bluuebunny/crossref_metadata_2025 huggingface dataset:
Deconstructing thermodynamic parameters of a coupled system from site-specific observables
Authors: Chowdhury Sandipan , Chanda Baron
Published: October 2010

Cooperative interactions mediate information transfer between structural domains of a protein molecule and are major determinants of protein function and modulation. The prevalent theories to understand the thermodynamic origins of cooperativity have been developed to reproduce the complex behavior of a global thermodynamic observable such as ligand binding or enzyme activity. However, in most cases the measurement of a single global observable cannot uniquely define all the terms that fully describe the energetics of the system. Here we establish a theoretical groundwork for analyzing protein thermodynamics using site-specific information. Our treatment involves extracting a site-specific parameter (defined as χ value) associated with a structural unit. We demonstrate that, under limiting conditions, the χ value is related to the direct interaction terms associated with the structural unit under observation and its intrinsic activation energy. We also introduce a site-specific interaction energy term (
χ
diff
) that is a function of the direct interaction energy of that site with every other site in the system. When combined with site-directed mutagenesis and other molecular level perturbations, analyses of χ values of site-specific observables may provide valuable insights into protein thermodynamics and structure.
Molecular and regulatory properties of a public good shape the evolution of cooperation
Authors: Kümmerli Rolf , Brown Sam P.
Published: October 2010

Public goods cooperation abounds in nature, occurring in organisms ranging from bacteria to humans. Although previous research focused on the behavioral and ecological conditions favoring cooperation, the question of whether the molecular and regulatory properties of the public good itself can influence selection for cooperation has received little attention. Using a metapopulation model, we show that extended molecular durability of a public good—allowing multiple reuse across generations—greatly reduces selection for cheating if (and only if) the production of the public good is facultatively regulated. To test the apparent synergy between public goods durability and facultative regulation, we examined the production of iron-scavenging pyoverdin molecules by the bacterium
Pseudomonas aeruginosa
, a cooperative behavior that is facultatively regulated in response to iron availability. We show that pyoverdin is a very durable public good and that extended durability significantly enhances fitness. Consistent with our model, we found that nonsiderophore-producing mutants (cheats) had a relative fitness advantage over siderophore producers (cooperators) when pyoverdin durability was low but not when durability was high. This was because cooperators facultatively reduced their investment in pyoverdin production when enough pyoverdin had accumulated in the media—a cost-saving strategy that minimized the ability of cheats to invade. These findings show how molecular properties of cooperative acts can shape the costs and benefits of cooperation.
Microautophagy of the Nucleus Coincides with a Vacuolar Diffusion Barrier at Nuclear–Vacuolar Junctions
Authors: Dawaliby Rosie , Mayer Andreas
Published: October 2010

Nuclei bind yeast vacuoles via nucleus-vacuole (NV) junctions. Under nutrient restriction, NV junctions invaginate and release vesicles filled with nuclear material into vacuoles, resulting in piecemeal microautophagy of the nucleus (PMN). We show that the electrochemical gradient across the vacuolar membrane promotes invagination of NV junctions. Existing invaginations persist independently of the gradient, but final release of PMN vesicles requires again V-ATPase activity. We find that NV junctions form a diffusion barrier on the vacuolar membrane that excludes V-ATPase but is enriched in the VTC complex and accessible to other membrane-integral proteins. V-ATPase exclusion depends on the NV junction proteins Nvj1p,Vac8p, and the electrochemical gradient. It also depends on factors of lipid metabolism, such as the oxysterol binding protein Osh1p and the enoyl-CoA reductase Tsc13p, which are enriched in NV junctions, and on Lag1p and Fen1p. Our observations suggest that NV junctions form in two separable steps: Nvj1p and Vac8p suffice to establish contact between the two membranes. The electrochemical potential and lipid-modifying enzymes are needed to establish the vacuolar diffusion barrier, invaginate NV junctions, and form PMN vesicles.
Cell Death or Survival Promoted by Alternative Isoforms of ErbB4
Authors: Sundvall Maria , Veikkolainen Ville , Kurppa Kari , Salah Zaidoun , Tvorogov Denis , van Zoelen E. Joop , Aqeilan Rami , Elenius Klaus
Published: October 2010

The significance of ErbB4 in tumor biology is poorly understood. The ERBB4 gene is alternatively spliced producing juxtamembrane (JM-a and JM-b) and cytoplasmic (CYT-1 and CYT-2) isoforms. Here, signaling via the two alternative ErbB4 JM isoforms (JM-a CYT-2 and JM-b CYT-2) was compared. Fibroblasts expressing ErbB4 JM-a demonstrated enhanced ErbB4 autophosphorylation, growth, and survival. In contrast, cells overexpressing ErbB4 JM-b underwent starvation-induced death. Both pro- and antisurvival responses to the two ErbB4 isoforms were sensitive to an ErbB kinase inhibitor. Platelet-derived growth factor receptor-alpha (PDGFRA) was identified as an ErbB4 target gene that was differentially regulated by the two ErbB4 isoforms. The soluble intracellular domain of ErbB4, released from the JM-a but not from the JM-b isoform, associated with the transcription factor AP-2 and promoted its potential to enhance PDGFRA transcription. Survival of cells expressing JM-a was suppressed by targeting either PDGFR-α or AP-2, whereas cells expressing JM-b were rescued from cell death by the PDGFR-α agonist, PDGF-BB. These findings indicate that two alternative ErbB4 isoforms may promote antagonistic cellular responses and suggest that pharmacological inhibition of ErbB4 kinase activity may lead to either suppression or promotion of cellular growth.
Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies
Authors: Geoffroy Marie-Claude , Jaffray Ellis G. , Walker Katherine J. , Hay Ronald T.
Published: October 2010

