bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of Independence in the Elderly
Authors: Cunningham David A. , Paterson Donald H. , Himann Joan E. , Rechnitzer Peter A.
Published: January 2008

The purpose of this study was to compare strength, flexibility, and cardiorespiratory fitness of the elderly living independently (n = 64) with those in rest or nursing homes (n = 61), and to identify those variables most strongly associated with an independent lifestyle. Quantitative levels of independence (Incapacity Index) and of activity were determined by questionnaires. Flexibility was measured using the Leighton Flexometer. Strength was measured using a modified sphygmomanometer. Cardiorespiratory fitness was measured using a self-paced walking test. Body size factors were also determined. Independent and dependent subjects were significantly different in age, which imposed a limitation on interpretation of these data. However, this factor was accounted for statistically in the analyses. Independent individuals compared to dependent ones showed significantly greater flexibility, activity levels, and choice of walking speed. Through multiple regression analysis, it was found that 40% of the variance in Incapacity Index was associated with participation in outdoor activities, greater shoulder flexibility, and a faster normal walking speed (> 1.0 m∙s−1). Key words: physical activity in the elderly, flexibility, strength, self-paced walking, physical fitness
Effects of Ageing on the Motor Unit: A Brief Review
Authors: Doherty Timothy J. , Vandervoort Anthony A. , Brown William F.
Published: January 2008

This review briefly summarizes the current state of knowledge regarding age related changes in skeletal muscle, followed by a more in-depth review of ageing effects on animal and human motor units (MUs). Ageing in humans is generally associated with reductions in muscle mass (atrophy), leading to reduced voluntary and electrically evoked contractile strength by the 7th decade for most muscle groups studied. As well, contraction and one-half relaxation times are typically prolonged in muscles of the elderly. Evidence from animal and human studies points toward age associated MU loss as the primary mechanism for muscle atrophy, and such losses may be greatest among the largest and fastest MUs. However, based on studies in animals and humans, it appears that at least some of the surviving MUs are able to partially compensate for MU losses, as indicated by an increase in the average MU size with age. The fact that muscles in the elderly have fewer, but on average larger and slower, MUs has important implications for motor control and function in this population. Key words: skeletal muscle, motor neuron, motor axon, contractile properties, adaptation
Caffeine and Exercise: Metabolism and Performance
Authors: Graham Terry E. , Rush James W. E. , Soeren Mary H. van
Published: January 2008

Caffeine ingestion prior to prolonged exercise delays fatigue. However, the mechanisms involved are very unclear. Caffeine is associated with elevated plasma epinephrine but the metabolic impact of this is uncertain. Glycogen sparing occurs in active muscle, at least in the first few minutes, but studies have generally failed to demonstrate enhanced fat metabolism. The demethylation of caffeine by the hepatic cytochrome P-450 oxygenases begins within minutes and dimethylxanthines (especially paraxanthine) are generated. These compounds appear in the plasma within an hour of caffeine ingestion and may have effects on tissues that have been attributed to caffeine and/or epinephrine. While the most widely supported theory is that caffeine and other methylxanthines are adenosine receptor antagonists, this action alone cannot explain all of the observed responses. Nevertheless, habituation to and withdrawal from caffeine are associated with up and down regulation of adenosine receptors. One study demonstrated marked differences in the effects of caffeine on the plasma concentrations of epinephrine and dimethylxanthines between caffeine users and nonusers. Caffeine is clearly a very active drug that has many effects on humans including increasing exercise endurance. This can be associated with muscle glycogen sparing and elevated plasma epinephrine, but the underlying mechanisms are unknown. Key words: methylxanthines, catecholamines, fatigue, endurance, P-450 system, adenosine receptors
Difference in the Cardiovascular Response to Prolonged Sitting in Men and Women
Authors: Gotshall Robert W. , Aten Laurie A. , Yumikura Sei
Published: January 2008

Orthostatic stress, sitting, results in adjustments of cardiovascular variables to maintain blood pressure and is prominent in a variety of occupations. Sitting serves as the control position for head-out water immersion studies. This study addressed gender differences in the cardiovascular response to prolonged sitting. Ten men and 10 women had cardiovascular measurements in the supine position compared with measurements during 2 hours in the seated position (Sit). Supine cardiovascular measurements were similar for both sexes. Heart rate changed similarly for both sexes with Sit. With Sit, men had elevated mean arterial pressure (9 ± 3%), total peripheral resistance (54 ± 9%), and decreased cardiac index (−27 ± 5%), while women had no change in mean arterial pressure, lesser elevations in total peripheral resistance (17 ± 7%), and lesser decreases in cardiac index (−12 ± 5%) than men. Thus men, compared to women, had an elevated mean arterial pressure response to prolonged orthostatic stress. Key words: posture, cardiac output, blood pressure, peripheral resistance, sex
Variability of Time to Exhaustion During Submaximal Exercise
Authors: McLellan Tom M. , Cheung Stephen S. , Jacobs Ira
Published: January 2008

