bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacts of Plant Symbiotic Fungi on Insect Herbivores: Mutualism in a Multitrophic Context
Authors: Hartley Sue E. , Gange Alan C.
Published: December 2008

We consider how fungi that form symbiotic associations with plants interact with insect herbivores attacking the same plants. Both endophytes and mycorrhizae have significant impacts on herbivores with which they are in relatively intimate contact, but weaker effects on those from which they are spatially separated. Generalist insects are usually adversely affected by the presence of endophytes and mycorrhizae, whereas specialist insects may often benefit. Effects on feeding guilds vary according to type of fungi; for example, aphids are often negatively affected by endophytes but respond positively to mycorrhizae, and leaf-chewers are usually negatively affected by both types of fungi. There is a strong taxonomic bias in the literature and many interactions remain little studied; laboratory studies predominate over field studies. Although some patterns emerge, there is a large amount of specificity and context dependency in the outcome of interactions, reflecting the influence of fungal and host genotype, fungal, host, and insect species, and environmental factors. Whereas some of the mechanisms underpinning these interactions are relatively well characterized, others remain unclear and await elucidation by molecular and metabolomic techniques.
Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue
Authors: Yin Jun , Gao Zhanguo , He Qing , Zhou Dequan , Guo ZengKui , Ye Jianping
Published: December 2008

Recent studies suggest that adipose tissue hypoxia (ATH) may contribute to endocrine dysfunction in adipose tissue of obese mice. In this study, we examined hypoxia's effects on metabolism in adipocytes. We determined the dynamic relationship of ATH and adiposity in ob/ob mice. The interstitial oxygen pressure (Po2) was monitored in the epididymal fat pads for ATH. During weight gain from 39.5 to 55.5 g, Po2 declined from 34.8 to 20.1 mmHg, which are 40–60% lower than those in the lean mice. Insulin receptor-β (IRβ) and insulin receptor substrate-1 (IRS-1) were decreased in the adipose tissue of obese mice, and the alteration was observed in 3T3-L1 adipocytes after hypoxia (1% oxygen) treatment. Insulin-induced glucose uptake and Akt Ser473 phosphorylation was blocked by hypoxia in the adipocytes. This effect of hypoxia exhibited cell type specificity, as it was not observed in L6 myotubes and βTC6 cells. In response to hypoxia, free fatty acid (FFA) uptake was reduced and lipolysis was increased in 3T3-L1 adipocytes. The molecular mechanism of decreased fatty acid uptake may be related to inhibition of fatty acid transporters (FATP1 and CD36) and transcription factors (PPARγ and C/EBPα) by hypoxia. The hypoxia-induced lipolysis was observed in vivo after femoral arterial clamp. Necrosis and apoptosis were induced by hypoxia in 3T3-L1 adipocytes. These data suggest that ATH may promote FFA release and inhibit glucose uptake in adipocytes by inhibition of the insulin-signaling pathway and induction of cell death.
Effects of exercise on energy-regulating hormones and appetite in men and women
Authors: Hagobian Todd A. , Sharoff Carrie G. , Stephens Brooke R. , Wade George N. , Silva J. Enrique , Chipkin Stuart R. , Braun Barry
Published: December 2008

When previously sedentary men and women follow exercise training programs with ad libitum feeding, men lose body fat, but women do not. The purpose of this study was to evaluate whether this observation could be related to sex differences in the way energy-regulating hormones and appetite perception respond to exercise. Eighteen (9 men, 9 women) overweight/obese individuals completed four bouts of exercise with energy added to the baseline diet to maintain energy balance (BAL), and four bouts without energy added to induce energy deficit (DEF). Concentrations of acylated ghrelin, insulin, and leptin, as well as appetite ratings were measured in response to a meal after a no-exercise baseline and both exercise conditions. In men, acylated ghrelin area under the curve (AUC) was not different between conditions. In women, acylated ghrelin AUC was higher after DEF (+32%) and BAL (+25%), and the change from baseline was higher than men ( P < 0.05). In men, insulin AUC was reduced (−17%) after DEF ( P < 0.05), but not BAL. In women, insulin AUC was lower ( P < 0.05) after DEF (−28%) and BAL (−15%). Leptin concentrations were not different across conditions in either sex. In men, but not in women, appetite was inhibited after BAL relative to DEF. The results indicate that, in women, exercise altered energy-regulating hormones in a direction expected to stimulate energy intake, regardless of energy status. In men, the response to exercise was abolished when energy balance was maintained. The data are consistent with the paradigm that mechanisms to maintain body fat are more effective in women.
Gain Modulation of Neuronal Responses by Subtractive and Divisive Mechanisms of Inhibition
Authors: Ayaz Asli , Chance Frances S.
Published: December 2008

