bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitumor effect of TNP‐470, an angiogenesis inhibitor, combined with ultrasound irradiation for human uterine sarcoma xenografts evaluated using contrast color Doppler ultrasound
Authors: Emoto Makoto , Tachibana Katsuro , Iwasaki Hiroshi , Kawarabayashi Tatsuhiko
Published: April 2007

Microvascular endothelial cells, which are recruited by tumors, have become an important target in cancer therapy. This study firstly examined the antitumor effect of angiogenesis inhibitor combined with ultrasound (US) irradiation for human cancer in vivo and evaluated its vascularity using color Doppler US in real time with a microbubble US contrast agent. A human uterine sarcoma cell line, FU‐MMT‐1, was used in vivo because this tumor is one of the most malignant neoplasms of the human solid tumors and it also has a poor response to any of the chemotherapeutic agents currently used, as well as to radiotherapy. In angiogenic inhibitors, TNP‐470 was selected to use in an in vivo study, because this agent showed a higher inhibitory effect in tube formation assay in vitro, than that of FR118487, or thalidomide. The FU‐MMT‐1 xenografts in nude mice were treated using US at a low‐intensity (2.0 w/cm2, 1MHZ) for 4 min three times per week each after the subcutaneous injection of TNP‐470 (30 mg/kg), an angiogenesis inhibitor, and this treatment was continued for 8 weeks. Either treatment of US alone or TNP‐470 alone showed a suppression of tumor growth, in comparison to the non‐treatment group (control), and a significantly enhanced effect was obtained using the combined treatment. A reduction in the intratumoral vascularity, which was evaluated using both color Doppler and immunohistochemistry, was significantly demonstrated using the combined treatment, in comparison to each treatment alone, and the control. No side‐effect was observed in any mice in the combined treatment group. These results suggest that the antitumor effect of TNP‐470 for uterine sarcoma was accelerated by US irradiation in vivo and this combination might be a potentially effective for new cancer therapy. (Cancer Sci 2007; 98: 929–935)
Provenance variation of ecologically important traits of forest trees: implications for restoration
Authors: O'BRIEN ELEANOR K. , MAZANEC RICHARD A. , KRAUSS SIEGFRIED L.
Published: April 2007

The source of seed or plant material can have profound implications for the success of restoration efforts because most species exhibit adaptive genetic variation within their range. Understanding the geographical distribution of ecologically relevant genetic variation and the environmental factors driving adaptive divergence within species will help to ensure appropriate sourcing of material for ecological restoration.

We present a study of geographical variation of ecologically important traits of the forest tree jarrah Eucalyptus marginata from a 15‐year‐old provenance trial in south‐western Australia. We assessed trait variation in association with rainfall, latitude and slope position at the site of origin.

Survival and stem diameter varied at the largest scale, between northern and southern jarrah forest provenances. Stem diameter also varied among rainfall zones, while latitude was a more important determinant of variation of reproductive traits (flowers and buds). None of the environmental variables accounted for significant variation of height, growth form or the presence of capsules. Slope position at the site of origin did not account for significant variation of any trait.

Trees from low rainfall sites had smaller stem diameters, possibly reflecting selection for slower growth. Such a strategy could prevent drought stress and may explain why trees from the high rainfall southern jarrah forest, which showed the fastest growth, had the poorest survival at the drier northern trial site.

Variation in the presence of buds and flowers among latitudinal divisions may be because of variation in flowering time, which has been observed previously among E. marginata populations. However, variation among replicate blocks within the trial suggests that the environment also strongly influences expression of these traits.

Synthesis and applications. We have demonstrated divergence of several ecologically important traits in association with different types of environmental variation. Our findings support an argument for ‘habitat matching’ when sourcing material for restoration; however, differences among trait types in the distribution of variation highlight the need to consider environmental variation at a range of geographical scales. Consideration of ecologically important genetic variation within species is important and this information should be integrated into seed collection strategies for ecological restoration.
The predictive value of cardiorespiratory fitness combined with coronary risk evaluation and the risk of cardiovascular and all‐cause death
Authors: Laukkanen J. A. , Rauramaa R. , Salonen J. T. , Kurl S.
Published: April 2007

Background.  There are no data on directly measured cardiorespiratory fitness combined coronary risk evaluation with respect to death from cardiovascular diseases and all‐causes. We investigated the prognostic significance of risk scores and cardiorespiratory fitness with respect to cardiovascular disease and all‐cause mortality.

Methods.  Cardiorespiratory fitness (maximal oxygen uptake, VO2peak) was measured by exercise test with an electrically braked cycle ergometer. The study is based on a random population‐based sample of 1639 men (42–60 years) without history of type 2 diabetes or atherosclerotic cardiovascular diseases.

Results.  During an average follow‐up of 16 years, a total of 304 deaths occurred. Independent predictors for all‐cause death were European Score (for 1% increment, RR 1.15, 95% CI 1.10–1.20), VO2peak (for 1 MET increment, RR 0.84, 95% CI 0.78–0.89), when adjusted for C‐reactive protein, alcohol consumption, serum high‐density lipoprotein, waist‐to‐hip ratio, family history of coronary heart disease, exercise‐induced ST changes and the use of medications for hypertension, dyslipidaemia or aspirin. Also, Framingham risk score was related to the risk of death (RR 1.05, 95% CI 1.03–1.07, P < 0.001). Subjects with high European or Framingham score and low VO2peak represent the highest risk group.

