-11

Cholera remains an important public health challenge globally. Several pandemics have occurred in different parts of the world and have been epidemiologically linked by different researchers to illustrate how the cases were spread and how they were related to index cases. Even though the risk factors associated with the 2014 cholera outbreak were investigated extensively, the link between index cases and the source of infection was not investigated to help break the transmission process. This study sought to show how the index cases from various districts of the Greater Accra Region may have been linked. We carried out a descriptive cross sectional study to investigate the epidemiological link of the 2014 cholera outbreak in the Greater Accra region of Ghana. An extensive review of all district records on cholera cases in the Greater Accra region was carried out. Index cases were identified with the help of line lists. Univariate analyses were expressed as frequency distributions, percentages, mean ± Standard Deviation, and rates (attack rates, case-fatality rates etc.) as appropriate. Maps were drawn using Arc GIS and Epi info software to describe the pattern of transmission. Up to 20,199 cholera cases were recorded. Sixty percent of the cases were between 20 and 40 years and about 58% (11,694) of the total cases were males. Almost 50% of the cases occurred in the Accra Metro district. Two-thirds of the index cases ate food prepared outside their home and had visited the Accra Metropolis. The 2014 cholera outbreak can be described as a propagated source outbreak linked to the Accra Metropolis. The link between index cases and the source of infection, if investigated earlier could have helped break the transmission process. Such investigations also inform decision-making about the appropriate interventions to be instituted to prevent subsequent outbreaks.

Communication-Link Approach to Actuation of Grade-Crossing Motorist-Warning Systems

DOT National Transportation Integrated Search

1975-07-01

Previous studies indicate that one promising avenue to grade-crossing motorist-warning systems, offering lower cost and independent of railroad-track circuits, is use of a radio-communication link for signal activation. By this means, the presence of...

BRAD BRDY and BRD1 GPS Station RINEX Files 09-17-2015

DOE Data Explorer

Corne Kreemer

2015-09-17

CSV files with links to RINEX data for stations BRAD and BRDY for all days after those reported previous (i.e., since 21-JAN-2015) Links to websites that show the position time-series of both stations.

Mapping of the serotonin 5-HT{sub 1D{beta}} autoreceptor gene on chromosome 6 and direct analysis for sequence variants

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

Lappalainen, J.; Dean, M.; Virkkunen, M.

1995-04-24

Abnormal brain serotonin function may be characteristic of several neuropsychiatric disorders. Thus, it is important to identify polymorphic genes and screen for functional variants at loci coding for genes that control normal serotonin functions. 5-HT{sub 1D{beta}} is a terminal serotonin autoreceptor which may play a role in regulating serotonin synthesis and release. Using an SSCP technique we screened for 5-HT{sub 1D{beta}} coding sequence variants in psychiatrically interviewed populations, which included controls, alcoholics, and alcoholic arsonists and alcoholic violent offenders with low CSF concentrations of the main serotonin metabolite 5-HIAA. A common polymorphism was identified in the 5-HT{sub 1D{beta}} gene withmore » allele frequencies of 0.72 and 0.28. The SSCP variant was caused by a silent G to C substitution at nucleotide 861 of the coding region. This polymorphism could also be detected as a HincII RFLP of amplified DNA. DNAs from informative CEPH families were typed for the HincII RFLP and analyzed with respect to 20 linked markers on chromosome 6. Multipoint analysis placed the 5-HT{sub 1D{beta}} receptor gene between markers D6S286 and D6S275. A maximum two-point lod score of 10.90 was obtained to D6S26, which had been previously localized on 6q14-15. Chromosomal aberrations involving this region have been previously shown to cause retinal anomalies, developmental delay, and abnormal brain development. This region also contains the gene for North Carolina-type macular dystrophy. 34 refs., 3 figs., 1 tab.« less

Deleting the Redundant TSH Receptor C-Peptide Region Permits Generation of the Conformationally Intact Extracellular Domain by Insect Cells.

PubMed

Chen, Chun-Rong; Salazar, Larry M; McLachlan, Sandra M; Rapoport, Basil

2015-07-01

The TSH receptor (TSHR) extracellular domain (ECD) comprises a N-terminal leucine-rich repeat domain and an hinge region (HR), the latter contributing to ligand binding and critical for receptor activation. The crystal structure of the leucine-rich repeat domain component has been solved, but previous attempts to generate conformationally intact complete ECD or the isolated HR component for structural analysis have failed. The TSHR HR contains a C-peptide segment that is removed during spontaneous TSHR intramolecular cleavage into disulfide linked A- and B-subunits. We hypothesized that deletion of the redundant C-peptide would overcome the obstacle to generating conformationally intact TSHR ECD protein. Indeed, lacking the C-peptide region, the TSHR ECD (termed ECD-D1) and the isolated HR (termed HR-D1) were secreted into medium of insect cells infected with baculoviruses coding for these modified proteins. The identities of TSHR ECD-D1 and HR-D1 were confirmed by ELISA and immunoblotting using TSHR-specific monoclonal antibodies. The TSHR-ECD-D1 in conditioned medium was folded correctly, as demonstrated by its ability to inhibit radiolabeled TSH binding to the TSH holoreceptor. The TSHR ECD-D1 purification was accomplished in a single step using a TSHR monoclonal antibody affinity column, whereas the HR-D1 required a multistep protocol with a low yield. In conclusion, we report a novel approach to generate the TSHR ECD, as well as the isolated HR in insect cells, the former in sufficient amounts for structural studies. However, such studies will require previous complexing of the ECD with a ligand such as TSH or a thyroid-stimulating antibody.

Genome-wide methylation analysis in Silver-Russell syndrome patients

PubMed Central

Böhm, S; Frost, JM; Puszyk, W; Abu-Amero, S; Stanier, P; Schulz, R; Moore, GE; Oakey, RJ

2015-01-01

Silver-Russell Syndrome (SRS) is a clinically heterogeneous disorder characterised by severe in utero growth restriction and poor postnatal growth, body asymmetry, irregular craniofacial features and several additional minor malformations. The aetiology of SRS is complex and current evidence strongly implicates imprinted genes. Approximately half of all patients exhibit DNA hypomethylation at the H19/IGF2 imprinted domain, and around 10% have maternal uniparental disomy of chromosome 7. We measured DNA methylation in 18 SRS patients at >485,000 CpG sites using DNA methylation microarrays. Using a novel bioinformatics methodology specifically designed to identify subsets of patients with a shared epimutation, we analysed methylation changes genome-wide as well as at known imprinted regions to identify SRS-associated epimutations. Our analysis identifies epimutations at the previously characterised domains of H19/IGF2 and at imprinted regions on chromosome 7, providing proof of principle that our methodology can detect DNA methylation changes at imprinted loci. In addition we discovered two novel epimutations associated with SRS and located at imprinted loci previously linked to relevant mouse and human phenotypes. We identify RB1 as an additional imprinted locus associated with SRS, with a region near the RB1 DMR hypermethylated in 13/18 (~70 %) patients. We also report 6/18 (~33 %) patients were hypermethylated at a CpG island near the ANKRD11 gene. We do not observe consistent cooccurrence of epimutations at multiple imprinted loci in single SRS individuals. SRS is clinically heterogeneous and the absence of multiple imprinted loci epimutations reflects the heterogeneity at the molecular level. Further stratification of SRS patients by molecular phenotypes might aid the identification of disease causes. PMID:25563730

Identification of a negative element in the human vimentin promoter: modulation by the human T-cell leukemia virus type I Tax protein.

PubMed Central

Salvetti, A; Lilienbaum, A; Li, Z; Paulin, D; Gazzolo, L

1993-01-01

The vimentin gene is a member of the intermediate filament multigene family and encodes a protein expressed, in vivo, in all mesenchymal derivatives and, in vitro, in cell types of various origin. We have previously demonstrated that the expression of this growth-regulated gene could be trans activated by the 40-kDa Tax protein of HTLV-I (human T-cell leukemia virus type I) and that responsiveness to this viral protein was mediated by the presence of an NF-kappa B binding site located between -241 and -210 bp upstream of the mRNA cap site (A. Lilienbaum, M. Duc Dodon, C. Alexandre, L. Gazzolo, and D. Paulin, J. Virol. 64:256-263, 1990). These previous assays, performed with deletion mutants of the vimentin promoter linked to the chloramphenicol acetyltransferase gene, also revealed the presence of an upstream negative region between -529 and -241 bp. Interestingly, the inhibitory activity exerted by this negative region was overcome after cotransfection of a Tax-expressing plasmid. In this study, we further characterize the vimentin negative element and define the effect of the Tax protein on the inhibitory activity of this element. We first demonstrate that a 187-bp domain (-424 to -237 bp) behaves as a negative region when placed upstream either of the NF-kappa B binding site of vimentin or of a heterologous enhancer such as that present in the desmin gene promoter. The negative effect can be further assigned to a 32-bp element which is indeed shown to repress the basal or induced activity of the NF-kappa B binding site.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8417364

Origin and domestication of papaya Yh chromosome.

PubMed

VanBuren, Robert; Zeng, Fanchang; Chen, Cuixia; Zhang, Jisen; Wai, Ching Man; Han, Jennifer; Aryal, Rishi; Gschwend, Andrea R; Wang, Jianping; Na, Jong-Kuk; Huang, Lixian; Zhang, Lingmao; Miao, Wenjing; Gou, Jiqing; Arro, Jie; Guyot, Romain; Moore, Richard C; Wang, Ming-Li; Zee, Francis; Charlesworth, Deborah; Moore, Paul H; Yu, Qingyi; Ming, Ray

2015-04-01

Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX, and two slightly different Y chromosomes distinguish males (XY) and hermaphrodites (XY(h)). The hermaphrodite-specific region of the Y(h) chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previously. We now report the sequence of the entire male-specific region of the Y (MSY). We used a BAC-by-BAC approach to sequence the MSY and resequence the Y regions of 24 wild males and the Y(h) regions of 12 cultivated hermaphrodites. The MSY and HSY regions have highly similar gene content and structure, and only 0.4% sequence divergence. The MSY sequences from wild males include three distinct haplotypes, associated with the populations' geographic locations, but gene flow is detected for other genomic regions. The Y(h) sequence is highly similar to one Y haplotype (MSY3) found only in wild dioecious populations from the north Pacific region of Costa Rica. The low MSY3-Y(h) divergence supports the hypothesis that hermaphrodite papaya is a product of human domestication. We estimate that Y(h) arose only ∼ 4000 yr ago, well after crop plant domestication in Mesoamerica >6200 yr ago but coinciding with the rise of the Maya civilization. The Y(h) chromosome has lower nucleotide diversity than the Y, or the genome regions that are not fully sex-linked, consistent with a domestication bottleneck. The identification of the ancestral MSY3 haplotype will expedite investigation of the mutation leading to the domestication of the hermaphrodite Y(h) chromosome. In turn, this mutation should identify the gene that was affected by the carpel-suppressing mutation that was involved in the evolution of males. © 2015 VanBuren et al.; Published by Cold Spring Harbor Laboratory Press.

