bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear-Cytoplasmic Partitioning of Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN) Differentially Regulates the Cell Cycle and Apoptosis
Authors: Chung Ji-Hyun , Eng Charis 
Published: September 2005

Abstract
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a tumor suppressor phosphatase that dephosphorylates both protein and lipid substrates, is found to be mutated in both heritable and sporadic breast cancer. Cellular PTEN has been shown to regulate Akt phosphorylation, mitogen-activated protein kinase (MAPK) phosphorylation, p27kip1, and cyclin D1 protein levels. Additionally, we and others have shown that PTEN can regulate not only the cell cycle but also cellular apoptosis. Until recently, the functions of PTEN have been thought to occur through cytoplasmic PTEN. However, we have shown that PTEN localizes to the nucleus and that this localization coincides with the G0-G1 phases of the cell cycle. Furthermore, we have shown that PTEN has bipartite nuclear localization sequence (NLS)-like sequences that are required for major vault protein-mediated nuclear import. These findings suggest that subcellular localization of PTEN may regulate its function and that nuclear-localized PTEN may regulate unique cellular functions that have been attributed to cytoplasmic PTEN. To examine this possibility, we analyzed downstream PTEN readouts using MCF-7 Tet-Off breast cancer cell lines stably transfected with two different NLS mutant PTEN constructs, which do not localize to the nucleus, and compared these with cells transfected with wild-type PTEN and empty vector control cells. We found that cytoplasmic PTEN down-regulates phosphorylation of Akt and up-regulates p27kip1, whereas nuclear PTEN down-regulates cyclin D1 and prevents the phosphorylation of MAPK. Additionally, whereas we observe that nuclear PTEN is required for cell cycle arrest, we found that cytoplasmic PTEN is required for apoptosis. Our observations show that nuclear-cytoplasmic partitioning differentially regulates the cell cycle and apoptosis and, in this manner, provide further evidence that nuclear import of PTEN should play a role in carcinogenesis.
Histone Deacetylase Inhibition Down-Regulates Cyclin D1 Transcription by Inhibiting Nuclear Factor-κB/p65 DNA Binding
Authors: Hu Jing , Colburn Nancy H. 
Published: September 2005

Abstract
Histone deacetylase (HDAC) inhibitors are emerging as a promising new class of cancer therapeutic agents. HDAC inhibitors relieve the deacetylation of histone proteins. However, little is known about the nonhistone targets of HDAC inhibitors and their roles in gene regulation. In this study, we addressed the molecular basis of the down-regulation of the nuclear factor-κB (NF-κB)–responsive gene cyclin D1 by the HDAC inhibitor trichostatin A in mouse JB6 cells. Cyclin D1 plays a critical role in cell proliferation and tumor progression. Trichostatin A inhibits cyclin D1 expression in a NF-κB-dependent manner in JB6 cells. Electrophoretic mobility shift assay studies showed that trichostatin A treatment prevents p65 dimer binding to NF-κB sites on DNA. Moreover, a chromatin immunoprecipitation assay shows that trichostatin A treatment inhibits endogenous cyclin D1 gene transcription by preventing p65 binding to the cyclin D1 promoter. However, acetylation of p65 is not affected by trichostatin A treatment. Instead, trichostatin A enhances p52 acetylation and increases p52 protein level by enhancing p100 processing. This is the first report that trichostatin A, a HDAC inhibitor, activates p100 processing and relieves the repression of p52 acetylation. The enhanced acetylation of p52 in the nuclei may operate to cause nuclear retention of p65 by increasing the p52/p65 interaction and preventing IκBα-p65 binding. The enhanced p52 acetylation coincides with decreased p65 DNA binding, suggesting a potential role of p52 acetylation in NF-κB regulation. Together, the results provide the first demonstration that HDAC inhibitor trichostatin A inhibits cyclin D1 gene transcription through targeting transcription factor NF-κB/p65 DNA binding. NF-κB is therefore identified as a transcription factor target of trichostatin A treatment.
Phosphorylation of AML1/RUNX1 Regulates Its Degradation and Nuclear Matrix Association
Authors: Biggs Joseph R. , Zhang Youhong , Peterson Luke F. , Garcia Marileila , Zhang Dong-Er , Kraft Andrew S. 
Published: September 2005