In acute promyelocytic leukemia (APL), the promyelocytic leukemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). Arsenic is an effective treatment for this disease as it induces SUMO-dependent ubiquitin-mediated proteasomal degradation of the PML-RAR fusion protein. Here we analyze the nuclear trafficking dynamics of PML and its SUMO-dependent ubiquitin E3 ligase, RNF4 in response to arsenic. After administration of arsenic, PML immediately transits into nuclear bodies where it undergoes SUMO modification. This initial recruitment of PML into nuclear bodies is not dependent on RNF4, but RNF4 quickly follows PML into the nuclear bodies where it is responsible for ubiquitylation of SUMO-modified PML and its degradation by the proteasome. While arsenic restricts the mobility of PML, FRAP analysis indicates that RNF4 continues to rapidly shuttle into PML nuclear bodies in a SUMO-dependent manner. Under these conditions FRET studies indicate that RNF4 interacts with SUMO in PML bodies but not directly with PML. These studies indicate that arsenic induces the rapid reorganization of the cell nucleus by SUMO modification of nuclear body-associated PML and uptake of the ubiquitin E3 ligase RNF4 leading to the ubiquitin-mediated degradation of PML.
Spatial niche partitioning in dinosaurs from the latest cretaceous (Maastrichtian) of North America
Authors: Lyson Tyler R. , Longrich Nicholas R.
Published: October 2010

We examine patterns of occurrence of associated dinosaur specimens (
n
= 343) from the North American Upper Cretaceous Hell Creek Formation and equivalent beds, by comparing their relative abundance in sandstone and mudstone. Ceratopsians preferentially occur in mudstone, whereas hadrosaurs and the small ornithopod
Thescelosaurus
show a strong association with sandstone. By contrast, the giant carnivore
Tyrannosaurus rex
shows no preferred association with either lithology. These lithologies are used as an indicator of environment of deposition, with sandstone generally representing river environments, and finer grained sediments typically representing floodplain environments. Given these patterns of occurrence, we argue that spatial niche partitioning helped reduce competition for resources between the herbivorous dinosaurs. Within coastal lowlands ceratopsians preferred habitats farther away from rivers, whereas hadrosaurs and
Thescelosaurus
preferred habitats in close proximity to rivers, and
T. rex
, the ecosystem's sole large carnivore, inhabited both palaeoenvironments. Spatial partitioning of the environment helps explain how several species of large herbivorous dinosaurs coexisted. This study emphasizes that different lithologies can preserve dramatically dissimilar vertebrate assemblages, even when deposited in close proximity and within a narrow window of time. The lithology in which fossils are preserved should be recorded as these data can provide unique insights into the palaeoecology of the animals they preserve.
Adaptation to local ultraviolet radiation conditions among neighbouringDaphniapopulations
Authors: Miner Brooks E. , Kerr Benjamin
Published: October 2010

Understanding the historical processes that generated current patterns of phenotypic diversity in nature is particularly challenging in subdivided populations. Populations often exhibit heritable genetic differences that correlate with environmental variables, but the non-independence among neighbouring populations complicates statistical inference of adaptation. To understand the relative influence of adaptive and non-adaptive processes in generating phenotypes requires joint evaluation of genetic and phenotypic divergence in an integrated and statistically appropriate analysis. We investigated phenotypic divergence, population-genetic structure and potential fitness trade-offs in populations ofDaphnia melanicainhabiting neighbouring subalpine ponds of widely differing transparency to ultraviolet radiation (UVR). Using a combination of experimental, population-genetic and statistical techniques, we separated the effects of shared population ancestry and environmental variables in predicting phenotypic divergence among populations. We found that native water transparency significantly predicted divergence in phenotypes among populations even after accounting for significant population structure. This result demonstrates that environmental factors such as UVR can at least partially account for phenotypic divergence. However, a lack of evidence for a hypothesized trade-off between UVR tolerance and growth rates in the absence of UVR prevents us from ruling out the possibility that non-adaptive processes are partially responsible for phenotypic differentiation in this system.
Birth order, individual sex and sex of competitors determine the outcome of conflict among siblings over parental care
Authors: Bonisoli-Alquati Andrea , Boncoraglio Giuseppe , Caprioli Manuela , Saino Nicola
Published: October 2010

Success in competition for limiting parental resources depends on the interplay between parental decisions over allocation of care and offspring traits. Birth order, individual sex and sex of competing siblings are major candidates as determinants of success in sib–sib competition, but experimental studies focusing on the combined effect of these factors on parent–offspring communication and within-brood competitive dynamics are rare. Here, we assessed individual food intake and body mass gain during feeding trials in barn swallow chicks differing for seniority and sex, and compared the intensity of their acoustic and postural solicitation (begging) displays. Begging intensity and success in competition depended on seniority in combination with individual sex and sex of the opponent. Junior chicks begged more than seniors, independently of satiation level (which was also experimentally manipulated), and obtained greater access to food. Females were generally weaker competitors than males. Individual sex and sex of the opponent also affected duration of begging bouts. Present results thus show that competition with siblings can make the rearing environment variably harsh for developing chicks, depending on individual sex, sex of competing broodmates and age ranking within the nest. They also suggest that parental decisions on the allocation of care and response of kin to signalling siblings may further contribute to the outcome of sibling competition.
Plasmodium relictuminfection and MHC diversity in the house sparrow (Passer domesticus)
Authors: Loiseau Claire , Zoorob Rima , Robert Alexandre , Chastel Olivier , Julliard Romain , Sorci Gabriele
Published: October 2010