Conclusion.  An important finding is that the risk scores can be used to identify men for whom low cardiorespiratory fitness predicts an especially high risk for death from cardiovascular and any other cause.
The effect of baseline physical activity on cardiovascular outcomes and new‐onset diabetes in patients treated for hypertension and left ventricular hypertrophy: the LIFE study
Authors: Fossum E. , Gleim G. W. , Kjeldsen S. E. , Kizer J. R. , Julius S. , Devereux R. B. , Brady W. E. , Hille D. A. , Lyle P. A. , Dahlöf B.
Published: April 2007

Objectives.  Physical activity (PA) is a preventive strategy for cardiovascular disease and for managing cardiovascular risk factors. There is little information on the effectiveness of PA for the prevention of cardiovascular outcomes once cardiovascular disease is present. Thus, we studied the relationship between PA at baseline and cardiovascular events in a high‐risk population.

Design.  A prespecified analyses of observational data in a prospective, randomized hypertension study.

Setting.  Losartan Intervention For Endpoint reduction in hypertension (LIFE) study

Subjects.  Hypertension and left ventricular hypertrophy (LVH) (n = 9193).

Interventions.  Losartan versus atenolol.

Main outcome measures.  Reported level of PA: never exercise, exercise ≤30 min twice per week, or exercise >30 min twice per week at baseline and after a mean of 4.8 years of treatment with losartan‐ versus atenolol‐based therapy. Risk reductions were calculated by level of PA for the primary composite end‐point and its components cardiovascular death, stroke and myocardial infarction, and also all‐cause mortality and new‐onset diabetes.

Results.  A modest level of PA (>30 min twice per week) was associated with significant reductions in risk for the primary composite end‐point [adjusted hazard ratio (aHR) 0.70, P < 0.001) and its components, all‐cause mortality (aHR 0.65, P < 0.001), and new‐onset diabetes (aHR 0.66, P < 0.001).

Conclusion.  A modest level of self‐reported PA (>30 min twice per week) in patients with hypertension and LVH in the LIFE study was associated with significant reductions in risk for the primary composite end‐point and its components of cardiovascular death, stroke, and myocardial infarction, all‐cause mortality, and new‐onset diabetes.
Relative durability of chert and rhyolite detritus in conglomerates and sandstones: with reference to the study of provenance geology
Authors: Yagishita Koji , Ohkubo Keiko
Published: April 2007

Modal changes in both gravel and sands occur because of unequal durability of some clastic materials to abrasion. Selective abrasion causes an elimination of undurable materials and a complimentary enrichment of competent components. The fluviatile Oligocene Noda Group, northeast Japan, consists of two formations that include both the competent and undurable clastics. Modal analyses of rhyolite‐ or chert‐rich sediments in both formations show that the amount of pebble‐ and granule‐size chert detritus is nearly constant, but the sand‐size chert fragments remarkably decrease with the decreasing grain size. The amount of rhyolite pebbles and the sands, however, is nearly unchangeable despite the variable clast size. Results of our study reveal that we need careful thoughts for a restricted size of sediments and the mode of fine‐grained detritus that include undurable chert sands tends to significantly underestimate the outcrop area of chert bedrocks in the provenance.
Spinal muscular atrophy type 1: Is long‐term mechanical ventilation ethical?
Authors: Ryan Monique M , Kilham Henry , Jacobe Stephen , Tobin Bernadette , Isaacs David
Published: April 2007

Abstract:  We present a baby with spinal muscular atrophy type 1, an inherited disorder causing progressive weakness, leading to complete paralysis of respiratory, facial and limb muscles. Without intervention, death occurs in infancy due to respiratory failure. Mechanical ventilatory support can prolong life, but the child’s quality of life is highly debatable. We discuss the appropriateness of initiating and continuing intensive care for this child and others in a similar position.
Ordering of renal tract imaging by paediatricians after urinary tract infection
Authors: Williams Gabrielle , Sureshkumar Premala , Chan Siew F , Macaskill Petra , Craig Jonathan C
Published: April 2007

Aim:  To describe paediatricians’ reported ordering of renal tract imaging of children following urinary tract infection.

Methods:  This is a piloted self‐administered survey. A total of 354 randomly sampled practising paediatricians in Australia participated in the survey. The survey included 12 clinical scenarios that varied with age, gender and fever. Respondents indicated their likelihood of ordering renal ultrasound, micturating cystourethrogram (MCU) and dimercaptosuccinic acid scan (DMSA) from 0 to 100%.

Results:  Response rate was 74.6% (264/354). For all clinical scenarios the median probability of ordering an ultrasound was 100% with little variability. For children aged 2 months, likelihood of ordering an MCU was 100%, with little variability, but was 70% for 3‐year‐olds with fever (45% without fever), and 5% for 6‐year‐olds with very large variability. Median likelihood of ordering a DMSA was 80% at 2 months, 60% at 3 years and 20% at 6 years (40%, 15%, 5% without fever, respectively). Variability was large for all scenarios and DMSA ordering. Child gender did not influence ordering practices.