Abstract
The acute myeloid leukemia 1 (AML1) transcription factors are key regulators of hematopoietic differentiation. Cellular AML1c protein is found in the nucleus and can be separated into two fractions, one soluble in buffers containing salt and nonionic detergent and the other insoluble and tightly bound to the nuclear matrix. We find that the AML1c protein is modified by both phosphorylation and ubiquitination. Our studies show that the majority of the ubiquitinated AML1c is associated with the insoluble nuclear matrix. Treatment of cells with the proteasome inhibitor PS341 (Velcade, Bortezomib) increases the levels of ubiquitinated AML1c. Mutation of the four phosphorylation sites necessary for transcriptional regulation (serine 276, serine 293, serine 303, and threonine 300) mimics the effects of the proteasome inhibitor, increasing the levels of ubiquitinated, matrix-bound AML1c. We find that the soluble and insoluble forms of AML1c are degraded at a similar rate. However, mutation of these four serine/threonine residues statistically increases the half-life of the matrix-associated AML1c. Thus, phosphorylation of AML1c on specific serine/threonine residues controls both transcriptional activity and rate of degradation.
The Loss of a Single Telomere Can Result in Instability of Multiple Chromosomes in a Human Tumor Cell Line
Authors: Sabatier Laure , Ricoul Michelle , Pottier Géraldine , Murnane John P. 
Published: September 2005

Abstract
Spontaneous telomere loss has been proposed as an important mechanism for initiating the chromosome instability commonly found in cancer cells. We have previously shown that spontaneous telomere loss in a human cancer cell line initiates breakage/fusion/bridge (B/F/B) cycles that continue for many cell generations, resulting in DNA amplification and translocations on the chromosome that lost its telomere. We have now extended these studies to determine the effect of the loss of a single telomere on the stability of other chromosomes. Our study showed that telomere acquisition during B/F/B cycles occurred mainly through translocations involving either the nonreciprocal transfer or duplication of the arms of other chromosomes. Telomere acquisition also occurred through small duplications involving the subtelomeric region of the other end of the same chromosome. Although all of these mechanisms stabilized the chromosome that lost its telomere, they differed in their consequences for the stability of the genome as a whole. Telomere acquisition involving nonreciprocal translocations resulted in the loss of a telomere on the donor chromosome, which consequently underwent additional translocations, isochromosome formation, or complete loss. In contrast, telomere acquisition involving duplications stabilized the genome, although the large duplications created substantial allelic imbalances. Thus, the loss of a single telomere can generate a variety of chromosome alterations commonly associated with human cancer, not only on a chromosome that loses its telomere but also on other chromosomes. Factors promoting telomere loss are therefore likely to have an important role in generating the karyotype evolution associated with human cancer.
Effects of Spatial Congruity on Audio-Visual Multimodal Integration
Authors: Teder-Sälejärvi W. A. , Russo F. Di , McDonald J. J. , Hillyard S. A. 
Published: September 2005

Abstract
Spatial constraints on multisensory integration of auditory (A) and visual (V) stimuli were investigated in humans using behavioral and electrophysiological measures. The aim was to find out whether cross-modal interactions between A and V stimuli depend on their spatial congruity, as has been found for multisensory neurons in animal studies (Stein & Meredith, 1993). Randomized sequences of unimodal (A or V) and simultaneous bimodal (AV) stimuli were presented to right-or left-field locations while subjects made speeded responses to infrequent targets of greater intensity that occurred in either or both modalities. Behavioral responses to the bimodal stimuli were faster and more accurate than to the uni-modal stimuli for both same-location and different-location AV pairings. The neural basis of this cross-modal facilitation was studied by comparing event-related potentials (ERPs) to the bimodal AV stimuli with the summed ERPs to the unimodal A and V stimuli. These comparisons revealed neural interactions localized to the ventral occipito-temporal cortex (at 190 msec) and to the superior temporal cortical areas (at 260 msec) for both same-and different-location AV pairings. In contrast, ERP interactions that differed according to spatial congruity included a phase and amplitude modulation of visual-evoked activity localized to the ventral occipito-temporal cortex at 100-400 msec and an amplitude modulation of activity localized to the superior temporal region at 260-280 msec. These results demonstrate overlapping but distinctive patterns of multisensory integration for spatially congruent and incongruent AV stimuli.
Cognitive Requirements for Vestibular and Ocular Motor Processing in Healthy Adults and Patients with Unilateral Vestibular Lesions
Authors: Talkowski M. E. , Redfern M. S. , Jennings J. R. , Furman J. M. 
Published: September 2005

