bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Activation During Response Interference in Twins Discordant or Concordant for Obsessive Compulsive Symptoms
Authors: den Braber Anouk , van ‘t Ent Dennis , Cath Danielle C. , Veltman Dick J. , Boomsma Dorret I. , de Geus Eco J. C.
Published: June 2012

One of the core behavioral features associated with obsessive compulsive symptomatology is the inability to inhibit thoughts and/or behaviors. Neuroimaging studies have indicated abnormalities in frontostriatal and dorsolateral prefrontal – anterior cingulate circuits during inhibitory control in patients with obsessive compulsive disorder compared with controls. In the present study, task performance and brain activation during Stroop color-word and Flanker interference were compared within monozygotic twin pairs discordant for obsessive compulsive symptoms and between groups of pairs scoring very low or very high on obsessive compulsive symptoms, in order to examine the differential impact of non-shared environmental versus genetic risk factors for obsessive compulsive symptomatology on inhibitory control related functional brain activation. Although performance was intact, brain activation during inhibition of distracting information differed between obsessive compulsive symptom high-scoring compared to low-scoring subjects. Regions affected in the discordant group (e.g., temporal and anterior cingulate gyrus) were partly different from those observed to be affected in the concordant groups (e.g., parietal gyrus and thalamus). A robust increase in dorsolateral prefrontal activity during response interference was observed in both the high-scoring twins of the discordant sample and the high-scoring twins of the concordant sample, marking this structure as a possible key region for disturbances in inhibitory control in obsessive compulsive disorder.
Neuroimaging and Genetics: Exploring, Searching, and Finding
Authors: Smit Dirk J. A. , van ‘t Ent Dennis , de Zubicaray Greig , Stein Jason L.
Published: June 2012

This issue on the genetics of brain imaging phenotypes is a celebration of the happy marriage between two of science's highly interesting fields: neuroscience and genetics. The articles collected here are ample evidence that a good deal of synergy exists in this marriage. A wide selection of papers is presented that provide many different perspectives on how genes cause variation in brain structure and function, which in turn influence behavioral phenotypes (including psychopathology). They are examples of the many different methodologies in contemporary genetics and neuroscience research. Genetic methodology includes genome-wide association (GWA), candidate-gene association, and twin studies. Sources of data on brain phenotypes include cortical gray matter (GM) structural/volumetric measures from magnetic resonance imaging (MRI); white matter (WM) measures from diffusion tensor imaging (DTI), such as fractional anisotropy; functional- (activity-) based measures from electroencephalography (EEG), and functional MRI (fMRI). Together, they reflect a combination of scientific fields that have seen great technological advances, whether it is the single-nucleotide polymorphism (SNP) array in genetics, the increasingly high-resolution MRI imaging, or high angular resolution diffusion imaging technique for measuring WM connective properties.
Individual Differences in EEG Spectral Power Reflect Genetic Variance in Gray and White Matter Volumes
Authors: Smit Dirk J. A. , Boomsma Dorret I. , Schnack Hugo G. , Hulshoff Pol Hilleke E. , de Geus Eco J. C.
Published: June 2012

The human electroencephalogram (EEG) consists of oscillations that reflect the summation of postsynaptic potentials at the dendritic tree of cortical neurons. The strength of the oscillations (EEG power) is a highly genetic trait that has been related to individual differences in many phenotypes, including intelligence and liability for psychopathology. Here, we investigated whether brain anatomy underlies these EEG power differences by correlating it to gray and white matter volumes (GMV, WMV), and additionally investigated whether this association can be attributed to genes or environmental factors. EEG was measured in a sample of 405 young adult twins and their siblings, and power in the theta (~4 Hz), alpha (~10 Hz), and beta (~20 Hz) frequency bands determined. A subset of 121 subjects were also scanned in a 1.5 T MRI scanner, and gray and white matter volumes defined as the total of cortical and subcortical volumes, excluding cerebellum. Both MRI-based volumes and EEG power spectra were highly heritable. GMV and WMV correlated .25 to .29 with EEG power for the slower oscillations (theta, alpha). Moreover, these phenotypic correlations largely reflected genetic covariation, irrespective of oscillation frequency and volume type. Genetic correlations (.31 < rA < .43) revealed that only moderate proportions of the heritable variance overlapped between MRI volumes and EEG power. The results suggest that MRI volumes and EEG power share genetic sources of variation, which may reflect such processes as myelination, synaptic density, and dendritic outgrowth.
Imaging and Cognitive Genetics: The Norwegian Cognitive NeuroGenetics Sample
Authors: Espeseth Thomas , Christoforou Andrea , Lundervold Astri J. , Steen Vidar M. , Le Hellard Stephanie , Reinvang Ivar
Published: June 2012

Data collection for the Norwegian Cognitive NeuroGenetics sample (NCNG) was initiated in 2003 with a research grant (to Ivar Reinvang) to study cognitive aging, brain function, and genetic risk factors. The original focus was on the effects of aging (from middle age and up) and candidate genes (e.g., APOE, CHRNA4) in cross-sectional and longitudinal designs, with the cognitive and MRI-based data primarily being used for this purpose. However, as the main topic of the project broadened from cognitive aging to imaging and cognitive genetics more generally, the sample size, age range of the participants, and scope of available phenotypes and genotypes, have developed beyond the initial project. In 2009, a genome-wide association (GWA) study was undertaken, and the NCNG proper was established to study the genetics of cognitive and brain function more comprehensively. The NCNG is now controlled by the NCNG Study Group, which consists of the present authors. Prominent features of the NCNG are the adult life-span coverage of healthy participants with high-dimensional imaging, and cognitive data from a genetically homogenous sample. Another unique property is the large-scale (sample size 300–700) use of experimental cognitive tasks focusing on attention and working memory. The NCNG data is now used in numerous ongoing GWA-based studies and has contributed to several international consortia on imaging and cognitive genetics. The objective of the following presentation is to give other researchers the information necessary to evaluate possible contributions from the NCNG to various multi-sample data analyses.
Estimation of Subject-Specific Heritabilities From Intra-Individual Variation: iFACE
Authors: Molenaar Peter C. M. , Smit Dirk J. A. , Boomsma Dorret I. , Nesselroade John R.
Published: June 2012