Antagonistic coevolution between hosts and parasites has been proposed as a mechanism maintaining genetic diversity in both host and parasite populations. In particular, the high level of genetic diversity usually observed at the major histocompatibility complex (MHC) is generally thought to be maintained by parasite-driven selection. Among the possible ways through which parasites can maintain MHC diversity, diversifying selection has received relatively less attention. This hypothesis is based on the idea that parasites exert spatially variable selection pressures because of heterogeneity in parasite genetic structure, abundance or virulence. Variable selection pressures should select for different host allelic lineages resulting in population-specific associations between MHC alleles and risk of infection. In this study, we took advantage of a large survey of avian malaria in 13 populations of the house sparrow (Passer domesticus) to test this hypothesis. We found that (i) several MHC alleles were either associated with increased or decreased risk to be infected withPlasmodium relictum, (ii) the effects were population specific, and (iii) some alleles had antagonistic effects across populations. Overall, these results support the hypothesis that diversifying selection in space can maintain MHC variation and suggest a pattern of local adaptation where MHC alleles are selected at the local host population level.
Expression and Functional Analyses ofEXO70Genes in Arabidopsis Implicate Their Roles in Regulating Cell Type-Specific Exocytosis
Authors: Li Shipeng , van Os Gwen M.A. , Ren Shichao , Yu Dali , Ketelaar Tijs , Emons Anne Mie C. , Liu Chun-Ming
Published: October 2010

During exocytosis, Golgi-derived vesicles are tethered to the target plasma membrane by a conserved octameric complex called the exocyst. In contrast to a single gene in yeast and most animals, plants have greatly increased number of EXO70 genes in their genomes, with functions very much unknown. Reverse transcription-polymerase chain reactions were performed on all 23 EXO70 genes in Arabidopsis (Arabidopsis thaliana) to examine their expression at the organ level. Cell-level expression analyses were performed using transgenic plants carrying β-glucuronidase reporter constructs, showing that EXO70 genes are primarily expressed in potential exocytosis-active cells such as tip-growing and elongating cells, developing xylem elements, and guard cells, whereas no expression was observed in cells of mature organs such as well-developed leaves, stems, sepals, and petals. Six EXO70 genes are expressed in distinct but partially overlapping stages during microspore development and pollen germination. A mutation in one of these genes, EXO70C1 (At5g13150), led to retarded pollen tube growth and compromised male transmission. This study implies that multiplications of EXO70 genes may allow plants to acquire cell type- and/or cargo-specific regulatory machinery for exocytosis.
Metabolic Engineering of Seeds Can Achieve Levels of ω-7 Fatty Acids Comparable with the Highest Levels Found in Natural Plant Sources
Authors: Nguyen Huu Tam , Mishra Girish , Whittle Edward , Pidkowich Mark S. , Bevan Scott A. , Merlo Ann Owens , Walsh Terence A. , Shanklin John
Published: October 2010

Plant oils containing ω-7 fatty acids (FAs; palmitoleic 16:1Ɗ9 and cis-vaccenic 18:1Ɗ11) have potential as sustainable feedstocks for producing industrially important octene via metathesis chemistry. Engineering plants to produce seeds that accumulate high levels of any unusual FA has been an elusive goal. We achieved high levels of ω-7 FA accumulation by systematic metabolic engineering of Arabidopsis (Arabidopsis thaliana). A plastidial 16:0-ACP desaturase has been engineered to convert 16:0 to 16:1Ɗ9 with specificity >100-fold than that of naturally occurring paralogs, such as that from cat's claw vine (Doxantha unguis-cati). Expressing this engineered enzyme (Com25) in seeds increased ω-7 FA accumulation from <2% to 14%. Reducing competition for 16:0-ACP by down-regulating the β-ketoacyl-ACP synthase II 16:0 elongase further increased accumulation of ω-7 FA to 56%. The level of 16:0 exiting the plastid without desaturation also increased to 21%. Coexpression of a pair of fungal 16:0 desaturases in the cytosol reduced the 16:0 level to 11% and increased ω-7 FA to as much as 71%, equivalent to levels found in Doxantha seeds.
Corosolic acid inhibits glioblastoma cell proliferation by suppressing the activation of signal transducer and activator of transcription‐3 and nuclear factor‐kappa B in tumor cells and tumor‐associated macrophages
Authors: Fujiwara Yukio , Komohara Yoshihiro , Ikeda Tsuyoshi , Takeya Motohiro
Published: October 2010