Origin and domestication of papaya Yh chromosome

PubMed Central

VanBuren, Robert; Zeng, Fanchang; Chen, Cuixia; Zhang, Jisen; Wai, Ching Man; Han, Jennifer; Aryal, Rishi; Gschwend, Andrea R.; Wang, Jianping; Na, Jong-Kuk; Huang, Lixian; Zhang, Lingmao; Miao, Wenjing; Gou, Jiqing; Arro, Jie; Guyot, Romain; Moore, Richard C.; Wang, Ming-Li; Zee, Francis; Charlesworth, Deborah; Moore, Paul H.; Yu, Qingyi; Ming, Ray

2015-01-01

Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX, and two slightly different Y chromosomes distinguish males (XY) and hermaphrodites (XYh). The hermaphrodite-specific region of the Yh chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previously. We now report the sequence of the entire male-specific region of the Y (MSY). We used a BAC-by-BAC approach to sequence the MSY and resequence the Y regions of 24 wild males and the Yh regions of 12 cultivated hermaphrodites. The MSY and HSY regions have highly similar gene content and structure, and only 0.4% sequence divergence. The MSY sequences from wild males include three distinct haplotypes, associated with the populations’ geographic locations, but gene flow is detected for other genomic regions. The Yh sequence is highly similar to one Y haplotype (MSY3) found only in wild dioecious populations from the north Pacific region of Costa Rica. The low MSY3-Yh divergence supports the hypothesis that hermaphrodite papaya is a product of human domestication. We estimate that Yh arose only ∼4000 yr ago, well after crop plant domestication in Mesoamerica >6200 yr ago but coinciding with the rise of the Maya civilization. The Yh chromosome has lower nucleotide diversity than the Y, or the genome regions that are not fully sex-linked, consistent with a domestication bottleneck. The identification of the ancestral MSY3 haplotype will expedite investigation of the mutation leading to the domestication of the hermaphrodite Yh chromosome. In turn, this mutation should identify the gene that was affected by the carpel-suppressing mutation that was involved in the evolution of males. PMID:25762551

Brain structure correlates of urban upbringing, an environmental risk factor for schizophrenia.

PubMed

Haddad, Leila; Schäfer, Axel; Streit, Fabian; Lederbogen, Florian; Grimm, Oliver; Wüst, Stefan; Deuschle, Michael; Kirsch, Peter; Tost, Heike; Meyer-Lindenberg, Andreas

2015-01-01

Urban upbringing has consistently been associated with schizophrenia, but which specific environmental exposures are reflected by this epidemiological observation and how they impact the developing brain to increase risk is largely unknown. On the basis of prior observations of abnormal functional brain processing of social stress in urban-born humans and preclinical evidence for enduring structural brain effects of early social stress, we investigated a possible morphological correlate of urban upbringing in human brain. In a sample of 110 healthy subjects studied with voxel-based morphometry, we detected a strong inverse correlation between early-life urbanicity and gray matter (GM) volume in the right dorsolateral prefrontal cortex (DLPFC, Brodmann area 9). Furthermore, we detected a negative correlation of early-life urbanicity and GM volumes in the perigenual anterior cingulate cortex (pACC) in men only. Previous work has linked volume reductions in the DLPFC to the exposure to psychosocial stress, including stressful experiences in early life. Besides, anatomical and functional alterations of this region have been identified in schizophrenic patients and high-risk populations. Previous data linking functional hyperactivation of pACC during social stress to urban upbringing suggest that the present interaction effect in brain structure might contribute to an increased risk for schizophrenia in males brought up in cities. Taken together, our results suggest a neural mechanism by which early-life urbanicity could impact brain architecture to increase the risk for schizophrenia. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Spiny trapdoor spiders (Euoplos) of eastern Australia: Broadly sympatric clades are differentiated by burrow architecture and male morphology.

PubMed

Wilson, Jeremy D; Hughes, Jane M; Raven, Robert J; Rix, Michael G; Schmidt, Daniel J

2018-05-01

Spiders of the infraorder Mygalomorphae are fast becoming model organisms for the study of biogeography and speciation. However, these spiders can be difficult to study in the absence of fundamental life history information. In particular, their cryptic nature hinders comprehensive sampling, and linking males with conspecific females can be challenging. Recently discovered differences in burrow entrance architecture and male morphology indicated that these challenges may have impeded our understanding of the trapdoor spider genus Euoplos in Australia's eastern mesic zone. We investigated the evolutionary significance of these discoveries using a multi-locus phylogenetic approach. Our results revealed the existence of a second, previously undocumented, lineage of Euoplos in the eastern mesic zone. This new lineage occurs in sympatry with a lineage previously known from the region, and the two are consistently divergent in their burrow entrance architecture and male morphology, revealing the suitability of these characters for use in phylogenetic studies. Divergent burrow entrance architecture and observed differences in microhabitat preferences are suggested to facilitate sympatry and syntopy between the lineages. Finally, by investigating male morphology and plotting it onto the phylogeny, we revealed that the majority of Euoplos species remain undescribed, and that males of an unnamed species from the newly discovered lineage had historically been linked, erroneously, to a described species from the opposite lineage. This paper clarifies the evolutionary relationships underlying life history diversity in the Euoplos of eastern Australia, and provides a foundation for urgently needed taxonomic revision of this genus. Copyright © 2018 Elsevier Inc. All rights reserved.

Diverse Genetic Regulon of the Virulence-Associated Transcriptional Regulator MucR in Brucella abortus 2308

PubMed Central

Caswell, Clayton C.; Elhassanny, Ahmed E. M.; Planchin, Emilie E.; Roux, Christelle M.; Weeks-Gorospe, Jenni N.; Ficht, Thomas A.; Dunman, Paul M.

2013-01-01

The Ros-type regulator MucR is one of the few transcriptional regulators that have been linked to virulence in Brucella. Here, we show that a Brucella abortus in-frame mucR deletion strain exhibits a pronounced growth defect during in vitro cultivation and, more importantly, that the mucR mutant is attenuated in cultured macrophages and in mice. The genetic basis for the attenuation of Brucella mucR mutants has not been defined previously, but in the present study the genes regulated by MucR in B. abortus have been elucidated using microarray analysis and real-time reverse transcription-PCR (RT-PCR). In B. abortus 2308, MucR regulates a wide variety of genes whose products may function in establishing and maintaining cell envelope integrity, polysaccharide biosynthesis, iron homeostasis, genome plasticity, and transcriptional regulation. Particularly notable among the MucR-regulated genes identified is arsR6 (nolR), which encodes a transcriptional regulator previously linked to virulence in Brucella melitensis 16 M. Importantly, electrophoretic mobility shift assays (EMSAs) determined that a recombinant MucR protein binds directly to the promoter regions of several genes repressed by MucR (including arsR6 [nolR]), and in Brucella, as in other alphaproteobacteria, MucR binds to its own promoter to repress expression of the gene that encodes it. Overall, these studies have uncovered the diverse genetic regulon of MucR in Brucella, and in doing so this work has begun to define the MucR-controlled genetic circuitry whose misregulation contributes to the virulence defect of Brucella mucR mutants. PMID:23319565

Whole-genome sequencing of Atacama skeleton shows novel mutations linked with dysplasia.

PubMed

Bhattacharya, Sanchita; Li, Jian; Sockell, Alexandra; Kan, Matthew J; Bava, Felice A; Chen, Shann-Ching; Ávila-Arcos, María C; Ji, Xuhuai; Smith, Emery; Asadi, Narges B; Lachman, Ralph S; Lam, Hugo Y K; Bustamante, Carlos D; Butte, Atul J; Nolan, Garry P

2018-04-01

Over a decade ago, the Atacama humanoid skeleton (Ata) was discovered in the Atacama region of Chile. The Ata specimen carried a strange phenotype-6-in stature, fewer than expected ribs, elongated cranium, and accelerated bone age-leading to speculation that this was a preserved nonhuman primate, human fetus harboring genetic mutations, or even an extraterrestrial. We previously reported that it was human by DNA analysis with an estimated bone age of about 6-8 yr at the time of demise. To determine the possible genetic drivers of the observed morphology, DNA from the specimen was subjected to whole-genome sequencing using the Illumina HiSeq platform with an average 11.5× coverage of 101-bp, paired-end reads. In total, 3,356,569 single nucleotide variations (SNVs) were found as compared to the human reference genome, 518,365 insertions and deletions (indels), and 1047 structural variations (SVs) were detected. Here, we present the detailed whole-genome analysis showing that Ata is a female of human origin, likely of Chilean descent, and its genome harbors mutations in genes ( COL1A1 , COL2A1 , KMT2D , FLNB , ATR , TRIP11 , PCNT ) previously linked with diseases of small stature, rib anomalies, cranial malformations, premature joint fusion, and osteochondrodysplasia (also known as skeletal dysplasia). Together, these findings provide a molecular characterization of Ata's peculiar phenotype, which likely results from multiple known and novel putative gene mutations affecting bone development and ossification. © 2018 Bhattacharya et al.; Published by Cold Spring Harbor Laboratory Press.

Double Dissociation in the Anatomy of Socioemotional Disinhibition and Executive Functioning in Dementia

PubMed Central

Krueger, Casey E.; Laluz, Victor; Rosen, Howard J.; Neuhaus, John M.; Miller, Bruce L.; Kramer, Joel H.

2010-01-01

Objective To determine if socioemotional disinhibition and executive dysfunction are related to dissociable patterns of brain atrophy in neurodegenerative disease. Previous studies have indicated that behavioral and cognitive dysfunction in neurodegenerative disease are linked to atrophy in different parts of the frontal lobe, but these prior studies did not establish that these relationships were specific, which would best be demonstrated by a double dissociation. Method Subjects included 157 patients with neurodegenerative disease. A semi-automated parcellation program (Freesurfer) was used to generate regional cortical volumes from structural MRI scans. Regions of interest (ROIs) included anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), middle frontal gyrus (MFG) and inferior frontal gyrus (IFG). Socioemotional disinhibition was measured using the Neuropsychiatric Inventory. Principal component analysis including three tasks of executive function (EF; verbal fluency, Stroop Interference, modified Trails) was used to generate a single factor score to represent EF. Results Partial correlations between ROIs, disinhibition, and EF were computed after controlling for total intracranial volume, MMSE, diagnosis, age, and education. Brain regions significantly correlated with disinhibition (ACC, OFC, IFG, and temporal lobes) and EF (MFG) were entered into separate hierarchical regressions to determine which brain regions predicted disinhibition and EF. OFC was the only brain region to significantly predict disinhibition and MFG significantly predicted executive functioning performance. A multivariate general linear model demonstrated a significant interaction between ROIs and cognitive-behavioral functions. Conclusions These results support a specific association between orbitofrontal areas and behavioral management as compared to dorsolateral areas and EF. PMID:21381829

Heads, Shoulders, Elbows, Knees, and Toes: Modular Gdf5 Enhancers Control Different Joints in the Vertebrate Skeleton

PubMed Central

Schoor, Michael; Mortlock, Doug P.; Reddi, A. Hari; Kingsley, David M.