A new genetic factor model for multivariate phenotypic time series, iFACE, is presented which allows for the estimation of subject-specific model parameters of genetic and environmental factors. The iFACE was applied to multivariate EEG registrations obtained with single dizygotic twin pairs. The results showed evidence for considerable subject-specificity in heritabilities and environmental effects. The assumption that the population is homogeneous (i.e., that each case in the population obeys the same parametric model), does not hold for these psychophysiological data, and its use should be critically reconsidered. We conclude that the iFACE provides a powerful new methodology to assess heterogeneity (subject-specificity) based on phenotypic observations.
Mechanisms of Vascular Disease
Authors: Fitridge Robert , Thompson Matthew
Published: June 2012

New updated edition first published with Cambridge University Press. This new edition includes 29 chapters on topics as diverse as pathophysiology of atherosclerosis, vascular haemodynamics, haemostasis, thrombophilia and post-amputation pain syndromes.
Modeling suggests that oblique extension facilitates rifting and continental break‐up
Authors: Brune Sascha , Popov Anton A. , Sobolev Stephan V.
Published: June 2012

In many cases the initial stage of continental break‐up was and is associated with oblique rifting. That includes break‐up in the Southern and Equatorial Atlantic, separation from eastern and western Gondwana as well as many recent rift systems, like Gulf of California, Ethiopia Rift and Dead Sea fault. Using a simple analytic mechanical model and advanced numerical, thermomechanical modeling techniques we investigate the influence of oblique extension on the required tectonic force in a three‐dimensional setting. While magmatic processes have been already suggested to affect rift evolution, we show that additional mechanisms emerge due to the three‐dimensionality of an extensional system. Focusing on non‐magmatic rift settings, we find that oblique extension significantly facilitates the rift process. This is due to the fact that oblique deformation requires less force in order to reach the plastic yield limit than rift‐perpendicular extension. The model shows that in the case of two competing non‐magmatic rifts, with one perpendicular and one oblique to the direction of extension but otherwise having identical properties, the oblique rift zone is mechanically preferred and thus attracts more strain.
A multiproxy record of terrestrial inputs to the coastal ocean using minor and trace elements (Ba/Ca, Mn/Ca, Y/Ca) and carbon isotopes (δ13C, Δ14C) in a nearshore coral from Puerto Rico
Authors: Moyer Ryan P. , Grottoli Andréa G. , Olesik John W.
Published: June 2012

Small mountainous rivers (SMRs), despite their disproportionate size relative to larger rivers, may contribute as much as one third of the total terrigenous material exported to the coastal ocean. Corals growing near the mouths of tropical SMRs have the potential to provide records of terrigenous material fluxes because they are long lived and elemental and isotope signatures within their skeletons are useful proxies of palaeoceanographic variability. Here, a 56 year record of coral skeletal Ba/Ca, Mn/Ca, Y/Ca, δ13C, and Δ14C measurements is presented from a Montastraea faveolata colony growing ∼1 km from the mouth of an SMR in eastern Puerto Rico. Coral Ba/Ca was coherent with river discharge and coral skeletal δ13C at annual periodicity corresponding to synchronous depletions of both δ13C and Δ14C in the coral skeleton, and Mn/Ca and Y/Ca were not coherent with river discharge at annual periodicity. Coherence between river discharge and Ba/Ca and the concurrent timing of increases in Ba/Ca with decreases in δ13C and Δ14C indicate that river discharge is simultaneously recorded by all three geochemical tracers. A reconstruction of Rio Fajardo discharge is presented for a period in which no instrumental discharge records exists shows good fidelity with the timing of increased discharge during the wet season. Thus, coral‐based multiple‐proxy records can be valuable tools for reconstructing the timing and variability of SMR discharge to the coastal ocean. Such records are critical to understanding changes in material fluxes and biogeochemical cycles in coastal environments due to land use and climate change.
Synkinematic magmatism, heterogeneous deformation, and progressive strain localization in a strike‐slip shear zone: The case of the right‐lateral Karakorum fault
Authors: Boutonnet Emmanuelle , Leloup P. H. , Arnaud N. , Paquette J.‐L. , Davis W. J. , Hattori K.
Published: June 2012