Exercise time to exhaustion (TE) is commonly used to evaluate the success or failure of such treatments as endurance training programs or nutritional supplements. The present study determined the variability of TE during submaximal exercise at 80% [Formula: see text]. Fifteen males performed cycle exercise to exhaustion on five occasions at the same time of day with a minimum of 72 hrs between sessions. There was no difference in TE (0.1 > p > 0.05) among the trials, with values ranging from 14.4 ± 1.1 min for Test 1 to 18.2 ± 2.4 min during the final test. Substantial variability in TE over the five trials was observed among subjects with coefficients of variation (CV) ranging from 2.8 to 31.4%. Subjects were divided into two groups using the median CV for TE. For the low CV group (n = 8), TE was significantly increased during Test 3 (14.9 ± 1.3 min) compared with Test 1 (12.8 ± 1.0 min) and Test 5 (12.5 ± 1.2 min). For the high CV group (n = 7), TE was increased during Test 5 (24.7 ± 3.7 min) compared with the other tests (18.5 ± 2.2 min). CV for [Formula: see text], [Formula: see text], pH, [Formula: see text], and rectal temperature were less than 5% and did not differ between groups. Post hoc power calculations revealed that if all subjects were considered as one group, sample size would have to increase to 40 to increase the power to 0.8. Due to the variability in TE that may be observed with males of average fitness, it is concluded that TE should not be the only dependent measure used to evaluate treatment effects during submaximal exercise. Key words: coefficient of variation, blood lactate, sample size, power
Vascular Actions of Insulin in Health and Disease
Authors: Shoemaker J. Kevin , Bonen Arend
Published: January 2008

Insulin has well known metabolic effects. However, depending on the magnitude and duration of the insulin stimulus, this hormone can also produce vasodilation and vascular smooth muscle growth. The association of hyperinsulinemia with the metabolic disorders of obesity and non-insulin-dependent diabetes, as well as with the cardiovascular pathologies of hypertension and atherosclerosis, has led to suggestions that perhaps elevated insulin levels are causally related to these diseases. Alternatively, insulin resistance may develop following an increase in skeletal muscle vascular resistance, with or without hypertension, such that a reduction in skeletal muscle blood flow leads to an attenuated glucose delivery and uptake. These hypotheses are explored in this review by examining the effects of insulin on vascular smooth muscle tissue during both acute and prolonged exposure. An interaction among hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with the insulin resistant state is described whereby insulin resistance can be both a cause and a result of elevated vascular resistance. The association between blood flow and insulin stimulated glucose uptake suggests that therapeutic intervention against the development of skeletal muscle vascular resistance should occur early in individuals genetically predisposed to cardiovascular pathology in order to attenuate, or avoid, insulin resistance and its sequelae. Key words: hyperinsulinemia, hyperglycemia, vascular smooth muscle, obesity, hypertension, atherosclerosis
Stress Proteins: The Exercise Response
Authors: Locke Marius , Noble Earl G.
Published: January 2008

A class of proteins that undergoes preferential synthesis following a variety of stressors has been demonstrated to carry out important cellular functions under both stressed and nonstressed conditions. These so-called heat shock (HSP) or stress (SP) proteins have been termed "molecular chaperones" and play important roles in cellular transportation, assembly/degradation, and cell survival. This review provides a basic introduction to the function and regulation of these proteins. Emphasis is placed on members of the HSP 70 family of proteins (especially HSP 72) and their role in cellular protection, their pattern of distribution in skeletal muscle, and changes in their expression following exercise and exercise training. Key words: exercise, heat shock, HSP 72, skeletal muscle
Exercise- and Cold-Induced Asthma
Authors: Giesbrecht Gordon G. , Younes Magdy
Published: January 2008

Exercise- and cold-induced asthma are commonly recognized respiratory disorders. The asthmatic response includes several factors contributing to airway narrowing, and thus increased airway resistance. These include airway smooth muscle contraction, mucus accumulation, and bronchial vascular congestion as well as epithelial damage and vascular leakage. The etiology for these disorders is nonantigenic. The primary stimulus is probably a combination of airway cooling and drying (leading to hypertonicity of airway lining fluid). Symptoms generally do not occur during the stimulus period (e.g., exercise) itself. This protection may in part be due to increased catecholamine levels during exercise. The early phase response, which occurs 5 to 15 min poststimulus, may be mediated through a combination of (a) direct influences, (b) vagal reflexes triggered by airway sensory receptors, or (c) responses to mediator release. Spontaneous recovery occurs within 30 min to 2 hrs. There is usually a refractory period of about 1 to 2 hrs during which responses to further stimuli are attenuated. This may be due to depletion of histamine and other mediators. As well, prostaglandin release (mediated via LTD4which is released during exercise) inhibits further airway narrowing. A late phase response has been reported 4 to 10 hrs poststimulus in some patients. These reactions are accompanied by a second release of histamine and other mediators that cause inflammatory responses and epithelial damage. However, the exercise dependence of this response is debated. Key words: respiratory heat loss, hyper osmolarity, pulmonary receptors, temperature receptors, inflammation, epithelial damage
Acid-Base Balance: Origin of Plasma [H+] During Exercise
Authors: Kowalchuk John M. , Scheuermann Barry W.
Published: January 2008

