bluuebunny/crossref_metadata_2025 huggingface dataset:
Baroreceptor reflex control of heart rate in rats studied by induced and autogenic changes in arterial pressure
Authors: Moffitt Julia A. , Grippo Angela J. , Johnson Alan Kim
Published: January 2005

The function of the arterial baroreflex has traditionally been assessed by measurement of reflex changes in heart rate (HR) or sympathetic nerve activity resulting from experimenter-induced manipulation of arterial blood pressure (the Oxford method, also termed the pharmacological method). However, logistical and flexibility limitations of this technique have promoted the development of new methods for assessing baroreflex function such as the evaluation of changes in spontaneous arterial pressure and HR. Although this new spontaneous method has been validated in dogs and humans, it has not been rigorously tested in rats. In the present study, the method of correlating spontaneous changes in systolic blood pressure and HR was evaluated in resting, normotensive Sprague-Dawley rats. This technique was found to be neither reliable nor valid under the conditions employed in the present protocol. We also tested a variation of the spontaneous method that evaluates particular sequences of data during which arterial pressure and pulse interval are changing in the same direction for at least three consecutive heartbeats (the sequence method). The sequence method did not provide extra reliability or validity over the spontaneous method. We conclude that due to the restricted range of variability obtained by measuring spontaneous blood pressure fluctuations, the spontaneous and sequence techniques do not provide data that are comparable to the traditional method of assessing HR changes triggered by arterial blood pressure increases and decreases induced by vasoactive drugs. However, it is possible that surgical stress obscured the relationship between blood pressure and HR, and therefore additional studies are needed to determine whether the spontaneous and sequence methods can be applied to rats during different behavioral states.
The anorectic effect of fenfluramine is influenced by sex and stage of the estrous cycle in rats
Authors: Eckel Lisa A. , Rivera Heidi M. , Atchley Deann P. D.
Published: January 2005

The controls of food intake differ in male and female rats. Daily food intake is typically greater in male rats, relative to female rats, and a decrease in food intake, coincident with the estrous stage of the ovarian reproductive cycle, is well documented in female rats. This estrous-related decrease in food intake has been attributed to a transient increase in the female rat's sensitivity to satiety signals generated during feeding bouts. Here, we investigated whether sex or stage of the estrous cycle modulate the satiety signal generated by fenfluramine, a potent serotonin (5-HT) releasing agent. To examine this hypothesis, food intake was monitored in male, diestrous female, and estrous female rats after intraperitoneal injections of 0, 0.25, and 1.0 mg/kg d-fenfluramine. The lower dose of fenfluramine decreased food intake only in diestrous and estrous females, suggesting that the minimally effective anorectic dose of fenfluramine is lower in female rats, relative to male rats. Although the larger dose of fenfluramine decreased food intake in both sexes, the duration of anorexia was greater in diestrous and estrous female rats, relative to male rats. Moreover, the magnitude of the anorectic effect of the larger dose of fenfluramine was greatest in estrous rats, intermediate in diestrous rats, and least in male rats. Thus our findings indicate that the anorectic effect of fenfluramine is modulated by gonadal hormone status.
Localization of Spinal Neurons Activated During Locomotion Using thec-fosImmunohistochemical Method
Authors: Dai X. , Noga B. R. , Douglas J. R. , Jordan L. M.
Published: January 2005

The c-fos immunohistochemical method of activity-dependent labeling was used to localize locomotor-activated neurons in the adult cat spinal cord. In decerebrate cats, treadmill locomotion was evoked by electrical stimulation of the mesencephalic locomotor region (MLR). Spontaneous or MLR-evoked fictive locomotion was produced in decerebrate animals paralyzed with a neuromuscular blocking agent. After bouts of locomotion during a 7- to 9-h time period, the animals were perfused and the L3–S1spinal cord segments removed for immunohistochemistry. Control animals were subjected to the same surgical procedures but no locomotor task. Labeled cells were concentrated in Rexed's laminae III and IV of the dorsal horn and laminae VII, VIII, and X of the intermediate zone/ventral horn after treadmill locomotion. Cells in laminae VII, VIII, and X were labeled after fictive locomotion, but labeling in the dorsal horn was much reduced. In control animals, c- fos labeling was a small fraction of that observed in the locomotor animals. The results suggest that labeled cells in laminae VII, VIII, and X are premotor interneurons involved in the production of locomotion, whereas the laminae III and IV cells are those activated during locomotion due to afferent feedback from the moving limb. c-fos-labeled cells were most numerous in the L5–L7segments, consistent with the distribution of locomotor activated neurons detected through the use of MLR-evoked field potentials.
Adenylate Cyclase-Mediated Forms of Neuronal Plasticity in Hippocampal Area CA1 Are Reduced With Aging
Authors: Reis Gerald F. , Lee Michael B. , Huang Alex S. , Parfitt Karen D.
Published: January 2005