New structural observations coupled with 15 U/Pb and 24 Ar/Ar new ages from the Karakorum shear zone (KSZ) constrain the timing and slip rate of the right‐lateral Karakorum fault zone (KFZ), one of the great continental Asian strike‐slip faults. In the Tangtse‐Darbuk area, the Tangtse (SW) and Muglib (NE) mylonitic strands of the KSZ frame the less deformed Pangong Range. Inherited U/Pb ages show that granitic protoliths are mostly from the Karakorum and Ladakh batoliths, with a major Miocene melting event lasting from ≥21.5 to 13.5 Ma. Some of the Miocene granitic bodies show structural evidence for intrusion synkinematic to the KSZ. The oldest of these granitoids is 18.8 ± 0.4 Ma old, implying that deformation started prior to ∼19 Ma. Microstructural data show that right‐lateral deformation pursued during cooling. Ar/Ar data show that ductile deformation stopped earlier in the Tangtse (∼11 Ma) than in the Muglib strand (∼7 Ma). Deformation ended at ∼11 Ma in the Tangtse strand while it is still active in the Muglib strand, suggesting a progressive localization of deformation. When merged with published observations along the KFZ, these data suggest that the KFZ nucleated in the North Ayilari range at least ∼22 Ma ago. The long‐term fault rate is 0.84 to 1.3 cm/yr, considering a total offset of 200 to 240 km. The KSZ collected magma produced within the shear zone and/or deeper in crust for which the producing mechanism stays unclear but was not the lower crustal channel flow.
Ensemble hydrological prediction‐based real‐time optimization of a multiobjective reservoir during flood season in a semiarid basin with global numerical weather predictions
Authors: Wang Fuxing , Wang Lei , Zhou Huicheng , Saavedra Valeriano Oliver C. , Koike Toshio , Li Wenlong
Published: June 2012

Future streamflow uncertainties hinder reservoir real‐time operation, but the ensemble prediction technique is effective for reducing the uncertainties. This study aims to combine ensemble hydrological predictions with real‐time multiobjective reservoir optimization during flood season. The ensemble prediction‐based reservoir optimization system (EPROS) takes advantage of 8 day lead time global numerical weather predictions (NWPs) by the Japan Meteorological Agency (JMA). Thirty‐member ensemble streamflows are generated through running the water and energy budget‐based distributed hydrological model fed with 30‐member perturbed quantitative precipitation forecasts (QPFs) and deterministic NWPs. The QPF perturbation amplitudes are calculated from the QPF intensity and location errors during previous 8 day periods. The reservoir objective function is established to minimize the maximum reservoir water level (reservoir and upstream safety), the downstream flood peak (downstream safety), and the difference between simulated reservoir end water level and target level (water use). The system is evaluated on the Fengman reservoir basin (semiarid), which often suffers from extreme floods in summer and serious droughts in spring. The results show the ensemble QPFs generated by EPROS are comparable to those for JMA by using probability‐based measures. The streamflow forecast error is significantly reduced by employing the ensemble prediction approach. The system has demonstrated high efficiency in optimizing reservoir objectives for both normal and critical flood events. Fifty‐member ensembles generate a wider streamflow and reservoir release range than 10‐member ensembles, but the ensemble mean end water levels and releases are comparable. The system is easy to operate and thereby feasible for practical operations in various reservoir basins.
Post‐fire changes in net shortwave radiation along a latitudinal gradient in boreal North America
Authors: Jin Yufang , Randerson James T. , Goulden Michael L. , Goetz Scott J.
Published: June 2012

Understanding how a changing boreal fire regime is likely to influence regional climate requires detailed information about fire effects on the surface radiation budget. We used time series of satellite observations of surface albedo from 2000–2011 and fire perimeters since 1970 to study post‐fire changes in surface net shortwave radiation along a latitudinal transect in central Canada. Fire‐induced surface shortwave forcing (SSF) integrated over an annual cycle for the first 30 years after fire was similar (−4.1 W m−2 with a 95% confidence interval of −4.5 to −3.7 W m−2) between southern and northern boreal regions. The lack of a latitudinal difference in SSF was caused by counteracting latitudinal trends in seasonal contributions. Spring (March, April, and May) SSF increased with latitude, from −7.2 W m−2 in the south to −10.1 W m−2in the north, primarily because of delayed snow melt, which amplified albedo differences between unburned forests and recovering stands. In contrast, winter incoming solar radiation and summer albedo change decreased from south to north, resulting in a decreasing latitudinal trend in winter and summer SSF. Vegetation recovery was slower in the north, leading to smaller increases in summer albedo during the first decade after fire, and a prolonged phase of elevated spring albedo during the second decade. Our results indicate that fires reduce surface net shortwave radiation considerably for many boreal forest ecosystems in North America, providing further evidence that disturbance‐mediated shifts in surface energy exchange need to be considered in efforts to manage these forests for climate change mitigation.
Monitoring the volcanic unrest of El Hierro (Canary Islands) before the onset of the 2011–2012 submarine eruption
Authors: López C. , Blanco M. J. , Abella R. , Brenes B. , Cabrera Rodríguez V. M. , Casas B. , Domínguez Cerdeña I. , Felpeto A. , de Villalta M. Fernández , del Fresno C. , García O. , García‐Arias M. J. , García‐Cañada L. , Gomis Moreno A. , González‐Alonso E. , Guzmán Pérez J. , Iribarren I. , López‐Díaz R. , Luengo‐Oroz N. , Meletlidis S. , Moreno M. , Moure D. , de Pablo J. Pereda , Rodero C. , Romero E. , Sainz‐Maza S. , Sentre Domingo M. A. , Torres P. A. , Trigo P. , Villasante‐Marcos V.
Published: June 2012