According to physicochemical principles, the plasma concentration of hydrogen ions ([H+]), bicarbonate ([HCO3−]), and other acid-base-dependent variables are determined by the plasma PCO2; the strong ion difference ([SID+] = Σ[strong cations] − Σ[strong anions]); and the concentration of weak acids ([ATOT] = [HA] + [A−]). The physicochemical interactions between the acid-base-independent and dependent variables must recognize the constraints imposed by the law of electrical neutrality, dissociation equilibrium of weak acids and water, and the conservation of mass. This review demonstrates the usefulness of the physicochemical approach in studying plasma acid-base control during progressive exercise to exhaustion where the work rate was increased as either a slow (8 W/min) or fast (65 W/min) ramp function. The factors contributing to changes in the concentration of the acid-base-independent variables, and the contribution of the acid-base-independent variables to the plasma [H+] and [HCO3−] during exercise, will be discussed. Key words: PCO2, strong ion difference, weak acids, lactate, potassium
Hemodynamics During a Machine-Aided Flexibility Protocol
Authors: Holt Laurence E. , Campagna Philip D. , Pel Ham Thomas W.
Published: January 2008

Heart rates and systolic and diastolic blood pressures of 15 subjects were measured before, during, and after a series of four proprioceptive neuromuscular facilitation (PNF) flexibility exercises. The protocol for the study involved the use of two new machines, one designed to increase flexibility of the erector spinae, the other the hamstrings. Each machine provided constant feedback of isometric force, angular displacements, time of contraction, repetitions, and other exercise variables. Each bout of exercise involved an isometric contraction of the lengthened agonist muscle group (12 sec) followed by a concentric contraction of its antagonist in order to place the body part in a more stretched position. Hemodynamic measurements were determined at both a perceived maximal voluntary isometric contraction (MVIC) and at 50% MVIC. Significant increases in hemodynamic factors were observed when exercise measures were compared to pre- and postexercise (resting) values. Higher values, though not significantly so, were found at MVIC than at 50% MVIC on both machines. All values were well within the guidelines of the American College of Sports Medicine. Key words: blood pressure, heart rate, exercise prescription, isometric contraction
Concentric and Eccentric Knee Extension Strength in Older and Younger Men and Women
Authors: Porter Michelle M. , Myint Aung , Kramer John F. , Vandervoort Anthony A.
Published: January 2008

Decrements in isometric and concentric (Conc) muscular strength with increased age are well documented. However, little information is available on the effects of aging on eccentric (Ecc) strength, even though Ecc or lengthening muscle actions are used in most physical activities. This study examined Conc and Ecc peak torques (PT) during knee extension at 90°/sec in healthy older (62 to 89 yrs) and younger (20 to 29 yrs) men and women. Conc PT decreased more with age than did Ecc (p < 0.01), for both men and women. PT values for the older men and women as a percentage of those of the younger ones were 58.3 and 46.6% for Conc, and 75.1 and 61.7% for Ecc, respectively. These age differences need to be considered during isokinetic evaluations of Conc versus Ecc strength. Other muscle groups should be investigated, and mechanisms remain to be determined. Key words: aging, muscle, isokinetics
NEW INVARIANT OF 4-MOVES
Authors: DABKOWSKI M. K. , SAHI R. K.
Published: January 2008

Study of equivalence classes of links up to n-moves plays an important role in the theory of invariants based on the skein relation and, in particular, skein modules. In this paper, we consider Nakanishi's 4-move conjecture [12]. The modification of the conjecture to 2-component link (homotopically trivial links) is a question proposed by Kawauchi [10]. We define a new invariant of links which is preserved by 4-moves and analyze its potential strength. In particular, we show that our invariant allows us to obtain results of [8, 9, 13] concerning 4-moves.
UNLINKING NUMBER AND UNLINKING GAP
Authors: JABLAN SLAVIK , SAZDANOVIĆ RADMILA
Published: January 2008

Computing unlinking number is usually very difficult and complex problem, therefore we define BJ-unlinking number and recall Bernhard–Jablan conjecture stating that the classical unknotting/unlinking number is equal to the BJ-unlinking number. We compute BJ-unlinking number for various families of knots and links for which the unlinking number is unknown. Furthermore, we define BJ-unlinking gap and construct examples of links with arbitrarily large BJ-unlinking gap. Experimental results for BJ-unlinking gap of rational links up to 16 crossings, and all alternating links up to 12 crossings are obtained using programs LinKnot and K2K. Moreover, we propose families of rational links with arbitrarily large BJ-unlinking gap and polyhedral links with constant non-trivial BJ-unlinking gap. Computational results suggest existence of families of non-alternating links with arbitrarily large BJ-unlinking gap.
RASMUSSEN INVARIANT, SLICE-BENNEQUIN INEQUALITY, AND SLICENESS OF KNOTS
Authors: SHUMAKOVITCH ALEXANDER N.
Published: January 2008

We use recently introduced Rasmussen invariant to find knots that are topologically locally-flatly slice but not smoothly slice. We note that this invariant can be used to give a combinatorial proof of the slice-Bennequin inequality. Finally, we compute the Rasmussen invariant for quasipositive knots and show that most of our examples of non-slice knots are not quasipositive and, to the best of our knowledge, were previously unknown.
PENDULUM TRACED CURVES AND DAMPED OSCILLATIONS IN THE PLANE
Authors: KAUFFMAN LOUIS H.
Published: January 2008

