bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical models of ionospheric electrodynamics and plasma transport
Authors: Withers Paul
Published: July 2008

A relationship between J, the current density, and E′, the electric field measured in the frame of the neutral wind, is derived for a planetary ionosphere: J = Q + E′. If pressure gradients and gravity are neglected, this reduces to the well‐known J = E′, where is the conductivity tensor. If J = 0, this reduces to ambipolar diffusion. Neither J = E′ nor ambipolar diffusion can describe the vertical motion of plasma in a dynamo region, a region where electrons are tied to fieldlines, but ions are not. This has prevented models from accurately describing how vertical plasma transport affects plasma densities in the martian ionosphere. The relationship J = Q + E′ is applied to a one‐dimensional ionospheric model to study ion velocities, electron velocities, currents, electric fields, and induced magnetic fields simultaneously and self‐consistently. In this model, ion and electron velocities transition smoothly from moving across fieldlines below the dynamo region to moving along fieldlines above the dynamo region. This relationship is valid for the terrestrial ionosphere; replacing J = E′ with J = Q + E′ in terrestrial models may alter some of their predictions.
Physical property changes in hydrate‐bearing sediment due to depressurization and subsequent repressurization
Authors: Waite W. F. , Kneafsey T. J. , Winters W. J. , Mason D. H.
Published: July 2008

Physical property measurements of sediment cores containing natural gas hydrate are typically performed on material exposed, at least briefly, to non‐in situ conditions during recovery. To examine the effects of a brief excursion from the gas‐hydrate stability field, as can occur when pressure cores are transferred to pressurized storage vessels, we measured physical properties on laboratory‐formed sand packs containing methane hydrate and methane pore gas. After depressurizing samples to atmospheric pressure, we repressurized them into the methane‐hydrate stability field and remeasured their physical properties. Thermal conductivity, shear strength, acoustic compressional and shear wave amplitudes, and speeds of the original and depressurized/repressurized samples are compared. X–ray computed tomography images track how the gas‐hydrate distribution changes in the hydrate‐cemented sands owing to the depressurizaton/repressurization process. Because depressurization‐induced property changes can be substantial and are not easily predicted, particularly in water‐saturated, hydrate‐bearing sediment, maintaining pressure and temperature conditions throughout the core recovery and measurement process is critical for using laboratory measurements to estimate in situ properties.
Integrated interpretation of physical properties of rocks of the borehole Yaxcopoil‐1 (Chicxulub impact structure)
Authors: Mayr S. I. , Wittmann A. , Burkhardt H. , Popov Y. , Romushkevich R. , Bayuk I. , Heidinger P. , Wilhelm H.
Published: July 2008

The borehole Yaxcopoil‐1, drilled within the Chicxulub meteoritic impact structure (Mexico), was completely cored from 404 to 1511 m through postimpact Tertiary limestones underlain by impactites. The impactites comprise impact melt‐rich, suevitic breccia followed by megablocks of Cretaceous limestones, calcarenites, dolomites, and anhydrites. Measurements of porosity, density, and thermal parameters on 450 samples (equidistant sampling, complete depth range) and of ultrasonic velocities and electric resistivity on 80 representative samples are used to investigate the physical properties of carbonate rocks and to study the influence of the impact. Experiments under elevated pressure, calculations using frequency‐dependent Biot‐Gassmann theory, and cross‐checking with borehole logs, where available, show that ultrasonic laboratory and sonic in situ data correspond. Sonic and electric quasi‐continuous logs are obtained from empirical correlations with thermal conductivity, density, and porosity and consideration of mineralogical composition and microstructure. These data give constraints on interpretation and geophysical modeling of, e.g., seismic and gravity data. In the Tertiary postimpact limestone section, the rock fabric (porosity) influences the physical properties. The upper boundary of the impactites is distinctly determined by the high inhomogeneity factor and anisotropy coefficient of thermal conductivity and by the temperature gradient from high‐resolution borehole temperature measurements. All physical properties indicate that the upper part of the suevitic breccia can be distinguished from the lower suevite unit. In the Cretaceous megablocks, a high variability of all properties (particularly, thermal conductivity, density of solid material, and temperature gradient) due to the high variability in the mineral composition (calcite, dolomite, anhydrite) is observed.
Global observations of HNO3 from the High Resolution Dynamics Limb Sounder (HIRDLS): First results
Authors: Kinnison D. E. , Gille J. , Barnett J. , Randall C. , Harvey V. L. , Lambert A. , Khosravi R. , Alexander M. J. , Bernath P. F. , Boone C. D. , Cavanaugh C. , Coffey M. , Craig C. , Dean V. C. , Eden T. , Ellis D. , Fahey D. W. , Francis G. , Halvorson C. , Hannigan J. , Hartsough C. , Hepplewhite C. , Krinsky C. , Lee H. , Mankin B. , Marcy T. P. , Massie S. , Nardi B. , Packman D. , Popp P. J. , Santee M. L. , Yudin V. , Walker K. A.
Published: July 2008