Conclusions:  Renal tract imaging practice across paediatricians shows consistent, ∼100% use of the least invasive modality, ultrasound. In contrast, there is considerable variation in the reported ordering of the more invasive tests MCU and DMSA. Doctors order these tests more in younger children and when fever is present.
Personality profiles and pulmonary function of children with sighing dyspnoea
Authors: Wong Kin‐Sun , Huang Yu‐Shu , Huang Yu‐Hsuan , Chiu Chih‐Yung
Published: April 2007

Aim:  This study compared the personality profiles of children with sighing dyspnoea with healthy children and tested the hypothesis of heightened anxiety scores in sighing dyspnoeic subjects using the Childhood Behavior Check List for Ages 4 to 18 (CBCL/4–18). The pulmonary function tests of these two groups of children were also compared.

Methods:  This prospective study enrolled paediatric patients with sighing dyspnoea presented to a paediatric pulmonary clinic but free from apparent cardiopulmonary diseases, and age‐matched healthy children were recruited for comparison. The psychological profiles of the patients were collected by the CBCL/4–18, which was completed by the parents. Spirometry was performed on sighing children as well as volunteer healthy children, before and after bronchodilator.

Results:  Twenty patients complained of sighing dyspnoea and 31 healthy children were included in the study. Both groups of children scored consistently within the normal ranges of all subscales including anxiety, somatic complaints or internalising behaviour on CBCL/4–18. The t‐scores were not significant different between children with sighing dyspnoea and age‐matched controls. Baseline forced vital capacity in the sighing patients appeared to be lower than the healthy children, but was not statistically significant.

Conclusions:  The CBCL/4–18 scores of children with sighing dyspnoea were not significant different from age‐matched healthy children and a heightened anxiety score was not confirmed in this study. Office spirometric values in patients with sighing dyspnoea were normal.
Prediction of severe hyperbilirubinaemia using the Bilicheck transcutaneous bilirubinometer
Authors: Boo Nem‐Yun , Ishak Shareena
Published: April 2007

Objectives:  To determine the sensitivity and specificity of different levels of bilirubin measured by the transcutaneous bilirubinometer Bilicheck on forehead and sternum for predicting severe hyperbilirubinaemia of total serum bilirubin (TSB) ≥ 300 µmol/L in Malay, Chinese and Indian infants.

Design:  A prospective observational study.

Setting:  A tertiary care University hospital.

Methods:  A total of 345 healthy jaundiced term infants were recruited prior to commencement of phototherapy or exchange transfusion. Transcutaneous bilirubin (TcB) level was measured with the Bilicheck from infants’ foreheads (TcBh) and sternums (TcBs) within 30 min of serum bilirubin measurement by the diazo method in the hospital laboratory.

Results:  The median serum TSB level of these infants was 233.0 µmol/L (range: 108.0–589.0). Ninety‐five (27.5%) infants had TSB ≥ 300 µmol/L. There was good correlation between log10TSB and TcB measured from the forehead (r = 0.80, P < 0.0001) and the sternum (r = 0.86, P < 0.0001). At TcBh cut‐off of 250 µmol/L, the Bilicheck detected TSB ≥ 300 µmol/L with a sensitivity of 100% and a specificity of 39.2%, the area under the receiver operative characteristic curve being 0.89 (95% confidence interval 0.85, 0.92). At TcBs cut‐off of 200 µmol/L, the Bilicheck detected TSB ≥ 300 µmol/L with a sensitivity of 100% and a specificity of 33.6%, the area under receiver operative characteristic curve being 0.93 (95% confidence interval 0.90, 0.96).

Conclusion:  The Bilicheck is not a substitute for measuring serum bilirubin. However, using predetermined TcB cut‐off values with reasonable sensitivity and specificity, it is a useful screening tool to identify infants with TSB ≥ 300 µmol/L requiring blood sampling, hospital admission and treatment.
Antenatal dexamethasone and renal vascular resistance in preterm infants
Authors: Amador‐Licona Norma , Guízar‐Mendoza Juan Manuel , Maciel‐Miranda Jesús Alejandro , Romero‐Gutiérrez Gustavo
Published: April 2007

Objective:  To compare vascular resistance, renal volume and insulin levels in preterm infants with and without antenatal steroids.

Methods:  We studied 61 preterm infants (37 with (group A) and 24 without antecedent of antenatal steroids (group B)). We measured insulin levels at birth in cord blood samples. Ultrasound measurements to evaluate renal arteries resistance index and renal volume were performed during the first 72 h of birth.

Results:  Preterm infants from group A tended to have lower weight and gestational age than those from group B. Resistance index in renal arteries was lower in preterm infants with steroid therapy compared with group B (right renal artery 0.73 vs. 0.80; P = 0.001, and left renal artery 0.75 vs. 0.79; P = 0.01, respectively). Renal volume and insulin levels were not different between the groups. In the multiple regression analysis for factors associated with resistance index of renal arteries, only antenatal steroids use was included in the model (R2 = 0.13; P = 0.003 and R2 = 0.10; P = 0.01 for left and right renal arteries, respectively).