This paper studies a non-linear model for the damped oscillations of a pendulum.
L-MOVES AND MARKOV THEOREMS
Authors: LAMBROPOULOU SOFIA
Published: January 2008

Given a knot theory (virtual, singular, knots in a 3-manifold etc.), there are deep relations between the diagrammatic knot equivalence in this theory, the braid structures and a corresponding braid equivalence. The L-moves between braids, due to their fundamental nature, may be adapted to any diagrammatic situation in order to formulate a corresponding braid equivalence. In this short paper, we discuss and compare various diagrammatic set-ups and results therein, in order to draw the underlying logic relating diagrammatic isotopy, braid structures, Markov theorems and L-move analogues. Finally, we apply our conclusions to singular braids.
The acetate recovery factor to correct tracer-derived dietary fat oxidation in humans
Authors: Bergouignan Audrey , Schoeller Dale A. , Votruba Susanne , Simon Chantal , Blanc Stéphane
Published: January 2008

When using 13C tracer to measure plasma fat oxidation, an acetate recovery factor should be determined in every subject to correct for label sequestration. Less is known regarding the acetate recovery factor for dietary fatty acid oxidation. We compiled data from six studies to investigate the determinants of the dietary acetate recovery factor (dARF) at rest and after physical activity interventions and compared the effects of different methods of dARF calculation on both the fat oxidation and its variability. In healthy lean subjects, dARF was 50.6 ± 5.4% dose ( n = 56) with an interindividual coefficient of variation of 10.6% at rest and 9.2% after physical activity modifications. The physical activity interventions did not impact dARF, and the intraindividual coefficient of variation was 4.6%. No major anthropological or physiological determinants were detected except for resting metabolic rate, which explains 7.4% of the dARF variability. Applying an individual or an average group dARF did not affect the mean and the variability of the derived dietary lipid oxidation at rest or after physical activity interventions. Using a mean dARF for a group leads to over- or underestimation of fat oxidation of less than 10% in individual subjects. Moreover, the use of a group or individual correction did not affect the significant relationship found between fasting respiratory exchange ratio and dietary fat oxidation. These data indicate that an average dARF can be applied for longitudinal and cross-sectional studies investigating dietary lipid metabolism.
Handedness in Captive Bonobos (Pan paniscus)
Authors: Harrison Rebecca M. , Nystrom Pia
Published: January 2008

Species level right-handedness is often considered to be unique to humans. Handedness is held to be interrelated to our language ability and has been used as a means of tracing the evolution of language. Here we examine handedness in 3 captive groups of bonobos(Pan paniscus)comprising 22 individuals. We found no evidence for species level handedness. Conclusions that can be drawn from these findings are: (1) species level handedness evolved after the divergence of thePanandHomolineages; (2) inconsistent preferences may represent precursors to human handedness, and (3)Panmay have language abilities but these cannot be measured using handedness.
Endothelin-A Receptor Blockade Increases Nutritive Skin Capillary Circulation in Patients with Type 2 Diabetes and Microangiopathy
Authors: Settergren Magnus , Pernow John , Brismar Kerstin , Jörneskog Gun , Kalani Majid
Published: January 2008

Aims: Endothelin-1 levels are elevated in patients with type 2 diabetes mellitus and may contribute to impaired microvascular function. We investigated the effect of selective endothelin-A (ETA) receptor blockade (BQ123) on skin microcirculation in patients with type 2 diabetes and albuminuria. Methods: Ten type 2 diabetes patients and 8 non-diabetic controls were investigated. Nutritive skin capillary circulation, investigated by videophotometric capillaroscopy, and total skin microcirculation, assessed by laser Doppler fluxmetry (LDF), were studied during intra-arterial infusion of saline for 15 min, followed by BQ123 infusion for 60 min. Results: Following BQ123 infusion there was a significant increase in resting capillary blood cell velocity (CBV) in patients with type 2 diabetes from 0.24 (0.20–0.34) mm/s at baseline to 0.61 (0.46–0.88) mm/s at 60 min, but no significant change in the control subjects [0.55 (0.10–0.68) vs. 0.38 (0.13–0.88) mm/s; p < 0.005 for difference between groups]. Peak CBV following arterial occlusion and skin temperature increased significantly in the type 2 diabetes group but not in the control group during BQ123 infusion. There were no significant changes in LDF parameters during infusion of BQ123 in either group. Conclusion: ETA receptor blockade improves nutritive skin capillary circulation in patients with type 2 diabetes and microangiopathy.
Subendothelial infiltration of neutrophil granulocytes and liberation of matrix-destabilizing enzymes in an experimental model of human neo-intima
Authors: Torzewski Michael , Dahm Manfred , Kirkpatrick Charles , Lackner Karl J. , Vahl Christian-Friedrich , Dorweiler Bernhard
Published: January 2008