We present the first evaluation of the HNO3 data product (version 2.04.09) from the High Resolution Dynamics Limb Sounder (HIRDLS) on the Earth Observing System (EOS) Aura satellite. The HIRDLS instrument obtains between 5000 and 7000 HNO3 profiles per day. HIRDLS HNO3 data are generally good over the latitude range of 64°S to 80°N and pressure range 100 to 10 hPa, with some profiles, depending on latitude, having useful information between 100 to 161 hPa. The individual profile “measured” precision is between 10 and 15%, but can be much larger if the HNO3 abundance is low or outside the 100 hPa to 10 hPa range. Global results are compared with the HNO3 observations from version 2.2 of the EOS Aura Microwave Limb Sounder (MLS), and it is found that large‐scale features are consistent between the two instruments. HIRDLS HNO3 is biased 0–20% low relative to Aura MLS in the mid‐to‐high latitudes and biased high in the tropical stratosphere. HIRDLS HNO3 is also compared with Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE‐FTS). In these mostly high‐latitude comparisons the HIRDLS HNO3 data are biased 10–30% low, depending on altitude. Finally, the HIRDLS HNO3 is compared to in situ data taken by the NOAA Chemical Ionization Mass Spectrometer (CIMS) instrument flown during the 2005 NASA Houston Aura Validation Experiment (AVE) and the ability of HIRDLS to measure HNO3 in the UTLS region is examined.
Quantifying above‐cloud aerosol using spaceborne lidar for improved understanding of cloudy‐sky direct climate forcing
Authors: Chand D. , Anderson T. L. , Wood R. , Charlson R. J. , Hu Y. , Liu Z. , Vaughan M.
Published: July 2008

Estimates of global mean direct climate forcing by absorbing aerosols located above boundary layer clouds are large, uncertain, and almost entirely unconstrained by observations. Spaceborne lidar offers a new opportunity for global constraints. Here we examine techniques for using liquid water clouds as lidar targets, allowing aerosol optical depth and Ångström exponent to be deduced directly from aerosol effects on light transmission. Two such techniques are examined using data from the Cloud‐Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO). The first is a previously reported method based on measurements of cloud depolarization ratio (DR) at 532‐nm wavelength. The second is a new method using measurements of cloud color ratio (CR), which is the ratio of the signal from the cloud at 1064 nm to that at 532 nm. Optical depth retrievals from these two methods compare favorably over the eastern tropical Atlantic Ocean during August 2006, when biomass burning aerosols are frequently advected over marine stratiform clouds. The CR technique is mainly sensitive to fine‐mode aerosols and essentially insensitive to clouds and coarse‐mode dust. Because anthropogenic aerosol is predominantly found in the fine mode, the CR technique can be used to help identify situations where anthropogenic cloudy‐sky direct radiative forcing is occurring. We demonstrate this capability using 6 months data over the eastern tropical Atlantic Ocean.
Inhomogeneous precipitation distribution and snow transport in steep terrain
Authors: Lehning M. , Löwe H. , Ryser M. , Raderschall N.
Published: July 2008

The inhomogeneous snow distribution found in alpine terrain is the result of wind and precipitation interacting with the (snow) surface over topography. We introduce and explain preferential deposition of precipitation as the deposition process without erosion of previously deposited snow and thus in absence of saltation. A numerical model is developed, describing the relevant processes of saltation, suspension, and preferential deposition. The model uses high‐resolution wind fields calculated with a meteorological model, ARPS. The model is used to simulate a 120 h snow storm period over a steep alpine ridge, for which snow distribution measurements are available. The comparison to measurements shows that the model captures the larger‐scale snow distribution patterns and predicts the total additional lee slope loading well. However, the spatial resolution of 25 m is still insufficient to capture the smaller‐scale deposition features observed. The model suggests that the snow distribution on the ridge scale is primarily caused by preferential deposition and that this result is not sensitive to model parameters such as turbulent diffusivity, drift threshold, or concentration in the saltation layer.
Characteristics of inertia‐gravity waves over Gadanki during the passage of a deep depression over the Bay of Bengal
Authors: Niranjan Kumar K. , Ramkumar T. K.
Published: July 2008

Using MST Radar located at the Indian tropical station of Gadanki (13.5°N, 79.2°E; near the eastern coast of India), studies have been made on the characteristics of inertia‐gravity waves generated in the lower troposphere during deep depression developed over the Bay of Bengal on 20–24 June 2007. Filtering and the hodograph analyses of horizontal winds indicate that the low‐pressure system has generated inertia gravity waves, propagating outward from the core of the depression. Strong enhancement of radar reflectivity (SNR) in the heights of ∼4–7 km for a few days around 22 June 2007 and the upward propagation of gravity wave energy above this height range indicate that the source of the waves is located at ∼4–7 km. This is in agreement with earlier theoretical expectations. The vertical and horizontal wavelengths of gravity waves are found to be ∼2.2 km and ∼240 km respectively in the troposphere.
Sea level anomaly signals in the Agulhas Current region
Authors: Byrne D. A. , McClean J. L.
Published: July 2008

In the Agulhas Current and its sources and sinks, variability in steric height derived from the 0.1° POP model is 3–11 times greater than the mass‐load signal at periods shorter than 20 days, the approximate limit of temporal resolution for the Jason series of satellite altimeters. Model output is evaluated for realism against in situ SLA data from a suite of moorings deployed in the southeastern South Atlantic Ocean in 2003–2005. The effects of temporal filtering and alongtrack smoothing on output sampled at 10‐day intervals is examined. In approximately 14% of the region, including much of the Agulhas Retroflection, aliasing is ≤10% only at periods of ≥120 days. Smoothing reduces that proportion by 40% but also sharply reduces variability at periods of ≤73 days indicating that use of Jason‐style altimetry for time series analysis of this current system should be confined to seasonal and longer scales.
Fracture propagation propensity in relation to snow slab avalanche release: Validating the Propagation Saw Test
Authors: Gauthier Dave , Jamieson Bruce
Published: July 2008