Conclusion:  Antenatal dexamethasone in preterm infants during the first 72 h of birth seems to decrease resistance index in renal arteries without affecting renal volume and insulin levels.
Bony lesions in BCG‐vaccinated children: Consider BCG osteitis
Authors: Twine Christopher , Coulston James , Tayton Keith
Published: April 2007

Abstract:  This instructive case describes a 31‐day‐old female infant presenting with left elbow swelling. Radiographs were initially consistent with non‐accidental injury, and she was investigated accordingly. After Paediatric Orthopaedic review, BCG osteitis was considered as a differential diagnosis. By this time it was too late to investigate for this uncommon condition. With the increasing incidence of tuberculosis in the Western world, BCG vaccination at birth will become more common. This case illustrates the need for multidisciplinary management of bony lesions in infants and children, involving paediatricians, orthopaedic surgeons and paediatric radiologists.
Granulomatous tissue response in germinoma, a diagnostic pitfall in endoscopic biopsy
Authors: Mueller Wolf , Schneider Gerd H. , Hoffmann Karl T. , Zschenderlein Rolf , Von Deimling Andreas
Published: April 2007

We report a case of a 24‐year‐old man with a right thalamic germinoma that initially mimicked a granulomatous inflammation, compatible with neurosarcoidosis based on clinical symptoms, imaging results and histology of an endoscopically navigated biopsy. A second biopsy, prompted by clinical course, and performed openly from parieto‐lateral revealed the underlying germinoma, obscured in the first biopsy by a granulomatous tissue response, particularly at the tumor edge. The present case highlights granulomatous inflammatory tissue response on the tumor edge of germinoma as a tumor‐immanent diagnostic challenge. This diagnostic problem is aggravated by stereotactic and endoscopic approaches. We conclude that granulomatous inflammation in a specimen obtained by biopsy of a midline lesion should always be considered for the differential diagnosis of germinoma. Stereotactic and endoscopic surgery should sample several different target points within the lesion. Because of tumor heterogeneity of germinoma, the open biopsy approach is advantageous compared to endoscopic or stereotactic techniques for germinoma and should be considered if a germinoma is in the differential diagnosis and if allowed by the clinical situation.
Long‐term aspects of nodular gastritis in children
Authors: AKCAM MUSTAFA , ARTAN REHA , GELEN TEKINALP , YILMAZ AYGEN , EREN ERDAL , UYGUN VEDAT , CIG HIKMET
Published: April 2007

Background: Close association of nodular gastritis and Helicobacter pylori infection has been initially proved by various studies. There have been some studies reporting microscopic and histologic recovery in a short time after eradication therapy. But there is not enough data about the long‐term course of this condition. The aim of this study is to document current clinical conditions, presence of H. pylori and results of endoscopic and histologic examination, after a long‐term period, in children with endoscopically diagnosed antral nodularity.

Methods: A total of 35 patients diagnosed as nodular antral gastritis by upper gastrointestinal endoscopy during a 2 year period, were invited for re‐evaluation and re‐endoscopy after 3 years. Histopathologically, H. pylori detected ones had been treated with standard triple eradication therapy. In total, 27 patients were accepted for enrollment in the study. Repeated endoscopy could be performed in all 27 patients.

Results: The persistence of antral nodularity was detected in 18 of 27 patients. Decrease in symptoms, absence of symptoms and presence of H. pylori infection were detected in 6, 8 and 16 (89%) of them, respectively. There was no statistical significance between the first and last endoscopic biopsies when activity, atrophy, intestinal metaplasia and presence of follicles were regarded. Malt lymphoma could not be detected in any of the patients.

Conclusion: There is a strong association between nodular gastritis and H. pylori. Presence of antral nodularity in the long‐term period may be related to H. pylori re‐infection. New therapeutic approaches are required for treatment and management of the patients diagnosed as nodular gastritis and living in areas endemic for H. pylori infection.
THE CASE FOR PAY‐AS‐YOU‐GO PENSIONS IN A SERVICE ECONOMY
Authors: Van Groezen Bas , Meijdam Lex , Verbon Harrie A. A.
Published: April 2007

The elderly consume more labour‐intensive services than young individuals. This makes them vulnerable to rising costs of services due to higher wages, which can be caused by increased capital accumulation. This paper shows that in a model with a service sector, the golden‐rule capital stock is lower and dynamic inefficiency is more likely to occur than in the conventional one‐sector model. This implies that in many cases, a positive Pay‐As‐You‐Go tax maximises long‐run welfare in a service economy. Calculations based on data from the United Kingdom and the Netherlands show that the long‐run optimal degree of funding coincides with the current situation in these countries.
Manufacturing Wages and Imports: Evidence from the NLSY
Authors: KOSTEAS VASILIOS D.
Published: April 2007

This paper analyses the effect of imports on US manufacturing wages using the NLSY79 data‐set, estimating differential impacts on blue‐ and white‐collar wages. I find that rising imports put downward pressure on wages between 1979 and 1988. This correlation holds for both white‐ and blue‐collar workers, with a somewhat stronger impact on the latter group. Evidence suggests that imports from low‐wage countries are responsible for the negative relationship between imports and wages, but only for blue‐collar wages. A one‐percentage‐point increase in the low‐wage import share is associated with a 2.8% decline in blue‐collar wages.
Leadership, Gender and Sense‐making
Authors: Grisoni Louise , Beeby Mick
Published: April 2007

This article examines the nature of sense‐making processes in teams and considers the extent to which leadership as a sense‐making process is impacted by gender. We conducted an in‐depth inquiry into the decision‐making behaviour of two single‐gender teams and a third, mixed gender team, as they worked together to produce gender‐specific leadership schema in an experimental setting. Our research question was, ‘To what extent is leadership as a sense‐making process impacted by gender?’ The article reports on the design, conduct and outcomes of this research project. We found that using a meeting as part of the research method created a specific instance of a gendered organizational context exerting a dominant and directive influence on individual and collective behaviour. The current trend toward team‐based leadership is likely to involve more meetings with increasing numbers of women in senior positions. This suggests to us that men and women need to be alert to the possibility that the gendered nature of meetings may be acting as a barrier to the expression of feminine forms of leadership.
France's North African Crisis, 1945–1955: Cold War and Colonial Imperatives
Authors: THOMAS MARTIN
Published: April 2007