It was the objective of this study to examine the role of human neutrophil granulocytes (PMN) in an in-vitro model of human neo-intima developed for the study of atherosclerosis. Human granulocytes were subjected to a co-culture model of human endothelial and smooth muscle cells. Subendothelial lipid accumulation was achieved by addition of native LDL to the culture medium. Tissue samples were analyzed by immunohistochemistry and scanning/transmission electron microscopy, and culture supernatants were examined for the presence of interleukin- 8 (IL-8), MCP-1, GRO-α, elastase and matrixmetalloproteinase-8 (MMP-8). Following addition of 2 mg/ml LDL, adherence, transmigration and infiltration depth of PMN was increased significantly when compared to controls. LDL challenging was paralleled by a time- and dose-dependent secretion of IL-8 from intimal smooth muscle cells. PMN infiltration was mediated by the IL-8-signalling pathway and accompanied by release of elastase and MMP-8 into the supernatant and induction of endothelial cell apoptosis. In conclusion, LDL-induced secretion of IL-8 by intimal smooth muscle cells provides a potential mechanism of PMN-recruitment into culprit lesions. The concomitant release of potent matrix-degrading enzymes and the induction of EC apoptosis may have implications for plaque destabilization and cardiovascular events.
Real-time measurement of non-lethal platelet thromboembolic responses in the anaesthetized mouse
Authors: Tymvios Charalambos , Jones Sarah , Moore Christopher , Pitchford Simon C. , Page Clive P. , Emerson Michael
Published: January 2008

Identifying and evaluating new therapeutic targets in platelets requires advanced animal models in which platelet responses can be measured directly and in situ.This is important because platelet function is strongly influenced by external factors such as those originating from the vascular endothelium. Our objectives were to record graded, non-lethal thromboembolic platelet responses to platelet agonists in situ in the mouse and to demonstrate an inhibitory effect of aspirin in our model. Radiolabelled platelets were infused into anaesthetized mice and responses to ADP, collagen and thrombin measured as changes in platelet associated counts in miniaturized detection probes placed over the thoracic region. All agonists induced dose-dependent changes in platelet counts due to accumulation of thrombi in the pulmonary vasculature. We confirmed a specific platelet effect by comparing platelet and erythrocyte responses and showing platelet aggregates in the lung vasculature histologically. Simultaneous injection of collagen and adrenaline induced increased and protracted synergistic platelet responses compared with individual injection of these agents and aspirin inhibited collagen-induced responses. We confirmed the clinical relevance of our model by showing that platelet thromboembolism in the mouse, like pulmonary embolism in humans, impaired cardiovascular performance. We present a refined method for measuring platelet agonist dose-responses and thromboembolism in real-time without inducing mortality in the mouse. Our technique will be useful in investigating the molecular determinants of physiological and pathophysiological platelet function in an in-vivo context and will enable investigations of both platelet and non-platelets mediators of thrombus formation.
The use of the VerifyNow P2Y12 point-of-care device to monitor platelet function across a range of P2Y12 inhibition levels following prasugrel and clopidogrel administration
Authors: Payne Christopher D. , Li Ying G. , Brandt John T. , Small David S. , Farid Nagy A. , Salazar Daniel E. , Winters Kenneth J. , Jakubowski Joseph A.
Published: January 2008

Variability in response to antiplatelet agents has prompted the development of point-of-care (POC) technology. In this study, we compared theVerifyNowTM P2Y12 (VN-P2Y12) POC device with light transmission aggregometry (LTA) in subjects switched directly from clopidogrel to prasugrel. Healthy subjects on aspirin were administered a clopidogrel 600 mg loading dose (LD) followed by a 75 mg/d maintenance dose (MD) for 10 days. Subjects were then switched to a prasugrel 60 mg LD and then 10 mg/d MD for 10 days (n=16), or to a prasugrel 10 mg/d MD for 11 days (n=19). Platelet function was measured by LTA andVN-P2Y12 at baseline and after dosing. Clopidogrel 600 mg LD/75 mg MD treatment led to a reduction in P2Y12 reaction units (PRU) from baseline. A switch from clopidogrel MD to prasugrel 60 mg LD/10 mg MD produced an immediate decrease in PRU, while a switch to prasugrel 10 mg MD resulted in a more gradual decline. Consistent with the reduction in PRU, device-reported percent inhibition increased during both clopidogrel and prasugrel regimens. Inhibition of platelet aggregation as measured by LTA showed a very similar pattern to that found with VN-P2Y12 measurement, irrespective of treatment regimens. The dynamic range of VN-P2Y12 appeared to be narrower than that of LTA. With two different thienopyridines, the VN-P2Y12 device, within a somewhat more limited range, reflected the overall magnitude of change in aggregation response determined by LTA. The determination of the clinical utility of such POC devices will require their use in clinical outcome studies.
Role of proteolysis in development of murine adipose tissue
Authors: Christiaens Valerie , Scroyen Ilse , Lijnen H. Roger
Published: January 2008

Obesity is a common disorder, and related diseases such as diabetes, atherosclerosis, hypertension, cardiovascular disease and cancer are a major cause of mortality and morbidity inWesterntype societies. Development of obesity is associated with extensive modifications in adipose tissue involving adipogenesis, angiogenesis and extracellular matrix proteolysis. The fibrinolytic (plasminogen/plasmin) and matrix metalloproteinase (MMP) systems cooperate in these processes. A nutritionally induced obesity model in transgenic mice has been used extensively to study the role of the fibrinolytic and MMP systems in the development of obesity. These studies support a role of both systems in adipogenesis and obesity, and suggest that modulation of proteolytic activity may affect development of adipose tissue.
Male-specific cardiac pathologies in mice lacking either the A or B subunit of factor XIII
Authors: Souri Masayoshi , Koseki-Kuno Shiori , Takeda Naoki , Yamakawa Mitsunori , Takeishi Yasuchika , Degen Jay L. , Ichinose Akitada
Published: January 2008