Tumor‐associated macrophages (TAM) of M2 phenotype promote tumor proliferation and are associated with a poor prognosis in patients with glioblastoma. We screened the natural compounds possessing an inhibitory effect on M2 polarization in human monocyte‐derived macrophages. Among 130 purified natural compounds examined, corosolic acid significantly inhibited the expression of CD163, one of the phenotype markers of M2 macrophages, and also suppressed the secretion of IL‐10, one of the anti‐inflammatory cytokines preferentially produced by M2 macrophages, thus suggesting that corosolic acid suppresses M2 polarization of macrophages. Furthermore, corosolic acid inhibited the proliferation of glioblastoma cells, U373 and T98G, and the activation of signal transducer and activator of transcription‐3 (STAT3) and nuclear factor‐kappa B (NF‐κB) in both human macrophages and glioblastoma cells. These results indicate that corosolic acid suppresses the M2 polarization of macrophages and tumor cell proliferation by inhibiting both STAT3 and NF‐κB activation. Therefore, corosolic acid might be a potential new tool for tumor prevention and therapy. (Cancer Sci 2011; 102: 206–211)
Modelling moisture‐induced soil reflectance changes in cultivated sandy soils: a case study in citrus orchards
Authors: Somers B. , Gysels V. , Verstraeten W. W. , Delalieux S. , Coppin P.
Published: October 2010

The value of hyperspectral imagery in agricultural management has been amply demonstrated. Despite this, image interpretation is often drastically impeded by changes in soil moisture content (SMC). Soil moisture variations dominate the spectral reflectance in the 350–2500‐nm wavelength domain and affect the effectiveness of spectral indices used to monitor variations in soil and vegetation properties. Consequently, removing soil moisture effects in spectral images is critical and would provide a significant breakthrough for agricultural remote sensing. Yet, current available soil moisture reflectance models fail to properly address the moisture‐induced reflectance changes occurring within soils of the same texture class. This very much limits the operational implementation of these models, particularly in agricultural fields where within‐field variations in soil characteristics such as organic matter and clay content prevail. In this study, the effect of SMC on the reflectance in the 400–2500‐nm spectral domain was studied for six sandy soils located in citrus orchards in the Western Cape Province, South Africa. In a series of experiments, novel insights into soil moisture reflectance modelling of sandy cultivated soils are provided. The wavelength and soil‐specific variations in model parameters are mechanistically modelled and a general model for moist reflectance of cultivated sand soils is presented and successfully tested. Model comparison and validation demonstrate that the model fit of soil‐type‐specific models can be approximated (R2= 0.82; RRMSE = 0.14) while a significant increase in model fit compared with the traditional general models (R2= 0.59; RRMSE = 0.28) was achieved.
The concepts of potential natural vegetation (PNV) and other abstractions (trying to pick up fish with wet hands)
Authors: Carrión José S.
Published: October 2010

This note follows from an earlier Commentary published in Journal of Biogeography (Carrión & Fernández, 2009, 36, 2202–2203), which provided palaeoecological data, and two replies in the form of Correspondence (Loidi et al., 2010, 37, 2209–2211; Farris et al., 2010, 37, 2211–2213). The latter papers attempt to invalidate the palaeoecological database as a source of comparison with the maps of potential vegetation. Here, some of the different interpretations of the term ‘potential natural vegetation’ (PNV), as used by the floristic phytosociological school, are discussed. It is suggested that there is a conceptual impasse that will not have a solution until a terminological consensus is reached. This terminology will open new methodological avenues that will facilitate the entry of new information derived from historical biogeography, palaeoecology, ecology, phylogeography, and niche and community modelling. One of the main sources of conflict arises from the link made between habitats and floristically‐determined associations, a confusion that has crucial repercussions in biological conservation, including in respect of the EU Habitats Directive.
Heterogeneous Stock Mice are Susceptible to Encephalomyelitis and Antibody‐initiated Arthritis but not to Collagen‐ and G6PI‐induced Arthritis
Authors: Klaczkowska D. , Raposo B. , Nandakumar K. S.
Published: October 2010

The strategy of using heterogeneous stock (HS) mice has proven to be successful in fine mapping of quantitative trait loci in complex diseases. However, whether these mice can be used for arthritis, encephalomyelitis and autoimmune phenotypes has not been addressed. Here, we screened the Northport HS mice for arthritis phenotypes using three different models: collagen‐induced arthritis (CIA), using rat, bovine or chicken collagen type II (CII); recombinant human glucose‐6‐phosphate isomerase (G6PI)‐induced arthritis; and collagen antibody–induced arthritis (CAIA). Irrespective of the origin of collagen, we found HS mice to be fairly resistant to CIA and G6PI‐induced arthritis, despite the development of antibodies against the respective antigens. On the other hand, HS mice were found to be susceptible for CAIA. Similarly, these mice developed encephalomyelitis (EAE) induced either with mouse or rat spinal cord homogenate (SCH), or with recombinant rat myelin oligodendrocyte glycoprotein, with elevated antibody levels against CNS proteins. Accordingly, we conclude that the use of HS mice for fine mapping and positional cloning of gene(s) involved in CAIA and EAE is possible, but not for collagen‐ and G6PI‐induced arthritis.
High‐resolution sequence stratigraphy of the Maastrichtian‐Ypresian succession along the eastern scarp face of Kharga Oasis, southern Western Desert, Egypt
Authors: EL‐AZABI MOUNIR H. , FAROUK SHERIF
Published: October 2010