The collapse of Europe's colonial empires after 1945 is not easily assimilated into the grand strategies of the cold war. Nevertheless, decolonization and east–west conflict were closely linked. This was certainly the case in the three territories of French North Africa – Morocco, Algeria and Tunisia – each of which emerged from the Second World War under continuing French imperial rule. Ten years later a vicious colonial war had erupted in Algeria, while in neighbouring Morocco and Tunisia the strength of popular nationalism precipitated French withdrawal from both countries in 1956. This article highlights some of the links between France's actions in post‐war North Africa, its changing strategic priorities in Europe, and French ambivalence about creeping American influence along the southern Mediterranean littoral. Although the determinants of French colonial policy are not reducible to any single cause, the developing crisis in French North Africa in the decade after 1945 is better understood when placed in the context of the developing cold war.
Whatever Happened to Thatcherism?
Authors: Hay Colin
Published: April 2007

Throughout the 1980s and the early 1990s the pages of journals such as this were filled with debate – invariably heated – on the nature, extent, significance and reversibility of Thatcherism. Today the echoes of a once deafening clamour have largely subsided. Thatcherism has all but disappeared from the lexicon of British political analysis. My aim in what follows is to reflect on this passing and what it indicates about the state of our understanding of this once most contentious of phenomena. I do so by considering the two most significant recent additions to the vast literature on the subject, Peter Kerr's Postwar British Politics: From Conflict to Consensus (2001) and Richard Heffernan's New Labour and Thatcherism: Political Change in Britain (2000). 1
Anti-Corruption: What Do We Know? Research on Preventing Corruption in the Post-Communist World
Authors: Schmidt Diana
Published: April 2007

This review assesses the anti-corruption literature in a first attempt to identify systematically significant trends so far and challenges remaining to future political science research. Research on anti-corruption is a young métier. While reflecting on the field at large, the review focuses on two issues that have been central to its development: the role of post-communist Eastern Europe and of civil society involvement. Organised in a chronological way, the review distinguishes and discusses four phases, in order to trace how scholars have addressed these two issues in the context of a rapid evolution of anti-corruption debates, ongoing transformations in Eastern Europe and increasing insight into the controversial matter of anti-corruption efforts. It considers four crucial periods: (1) earlier scholarly debates on corruption (pre-1990s); (2) initial anti-corruption debates (1990s); (3) a period of reorientation (early 2000s); and (4) latest anti-corruption debates (mid-2000s). Changing perspectives on anti-corruption in relation to post-communism and civil society involvement are discussed for each of the four phases in order to delineate the different research trajectories. This leads to the conclusion that future research, while addressing the theory deficit, needs to take account of increasingly complex conceptual challenges posed by the (interrelated) changes in international and domestic governance.
Light triggers expression of philanthotoxin‐insensitive Ca2+‐permeable AMPA receptors in the developing rat retina
Authors: Osswald Ingrid K. , Galan Alba , Bowie Derek
Published: April 2007

Ca2+‐permeable AMPA receptors (AMPARs) are expressed throughout the adult CNS but yet their role in development is poorly understood. In the developing retina, most investigations have focused on Ca2+ influx through NMDARs in promoting synapse maturation and not on AMPARs. However, NMDARs are absent from many retinal cells suggesting that other Ca2+‐permeable glutamate receptors may be important to consider. Here we show that inhibitory horizontal and AII amacrine cells lack NMDARs but express Ca2+‐permeable AMPARs. Before eye‐opening, AMPARs were fully blocked by philanthotoxin (PhTX), a selective antagonist of Ca2+‐permeable AMPARs. After eye‐opening, however, a subpopulation of Ca2+‐permeable AMPARs were unexpectedly PhTX resistant. Furthermore, Joro spider toxin (JSTX) and IEM‐1460 also failed to antagonize, demonstrating that this novel pharmacology is shared by several AMPAR channel blockers. Interestingly, PhTX‐insensitive AMPARs failed to express in retinae from dark‐reared animals demonstrating that light entering the eye triggers their expression. Eye‐opening coincides with the consolidation of inhibitory cell connections suggesting that the developmental switch to a Ca2+‐permeable AMPAR with novel pharmacology may be critical to synapse maturation in the mammalian retina.
Effects of a R133W β‐tropomyosin mutation on regulation of muscle contraction in single human muscle fibres
Authors: Ochala Julien , Li Mingxin , Tajsharghi Homa , Kimber Eva , Tulinius Mar , Oldfors Anders , Larsson Lars
Published: April 2007