Beta-adrenergic receptors and the cyclic AMP signaling pathway play an important role in neuronal plasticity and in learning and memory and are known to change with aging. We examined the effects of β-adrenergic stimulation paired with 5-Hz low frequency stimulation (LFS) of Schaffer collateral-commissural afferents on population spike amplitude in area CA1 of hippocampal slices from young (3 mo) and aged (22 mo) Fischer 344 rats. Application of the β-adrenergic agonist isoproterenol (1 μM) for 10 min followed immediately by 3 min LFS produced long-lasting potentiation in young hippocampi, but the magnitude of potentiation in aged rats was significantly attenuated and was not long-lasting. In slices prepared from young rats, long-term potentiation (LTP) induced by this protocol occludes subsequent attempts to produce conventional high frequency stimulation-induced LTP, and vice versa, suggesting that these two forms of potentiation share one or more molecular mechanisms. Age-related differences in response to LFS alone were not observed, but significant differences in response to β-adrenergic stimulation were apparent. Similarly, significant age-related differences in response to direct activation of adenylate cyclase with forskolin (10 μM) were observed. In both age groups, this enhancement produced by isoproterenol or forskolin is only transient, returning to baseline within 60 or 90 min, respectively. Taken together, these studies of adenylate cyclase-mediated forms of potentiation in area CA1 suggest that there is an age-related defect, either upstream or downstream of adenylate cyclase activation, in this important signaling system. Such changes may contribute to the compromised performance on memory tasks that is often observed with normal aging.
Neuronal Activity Representing Temporal Prediction of Reward in the Primate Prefrontal Cortex
Authors: Tsujimoto Satoshi , Sawaguchi Toshiyuki
Published: January 2005

Temporal prediction of future events, especially regarding reward delivery, is critical for controlling/learning purposeful behavior. The dorsolateral prefrontal cortex (DLPFC) has been considered to be involved in behavioral control based on prospective coding for future events, including reward. Thus this area is likely to have a neuronal mechanism responsible for temporal prediction of forthcoming reward. To address this hypothesis, we recorded the neuronal activity from the DLPFC of macaque monkeys while they performed an oculomotor delayed-response task under two conditions regarding the time of reward delivery. In this task, when the subjects made a correct response, the reward was delivered after a reward-delay period of 0.5 or 2 s. At the behavioral level, the onset latency for saccades was significantly faster in the shorter reward-delay trials (0.5 s) than in longer reward-delay trials (2 s), indicating that our subjects actually predicted the time of reward delivery. At the neuronal level, we found that many DLPFC neurons showed differential activity depending on the predicted time of reward delivery during the cue and/or delay periods. These results suggest that a fraction of neurons in the DLPFC represent the temporal prediction of reward and probably a variety of other future events.
Complete Deficiency of the Low-Density Lipoprotein Receptor Is Associated With Increased Apolipoprotein B-100 Production
Authors: Millar John S. , Maugeais Cyrille , Ikewaki Katsunori , Kolansky Daniel M. , Barrett P.Hugh R. , Budreck Elaine C. , Boston Raymond C. , Tada Norio , Mochizuki Seibu , Defesche Joep C. , Wilson James M. , Rader Daniel J.
Published: January 2005

Objective—

We addressed the role of the low-density lipoprotein (LDL) receptor in determining clearance rates and production rate (PR) of apolipoprotein B (apoB) in humans.

Methods and Results—

Kinetic studies using endogenous labeling of apoB with deuterated leucine were performed in 7 genetically defined patients with homozygous familial hypercholesterolemia (FH) and compared with 4 controls. The fractional catabolic rates (FCR) and PRs for apoB were determined by multicompartmental modeling. The FCRs of very-low-density lipoprotein 1 (VLDL1), VLDL2, intermediate-density lipoprotein (IDL), and LDL apoB were lower in FH than in controls, with the LDL apoB FCR being significantly lower (0.148±0.049 versus 0.499±0.099 pools · d
−1
;
P
=0.008). Whereas receptor-defective FH patients had a total apoB PR similar to controls, receptor-null FH patients had a significantly greater total apoB PR than controls (35.97±10.51 versus 21.32±4.21 mg · kg
−1
· d
−1
, respectively;
P
=0.02).

Conclusions—

This first study of apoB metabolism in homozygous FH using endogenous labeling with stable isotopes demonstrates that the LDL receptor contributes significantly to the clearance of LDL from plasma but plays a lesser role in the clearance of larger apoB-containing lipoproteins. Furthermore, these data also indicate that absence of a LDL receptor in humans substantially influences the apoB PR in vivo.
Organisational Adventures in District Government in Long An Province: Central Regulation Versus Local Initiative
Authors: Hicks Natalie
Published: January 2005

This article explores the role of district government in agricultural development in Vietnam's Long An province from 1954 to the present. It argues that it is only in the reform era that the district has begun to realise its potential as a 'transmission belt' between the higher authorities and the grassroots. Under the South Vietnamese regime and in the pre-reform era of the Socialist Republic of Vietnam, local initiative was stifled as policy was dictated from on high by central government, with disastrous consequences. In the reform era, district officials have been joined by 'associates of the state', such as agricultural extension officers, to develop innovative 'local' approaches to agricultural development. This has led to increased prosperity but also rising inequality. While the central government has been more willing to allow local experimentation under reform, its influence and interests are still felt, even at the district level. Most scholars emphasise a sharp break between pre-1975 and post-1975 Vietnam. By contrast, this article highlights the way in which there are important elements of continuity both between regimes and between the pre-reform and post-reform eras.
A Bias-Corrected Precipitation Climatology for China
Authors: Ye Baisheng , Yang Daqing , Ding Yongjian , Han Tianding , Koike Toshio
Published: January 2005

