bluuebunny/crossref_metadata_2025_split huggingface dataset:
Processing Words with Emotional Connotation: An fMRI Study of Time Course and Laterality in Rostral Frontal and Retrosplenial Cortices
Authors: Cato M. Allison , Crosson Bruce , Gökçay Didem , Soltysik David , Wierenga Christina , Gopinath Kaundinya , Himes Nathan , Belanger Heather , Bauer Russell M. , Fischler Ira S. , Gonzalez-Rothi Leslie , Briggs Richard W. 
Published: April 2004

AbstractResponses of rostral frontal and retrosplenial cortices to the emotional significance of words were measured using functional magnetic resonance imaging (fMRI). Twenty-six strongly righthanded participants engaged in a language task that alternated between silent word generation to categories with positive, negative, or neutral emotional connotation and a baseline task of silent repetition of emotionally neutral words. Activation uniquely associated with word generation to categories with positive or negative versus neutral emotional connotation occurred bilaterally in rostral frontal and retrosplenial cortices. Furthermore, the time courses of activity in these areas differed, indicating that they subserve different functions in processing the emotional connotation of words. Namely, the retrosplenial cortex appears to be involved in evaluating the emotional salience of information from external sources, whereas the rostral frontal cortex also plays a role in internal generation of words with emotional connotation. In both areas, activity associated with positive or negative emotional connotation was more extensive in the left hemisphere than the right, regardless of valence, presumably due to the language demands of word generation. The present findings localize specific areas in the brain that are involved in processing emotional meaning of words within the brain's distributed semantic system. In addition, time course analysis reveals diverging mechanisms in anterior and posterior cortical areas during processing of words with emotional significance.
Eye Movements during Task Switching: Reflexive, Symbolic, and Affective Contributions to Response Selection
Authors: Hodgson Timothy Lewis , Golding Charlotte , Molyva Dimitra , Rosenthal Clive R. , Kennard Christopher 
Published: April 2004

Abstract
Active vision is a dynamic process involving the flexible coordination of different gaze strategies to achieve behavioral goals. Although many complex behaviors rely on an ability to efficiently switch between gaze-control strategies, few studies to date have examined mechanisms of task level oculomotor control in detail. Here, we report five experiments in which subjects alternated between conflicting stimulus-saccade mappings within a block of trials. The first experiment showed that there is no performance cost associated with switching between pro and anti saccades. However, follow-up experiments demonstrate that whenever subjects alternate between arbitrary stimulus-saccade mappings, latency costs are apparent on the first trial after a task change. More detailed analysis of switch costs showed that latencies were particularly elevated for saccades directed toward the same location that had been the target for a saccade on the preceeding trial. This saccade “inhibition of return” effect was most marked when unexpected error feedbacks cued task switches, suggesting that saccade selection processes are modulated by reward. We conclude that there are two systems for saccade control that differ in their characteristics following a task switch. The “reflexive” control system can be enabled/disabled in advance of saccade execution without incurring any performance cost. Switch costs are only observed when two or more arbitrary stimulus-saccade mappings have to be coordinated by a “symbolic” control system.
Extrinsic Cues Suppress the Encoding of Intrinsic Cues
Authors: Sheth Bhavin R. , Shimojo Shinsuke 
Published: April 2004

Abstract
Remembering where objects are in space is fundamental to adaptive behavior. Little is known about how intact humans combine information from intrinsic (egocentric) and extrinsic (exocentric, allocentric, or landmark-based) coordinate systems to locate objects. Using a simple location estimation paradigm, this study finds that we mostly remember position in extrinsic coordinates. Intrinsic-coordinate-based mapping of space is less precise in the presence of landmarks or extrinsic cues than in their absence. Thus, not only do extrinsic frames of reference dominate internal representations of space, they suppress intrinsic-based representations as well. We speculate that this dominance-suppression hierarchy undercuts intersystem conflicts and underlies a single, undissociated spatial map in intact humans.
Pursuit deterrent signalling by the bonaire whiptail lizard Cnemidophorus murinus
Authors: Baird Troy , Cooper William , Caldwell Janalee , Pérez-Mellado Valentín , Vitt Laurie 
Published: April 2004