2016-01-01

Synovial joints are crucial for support and locomotion in vertebrates, and are the frequent site of serious skeletal defects and degenerative diseases in humans. Growth and differentiation factor 5 (Gdf5) is one of the earliest markers of joint formation, is required for normal joint development in both mice and humans, and has been genetically linked to risk of common osteoarthritis in Eurasian populations. Here, we systematically survey the mouse Gdf5 gene for regulatory elements controlling expression in synovial joints. We identify separate regions of the locus that control expression in axial tissues, in proximal versus distal joints in the limbs, and in remarkably specific sub-sets of composite joints like the elbow. Predicted transcription factor binding sites within Gdf5 regulatory enhancers are required for expression in particular joints. The multiple enhancers that control Gdf5 expression in different joints are distributed over a hundred kilobases of DNA, including regions both upstream and downstream of Gdf5 coding exons. Functional rescue tests in mice confirm that the large flanking regions are required to restore normal joint formation and patterning. Orthologs of these enhancers are located throughout the large genomic region previously associated with common osteoarthritis risk in humans. The large array of modular enhancers for Gdf5 provide a new foundation for studying the spatial specificity of joint patterning in vertebrates, as well as new candidates for regulatory regions that may also influence osteoarthritis risk in human populations. PMID:27902701

Tandem repeats of the 5' non-transcribed spacer of Tetrahymena rDNA function as high copy number autonomous replicons in the macronucleus but do not prevent rRNA gene dosage regulation.

PubMed Central

Pan, W J; Blackburn, E H

1995-01-01

The rRNA genes in the somatic macronucleus of Tetrahymena thermophila are normally on 21 kb linear palindromic molecules (rDNA). We examined the effect on rRNA gene dosage of transforming T.thermophila macronuclei with plasmid constructs containing a pair of tandemly repeated rDNA replication origin regions unlinked to the rRNA gene. A significant proportion of the plasmid sequences were maintained as high copy circular molecules, eventually consisting solely of tandem arrays of origin regions. As reported previously for cells transformed by a construct in which the same tandem rDNA origins were linked to the rRNA gene [Yu, G.-L. and Blackburn, E. H. (1990) Mol. Cell. Biol., 10, 2070-2080], origin sequences recombined to form linear molecules bearing several tandem repeats of the origin region, as well as rRNA genes. The total number of rDNA origin sequences eventually exceeded rRNA gene copies by approximately 20- to 40-fold and the number of circular replicons carrying only rDNA origin sequences exceeded rRNA gene copies by 2- to 3-fold. However, the rRNA gene dosage was unchanged. Hence, simply monitoring the total number of rDNA origin regions is not sufficient to regulate rRNA gene copy number. Images PMID:7784211

Nuclease footprint analyses of the interactions between RNase P ribozyme and a model mRNA substrate.

PubMed Central

Trang, P; Hsu, A W; Liu, F

1999-01-01

RNase P ribozyme cleaves an RNA helix substrate which resembles the acceptor stem and T-stem structures of its natural tRNA substrate. By linking the ribozyme covalently to a sequence (guide sequence) complementary to a target RNA, the catalytic RNA can be converted into a sequence-specific ribozyme, M1GS RNA. We have previously shown that M1GS RNA can efficiently cleave the mRNA sequence encoding thymidine kinase (TK) of herpes simplex virus 1. In this study, a footprint procedure using different nucleases was carried out to map the regions of a M1GS ribozyme that potentially interact with the TK mRNA substrate. The ribozyme regions that are protected from nuclease degradation in the presence of the TK mRNA substrate include those that interact with the acceptor stem and T-stem, the 3' terminal CCA sequence and the cleavage site of a tRNA substrate. However, some of the protected regions (e.g. P13 and P14) are unique and not among those protected in the presence of a tRNA substrate. Identification of the regions that interact with a mRNA substrate will allow us to study how M1GS RNA recognizes a mRNA substrate and facilitate the development of mRNA-cleaving ribozymes for gene-targeting applications. PMID:10556315

Neural correlates of word production stages delineated by parametric modulation of psycholinguistic variables.

PubMed

Wilson, Stephen M; Isenberg, Anna Lisette; Hickok, Gregory

2009-11-01

Word production is a complex multistage process linking conceptual representations, lexical entries, phonological forms and articulation. Previous studies have revealed a network of predominantly left-lateralized brain regions supporting this process, but many details regarding the precise functions of different nodes in this network remain unclear. To better delineate the functions of regions involved in word production, we used event-related functional magnetic resonance imaging (fMRI) to identify brain areas where blood oxygen level-dependent (BOLD) responses to overt picture naming were modulated by three psycholinguistic variables: concept familiarity, word frequency, and word length, and one behavioral variable: reaction time. Each of these variables has been suggested by prior studies to be associated with different aspects of word production. Processing of less familiar concepts was associated with greater BOLD responses in bilateral occipitotemporal regions, reflecting visual processing and conceptual preparation. Lower frequency words produced greater BOLD signal in left inferior temporal cortex and the left temporoparietal junction, suggesting involvement of these regions in lexical selection and retrieval and encoding of phonological codes. Word length was positively correlated with signal intensity in Heschl's gyrus bilaterally, extending into the mid-superior temporal gyrus (STG) and sulcus (STS) in the left hemisphere. The left mid-STS site was also modulated by reaction time, suggesting a role in the storage of lexical phonological codes.

Growth Decline Linked to Warming-Induced Water Limitation in Hemi-Boreal Forests

PubMed Central

Wu, Xiuchen; Liu, Hongyan; Guo, Dali; Anenkhonov, Oleg A.; Badmaeva, Natalya K.; Sandanov, Denis V.

2012-01-01

Hemi-boreal forests, which make up the transition from temperate deciduous forests to boreal forests in southern Siberia, have experienced significant warming without any accompanying increase in precipitation during the last 80 years. This climatic change could have a profound impact on tree growth and on the stability of forest ecosystems in this region, but at present evidence for these impacts is lacking. In this study, we report a recent dramatic decline in the growth of hemi-boreal forests, based on ring width measurements from three dominant tree-species (Pinus sylvestris, Larix sibirica and Larix gmelinii), sampled from eight sites in the region. We found that regional tree growth has become increasingly limited by low soil water content in the pre- and early-growing season (from October of the previous year to July of the current year) over the past 80 years. A warming-induced reduction in soil water content has also increased the climate sensitivity of these three tree species. Beginning in the mid-1980s, a clear decline in growth is evident for both the pine forests and the larch forests, although there are increasing trends in the proxy of soil water use efficiencies. Our findings are consistent with those from other parts of the world and provide valuable insights into the regional carbon cycle and vegetation dynamics, and should be useful for devising adaptive forest management strategies. PMID:22916142

Mapping of a binding site for ATP within the extracellular region of the Torpedo nicotinic acetylcholine receptor beta-subunit.

PubMed

Schrattenholz, A; Roth, U; Godovac-Zimmermann, J; Maelicke, A

1997-10-28

Using 2,8,5'-[3H]ATP as a direct photoaffinity label for membrane-bound nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata, we have identified a binding site for ATP in the extracellular region of the beta-subunit of the receptor. Photolabeling was completely inhibited in the presence of saturating concentrations of nonradioactive ATP, whereas neither the purinoreceptor antagonists suramin, theophyllin, and caffeine nor the nAChR antagonists alpha-bungarotoxin and d-tubocurarine affected the labeling reaction. Competitive and noncompetitive nicotinic agonists and Ca2+ increased the yield of the photoreaction by up to 50%, suggesting that the respective binding sites are allosterically linked with the ATP site. The dissociation constant KD of binding of ATP to the identified site on the nAChR was of the order of 10(-4) M. Sites of labeling were found in the sequence regions Leu11-Pro17 and Asp152-His163 of the nAChR beta-subunit. These regions may represent parts of a single binding site for ATP, which is discontinuously distributed within the primary structure of the N-terminal extracellular domain. The existence of an extracellular binding site for ATP confirms, on the molecular level, that this nucleotide can directly act on nicotinic receptors, as has been suggested from previous electrophysiological and biochemical studies.

Growth decline linked to warming-induced water limitation in hemi-boreal forests.

PubMed

Wu, Xiuchen; Liu, Hongyan; Guo, Dali; Anenkhonov, Oleg A; Badmaeva, Natalya K; Sandanov, Denis V

2012-01-01

Hemi-boreal forests, which make up the transition from temperate deciduous forests to boreal forests in southern Siberia, have experienced significant warming without any accompanying increase in precipitation during the last 80 years. This climatic change could have a profound impact on tree growth and on the stability of forest ecosystems in this region, but at present evidence for these impacts is lacking. In this study, we report a recent dramatic decline in the growth of hemi-boreal forests, based on ring width measurements from three dominant tree-species (Pinus sylvestris, Larix sibirica and Larix gmelinii), sampled from eight sites in the region. We found that regional tree growth has become increasingly limited by low soil water content in the pre- and early-growing season (from October of the previous year to July of the current year) over the past 80 years. A warming-induced reduction in soil water content has also increased the climate sensitivity of these three tree species. Beginning in the mid-1980s, a clear decline in growth is evident for both the pine forests and the larch forests, although there are increasing trends in the proxy of soil water use efficiencies. Our findings are consistent with those from other parts of the world and provide valuable insights into the regional carbon cycle and vegetation dynamics, and should be useful for devising adaptive forest management strategies.