The ‘Propagation Saw Test’ (PST) was designed to assess the fracture propagation propensity of weak snowpack layers in relation to snow slab avalanche release. Its predictions were tested against independent field observations of weak layer fracture initiation and slope‐scale fracture propagation (e.g., avalanche release). A total of 170 tests were performed at 23 sites. Approximately 76% of tests correctly predicted the observed slope‐scale fracture propagation or lack thereof; however, 20% of tests predicted that propagation would not occur at sites that had recently propagated fractures. The predictive accuracy of the dataset improves if only test columns approximately 1.0 m long are selected. Critical fracture energy release rate calculations show that the lowest values are found in snowpacks where fractures initiated but did not propagate. This suggests that physical descriptions of propagation propensity in weak snowpack layers should include a sustainability term.
Episodic growth of fault‐related fold in northern Japan observed by SAR interferometry
Authors: Nishimura Takuya , Tobita Mikio , Yarai Hiroshi , Amagai Tomomi , Fujiwara Midori , Une Hiroshi , Koarai Mamoru
Published: July 2008

The interferometric analysis using ALOS SAR data allows us to map the detailed spatial pattern of the deformation associated with the 2007 M6.8 Niigataken Chuetsu‐oki earthquake. The interferograms reveal not only a large deformation near the source area of the earthquake but also a local uplift in the region of active folding, 15 km east of the earthquake epicenter. The 1.5‐km‐wide and 15‐km‐long band of uplift is located along the anticline axis of an active fold and cannot be explained by the elastic deformation resulting from the mainshock of the earthquake. This uplift suggests the episodic growth of active folds. The analysis of the range changes along two directions and the vertical displacement by leveling reveals that episodic creep on an east‐dipping reverse fault just beneath the uplift band has caused the growth of the fault‐related fold. The acceleration of this creep has been probably triggered by an increase in static stress due to the earthquake
Oceanic origin of the interannual and interdecadal variability of the summertime western Pacific subtropical high
Authors: Wu Bo , Zhou Tianjun
Published: July 2008

A recent study found that the western Pacific Subtropical High (WPSH) exhibits both quasi‐biennial (2–3 years) and low‐frequency (3–5 years) oscillations. While the quasi‐biennial oscillation is prominent in 1990s, the 3–5 year oscillation is dominant in 1980s. The two oscillations were attributed to the atmospheric response to the remote forcing of sea surface temperature (SST) in the maritime continent and equatorial central‐eastern Pacific, respectively. The present study confirms this hypothesis. When forced by observational SST, the ensemble simulation with the NCAR CAM2 model reasonably reproduces the main characteristics of quasi‐biennial oscillation and low‐frequency oscillations of the WPSH. The quasi‐biennial oscillation is associated with anomalous overturning circulation characterized by enhanced convection over the maritime continent and subsidence over the western North Pacific. The low‐frequency oscillation is mainly modulated by remote forcing of SSTA in the equatorial central‐eastern Pacific. The model reasonably reproduces the interdecadal transition of the WPSH from low‐frequency oscillation in 1980s to quasi‐biennial oscillation in 1990s, suggesting that the SST forcing is an essential factor to modulate the interdecadal variation of the WPSH.
Intravenous Grafts Recapitulate the Neurorestoration Afforded by Intracerebrally Delivered Multipotent Adult Progenitor Cells in Neonatal Hypoxic-Ischemic Rats
Authors: Yasuhara Takao , Hara Koichi , Maki Mina , Mays Robert W , Deans Robert J , Hess David C , Carroll James E , Borlongan Cesar V
Published: July 2008

Once hypoxic-ischemic (HI) injury ensues in the human neonate at birth, the resulting brain damage lasts throughout the individual's lifetime, as no ameliorative treatments are currently available. We have recently shown that intracerebral transplantation of multipotent adult progenitor cells (MAPCs) results in behavioral improvement and reduction in ischemic cell loss in neonatal rat HI-injury model. In an attempt to advance this cellular therapy to the clinic, we explored the more practical and less invasive intravenous administration of MAPCs. Seven-day-old Sprague-Dawley rats were initially subjected to unilateral HI injury, then 7 days later received intracerebral or intravenous injections of allogeneic rat MAPCs. On post-transplantation days 7 and 14, the animals that received MAPCs via the intracerebral or intravenous route exhibited improved motor and neurologic scores compared with those that received vehicle infusion alone. Immunohistochemical evaluations at day 14 after transplantation revealed that both intracerebrally and intravenously transplanted MAPCs were detected in the ischemic hippocampal area. The degree of hippocampal cell preservation was almost the same in the two treatment groups and greater than that in the vehicle group. These results show that intravenous delivery of MAPCs is a feasible and efficacious cell therapy with potential for clinical use.
Induction of Cerebral Arteriogenesis Leads to Early-Phase Expression of Protease Inhibitors in Growing Collaterals of the Brain
Authors: Hillmeister Philipp , Lehmann Kerstin E , Bondke Anja , Witt Henning , Duelsner André , Gruber Clemens , Busch Hans-Jörg , Jankowski Joachim , Ruiz-Noppinger Patricia , Hossmann Konstantin-Alexander , Buschmann Ivo R
Published: July 2008