On 10 October 2011, a submarine volcanic eruption started 2 km south from El Hierro Island (Spain). Since July 2011 a dense multiparametric monitoring network was deployed all over the island by Instituto Geográfico Nacional (IGN). By the time the eruption started, almost 10000 earthquakes had been located and the deformation analyses showed a maximum deformation of more than 5 cm. Earthquake migration from the north to the south of the island and acceleration of seismicity are in good correlation with changes in the deformation pattern as well as with some anomalies in geochemical and geomagnetic parameters. An earthquake of local magnitude 4.3 at 12 km depth (8 October 2011) and shallower seismicity a day after, preceded the onset of the eruption. This is the first time that a volcanic eruption is fully monitored in the Canary Islands. Data recorded during this unrest episode at El Hierro will contribute to understand reawakening of volcanic activity in this region and others of similar characteristics.
Perchlorate induced low temperature carbonate decomposition in the Mars Phoenix Thermal and Evolved Gas Analyzer (TEGA)
Authors: Cannon K. M. , Sutter B. , Ming D. W. , Boynton W. V. , Quinn R.
Published: June 2012

Simulated Thermal Evolved Gas Analyzer (TEGA) analyses have shown that a CO2 release detected between 400°C and 680°C by the Phoenix Lander's TEGA instrument may have been caused by a reaction between calcium carbonate and hydrated magnesium perchlorate. In our experiments a CO2release beginning at 385 ± 12°C was attributed to calcite reacting with water vapor and HCl gas from the dehydration and thermal decomposition of Mg‐perchlorate. The release of CO2 is consistent with the TEGA detection of CO2 released between 400 and 680°C, with the amount of CO2increasing linearly with added perchlorate. X‐ray diffraction (XRD) experiments confirmed CaCl2 formation from the reaction between calcite and HCl. These results have important implications for the Mars Science Laboratory (MSL) Curiosity rover. Heating soils may cause inorganic release of CO2; therefore, detection of organic fragments, not CO2 alone, should be used as definitive evidence for organics in Martian soils.
On the sensitivity of droplet size relative dispersion to warm cumulus cloud evolution
Authors: Tas E. , Koren I. , Altaratz O.
Published: June 2012

Relative dispersion (ε), defined as the ratio between cloud droplet size distribution width (σ) and cloud droplet average radius (〈r〉), is a key factor used to parameterize various cloud processes in global circulation models (GCMs) and bulk microphysical scheme models (BSMs). Recent studies indicate that the impact of aerosol loading (N) and atmospheric thermodynamic conditions on ε are far from fully understood. Currently, a fixed value per hydrometeor type is used in most BSMs and GCMs, which imposes significant limitations on our ability to model and predict cloud processes and their impact on the environment, on regional to global scales. In this study, we use a detailed bin microphysics single cloud model to investigate the combined impact of atmospheric thermodynamic conditions and N on ε, in warm cumulus clouds. As initial conditions, we used different lapse‐rates combined with 8 scenarios of aerosol loading, representing very clean (N = 25 cm−3) to heavily polluted (N = 1600 cm−3) conditions. Moreover, the results are analyzed per cloud evolutionary stage according to the dominance of microphysical processes. The use of this method indicated a different pattern of ε at each stage. Specifically, during the mature stage fitting of ε to rv is relatively resilient to changes in the environmental conditions. Such findings suggest a new view of the effect of aerosols on clouds, via changes in the cloud evolution patterns and a new approach to parameterization of ε based on rv, which can significantly improve the prediction of cloud processes by GCMs and BSMs.
Formation of Martian araneiforms by gas‐driven erosion of granular material
Authors: de Villiers S. , Nermoen A. , Jamtveit B. , Mathiesen J. , Meakin P. , Werner S. C.
Published: June 2012

Sublimation at the lower surface of a seasonal sheet of translucent CO2 ice at high southern latitudes during the Martian spring, and rapid outflow of the CO2 gas generated in this manner through holes in the ice, has been proposed as the origin of dendritic 100 m–1 km scale branched channels known as spiders or araneiforms and dark dust fans deposited on top of the ice. We show that patterns very similar to araneiforms are formed in a Hele‐Shaw cell filled with an unconsolidated granular material by slowly deforming the upper wall upward and allowing it to return rapidly to its original position to drive air and entrained particles through a small hole in the upper wall. Straight, braided and quasiperiodic oscillating channels, unlike meandering channels on Earth were also formed.
First measurements of radar coherent scatter by the Radio Aurora Explorer CubeSat
Authors: Bahcivan H. , Cutler J. W. , Bennett M. , Kempke B. , Springmann J. C. , Buonocore J. , Nicolls M. , Doe R.
Published: June 2012

The Radio Aurora Explorer CubeSat detected the first radar echoes during the solar storm of March 8, 2012. The 300 s ground‐to‐space bi‐static radar experiment was conducted in conjunction with the Poker Flat Incoherent Scatter Radar in the local morning (∼8 am) over Poker Flat, Alaska. The geomagnetic conditions for theEregion field‐aligned irregularity generation were optimal due to strong (about 1500 m/s)F region ion drifts and sufficient E region ionization (electron densities were ∼2 × 1011 m−3). The corresponding Eregion electric field of ∼80 mV/m was larger than the excitation threshold for the Farley‐Buneman instability. An auto‐correlation analysis resolved, for the first time, the distribution of auroralEregion backscatter with 3 km resolution in altitude and sub‐degree resolution in aspect angle. Moreover, the measured Doppler velocities of the UHF scatter shows the phase speed saturation of the meter‐scale plasma waves. The measured Doppler velocity is in excellent agreement with theCs cos θ formula for auroral E region irregularities.
Coseismic slip distribution of the 2011 off the Pacific Coast of Tohoku Earthquake (M9.0) refined by means of seafloor geodetic data
Authors: Iinuma T. , Hino R. , Kido M. , Inazu D. , Osada Y. , Ito Y. , Ohzono M. , Tsushima H. , Suzuki S. , Fujimoto H. , Miura S.
Published: June 2012