A novel R133W β‐tropomyosin (β‐Tm) mutation, associated with muscle weakness and distal limb deformities, has recently been identified in a woman and her daughter. The muscle weakness was not accompanied by progressive muscle wasting or histopathological abnormalities in tibialis anterior muscle biopsy specimens. The aim of the present study was to explore the mechanisms underlying the impaired muscle function in patients with the β‐Tm mutation. Maximum force normalized to fibre cross‐sectional area (specific force, SF), maximum velocity of unloaded shortening (V0), apparent rate constant of force redevelopment (ktr) and force–pCa relationship were evaluated in single chemically skinned muscle fibres from the two patients carrying the β‐Tm mutation and from healthy control subjects. Significant differences in regulation of muscle contraction were observed in the type I fibres: a lower SF (P < 0.05) and ktr (P < 0.01), and a faster V0 (P < 0.05). The force–pCa relationship did not differ between patient and control fibres, indicating an unaltered Ca2+ activation of contractile proteins. Collectively, these results indicate a slower cross‐bridge attachment rate and a faster detachment rate caused by the R133W β‐Tm mutation. It is suggested that the R133W β‐Tm mutation induces alteration in myosin–actin kinetics causing a reduced number of myosin molecules in the strong actin‐binding state, resulting in overall muscle weakness in the absence of muscle wasting.
Brief hyperglycaemia in the early pregnant rat increases fetal weight at term by stimulating placental growth and affecting placental nutrient transport
Authors: Ericsson Anette , Säljö Karin , Sjöstrand Eleonor , Jansson Nina , Prasad Puttur D. , Powell Theresa L. , Jansson Thomas
Published: April 2007

In pregnant women with type 1 diabetes, suboptimal glucose control in the first trimester is a strong predictor for giving birth to a large fetus. However, the mechanisms underlying this association are unknown. We hypothesized that transient hyperglycaemia in early pregnancy results in (1) increased placental growth and (2) an up‐regulation of placental nutrient transport capacity, which leads to fetal overgrowth at term. In order to test this hypothesis, pregnant rats were given intraperitoneal injections of glucose (2 g kg−1, resulting in a 50–100% increase in blood glucose level during 90 min) or saline (control) in either early or late gestation using four different protocols: one single injection on gestational day (GD) 10 (n= 5), three injections on GD 10 (n= 8–9), six injections on GD 10 and 11 (n= 9–11) or three injections on GD 19 (n= 7–8). Multiple injections were given approximately 4 h apart. Subsequently, animals were studied on GD 21. Three glucose injections in early pregnancy significantly increased placental weight by 10%, whereas fetal weight was found to be increased at term in response to both three (9% increase in fetal weight, P < 0.05) and six glucose injections (7%, P= 0.05) in early gestation. A single glucose injection on GD 10 or three injections of glucose on GD 19 had no effect on placental or fetal growth. In groups where a change in feto‐placental growth was observed, we measured placental system A and glucose transport activity in the awake animals on GD 21 and placental expression of the glucose and amino acid transporters GLUT1, GLUT3, SNAT2 (system A), LAT1 and LAT 2 (system L). Placental system A transport at term was down‐regulated by six glucose injections in early pregnancy (by −33%, P < 0.05), whereas placental mRNA and protein levels were unchanged. No long‐term alterations in maternal metabolic status were detected. In conclusion, we demonstrate that transient hyperglycaemia in early pregnancy is sufficient to increase fetal weight close to term. In contrast, brief hyperglycaemia in late pregnancy did not stimulate fetal growth. Increased fetal growth may be explained by a larger placenta, which would allow for more nutrients to be transferred to the fetus. These data suggest that maternal metabolic control in early pregnancy is an important determinant for feto‐placental growth and placental function throughout the remainder of gestation. We speculate that maternal metabolism in early pregnancy represents a key environmental cue to which the placenta responds in order to match fetal growth rate with the available resources of the mother.
Pervasive Seismic Wave Reflectivity and Metasomatism of the Tonga Mantle Wedge
Authors: Zheng Yingcai , Lay Thorne , Flanagan Megan P. , Williams Quentin
Published: April 2007

Subduction zones play critical roles in the recycling of oceanic lithosphere and the generation of continental crust. Seismic imaging can reveal structures associated with key dynamic processes occurring in the upper-mantle wedge above the sinking oceanic slab. Three-dimensional images of reflecting interfaces throughout the upper-mantle wedge above the subducting Tonga slab were obtained by migration of teleseismic recordings of underside
P-
and
S
-wave reflections. Laterally continuous weak reflectors with tens of kilometers of topography were detected at depths near 90, 125, 200, 250, 300, 330, 390, 410, and 450 kilometers.
P-
and
S-
wave impedances decreased at the 330-kilometer and 450-kilometer reflectors, and
S
-wave impedance decreased near 200 kilometers in the vicinity of the slab and near 390 kilometers, just above the global 410-kilometer increase. The pervasive seismic reflectivity results from phase transitions and compositional zonation associated with extensive metasomatism involving slab-derived fluids rising through the wedge.
Caspase-8-mediated apoptosis induced by oxidative stress is independent of the intrinsic pathway and dependent on cathepsins
Authors: Baumgartner Heidi K. , Gerasimenko Julia V. , Thorne Christopher , Ashurst Louise H. , Barrow Stephanie L. , Chvanov Michael A. , Gillies Stuart , Criddle David N. , Tepikin Alexei V. , Petersen Ole H. , Sutton Robert , Watson Alastair J. M. , Gerasimenko Oleg V.
Published: April 2007