Cerebral arteriogenesis constitutes a promising therapeutic concept for cerebrovascular ischaemia; however, transcriptional profiles important for therapeutic target identification have not yet been investigated. This study aims at a comprehensive characterization of transcriptional and morphologic activation during early-phase collateral vessel growth in a rat model of adaptive cerebral arteriogenesis. Arteriogenesis was induced using a three-vessel occlusion (3-VO) rat model of nonischaemic cerebral hypoperfusion. Collateral tissue from growing posterior cerebral artery (PCA) and posterior communicating artery (Pcom) was selectively isolated avoiding contamination with adjacent tissue. We detected differential gene expression 24 h after 3-VO with 164 genes significantly deregulated. Expression patterns contained gene transcripts predominantly involved in proliferation, inflammation, and migration. By using scanning electron microscopy, morphologic activation of the PCA endothelium was detected. Furthermore, the PCA showed induced proliferation (PCNA staining) and CD68+ macrophage staining 24 h after 3-VO, resulting in a significant increase in diameter within 7 days after 3-VO, confirming the arteriogenic phenotype. Analysis of molecular annotations and networks associated with differentially expressed genes revealed that early-phase cerebral arteriogenesis is characterised by the expression of protease inhibitors. These results were confirmed by quantitative real-time reverse transcription-PCR, and in situ hybridisation localised the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and kininogen to collateral arteries, showing that TIMP-1 and kininogen might be molecular markers for early-phase cerebral arteriogenesis.
Hypoperfusion of the Cerebral White Matter in Multiple Sclerosis: Possible Mechanisms and Pathophysiological Significance
Authors: De Keyser Jacques , Steen Christel , Mostert Jop P , Koch Marcus W
Published: July 2008

Multiple sclerosis (MS) is a disease of the central nervous system characterized by patchy areas of demyelination, inflammation, axonal loss and gliosis, and a diffuse axonal degeneration throughout the so-called normal-appearing white matter (NAWM). A number of recent studies using perfusion magnetic resonance imaging in both relapsing and progressive forms of MS have shown a decreased perfusion of the NAWM, which does not appear to be secondary to axonal loss. The reduced perfusion of the NAWM in MS might be caused by a widespread astrocyte dysfunction, possibly related to a deficiency in astrocytic β2-adrenergic receptors and a reduced formation of cAMP, resulting in a reduced uptake of K+ at the nodes of Ranvier and a reduced release of K+ in the perivascular spaces. Pathologic and imaging studies suggest that ischemic changes might be involved in the development of a subtype of focal demyelinating lesions (type III lesions), and there appears to exist a relationship between decreased white matter perfusion and cognitive dysfunction in patients with MS.
Enhanced sialylation of recombinant erythropoietin in genetically engineered Chinese‐hamster ovary cells
Authors: Jeong Yeon Tae , Choi One , Son Young Dok , Park Seung Yeol , Kim Jung Hoe
Published: July 2008

Sialic acid, the terminal sugar in N‐linked complex glycans, is usually found in glycoproteins and plays a major role in determining the circulatory lifespan of glycoproteins. In the present study we attempted to enhance the sialylation of recombinant EPO (erythropoietin) in CHO (Chinese‐hamster ovary) cells. To enhance EPO sialylation, we introduced human α2,3‐ST (α2,3‐sialyltransferase) and CMP‐SAS (CMP‐sialic acid synthase) into recombinant human EPO‐producing CHO cells. The sialylation of EPO was increased by the expression of α2,3‐ST alone. Although the co‐expression of α2,3‐ST and CMP‐SAS did not further increase sialylation, an increase in the intracellular pool of CMP‐sialic acid was noted. On the basis of these observations, it was postulated that the transport capacity of CMP‐sialic acid into the Golgi lumen was limited, thereby causing the reduced availability of CMP‐sialic acid substrate for sialylation. Therefore, we co‐expressed human α2,3‐ST and CMP‐SAS, as well as overexpress Chinese hamster CMP‐sialic acid transporter (CMP‐SAT) in CHO cells, which produced recombinant human EPO. When α2,3‐ST, CMP‐SAS, and CMP‐SAT were overexpressed in CHO cells, there was a corresponding increase in sialylation compared with the co‐expression of α2,3‐ST and CMP‐SAS. The present study provides a useful strategy for enhancing the sialylation of therapeutic glycoproteins produced in CHO cells.
Renal oxidative stress and nitric oxide production in streptozotocin‐induced diabetic nephropathy in rats: the possible modulatory effects of garlic (Allium sativumL.)
Authors: Mariee Amr D. , Abd‐Allah Gamil M. , El‐Yamany Mohamad F.
Published: July 2008

The purpose of the present study was to investigate the effects of garlic (Allium sativumL.) on the diabetic nephropathy and oxidative stress induced by STZ (streptozotocin) in rats. Diabetes was induced in Male Sprague–Dawley rats by administering a single intraperitoneal injection of STZ (60 mg/kg of body weight). Administration of garlic, prepared as FGH (fresh garlic homogenate) significantly attenuated STZ‐induced diabetic nephropathy as evaluated by assessment of serum glucose, insulin, total TAG (triacylglycerol), TC (total cholesterol) and Ccr (creatinine clearance) in control and STZ‐induced diabetic rats. Urinary excretions of albumin and NAG (N‐acetyl‐β‐D‐glucosaminidase) were also reduced following the treatment with FGH. In addition, significant inhibition of TBARSs (thiobarbituric acid‐reacting substances) with a marked improvement of GSH content in the kidney homogenates was also observed. Moreover, renal tissue content and urinary excretion of nitrites were markedly decreased in this model, and virtually enhanced to the same levels as in the non‐diabetic kidney following FGH supplementation. These data revealed that FGH has the ability to ameliorate STZ‐induced diabetic nephropathy possibly through participation in the inhibition of oxidative damage to kidney and/or increased kidney nitric oxide bioavailability.
Functional analysis of the SRY—KRAB interaction in mouse sex determination
Authors: Polanco Juan Carlos , Wilhelm Dagmar , Mizusaki Hirofumi , Jackson Andrew , Browne Catherine , Davidson Tara , Harley Vincent , Sinclair Andrew , Koopman Peter
Published: July 2008