This paper presents the results of bias corrections of Chinese standard precipitation gauge (CSPG) measurements for wind-induced undercatch, a trace amount of precipitation, and wetting loss. Long-term daily data of precipitation, temperature, and wind speed during 1951–98 at 710 meteorological stations in China were used for this analysis. It is found that wind-induced gauge undercatch is the greatest error in most regions, and wetting loss and a trace amount of precipitation are important in the low-precipitation regions in northwest China. Monthly correction factors ratio of corrected amount to measured amount of precipitation differ by location and by type of precipitation. Considerable interannual variation of the corrections exists in China due to the fluctuations of wind speed and frequency of precipitation. More importantly, annual precipitation has been increased by 8 to 740 mm with an overall mean of 130 mm at the 710 stations over China because of the bias corrections for the study period. This corresponds to 6%–62% increases (overall mean of 19% at the 710 stations over China) in gauge-measured yearly total precipitation over China. This important finding clearly suggests that annual precipitation in China is much higher than previously reported. The results of this study will be useful to hydrological and climatic studies in China.
Realistic Initialization of Land Surface States: Impacts on Subseasonal Forecast Skill
Authors: Koster Randal D. , Suarez Max J. , Liu Ping , Jambor Urszula , Berg Aaron , Kistler Michael , Reichle Rolf , Rodell Matthew , Famiglietti Jay
Published: January 2005

Forcing a land surface model (LSM) offline with realistic global fields of precipitation, radiation, and near-surface meteorology produces realistic fields (within the context of the LSM) of soil moisture, temperature, and other land surface states. These fields can be used as initial conditions for precipitation and temperature forecasts with an atmospheric general circulation model (AGCM). Their usefulness is tested in this regard by performing retrospective 1-month forecasts (for May through September, 1979–93) with the NASA Global Modeling and Assimilation Office (GMAO) seasonal prediction system. The 75 separate forecasts provide an adequate statistical basis for quantifying improvements in forecast skill associated with land initialization.

Evaluation of skill is focused on the Great Plains of North America, a region with both a reliable land initialization and an ability of soil moisture conditions to overwhelm atmospheric chaos in the evolution of the meteorological fields. The land initialization does cause a small but statistically significant improvement in precipitation and air temperature forecasts in this region. For precipitation, the increases in forecast skill appear strongest in May through July, whereas for air temperature, they are largest in August and September. The joint initialization of land and atmospheric variables is considered in a supplemental series of ensemble monthly forecasts. Potential predictability from atmospheric initialization dominates over that from land initialization during the first 2 weeks of the forecast, whereas during the final 2 weeks, the relative contributions from the two sources are of the same order. Both land and atmospheric initialization contribute independently to the actual skill of the monthly temperature forecast, with the greatest skill derived from the initialization of both. Land initialization appears to contribute the most to monthly precipitation forecast skill.
Winter Orographic Precipitation Ratios in the Sierra Nevada—Large-Scale Atmospheric Circulations and Hydrologic Consequences
Authors: Dettinger Michael , Redmond Kelly , Cayan Daniel
Published: January 2005

The extent to which winter precipitation is orographically enhanced within the Sierra Nevada of California varies from storm to storm, and season to season, from occasions when precipitation rates at low and high altitudes are almost the same to instances when precipitation rates at middle elevations (considered here) can be as much as 30 times more than at the base of the range. Analyses of large-scale conditions associated with orographic precipitation variations during storms and seasons from 1954 to 1999 show that strongly orographic storms most commonly have winds that transport water vapor across the range from a more nearly westerly direction than during less orographic storms and than during the largest overall storms, and generally the strongly orographic storms are less convectively stable. Strongly orographic conditions often follow heavy precipitation events because both of these wind conditions are present in midlatitude cyclones that form the cores of many Sierra Nevada storms. Storms during La Niña winters tend to yield larger orographic ratios (ORs) than do those during El Niños. A simple experiment with a model of streamflows from a river basin draining the central Sierra Nevada indicates that, for a fixed overall basin-precipitation amount, a decrease in OR contributes to larger winter flood peaks and smaller springtime flows, and thus to an overall hastening of the runoff season.
Coupling between Large-Scale Atmospheric Processes and Mesoscale Land–Atmosphere Interactions in the U.S. Southern Great Plains during Summer. Part I: Case Studies
Authors: Weaver Christopher P.
Published: January 2005

