bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondria Are an Essential Mediator of Nitric Oxide/Cyclic Guanosine 3′,5′-Monophosphate Blocking of Glucose Depletion–Induced Cytotoxicity in Human HepG2 Cells
Authors: Hsu Yi-Chiung , Lee Hsin-Chen , Ping Yueh-Hsin , Liu Tsung-Yun , Lui Wing-Yiu , Chi Chin-Wen 
Published: September 2007

Abstract
It is well known that glucose is a major energy source in tumors and that mitochondria are specialized organelles required for energy metabolism. Previous studies have revealed that nitric oxide (NO) protects against glucose depletion–induced cytotoxicity in mouse liver cells and in rat hepatocytes, but the detailed mechanism is not well understood. Therefore, we investigated the involvement of mitochondria in the NO protective effect in human hepatoma HepG2 cells. In this study, we showed that glucose depletion resulted in a time-dependent decrease in intracellular NO and in the protein expression of NO synthases. This glucose depletion–induced decrease in NO was blocked by NO donors. Next, we showed that the cytoprotective effect of NO is via a cyclic guanosine 3′,5′-monophosphate–dependent pathway. Additionally, SNP blocked a glucose depletion–induced decrease in mitochondrial mass, mitochondrial DNA copies, and ATP level in HepG2 cells. Moreover, glucose depletion decreased the expression of various mitochondrial proteins, including cytochrome c, complex I (NADH dehydrogenase), complex III (cytochrome c reductase), and heat shock protein 60; these glucose depletion–induced effects were blocked by SNP. Furthermore, we found that rotenone and antimycin A (mitochondria complex I and III inhibitors, respectively) blocked SNP cytoprotection against glucose depletion–induced cytotoxicity. Taken together, our results indicated that the mitochondria serve as an important cellular mediator of NO during protection against glucose deprivation–induced damage. (Mol Cancer Res 2007;5(9):923–32)
Breast Cancer Molecular Signatures as Determined by SAGE: Correlation with Lymph Node Status
Authors: Abba Martín C. , Sun Hongxia , Hawkins Kathleen A. , Drake Jeffrey A. , Hu Yuhui , Nunez Maria I. , Gaddis Sally , Shi Tao , Horvath Steve , Sahin Aysegul , Aldaz C. Marcelo 
Published: September 2007

Abstract
Global gene expression measured by DNA microarray platforms have been extensively used to classify breast carcinomas correlating with clinical characteristics, including outcome. We generated a breast cancer Serial Analysis of Gene Expression (SAGE) high-resolution database of ∼2.7 million tags to perform unsupervised statistical analyses to obtain the molecular classification of breast-invasive ductal carcinomas in correlation with clinicopathologic features. Unsupervised statistical analysis by means of a random forest approach identified two main clusters of breast carcinomas, which differed in their lymph node status (P = 0.01); this suggested that lymph node status leads to globally distinct expression profiles. A total of 245 (55 up-modulated and 190 down-modulated) transcripts were differentially expressed between lymph node (+) and lymph node (−) primary breast tumors (fold change, ≥2; P &lt; 0.05). Various lymph node (+) up-modulated transcripts were validated in independent sets of human breast tumors by means of real-time reverse transcription-PCR (RT-PCR). We validated significant overexpression of transcripts for HOXC10 (P = 0.001), TPD52L1 (P = 0.007), ZFP36L1 (P = 0.011), PLINP1 (P = 0.013), DCTN3 (P = 0.025), DEK (P = 0.031), and CSNK1D (P = 0.04) in lymph node (+) breast carcinomas. Moreover, the DCTN3 (P = 0.022) and RHBDD2 (P = 0.002) transcripts were confirmed to be overexpressed in tumors that recurred within 6 years of follow-up by real-time RT-PCR. In addition, meta-analysis was used to compare SAGE data associated with lymph node (+) status with publicly available breast cancer DNA microarray data sets. We have generated evidence indicating that the pattern of gene expression in primary breast cancers at the time of surgical removal could discriminate those tumors with lymph node metastatic involvement using SAGE to identify specific transcripts that behave as predictors of recurrence as well. (Mol Cancer Res 2007;5(9):881–90)
Increased Expression and Activity of Nuclear Cathepsin L in Cancer Cells Suggests a Novel Mechanism of Cell Transformation
Authors: Goulet Brigitte , Sansregret Laurent , Leduy Lam , Bogyo Matthew , Weber Ekkehard , Chauhan Shyam S. , Nepveu Alain 
Published: September 2007