Background information. SRY (sex‐determining region Y), the master regulator of male development in mammals, has been studied extensively for more than 17 years, but how the SRY protein triggers the chain of events leading to testis development remains unclear. SRY probably requires a partner protein to elicit its molecular function. KRAB‐O, a novel protein containing a KRAB (Krüppel‐associated box) domain only, was suggested recently as a candidate SRY partner. In order to investigate the possible role of KRAB‐O in sex determination, we studied its expression and conducted functional assays of the SRY—KRAB interaction.

Results. More than 100 KRAB genes were found to be expressed in mouse developing gonads, including 19 transcripts encoded by the KRAB‐O cluster that were found to be expressed in somatic cells at 11.5 dpc (days post‐coitum). Loss‐of‐function analysis in Sry‐expressing cultured cells, using shRNA (small hairpin RNA) constructs directed against KRAB‐O and its homologous genes, resulted in a reduced ability to up‐regulate Sox9 [SRY‐related HMG (high‐mobility group)‐box 9]; however, KRAB‐knockdown mice exhibited normal testis development.

Conclusions. Reduced Sox9 expression in KRAB‐knockdown cells supports a role for KRAB‐O and perhaps other KRAB genes in mediating SRY function. Overlapping expression and potential redundancy between members of the large KRAB‐O gene cluster may mask any loss‐of‐function in vivo, presenting clear challenges for further functional analysis.
Phospholipase Cδ1 regulates cell proliferation and cell-cycle progression from G1- to S-phase by control of cyclin E–CDK2 activity
Authors: Kaproth-Joslin Katherine A. , Li Xiangquan , Reks Sarah E. , Kelley Grant G.
Published: July 2008

In the present study, we examined the role of PLCδ1 (phospholipase C δ1) in the regulation of cellular proliferation. We demonstrate that RNAi (RNA interference)-mediated knockdown of endogenous PLCδ1, but not PLCβ3 or PLCϵ, induces a proliferation defect in Rat-1 and NIH 3T3 fibroblasts. The decreased proliferation was not due to an induction of apoptosis or senescence, but was associated with an approx. 60% inhibition of [3H]thymidine incorporation. Analysis of the cell cycle with BrdU (bromodeoxyuridine)/propidium iodide-labelled FACS (fluorescence-activated cell sorting) demonstrated an accumulation of cells in G0/G1-phase and a corresponding decrease in cells in S-phase. Further examination of the cell cycle after synchronization by serum-starvation demonstrated normal movement through G1-phase but delayed entry into S-phase. Consistent with these findings, G1 cyclin (D2 and D3) and CDK4 (cyclin-dependent kinase 4) levels and associated kinase activity were not affected. However, cyclin E-associated CDK2 activity, responsible for G1-to-S-phase progression, was inhibited. This decreased activity was accompanied by unchanged CDK2 protein levels and paradoxically elevated cyclin E and cyclin E-associated CDK2 levels, suggesting inhibition of the cyclin E–CDK2 complex. This inhibition was not due to altered stimulatory or inhibitory phosphorylation of CDK2. However, p27, a Cip/Kip family CKI (CDK inhibitor)-binding partner, was elevated and showed increased association with CDK2 in PLCδ1-knockdown cells. The result of the present study demonstrate a novel and critical role for PLCδ1 in cell-cycle progression from G1-to-S-phase through regulation of cyclin E–CDK2 activity and p27 levels.
ERα suppresses slug expression directly by transcriptional repression
Authors: Ye Yin , Xiao Yi , Wang Wenting , Yearsley Kurtis , Gao Jian-Xin , Barsky Sanford H.
Published: July 2008

Two of the most common signalling pathways in breast cancer are the ER (oestrogen receptor) ligand activation pathway and the E-cadherin snai1 slug EMT (epithelial–mesenchymal transition) pathway. Although these pathways have been thought to interact indirectly, the present study is the first to observe direct interactions between these pathways that involves the regulation of slug expression. Specifically we report that ligand-activated ERα suppressed slug expression directly by repression of transcription and that knockdown of ERα with RNA interference increased slug expression. More specifically, slug expression was down-regulated in ERα-negative MDA-MB-468 cells transfected with ERα after treatment with E2 (17β-oestradiol). The down-regulation of slug in the ERα-positive MCF-7 cell line was mediated by direct repression of slug transcription by the formation of a co-repressor complex involving ligand-activated ERα protein, HDAC1 (histone deacetylase 1) and N-CoR (nuclear receptor co-repressor). This finding was confirmed by sequential ChIP (chromatin immunoprecipitation) studies. In the MCF-7 cell line, slug expression normally was low. In addition, knockdown of ERα with RNA interference in this cell line increased slug expression. This effect could be partially reversed by treatment of the cells with E2. The efficacy of the effect of ERα on slug repression was dependent on the overall level of ERα. These observations confirmed that slug was an E2-responsive gene.
Characterization of the DNA-binding motif of the arsenic-responsive transcription factor Yap8p
Authors: Ilina Yulia , Sloma Ewa , Maciaszczyk-Dziubinska Ewa , Novotny Marian , Thorsen Michael , Wysocki Robert , Tamás Markus J.
Published: July 2008