Fine Mapping for Identification of Citrus Alternaria Brown Spot Candidate Resistance Genes and Development of New SNP Markers for Marker-Assisted Selection

PubMed Central

Cuenca, Jose; Aleza, Pablo; Garcia-Lor, Andres; Ollitrault, Patrick; Navarro, Luis

2016-01-01

Alternaria brown spot (ABS) is a serious disease affecting susceptible citrus genotypes, which is a strong concern regarding citrus breeding programs. Resistance is conferred by a recessive locus (ABSr) previously located by our group within a 3.3 Mb genome region near the centromere in chromosome III. This work addresses fine-linkage mapping of this region for identifying candidate resistance genes and develops new molecular markers for ABS-resistance effective marker-assisted selection (MAS). Markers closely linked to ABSr locus were used for fine mapping using a 268-segregating diploid progeny derived from a heterozygous susceptible × resistant cross. Fine mapping limited the genomic region containing the ABSr resistance gene to 366 kb, flanked by markers at 0.4 and 0.7 cM. This region contains nine genes related to pathogen resistance. Among them, eight are resistance (R) gene homologs, with two of them harboring a serine/threonine protein kinase domain. These two genes along with a gene encoding a S-adenosyl-L-methionine-dependent-methyltransferase protein, should be considered as strong candidates for ABS-resistance. Moreover, the closest SNP was genotyped in 40 citrus varieties, revealing very high association with the resistant/susceptible phenotype. This new marker is currently used in our citrus breeding program for ABS-resistant parent and cultivar selection, at diploid, triploid and tetraploid level. PMID:28066498

Surface Diversity in Mycoplasma agalactiae Is Driven by Site-Specific DNA Inversions within the vpma Multigene Locus

PubMed Central

Glew, Michelle D.; Marenda, Marc; Rosengarten, Renate; Citti, Christine

2002-01-01

The ruminant pathogen Mycoplasma agalactiae possesses a family of abundantly expressed variable surface lipoproteins called Vpmas. Phenotypic switches between Vpma members have previously been correlated with DNA rearrangements within a locus of vpma genes and are proposed to play an important role in disease pathogenesis. In this study, six vpma genes were characterized in the M. agalactiae type strain PG2. All vpma genes clustered within an 8-kb region and shared highly conserved 5′ untranslated regions, lipoprotein signal sequences, and short N-terminal sequences. Analyses of the vpma loci from consecutive clonal isolates showed that vpma DNA rearrangements were site specific and that cleavage and strand exchange occurred within a minimal region of 21 bp located within the 5′ untranslated region of all vpma genes. This process controlled expression of vpma genes by effectively linking the open reading frame (ORF) of a silent gene to a unique active promoter sequence within the locus. An ORF (xer1) immediately adjacent to one end of the vpma locus did not undergo rearrangement and had significant homology to a distinct subset of genes belonging to the λ integrase family of site-specific xer recombinases. It is proposed that xer1 codes for a site-specific recombinase that is not involved in chromosome dimer resolution but rather is responsible for the observed vpma-specific recombination in M. agalactiae. PMID:12374833

New COL6A6 variant detected by whole-exome sequencing is linked to break points in intron 4 and 3′-UTR, deleting exon 5 of RHO, and causing adRP

PubMed Central

de Sousa Dias, Miguel; Hernan, Imma; Delás, Barbara; Pascual, Beatriz; Borràs, Emma; Gamundi, Maria José; Mañé, Begoña; Fernández-San José, Patricia; Ayuso, Carmen

2015-01-01

Purpose This study aimed to test a newly devised cost-effective multiplex PCR assay for the molecular diagnosis of autosomal dominant retinitis pigmentosa (adRP), as well as the use of whole-exome sequencing (WES) to detect disease-causing mutations in adRP. Methods Genomic DNA was extracted from peripheral blood lymphocytes of index patients with adRP and their affected and unaffected family members. We used a newly devised multiplex PCR assay capable of amplifying the genetic loci of RHO, PRPH2, RP1, PRPF3, PRPF8, PRPF31, IMPDH1, NRL, CRX, KLHL7, and NR2E3 to molecularly diagnose 18 index patients with adRP. We also performed WES in affected and unaffected members of four families with adRP in whom a disease-causing mutation was previously not found. Results We identified five previously reported mutations (p.Arg677X in the RP1 gene, p.Asp133Val and p.Arg195Leu in the PRPH2 gene, and p.Pro171Leu and p.Pro215Leu in the RHO gene) and one novel mutation (p.Val345Gly in the RHO gene) representing 33% detection of causative mutations in our adRP cohort. Comparative WES analysis showed a new variant (p.Gly103Arg in the COL6A6 gene) that segregated with the disease in one family with adRP. As this variant was linked with the RHO locus, we sequenced the complete RHO gene, which revealed a deletion in intron 4 that encompassed all of exon 5 and 28 bp of the 3′-untranslated region (UTR). Conclusions The novel multiplex PCR assay with next-generation sequencing (NGS) proved effective for detecting most of the adRP-causing mutations. A WES approach led to identification of a deletion in RHO through detection of a new linked variant in COL6A6. No pathogenic variants were identified in the remaining three families. Moreover, NGS and WES were inefficient for detecting the complete deletion of exon 5 in the RHO gene in one family with adRP. Carriers of this deletion showed variable clinical status, and two of these carriers had not previously been diagnosed with RP. PMID:26321861

40 CFR 1.27 - Offices of the Associate Administrators.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Agency decision-making processes, assessing the impact of Headquarters actions on Regional operations... Regional Operations. The Office of Regional Operations, under the supervision of an Associate Administrator... communications link between the Administrator/Deputy Administrator and the Regional Administrators. It provides a...

MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain

PubMed Central

Somel, Mehmet; Guo, Song; Fu, Ning; Yan, Zheng; Hu, Hai Yang; Xu, Ying; Yuan, Yuan; Ning, Zhibin; Hu, Yuhui; Menzel, Corinna; Hu, Hao; Lachmann, Michael; Zeng, Rong; Chen, Wei; Khaitovich, Philipp

2010-01-01

Changes in gene expression levels determine differentiation of tissues involved in development and are associated with functional decline in aging. Although development is tightly regulated, the transition between development and aging, as well as regulation of post-developmental changes, are not well understood. Here, we measured messenger RNA (mRNA), microRNA (miRNA), and protein expression in the prefrontal cortex of humans and rhesus macaques over the species' life spans. We find that few gene expression changes are unique to aging. Instead, the vast majority of miRNA and gene expression changes that occur in aging represent reversals or extensions of developmental patterns. Surprisingly, many gene expression changes previously attributed to aging, such as down-regulation of neural genes, initiate in early childhood. Our results indicate that miRNA and transcription factors regulate not only developmental but also post-developmental expression changes, with a number of regulatory processes continuing throughout the entire life span. Differential evolutionary conservation of the corresponding genomic regions implies that these regulatory processes, although beneficial in development, might be detrimental in aging. These results suggest a direct link between developmental regulation and expression changes taking place in aging. PMID:20647238

Characterization of an estrogen-responsive element implicated in regulation of the rainbow trout estrogen receptor gene.

PubMed

Le Dréan, Y; Lazennec, G; Kern, L; Saligaut, D; Pakdel, F; Valotaire, Y

1995-08-01

We previously reported that the expression of the rainbow trout estrogen receptor (rtER) gene is markedly increased by estradiol (E2). In this paper, we have used transient transfection assays with reporter plasmids expressing chloramphenicol acetyl transferase (CAT), linked to 5' flanking regions of the rtER gene promoter, to identify cis-elements responsible for E2 inducibility. Deletion analysis localized an estrogen-responsive element (ERE), at position +242, with one mutation on the first base compared with the consensus sequence. This element confers estrogen responsiveness to CAT reporter linked to both the herpes simplex virus thymidine kinase promoter and the homologous rtER promoter. Moreover, using a 0.2 kb fragment of the rtER promoter encompassing the ERE and the rtER DNA binding domain obtained from a bacterial expression system, DNase I footprinting experiments demonstrated a specific protection covering 20 bp (+240/+260) containing the ERE sequence. Based on these studies, we believe that this ERE sequence, identified in the rtER gene promoter, may be a major cis-acting element involved in the regulation of the gene by estrogen.

Structures of asparagine-linked oligosaccharides from hen egg-yolk antibody (IgY). Occurrence of unusual glucosylated oligo-mannose type oligosaccharides in a mature glycoprotein.

PubMed

Ohta, M; Hamako, J; Yamamoto, S; Hatta, H; Kim, M; Yamamoto, T; Oka, S; Mizuochi, T; Matsuura, F

1991-10-01

Asparagine-linked oligosaccharides present on hen egg-yolk immunoglobulin, termed IgY, were liberated from the protein by hydrazinolysis. After N-acetylation, the oligosaccharides were labelled with a UV-absorbing compound, p-aminobenzoic acid ethyl ester (ABEE). The ABEE-derivatized oligosaccharides were fractionated by anion exchange, normal phase and reversed phase HPLC, and their structures were determined by a combination of sugar composition analysis, methylation analysis, negative ion FAB-MS, 500 MHz 1H-NMR and sequential exoglycosidase digestions. IgY contained monoglucosylated oligomannose type oligosaccharides with structures of Glc alpha 1-3Man7-9-GlcNAc-GlcNAc, oligomannose type oligosaccharides with the size range of Man5-9GlcNAc-GlcNAc, and biantennary complex type oligosaccharides with core region structure of Man alpha 1-6(+/- GlcNAc beta 1-4)(Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(+/- Fuc alpha 1-6)GlcNAc. The glucosylated oligosaccharides, Glc1Man8GlcNAc2 and Glc1Man7GlcNAc2, have not previously been reported in mature glycoproteins from any source.

Differential investment in visual and olfactory brain areas reflects behavioural choices in hawk moths

PubMed Central

Stöckl, Anna; Heinze, Stanley; Charalabidis, Alice; el Jundi, Basil; Warrant, Eric; Kelber, Almut

2016-01-01

Nervous tissue is one of the most metabolically expensive animal tissues, thus evolutionary investments that result in enlarged brain regions should also result in improved behavioural performance. Indeed, large-scale comparative studies in vertebrates and invertebrates have successfully linked differences in brain anatomy to differences in ecology and behaviour, but their precision can be limited by the detail of the anatomical measurements, or by only measuring behaviour indirectly. Therefore, detailed case studies are valuable complements to these investigations, and have provided important evidence linking brain structure to function in a range of higher-order behavioural traits, such as foraging experience or aggressive behaviour. Here, we show that differences in the size of both lower and higher-order sensory brain areas reflect differences in the relative importance of these senses in the foraging choices of hawk moths, as suggested by previous anatomical work in Lepidopterans. To this end we combined anatomical and behavioural quantifications of the relative importance of vision and olfaction in two closely related hawk moth species. We conclude that differences in sensory brain volume in these hawk moths can indeed be interpreted as differences in the importance of these senses for the animal’s behaviour. PMID:27185464

Function and structure in social brain regions can link oxytocin-receptor genes with autistic social behavior.