This paper is Part I of a two-part study that uses high-resolution Regional Atmospheric Modeling System (RAMS) simulations to investigate mesoscale land–atmosphere interactions in the summertime U.S. Southern Great Plains. The focus is on the atmospheric dynamics associated with mesoscale heterogeneity in the underlying surface fluxes: how shifts in meteorological regimes modulate these diurnal, mesoscale processes, and their overall impact at larger scales and over multiple diurnal cycles. Part I examines individual case study time periods drawn from the simulations that illustrate general points about the key land–atmosphere interactions. The main findings are as follows: The mesoscale processes are embedded within a synoptic-scale organization that controls the background meteorological regime at a given location. During the clear, dry days in the simulated months, heterogeneity in the surface fluxes forces strong, lower-tropospheric, mesoscale circulations that exhibit a characteristic dynamical life cycle over diurnal time scales. In general, the background large-scale flow does not affect the overall intensity of these coherent roll structures, though strong large-scale subsidence can sometimes dampen them. In addition, depending on the thermodynamic profile, the strong vertical motions associated with these circulations are sufficient to trigger shallow or even deep convection, with associated clouds and precipitation. Furthermore, surface heterogeneity sufficient to force such circulations can arise even without heterogeneity in preexisting land cover characteristics such as vegetation, for example, solely as a result of spatial variability in rainfall and other atmospheric processes. In Part II the mesoscale land–atmosphere interactions in these case study periods are placed in the larger context of the full, monthlong simulations.
The Role of Atmospheric Processes Associated with Hurricane Olga in the December 2001 Floods in Israel
Authors: Krichak Simon O. , Alpert Pinhas , Dayan Melina
Published: January 2005

Over the period from 0000 UTC 3 December to 0000 UTC 5 December 2001, heavy rains fell in northern Israel. Intensity of the rainfall in some areas exceeded 250 mm (24 h)−1. Results of an investigation of the case including back-trajectory evaluations, numerical simulation experiments, and a potential vorticity (PV) analysis are presented. It is demonstrated that the unusual eastern Mediterranean process has been initiated by the formation of a tropical storm that later became Hurricane Olga from 25 to 29 November. The consequent synoptic processes were associated with the development of a large-scale anticyclone to the NE of the tropical storm. Large-scale subsidence in the anticyclone played a central role in the process by leading to a convergence of the moist air masses in a narrow band on the outskirts of the system. The air masses from the area were later transported into the midtroposphere over western Europe. The interaction of these relatively warm and wet air masses with the cold and dry upper-tropospheric air over Europe has led to an intensification of the upper-tropospheric northerly airflow, extrusion of stratospheric air into the upper troposphere, and formation of a PV streamer system over southern Europe. Finally, the positioning and intensity of the PV streamer, as well as the large amounts of air moisture over the Mediterranean region, contributed to the intensity of the 3–5 December 2001 torrential rains over Israel.
Modeling Creative and Courageous School Leadership Through District-Community-University Partnerships
Authors: Goldring Ellen , Sims Pearl
Published: January 2005

This article examines the Principals Leadership Academy of Nashville (PLAN) to explore the question How do university-community-district partnerships develop as successful cooperative endeavors? Interviews conducted with key stakeholders are analyzed to study critical aspects of the partnership’s governance structure, guiding principles, and political decision-making processes. PLAN demonstrates that cooperative interorganizational relationships can take firm root and flourish under an innovative leadership structure that is grounded in principles of shared power and shared learning. Such a partnership requires strong commitment and leadership from three levels of leaders. Top-level leaders (the public school superintendent, the dean of the college of education, and key community leaders) must be highly visible in their support of the partnership. Frontline leaders must design and implement the partnership’s programs and must be champions within their respective organizations. Finally, the critical role of a bridge-building leader (boundary spanner)is discussed.
Effects of an ankle-foot orthosis on balance performance in patients with hemiparesis of different durations
Authors: Wang Ray-Yau , Yen Lu-Lu , Lee Chao-Chung , Lin Pei-Yi , Wang Mei-Fang , Yang Yea-Ru
Published: January 2005

Objective: To examine the effects of an ankle-foot orthosis (AFO) on balance performance in patients with hemiparesis of short and long duration.

Design: Within-subject random order of intervention, cross-sectional study design.

Settings: Medical centres and district hospitals.

Subjects: Forty-two subjects with hemiparesis of short duration (B=six months) and 61 subjects of long duration (=12 months).

Measurements: The balance and gait ability of subjects were evaluated both with an AFO and without. The static and dynamic balance activities were evaluated by the Balance Master System, whereas the functional balance was assessed with the Berg Balance Scale. The speed and cadence were also measured during a 10-metre walk. Paired t-test was used to determine the effect of the AFO.

Results: In subjects with hemiparesis of short duration, we found that subjects wearing an AFO showed significant improvements in (1) weight-bearing distribution during quiet standing (p / 0.042, 95% confidence interval (CI) 0.521, 7.325), (2) body sway during standing on foam surface with eyes open (p / 0.020, 95% CI 0.020, 0.680) and eyes closed (p / 0.041, 95% CI 0.023, 0.921), (3) movement velocity during limit of stability test (LOS) / toward the affected side (p / 0.037, 95% Cl / 0.978, / 0.042) and nonaffected side (p / 0.008, 95% CI / 2.223, / 0.377), (4) maximal excursion toward the affected side (p / 0.042, 95% CI / 19.546,=0.071), and (5) speed (p / 0.028, 95% CI / 0.204, / 0.017) and cadence (p / 0.021, 95% CI / 22.983, / 1.864). Such effects were not observed in subjects with hemiparesis of long duration.