Saccharomyces cerevisiae uses several mechanisms for arsenic detoxification including the arsenate reductase Acr2p and the arsenite efflux protein Acr3p. ACR2 and ACR3 are transcribed in opposite directions from the same promoter and expression of these genes is regulated by the AP-1 (activator protein 1)-like transcription factor Yap8p. Yap8p has been shown to permanently associate with this promoter and to stimulate ACR2/ACR3 expression in response to arsenic. In the present study we characterized the DNA sequence that is targeted by Yap8p. We show that Yap8p binds to a pseudo-palindromic TGATTAATAATCA sequence that is related to, but distinct from, the sequence recognized by other fungal AP-1 proteins. Probing the promoter by mutational analysis, we confirm the importance of the TTAATAA core element and pin-point nucleotides that flank this element as crucial for Yap8p binding and in vivo activation of ACR3 expression. A genome-wide search for this element combined with global gene expression analysis indicates that the principal function of Yap8p is to control expression of ACR2 and ACR3. We conclude that Yap8p and other yeast AP-1 proteins require distinct DNA-binding motifs to induce gene expression and propose that this fact contributed towards a separation of function between AP-1 proteins during evolution.
Comparison of the EGFR resistance mutation profiles generated by EGFR-targeted tyrosine kinase inhibitors and the impact of drug combinations
Authors: Avizienyte Egle , Ward Richard A. , Garner Andrew P.
Published: July 2008

Recent clinical data indicates that the emergence of mutant drug-resistant kinase alleles may be particularly relevant for targeted kinase inhibitors. In order to explore how different classes of targeted therapies impact upon resistance mutations, we performed EGFR (epidermal-growth-factor receptor) resistance mutation screens with erlotinib, lapatinib and CI-1033. Distinct mutation spectra were generated with each inhibitor and were reflective of their respective mechanisms of action. Lapatinib yielded the widest variety of mutations, whereas mutational variability was lower in the erlotinib and CI-1033 screens. Lapatinib was uniquely sensitive to mutations of residues located deep within the selectivity pocket, whereas mutation of either Gly796 or Cys797 resulted in a dramatic loss of CI-1033 potency. The clinically observed T790M mutation was common to all inhibitors, but occurred with varying frequencies. Importantly, the presence of C797S with T790M in the same EGFR allele conferred complete resistance to erlotinib, lapatinib and CI-1033. The combination of erlotinib and CI-1033 effectively reduced the number of drug-resistant clones, suggesting a possible clinical strategy to overcome drug resistance. Interestingly, our results also indicate that co-expression of ErbB2 (v-erb-b2 erythroblastic leukaemia viral oncogene homologue 2) has an impact upon the EGFR resistance mutations obtained, suggesting that ErbB2 may play an active role in the acquisition of drug-resistant mutations.
α Isoforms of soluble and membrane-linked folate-binding protein in human blood
Authors: Høier-Madsen Mimi , Holm Jan , Hansen Steen I.
Published: July 2008

The high-affinity FBP/FR (folate-binding protein/folate receptor) is expressed in three isoforms. FRα and FRβ are attached to cell membranes by hydrophobic GPI (glycosylphosphatidylinositol) anchors, whereas FBPγ is a secretory protein. Mature neutrophil granulocytes contain a non-functional FRβ on the surface, and, in addition, nanomolar concentrations of a secretory functional FBP (29 kDa) can be present in the secondary granules. A statistically significant correlation between the concentrations of functional FBP, probably a γ isoform, in granulocytes and serum supported the hypothesis that serum FBP (29 kDa) mainly originates from neutrophils. The presence of FBP/FRα isoforms were established for the first time in human blood using antibodies specifically directed against human milk FBPα. The α isoforms identified on erythrocyte membranes, and in granulocytes and serum, only constituted an almost undetectable fraction of the functional FBP. The FBPα in neutrophil granulocytes was identified as a cytoplasmic component by indirect immunofluorescence. Gel filtration of serum revealed a peak of FBPα (>120 kDa), which could represent receptor fragments from decomposed erythrocytes and granulocytes. The soluble FBPs may exert bacteriostatic effects and protect folates in plasma from biological degradation, whereas FRs on the surface of blood cells could be involved in intracellular folate uptake or serve as signal proteins. The latter receptors have also been used for therapeutic targeting in malignancy.
The NgAOX1a gene cloned from Nicotiana glutinosa is implicated in the response to abiotic and biotic stresses
Authors: Wang Jian , Wang Xia , Liu Cheng , Zhang Jiedao , Zhu Changxiang , Guo Xingqi
Published: July 2008