PubMed

Yamasue, Hidenori

2013-02-01

Difficulties in appropriate social and communicative behaviors are the most prevalent and core symptoms of autism spectrum disorders (ASDs). Although recent intensive research has focused on the neurobiological background of these difficulties, many aspects of them were not yet elucidated. Recent studies have employed multimodal magnetic resonance imaging (MRI) indices as intermediate phenotypes of this behavioral phenotype to link candidate genes with the autistic social difficulty. As MRI indices, functional MRI (fMRI), structural MRI, and MR-spectroscopy have been examined in subjects with autism spectrum disorders. As candidate genes, this mini-review has much interest in oxytocin-receptor genes (OXTR), since recent studies have repeatedly reported their associations with normal variations in social cognition and behavior as well as with their extremes, autistic social dysfunction. Through previous increasing studies, medial prefrontal cortex, hypothalamus and amygdala have repeatedly been revealed as neural correlates of autistic social behavior by MRI multimodalities and their relationship to OXTR. For further development of this research area, this mini-review integrates recent accumulating evidence about human behavioral and neural correlates of OXTR. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation

PubMed Central

Madrigal, I; Rodríguez-Revenga, L; Armengol, L; González, E; Rodriguez, B; Badenas, C; Sánchez, A; Martínez, F; Guitart, M; Fernández, I; Arranz, JA; Tejada, MI; Pérez-Jurado, LA; Estivill, X; Milà, M

2007-01-01

Background Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects. Results Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%). Conclusion This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients. PMID:18047645

Linkage and association analysis of ADHD endophenotypes in extended and multigenerational pedigrees from a genetic isolate

PubMed Central

Mastronardi, C A; Pillai, E; Pineda, D A; Martinez, A F; Lopera, F; Velez, J I; Palacio, J D; Patel, H; Easteal, S; Acosta, M T; Castellanos, F X; Muenke, M; Arcos-Burgos, M

2016-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a heritable, chronic, neurodevelopmental disorder with serious long-term repercussions. Despite being one of the most common cognitive disorders, the clinical diagnosis of ADHD is based on subjective assessments of perceived behaviors. Endophenotypes (neurobiological markers that cosegregate and are associated with an illness) are thought to provide a more powerful and objective framework for revealing the underlying neurobiology than syndromic psychiatric classification. Here, we present the results of applying genetic linkage and association analyses to neuropsychological endophenotypes using microsatellite and single nucleotide polymorphisms. We found several new genetic regions linked and/or associated with these endophenotypes, and others previously associated to ADHD, for example, loci harbored in the LPHN3, FGF1, POLR2A, CHRNA4 and ANKFY1 genes. These findings, when compared with those linked and/or associated to ADHD, suggest that these endophenotypes lie on shared pathways. The genetic information provided by this study offers a novel and complementary method of assessing the genetic causes underpinning the susceptibility to behavioral conditions and may offer new insights on the neurobiology of the disorder. PMID:26598068

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

PubMed

Savage, Jeanne E; Jansen, Philip R; Stringer, Sven; Watanabe, Kyoko; Bryois, Julien; de Leeuw, Christiaan A; Nagel, Mats; Awasthi, Swapnil; Barr, Peter B; Coleman, Jonathan R I; Grasby, Katrina L; Hammerschlag, Anke R; Kaminski, Jakob A; Karlsson, Robert; Krapohl, Eva; Lam, Max; Nygaard, Marianne; Reynolds, Chandra A; Trampush, Joey W; Young, Hannah; Zabaneh, Delilah; Hägg, Sara; Hansell, Narelle K; Karlsson, Ida K; Linnarsson, Sten; Montgomery, Grant W; Muñoz-Manchado, Ana B; Quinlan, Erin B; Schumann, Gunter; Skene, Nathan G; Webb, Bradley T; White, Tonya; Arking, Dan E; Avramopoulos, Dimitrios; Bilder, Robert M; Bitsios, Panos; Burdick, Katherine E; Cannon, Tyrone D; Chiba-Falek, Ornit; Christoforou, Andrea; Cirulli, Elizabeth T; Congdon, Eliza; Corvin, Aiden; Davies, Gail; Deary, Ian J; DeRosse, Pamela; Dickinson, Dwight; Djurovic, Srdjan; Donohoe, Gary; Conley, Emily Drabant; Eriksson, Johan G; Espeseth, Thomas; Freimer, Nelson A; Giakoumaki, Stella; Giegling, Ina; Gill, Michael; Glahn, David C; Hariri, Ahmad R; Hatzimanolis, Alex; Keller, Matthew C; Knowles, Emma; Koltai, Deborah; Konte, Bettina; Lahti, Jari; Le Hellard, Stephanie; Lencz, Todd; Liewald, David C; London, Edythe; Lundervold, Astri J; Malhotra, Anil K; Melle, Ingrid; Morris, Derek; Need, Anna C; Ollier, William; Palotie, Aarno; Payton, Antony; Pendleton, Neil; Poldrack, Russell A; Räikkönen, Katri; Reinvang, Ivar; Roussos, Panos; Rujescu, Dan; Sabb, Fred W; Scult, Matthew A; Smeland, Olav B; Smyrnis, Nikolaos; Starr, John M; Steen, Vidar M; Stefanis, Nikos C; Straub, Richard E; Sundet, Kjetil; Tiemeier, Henning; Voineskos, Aristotle N; Weinberger, Daniel R; Widen, Elisabeth; Yu, Jin; Abecasis, Goncalo; Andreassen, Ole A; Breen, Gerome; Christiansen, Lene; Debrabant, Birgit; Dick, Danielle M; Heinz, Andreas; Hjerling-Leffler, Jens; Ikram, M Arfan; Kendler, Kenneth S; Martin, Nicholas G; Medland, Sarah E; Pedersen, Nancy L; Plomin, Robert; Polderman, Tinca J C; Ripke, Stephan; van der Sluis, Sophie; Sullivan, Patrick F; Vrieze, Scott I; Wright, Margaret J; Posthuma, Danielle

2018-06-25

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7 , but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.

Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells.

PubMed

Bullwinkel, Jörn; Baron-Lühr, Bettina; Lüdemann, Anja; Wohlenberg, Claudia; Gerdes, Johannes; Scholzen, Thomas

2006-03-01

The nuclear Ki-67 protein (pKi-67) has previously been shown to be exclusively expressed in proliferating cells. As a result, antibodies against this protein are widely used as prognostic tools in cancer diagnostics. Here we show, that despite the strong downregulation of pKi-67 expression in non-proliferating cells, the protein can nevertheless be detected at sites linked to ribosomal RNA (rRNA) synthesis. Although this finding does not argue against the use of pKi-67 as a proliferation marker, it has wide ranging implications for the elucidation of pKi-67 function. Employing the novel antibody TuBB-9, we could further demonstrate that also in proliferating cells, a fraction of pKi-67 is found at sites linked to the rRNA transcription machinery during interphase and mitosis. Moreover, chromatin immunoprecipitation (ChIP) assays provided evidence for a physical association of pKi-67 with chromatin of the promoter and transcribed region of the rRNA gene cluster. These data strongly suggest a role for pKi-67 in the early steps of rRNA synthesis. Copyright 2005 Wiley-Liss, Inc.

The Vulcan Project: Recent advances and emissions estimation for the NACP mid-continent intensive campaign region

NASA Astrophysics Data System (ADS)

Gurney, K. R.; Zhou, Y.; Geethakumar, S.; Godbole, A.; Mendoza, D. L.; Vaidhyanathan, M.; Sahni, N.

2009-12-01

The Vulcan Project has quantified 2002 fossil fuel CO2 for the US at the sub-county/hourly scale and is a key component of attributing CO2 fluxes within the North American Carbon Program. Vulcan approached quantification of CO2 emissions by leveraging information already contained within regulatory and monitoring agencies including the US EPA’s Acid Rain Program, the EPA’s National Emissions Inventory for the assessment of nationally regulated air pollution, the Department of Energy, the U.S. Census and the Department of Transportation. By utilizing the inventory emissions of carbon monoxide combined with fuel/device-specific emission factors, we have calculated CO2 emissions for industrial point sources, power plants, mobile sources, residential and commercial sectors with information on fuel used and source classification information. In this presentation, I provide critical recent advances in the Vulcan Project with particular emphasis on our contribution to the NACP mid-continent intensive campaign. Version 1.2 of the Vulcan fossil fuel CO2 emissions inventory includes the 2008 US Census road atlas, overcoming many of the missing roads and links that were prevalent in previous road atlas releases. This offers better spatial allocation of the onroad emissions. Figure 1 shows the improved road layer density for the MCI study region. Furthermore the temporal dimension of onroad emissions have been improved through the use of hourly traffic monitoring data at roughly 6000 monitoring locations across the US. The residential and commercial sector emissions now have hourly time structure via a spatially explicit heating degree day calculation utilizing the North American Regional Reanalysis temperature output. Finally, we have generated a multiyear (1997-2008) data product for the MCI region through use of Energy Information Administration state-level fuel sales data. Figure 1. improved road density via utilization of the new 2008 US census road layer. Left: previous Vulcan release road density; Right: latest Vulcan release road density

A previously unreported, dominantly inherited syndrome of shortness of stature, ear malformations, and hip dislocation: the coxoauricular syndrome--autosomal or X-linked male-lethal.

PubMed

Duca, D; Pană, I; Ciovirnache, M; Simionesu, L; Ispas, I; Maxililian, C

1981-01-01

We reported an apparently previously undescribed syndrome, designated the coxoauricular syndrome, in a mother and her 3 daughters, all of whom shared in variable manner shortness of stature, minor vertebral and pelvic changes, dislocated hip(s), and microtia with corresponding hearing loss. The oldest daughter had coincidental Ullrich-Turner syndrome with 46, Xdel(X)(q 13) chromosome constitution. Inheritance of the trait in this family is dominant, either autosomal or X-linked, with hemizygote lethality.

Effect of carbon nanotube dispersion on glass transition in cross-linked epoxy-carbon nanotube nanocomposites: role of interfacial interactions.

PubMed

Khare, Ketan S; Khare, Rajesh

2013-06-20

We have used atomistic molecular simulations to study the effect of nanofiller dispersion on the glass transition behavior of cross-linked epoxy-carbon nanotube (CNT) nanocomposites. Specific chemical interactions at the interface of CNTs and cross-linked epoxy create an interphase region, whose impact on the properties of their nanocomposites increases with an increasing extent of dispersion. To investigate this aspect, we have compared the volumetric, structural, and dynamical properties of three systems: neat cross-linked epoxy, cross-linked epoxy nanocomposite containing dispersed CNTs, and cross-linked epoxy nanocomposite containing aggregated CNTs. We find that the nanocomposite containing dispersed CNTs shows a depression in the glass transition temperature (Tg) by ~66 K as compared to the neat cross-linked epoxy, whereas such a large depression is absent in the nanocomposite containing aggregated CNTs. Our results suggest that the poor interfacial interactions between the CNTs and the cross-linked epoxy matrix lead to a more compressible interphase region between the CNTs and the bulk matrix. An analysis of the resulting dynamic heterogeneity shows that the probability of percolation of immobile domains becomes unity near the Tg calculated from volumetric properties. Our observations also lend support to the conceptual analogy between polymer nanocomposites and the nanoconfinement of polymer thin films.

Four novel RS1 gene mutations in Polish patients with X-linked juvenile retinoschisis.

PubMed

Skorczyk, Anna; Krawczyński, Maciej R

2012-01-01

To determine the clinical features and to identify mutations in the retinoschisis gene (RS1) in ten patients with X-linked retinoschisis (XLRS). Ten male patients from nine Polish families were included in this study. Ophthalmologic examinations, including optical coherence tomography (OCT) and full-field electroretinography (ERG), were performed in all affected boys. The entire coding region encompassing six exons of the RS1 gene was amplified with PCR and directly sequenced in all the patients. All affected individuals showed typical retinoschisis signs and symptoms, and all appeared to have a mutation in the RS1 gene. Seven different mutations were identified, including two novel missense substitutions: c.176G>C (p.Cys59Ser), c.451T>A (p.Tyr151Asp); one novel nonsense substitution: c.218C>A (p.Ser73*); and one novel frameshift mutation: c.354_355delCA (p.Asp118Glufs*2). We also found two missense substitutions that had been previously described: c.214G>A (p.Glu72Lys) and c.626G>T (p.Arg209Leu) and one known splice site mutation in intron 5: c.522+1G>T (IVS5+1G>T). This study provides the first molecular genetic characteristics of patients with juvenile retinoschisis from the previously unexplored Polish population. We investigated the molecular background of XLRS in ten boys. The present study reports for the first time four novel mutations, including two missense substitutions, one nonsense substitution, and one frameshift deletion. One of these substitutions and 2-bp deletion created stop codons. Moreover, we described three substitutions that had been previously reported (one is a splicing mutation). Further genetic characterization of Polish patients with XLRS will be helpful in understanding the worldwide spectrum of RS1 mutations. Despite the mutation heterogeneity found in a small group of our patients, they presented a relatively uniform clinical picture. Identifying the causative mutation is helpful in confirming diagnosis and counseling, but cannot provide prognostic data.