Conclusions: For the subjects with hemiparesis of short duration, the AFO improves the symmetry in quiet and dynamic standing balances. It also increases speed and cadence. However, its effectiveness is minimal for patients of long duration.
The development and validation of a handicap questionnaire for children with a chronic illness
Authors: Detmar S B , Hosli E J , Chorus A MJ , van Beekum T , Vogels T , Mourad-Baars P EC , Engelberts A C , Groothuis-Oudshoorn C GM , Verrips G HW
Published: January 2005

Introduction: This paper describes the development and initial psychometric evaluation of the Handicap Scale for Children (HSC). This questionnaire is based on the London Handicap Scale (LHS), a valid and reliable utility instrument for measuring social participation in adults.

Methods: A multidisciplinary research group was involved in developing the HSC. The questionnaire was tested in 114 children with a chronic disease and 239 healthy children in the 8-18 age range. Relating the Health Utility Index Mark 3 (HUI3) attributes to corresponding HSC scores tested the assumption that a negative health status would lead to participation problems.

Results: Questionnaire development resulted in a five-dimension questionnaire: mobility, physical independence, daily activities, social integration and orientation. Each dimension included one item with a six-point response scale. A higher score indicates greater handicap. Feasibility testing with 10 children showed that none of the children experienced difficulties in filling in the questionnaire. Conceptual validity, measured by correlations between the dimensions of the HSC and HUI3, was satisfactory. As expected, moderate correlation coefficients between predefined pairs of HUI and HSC attributes were found; other correlation coefficients were low. Criterion validity was also satisfactory, as shown by large differences between the healthy and the chronically ill group and by several criteria within the chronically ill group.

Conclusion: Based on this initial evaluation, the questionnaire seems feasible and valid for use with children in the age range 8-18 years.
Physicians' knowledge of transdermal fentanyl
Authors: Welsh John , Reid Anne , Graham Julie , Curto Jorge , MacLeod Karen , O'Neill Claire
Published: January 2005

Background: Different opioids for use in the control of moderate to severe cancer pain have become widely available. More recently, sophisticated formulations such as transdermal patches have been developed. One example, transdermal fentanyl (TF), has characteristic pharmacokinetics and along with the other opioids, equivalency conversions are often made when changing from or to other opioids. Aim of study: To explore the knowledge of general practitioners (GPs), hospital consultants and oncologists about the pharmacology and use of TF in the management of moderate/severe cancer pain. Method: During 2001 and 2002 a questionnaire survey was carried out. A randomized selection of GPs, hospital consultants and oncologists (n-1167) from the UK and Ireland were sent a questionnaire and 576 (49%) were returned and evaluated. Results: The results show doctors who had previously prescribed TF are more confident and knowledgeable about the indications and pharmacology of TF than doctors who had never prescribed TF. Overall knowledge and confidence in using TF was poor.
Direct crossregulation between retinoic acid receptor β and Hox genes during hindbrain segmentation
Authors: Serpente Patricia , Tümpel Stefan , Ghyselinck Norbert B. , Niederreither Karen , Wiedemann Leanne M. , Dollé Pascal , Chambon Pierre , Krumlauf Robb , Gould Alex P.
Published: January 2005

During anteroposterior (AP) patterning of the developing hindbrain, the expression borders of many transcription factors are aligned at interfaces between neural segments called rhombomeres (r). Mechanisms regulating segmental expression have been identified for Hox genes, but for other classes of AP patterning genes there is only limited information. We have analysed the murine retinoic acid receptor β gene (Rarb) and show that it is induced prior to segmentation, by retinoic-acid (RA) signalling from the mesoderm. Induction establishes a diffuse expression border that regresses until, at later stages, it is stably maintained at the r6/r7 boundary by inputs from Hoxb4 and Hoxd4. Separate RA- and Hox-responsive enhancers mediate the two phases of Rarb expression: a regulatory mechanism remarkably similar to that of Hoxb4. By showing that Rarb is a direct transcriptional target of Hoxb4, this study identifies a new molecular link, completing a feedback circuit between Rarb, Hoxb4 and Hoxd4. We propose that the function of this circuit is to align the initially incongruent expression of multiple RA-induced genes at a single segment boundary.
Tbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis
Authors: Brown Daniel D. , Martz Shauna N. , Binder Olav , Goetz Sarah C. , Price Brenda M. J. , Smith Jim C. , Conlon Frank L.
Published: January 2005

Members of the T-box family of proteins play a fundamental role in patterning the developing vertebrate heart; however, the precise cellular requirements for any one family member and the mechanism by which individual T-box genes function remains largely unknown. In this study, we have investigated the cellular and molecular relationship between two T-box genes, Tbx5 and Tbx20. We demonstrate that blocking Tbx5or Tbx20 produces phenotypes that display a high degree of similarity, as judged by overall gross morphology, molecular marker analysis and cardiac physiology, implying that the two genes are required for and have non-redundant functions in early heart development. In addition, we demonstrate that although co-expressed, Tbx5 and Tbx20 are not dependent on the expression of one another, but rather have a synergistic role during early heart development. Consistent with this proposal, we show that TBX5 and TBX20 can physically interact and map the interaction domains,and we show a cellular interaction for the two proteins in cardiac development, thus providing the first evidence for direct interaction between members of the T-box gene family.
Transcriptional program controlled by the floral homeotic geneAGAMOUSduring early organogenesis
Authors: Gómez-Mena Concepción , de Folter Stefan , Costa Maria Manuela R. , Angenent Gerco C. , Sablowski Robert
Published: January 2005