Cell-death programs executed in the pancreas under pathological conditions remain largely undetermined, although the severity of experimental pancreatitis has been found to depend on the ratio of apoptosis to necrosis. We have defined mechanisms by which apoptosis is induced in pancreatic acinar cells by the oxidant stressor menadione. Real-time monitoring of initiator caspase activity showed that caspase-9 (66% of cells) and caspase-8 (15% of cells) were activated within 30 min of menadione administration, but no activation of caspase-2, -10, or -12 was detected. Interestingly, when caspase-9 activation was inhibited, activation of caspase-8 was increased. Half-maximum activation ( t0.5) of caspase-9 occurred within ∼2 min and was identified at or in close proximity to mitochondria, whereas t0.5 for caspase-8 occurred within ∼26 min of menadione application and was distributed homogeneously throughout cells. Caspase-9 but not caspase-8 activation was blocked completely by the calcium chelator BAPTA or bongkrekic acid, an inhibitor of the mitochondrial permeability transition pore. In contrast, caspase-8 but not caspase-9 activation was blocked by the destruction of lysosomes (preincubation with Gly-Phe β-naphthylamide, a cathepsin C substrate), loss of lysosomal acidity (bafilomycin A1), or inhibition of cathepsin L or D. Using pepstatin A-BODIPY FL conjugate, we confirmed translocation of cathepsin D out of lysosomes in response to menadione. We conclude that the oxidative stressor menadione induces two independent apoptotic pathways within pancreatic acinar cells: the classical mitochondrial calcium-dependent pathway that is initiated rapidly in the majority of cells, and a slower, caspase-8-mediated pathway that depends on the lysosomal activities of cathepsins and is used when the caspase-9 pathway is disabled.
Increased cardiac sympathetic nerve activity in heart failure is not due to desensitization of the arterial baroreflex
Authors: Watson A. M. D. , Hood S. G. , Ramchandra R. , McAllen R. M. , May C. N.
Published: April 2007

Increased sympathetic drive to the heart worsens prognosis in heart failure, but the level of cardiac sympathetic nerve activity (CSNA) has been assessed only by indirect methods, which do not permit testing of whether its control by arterial baroreceptors is defective. To do this, CSNA was measured directly in 16 female sheep, 8 of which had been ventricularly paced at 200–220 beats/min for 4–6 wk, until their ejection fraction fell to between 35 and 40%. Recording electrodes were surgically implanted in the cardiac sympathetic nerves, and after 3 days' recovery the responses to intravenous phenylephrine and nitroprusside infusions were measured in conscious sheep. Electrophysiological recordings showed that resting CSNA (bursts/100 heartbeats) was significantly elevated in heart-failure sheep (89 ± 3) compared with normal animals (46 ± 6; P < 0.001). This increased CSNA was not accompanied by any increase in the low-frequency power of heart-rate variability. The baroreceptor-heart rate reflex was significantly depressed in heart failure (maximum gain −3.29 ± 0.56 vs. −5.34 ± 0.66 beats·min−1·mmHg−1 in normal animals), confirming published findings. In contrast, the baroreflex control of CSNA was undiminished (maximum gain in heart failure −6.33 ± 1.06 vs. −6.03 ± 0.95%max/mmHg in normal sheep). Direct recordings in a sheep model of heart failure thus show that resting CSNA is strikingly increased, but this is not due to defective control by arterial baroreceptors.
Electromechanical stimulation ameliorates inactivity-induced adaptations in the medial gastrocnemius of adult rats
Authors: Kim Soo J. , Roy Roland R. , Zhong Hui , Suzuki Hideki , Ambartsumyan Lusine , Haddad Fadia , Baldwin Kenneth M. , Edgerton V. Reggie
Published: April 2007

The efficacy of high-load, short-duration isometric contractions, delivered as one vs. two sessions per day, on blunting inactivity-induced adaptations in the medial gastrocnemius (MG) were compared. Adult rats were assigned to a control (Con) or spinal cord-isolated (SI) group where one limb was stimulated (SI-Stim) while the other served as a SI control (SI-C). One bout of stimulation (BION microstimulator) consisted of a 100-Hz, 1-s stimulus, delivered every 30 s for 5 min with a 5-min rest period. This bout was repeated six times consecutively (SI-Stim1) or with a 9-h rest interval after the third bout (SI-Stim2) for 30 consecutive days. MG weights (relative to body weight) were 63, 72, and 79% of Con in SI-C, SI-Stim1, and SI-Stim2, respectively. Mean fiber size was 56% smaller in SI-C than in Con, and it was 19 and 31% larger in SI-Stim1 and SI-Stim2, respectively, compared with SI-C. Maximum tetanic tension was 42, 60, and 73% of Con in SI-C, SI-Stim1, and SI-Stim2, respectively. Specific tension was 77% of Con in SI-C, and at Con levels in both SI-Stim groups. SI increased the percent IIb myosin heavy chain composition (from 49 to 77%) and IIb+ fibers (from 63 to 79%): these adaptations were prevented by both Stim paradigms. These results demonstrate that 1) brief periods of high-load isometric contractions are effective in reducing inactivity-induced atrophy, functional deficits, and phenotypic adaptations in a fast hindlimb extensor, and 2) the same amount of stimulation distributed in two compared with one session per day is more effective in ameliorating inactivity-related adaptations.
Mapping of the silver gene in mink and its association with the dilution gene in dog
Authors: Anistoroaei R. , Christensen K.
Published: April 2007