Variability in results from negative binomial models for Lyme disease measured at different spatial scales.

PubMed

Tran, Phoebe; Waller, Lance

2015-01-01

Lyme disease has been the subject of many studies due to increasing incidence rates year after year and the severe complications that can arise in later stages of the disease. Negative binomial models have been used to model Lyme disease in the past with some success. However, there has been little focus on the reliability and consistency of these models when they are used to study Lyme disease at multiple spatial scales. This study seeks to explore how sensitive/consistent negative binomial models are when they are used to study Lyme disease at different spatial scales (at the regional and sub-regional levels). The study area includes the thirteen states in the Northeastern United States with the highest Lyme disease incidence during the 2002-2006 period. Lyme disease incidence at county level for the period of 2002-2006 was linked with several previously identified key landscape and climatic variables in a negative binomial regression model for the Northeastern region and two smaller sub-regions (the New England sub-region and the Mid-Atlantic sub-region). This study found that negative binomial models, indeed, were sensitive/inconsistent when used at different spatial scales. We discuss various plausible explanations for such behavior of negative binomial models. Further investigation of the inconsistency and sensitivity of negative binomial models when used at different spatial scales is important for not only future Lyme disease studies and Lyme disease risk assessment/management but any study that requires use of this model type in a spatial context. Copyright © 2014 Elsevier Inc. All rights reserved.

Intrinsic DNA curvature in trypanosomes.

PubMed

Smircich, Pablo; El-Sayed, Najib M; Garat, Beatriz

2017-11-09

Trypanosoma cruzi and Trypanosoma brucei are protozoan parasites causing Chagas disease and African sleeping sickness, displaying unique features of cellular and molecular biology. Remarkably, no canonical signals for RNA polymerase II promoters, which drive protein coding genes transcription, have been identified so far. The secondary structure of DNA has long been recognized as a signal in biological processes and more recently, its involvement in transcription initiation in Leishmania was proposed. In order to study whether this feature is conserved in trypanosomatids, we undertook a genome wide search for intrinsic DNA curvature in T. cruzi and T. brucei. Using a region integrated intrinsic curvature (RIIC) scoring that we previously developed, a non-random distribution of sequence-dependent curvature was observed. High RIIC scores were found to be significantly correlated with transcription start sites in T. cruzi, which have been mapped in divergent switch regions, whereas in T. brucei, the high RIIC scores correlated with sites that have been involved not only in RNA polymerase II initiation but also in termination. In addition, we observed regions with high RIIC score presenting in-phase tracts of Adenines, in the subtelomeric regions of the T. brucei chromosomes that harbor the variable surface glycoproteins genes. In both T. cruzi and T. brucei genomes, a link between DNA conformational signals and gene expression was found. High sequence dependent curvature is associated with transcriptional regulation regions. High intrinsic curvature also occurs at the T. brucei chromosome subtelomeric regions where the recombination processes involved in the evasion of the immune host system take place. These findings underscore the relevance of indirect DNA readout in these ancient eukaryotes.

Brain mediators of predictive cue effects on perceived pain

PubMed Central

Atlas, Lauren Y.; Bolger, Niall; Lindquist, Martin A.; Wager, Tor D.

2010-01-01

Information about upcoming pain strongly influences pain experience in experimental and clinical settings, but little is known about the brain mechanisms that link expectation and experience. To identify the pathways by which informational cues influence perception, analyses must jointly consider both the effects of cues on brain responses and the relationship between brain responses and changes in reported experience. Our task and analysis strategy were designed to test these relationships. Auditory cues elicited expectations for low or high painful thermal stimulation, and we assessed how cues influenced human subjects’ pain reports and BOLD fMRI responses to matched levels of noxious heat. We used multi-level mediation analysis to identify brain regions that 1) are modulated by predictive cues, 2) predict trial-to-trial variations in pain reports, and 3) formally mediate the relationship between cues and reported pain. Cues influenced heat-evoked responses in most canonical pain-processing regions, including both medial and lateral pain pathways. Effects on several regions correlated with pre-task expectations, suggesting that expectancy plays a prominent role. A subset of pain-processing regions, including anterior cingulate cortex, anterior insula, and thalamus, formally mediated cue effects on pain. Effects on these regions were in turn mediated by cue-evoked anticipatory activity in the medial orbitofrontal cortex (OFC) and ventral striatum, areas not previously directly implicated in nociception. These results suggest that activity in pain-processing regions reflects a combination of nociceptive input and top-down information related to expectations, and that anticipatory processes in OFC and striatum may play a key role in modulating pain processing. PMID:20881115

Evidence of linkage and association on chromosome 20 for late-onset Alzheimer disease.

PubMed

Goddard, Katrina A B; Olson, Jane M; Payami, Haydeh; van der Voet, Monique; Kuivaniemi, Helena; Tromp, Gerard

2004-06-01

Recently, we reported evidence of linkage on chromosome 20 for Alzheimer disease (AD) using a novel statistical approach to incorporate covariates (e.g., age, ApoE genotype) into the analysis. These results suggest that very elderly subjects (>85 years), and individuals who carry an epsilon2 allele at the ApoE locus are more likely to be linked to this candidate region. The region on chromosome 20 includes a strong candidate gene, cystatin C (CST3), which has previously been associated with AD in case-control studies. We investigated these findings further by genotyping additional markers to narrow the candidate region, and to identify evidence of linkage disequilibrium as additional support for a susceptibility locus on chromosome 20. We selected 43 elderly sibships (89 subjects) from the NIMH AD Genetics Initiative based on current age older than 84 years, and identified 129 unrelated control subjects who were older than 84 years from the Oregon Brain Aging Study to conduct linkage and association studies in this region. Fourteen additional markers were evaluated, including 4 markers located within or near CST3. We narrowed the candidate region on chromosome 20 to an 11.8-cM region between markers D20S174 and D20S471, which includes the CST3 candidate gene. In addition, we observed evidence of association for markers located near the CST3 candidate gene, with P values between 0.002 and 0.08 for two-locus haplotypes. These results support the presence of a susceptibility locus for AD in the vicinity of CST3 for very elderly subjects with AD.

Mesolimbic effects of the antidepressant fluoxetine in Holtzman rats, a genetic strain with increased vulnerability to stress

PubMed Central

Padilla, Eimeira; Shumake, Jason; Barrett, Douglas W.; Sheridan, Eva C.; Gonzalez-Lima, F.

2011-01-01

This is the first metabolic mapping study of the effects of fluoxetine after learned helplessness training. Antidepressants are the most commonly prescribed medications, but the regions underlying treatment effects in affectively disordered brains are poorly understood. We hypothesized the antidepressant action of fluoxetine would produce adaptations in mesolimbic regions after two weeks of treatment. We used Holtzman rats, a genetic strain showing susceptibility to novelty-evoked hyperactivity and stress-evoked helplessness, to map regional brain metabolic effects caused by fluoxetine treatment. Animals underwent learned helplessness, and subsequently immobility time was scored in the forced swim test (FST). On the next day, animals began receiving two weeks of fluoxetine (5 mg/kg/day) or vehicle and were retested in the FST at the end of drug treatment. Antidepressant behavioral effects of fluoxetine were analyzed using a ratio of immobility during pre- and post-treatment FST sessions. Brains were analyzed for regional metabolic activity using quantitative cytochrome oxidase histochemistry as in our previous study using congenitally helpless rats. Fluoxetine exerted a protective effect against FST-induced immobility behavior in Holtzman rats. Fluoxetine also caused a significant reduction in the mean regional metabolism of the nucleus accumbens shell and the ventral hippocampus as compared to vehicle-treated subjects. Additional networks affected by fluoxetine treatment included the prefrontal-cingulate cortex and brainstem nuclei linked to depression (e.g. habenula, dorsal raphe and interpeduncular nucleus). We concluded that corticolimbic regions such as the prefrontal-cingulate cortex, nucleus accumbens, ventral hippocampus and key brainstem nuclei represent important contributors to the neural network mediating fluoxetine antidepressant action. PMID:21376019

Genome-Wide Analysis of Syntenic Gene Deletion in the Grasses

PubMed Central

Schnable, James C.; Freeling, Michael; Lyons, Eric

2012-01-01

The grasses, Poaceae, are one of the largest and most successful angiosperm families. Like many radiations of flowering plants, the divergence of the major grass lineages was preceded by a whole-genome duplication (WGD), although these events are not rare for flowering plants. By combining identification of syntenic gene blocks with measures of gene pair divergence and different frequencies of ancient gene loss, we have separated the two subgenomes present in modern grasses. Reciprocal loss of duplicated genes or genomic regions has been hypothesized to reproductively isolate populations and, thus, speciation. However, in contrast to previous studies in yeast and teleost fishes, we found very little evidence of reciprocal loss of homeologous genes between the grasses, suggesting that post-WGD gene loss may not be the cause of the grass radiation. The sets of homeologous and orthologous genes and predicted locations of deleted genes identified in this study, as well as links to the CoGe comparative genomics web platform for analyzing pan-grass syntenic regions, are provided along with this paper as a resource for the grass genetics community. PMID:22275519

ARGONAUTE9-dependent silencing of transposable elements in pericentromeric regions of Arabidopsis.

PubMed

Durán-Figueroa, Noé; Vielle-Calzada, Jean-Philippe

2010-11-01

Recent evidence indicates that the establishment of the haploid phase of the plant life cycle requires epigenetic mechanisms that control reproductive cell fate. We previously showed that in Arabidopsis thaliana (Arabidopsis) mutations in ARGONAUTE9 (AGO9) result in defective cell specification during megasporogenesis. AGO9 preferentially interacts with 24 nucleotide (nt) small RNAs (sRNAs) derived from transposable elements (TEs), and its sporophytic activity is required to silence TEs in the female gametophyte. Here we show that AGO9 can bind in vitro to 24 nt sRNAs corresponding to Athila retrotransposons expressed in the ovule prior to pollination. We also show that AGO9 is necessary to inactivate a significant proportion of long terminal repeat retrotransposons (LTRs) in the ovule, and that its predominant TE targets are located in the pericentromeric regions of all 5 chromosomes, suggesting a link between the AGO9-dependent sRNA pathway and heterochromatin formation. Our extended results point towards the existence of a tissue-specific mechanism of sRNA-dependent TE silencing in the ovule.

Further refinement of the location for autosomal dominant retinitis pigmentosa on chromosome 7p (RP9)

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

Inglehearn, C.F.; Keen, T.J.; Al-Maghtheh, M.