Floral organs, whose identity is determined by specific combinations of homeotic genes, originate from a group of undifferentiated cells called the floral meristem. In Arabidopsis, the homeotic gene AGAMOUS(AG) terminates meristem activity and promotes development of stamens and carpels. To understand the program of gene expression activated by AG, we followed genome-wide expression during early stamen and carpel development. The AG target genes included most genes for which mutant screens revealed a function downstream of AG. Novel targets were validated by in situ hybridisation and binding to AG in vitro and in vivo. Transcription factors formed a large fraction of AG targets, suggesting that during early organogenesis, much of the genetic program is concerned with elaborating gene expression patterns. The results also suggest that AG and other homeotic proteins with which it interacts (SEPALLATA3, APETALA3,PISTILLATA) are coordinately regulated in a positive-feedback loop to maintain their own expression, and that AG activates biosynthesis of gibberellin, which has been proposed to promote the shift from meristem identity to differentiation.
FGF signalling and the mechanism of mesoderm spreading inDrosophilaembryos
Authors: Wilson Robert , Vogelsang Elisabeth , Leptin Maria
Published: January 2005

FGF signalling is needed for the proper establishment of the mesodermal cell layer in Drosophila embryos. The activation of the FGF receptor Heartless triggers the di-phosphorylation of MAPK in the mesoderm, which accumulates in a graded fashion with the highest levels seen at the dorsal edge of the mesoderm. We have examined the specific requirement for FGF signalling in the spreading process. We show that only the initial step of spreading, specifically the establishment of contact between the ectoderm and the mesoderm, depends upon FGF signalling, and that unlike the role of FGF signalling in the differentiation of heart precursors this function cannot be replaced by other receptor tyrosine kinases. The initiation of mesoderm spreading requires the FGF receptor to possess a functional kinase domain, but does not depend upon the activation of MAPK. Thus, the dispersal of the mesoderm at early stages is regulated by pathways downstream of the FGF receptor that are independent of the MAPK cascade. Furthermore, we demonstrate that the activation of MAPK by Heartless needs additional cues from the ectoderm. We propose that FGF signalling is required during the initial stages of mesoderm spreading to promote the efficient interaction of the mesoderm with the ectoderm rather than having a long range chemotactic function, and we discuss this in relation to the cellular mechanism of mesoderm spreading.
ERK1 activation is required for S-phase onset and cell cycle progression after fertilization in sea urchin embryos
Authors: Philipova Rada , Kisielewska Jolanta , Lu Pin , Larman Mark , Huang Jun-Yong , Whitaker Michael
Published: January 2005

Fertilization of sea urchin eggs results in a large, transient increase in intracellular free Ca2+ concentration that is responsible for re-initiation of the cell division cycle. We show that activation of ERK1, a Ca2+-dependent MAP kinase response, is required for both DNA synthesis and cell cycle progression after fertilization. We combine experiments on populations of cells with analysis at the single cell level,and develop a proxy assay for DNA synthesis in single embryos, using GFP-PCNA. We compare the effects of low molecular weight inhibitors with a recombinant approach targeting the same signalling pathway. We find that inhibition of the ERK pathway at fertilization using either recombinant ERK phosphatase or U0126, a MEK inhibitor, prevents accumulation of GFP-PCNA in the zygote nucleus and that U0126 prevents incorporation of [3H]-thymidine into DNA. Abrogation of the ERK1 signalling pathway also prevents chromatin decondensation of the sperm chromatin after pronuclear fusion, nuclear envelope breakdown and formation of a bipolar spindle.
Diagnosis of Gastric Inflammation and Malignancy in Endoscopic Biopsies Based on Fourier Transform Infrared Spectroscopy
Authors: Li Qing-Bo , Sun Xue-Jun , Xu Yi-Zhuang , Yang Li-Min , Zhang Yuan-Fu , Weng Shi-Fu , Shi Jing-Sen , Wu Jin-Guang
Published: January 2005

Background: Fourier transform infrared (FT-IR) spectroscopy is an effective tool for investigation of chemical changes at the molecular level. We previously demonstrated that FT-IR spectroscopy can reliably distinguish multiple types of carcinoma from healthy tissue. Because various stomach diseases are common, it is important to explore a noninvasive and rapid method to detect malignancy and gastritis in endoscopic biopsies. Our aim was to classify endoscopic biopsies into healthy, gastritis, and malignancy through the use of FT-IR spectroscopy.

Methods: A total of 103 endoscopic samples, including 19 cases of cancer, 35 cases of chronic atrophic gastritis, 29 cases of chronic superficial gastritis, and 20 healthy tissue samples, were obtained at the First Hospital of Xi’an Jiaotong University, China. A modified attenuated total reflectance accessory was linked to a WQD-500 FT-IR spectrometer for biopsy measurement. The spectral characteristics for different types of tissues were correlated with the corresponding pathology results. The gastric biopsies were classified by FT-IR spectroscopy and a discriminant analysis method.

Results: There were significant differences in the FT-IR spectra of four types of gastric biopsies. The discriminant analysis results demonstrated that the sensitivity of FT-IR detection for healthy, superficial gastritis, atrophic gastritis, and gastric cancer was 90%, 90%, 66%, 74%, respectively, which could help satisfy clinical diagnostic requirements.