On 11 March 2011, the devastating M9.0 Tohoku Earthquake occurred on the interface of the subducting Pacific plate, and was followed by a huge tsunami that killed about 20,000 people. Several geophysical studies have already suggested that the very shallow portion of the plate interface might have played an important role in producing such a large earthquake and tsunami. However, the sparsity of seafloor observations leads to insufficient spatial resolution of the fault slip on such a shallow plate interface. For this reason, the location and degree of the slip has not yet been estimated accurately enough to assess future seismic risks. Thus, we estimated the coseismic slip distribution based on terrestrial GPS observations and all available seafloor geodetic data that significantly improve the spatial resolution at the shallow portion of the plate interface. The results reveal that an extremely large (greater than 50 m) slip occurred in a small (about 40 km in width and 120 km in length) area near the Japan Trench and generated the huge tsunami. The estimated slip distribution and a comparison of it with the coupling coefficient distribution deduced from the analysis of the small repeating earthquakes suggest that the 2011 Tohoku Earthquake released strain energy that had accumulated over the past 1000 years, probably since the Jogan Earthquake in 869. The accurate assessments of seismic risks on very shallow plate interfaces in subduction zones throughout the world can be obtained by improving the quality and quantity of seafloor geodetic observations.
Response of the equatorial basin‐wide SST to non‐breaking surface wave‐induced mixing in a climate model: An amendment to tropical bias
Authors: Song Zhenya , Qiao Fangli , Song Yajuan
Published: June 2012

One of the common problems of the coupled atmosphere‐ocean general circulation models (AOGCMs) without flux correction is that the simulated sea surface temperature (SST) deviates noticeably from the observation especially in the tropics, such as the too cold tongue in the eastern Pacific and a reversed SST zonal gradient in the equatorial Atlantic. The coupled atmosphere‐wave‐ocean general circulation model, which incorporates the non‐breaking surface wave‐induced mixing into the CCSM3 through a coupler, can improve the simulation of the tropical SST. On the ocean‐basin scale, the wave‐induced vertical mixing can generate “West‐Positive and East‐Negative” pattern for the equatorial SST that much alleviates the tropical bias. The formation mechanism for this basin‐wide response to the wave‐induced mixing is analyzed through sensitive experiments of AOGCMs and stand‐alone ocean general circulation models (OGCMs). First, in each basin, the SST becomes colder under the direct effect of the wave‐induced mixing, and the SST in the eastern part of each basin is colder due to the shallower ocean mixed layer than that of the western part. The SST in the western basin (or central basin in the Pacific Ocean) increases due to the weakened eastward zonal current. Then, the pattern of warm SST in the west and cold SST in the east is amplified due to the Bjernkes feedback in a climate system. The net heat flux feedback plays a negative role in this kind of SST response.
Engineering and ethical perspectives in synthetic biology
Authors: Anderson James , Strelkowa Natalja , Stan Guy‐Bart , Douglas Thomas , Savulescu Julian , Barahona Mauricio , Papachristodoulou Antonis
Published: June 2012

The applications of synthetic biology will involve the release of artificial life forms into the environment. These organisms will present unique safety challenges that need to be addressed by researchers and regulators to win public engagement and support
Kindlin 2 forms a transcriptional complex with β‐catenin and TCF4 to enhance Wnt signalling
Authors: Yu Yu , Wu Junzhou , Wang Yunling , Zhao Ting , Ma Bo , Liu Yuqing , Fang Weigang , Zhu Wei‐Guo , Zhang Hongquan
Published: June 2012

Kindlin 2, as a focal adhesion protein, controls integrin activation. However, the association of Kindlin 2 with cancer‐related signalling pathways is unknown. Here we identified a new direct interaction between Kindlin 2 and the active β‐catenin. Importantly, Kindlin 2 forms a tripartite complex with β‐catenin and TCF4. Mechanistically, Kindlin 2 selectively strengthens the occupancy of β‐catenin on the Wnt target gene Axin2 and enhances Axin2 gene expression. Functionally, the β‐catenin–Axin2–Snail cascade is required for Kindlin 2‐induced tumour cell invasion. Our data indicate that Kindlin 2 is a new regulator of Wnt signalling, providing a mechanistic insight into the role of Kindlin 2 in cancer progression.
The G-protein regulator LGN modulates the activity of the NO receptor soluble guanylate cyclase
Authors: Chauhan Swati , Jelen Filip , Sharina Iraida , Martin Emil
Published: June 2012

sGC (soluble guanylate cyclase) is the main mediator of NO signalling. Biochemical and physiological studies suggest that, besides NO, in vivo regulation of sGC involves direct interaction with other proteins. Using yeast two-hybrid screening, we identified that the multidomain LGN (Leu-Gly-Asn repeat-enriched protein) interacts with both α1 and β1 sGC subunits. LGN and sGC co-localized in the cell cytoplasm, and the LGN–sGC complex was co-immunoprecipitated from cells expressing both proteins and from native tissues. Their interaction requires the N-terminal tetratricopeptide repeats of LGN, but does not require the N-terminal portions of α1 or β1 sGC subunits. Overexpression of LGN decreases the activity of cellular sGC, whereas knockdown of LGN mRNA and protein correlated with increased sGC activity. Although purified LGN interacts directly with purified sGC, the inhibitory effect in vitro is observed only after supplementation of cell lysate to the reaction. Although resting sGC and sGC activated by the stimulator BAY41-2272 have very similar LGN-IC50 values to the NO-stimulated sGC, they have a much higher Hill coefficient, suggesting co-operative binding with respect to LGN in the low-activated state of sGC. AGS3 (activator of G-protein signalling 3), the closest LGN homologue, also inhibits sGC. The interaction of sGC with these scaffolding proteins may expand the cross-talk between NO/cGMP signalling and other cellular pathways and tailor sGC function to specific tissues or signals.
Endoplasmic reticulum factor ERLIN2 regulates cytosolic lipid content in cancer cells
Authors: Wang Guohui , Zhang Xuebao , Lee Jin-Sook , Wang Xiaogang , Yang Zeng-Quan , Zhang Kezhong
Published: June 2012