Abstract
It is generally accepted that the role of cathepsin L in cancer involves its activities outside the cells once it has been secreted. However, cathepsin L isoforms that are devoid of a signal peptide were recently shown to be present in the nucleus where they proteolytically process the CCAAT-displacement protein/cut homeobox (CDP/Cux) transcription factor. A role for nuclear cathepsin L in cell proliferation could be inferred from the observation that the CDP/Cux processed isoform can accelerate entry into S phase. Here, we report that in many transformed cells the proteolytic processing of CDP/Cux is augmented and correlates with increased cysteine protease expression and activity in the nucleus. Taking advantage of an antibody that recognizes the prodomain of human cathepsin L, we showed that human cells express short cathepsin L species that do not contain a signal peptide, do not transit through the endoplasmic reticulum, are not glycosylated, and localize to the nucleus. We also showed that transformation by the ras oncogene causes rapid increases both in the production of short nuclear cathepsin L isoforms and in the processing of CDP/Cux. Using a cell-based assay, we showed that a cell-permeable inhibitor of cysteine proteases is able to delay the progression into S phase and the proliferation in soft agar of ras-transformed cells, whereas the non–cell-permeable inhibitor had no effect. Taken together, these results suggest that the role of cathepsin L in cancer might not be limited to its extracellular activities but may also involve its processing function in the nucleus. (Mol Cancer Res 2007;5(9):899–907)
On Phrase Structure and Brain Responses: A Comment on Bahlmann, Gunter, and Friederici (2006)
Authors: Corballis Michael C. 
Published: September 2007

Abstract
Bahlmann et al. (2006) reported an experiment on event-related brain potentials of sequences of syllables obeying two rules, one defined by AnBn and the other by (AB)n, where the As and Bs are different classes of syllables. They interpreted their findings on the assumption that AnBn are parsed according a center-embedded phrase-structure grammar. In fact, such sequences are much more likely to be parsed in terms of the repetition of element types, without reference to phrase structure. This raises a general issue about attempting to study syntactic processing independently of semantics.
Neural Biases to Covert and Overt Signals of Fear: Dissociation by Trait Anxiety and Depression
Authors: Williams Leanne M. , Kemp Andrew H. , Felmingham Kim , Liddell Belinda J. , Palmer Donna M. , Bryant Richard A. 
Published: September 2007

Abstract
Although biases toward signals of fear may be an evolutionary adaptation necessary for survival, heightened biases may be maladaptive and associated with anxiety or depression. In this study, event-related potentials (ERPs) were used to examine the time course of neural responses to facial fear stimuli (versus neutral) presented overtly (for 500 msec with conscious attention) and covertly (for 10 msec with immediate masking to preclude conscious awareness) in 257 nonclinical subjects. We also examined the impact of trait anxiety and depression, assessed using psychometric ratings, on the time course of ERPs. In the total subject group, controlled biases to overtly processed fear were reflected in an enhancement of ERPs associated with structural encoding (120–220 msec) and sustained evaluation persisting from 250 msec and beyond, following a temporo-occipital to frontal topography. By contrast, covert fear processing elicited automatic biases, reflected in an enhancement of ERPs prior to structural encoding (80–180 msec) and again in the period associated with automatic orienting and emotion encoding (230–330 msec), which followed the reverse frontal to temporo-occipital topography. Higher levels of trait anxiety (in the clinical range) were distinguished by a heightened bias to covert fear (speeding of early ERPs), compared to higher depression which was associated with an opposing bias to overt fear (slowing of later ERPs). Anxiety also heightened early responses to covert fear, and depression to overt fear, with subsequent deficits in emotion encoding in each case. These findings are consistent with neural biases to signals of fear which operate automatically and during controlled processing, feasibly supported by parallel networks. Heightened automatic biases in anxiety may contribute to a cycle of hypervigilance and anxious thoughts, whereas depression may represent a “burnt out” emotional state in which evaluation of fear stimuli is prolonged only when conscious attention is allocated.
Early MEG Activation Dynamics in the Left Temporal and Inferior Frontal Cortex Reflect Semantic Context Integration
Authors: Shtyrov Yury , Pulvermüller Friedemann 
Published: September 2007