Conclusion: FT-IR spectroscopy can distinguish disease processes in gastric endoscopic biopsies.
Predictive Markers in Breast and Other Cancers: A Review
Authors: Duffy Michael J
Published: January 2005

Background: Unpredictable efficacy and toxicity are hallmarks of most anticancer therapies. Predictive markers are factors that are associated with response or resistance to a particular therapy.

Methods: The English literature relating to predictive markers in oncology was reviewed. Particular attention was paid to metaanalyses, systematic reviews, prospective trials, and guidelines issued by expert panels.

Results: The prototype predictive tests in oncology are the estrogen receptor (ER) and progesterone receptor (PR), which are used to select patients with breast cancer likely to respond to hormone therapy. A more recently introduced predictive marker is HER-2 for selecting patients with advanced breast cancer for treatment with the therapeutic antibody trastuzumab (Herceptin). In adjuvant breast cancer, overproduction of HER-2 may also indicate an enhanced sensitivity to high-dose anthracycline-based regimens. On the other hand, in both early and advanced breast cancer, high concentrations of HER-2 appear to correlate with a lower probability of response to hormone therapy. Although many different anticancer drugs appear to mediate tumor regression by inducing apoptosis, there is currently no consistent evidence that any of the molecules implicated in this process can be used as predictive markers.

Conclusions: Currently, the only recommended predictive markers in oncology are ER and PR for selecting endocrine-sensitive breast cancers and HER-2 for identifying breast cancer patients with metastatic disease who may benefit from trastuzumab. For malignancies other than breast cancers, validated predictive markers do not exist at present.
Monitoring of fibrinolysis parameters during myocardial revascularization according to type of procedure
Authors: Živković Marcela , Brkić Kristina , Nikić Nada , Hašperger Dragica , Juriček Jasna , Husedžinović Ino , Sutlić Željko
Published: January 2005

The aim of the study was to assess the effect of cardiothoracic surgery on the dynamics of plasminogen, D-dimers and plasminogen activator inhibitor (PAI-I) during the first 24h after surgery. The study included 14 patients operated with (on-pump) and 14 without (off-pump) the use of extracorporeal circulation (ECC). Blood sampling was carried out on induction of anesthesia (timepoint 1), on introduction of heparin (point 2) and protamine (point 3), at the end of surgery (point 4), and the next morning (point 5). Relative to point 1, the utilization of plasminogen at point 2 was 24% and 17% in the on-pump and off-pump groups, respectively (p=0.001 both). Increased D-dimer concentration from the baseline was more pronounced in the on-pump group (p=0.001). At point 5, D-dimer concentrations were comparable in both groups and different from baseline levels. PAI-I activity showed within-group differences from baseline at point 5 in the off-pump group (p=0.001), and at points 3 and 5 in the on-pump group (p=0.002 and 0.001, respectively). At point 5, the activity of PAI-I was comparable in both groups, yielding p=0.001 vs. baseline. Fibrinolysis was more pronounced and more dynamic in the on-pump group due to activation of the systemic inflammatory response induced by the use of ECC. In the off-pump group, fibrinolysis was a normal physiological response to the surgical procedure.
Recovering From Interruptions: Implications for Driver Distraction Research
Authors: Monk Christopher A. , Boehm-Davis Deborah A. , Mason George , Trafton J. Gregory
Published: January 2005

This research adopted a model of goal activation to study the mechanisms underlying interrupted task performance. The effects of interruption timing, type of interruption, and age on task time and primary task resumption time were explored under conditions in which attention was switched back and forth between two tasks, much as when drivers shift attention between attending to the road and to an in-vehicle task. The timing of interruptions had a significant impact on task resumption times, indicating that the most costly time to interrupt task performance is during the middle of a task. However, this effect was overshadowed by age-related performance decrements for older participants. Interruptions that prevented strategic rehearsal of goals resulted in longer resumption times as compared with interruptions that allowed rehearsal. Actual or potential applications of this research include the design of in-vehicle device user interfaces, the timing of in-vehicle messages, and current metrics for assessing driver distraction.
Verbal Estimation of Peak Exertion Intensity
Authors: Marshall Matthew M. , Armstrong Thomas J. , Ebersole Marissa L.
Published: January 2005

The objectives of this research were to investigate the accuracy and precision with which trained and untrained participants estimate the magnitude of forceful exertion and to evaluate the mathematical relationship between actual and estimated exertion. Three groups of participants estimated, as a percentage of maximum voluntary contraction (%MVC), the magnitude of submaximal exertion for 12 simulated tasks. In addition to the control group, one group was exposed to one physical benchmark (100% MVC) and another to three benchmarks (25%, 75%, and 100% MVC) prior to force estimation. Error (estimated minus actual) significantly decreased (p < .0001) from 14% MVC to 4% MVC with one benchmark and to -3% MVC with three benchmarks, as compared with the control group. Furthermore, the standard deviation decreased significantly (p < .0001) from the control group (16.6% MVC) to the one-benchmark group (13.8% MVC) to the three-benchmark group (11.6% MVC), indicating improved precision. Significant interaction effects were observed, but their impact on main effects was negligible. Also, linear, power, and logarithmic regression models described the relationship between perceived and actual exertion equally well (R2 = .64-.81). Applications of this research include improving the accuracy and precision of field-based psychophysical estimates of forceful exertion for epidemiological research and other field-based analyses.
Unprotected Anal Intercourse Among HIV-Positive Men Who Have a Steady Male Sex Partner With Negative or Unknown HIV Serostatus
Authors: Denning Paul H. , Campsmith Michael L.
Published: January 2005

Objectives. We sought to determine the prevalence and predictors of unprotected anal intercourse (UAI) among HIV-positive men who have a single steady male partner with negative or unknown HIV serostatus.