Increased de novo lipogenesis is a hallmark of aggressive cancers. Lipid droplets, the major form of cytosolic lipid storage, have been implicated in cancer cell proliferation and tumorigenesis. Recently, we identified the ERLIN2 [ER (endoplasmic reticulum) lipid raft-associated 2) gene that is amplified and overexpressed in aggressive human breast cancer. Previous studies demonstrated that ERLIN2 plays a supporting oncogenic role by facilitating the transformation of human breast cancer cells. In the present study, we found that ERLIN2 supports cancer cell growth by regulating cytosolic lipid droplet production. ERLIN2 is preferably expressed in human breast cancer cells or hepatoma cells and is inducible by insulin signalling or when cells are cultured in lipoprotein-deficient medium. Increased expression of ERLIN2 promotes the accumulation of cytosolic lipid droplets in breast cancer cells or hepatoma cells in response to insulin or overload of unsaturated fatty acids. ERLIN2 regulates activation of SREBP (sterol regulatory element-binding protein) 1c, the key regulator of de novo lipogenesis, in cancer cells. ERLIN2 was found to bind to INSIG1 (insulin-induced gene 1), a key ER membrane protein that blocks SREBP activation. Consistent with the role of ERLIN2 in regulating cytosolic lipid content, down-regulation of ERLIN2 in breast cancer or hepatoma cells led to lower cell proliferation rates. The present study revealed a novel role for ERLIN2 in supporting cancer cell growth by promoting the activation of the key lipogenic regulator SREBP1c and the production of cytosolic lipid droplets. The identification of ERLIN2 as a regulator of cytosolic lipid content in cancer cells has important implications for understanding the molecular basis of tumorigenesis and the treatment of cancer.
The apoptotic effect and associated signalling of HSP90 inhibitor 17‐DMAG in hepatocellular carcinoma cells
Authors: Leng Ai‐min , Liu Ting , Yang Jing , Cui Jian‐fang , Li Xiu‐hua , Zhu Ya‐nan , Xiong Ting , Zhang Guiying , Chen Yuxiang
Published: June 2012

Primary liver cancer is one of the highly malignant tumours. The traditional surgery, chemotherapy and radiation therapy only established 6% of 5‐year survival rate in HCC (hepatocellular carcinoma). Therefore there is an urgent need to develop new therapeutic strategies. HSP90 (heat shock protein 90) is one of the important molecular chaperones and was identified with high expression in the primary liver cancer. In this study, we evaluated the therapeutic effect of specific HSP90 inhibitor 17‐DMAG (17‐dimethylaminoethylamino‐17‐demethoxy geldanamycin) in HCC cells. The time and concentration effects of 17‐DMAG were investigated in HCC cells. Cell proliferation was measured by MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide] assay and cell counting. Apoptosis was detected by flow cytometry with staining of Annexin V‐FITC/PI (propidium iodide). The protein levels of survivin, cyclin D1, p53 and NF‐κB (nuclear factor κB) were measured by Western blotting. 17‐DMAG inhibited the proliferation of HCC cells in a time‐ and concentration‐dependent manner. Treatment with 400 nmol/l 17‐DMAG for 48 h significantly induced early‐stage apoptosis (22.4%). Conversely, it induced less late‐stage apoptosis (3.03%). The 5 mg/l of cisplatin induced significantly less early‐stage apoptosis (6.5%), but similar proportion of late‐stage apoptosis (4.89%) compared with 17‐DMAG. Inhibition of HSP90 activity by 400 nmol/l 17‐DMAG decreased protein levels of survivin, cyclin D1 and NF‐κB protein levels, whereas increased p53 protein level. HSP90 plays a key role in HCC cell growth and survival through regulation of survivin, cyclin D1, p53 and nucleus NF‐κB protein levels and the specific HSP90 inhibitor 17‐DMAG can play a therapeutic role in HCC treatment.
Mesenchymal stem cells derived from different origins have unique sensitivities to different chemotherapeutic agents
Authors: Qi Zhengyu , Zhang Yanmin , Liu Lin , Guo Xin , Qin Jie , Cui Guanghui
Published: June 2012