AbstractPursuit-deterrent signalling may account for several behaviors, often subtle, that have no current satisfactory explanation. We conducted field observations and experiments to determine whether arm-waving by Bonaire whiptail lizards, Cnemidophorus murinus, is consistent with pursuit deterrent signalling. The hypotheses that lizards wave their arms to remove feet from hot substrates and that arm-waving is solely a social signal were falsified. Lizards preferentially waved the arm closer to an investigator simulating a predator, typically while looking directly at the predator. This strongly suggests signalling and contradicts the hypothesis that arm-waving is merely a flight intention movement. Most individuals retreat, providing a margin of safety, and then wave. As expected for a pursuit-deterrent signal, arm-waving is related to risk. During direct approaches lizards waved when the predator drew within 3-6 m if approached slowly, but fled without signalling if approached rapidly. Lizards approached tangentially signalled frequently when the minimum bypass distance was 2-4 m, but rarely when it was 10 m. They arm-waved when predators approached, but rarely while they retreated. Arm-waving was rare where lizards were habituated to human presence, but frequent elsewhere. Collectively, the data strongly suggest that arm-waving has a pursuit-deterrent function.
Long-term persistence of song performance rules in nightingales (Luscinia megarhynchos): a longitudinal field study on repertoire size and composition
Authors: Hultsch Henrike , Kipper Silke , Mundry Roger , Todt Dietmar 
Published: April 2004

AbstractCommon nightingales (Luscinia megarhynchos) are among those bird species that possess an extremely large repertoire and perform it in a versatile singing style. Thereby, repertoire size, composition, and performance differs considerably among individuals. In this longitudinal field study, we investigated the long-term stability of these differences in the song characteristics of free-ranging nightingales. We determined the repertoire characteristics for nine adult male individuals in two successive years (three of these individuals were investigated over the course of three years) and compared these to similar measurements obtained from comparisons of song samples of different birds. Comparisons revealed remarkable differences among males, but we did not find systematic differences in the song performance of birds in successive years. Instead, song characteristics were remarkably stable within successive years. The long-term persistence of individual song characteristics suggests that they are not related to dynamically changing individual attributes, but may reflect long-term storage of information during song acquisition as juveniles. In addition, we found that the repertoire performance of adult nightingales allows fine-tuned vocal interactions among several neighbouring males.
The prothrombin 3′end formation signal reveals a unique architecture that is sensitive to thrombophilic gain-of-function mutations
Authors: Danckwardt Sven , Gehring Niels H. , Neu-Yilik Gabriele , Hundsdoerfer Patrick , Pforsich Margit , Frede Ute , Hentze Matthias W. , Kulozik Andreas E. 
Published: April 2004

Abstract
The functional analysis of the common prothrombin 20210 G&gt;A(F2 20210*A) mutation has recently revealed gain of function of 3′end processing as a novel genetic mechanism predisposing to human disease. We now show that the physiologic G at the cleavage site at position 20210 is the functionally least efficient nucleotide to support 3′end processing but has evolved to be physiologically optimal. Furthermore, the F2 3′end processing signal is characterized by a weak downstream cleavage stimulating factor (CstF) binding site with a low uridine density, and the functional efficiency of F2 3′end processing can be enhanced by the introduction of additional uridine residues. The recently identified thrombosis-related mutation (F2 20221*T) within the CstF binding site up-regulates F2 3′end processing and prothrombin biosynthesis in vivo. F2 20221*T thus represents the first example of a likely pathologically relevant mutation of the putative CstF binding site in the 3′flanking sequence of a human gene. Finally, we show that the low-efficiency F2 cleavage and CstF binding sites are balanced by a stimulatory upstream uridine-rich element in the 3′UTR. The architecture of the F2 3′end processing signal is thus characterized by a delicate balance of positive and negative signals. This balance appears to be highly susceptible to being disturbed by clinically relevant gain-of-function mutations. (Blood. 2004;104:428-435)
LDL oxidized by hypochlorous acid causes irreversible platelet aggregation when combined with low levels of ADP, thrombin, epinephrine, or macrophage-derived chemokine (CCL22)
Authors: Coleman Leon G. , Polanowska-Grabowska Renata K. , Marcinkiewicz Marek , Gear Adrian R. L. 
Published: April 2004