1994-04-01

A form of autosomal dominant retinitis pigmentosa (adRP) mapping to chromosome 7p was recently reported by this laboratory, in a single large family from southeastern England. Further sampling of the family and the use a number of genetic markers from 7p have facilitated the construction of a series of multipoint linkage maps of the region with the most likely disease gene location. From this and haplotype data, the locus can now be placed between the markers D7S484 and D7S526, in an interval estimated to be 1.6-4 cM. Genetic distances between the markers previously reported to be linked to this regionmore » and those described in the recent whole-genome poly-CA map were estimated from data in this and other families. These data should assist in the construction of a physical map of the region and will help to identify candidate genes for the 7p adRP locus. 21 refs., 3 figs., 1 tab.« less

Future air pollution in the Shared Socio-economic Pathways

DOE PAGES

Rao, Shilpa; Klimont, Zbigniew; Smith, Steven J.; ...

2016-07-15

Emissions of air pollutants such as sulfur and nitrogen oxides and particulates have significant health impacts as well as effects on natural and anthropogenic ecosystems. These same emissions also can change atmospheric chemistry and the planetary energy balance, thereby impacting global and regional climate. Long-term scenarios for air pollutant emissions are needed as inputs to global climate and chemistry models, and for analysis linking air pollutant impacts across sectors. In this paper we present methodology and results for air pollutant emissions in Shared Socioeconomic Pathways (SSP) scenarios. We first present a set of three air pollution narratives that describe high,more » central, and low pollution control ambitions over the 21 st century. These narratives are then translated into quantitative guidance for use in integrated assessment models. We provide an overview of pollutant emission trajectories under the SSP scenarios. Pollutant emissions in these scenarios cover a wider range than the scenarios used in previous international climate model comparisons. Furthermore, the SSP scenarios provide the opportunity to access a more comprehensive range of future global and regional air quality outcomes.« less

Hydropower in Southeast United States, -a Hydroclimatological Perspective

NASA Astrophysics Data System (ADS)

Engstrom, J.

2016-12-01

Hydropower is unique among renewable energy sources for the ability to store its fuel (water) in reservoirs. The relationship between discharge, macro-scale drivers, and production is complex since production depends not only on water availability, but also upon decisions made by the institution owning the facility that has to consider many competing interests including economics, drinking water supply, recreational uses, etc. This analysis shows that the hydropower plants in Southeast U.S. (AL, GA, NC, SC, and TN) exhibit considerable year to year variability in production. Although the hydroclimatology of the Southeast U.S. has been analyzed partially, no previous study has linked the region's hydroelectricity production to any reported causes of interannual hydroclimatological variability, as has been completed in other regions. Due to the current short-term hydroelectricity production forecasts, the water resource is not optimized from a hydropower perspective as electricity generating potential is not maximized. The results of this study highlight the amount of untapped hydroelectricity that could be produced if long term hydroclimate and large-scale climate drivers were considered in production forecasts.

Ets-1 interacts through a similar binding interface with Ku70 and Poly (ADP-Ribose) Polymerase-1.

PubMed

Choul-Li, Souhaila; Legrand, Arnaud J; Vicogne, Dorothée; Villeret, Vincent; Aumercier, Marc

2018-06-18

The Ets-1 transcription factor plays an important role in various physiological and pathological processes. These diverse roles of Ets-1 are likely to depend on its interaction proteins. We have previously showed that Ets-1 interacted with DNA-dependent protein kinase (DNA-PK) complex including its regulatory subunits, Ku70 and Ku86 and with poly (ADP-ribose) polymerase-1 (PARP-1). In this study, the binding domains for the interaction between Ets-1 and these proteins were reported. We demonstrated that the interaction of Ets-1 with DNA-PK was mediated through the Ku70 subunit and was mapped to the C-terminal region of Ets-1 and the C-terminal part of Ku70 including SAP domain. The interactive domains between Ets-1 and PARP-1 have been mapped to the C-terminal region of Ets-1 and the BRCA1 carboxy-terminal (BRCT) domain of PARP-1. The results presented in this study may advance our understanding of the functional link between Ets-1 and its interaction partners, DNA-PK and PARP-1.

Modelling Cerebral Blood Flow and Temperature Using a Vascular Porous Model

NASA Astrophysics Data System (ADS)

Blowers, Stephen; Thrippleton, Michael; Marshall, Ian; Harris, Bridget; Andrews, Peter; Valluri, Prashant

2016-11-01

Macro-modelling of cerebral blood flow can assist in determining the impact of temperature intervention to reduce permanent tissue damage during instances of brain trauma. Here we present a 3D two phase fluid-porous model for simulating blood flow through the capillary region linked to intersecting 1D arterial and venous vessel trees. This combined vasculature porous (VaPor) model simulates both flow and energy balances, including heat from metabolism, using a vasculature extracted from MRI data which are expanded upon using a tree generation algorithm. Validation of temperature balance has been achieved using rodent brain data. Direct flow validation is not as straight forward due to the method used in determining regional cerebral blood flow (rCBF). In-vivo measurements are achieved using a tracer, which disagree with direct measurements of simulated flow. However, by modelling a virtual tracer, rCBF values are obtained that agree with those found in literature. Temperature profiles generated with the VaPor model show a reduction in core brain temperature after cooling the scalp not seen previously in other models.

Future air pollution in the Shared Socio-economic Pathways

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

Rao, Shilpa; Klimont, Zbigniew; Smith, Steven J.

Emissions of air pollutants such as sulfur and nitrogen oxides and particulates have significant health impacts as well as effects on natural and anthropogenic ecosystems. These same emissions also can change atmospheric chemistry and the planetary energy balance, thereby impacting global and regional climate. Long-term scenarios for air pollutant emissions are needed as inputs to global climate and chemistry models, and for analysis linking air pollutant impacts across sectors. In this paper we present methodology and results for air pollutant emissions in Shared Socioeconomic Pathways (SSP) scenarios. We first present a set of three air pollution narratives that describe high,more » central, and low pollution control ambitions over the 21 st century. These narratives are then translated into quantitative guidance for use in integrated assessment models. We provide an overview of pollutant emission trajectories under the SSP scenarios. Pollutant emissions in these scenarios cover a wider range than the scenarios used in previous international climate model comparisons. Furthermore, the SSP scenarios provide the opportunity to access a more comprehensive range of future global and regional air quality outcomes.« less

Up-regulation of neural indicators of empathic concern in an offender population.

PubMed

Arbuckle, Nathan L; Shane, Matthew S

2017-08-01

Empathic concern has traditionally been conceived of as a spontaneous reaction to others experiencing pain or distress. As such, the potential role of more deliberate control over empathic responses has frequently been overlooked. The present fMRI study evaluated the role of such deliberate control in empathic concern by examining the extent to which a sample of offenders recruited through probation/parole could voluntarily modulate their neural activity to another person in pain. Offenders were asked to either passively view pictures of other people in painful or non-painful situations, or to actively modulate their level of concern for the person in pain. During passive viewing of painful versus non-painful pictures, offenders showed minimal neural activity in regions previously linked to empathy for pain (e.g., dorsal anterior cingulate cortex and bilateral insula). However, when instructed to try to increase their concern for the person in pain, offenders demonstrated significant increases within these regions. These findings are consistent with recent theories of empathy as motivational in nature, and suggest that limitations in empathic concern may include a motivational component.

Genetic mapping of a locus for multiple ephiphyseal dysplasia (EDM2) to a region of chromosome 1 containing a type IX collagen gene

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

Briggs, M.D.; Choi, HiChang; Warman, M.L.

1994-10-01

Multiple epiphyseal dysplasia (MED) is a dominantly inherited chondrodysplasia characterized by mild short stature and early-onset osteoarthrosis. Some forms of MED clinically resemble another chondrodysplasia phenotype, the mild form of pseudoachondroplasia (PSACH). On the basis of their clinical similarities as well as similar ultra-structural and biochemical features in cartilage from some patients, it has been proposed that MED and PSACH belong to a single bone-dysplasia family. Recently, both mild and severe PSACH as well as a form of MED have been linked to the same interval on chromosome 19, suggesting that they may be allelic disorders. Linkage studies with themore » chromosome 19 markers were carried out in a large family with MED and excluded the previously identified interval. Using this family, we have identified a MED locus on the short arm of chromosome 1, in a region containing the gene (COL9A2) that encodes the {alpha}2 chain of type IX collagen, a structural component of the cartilage extracellular matrix. 39 refs., 3 figs., 3 tabs.« less

White/blue-emitting, water-dispersible CdSe quantum dots prepared by counter ion-induced polymer collapse

NASA Astrophysics Data System (ADS)

Wang, Jing; Goh, Jane Betty; Goh, M. Cynthia; Giri, Neeraj Kumar; Paige, Matthew F.

2015-09-01

The synthesis and characterization of water-dispersible, luminescent CdSe/ZnS semiconductor quantum dots that exhibit nominal "white" fluorescence emission and have potential applications in solid-state lighting is described. The nanomaterials, prepared through counter ion-induced collapse and UV cross-linking of high-molecular weight polyacrylic acid in the presence of appropriate aqueous inorganic ions, were of ∼2-3 nm diameter and could be prepared in gram quantities. The quantum dots exhibited strong luminescence emission in two bands, the first in the blue-region (band edge) of the optical spectrum and the second, a broad emission in the red-region (attributed to deep trap states) of the optical spectrum. Because of the relative strength of emission of the band edge and deep trap state luminescence, it was possible to achieve visible white luminescence from the quantum dots in aqueous solution and in dried, solid films. The optical spectroscopic properties of the nanomaterials, including ensemble and single-molecule spectroscopy, was performed, with results compared to other white-emitting quantum dot systems described previously in the literature.

UniPrime2: a web service providing easier Universal Primer design.

PubMed

Boutros, Robin; Stokes, Nicola; Bekaert, Michaël; Teeling, Emma C

2009-07-01

The UniPrime2 web server is a publicly available online resource which automatically designs large sets of universal primers when given a gene reference ID or Fasta sequence input by a user. UniPrime2 works by automatically retrieving and aligning homologous sequences from GenBank, identifying regions of conservation within the alignment, and generating suitable primers that can be used to amplify variable genomic regions. In essence, UniPrime2 is a suite of publicly available software packages (Blastn, T-Coffee, GramAlign, Primer3), which reduces the laborious process of primer design, by integrating these programs into a single software pipeline. Hence, UniPrime2 differs from previous primer design web services in that all steps are automated, linked, saved and phylogenetically delimited, only requiring a single user-defined gene reference ID or input sequence. We provide an overview of the web service and wet-laboratory validation of the primers generated. The system is freely accessible at: http://uniprime.batlab.eu. UniPrime2 is licenced under a Creative Commons Attribution Noncommercial-Share Alike 3.0 Licence.

Looking to the eyes influences the processing of emotion on face-sensitive event-related potentials in 7-month-old infants.