Abstract
This study investigated the role of cognition in the vestibulo-ocular reflex (VOR) and ocular pursuit using a dual-task paradigm in patients with unilateral peripheral vestibular loss and healthy adults. We hypothesized that cognitive resources are involved in successful processing and integration of vestibular and ocular motor sensory information, and this requirement would be greater in patients with vestibular dys-function. Sixteen well-compensated patients with surgically confirmed absent unilateral peripheral vestibular function and 16 healthy age-and sex-matched controls underwent seven combinations of vestibular-only, visual-only, and visual-vestibular stimuli while performing three different information processing tasks. Visual-vestibular stimuli included a semi-circular canal and an otolith stimulus provided through seated chair rotations; fixation on a laser target and sinusoidal smooth pursuit while still; and fixation on a head-fixed laser target during chair rotations. The information processing tasks were three different auditory reaction time (RT) tasks: (1) simple RT (2) disjunctive RT, and (3) choice RT. Our results showed increases in RTs in both patients and controls under all vestibular-only stimulation conditions and during ocular pursuit. Patients showed greater increases in RTs during vestibular stimulation and the more complex disjunctive and choice RT tasks. No differences between the groups were found during the visual-only or visual-vestibular interaction conditions. These results reveal interference between vestibulo-ocular processing and a concurrent RT task, suggesting that the VOR and the ocular motor system are dependent upon cognitive resources to some extent, and thus, are not fully automatic systems. We speculate that this interference with cognition occurs as a result of the sensory integration required for resolving inputs from multiple sensory streams. The particularly large decrement in information processing task performance of the patients compared with controls during vestibular stimulation suggests that compensation for unilateral vestibular loss requires continued cognitive resources.
Unattended Facial Expressions Asymmetrically Bias the Concurrent Processing of Nonemotional Information
Authors: Maxwell Jeffrey S. , Shackman Alexander J. , Davidson Richard J. 
Published: September 2005

Abstract
Planned and reflexive behaviors often occur in the presence of emotional stimuli and within the context of an individual's acute emotional state. Therefore, determining the manner in which emotion and attention interact is an important step toward understanding how we function in the real world. Participants in the current investigation viewed centrally displayed, task-irrelevant, face distractors (angry, neutral, happy) while performing a lateralized go/no-go continuous performance task. Lateralized go targets and no-go lures that did not spatially overlap with the faces were employed to differentially probe processing in the left (LH) and right (RH) cerebral hemispheres. There was a significant interaction between expression and hemisphere, with an overall pattern such that angry distractors were associated with relatively more RH inhibitory errors than neutral or happy distractors and happy distractors with relatively more LH inhibitory errors than angry or neutral distractors. Simple effects analyses confirmed that angry faces differentially interfered with RH relative to LH inhibition and with inhibition in the RH relative to happy faces. A significant three-way interaction further revealed that state anxiety moderated relations between emotional expression and hemisphere. Under conditions of low cognitive load, more intense anxiety was associated with relatively greater RH than LH impairment in the presence of both happy and threatening distractors. By contrast, under high load, only angry dis-tractors produced greater RH than LH interference as a function of anxiety.
Ocean Model Diagnosis of Interannual Coevolving SST Variability in the South Indian and South Atlantic Oceans
Authors: Hermes J. C. , Reason C. J. C. 
Published: September 2005