A thick Maastrichtian‐Ypresian succession, dominated by marine siliciclastic and carbonate deposits of the regionally recognized Nile Valley and Garra El‐Arbain facies associations, is exposed along the eastern escarpment face of Kharga Oasis, located in the Western Desert of Egypt. The main objectives of the present study are: (i) to establish a detailed biostratigraphic framework; (ii) to interpret the depositional environments; and (iii) to propose a sequence stratigraphic framework in order to constrain the palaeogeographic evolution of the Kharga sub‐basin during the Maastrichtian‐Ypresian time interval. The biostratigraphic analysis suggests the occurrence of 10 planktonic zones; two in the Early Maastrichtian (CF8b and CF7), four in the Palaeocene (P2, P3, P4c and P5) and four in the Early Eocene (E1, E2, E3 and E4). Recorded zonal boundaries and biostratigraphic zones generally match with those proposed elsewhere in the region. The stratigraphic succession comprises seven third‐order depositional sequences which are bounded by unconformities and their correlative conformities which can be correlated within and outside Egypt. These depositional sequences are interpreted as the result of eustatic sea‐level changes coupled with local tectonic activities. Each sequence contains a lower retrogradational parasequence set bounded above by a marine‐flooding surface and an upper progradational parasequence set bounded above by a sequence boundary. Parasequences within parasequence sets are stacked in landward‐stepping and seaward‐stepping patterns indicative of transgressive and highstand systems tracts, respectively. Lowstand systems tracts were not developed in the studied sections, presumably due to the low‐relief ramp setting. The irregular palaeotopography of the Dakhla Basin, which was caused by north‐east to south‐west trending submerged palaeo‐highs and lows, together with the eustatic sea‐level fluctuations, controlled the development and location of the two facies associations in the Kharga Oasis, the Nile Valley (open marine) and Garra El‐Arbain (marginal marine).
Cenozoic temperate and sub‐tropical carbonate sedimentation on an oceanic volcano – Chatham Islands, New Zealand
Authors: JAMES NOEL P. , JONES BRIAN , NELSON CAMPBELL S. , CAMPBELL HAMISH J. , TITJEN JEREMY
Published: October 2010

The Chatham Islands, at the eastern end of the Chatham Rise in the South‐west Pacific, are the emergent part of a Late Cretaceous to Cenozoic stratovolcano complex that is variably covered with limestones and fossiliferous tuffs. Most of these deposits accumulated in relatively shallow, high‐energy, tide‐influenced palaeoenvironments with deposition punctuated by periods of deeper‐water pelagic accumulation. Carbonate components in these neritic deposits are biogenic and dominated by molluscs and bryozoans – a heterozoan assemblage. The widespread Middle to Late Eocene Matanginui Limestone contains local photozoan elements such as large benthonic foraminifera (especially Asterocyclina) and calcareous green algae, reflecting the general Palaeogene sub‐tropical oceanographic setting. More localized Late Eocene to Oligocene deposits (Te One Limestone) as well as Pliocene carbonates (Onoua Limestone) are, however, wholly heterozoan and confirm a generally cooler‐water oceanographic setting, similar to today. Early sea floor diagenesis is interpreted to have removed most aragonite components (infaunal bivalves and epifaunal gastropods). Lack of aragonite resulted in the absence of intergranular calcite cementation during subaerial exposure, such that most carbonates are friable or unlithified. Cementation is, however, present at nodular hardground–firmground caps to metre‐scale cycles. Such cements are microcrystalline or micrometre‐thick isopachous circumgranular rinds with insufficient definitive attributes to pinpoint their environment of formation. The overall palaeoenvironment of deposition is interpreted as mesotrophic, resulting in part from upwelling about the Chatham volcanic massif and in part from nutrient element delivery from the adjacent volcanic terrane and coeval volcanism. Biotic diversity in tuffs is two to three times that in limestones, supporting the notion of especially high nutrient availability during periods of volcanism. These mid‐latitude deposits are strikingly different from their low‐latitude, tropical, photozoan counterparts in the volcanic island–coral reef ecosystem. Ground water seepage and fluvial runoff attenuate coral growth and promote microbial carbonate precipitation in these warm‐water settings. In contrast, nutrients from the same sources feed the system in the Chatham Islands cool‐water setting, promoting active heterozoan carbonate sedimentation.
Relationships between high‐magnitude relative sea‐level changes and filling of a coarse‐grained submarine canyon (Pleistocene, Ionian Calabria, Southern Italy)
Authors: ZECCHIN MASSIMO , CAFFAU MAURO , RODA CESARE
Published: October 2010

A middle Pleistocene coarse‐grained canyon fill succession (the Serra Mulara Formation) crops out in the northern sector of the Crotone Basin, a forearc basin located on the Ionian side of the Calabrian Arc and active from the Serravallian to middle Pleistocene. This succession is an example of coarse‐grained submarine canyon fill, which consists of a north‐west to south‐east elongated body (4·25 km long and up to 1·5 km wide) laterally confined by a deep‐water clayey and silty succession and located behind the modern Neto delta (north of Crotone). The thickness of the unit reaches 178 m. The lower part of the canyon fill is dominated by gravelly to sandy density‐flow deposits containing abundant bivalve and gastropod fragments, passing upward into a succession composed of metre‐scale to decimetre‐scale density‐flow deposits forming sandstone–mudstone couplets. Sandstone deposits are mostly structureless and planar‐laminated, whereas the clayey layers record hemipelagic deposition during quieter phases. This succession is overlain by another composed of thicker structureless sandstones alternating with layers of interlaminated mudstones and sandstones, which contain leaf remnants and fresh water ostracods, and are linked directly to river floods. The canyon fill is overlain by gravelly to sandy continental deposits recording a later stage of emergence. Facies analysis, together with micropalaeontological data from the hemipelagic units, suggests that the studied canyon fill records, firstly, a progressive gravel material cut‐off during deposition due to an overall relative sea‐level rise, leading to a progressive increase in the entrapment of sediment in fluvial to shallow‐marine systems, and secondly, a generalized relative sea‐level lowering. This trend probably reflects high‐magnitude glacio‐eustatic changes combined with the regional uplift of the region, ultimately leading to emergence.
Tectonic and climatic controls on Holocene channel migration, incision and terrace formation by the Rio Grande in the Palomas half graben, southern Rio Grande rift, USA
Authors: MACK GREG H. , LEEDER MIKE , PEREZ‐ARLUCEA MARTA , DURR MEREDITH
Published: October 2010