Factor XIII (FXIII) is a proenzyme of plasma transglutaminase consisting of enzymatic A subunits (FXIII-A) and non-catalytic B subunits (FXIII-B), and acts in haemostasis and wound healing. We generated mice lacking either FXIII-A or FXIII-B to investigate the physiological functions of FXIII in vivo. A longitudinal study was carried out using the gene-targeted mice to explore the possible effects of FXIII deficiency on aging. Survival rates of FXIII-A-/- males decreased to approximately 50% at 10 months after birth, although most FXIII-A-/- females and both genders of wild-type mice survived. Four FXIII-A-/- males died of severe intra-thoracic haemorrhage, and a large haematoma was found in their hearts. Haemorrhage, haemosiderin deposition and/or fibrosis were observed in the hearts of other dead FXIII-A-/- males. Fibrosis together with haemosiderin deposition was also found in the hearts of FXIII-A-/- males sacrificed. The in-vivo cardiac function was normal in FXIII-A-/- mice when compared with wild-type mice despite the presence of significant cardiac fibrosis. Although survival rates for both genders of the FXIII-B-/- and wild-type mice did not differ, mild fibrosis together with haemosiderin deposits were only found in the hearts of the sacrificed FXIII-B-/- males. Carditis and fibrosis in FXIII-deficient mice might be caused by a faulty or delayed reparative process that was initiated by abnormal haemorrhagic events within heart tissue. It is important therefore to examine possible cardiac involvement in human patients with congenital FXIII deficiency.
Clearance of von Willebrand factor
Authors: Christophe Olivier D. , Oortwijn Beatrijs D. , Lenting Peter J. , Denis Cécile V.
Published: January 2008

The life cycle of von Willebrand factor (VWF) comprises a number of distinct steps, ranging from the controlled expression of theVWF gene in endothelial cells and megakaryocytes to the removal of VWF from the circulation. The various aspects of VWF clearance have been the objects of intense research in the last few years, stimulated by observations thatVWF clearance is a relatively common component of the pathogenesis of type 1 von Willebrand disease (VWD). Moreover, improving the survival of VWF is now considered as a viable therapeutic strategy to prolong the half-life of factor VIII in order to optimise treatment of haemophilia A. The present review aims to provide an overview of recent findings with regard to the molecular basis of VWF clearance. A number of parameters have been identified that influence VWF clearance, including its glycosylation profile and a number of VWF missense mutations. In addition, in-vivo studies have been used to identify cells that contribute to the catabolism of VWF, providing a starting point for the identification of receptors that mediate the cellular uptake ofVWF.Finally, we discuss recent data describing chemically modification of VWF as an approach to prolong the half-life of the VWF/FVIII complex.
Factor VII-activating protease (FSAP): Vascular functions and role in atherosclerosis
Authors: Parahuleva Mariana , Muhl Lars , Kemkes-Matthes Bettina , Sedding Daniel , Preissner Klaus T. , Kanse Sandip M.
Published: January 2008

FSAP is a plasma serine protease for which a potential role in the regulation of coagulation and fibrinolysis is postulated, based on its property to activate factorVII (FVII) as well as pro-urokinase (uPA). In clinical studies, the G534E single nucleotide polymorphism (Marburg I) of FSAP has been linked to late complications of atherothrombosis and is associated with a low proteolytic activity, particularly, towards pro-uPA. This has stimulated much interest in a search for additional functions of FSAP in the cardiovascular system. FSAP is a potent inhibitor of vascular smooth muscle cell proliferation and migration in vitro and local application of FSAP (but not Marburg I variant) in animal models reduces neointima formation. This is due to a reduced proteolytic activity of the variant isoform towards platelet derived growth factor-BB, a key mediator of neointima development. Moreover, appreciable quantities of FSAP are localized to unstable atherosclerotic plaques and may contribute to plaque instability. These data indicate that the cellular regulatory effects of FSAP may be more important than its influence on haemostasis. In this review the contribution of FSAP to vascular fibroproliferative inflammatory diseases in the context of pericellular proteolysis of the extracellular matrix, growth factor activity and haemostasis will be highlighted.
Meeting George Bush versus Meeting Cinderella: The Neural Response When Telling Apart What is Real from What is Fictional in the Context of Our Reality
Authors: Abraham Anna , von Cramon D. Yves , Schubotz Ricarda I.
Published: January 2008