Abstract
Traditional views link semantic context integration to neurophysiological activity at 300–500 msec. To study possible early dynamics related to semantic context integration, we recorded, in passive oddball paradigm, magnetic evoked responses to spoken word pairs, the second word being either congruent or incongruent with the first one. The same experimental words were placed in orthogonally varied context, thus providing a strict control for any effects of acoustic, phonological, and psycholinguistic stimulus features. Responses to the same critical words were obtained also outside of semantic context. We found that regardless of their acoustic features, semantically incongruent stimuli elicited a brain response already at ∼115 msec after the critical word onset. The same words did not produce such deflection in semantically legal context. The responses were maximal at left temporal and inferior frontal cortical sites, which was also confirmed by distributed current source analysis. The left temporal activation preceded the frontal one by ∼16 msec. No late response dynamics (&gt;350 msec) were found that would reflect the semantic modulation in this nonattend passive design, indicating the possible role of attention in generating the later responses. Our results suggest that the earliest brain processes of semantic context integration can occur at ∼100 msec after the onset of spoken words in the left inferior frontal and superior temporal cortex.
The Neural Substrates of Visual Perceptual Learning of Words: Implications for the Visual Word Form Area Hypothesis
Authors: Xue Gui , Poldrack Russell A. 
Published: September 2007

Abstract
It remains under debate whether the fusiform visual word form area (VWFA) is specific to visual word form and whether visual expertise increases its sensitivity (Xue et al., 2006; Cohen et al., 2002). The present study examined three related issues: (1) whether the VWFA is also involved in processing foreign writing that significantly differs from the native one, (2) the effect of visual word form training on VWFA activation after controlling the task difficulty, and (3) the transfer of visual word form learning. Eleven native English speakers were trained, during five sessions, to judge whether two subsequently flashed (100-msec duration with 200-msec interval) foreign characters (i.e., Korean Hangul) were identical or not. Visual noise was added to the stimuli to manipulate task difficulty. In functional magnetic resonance imaging scans before and after training, subjects performed the task once with the same noise level (i.e., parameter-matched scan) and once with noise level changed to match performance from pretraining to posttraining (i.e., performance-matched scan). Results indicated that training increased the accuracy in parameter-matched condition but remained constant in performance-matched condition (because of increasing task difficulty). Pretraining scans revealed stronger activation for English words than for Korean characters in the left inferior temporal gyrus and the left inferior frontal cortex, but not in the VWFA. Visual word form training significantly decreased the activation in the bilateral middle and left posterior fusiform when either parameters or performance were matched and for both trained and new items. These results confirm our conjecture that the VWFA is not dedicated to words, and visual expertise acquired with training reduces rather than increases its activity.
Human Attentional Networks: A Connectionist Model
Authors: Wang Hongbin , Fan Jin 
Published: September 2007

Abstract
Recent evidence in cognitive neuroscience has suggested that attention is a complex organ system subserved by at least three attentional networks in the brain, for alerting, orienting, and executive control functions. However, how these different networks work together to give rise to the seemingly unitary mental faculty of attention remains unclear. We describe a connectionist model of human attentional networks to explore the possible interplays among the networks from a computational perspective. This model is developed in the framework of leabra (local, error-driven, and associative, biologically realistic algorithm) and simultaneously involves these attentional networks connected in a biologically inspired way. We evaluate the model by simulating the empirical data collected on normal human subjects using the Attentional Network Test (ANT). The simulation results fit the experimental data well. In addition, we show that the same model, with a single parameter change that affects executive control, is able to simulate the empirical data collected from patients with schizophrenia. This model represents a plausible connectionist explanation for the functional structure and interaction of human attentional networks.
Rapid Onset Relational Memory Effects Are Evident in Eye Movement Behavior, but Not in Hippocampal Amnesia
Authors: Hannula Deborah E. , Ryan Jennifer D. , Tranel Daniel , Cohen Neal J. 
Published: September 2007