Gain modulation of neuronal responses is widely observed in the cerebral cortex of both anesthetized and behaving animals. Does this multiplicative effect on neuronal tuning curves require underlying multiplicative mechanisms of integration? We compare the effects of a divisive mechanism of inhibition (noisy excitatory and inhibitory synaptic inputs) with the effects of two subtractive mechanisms (shunting conductance and hyperpolarizing current) on the tuning curves of a model cortical neuron. We find that, although the effects of subtractive inhibition can appear nonlinear, they are accompanied by a change in response threshold and are best described as a vertical shift along the response axis. Increasing noisy synaptic activity divisively scales the model responses, reproducing a response-gain control effect. When mutual inhibition between subpopulations of local neurons is included, the model exhibits a gain modulation effect that is better described as input-gain control. We apply these findings to experimental data by examining how noisy synaptic input may underlie divisive surround suppression and attention-driven gain modulation of neuronal responses in the visual system.
Optokinetic and Vestibular Responsiveness in the Macaque Rostral Vestibular and Fastigial Nuclei
Authors: Bryan Ayanna S. , Angelaki Dora E.
Published: December 2008

We recorded from rostral vestibular (VN) and rostral fastigial nuclei (FN) neurons that did not respond to eye movements during three-dimensional (3D) vestibular and optokinetic stimulation (OKS). The majority of neurons in both areas (76 and 69% in VN and FN, respectively) responded during both rotational and translational motion. Preferred directions scattered throughout 3D space for translation but showed some preference for pitch/roll over yaw for rotation. VN/FN neurons were also tested during OKS while monkeys suppressed their optokinetic nystagmus by fixating a head-fixed target. Only a handful of cells (VN: 17%, FN: 6%) modulated during 0.5-Hz OKS suppression, but the number of responsive cells increased (VN: 40%, FN: 48%) during 0.02-Hz OKS. Preferred directions for rotation and OKS were not matched on individual neurons, and OKS gains were smaller than the respective gains during rotation. These results were generally similar for VN and FN neurons. We conclude that optokinetic-vestibular convergence might not be as prevalent as earlier studies have suggested.
Impact of Rhythmic Oral Activity on the Timing of Muscle Activation in the Swallow of the Decerebrate Pig
Authors: Thexton Allan J. , Crompton A. W. , Owerkowicz Tomasz , German Rebecca Z.
Published: December 2008

The pharyngeal swallow can be elicited as an isolated event but, in normal animals, it occurs within the context of rhythmic tongue and jaw movement (RTJM). The response includes activation of the multifunctional geniohyoid muscle, which can either protract the hyoid or assist jaw opening; in conscious nonprimate mammals, two bursts of geniohyoid EMG activity (GHemg) occur in swallow cycles at times consistent with these two actions. However, during experimentally elicited pharyngeal swallows, GHemg classically occurs at the same time as hyoglossus and mylohyoid activity (short latency response) but, when the swallow is elicited in the decerebrate in the absence of RTJM, GHemg occurs later in the swallow (long latency response). We tested the hypothesis that it was not influences from higher centers but a brain stem mechanism, associated with RTJM, which caused GHemg to occur earlier in the swallow. In 38 decerebrate piglets, RTJM occurred sporadically in seven animals. Before RTJM, GHemg had a long latency, but, during RTJM, swallow related GHemg occurred synchronously with activity in hyoglossus and mylohyoid, early in the swallow. Both early and late responses were present during the changeover period. During this changeover period, duplicate electrodes in the geniohyoid could individually detect either the early or the late burst in the same swallow. This suggested that two sets of geniohyoid task units existed that were potentially active in the swallow and that they were differentially facilitated or inhibited depending on the presence or absence of rhythmic activity originating in the brain stem.
Blood pressure and heart rate QTL in mice of the B6/D2 lineage: sex differences and environmental influences
Authors: Blizard David A. , Lionikas Arimantas , Vandenbergh David J. , Vasilopoulos Terrie , Gerhard Glenn S. , Griffith James W. , Klein Laura C. , Stout Joseph T. , Mack Holly A. , Lakoski Joan M. , Larsson Lars , Spicer Jeanne M. , Vogler George P. , McClearn Gerald E.
Published: December 2008