In mink, recessive and dominant genes carry standard colors from generation to generation but breeding and cross breeding of naturally occurring mutations (color changes) has resulted in farmed animals bearing colors that do not exist in nature. The silver blue color type is one of the most used recessive mutations within mink fur farming being part of some of the popular color types which combine more recessive mutations. We report here the mapping of the ‘silver’ gene on MVI3 by means of the first linkage genetic map in the American mink (Mustela vison). A Canis familiaris BAC clone containing the melanophilin gene (which generates ‘silver-like’ phenotype in dog) was in situ cross-hybridized onto the mink chromosomes and the result strongly supports the linkage data. Therefore the silver phenotype in the American mink presumably involves the melanophilin gene (MLPH).
A Diagnosis of Thickness Fluxes in an Eddy-Resolving Model
Authors: Eden Carsten , Greatbatch Richard J. , Willebrand Jürgen
Published: April 2007

Output from an eddy-resolving model of the North Atlantic Ocean is used to estimate values for the thickness diffusivity κ appropriate to the Gent and McWilliams parameterization. The effect of different choices of rotational eddy fluxes on the estimated κ is discussed. Using the raw fluxes (no rotational flux removed), large negative values (exceeding −5000 m2 s−1) of κ are diagnosed locally, particularly in the Gulf Stream region and in the equatorial Atlantic. Removing a rotational flux based either on the suggestion of Marshall and Shutts or the more general theory of Medvedev and Greatbatch leads to a reduction of the negative values, but they are still present. The regions where κ < 0 correspond to regions where eddies are acting to increase, rather than decrease (as in baroclinic instability) the mean available potential energy. In the subtropical gyre, κ ranges between 500 and 2000 m2 s−1, rapidly decreasing to zero below the thermocline in all cases. Rotational fluxes and κ are also estimated using an optimization technique. In this case, |κ| can be reduced or increased by construction, but the regions where κ < 0 are still present and the optimized rotational fluxes also remain similar to a priori values given by the theoretical considerations. A previously neglected component (ν) of the bolus velocity is associated with the horizontal flux of buoyancy along, rather than across, the mean buoyancy contours. The ν component of the bolus velocity is interpreted as a streamfunction for eddy-induced advection, rather than diffusion, of mean isopycnal layer thickness, showing up when the lateral eddy fluxes cannot be described by isotropic diffusion only. All estimates show a similar large-scale pattern for ν, implying westward advection of isopycnal thickness over much of the subtropical gyre. Comparing ν with a mean streamfunction shows that it is about 10% of the mean in midlatitudes and even larger than the mean in the Tropics.
Temporal Characteristics of Abyssal Finescale Motions above Rough Bathymetry
Authors: Toole John M.
Published: April 2007

Current-meter data from a two-year mooring within a fracture zone on the western flank of the Mid-Atlantic Ridge in the South Atlantic Ocean are reported. The mooring, deployed in conjunction with the Brazil Basin Tracer Release Experiment, was placed in the general area where enhanced diapycnal mixing had previously been inferred. The current-meter data characterize the velocity, temperature, shear, and temperature gradient variability as a function of frequency. Energetic velocities and shears were observed at the mooring at a variety of frequencies. In addition to semidiurnal flows, a significant amount of shear variance derived from near-inertial motions, as has been seen in a recent numerical modeling study of tidal-frequency internal wave radiation and wave–wave interaction. At times, a fortnightly modulation of the total superinertial shear variance was indicated in the data, but this signal did not dominate the records. Wave ray tracing indicates that the deeper current meters may have been placed in a shadow zone for locally generated internal tides. At shallower levels, it is suggested that dispersion, wave–wave interaction, and wave breaking effectively obscured the sources of the finescale energy. Average diapycnal diffusivity estimates inferred from a Richardson-number-based parameterization and from observations of temperature inversions at 4648 m were of the same order of magnitude as those derived from turbulent dissipation estimates and from the rate of diapycnal tracer dispersion. The mooring data thus add additional support to the idea that energetic finescale motions above rough bathymetry support enhanced turbulent diapycnal mixing in these regions.
Climatology of Ocean Features in the Gulf of Mexico Using Satellite Remote Sensing Data
Authors: Vukovich Fred M.
Published: April 2007

A climatology of various ocean features in the Gulf of Mexico (GOM) was developed using the combination of satellite remote sensing and in situ data that spanned periods as long as 32 years. Twelve separate statistics were created, some of which described characteristics of the Loop Current, while others are involved with warm core rings that separate from the Loop Current and cold core rings. These statistics examined the frequency with which the Loop Current was found in the GOM, the orientation of the Loop Current, the frequency of intrusion of Loop Current water onto the west Florida shelf and into the GOM common water region, ring separation period from the Loop Current, ring dissipation, ring speed, ring path, frequency of ring water in the western GOM, and the frequency of warm and cold core rings (WCRs and CCRs, respectively) in the GOM. The results indicate that CCRs were principally responsible for mass and heat redistribution in the eastern GOM (EGOM) and WCRs are responsible for mass and heat redistribution in the western GOM (WGOM). The average period for WCR separation from the Loop Current was 11 months and the range from 5 to 19 months. WCRs moved through the WGOM most often using the central path (i.e., their trajectory was found between 24° and 26°N latitude) and they decreased to about 55% of their initial size when they reach the western wall of the GOM. CCRs were most often found in the EGOM, and their frequency of occurrence in the EGOM surpassed that of WCRs anywhere in the GOM.