A novel gene, named NgAOX1a, was isolated from Nicotiana glutinosa by RT-PCR (reverse transcription-PCR). The full-length cDNA of NgAOX1a was 1448 bp, including a 1062-bp ORF (open reading frame), a 124 bp 5′ UTR (untranslated region) and a 262 bp 3′ UTR. The ORF encodes a 353-amino-acid protein which contains two conserved cysteine residues, four iron-binding motifs, five α-helix regions and six conserved histidine residues. The phylogenetic tree showed that NgAOX1a belongs to the AOX1 (alternative oxidase 1)-type group. Alignment analysis showed that NgAOX1a shares a high similarity with other known AOXs. Four exons and three introns were detected in the genomic DNA sequence, and Southern-blotting analysis suggested that NgAOX1a is a single-copy gene. A series of putative cis-acting elements were examined in the 5′-flanking region of NgAOX1a. Northern-blotting analysis showed that the transcript levels of NgAOX1a can be markedly accumulated when tobacco seedlings are treated with various abiotic stimuli, such as exogenous signalling molecules for plant defence response, salicylic acid and H2O2, and the exogenous TCA (tricarboxylic acid) cycle metabolite citrate. However, it could be suppressed by abiotic stress, such as CoCl2, an inhibitor of ethylene, which indicates that the expression of NgAOX1a may be regulated by ethylene. In addition, NgAOX1a can also be strongly induced by three viral pathogens, tobacco mosaic virus, potato virus X and potato virus Y. These results indicate that NgAOX1a may be involved in multi-signal transduction pathways and may play an important role in defence response.
Identification and characterization of mature β-hexosaminidases associated with human placenta lysosomal membrane
Authors: Magini Alessandro , Mencarelli Simona , Tancini Brunella , Ciccarone Virginia , Urbanelli Lorena , Hasilik Andrej , Emiliani Carla
Published: July 2008

Hex (β-hexosaminidase) is a soluble glycohydrolase involved in glycoconjugate degradation in lysosomes, however its localization has also been described in the cytosol and PM (plasma membrane). We previously demonstrated that Hex associated with human fibroblast PM as the mature form, which is functionally active towards GM2 ganglioside. In the present study, Hex was analysed in a lysosomal membrane-enriched fraction obtained by purification from highly purified human placenta lysosomes. These results demonstrate the presence of mature Hex associated with the lysosomal membrane and displaying, as observed for the PM-associated form, an acidic optimum pH. When subjected to sodium carbonate extraction, the enzyme behaved as a peripheral membrane protein, whereas Triton X-114 phase separation confirmed its partially hydrophilic nature, characteristics which are shared with the PM-associated form of Hex. Moreover, two-dimensional electrophoresis indicated a slight difference in the pI of β-subunits in the membrane and the soluble forms of the lysosomal Hex. These results reveal a new aspect of Hex biology and suggest that a fully processed membrane-associated form of Hex is translocated from the lysosomal membrane to the PM by an as yet unknown mechanism. We present a testable hypothesis that, at the cell surface, Hex changes the composition of glycoconjugates that are known to be involved in intercellular communication and signalling.
In vitro characterization of native mammalian smooth-muscle protein synaptopodin 2
Authors: Schroeter Mechthild M. , Beall Brent , Heid Hans W. , Chalovich Joseph M.
Published: July 2008

An analysis of the primary structure of the actin-binding protein fesselin revealed it to be the avian homologue of mammalian synaptopodin 2 [Schroeter, Beall, Heid, and Chalovich (2008) Biochem. Biophys. Res. Commun. 371, 582–586]. We isolated two synaptopodin 2 isoforms from rabbit stomach that corresponded to known types of human synaptopodin 2. The purification scheme used was that developed for avian fesselin. These synaptopodin 2 forms shared several key functions with fesselin. Both avian fesselin and mammalian synaptopodin 2 bound to Ca2+–calmodulin, α-actinin and smooth-muscle myosin. In addition, both proteins stimulated the polymerization of actin in a Ca2+–calmodulin-dependent manner. Synaptopodin 2 has never before been shown to polymerize actin in the absence of α-actinin, to polymerize actin in a Ca2+–calmodulin-dependent manner, or to bind to Ca2+–calmodulin or myosin. These properties are consistent with the proposed function of synaptopodin 2 in organizing the cytoskeleton.
Procedures for Using Clinical Practice Guidelines
Authors: Hargrove Patricia , Griffer Mona , Lund Bonnie
Published: July 2008

Purpose

This article provides information about clinical practice guidelines (CPGs) to facilitate their application to the practice of speech-language pathology. CPGs are sets of recommendations based on evidence, including expert clinical opinion, that have been developed by a panel of reviewers. In this article, CPGs are defined and their components and rationale for use are discussed. A guide for analyzing CPGs critically and recommendations for applying them to clinical practice are also described.

Method

Two of the authors and 1 graduate student in speech-language pathology independently evaluated a CPG from the early intervention literature using the guide described in the article. An illustrative evaluation of a CPG is presented to facilitate application of the proposed critiquing guide.

Results

The guide was revealed to have high interrater reliability. However, analysis of the raters' responses to the individual items revealed problems with 3 items. The authors present possible resolutions and/or explanations for the problems.

Conclusion

By using the proposed guide, speech-language pathologists can increase their application of research to clinical practice, thereby enhancing their skills in informed clinical decision making.
Effect of Minimal Hearing Loss on Children’s Ability to Multitask in Quiet and in Noise
Authors: McFadden Brittany , Pittman Andrea
Published: July 2008

Purpose

The purpose of the present study was to examine the effect of minimal hearing loss (HL) on children’s ability to perform simultaneous tasks in quiet and in noise.

Method

Ten children with minimal HL and 11 children with normal hearing (NH) participated. Both groups ranged in age from 8 to 12 years. The children categorized common words (primary task) while completing dot-to-dot games (secondary task) in quiet as well as in noise presented at 0 dB and +6 dB signal-to-noise ratios (SNRs). It was hypothesized that the children’s progression through the dot-to-dot games would slow as they encountered more difficult listening environments. This hypothesis was based on the theory that listeners have limited cognitive resources to allocate to any combination of tasks.

Results

The dot rate of both groups decreased similarly in the multitasking conditions relative to baseline. However, no other differences between groups or listening conditions were revealed. Significantly poorer word categorization was observed for the children with minimal HL in noise.