AbstractThe in vitro oxidation of low-density lipoprotein (LDL) by hypochlorous acid produces a modified form (HOCl-LDL) capable of stimulating platelet function. We now report that HOCl-LDL is highly effective at inducing platelet function, causing stable aggregation and α-granule secretion. Such stimulation depended on the presence of low levels of primary agonists such as adenosine diphosphate (ADP) and thrombin, or others like epinephrine (EPI) and macrophage-derived chemokine (MDC, CCL22). Agonist levels, which by themselves induced little or reversible aggregation, caused strong stable aggregation when combined with low levels of HOCl-LDL. Platelet activation by HOCl-LDL and ADP (1 μM) caused P-selectin (CD62P) exposure, without serotonin or adenosine triphosphate (ATP) secretion. Intracellular calcium levels rose slowly (from 100 to 200 nM) in response to HOCl-LDL alone and rapidly when combined with ADP to about 300 nM. p38 mitogen-activated protein kinase (MAPK) became phosphorylated in response to HOCl-LDL alone. This phosphorylation was not blocked by the protein kinase C (PKC) inhibitor bisindolylmaleimide, which reduced the extent of aggregation and calcium increase. However, the p38 MAPK inhibitor SB203580 blocked platelet aggregation and phosphorylation of p38 MAPK. These findings suggest that HOCl-LDL exposed during atherosclerotic plaque rupture, coupled with low levels of primary agonists, can rapidly induce extensive and stable thrombus formation. (Blood. 2004;104:380-389)
Matching at the MHC class I K locus is essential for long-term engraftment of purified hematopoietic stem cells: a role for host NK cells in regulating HSC engraftment
Authors: Huang Yiming , Rezzoug Francine , Chilton Paula M. , Grimes H. Leighton , Cramer Daniel E. , Ildstad Suzanne T. 
Published: April 2004

AbstractThe events that regulate engraftment and long-term repopulating ability of hematopoietic stem cells (HSCs) after transplantation are not well defined. We report for the first time that major histocompatibility complex (MHC) class I K plays a critical role in HSC engraftment via interaction with recipient natural killer (NK) cells. Durable engraftment of purified HSCs requires MHC class I K matching between HSC donor and recipient. In the absence of MHC class I K matching, HSCs exhibit impaired long-term engraftment (P = .01). Dependence on MHC class I K matching is eliminated in B6 beige mice that lack NK cell function, as well as in wild-type mice depleted of NK cells, implicating a possible regulatory role of NK cells for HSC engraftment. The coadministration of CD8+/T-cell receptor–negative (TCR-) graft facilitating cells (FCs) matched at MHC class I K to the HSC donor overcomes the requirement for MHC class I K matching between HSCs and recipient. These data demonstrate that FCs inhibit NK cell effects on the HSCs. Notably, FCs do not suppress the cytotoxic activity of activated NK cells. Enhanced green fluorescent protein–positive (EGFP+) FCs persist for one month following allogeneic transplantation, making cold target inhibition an unlikely mechanism. Therefore, MHC class I may play a critical role in the initiating events that dictate HSC engraftment and/or NK-mediated rejection following allogeneic transplantation.
Relation between CXCR-4 expression, Flt3 mutations, and unfavorable prognosis of adult acute myeloid leukemia
Authors: Rombouts Elwin J. C. , Pavic Biljana , Löwenberg Bob , Ploemacher Rob E. 
Published: April 2004

AbstractRecently it was shown that, analogous to normal hematopoietic cells, the level of CXC chemokine receptor 4 (CXCR-4) expression on acute myeloid leukemia (AML) cells correlates with stromal cell derived factor-1 alpha (SDF-1)-induced chemotaxis. As we speculated that an anomalous organ distribution of AML cells could affect cell survival and thus result in an altered fraction surviving chemotherapy, we examined a possible correlation between patient prognosis and CXCR-4 expression in AML patients. We found that patients with a high CXCR-4 expression in the CD34+ subset had a significantly reduced survival and a higher probability of relapse, resulting in a median relapse-free survival (RFS) of only 8.3 months. CXCR-4 expression was significantly higher in fetal liver tyrosine kinase-3 (Flt3)/internal tandem duplication (ITD) AML than in Flt3/wild-type (wt) AML. Covariate analysis indicated that the prognostic significance of Flt3/ITDs with respect to RFS was no more apparent when analyzed in conjunction with the expression of CXCR-4 in the CD34+ subset, suggesting that the poor prognosis of Flt3/ITD AML might be subordinate to the increased CXCR-4 expression. Using a granulocyte colony-stimulating factor receptor (G-CSF-R)-expressing 32D cell line, we observed that SDF-1/CXCR-4 interaction is required for the survival of myeloid differentiating cells, and it also induces a block in G-CSF-induced myeloid differentiation. These data suggest that the SDF-1/CXCR-4 axis may influence therapy responsiveness and defines unfavorable prognosis in AML. (Blood. 2004;104:550-557)
Impact of T and N Stage and Treatment on Survival and Relapse in Adjuvant Rectal Cancer
Authors: Gunderson Leonard L. , Sargent Daniel J. , Tepper Joel E. , Wolmark Norman , O'Connell Michael J. , Begovic Mirsada , Allmer Cristine , Colangelo Linda , Smalley Steven R. , Haller Daniel G. , Martenson James A. , Mayer Robert J. , Rich Tyvin A. , Ajani Jaffer A. , MacDonald John S. , Willett Christopher G. , Goldberg Richard M. 
Published: April 2004