In order to evaluate potential effects of tectonics and climate change on the behaviour of the axial Rio Grande in the Rio Grande rift, a 16·5 km stretch of modern floodplain and Holocene terraces were mapped in the tectonically active Palomas half graben, south‐central New Mexico, USA. In addition, 51 cores and natural exposures were logged and 20 radiocarbon dates were obtained from charcoal, bulk organic matter, mollusc shells and pedogenic calcite. The Holocene alluvium comprises four terraces above the modern floodplain, each of which formed by a period of river incision followed by stability and renewed floodplain construction to a level below that of the previous terraces. Estimated times of incision between Terraces I and II, II and III, and III and IV are after 12 400, 8040 to 5310, and 760 to 550 yr bp, respectively, whereas the incision between Terrace IV and the modern floodplain occurred within the last 260 years. Although there is some evidence for tectonic control on river behaviour in the southern part of the basin, terrace formation is interpreted as being related to climate change, with periods of incision corresponding to times of increased aridity and low sediment/water discharge ratio in the Rio Grande. This process may have resulted from a reduction in intensity and magnitude of summer storms which supply sediment to the axial river, coupled with an increase in spring discharge peak caused by snowmelt in upstream mountain catchments.
Virus‐mediated efficient induction of epigenetic modifications of endogenous genes with phenotypic changes in plants
Authors: Kanazawa Akira , Inaba Jun‐ichi , Shimura Hanako , Otagaki Shungo , Tsukahara Sayuri , Matsuzawa Akihiko , Kim Bo Min , Goto Kazunori , Masuta Chikara
Published: October 2010

Gene silencing through transcriptional repression can be induced by targeting double‐stranded RNA (dsRNA) to a gene promoter. It has been reported that a transgene was silenced by targeting dsRNA to the promoter, and the silenced state was inherited to the progeny plant even after removal of the silencing inducer from cells. In contrast, no plant has been produced that harbors silenced endogenous gene after removal of promoter‐targeting dsRNA. Here, we show that heritable gene silencing can be induced by targeting dsRNA to the endogenous gene promoters in petunia and tomato plants, using the Cucumber mosaic virus (CMV)‐based vector. We found that efficient silencing of endogenous genes depends on the function of the 2b protein encoded in the vector virus, which has the ability to facilitate epigenetic modifications through the transport of short interfering RNA to nucleus. Bisulfite sequencing analyses on the targeted promoter in the virus‐infected and its progeny plants revealed that cytosine methylation was found not only at CG or CNG but also at CNN sites. The observed inheritance of asymmetric DNA methylation is quite unique, suggesting that plants have a mechanism to maintain even asymmetric methylation. This CMV‐based gene silencing system provides a useful tool to artificially modify DNA methylation in plant genomes and elucidate the mechanism for epigenetic controls.
Inactivation of the STT7 gene protects PsaF‐deficient Chlamydomonas reinhardtii cells from oxidative stress under high light
Authors: Berry Lindsay L. , Brzezowski Pawel , Wilson Kenneth E.
Published: October 2010

Photosystem I (PSI) utilizes light energy to excite electrons for the reduction of NADP+, and like photosystem II, it is sensitive to excess light. When PSI is excited and unable to be reduced by the electron transport chain, the special pair of chlorophyll molecules, P700+, will take electrons from neighboring sources leading to cellular damage. A Chlamydomonas reinhardtii mutant, which is defective in the production of the PsaF subunit of PSI, provides an ideal platform for studying the processes involved in protecting PSI from excess light. This strain dies following the exposure to high light (HL) because of photo‐oxidative damage. We used a second‐site suppressor screen to identify genes involved in protecting PsaF‐deficient PSI from excess light. In doing so, we demonstrated that the absence of the STT7 protein, which is required for LHCII phosphorylation and the process of state transitions suppresses the psaF HL‐lethal phenotype. On the basis of chlorophyll fluorescence measurements, the psaF mutant has a more reduced plastoquinone pool at a given photosynthetic photon flux density than the wild‐type cells. Under these conditions the process of state transitions will become active, resulting in the transfer of phosphorylated LHCII proteins to PSI, further increasing the excitation of PSI. However, in the psaF stt7 double mutant, the LHCII proteins will not be transferred to PSI, and thus the level of PSI excitation will remain lower. This study provides clear genetic evidence that the HL‐lethal phenotype of the psaF mutant is because of PSI overexciation.
Mutation surfing and the evolution of dispersal during range expansions
Authors: TRAVIS J. M. J. , MÜNKEMÜLLER T. , BURTON O. J.
Published: October 2010