A quantitative trait locus (QTL) approach was used to define the genetic architecture underlying variation in systolic blood pressure (SBP) and heart rate (HR), measured indirectly on seven occasions by the tail cuff procedure. The tests were conducted in 395 F2adult mice (197 males, 198 females) derived from a cross of the C57BL/6J (B6) and DBA/2J (D2) strains and in 22 BXD recombinant-inbred (RI) strains. Interval mapping of F2data for the first 5 days of measurement nominated one statistically significant and one suggestive QTL for SBP on chromosomes (Chr) 4 and 14, respectively, and two statistically significant QTL for HR on Chr 1 (which was specific to female mice) and Chr 5. New suggestive QTL emerged for SBP on Chr 3 (female-specific) and 8 and for HR on Chr 11 for measurements recorded several weeks after mice had undergone stressful blood sampling procedures. The two statistically significant HR QTL were confirmed by analyses of BXD RI strain means. Male and female F2mice did not differ in SBP or HR but RI strain analyses showed pronounced strain-by-sex interactions and a negative genetic correlation between the two measures in both sexes. Evidence for a role for mitochondrial DNA was found for both HR and SBP. QTL for HR and SBP may differ in males and females and may be sensitive to different environmental contexts.
Biological Markers in Induced Sputum of Patients with Different Phenotypes of Chronic Airway Obstruction
Authors: Bartoli Maria Laura , Di Franco Antonella , Vagaggini Barbara , Bacci Elena , Cianchetti Silvana , Dente Federico Lorenzo , Tonelli Monica , Paggiaro Pier Luigi
Published: December 2008

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by a combination of 3 different disorders, namely chronic asthma, chronic bronchitis and pulmonary emphysema, sometimes simultaneously present in the same subject. Objectives: The aim of our study was to compare sputum inflammatory markers in patients with different phenotypes of chronic airway obstruction. Methods: Forty-five subjects (forced expiratory volume in 1 s/vital capacity, FEV1/VC: 58.8 ± 12.2%; FEV1: 49.8 ± 11.5% of predicted) were classified as chronic asthma (n = 10) or COPD patients (n = 35); the latter were further divided into patients with prevalent chronic bronchitis (n = 24) or prevalent pulmonary emphysema (n = 11) according to clinical history and functional evaluation, and underwent sputum induction and analysis of inflammatory cell and soluble mediators. Results: Patients with chronic asthma showed higher sputum eosinophil percentages and eosinophilic cationic protein levels, and lower neutrophil percentages and neutrophil elastase levels than COPD patients. Neutrophil chemotactic activity in sputum supernatant was higher than the pool of normal subjects both in chronic asthma and COPD patients. No difference in sputum cell composition and levels of soluble mediators was observed between patients with chronic bronchitis and patients with pulmonary emphysema. Conclusions: The pattern of airway inflammation in induced sputum of patients with chronic asthma is different from that of COPD patients with a similar FEV1. Among COPD patients, however, the pattern of airway inflammation shows no difference between chronic bronchitis and patients with pulmonary emphysema, suggesting that these two clinically and functionally distinct phenotypes share a common inflammatory pattern as detected by induced sputum.
Ischaemic stroke patients with heterozygous factor V Leiden present with multiple brain infarctions and widespread atherothrombotic disease
Authors: Helenius Johanna , Jakovljeviâ Dimitrije , Soinne Lauri , Syrjälä Martti , Kaste Markku , Lassila Riitta , Tatlisumak Turgut , Haapaniemi Elena
Published: December 2008

Factor V Leiden (FVL) mutation is a risk factor for venous and, to a degree, arterial thrombosis. It is unknown whether and how FVL affects the manifestations of ischaemic stroke (IS). We assessed the clinical, laboratory, radiological, and prognostic characteristics in an observational study with adult IS patients having FVL. We tested 860 patients with first-ever IS for FVL and found 48 FVL positive patients. Detailed clinical, laboratory, and radiological evaluation were compared with that of 144 (1:3) gender and age matched IS patients without FVL. All patients underwent a prognostic evaluation at an average of five years follow-up. Despite the relatively young age (mean 48.5 years, range 44–54 years) of the FVL positive IS patients, peripheral arterial occlusive disease (PAOD), coronary artery disease (CAD), and previous transient cerebrovascular event occurred more frequently compared with controls. Family history of cardiovascular disease (CVD) and multiple silent brain infarctions were revealed in half of the FVL positive patients, whereas these were seldom encountered among controls. Stroke severity, long-term recovery, and recurrence rates seemed similar irrespective of FVL status. Our findings indicate that the clinical profile of IS patients with FVL associated with wider manifestation of atherothrombosis, positive family history of arterial thrombosis, and presence of multiple silent infarctions on brain images.
No effect of lipid lowering on platelet activity in patients with coronary artery disease and type 2 diabetes or impaired glucose tolerance
Authors: Settergren Magnus , Böhm Felix , Pernow John , Hjemdahl Paul , Malmström Rickard
Published: December 2008