Purpose To determine survival and relapse rates by T and N stage and treatment method in five randomized phase III North American rectal adjuvant studies. Patients and Methods Data were pooled from 3,791 eligible patients enrolled onto North Central Cancer Treatment Group (NCCTG) 79-47-51, NCCTG 86-47-51, US Gastrointestinal Intergroup 0114, National Surgical Adjuvant Breast and Bowel Project (NSABP) R01, and NSABP R02. Surgery alone (S) was the treatment arm in 179 patients. The remaining patients received adjuvant treatment as follows: irradiation (RT) alone (n = 281), RT + fluorouracil (FU) ± semustine bolus chemotherapy (CT; n = 779), RT + protracted venous infusion CT (n = 325), RT + FU ± leucovorin or levamisole bolus CT (n = 1,695), or CT alone (n = 532). Five-year follow-up was available in 94% of surviving patients, and 8-year follow-up, in 62%. Results Overall (OS) and disease-free survival were dependent on TN stage, NT stage, and treatment method. Even among N2 patients, T substage influenced 5-year OS (T1-2, 67%; T3, 44%; T4, 37%; P < .001). Three risk groups of patients were defined: (1) intermediate (T1-2/N1, T3/N0), (2) moderately high (T1-2/N2, T3/N1, T4/N0), and (3) high (T3/N2, T4/N1, T4/N2). For intermediate-risk patients, those receiving S plus CT had 5-year OS rates of 85% (T1-2/N1) and 84% (T3/N0), which was similar to results with S plus RT plus CT (T1-2/N1, 78% to 83%; T3/N0, 74% to 80%). For moderately high-risk lesions, 5-year OS ranged from 43% to 70% with S plus CT, and 44% to 80% with S plus RT plus CT. For high-risk lesions, 5-year OS ranged from 25% to 45% with S plus CT, and 29% to 57% with S plus RT plus CT. Conclusion Different treatment strategies may be indicated for intermediate-risk versus moderately high- or high-risk patients based on differential survival rates and rates of relapse. Use of trimodality treatment for all patients with intermediate-risk lesions may be excessive, since S plus CT resulted in 5-year OS of approximately 85%; however, 5-year disease-free survival rates with S plus CT were 78% (T1-2/N1) and 69%(T3/N0), indicating room for improvement.
Forkhead L2 Is Expressed in the Ovary and Represses the Promoter Activity of the Steroidogenic Acute Regulatory Gene
Authors: Pisarska Margareta D. , Bae Jeehyeon , Klein Cynthia , Hsueh Aaron J. W. 
Published: April 2004

AbstractPremature ovarian failure in a subgroup of women with blepharophimosis-ptosis-epicanthus inversus type 1 syndrome has been associated with nonsense mutations in the gene encoding a Forkhead transcription factor, Forkhead L2 (FOXL2). However, the exact function of FOXL2 in the ovary is unclear. We investigated the expression of FOXL2 in the mouse ovary during follicular development and maturation by RT-PCR and in situ hybridization. The FOXL2 mRNA is expressed in ovaries throughout development and adulthood and is localized to the undifferentiated granulosa cells in small and medium follicles as well as cumulus cells of preovulatory follicles. FOXL2 belongs to a group of transcription factors capable of interacting with specific DNA sequences in diverse gene promoters. With the presence of multiple putative forkhead DNA consensus sites, the promoter of the human steroidogenic acute regulatory (StAR) gene was used to test for regulation by FOXL2. Cotransfection studies revealed that wild-type FOXL2 represses the activity of the StAR promoter, and the first 95 bp upstream of the transcriptional start site of the StAR gene is sufficient for FOXL2 repression. EMSAs confirmed that FOXL2 interacts directly with this region. Analyses using FOXL2 mutants also demonstrated the importance of the entire alanine/proline-rich carboxyl terminus of FOXL2 for transcriptional repression. Furthermore, these mutations produce a protein with a dominant-negative effect that disables the transcriptional repressor activity of wild-type FOXL2. Dominant-negative mutations of FOXL2 could increase expression of StAR and other follicle differentiation genes in small and medium follicles to accelerate follicle development, resulting in increased initial recruitment of dormant follicles and thus the premature ovarian failure phenotype.
Neuropeptide Y Is Required for Hyperphagic Feeding in Response to Neuroglucopenia
Authors: Sindelar Dana K. , Ste. Marie Linda , Miura Grant I. , Palmiter Richard D. , McMinn Julie E. , Morton Gregory J. , Schwartz Michael W. 
Published: April 2004