A growing body of empirical evidence demonstrates that at an expanding front, there can be strong selection for greater dispersal propensity, whereas recent theory indicates that mutations occurring towards the front of a spatially expanding population can sometimes ‘surf’ to high frequency and spatial extent. Here, we consider the potential interplay between these two processes: what role may mutation surfing play in determining the course of dispersal evolution and how might dispersal evolution itself influence mutation surfing? Using an individual‐based coupled‐map lattice model, we first run simulations to determine the fate of dispersal mutants that occur at an expanding front. Our results highlight that mutants that have a slightly higher dispersal propensity than the wild type always have a higher survival probability than those mutants with a dispersal propensity lower than, or very similar to, the wild type. However, it is not always the case that mutants with very high dispersal propensity have the greatest survival probability. When dispersal mortality is high, mutants of intermediate dispersal survive most often. Interestingly, the rate of dispersal that ultimately evolves at an expanding front is often substantially higher than that which confers a novel mutant with the greatest probability of survival. Second, we run a model in which we allow dispersal to evolve over the course of a range expansion and ask how the fate of a neutral or nonneutral mutant depends upon when and where during the expansion it arises. These simulations highlight that the success of a neutral mutant depends upon the dispersal genotypes that it is associated with. An important consequence of this is that novel mutants that arise at the front of an expansion, and survive, typically end up being associated with more dispersive genotypes than the wild type. These results offer some new insights into causes and the consequences of dispersal evolution during range expansions, and the methodology we have employed can be readily extended to explore the evolutionary dynamics of other life history characteristics.
Heart rate recovery after six‐minute walk test predicts pulmonary hypertension in patients with idiopathic pulmonary fibrosis
Authors: SWIGRIS JEFFREY J. , OLSON AMY L. , SHLOBIN OKSANA A. , AHMAD SHAHZAD , BROWN KEVIN K. , NATHAN STEVEN D.
Published: October 2010

Background and objective: In patients with IPF, we sought to validate that abnormal heart rate recovery at 1 min (HRR1) after six‐minute walk test (6MWT) predicts mortality and to explore the relationship between abnormal HRR1 and pulmonary hypertension (PH).

Methods: We identified IPF patients who performed a 6MWT as part of their clinical evaluation between 2006 and 2009 and were followed to lung transplantation or death. Right heart catheterization (RHC) data were collated and analysed for the subgroup who had this procedure.

Results: There were 160 subjects who qualified for the survival analysis, and those with an abnormal HRR1 had worse survival than subjects with normal HRR1 (log‐rankP = 0.01). Eighty‐two subjects had a right heart catheter (RHC); among them, abnormal HRR1 was associated with RHC‐confirmed PH (χ2 = 4.83,P = 0.03) and had a sensitivity, specificity, positive predictive value and negative predictive value of 52%, 74%, 41% and 82%, respectively, for PH. In bivariate and multivariable analyses, abnormal HRR1 appeared to be the strongest predictor of RHC‐confirmed PH (odds ratio (OR) = 4.0, 95% CI: 1.17–13.69,P = 0.02 in the multivariable analysis).

Conclusions: This study adds to data that support the validity of abnormal HRR1 as a predictor of mortality and of RHC‐confirmed PH in IPF. Research is needed to further investigate the link between abnormal HRR1 and PH and to elucidate heart–lung interactions at work during exercise and recovery in patients with IPF.
Sound stimulation modulates high‐threshold K+ currents in mouse auditory brainstem neurons
Authors: Leão Katarina E. , Leão Richardson N. , Deardorff Adam S. , Garrett Andrew , Fyffe Robert , Walmsley Bruce
Published: October 2010

The auditory system provides a valuable experimental model to investigate the role of sensory activity in regulating neuronal membrane properties. In this study, we have investigated the role of activity directly by measuring changes in medial nucleus of the trapezoid body (MNTB) neurons in normal hearing mice subjected to 1‐h sound stimulation. Broadband (4–12 kHz) chirps were used to activate MNTB neurons tonotopically restricted to the lateral MNTB, as confirmed by c‐Fos‐immunoreactivity. Following 1‐h sound stimulation a substantial increase in Kv3.1b‐immunoreactivity was measured in the lateral region of the MNTB, which lasted for 2 h before returning to control levels. Electrophysiological patch‐clamp recordings in brainstem slices revealed an increase in high‐threshold potassium currents in the lateral MNTB of sound‐stimulated mice. Current‐clamp and dynamic‐clamp experiments showed that MNTB cells from the sound‐stimulated mice were able to maintain briefer action potentials during high‐frequency firing than cells from control mice. These results provide evidence that acoustically driven auditory activity can selectively regulate high‐threshold potassium currents in the MNTB of normal hearing mice, likely due to an increased membrane expression of Kv3.1b channels.
Phenotypic approach to the management of the chronic prostatitis/chronic pelvic pain syndrome
Authors: Nickel J. Curtis , Shoskes Daniel A.
Published: October 2010

• Our traditional approach to managing the chronic prostatitis (CP) syndromes has not been very successful for many of our patients.

• Our developing understanding of CP/chronic pelvic pain syndrome (CP/CPPS) as a heterogeneous syndrome rather than a homogenous disease has allowed us to develop treatment strategies based on individual patient characteristics.

• By considering each patient as a unique individual and tailoring treatments to a specific patient’s clinical ‘phenotype’ we improve our therapeutic outcomes.
HbA1c measurement for the diagnosis of diabetes: is it enough?
Authors: Cavagnolli G. , Comerlato J. , Comerlato C. , Renz P. B. , Gross J. L. , Camargo J. L.
Published: October 2010

Diabet. Med. 28, 31–35 (2011)

Aim  To analyse the performance of HbA1c in diagnosing Type 2 diabetes based on fasting plasma glucose and/or 2‐h plasma glucose measurements after a 75‐g oral glucose tolerance test.