In addition to lowering cholesterol, statins may reduce platelet activity and exert beneficial non-lipid (pleiotropic) effects. We evaluated the effects of two different simvastatin based treatment regimens on platelet reactivity in patients with dysglycemia and coronary artery disease (CAD). Thirty-two patients with type 2 diabetes or impaired glucose tolerance and stable CAD received six weeks of double-blind treatment with simvastatin 80 mg daily (S80; n=16) or ezetimibe 10 mg and simvastatin 10 mg daily (E10/S10; n=16). Total and low-density lipoprotein (LDL) cholesterol, and high sensitivity C-reactive protein (CRP) decreased similarly in the two groups. LDL (mM) decreased from 3.2 ± 0.6 to 1.7 ± 0.7 with E10/S10 and from 3.0 ± 1.0 to 1.4 ± 0.5 with S80 treatment. Platelet function was evaluated by whole blood flow cytometry and turbidimetric aggregometry with agonist stimulation ex vivo before and after treatment. Neither treatment affected basal or adenosine diphosphate (ADP)- or thrombin-induced platelet P-selectin expression, or fibrinogen binding, or platelet-leukocyte aggregation. Similarly, neither treatment affected ADP-induced platelet aggregation. In conclusion, lipid lowering treatment with high dose simvastatin or low dose simvastatin plus ezetimibe did not exert any substantial inhibitory effects on the basal or agonist-stimulated activity of circulating platelets in patients with stable CAD and type 2 diabetes or impaired glucose tolerance.
Laboratory detection of the antiphospholipid syndrome via calibrated automated thrombography
Authors: Devreese Katrien , Peerlinck Kathelijne , Arnout Jef , Hoylaerts Marc
Published: December 2008

Lupus anticoagulants (LAC) consist of antiphospholipid antibodies, detected via their anticoagulant properties in vitro. Strong LAC relate to thromboembolic events, a hallmark of the anti-phospholipid syndrome. We have analyzed whether detection of this syndrome would benefit from thrombin generation measurements. Therefore, calibrated automated thrombography was done in normal plasma (n=30) and LAC patient plasma (n=48 non-anticoagulated, n=12 on oral anticoagulants), diluted 1:1 with a normal plasma pool. The anti-β2-glycoprotein I monoclonal antibody 23H9, with known LAC properties, delayed the lag time and reduced the peak height during thrombin generation induction in normal plasma dose-dependently (0–150 μg/ml). At variance, LAC patient 1:1 plasma mixtures manifested variable lag time prolongations and/or peak height reductions. Coupling these two most informative thrombin generation parameters in a peak height/lag time ratio, and upon normalization versus the normal plasma pool, this ratio distributed normally and was reduced in the plasma mixtures, for 59/60 known LAC plasmas. The normalized peak height/lag time ratio correlated well with the normalized dilute prothrombin time, diluted Russell’s viper venom time and silica clotting time, measured in 1:1 plasma mixtures (correlation coefficients 0.59–0.72). The anticoagulant effects of activated protein C (0–7.5 nM) or 23H9 (0–150 μg/ml), spiked in the 1:1 LAC plasma mixtures were reduced for the majority of patients, compatible with functional competition between patient LAC and activated protein C and LAC and 23H9, respectively. Hence, the normalized thrombin generation-derived peak height/lag time ratio identifies LAC in plasma with high sensitivity in a single assay, irrespective of the patient’s treatment with oral anticoagulants.
Prasugrel development – Claims and achievements
Authors: Shalito Inna , Kopyleva Olga , Serebruany Victor
Published: December 2008

The priority task to develop better and safer antiplatelet agents is difficult to overestimate. In fact, oral antiplatelet agents, such as aspirin in ISIS-2 study, and clopidogrel in COMMIT mega trial in moderate doses are among the very few classes of drugs, which lead to the absolute mortality reduction benefit in patients after acute vascular thrombotic events. Prasugrel is an experimental thienopyridine, and irreversible antagonist of ADP P2Y12 receptor leading to inhibition of platelet activation and aggregation. The recent TRITON trial, assessing head-to-head prasugrel versus standard of care clopidogrel, both on top of aspirin, reveals numerous controversies with regard to the trial design, definition of events, interpretation of the results, and suitability of the high maintenance prasugrel dose for chronic preventive human use. We critically review various aspects of prasugrel development, focusing on the discrepancies between claims and achievements. We conclude that the benefits of prasugrel are overestimated, and the risks, especially during chronic use are underestimated. Very careful maintenance-dose selection with the main focus on long-term safety profile for the new agents will become a key to success for the future oral antiplatelet drug development.
A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT)
Authors: Bauer Kenneth , Davidson Bruce , Fisher William , Gent Michael , Huo Michael , Sinha Uma , Gretler Daniel , Turpie Alexander ,   for the EXPERT Study Group
Published: December 2008