BMSCs (bone‐marrow‐derived mesenchymal stem cells) and ADSCs (adipose tissue‐derived mesenchymal stem cells) are virtually identical in cell surface marker profile and differentiation potential. These cell populations have promising characteristics for clinical application. We have investigated the sensitivity of these cell populations to various chemotherapeutic agents by testing the inhibition of cell proliferation, low molecular DNA bands formation, in situ apoptosis, apoptosis‐related gene expression and cell senescence after treatment. BU (busulfan), methotrexate and doxorubicin treatment led to a marked and dose‐dependent reduction in cell viability compared with 5‐FU (5‐fluorouracil) treatment. Different expression patterns of apoptosis‐related genes were found in the BMSCs and ADSCs following treatment with the agents, but no low molecular mass DNA bands were detected. BMSCs had a higher percentage of apoptotic and senescent cells following treatment with chemotherapeutic agents compared with ADSCs. These findings suggest that these two cell populations respond differently to chemotherapy treatment. ADSCs are more resistant than BMSCs to chemotherapy‐induced senescence and apoptosis, indicating that they might be more advantageous to use in the clinic than BMSCs.
Small region of Rtf1 protein can substitute for complete Paf1 complex in facilitating global histone H2B ubiquitylation in yeast
Authors: Piro Anthony S. , Mayekar Manasi K. , Warner Marcie H. , Davis Christopher P. , Arndt Karen M.
Published: June 2012

Histone modifications regulate transcription by RNA polymerase II and maintain a balance between active and repressed chromatin states. The conserved Paf1 complex (Paf1C) promotes specific histone modifications during transcription elongation, but the mechanisms by which it facilitates these marks are undefined. We previously identified a 90-amino acid region within the Rtf1 subunit of Paf1C that is necessary for Paf1C-dependent histone modifications in
Saccharomyces cerevisiae
. Here we show that this histone modification domain (HMD), when expressed as the only source of Rtf1, can promote H3 K4 and K79 methylation and H2B K123 ubiquitylation in yeast. The HMD can restore histone modifications in
rtf1Δ
cells whether or not it is directed to DNA by a fusion to a DNA binding domain. The HMD can facilitate histone modifications independently of other Paf1C subunits and does not bypass the requirement for Rad6–Bre1. The isolated HMD localizes to chromatin, and this interaction requires residues important for histone modification. When expressed outside the context of full-length Rtf1, the HMD associates with and causes Paf1C-dependent histone modifications to appear at transcriptionally inactive loci, suggesting that its function has become deregulated. Finally, the Rtf1 HMDs from other species can function in yeast. Our findings suggest a direct and conserved role for Paf1C in coupling histone modifications to transcription elongation.
Neuronal representations of distance in human auditory cortex
Authors: Kopčo Norbert , Huang Samantha , Belliveau John W. , Raij Tommi , Tengshe Chinmayi , Ahveninen Jyrki
Published: June 2012

Neuronal mechanisms of auditory distance perception are poorly understood, largely because contributions of intensity and distance processing are difficult to differentiate. Typically, the received intensity increases when sound sources approach us. However, we can also distinguish between soft-but-nearby and loud-but-distant sounds, indicating that distance processing can also be based on intensity-independent cues. Here, we combined behavioral experiments, fMRI measurements, and computational analyses to identify the neural representation of distance independent of intensity. In a virtual reverberant environment, we simulated sound sources at varying distances (15–100 cm) along the right-side interaural axis. Our acoustic analysis suggested that, of the individual intensity-independent depth cues available for these stimuli, direct-to-reverberant ratio (D/R) is more reliable and robust than interaural level difference (ILD). However, on the basis of our behavioral results, subjects’ discrimination performance was more consistent with complex intensity-independent distance representations, combining both available cues, than with representations on the basis of either D/R or ILD individually. fMRI activations to sounds varying in distance (containing all cues, including intensity), compared with activations to sounds varying in intensity only, were significantly increased in the planum temporale and posterior superior temporal gyrus contralateral to the direction of stimulation. This fMRI result suggests that neurons in posterior nonprimary auditory cortices, in or near the areas processing other auditory spatial features, are sensitive to intensity-independent sound properties relevant for auditory distance perception.
Hydrodynamic trapping of molecules in lipid bilayers
Authors: Jönsson Peter , McColl James , Clarke Richard W. , Ostanin Victor P. , Jönsson Bengt , Klenerman David
Published: June 2012

In this work we show how hydrodynamic forces can be used to locally trap molecules in a supported lipid bilayer (SLB). The method uses the hydrodynamic drag forces arising from a flow through a conical pipette with a tip radius of 1–1.5 μm, placed approximately 1 μm above the investigated SLB. This results in a localized forcefield that acts on molecules protruding from the SLB, yielding a hydrodynamic trap with a size approximately given by the size of the pipette tip. We demonstrate this concept by trapping the protein streptavidin, bound to biotin receptors in the SLB. It is also shown how static and kinetic information about the intermolecular interactions in the lipid bilayer can be obtained by relating how the magnitude of the hydrodynamic forces affects the accumulation of protein molecules in the trap.
Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin
Authors: Matt Tanja , Ng Chyan Leong , Lang Kathrin , Sha Su-Hua , Akbergenov Rashid , Shcherbakov Dmitri , Meyer Martin , Duscha Stefan , Xie Jing , Dubbaka Srinivas R. , Perez-Fernandez Déborah , Vasella Andrea , Ramakrishnan V. , Schacht Jochen , Böttger Erik C.
Published: June 2012

Aminoglycosides are potent antibacterials, but therapy is compromised by substantial toxicity causing, in particular, irreversible hearing loss. Aminoglycoside ototoxicity occurs both in a sporadic dose-dependent and in a genetically predisposed fashion. We recently have developed a mechanistic concept that postulates a key role for the mitochondrial ribosome (mitoribosome) in aminoglycoside ototoxicity. We now report on the surprising finding that apramycin, a structurally unique aminoglycoside licensed for veterinary use, shows little activity toward eukaryotic ribosomes, including hybrid ribosomes which were genetically engineered to carry the mitoribosomal aminoglycoside-susceptibility A1555G allele. In ex vivo cultures of cochlear explants and in the in vivo guinea pig model of chronic ototoxicity, apramycin causes only little hair cell damage and hearing loss but it is a potent antibacterial with good activity against a range of clinical pathogens, including multidrug-resistant
Mycobacterium tuberculosis
. These data provide proof of concept that antibacterial activity can be dissected from aminoglycoside ototoxicity. Together with 3D structures of apramycin-ribosome complexes at 3.5-Å resolution, our results provide a conceptual framework for further development of less toxic aminoglycosides by hypothesis-driven chemical synthesis.
Risk Analysis of Barramundi Perch Lates calcarifer Aquaculture in Florida
Authors: Hardin Scott , Hill Jeffrey E.
Published: June 2012