Methods. We analyzed behavioral surveillance data from HIV-positive men who have sex with men (MSM) interviewed in 12 states between 1995 and 2000.

Results. Of 970 HIV-positive MSM who had a single steady male sex partner with negative or unknown serostatus, 278 (29%) reported UAI during the previous year. In a subset of 674 men who were aware of their infection, 144 (21%) had UAI. Among the men who were aware of their infection, factors found to be predictive of UAI in multivariate modeling were heterosexual self-identification, crack cocaine use, no education beyond high school, and a partner with unknown serostatus.

Conclusions. Even after learning of their infection, one fifth of HIV-positive MSM who had a single steady male partner with negative or unknown serostatus engaged in UAI, underscoring the need to expand HIV prevention interventions among these men.
Drive-by Readings: A Creative Strategy for Tuberculosis Control Among Immigrants
Authors: Gany Francesca M. , Trinh-Shevrin Chau , Changrani Jyotsna
Published: January 2005

Objectives. We explored an innovative strategy for targeted testing and disease management among immigrant communities at risk for tuberculosis.

Methods. Taxi drivers were recruited at an airport holding lot to undergo tuberculin skin testing (Mantoux). After receiving their test results in a location convenient for them, drivers with positive results were referred for evaluation and treatment. We conducted baseline and follow-up assessments.

Results. Of 123 drivers who participated, two thirds (82) were at high risk for tuberculosis. Seventy-eight (63%) of the 123 returned for test readings; 62% of these drivers had positive test results. All drivers with positive results received a complete physician evaluation, but 64% of those evaluated were not treated for latent TB infection. Of the untreated drivers, 37.5% were at high risk. Systemic and physician barriers (e.g., lack of knowledge, erroneous beliefs regarding vaccines) affected adherence to evaluation and treatment.

Conclusions. Targeted testing and treatment are important to the control of tuberculosis. The results of this study highlight the need for an aggressive physician educational campaign to identify latent tuberculosis infection and to tailor service delivery to meet the unique needs of foreign-born communities.
Organizing, Educating, and Advocating for Health and Human Rights in Vieques, Puerto Rico
Authors: Torres Maria Idalí
Published: January 2005

I briefly review the process of community organization, education, and advocacy activities that ended the harmful military practices in the island-municipality of Vieques, Puerto Rico, while drawing attention to the intersection of human rights and social justice in the context of local and global implications.

The Viequense experience was one of building an organization based on people’s experiences and strengths, educating people to increase individual and collective efficacy and power, and advocating for policy change with an assertive cohesive action. Public health practitioners must continue supporting community-led interventions in the restoration of the island’s environment and other resources vital for people’s health and well-being.
US College Students’ Exposure to Tobacco Promotions: Prevalence and Association With Tobacco Use
Authors: Rigotti Nancy A. , Moran Susan E. , Wechsler Henry
Published: January 2005

Objectives. We assessed young adults’ exposure to the tobacco industry marketing strategy of sponsoring social events at bars, nightclubs, and college campuses.

Methods. We analyzed data from the 2001 Harvard College Alcohol Study, a random sample of 10904 students enrolled in 119 nationally representative 4-year colleges and universities.

Results. During the 2000–2001 school year, 8.5% of respondents attended a bar, nightclub, or campus social event where free cigarettes were distributed. Events were reported by students attending 118 of the 119 schools (99.2%). Attendance was associated with a higher student smoking prevalence after we adjusted for demographic factors, alcohol use, and recent bar/nightclub attendance. This association remained for students who did not smoke regularly before 19 years of age but not for students who smoked regularly by 19 years of age.

Conclusions. Attendance at a tobacco industry–sponsored event at a bar, nightclub, or campus party was associated with a higher smoking prevalence among college students. Promotional events may encourage the initiation or the progression of tobacco use among college students who are not smoking regularly when they enter college.
Understanding and Addressing AIDS-Related Stigma: From Anthropological Theory to Clinical Practice in Haiti
Authors: Castro Arachu , Farmer Paul
Published: January 2005

For the past several years, diverse and often confused concepts of stigma have been invoked in discussions on AIDS. Many have argued compellingly that AIDS-related stigma acts as a barrier to voluntary counseling and testing. Less compelling are observations regarding the source of stigma or its role in decreasing interest in HIV care.

We reviewed these claims as well as literature from anthropology, sociology, and public health. Preliminary data from research in rural Haiti suggest that the introduction of quality HIV care can lead to a rapid reduction in stigma, with resulting increased uptake of testing. Rather than stigma, logistic and economic barriers determine who will access such services. Implications for scale-up of integrated AIDS prevention and care are explored.