Abstract
A global ocean model (ORCA2) forced with 50 yr of NCEP–NCAR reanalysis winds and heat fluxes has been used to investigate the evolution and forcing of interannual dipolelike sea surface temperature (SST) variability in the South Indian and South Atlantic Oceans. Although such patterns may also exist at times in only one of these basins and not the other, only events where there are coherent signals in both basins during the austral summer have been chosen for study in this paper. A positive (negative) event occurs when there is a significant warm (cool) SST anomaly evident in the southwest of both the South Indian and South Atlantic Oceans and a cool (warm) anomaly in the eastern subtropics.
The large-scale forcing of these events appears to consist of a coherent modulation of the wavenumber-3 or -4 pattern in the Southern Hemisphere atmospheric circulation such that the semipermanent subtropical anticyclone in each basin is shifted from its summer mean position and its strength is modulated. A relationship to the Antarctic Oscillation is also apparent, and seems to strengthen after the mid-1970s. The modulated subtropical anticyclones lead to changes in the tropical easterlies and midlatitude westerlies in the South Atlantic and South Indian Oceans that result in anomalies in latent heat fluxes, upwelling, and Ekman heat transports, all of which contribute to the SST variability. In addition, there are significant modulations to the strong Rossby wave signals in the South Indian Ocean. The results of this study confirm the ability of the ORCA2 model to represent these dipole patterns and indicate connections between large-scale modulations of the Southern Hemisphere midlatitude atmospheric circulation and coevolving SST variability in the South Atlantic and South Indian Oceans.
Land Surface Model Development for the GISS GCM: Effects of Improved Canopy Physiology on Simulated Climate
Authors: Friend Andrew D. , Kiang Nancy Y. 
Published: September 2005

Abstract
A new physiology-based model of canopy stomatal conductance and photosynthesis is described and included in the latest version of the Goddard Institute for Space Studies (GISS) GCM, ModelE1. The submodel includes responses to atmospheric humidity and CO2 concentration, responses missing from previous GISS GCM land surface schemes. Measurements of moisture, energy, and CO2 fluxes over four vegetation types are used to test and calibrate the submodel. Photosynthetic leaf N is calibrated for each vegetation type from the flux measurements.
The new submodel results in surface cooling over many regions previously too warm. Some warm biases of over 2°C are cooled by more than 0.5°C, including over central Eurasia, South America, the western United States, and Australia. In addition, some regions that were previously too cool are warmed, such as northern Eurasia and the Tibetan Plateau. A number of precipitation biases are also reduced, particularly over South America (by up to 1 mm day−1) and the oceanic ITCZs (by over ±1 mm day−1); coastal west Africa becomes significantly wetter. Cloud cover increases over many land areas previously too clear.
Higher absolute canopy conductances, and positive feedbacks with atmospheric humidity, are largely responsible for the simulated vegetation influence on the atmosphere. High-latitude climate changes through remote effects of increased tropical latent heating, resulting directly from improved characterization of tropical forest canopy conductance. Realistic representation of the stomatal control on land evaporation is critical for accurate simulation of atmospheric dynamics in the GISS GCM.
Influences of ENSO-Induced Indo–Western Pacific SST Anomalies on Extratropical Atmospheric Variability during the Boreal Summer
Authors: Lau Ngar-Cheung , Leetmaa Ants , Nath Mary Jo , Wang Hai-Lan 
Published: September 2005