A considerable part of our lives is spent engaging in the entertaining worlds of fiction that are accessible through media such as books and television. Little is known, however, about how we are able to readily understand that fictional events are distinct from those occurring within our real world. The present functional imaging study explored the brain correlates underlying such abilities by having participants make judgments about the possibility of different scenarios involving either real or fictional characters being true, given the reality of our world. The processing of real and fictional scenarios activated a common set of regions including medial-temporal lobe structures. When the scenarios involved real people, brain regions associated with episodic memory retrieval and self-referential thinking, the anterior prefrontal cortex and the precuneus/posterior cingulate, were more active. In contrast, areas along the left lateral inferior frontal gyrus, associated with semantic memory retrieval, were implicated for scenarios with fictional characters. This implies that there is a fine distinction in the manner in which conceptual information concerning real persons in contrast to fictional characters is represented. In general terms, the findings suggest that fiction relative to reality tends to be represented in more factual terms, whereas our representations of reality relative to fiction are colored by personal subjectivity. What modulates our understanding of the relative difference between reality and fiction seems to be whether such character-type information is coded in self-relevant terms or not.
Item-specific Training Reduces Prefrontal Cortical Involvement in Perceptual Awareness
Authors: Eriksson Johan , Larsson Anne , Nyberg Lars
Published: January 2008

Previous studies on the neural correlates of perceptual awareness implicate sensory-specific regions and higher cortical regions such as the prefrontal cortex (PFC) in this process. The specific role of PFC regions is, however, unknown. PFC activity could be bottom-up driven, integrating signals from sensory regions. Alternatively, PFC regions could serve more active top-down processes that help to define the content of consciousness. To compare these alternative views of PFC function, we used functional magnetic resonance imaging and measured brain activity specifically related to conscious perception of items that varied in ease of identification (by being presented 0, 12, or 60 times previously). A bottom-up account predicts that PFC activity would be largely insensitive to stimulus difficulty, whereas a top-down account predicts reduced PFC activity as identification becomes easier. The results supported the latter prediction by showing reduced activity for previously presented compared to novel items in the PFC and several other regions. This was further confirmed by a functional connectivity analysis showing that the interaction between frontal and visual sensory regions declined as a function of ease of identification. Given the attribution of top-down processing to PFC regions in combination with the marked decline in PFC activity for easy items, these findings challenge the prevailing notion that the PFC is necessary for consciousness.
An Agent Harms a Victim: A Functional Magnetic Resonance Imaging Study on Specific Moral Emotions
Authors: Kédia Gayannée , Berthoz Sylvie , Wessa Michele , Hilton Denis , Martinot Jean-Luc
Published: January 2008

The statement: “An agent harms a victim,” depicts a situation that triggers moral emotions. Depending on whether the agent and the victim are the self or someone else, it can lead to four different moral emotions: self-anger (“I harm myself”), guilt (“I harm someone”), other-anger (“someone harms me”), and compassion (“someone harms someone”). In order to investigate the neural correlates of these emotions, we examined brain activation patterns elicited by variations in the agent (self vs. other) and the victim (self vs. other) of a harmful action. Twenty-nine healthy participants underwent functional magnetic resonance imaging while imagining being in situations in which they or someone else harmed themselves or someone else. Results indicated that the three emotional conditions associated with the involvement of other, either as agent or victim (guilt, other-anger, and compassion conditions), all activated structures that have been previously associated with the Theory of Mind (ToM, the attribution of mental states to others), namely, the dorsal medial prefrontal cortex, the precuneus, and the bilateral temporo-parietal junction. Moreover, the two conditions in which both the self and other were concerned by the harmful action (guilt and other-anger conditions) recruited emotional structures (i.e., the bilateral amygdala, anterior cingulate, and basal ganglia). These results suggest that specific moral emotions induce different neural activity depending on the extent to which they involve the self and other.
Working Memory Load for Faces Modulates P300, N170, and N250r
Authors: Morgan Helen M. , Klein Christoph , Boehm Stephan G. , Shapiro Kimron L. , Linden David E. J.
Published: January 2008

We used event-related potential (ERP) methodology to examine neural activity associated with visual working memory (WM) for faces. There were two main goals. First, to extend previous findings of P300 load modulation to WM for faces. Second, to examine whether N170 and N250r are also influenced by WM load. Between one and four unfamiliar faces were simultaneously presented for memory encoding. After a 1-sec delay, a target face appeared, and participants had to judge whether this face was part of the previous face array. P300 amplitude decreased as WM load increased, and this P300 suppression was observed at both encoding and retrieval. WM load was also found to modulate other ERPs. The amplitude of the N170 elicited by the target face decreased with load, and this N170 decrease leveled off at load 2, reflecting the behavioral WM capacity of around two faces. In addition, the N250r, observed as an ERP difference for target faces that were present in the encoding array relative to target faces that were absent, was also reduced for higher WM loads. These findings extend previous work by showing that P300 modulation by WM load also occurs for faces. Furthermore, we show, for the first time, that WM load affects the N250r and the early visual N170 component. This suggests that higher visual areas play an important role in WM for faces.
Involvement of the Supplementary Eye Field in Oculomotor Predictive Behavior
Authors: Nyffeler Thomas , Rivaud-Pechoux Sophie , Wattiez Nicolas , Gaymard Bertrand
Published: January 2008