Two Florida state agencies (Florida Fish and Wildlife Conservation Commission [FWC] and Florida Department of Agriculture and Consumer Services) have regulatory and management programs to reduce the potential for escape or release of nonnative fishes from aquaculture facilities. The barramundi perch Lates calcarifer, a large, predatory euryhaline fish native to the Indo-Pacific, is classified as a conditional species by the FWC. Aquaculturists may possess this species only under strict biosecurity requirements. In 2006, a barramundi perch aquaculturist in central Florida initiated fee fishing by the public in outdoor culture ponds. The FWC conducted a risk analysis to assess the probability and potential consequences of barramundi perch population establishment in Florida, specifically considering the increased risk of illegal barramundi perch introduction into state waters to create a sport fishery. Using a generic risk analysis review process, a stakeholder panel determined that the overall risk from barramundi perch aquaculture was medium or high; a subsequent assessment by FWC biologists found the overall risk to be high. Nonregulatory risk management options to reduce the chance of escape and to prevent reproduction were considered impractical or ineffective, and a regulatory solution was recommended to mitigate the risk. The FWC enacted regulations that prohibited outdoor culture and fee fishing for facilities that acquire barramundi perch in the future, while allowing the existing facility to continue operations only under current ownership. The generic risk analysis provides a useful and flexible framework for conducting risk analyses involving assessors with varied technical backgrounds. We strongly recommend face-to-face meetings to increase the opportunities to reach consensus on risk estimates and uncertainty. Providing specific factors for risk assessors to consider (e.g., translocation of barramundi perch by wildlife, likelihood of successful spawning, and impacts to sportfishing) facilitates development of focused risk management options.

Received August 15, 2011; accepted February 9, 2012
The periodic logistic equation with spatial and temporal degeneracies
Authors: Du Yihong , Peng Rui
Published: June 2012

In this article, we study the degenerate periodic logistic equation with homogeneous Neumann boundary conditions:
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartLayout Enlarged left-brace 1st Row 1st Column partial-differential Subscript t Baseline u minus normal upper Delta u equals a u minus b left-parenthesis x comma t right-parenthesis u Superscript p Baseline 2nd Column a m p semicolon in normal upper Omega times left-parenthesis 0 comma normal infinity right-parenthesis comma 2nd Row 1st Column partial-differential Subscript nu Baseline u equals 0 2nd Column a m p semicolon on partial-differential normal upper Omega times left-parenthesis 0 comma normal infinity right-parenthesis comma 3rd Row 1st Column u left-parenthesis x comma 0 right-parenthesis equals u 0 left-parenthesis x right-parenthesis greater-than-or-equal-to comma not-identical-to 0 2nd Column a m p semicolon in normal upper Omega comma EndLayout">

{

∂
t

u
−
Δ
u
=
a
u
−
b
(
x
,
t
)

u
p

a
m
p
;

in 

Ω
×
(
0
,
∞
)

,

∂
ν

u
=
0

a
m
p
;

on 

∂
Ω
×
(
0
,
∞
)

,

u
(
x
,
0
)
=

u
0

(
x
)
≥
,

≢

0

a
m
p
;

in 

Ω

,

\begin{equation*} \begin {cases} \partial _t u-\Delta u=a u-b(x,t)u^p & \text {in $\Omega \times (0,\infty )$},\\ \partial _\nu u=0 & \text {on $\partial \Omega \times (0,\infty )$},\\ u(x,0) = u_0(x)\geq , \nequiv 0 & \text {in $\Omega $}, \end{cases} \end{equation*}

where

Ω
⊂

R

N

 
(
N
≥
2
)

\Omega \subset \mathbb {R}^N\ (N\geq 2)

is a bounded domain with smooth boundary

∂
Ω

\partial \Omega

,

a
a

and

p
>
1

p>1

are constants. The function

b
∈

C

θ
,
θ

/

2

(

Ω
¯

×

R

)

b\in C^{\theta ,\theta /2}(\overline \Omega \times \mathbb {R})

(
0
>
θ
>
1
)

(0>\theta >1)

is T-periodic in

t
t

, nonnegative, and vanishes (i.e., has a degeneracy) in some subdomain of

Ω
×

R

\Omega \times \mathbb {R}

. We examine the effects of various natural spatial and temporal degeneracies of

b
(
x
,
t
)

b(x,t)

on the long-time dynamical behavior of the positive solutions. Our analysis leads to a new eigenvalue problem for periodic-parabolic operators over a varying cylinder and certain parabolic boundary blow-up problems not known before. The investigation in this paper shows that the temporal degeneracy causes a fundamental change of the dynamical behavior of the equation only when spatial degeneracy also exists; but in sharp contrast, whether or not temporal degeneracy appears in the equation, the spatial degeneracy always induces fundamental changes of the behavior of the equation, though such changes differ significantly according to whether or not there is temporal degeneracy.