PubMed

Vanderwert, Ross E; Westerlund, Alissa; Montoya, Lina; McCormick, Sarah A; Miguel, Helga O; Nelson, Charles A

2015-10-01

Previous studies in infants have shown that face-sensitive components of the ongoing electroencephalogram (the event-related potential, or ERP) are larger in amplitude to negative emotions (e.g., fear, anger) versus positive emotions (e.g., happy). However, it is still unclear whether the negative emotions linked with the face or the negative emotions alone contribute to these amplitude differences. We simultaneously recorded infant looking behaviors (via eye-tracking) and face-sensitive ERPs while 7-month-old infants viewed human faces or animals displaying happy, fear, or angry expressions. We observed that the amplitude of the N290 was greater (i.e., more negative) to angry animals compared to happy or fearful animals; no such differences were obtained for human faces. Eye-tracking data highlighted the importance of the eye region in processing emotional human faces. Infants that spent more time looking to the eye region of human faces showing fearful or angry expressions had greater N290 or P400 amplitudes, respectively. © 2014 Wiley Periodicals, Inc.

Possible association between serotonin transporter promoter region polymorphism and extremely violent crime in Chinese males.

PubMed

Liao, Ding-Lieh; Hong, Chen-Jee; Shih, Hao-Ling; Tsai, Shih-Jen

2004-01-01

The neurotransmitter, serotonin, has been implicated in aggressive behavior. The serotonin transporter (5-HTT), which reuptakes serotonin into the nerve terminal, plays a critical role in the regulation of serotonergic function. Previous western reports have demonstrated that the low-activity short (S) allele of the 5-HTT gene-linked polymorphic-region (5-HTTLPR) polymorphism is associated with aggressive behavior and associated personality traits. In the present study, we investigated this 5-HTTLPR genetic polymorphism in a group of Chinese males who had been convicted for extremely violent crime (n = 135) and a normal control group (n = 111). The proportion of S-allele carriers was significantly higher in the criminal group than in the controls (p = 0.006). A significant association was not demonstrated for the relationship between the 5-HTTLPR polymorphism and antisocial personality disorder, substance abuse or alcohol abuse in the criminal group. Our findings demonstrate that carriage of the low-activity S allele is associated with extremely violent criminal behavior in Chinese males, and suggests that the 5-HTT may be implicated in the mechanisms underlying violent behaviors.

ChIP-Chip Identifies SEC23A, CFDP1, and NSD1 as TFII-I Target Genes in Human Neural Crest Progenitor Cells.

PubMed

Makeyev, Aleksandr V; Bayarsaihan, Dashzeveg

2013-05-01

Objectives :  GTF2I and GTF2IRD1 genes located in Williams-Beuren syndrome (WBS) critical region encode TFII-I family transcription factors. The aim of this study was to map genomic sites bound by these proteins across promoter regions of developmental regulators associated with craniofacial development. Design :  Chromatin was isolated from human neural crest progenitor cells and the DNA-binding profile was generated using the human RefSeq tiling promoter ChIP-chip arrays. Results :  TFII-I transcription factors are recruited to the promoters of SEC23A, CFDP1, and NSD1 previously defined as TFII-I target genes. Moreover, our analysis revealed additional binding elements that contain E-boxes and initiator-like motifs. Conclusions :  Genome-wide promoter binding studies revealed SEC23A, CFDP1, and NSD1 linked to craniofacial or dental development as direct TFII-I targets. Developmental regulation of these genes by TFII-I factors could contribute to the WBS-specific facial dysmorphism.

A Genome-Wide Association Study Identifies Genomic Regions for Virulence in the Non-Model Organism Heterobasidion annosum s.s

PubMed Central

Dalman, Kerstin; Himmelstrand, Kajsa; Olson, Åke; Lind, Mårten; Brandström-Durling, Mikael; Stenlid, Jan

2013-01-01

The dense single nucleotide polymorphisms (SNP) panels needed for genome wide association (GWA) studies have hitherto been expensive to establish and use on non-model organisms. To overcome this, we used a next generation sequencing approach to both establish SNPs and to determine genotypes. We conducted a GWA study on a fungal species, analysing the virulence of Heterobasidion annosum s.s., a necrotrophic pathogen, on its hosts Picea abies and Pinus sylvestris. From a set of 33,018 single nucleotide polymorphisms (SNP) in 23 haploid isolates, twelve SNP markers distributed on seven contigs were associated with virulence (P<0.0001). Four of the contigs harbour known virulence genes from other fungal pathogens and the remaining three harbour novel candidate genes. Two contigs link closely to virulence regions recognized previously by QTL mapping in the congeneric hybrid H. irregulare × H. occidentale. Our study demonstrates the efficiency of GWA studies for dissecting important complex traits of small populations of non-model haploid organisms with small genomes. PMID:23341945

Information trade-offs for optical quantum communication.

PubMed

Wilde, Mark M; Hayden, Patrick; Guha, Saikat

2012-04-06

Recent work has precisely characterized the achievable trade-offs between three key information processing tasks-classical communication (generation or consumption), quantum communication (generation or consumption), and shared entanglement (distribution or consumption), measured in bits, qubits, and ebits per channel use, respectively. Slices and corner points of this three-dimensional region reduce to well-known protocols for quantum channels. A trade-off coding technique can attain any point in the region and can outperform time sharing between the best-known protocols for accomplishing each information processing task by itself. Previously, the benefits of trade-off coding that had been found were too small to be of practical value (viz., for the dephasing and the universal cloning machine channels). In this Letter, we demonstrate that the associated performance gains are in fact remarkably high for several physically relevant bosonic channels that model free-space or fiber-optic links, thermal-noise channels, and amplifiers. We show that significant performance gains from trade-off coding also apply when trading photon-number resources between transmitting public and private classical information simultaneously over secret-key-assisted bosonic channels. © 2012 American Physical Society

Martian polar expeditions: problems and solutions.

PubMed

Cockell, C S

2001-12-01

The Martian polar ice caps are regions of substantial scientific interest, being the most dynamic regions of Mars. They are volatile sinks and thus closely linked to Martian climatic conditions. Because of their scale and the precedent set by the past history of polar exploration on Earth, it is likely that an age of polar exploration will emerge on the surface of Mars after the establishment of a capable support structure at lower latitudes. Expeditions might be launched either from a lower latitude base camp or from a human-tended polar base. Based on previously presented expeditionary routes to the Martian poles, in this paper a "spiral in-spiral out" unsupported transpolar assault on the Martian north geographical pole is used as a Reference expedition to propose new types of equipment for the human polar exploration of Mars. Martian polar "ball" tents and "hover" modifications to the Nansen sledge for sledging on CO2-containing water ice substrates under low atmospheric pressures are suggested as elements for the success of these endeavours. Other challenges faced by these expeditions are quantitatively and qualitatively addressed. c 2001 Elsevier Science Ltd. All rights reserved.

Magnetic Evolution Linked to the Interrelated Activity Complexes Involving Transequatorial Coronal Holes

NASA Astrophysics Data System (ADS)

Gutiérrez, Heidy; Taliashvili, Lela; Lazarian, Alexandre

2018-06-01

We studied a magnetic evolution linked to a cadence of interrelated activities developed in a large solar region during Carrington rotations, CRs 2119 - 2121, based on multi-wavelength and multi-spacecraft observations. Three coronal holes (CHs), two transequatorial and one isolated, eight filaments and some active regions were distributed closely in the region. Every of these filaments partial and/or complete eruption was linked to a Coronal Mass Ejection (CME) or coronal jet. We found different types of interrelated activities: eruptions of three pairs of interrelated filaments close to a CH and eruptions of two filaments close to the active region and CH. Some indicators of the magnetic reconnection were observed frequently during the pre- as well as post-filament eruptions. Additionally, post-filament eruption and/or post-CME processes show their implication in the evolution of nearby CHs and newly formed transient CHs or dimming regions, including a new CH formation. We discussed the small- and large-scale magnetic reconfigurations associated with these interrelated activity complexes, the ones involving long-lived transequatorial CHs, and their possible implication in the evolution of the global solar magnetic field, especially with the starting processes of quadruple configuration and polarity reversal of the solar cycle 24.

Linking Landsat observations with MODIS derived Land Surface Phenology data to map agricultural expansion and contraction in Russia

NASA Astrophysics Data System (ADS)

Caliskan, S.; de Beurs, K.

2010-12-01

Direct human impacts on the land surface are especially pronounced in agricultural regions that cover a substantial portion of the global land surface: 12% of the terrestrial surface is under active agricultural management. Crops display phenologies distinct from natural vegetation; the growing seasons are often shifted in time, crop establishment is generally fast and the vegetation is rapidly removed at harvest. Previously we have demonstrated that agricultural land abandonment alters land surface phenology sufficiently to be detectable from a time series of coarse resolution imagery. With land surface phenology models based on accumulated growing degree-days (AGDD) and AVHRR NDVI, we demonstrated that abandoned croplands covered with native grasses and weeds typically greened-up and peaked sooner than active croplands. Here we present an expansion of these analyses for the MODIS time period with the ultimate goal to map agricultural abandonment and expansion in European Russia from 2000 to 2010. We used the 8-day, 1km L3 Land Surface Temperature data (MOD11A2) to generate the accumulated growing degree days and the 16-day L3 Nadir BRDF-Adjusted reflectance data at 500m resolution (MCD43A4) to calculate NDVI. We calculated phenological metrics based on three methods: 1) Double-logistic models such as those applied to produce the standard MODIS phenology product (MOD12Q2); 2) A combination of NDII and NDVI; this method has been shown to provide start/end of season measurement closest to field observations in snowy areas; and 3) A quadratic model linking accumulated growing degree days and vegetation indices which we successfully applied in agricultural areas of Kazakhstan and semi-arid Africa. We selected Landsat imagery for two vastly different regions in Russia and present a Landsat-guided probabilistic detection of abandoned and active croplands for all available years of the MODIS image time series (2000-2010). For each region, we selected at least two images during the growing season and calculated the following indices: Normalized Difference Vegetation Index (NDVI), Tasseled Cap indices (Brightness, Greenness, Wetness), as well as the first three principal components for each image. We used the selected images to distinguish between the basic classes of agriculture, water, forest and urban areas, with the primary goal to separate between agricultural and non-agricultural regions. We compared class membership with ancillary regional agricultural statistics and targeted field observations collected in the summer of 2010. In the last part, we linked the Landsat based agricultural estimates and the MODIS phenological measurements using logistic regression and compared the agricultural maps with globally available land cover classifications.

Refined genetic mapping of X-linked Charcot-Marie-Tooth neuropathy

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

Fain, P.R.; Barker, D.F.; Chance, P.F.

1994-02-01

Genetic linkage studies were conducted in four multigenerational families with X-linked Charcot-Marie-Tooth disease (CMTX), using 12 highly polymorphic short-tandem-repeat markers for the pericentromeric region of the X Chromosome. Pairwise linkage analysis with individual markers confirmed tight linkage of CMTX to the pericentromeric region in each family. Multipoint analyses strongly support the order DXS337-CMTX-DXS441-(DXS56, PGK1). 38 refs., 2 figs., 1 tab.