Abstract
Little is known about the mechanisms by which memory for relations is accomplished, or about the time course of the critical processes. Here, eye movement measures were used to examine the time course of subjects' access to and use of relational memory. In four experiments, participants studied faces superimposed on scenic backgrounds and were tested with three-face displays superimposed on the scenes viewed earlier. Participants exhibited disproportionate viewing of the face originally studied with the scene, compared to other equally familiar faces in the test display. When a preview of a previously viewed scene was provided, permitting expectancies about the to-be-presented face to emerge, disproportionate viewing was manifested within 500–750 msec after test display onset, more than a full second in advance of explicit behavioral responses, and occurred even when overt responses were not required. In the absence of preview, the viewing effects were delayed by approximately 1 sec. Relational memory effects were absent in the eye movement behavior of amnesic patients with hippocampal damage, suggesting that these effects depend critically on the hippocampal system. The results provide an index of memory for face-scene relations, indicate the time by which retrieval and identification of these relations occur, and suggest that retrieval and use of relational memory depends critically on the hippocampus and occurs obligatorily, regardless of response requirements.
Estuarine Adjustment
Authors: MacCready Parker 
Published: September 2007

Abstract
Subtidal adjustment of estuarine salinity and circulation to changing river flow or tidal mixing is explored using a simplified numerical model. The model employs tidally averaged, width-averaged physics, following Hansen and Rattray, extended to include 1) time dependence, 2) tidally averaged mixing parameterizations, and 3) arbitrary variation of channel depth and width. By linearizing the volume-integrated salt budget, the time-dependent system may be distilled to a first-order, forced, damped, ordinary differential equation. From this equation, analytical expressions for the adjustment time and sensitivity of the length of the salt intrusion are developed. For estuaries in which the up-estuary salt flux is dominated by vertically segregated gravitational circulation, this adjustment time is predicted to be TADJ = (1/6)L/u, where L is the length of the salt intrusion and u is the section-averaged velocity (i.e., that due to the river flow). The importance of the adjustment time becomes apparent when considering forcing time scales. Seasonal river-flow variation is much slower than typical adjustment times in systems such as the Hudson River estuary, and thus the response may be quasi steady. Spring–neap mixing variation, in contrast, has a period comparable to typical adjustment times, and so unsteady effects are more important. In this case, the stratification may change greatly while the salt intrusion is relatively unperturbed.
Triad Instability of Planetary Rossby Waves
Authors: Zhang Yu , Pedlosky Joseph 
Published: September 2007

Abstract
The triad instability of the large-scale, first-mode, baroclinic Rossby waves is studied in the context of the planetary scale when the Coriolis parameter is to its lowest order varying with latitude. Accordingly, rather than remain constant as in quasigeostrophic theory, the deformation radius also changes with latitude, yielding new and interesting features to the propagation and triad instability processes. On the planetary scale, baroclinic waves vary their meridional wavenumbers along group velocity rays while they conserve both frequencies and zonal wavenumbers. The amplitudes of both barotropic and baroclinic waves would change with latitude along a ray path in the same way that the Coriolis parameter does if effects of the nonlinear interaction are ignored. The triad interaction for a specific triad is localized within a small latitudinal band where the resonance conditions are satisfied and quasigeostrophic theory is applicable locally. Using the growth rate from that theory as a measure, at each latitude along the ray path of the basic wave, a barotropic wave and a secondary baroclinic wave are picked up to form the most unstable triad and the distribution of this maximum growth rate is examined. It is found to increase southward under the assumption that triad interactions do not cause a noticeable decrease in the quantity of the basic wave’s amplitude divided by the Coriolis parameter. Different barotropic waves that maximize the growth rate at different latitudes have almost the same meridional length scale, on the order of the deformation radius. With many rays starting from different latitudes on the eastern boundary and with wavenumbers on each of them satisfying the no-normal-flow condition, the resulting two-dimensional distribution of the growth rate is a complicated function of the relative relations of zonal wavenumbers or frequencies on different rays and the orientation of the eastern boundary. In general, the growth rate is largest on rays originating to the north.
The Role of Bottom Vortex Stretching on the Path of the North Atlantic Western Boundary Current and on the Northern Recirculation Gyre
Authors: Zhang Rong , Vallis Geoffrey K. 
Published: September 2007