Conclusion

These data suggest that children with minimal HL may be unable to respond to a difficult listening task by drawing resources from other tasks to compensate.
Considering Linguistic Input in a Bilingual Situation: Implications for Acquisition
Authors: Jacobson Peggy F. , Cairns Helen S.
Published: July 2008

One aspect of linguistic input that may vary in bilingual speech communities is the use of overregularization (e.g.,catched). In an earlier study, typically developing bilingual Spanish/English-speaking children were noted to use overregularizations in an elicited production task, accept these forms in a grammaticality judgment task, and reject standard irregular forms (e.g.,caught) at surprising rates in favor of the overregularization (P. F. Jacobson, 2002).

Purpose

This study examined the extent to which bilingual adult speakers reported hearing and using overregularized forms.

Method

Thirty Spanish/English-speaking adults who worked in settings with bilingual children served as informants. The stimuli included 15 regular and 15 irregular verbs—each as a correct irregular form and as an overregularization (e.g.,caughtandcatched) or as a correct regular form and as an irregularization (e.g.,helpedandholp). Employing a modified grammaticality judgment task, the informants were instructed to state whether they heard these forms produced by bilingual adults and whether or not they themselves ever used the forms.

Results

Although monolingual English speakers overwhelmingly rejected hearing or using overregularizations, the bilingual adults responded differently. They acknowledged hearing the correct regular and irregular forms in 96% of the instances presented. However, they also reported hearing 62%, and using 20%, of the overregularizations.

Discussion

These results prompt speculation regarding possible variation in the nature of linguistic input in the bilingual community and address learnability issues in the acquisition of the English past tense by bilingual children. The challenges facing speech-language pathologists who work with children from bilingual communities are discussed.
The Use of Nonspeech Oral Motor Treatments for Developmental Speech Sound Production Disorders: Interventions and Interactions
Authors: Powell Thomas W.
Published: July 2008

Purpose

The use of nonspeech oral motor treatments (NSOMTs) in the management of pediatric speech sound production disorders is controversial. This article serves as a prologue to a clinical forum that examines this topic in depth.

Method

Theoretical, historical, and ethical issues are reviewed to create a series of clinical questions that should be considered before one incorporates new methods into clinical practice.

Conclusion

Speech production disorders are complex and multifaceted. Speech-language pathologists are encouraged to advocate on behalf of clients by adopting the highest standards of clinical practice and by evaluating treatment options in a systematic, critical, and ethical manner.
A Nationwide Survey of Nonspeech Oral Motor Exercise Use: Implications for Evidence-Based Practice
Authors: Lof Gregory L. , Watson Maggie M.
Published: July 2008

Purpose

A nationwide survey was conducted to determine if speech-language pathologists (SLPs) use nonspeech oral motor exercises (NSOMEs) to address children’s speech sound problems. For those SLPs who used NSOMEs, the survey also identified (a) the types of NSOMEs used by the SLPs, (b) the SLPs' underlying beliefs about why they use NSOMEs, (c) clinicians' training for these exercises, (d) the application of NSOMEs across various clinical populations, and (e) specific tasks/procedures/tools that are used for intervention.

Method

A total of 2,000 surveys were mailed to a randomly selected subgroup of SLPs, obtained from the American Speech-Language-Hearing Association (ASHA) membership roster, who self-identified that they worked in various settings with children who have speech sound problems. The questions required answers that used both a forced choice and Likert-type scales.

Results

The response rate was 27.5% (537 out of 2,000). Of these respondents, 85% reported using NSOMEs to deal with children’s speech sound production problems. Those SLPs reported that the research literature supports the use of NSOMEs, and that they learned to use these techniques from continuing education events. They also stated that NSOMEs can help improve the speech of children from disparate etiologies, and “warming up” and strengthening the articulators are important components of speech sound therapy.

Conclusion

There are theoretical and research data that challenge both the use of NSOMEs and the efficacy of such exercises in resolving speech sound problems. SLPs need to follow the concepts of evidence-based practice in order to determine if these exercises are actually effective in bringing about changes in speech productions.
An Integrated Evaluation of Nonspeech Oral Motor Treatments
Authors: Powell Thomas W.
Published: July 2008

Purpose

This article functions as an epilogue to the clinical forum examining the use of nonspeech oral motor treatments (NSOMTs) to remediate speech sound disorders in children.

Method

Conclusions to eight clinical questions are formed based on the findings that were reported in the clinical forum. Theoretical and clinical challenges are also identified.

Conclusion

NSOMTs have serious theoretical and empirical shortcomings. At present, there is insufficient evidence to support the routine clinical application of these procedures to remediate developmental speech sound disorders.
The natural order of events: How speakers of different languages represent events nonverbally
Authors: Goldin-Meadow Susan , So Wing Chee , Özyürek Aslı , Mylander Carolyn
Published: July 2008

To test whether the language we speak influences our behavior even when we are not speaking, we asked speakers of four languages differing in their predominant word orders (English, Turkish, Spanish, and Chinese) to perform two nonverbal tasks: a communicative task (describing an event by using gesture without speech) and a noncommunicative task (reconstructing an event with pictures). We found that the word orders speakers used in their everyday speech did not influence their nonverbal behavior. Surprisingly, speakers of all four languages used the same order and on both nonverbal tasks. This order, actor–patient–act, is analogous to the subject–object–verb pattern found in many languages of the world and, importantly, in newly developing gestural languages. The findings provide evidence for a natural order that we impose on events when describing and reconstructing them nonverbally and exploit when constructing language anew.