Abstract
The causes for the observed occurrence of anomalous zonally symmetric upper-level pressure ridges in the midlatitude belts of both hemispheres during the year after warm El Niño–Southern Oscillation (ENSO) events have been investigated. Sea surface temperature (SST) anomalies in the Indo–western Pacific (IWP) sector were simulated by allowing an oceanic mixed layer model for that region to interact with local atmospheric changes forced remotely by observed ENSO episodes in the eastern/central tropical Pacific. The spatiotemporal evolution of these SST conditions through a composite ENSO cycle was then inserted as lower boundary conditions within the IWP domain in an ensemble of atmospheric general circulation model (GCM) integrations. This experimental setup is seen to reproduce zonally symmetric geopotential height anomalies with maximum amplitudes being attained over the extratropics in the boreal summer after the peak phase of ENSO. The model evidence hence supports the notion that these global-scale atmospheric changes are primarily responses to SST perturbations in IWP, which are in turn linked to ENSO variability in the equatorial Pacific by the “atmospheric bridge” mechanism.
Experimentation with a stationary wave model indicates that the Eastern Hemisphere portion of the aforementioned atmospheric signals are attributable to forcing by tropical heat sources and sinks associated with precipitation anomalies in the IWP region, which are closely related to the underlying SST changes. Diagnosis of the output from the GCM integrations reveals that these circulation changes due to diabatic heating are accompanied by alterations of the propagation path and intensity of the high-frequency eddies at locations farther downstream. The geopotential tendencies associated with the latter disturbances bear some resemblance to the anomalous height pattern in the Western Hemisphere. Such local eddy–mean flow feedbacks hence contribute to the zonal symmetry of the atmospheric response pattern to forcing in the IWP region. Analysis of zonally averaged circulation statistics indicates that the mean meridional circulation induced by divergence of anomalous transient eddy momentum fluxes in ENSO events could also generate zonally symmetric perturbations in midlatitudes.
The model-simulated precipitation and surface temperature anomalies in the North American sector in response to SST changes in IWP suggest an increased frequency of droughts and heat waves in that region during the summer season after warm ENSO events.
On the Stochastic Forcing of Modes of Interannual Southern Ocean Sea Surface Temperature Variability
Authors: Aiken Christopher M. , England Matthew H. 
Published: September 2005

Abstract
A simple linearized transport model of anomalous Southern Ocean sea surface temperature (SST) is studied to determine whether it can sustain anomalies of realistic amplitudes under a physically based stochastic forcing. As noted in previous studies, eigenmodes of this system with zonal wavenumbers 2 and 3 share key propagation characteristics with the SST anomalies associated with the Antarctic Circumpolar Wave (ACW). The system is solved on a grid that follows the path of the Antarctic Circumpolar Current (ACC) and is forced by a stochastic heat flux. The forcing is white in space and time and represents the advection of the mean SST gradient by high-frequency variations in the cross-ACC velocity, due to mesoscale eddy variability. The magnitude of the stochastic forcing is determined from a global eddy-permitting ocean model. Anomalous ocean surface velocity variability (8 cm s−1) coupled to a mean cross-ACC SST gradient of 0.8°C (°latitude)−1 sustains anomalous interannual SST variability at low wavenumbers and amplitudes of the order of 1°C, consistent with those associated with the ACW. In the long-term mean, variance is broadly spread among low wavenumbers, in contrast to the dominance of one or two zonal wavenumbers in the ACW observations. It is found, however, that the model produces single dominant wavenumbers over individual periods of decades, suggesting that the apparent unimodal nature of the ACW may be an artifact of the short observational record used to infer it. Alternatively, it is shown that a nonisotropic forcing may also result in a stronger preference for particular zonal wavenumbers. It is shown that if the atmosphere at mid to high southern latitudes has an equivalent barotropic response to heating, then the resulting sea level pressure anomalies reproduce the phase relationship of the observed ACW. These results are consistent with the notion that a simple stochastically forced advection of SST anomalies can explain SST variability associated with the ACW to leading order.
Western North Pacific Tropical Cyclone Intensity and ENSO
Authors: Camargo Suzana J. , Sobel Adam H. 
Published: September 2005

Abstract
The influence of the El Niño–Southern Oscillation (ENSO) on tropical cyclone intensity in the western North Pacific basin is examined. Accumulated cyclone energy (ACE), constructed from the best-track dataset for the region for the period 1950–2002, and other related variables are analyzed. ACE is positively correlated with ENSO indices. This and other statistics of the interannually varying tropical cyclone distribution are used to show that there is a tendency in El Niño years toward tropical cyclones that are both more intense and longer-lived than in La Niña years. ACE leads ENSO indices: during the peak season (northern summer and fall), ACE is correlated approximately as strongly with ENSO indices up to six months later (northern winter), as well as simultaneously. It appears that not all of this lead–lag relationship is easily explained by the autocorrelation of the ENSO indices, though much of it is. Interannual variations in the annual mean lifetime, intensity, and number of tropical cyclones all contribute to the ENSO signal in ACE, though the lifetime effect appears to be the most important of the three.