Abstract
The mechanisms affecting the path of the depth-integrated North Atlantic western boundary current and the formation of the northern recirculation gyre are investigated using a hierarchy of models, namely, a robust diagnostic model, a prognostic model using a global 1° ocean general circulation model coupled to a two-dimensional atmospheric energy balance model with a hydrological cycle, a simple numerical barotropic model, and an analytic model. The results herein suggest that the path of this boundary current and the formation of the northern recirculation gyre are sensitive to both the magnitude of lateral viscosity and the strength of the deep western boundary current (DWBC). In particular, it is shown that bottom vortex stretching induced by a downslope DWBC near the south of the Grand Banks leads to the formation of a cyclonic northern recirculation gyre and keeps the path of the depth-integrated western boundary current downstream of Cape Hatteras separated from the North American coast. Both south of the Grand Banks and at the crossover region of the DWBC and Gulf Stream, the downslope DWBC induces strong bottom downwelling over the steep continental slope, and the magnitude of the bottom downwelling is locally stronger than surface Ekman pumping velocity, providing strong positive vorticity through bottom vortex-stretching effects. The bottom vortex-stretching effect is also present in an extensive area in the North Atlantic, and the contribution to the North Atlantic subpolar and subtropical gyres is on the same order as the local surface wind stress curl. Analytic solutions show that the bottom vortex stretching is important near the western boundary only when the continental slope is wider than the Munk frictional layer scale.
Regimes of Thermocline Scaling: The Interaction of Wind Stress and Surface Buoyancy
Authors: Cessi Paola 
Published: September 2007

Abstract
The role of the relative geometry of mechanical forcing (wind stress) and buoyancy forcing (prescribed surface temperature) in the maintenance of the main thermocline is explored. In particular, the role of the wind stress curl in enhancing or suppressing the generation of baroclinic eddies is studied in simplified domains. The dependence of key quantities, such as the depth of the thermocline and the maximum heat transport, on the external parameters such as diapycnal mixing and dissipation rate is examined. Qualitatively different regimes are found depending on the relative phase of the wind stress and surface buoyancy distribution. The most efficient arrangement for eddy generation has Ekman pumping (suction) in conjunction with high (low) surface buoyancy. This corresponds to the situation found in the midlatitudes, where the surface Ekman flow carries heat toward the warmer region (i.e., upgradient of the surface temperature). In this case, strong eddy fluxes are generated in order to counteract the upgradient heat transport by the Ekman cell. The result is a thermocline whose depth is independent of the diapycnal diffusivity. However, the competition between these opposing heat fluxes leads to a weak net heat transport, proportional to the diffusivity responsible for the diabatic forcing. This arrangement of wind stress provides a large source of available potential energy on which eddies can grow, so the mechanical energy balance for the eddies is consistent with a substantial eddy heat flux. When the same surface temperature distribution is paired with the opposite wind stress curl, the mean flow produces a sink, rather than a source, of available potential energy and eddies are suppressed. With this arrangement, typical of low latitudes and the subpolar regions, the Ekman overturning cell carries heat downgradient of the surface temperature. Thus, the net heat transport is almost entirely due to the Ekman flow and is independent of the diapycnal diffusivity. At the same time the thermocline is a thin, diffusive boundary layer. Quantitative scalings for the thermocline depth and the poleward heat transport in these two limiting cases are contrasted and successfully compared with eddy-resolving computations.