Abstract
To investigate the role played by the orexigenic peptide, neuropeptide Y (NPY), in adaptive responses to insulin-induced hypoglycemia, we measured hypothalamic, feeding, and hormonal responses to this stimulus in both wild-type (Npy+/+) and NPY-deficient (Npy−/−) mice. After administration of insulin at a dose (60 mU ip) sufficient to cause moderate hypoglycemia (plasma glucose levels, 40 ± 3 and 37 ± 2 mg/dl for Npy+/+ and Npy−/− mice, respectively; P = not significant), 4-h food intake was increased 2.5-fold in Npy+/+ mice relative to saline-injected controls. By comparison, the increase of intake in Npy−/− mice was far smaller (45%) and did not achieve statistical significance (P = 0.08). Hyperphagic feeding in response to insulin-induced hypoglycemia was therefore markedly attenuated in mice lacking NPY, and a similar feeding deficit was detected in these animals after neuroglucopenia induced by 2-deoxyglucose (500 mg/kg ip). A role for NPY in glucoprivic feeding is further supported by our finding that Npy mRNA content (measured by real-time PCR) increased 2.4-fold in the hypothalamus of Npy+/+ mice by 7 h after insulin injection. Unlike the feeding deficits observed in mice lacking NPY, the effect of hypoglycemia to increase plasma glucagon and corticosterone levels was fully intact in these animals, as were both the nadir glucose value and time to recovery of euglycemia after insulin injection (P = not significant). We conclude that NPY signaling is required for hyperphagic feeding, but not neuroendocrine responses to moderate hypoglycemia.
Absorption of taurocholic acid by the ileum of normal and transgenic ΔF508 cystic fibrosis mice
Authors: Hardcastle J , Harwood M D , Taylor C J 
Published: April 2004

Abstract
Changes in intestinal transport in cystic fibrosis (CF) include both defective Cl− secretion and alterations in absorption. This study focused on the effects of CF on the active re-absorption of bile acids in the ileum of normal and transgenic CF mice. Taurocholic acid absorption was monitored as changes in short-circuit current (SCC) in intact and stripped ileal sheets from normal (Swiss) and transgenic CF (Cftrtm2Cam) mice with the ΔF508 mutation. Taurocholic acid uptake was measured directly in everted ileal sacs and in brush-border membrane vesicles (BBMVs) using radiolabelled bile acid. Taurocholic acid caused a biphasic increase in SCC in both intact and stripped ileal sheets from Swiss mice. The initial phase of the response was associated with active bile acid absorption as it was inhibited by a low mucosal Na+ concentration, but unaffected by Cl−-free conditions, serosal furosemide or mucosal diphenylamine-2-carboxylic acid (DPC). The first phase was concentration-dependent and was reduced in the presence of other actively transported bile acids. Intact ileal sheets from wild-type Cftrtm2Cam mice also exhibited a biphasic SCC response to taurocholic acid, but in CF tissues the initial phase was reduced and the second phase was absent. Taurocholic acid was actively taken up by everted ileal sacs from Swiss mice. This process was inhibited by a low mucosal Na+ concentration or the presence of other actively transported bile acids. A similar taurocholic acid uptake was observed in ileal sacs from wild-type mice, but in those from CF mice transport of the bile acid was significantly reduced. However, taurocholic acid uptake was similar in BBMVs from wildtype and CF ilea. Active absorption of taurocholic acid occurs in mouse ileum and this process is reduced in transgenic mouse models of CF with the ΔF508 mutation. However, this difference cannot be detected in an isolated preparation of brush-border membranes.