The presentation of saccadic and smooth pursuit eye movements as two separate systems has recently been reconsidered: The two subsystems share a number of anatomical structures, and recent data suggest that this sharing also extends to physiological processes. The aim of our study was first to test whether these two subsystems share a common predictive process. We designed a new predictive smooth pursuit paradigm that requires the triggering of unpredictable saccades, performed either during low (ongoing pursuit) or high (pursuit direction reversal) predictive behavior. Saccade latency was used as a probe to reveal a possible sharing of prediction between the two subsystems. The main finding was that saccade latencies were markedly decreased when triggered around pursuit direction reversal and performed in the direction of the predicted pursuit. The aim of the second part of this study was to determine the neural substrate of this common predictive process. According to previous studies, the supplementary eye field (SEF) would be involved in the control of predictive pursuit. The same subjects therefore performed the same tasks, and transcranial magnetic stimulation (TMS) was applied over this area: Decreased saccade latencies were no longer observed, whereas it continued to be observed when applied over the occipital cortex. These results are consistent with (1) The existence of a common predictive process shared by both oculomotor subsystems; (2) The view of the SEF not as a primary oculomotor area but as a higher order structure able to elaborate complex processes, such as prediction, independently of the oculomotor output.
Basal Ganglia Play a Unique Role in Task Switching within the Frontal-Subcortical Circuits: Evidence from Patients with Focal Lesions
Authors: Yehene Einat , Meiran Nachshon , Soroker Nachum
Published: January 2008

The performance of patients with lesions involving the basal ganglia (BG) was compared to that of patients with prefrontal (PFC) lesions, thalamic (TH) lesions, and age-matched controls in order to examine the specific role of the BG within the frontal-subcortical circuits (FSCC) in task switching. All the BG patients and none of the other participants showed a marked increase in error rate in incongruent trials where correct responses depended upon the choice of the correct task rule. Some BG patients erred in failing to switch tasks and others failed despite their attempt to switch tasks. Additionally, reaction time results indicate abnormal response repetition effects among the BG patients; failure in benefiting from advance task information among all the patients; and increased task mixing costs following PFC lesions. The authors conclude that although the frontal-subcortical circuits jointly determine some behaviors (such as benefiting from preparation), the BG play a unique role within the FSCC in action selection and/or the inhibition of irrelevant information.
African American Resiliency: Examining Racial Socialization and Social Support as Protective Factors
Authors: Brown Danice L.
Published: January 2008

The purpose of this study was to examine the relative importance of racial socialization and social support in the resiliency of African Americans. It was hypothesized that social support and racial socialization would predict the resiliency of 154 African American undergraduate students at a large midwestern university. They completed the Multidimensional Scale of Perceived Social Support (MPSS), the Teenager Experience of Racial Socialization Scale (TERS), and the Connor-Davidson Resilience Scale (CD-RISC). Findings from hierarchical multiple regression analyses indicated that receiving racial socialization messages and perceiving that one had social support accounted for the largest proportion of variance in resiliency scores. Implications for parents and mental health providers are discussed.
Sociocultural Stress, Smoking Risk, and Cessation Among African American Women
Authors: Fernander Anita , Schumacher Mitzi , Nasim Aashir
Published: January 2008

The common explanation as to why individuals smoke is that the act of smoking relieves psychological stress, yet very few studies have examined the association between stress and smoking from a sociocultural perspective among African American women. The current study examined the paradigm of sociocultural stress and its association between smoking risk and likelihood of quitting among African American women. One hundred ninety-eight African American women, approximately half of whom were current smokers, completed a battery of questionnaires that included a smoking risk survey and measures of acculturation, stress, and coping. A theoretically based path analytic model revealed that the acculturative stress factors of cultural mistrust (β = .39) and socialization (β = .17) were predictive of perceptions of race-related stress (R 2 = .18), which were predictive of the number of race-related events experienced (R 2 = .51), which contributed to reports of general life stress (R 2 = .07), which was subsequently associated with smoking risk (R 2 = .03). The findings suggest that smoking cessation intervention programs for African American women should be tailored to address sociocultural issues related to stress that impacts their smoking.
Flow and Regulatory Compatibility: An Experimental Approach to the Flow Model of Intrinsic Motivation
Authors: Keller Johannes , Bless Herbert
Published: January 2008

The authors propose that the experience of flow (Csikszentmihalyi, 2000) as reflected in the deep involvement in an activity perceived as intrinsically rewarding represents a regulatory compatibility experience. The research addresses the notion that the compatibility of critical person (e.g., skills) and environmental factors (e.g., demands) involved in a given activity elicits subjective experiences that render the respective activity rewarding. Two studies are reported that investigate the consequences of compatibility of skills and task demands during task engagement. Departing from correlational research, the present studies employ a newly developed experimental paradigm to document the causal impact of such a skills/demands compatibility on the emergence of flow. Experiment 2 revealed that individuals characterized by a strong habitual action-orientation were most sensitive to the manipulation of the skills—demands compatibility.
The Perceived Informational Basis of Attitudes: Implications for Subjective Ambivalence
Authors: Tormala Zakary L. , DeSensi Victoria L.
Published: January 2008

Three studies tested the hypothesis that when people receive persuasive messages, their perceptions of the information on which they base their attitudes can determine feelings of subjective ambivalence. Across studies, it is shown that when elaboration (e.g., need for cognition, personal relevance) is high, people have more subjective ambivalence when they perceive that they have based their attitudes on the source of a message rather than the arguments contained in that message. When elaboration is low, this effect is reversed. These findings suggest that people can assess the informational basis of their attitudes and that these assessments influence feelings of attitude ambivalence.