Methods  This is a study of diagnostic test accuracy in individuals referred to the Clinical Pathology Department for oral glucose tolerance testing. After fasting overnight, HbA1c, fasting plasma glucose and 2‐h plasma glucose were measured. The receiver operating characteristic curve was used to evaluate the diagnostic performance of HbA1c.

Results  Four hundred and ninety‐eight subjects (195 male, mean age 56 years) were enrolled and 115 (23.1%) were diagnosed with diabetes according to glucose‐based methods and only 56 (11.2%) individuals were identified by HbA1c≥ 6.5% (48 mmol/mol) (sensitivity 20.9%, specificity 95.3%). There is poor agreement between the newly recommended criterion and the current glucose‐based diagnostic criteria (κ = 0.217; P < 0.001), probably because the diagnostic methods identify different populations of patients. Adding a glucose‐based method into an algorithm, as proposed by the UK Department of Health, improved HbA1c performance.

Conclusions  HbA1c≥ 6.5% (48 mmol/mol) showed limited sensitivity to diabetes diagnosis, although with high specificity. The results suggest that this cut‐off point would not be enough to diagnose diabetes. Its use as the sole diabetes diagnostic test should be interpreted with caution to assure the correct classification of diabetic individuals.
Association between childhood obesity and subsequent Type 1 diabetes: a systematic review and meta‐analysis
Authors: Verbeeten K. C. , Elks C. E. , Daneman D. , Ong K. K.
Published: October 2010

Diabet. Med. 28, 10–18 (2011)

Aims  To review and synthesize the published evidence on the possible association between childhood obesity and the subsequent risk of Type 1 diabetes.

Methods  The PubMed database was systematically searched for studies using childhood obesity, BMI or %weight‐for‐height as the exposure variable and subsequent Type 1 diabetes as the outcome. Studies were only included if assessment of obesity preceded the diagnosis of Type 1 diabetes.

Results  Eight case–control studies and one cohort study were included, comprising a total of 2658 cases. Of these nine studies, seven reported a significant association between childhood obesity, BMI or %weight‐for‐height and increased risk for Type 1 diabetes. Meta‐analysis of the four studies that reported childhood obesity as a categorical exposure produced a pooled odds ratio of 2.03 (95% CI 1.46–2.80) for subsequent Type 1 diabetes; however, in those studies, age at obesity assessment varied from age 1 to 12 years. A dose–response relationship was supported by a continuous association between childhood BMI and subsequent Type 1 diabetes in a meta‐analysis of five studies (pooled odds ratio 1.25 (95%CI 1.04–1.51) per 1 sd higher BMI).

Conclusion  There is overall evidence for an association between childhood obesity, or higher BMI, and increased risk of subsequent Type 1 diabetes. Several theories have been proposed for a causal relationship. Reduction in Type 1 diabetes should be considered as a potential additional benefit of preventing childhood obesity.
Sexual Harassment Judgments by British Employment Tribunals 1995–2005: Implications for Claimants and their Advocates
Authors: Rosenthal Patrice , Budjanovcanin Alexandra
Published: October 2010

This article reports on the first large‐scale study of sexual harassment litigation in Britain based on analysis of official case records. Its aim is to identify key factors distinguishing successful and unsuccessful claims. Five themes drive the analysis: credibility and its construction, the various types of sexual harassment, power resources, the time period in which the case was heard, and the gender composition of the tribunal. Hypotheses are tested on a random sample of 183 cases heard between 1995 and 2005. Some important disconnections between workplace realities and the operation of the tribunal system were revealed. Credibility of claimants turns importantly on how they initially reacted to the harassment of which they later complained and on the number of complementary claims they bring. Workers in elementary occupations experience a lower success rate before tribunals. Power resources in the form of legal representation significantly affect case outcomes. Implications for claimants and their advocates are discussed.
High School Clubs Participation and Future Supervisory Status
Authors: Kosteas Vasilios D.
Published: October 2010

This article examines the relationship between high school clubs participation and the probability that a worker will become a supervisor and the types of responsibility she will have, using the National Longitudinal Surveys of Youth 1979 dataset. While other articles have tried to explain what affects a worker's probability of being a supervisor, this article focuses on the impact of participation in extracurricular activities during high school. Both probit and household fixed effects estimates show that clubs participation raises the probability that an individual will be a supervisor and have high‐level supervisory responsibilities.
3. The Foundations of Causal Inference
Authors: Pearl Judea
Published: October 2010

This paper reviews recent advances in the foundations of causal inference and introduces a systematic methodology for defining, estimating, and testing causal claims in experimental and observational studies. It is based on nonparametric structural equation models (SEM)—a natural generalization of those usedby econometricians and social scientists in the 1950s and 1960s, which provides a coherent mathematical foundation for the analysis of causes and counterfactuals. In particular, the paper surveys the development of mathematical tools for inferring the effects of potential interventions (also called “causal effects” or “policy evaluation”), as well as direct and indirect effects (also known as “mediation”), in both linear and nonlinear systems. Finally, the paper clarifies the role of propensity score matching in causal analysis, defines the relationships between the structural and potential-outcome frameworks, and develops symbiotic tools that use the strong features of both.