Betrixaban is an oral direct inhibitor of factor Xa (FXa) being developed for the prevention of venous thromboembolism (VTE). Its antithrombotic effects had not been previously tested in patients. This exploratory clinical trial in the US and Canada randomized 215 patients undergoing elective total knee replacement (TKR) in a 2:2:1 ratio to receive post-operative betrixaban 15 mg or 40 mg p.o. bid or enoxaparin 30 mg s.c. q12h, respectively, for 10–14 days. The betrixaban dosage was blinded, but enoxaparin was not. Primary efficacy outcome was the incidence of VTE, consisting of deep-vein thrombosis (DVT) on mandatory unilateral (operated leg) venography, symptomatic proximal DVT, or pulmonary embolism (PE) through Day 10–14. Safety outcomes included major and clinically significant non-major bleeds through 48 h after treatment. All efficacy and bleeding outcomes were adjudicated by a blinded independent central adjudication committee. Of 214 treated patients, 175 (82%) were evaluable for primary efficacy. VTE incidence was 14/70 (20%; 95% CI: 11, 31) for betrixaban 15 mg, 10/65 (15%; 95% CI: 8, 27) for betrixaban 40 mg, and 4/40 (10%; 95% CI: 3, 24) for enoxaparin. No bleeds were reported for betrixaban 15 mg, 2 (2.4%) clinically significant non-major bleeds with betrixaban 40 mg, and one (2.3%) major and two (4.6%) clinically significant non-major bleeds with enoxaparin. A dose- and concentration-dependent effect of betrixaban on inhibition of thrombin generation and anti-Xa levels was observed. Betrixaban demonstrated antithrombotic activity and appeared well tolerated in knee replacement patients at the doses studied.
Functional variability of platelet response to clopidogrel correlates with P2Y12 receptor occupancy
Authors: Sollier Claire Bal dit , Berge Natacha , Boval Bernadette , Hovsepian Lionel
Published: December 2008

Summary Interindividual variability of response to clopidogrel is currently a subject of much interest. We tested the hypothesis that functional variability in the platelet response to clopidogrel correlates with occupancy of the platelet P2Y12 receptor by clopidogrel active metabolite. Healthy subjects were screened after seven days’ treatment with clopidogrel 75 mg/day to select three clopidogrel-response groups (n=12/group), defined as ‘average’ (40–60% inhibition of platelet aggregation [IPA]), ‘low’ (<10% IPA) or ‘high’ (>80% IPA) responders. After a two- to six-week wash-out period, subjects were randomized (double-blind) to clopidogrel 75 mg/day (n=10/group) for 10 days, followed by clopidogrel 300 mg on day 11, or placebo (n=2/group). IPA induced by adenosine diphosphate (ADP), and P2Y12 receptor occupancy were measured repeatedly. The incidence of low responders was 3.7%, and low responses to clopidogrel were maintained during the randomized evaluation phase. Treatment with clopidogrel for 10 days induced a significant increase in P2Y12 receptor occupancy in each group of responders versus placebo; receptor affinity was unchanged. This reduction correlated with IPA response (r=0.54). The additional 300 mg dose of clopidogrel on top of 75 mg chronic treatment increased IPA and P2Y12 receptor occupancy in all groups, but relatively more in low responders. Variability in the response to clopidogrel appears to be linked to differences in P2Y12 receptor occupancy. An additional 300 mg dose of clopidogrel improves both IPA and P2Y12 receptor occupancy mostly in the subset of ‘low’ responders.
Prothrombin amino terminal region helps protect coagulation factor Va from proteolytic inactivation by activated protein C
Authors: Yegneswaran Subramanian , Nguyen Phuong , Griffin John , Gale Andrew
Published: December 2008

The hypothesis that prothrombin (FII) protects coagulation factor Va (FVa) from proteolytic inactivation by activated protein C (APC) was tested using purified proteins. FII dose-dependently protected FVa from APC proteolysis under conditions where competition of proteins for binding to negatively-charged phospholipid surface was not relevant (i.e. either at high phospholipid vesicle concentrations or using soluble dicaproylphosphatidylserine at levels below its critical micellar concentration). Cleavages in FVa at both Arg506 and Arg306 by APC were inhibited by FII. FII did not alter the amidolytic activity of APC towards chromogenic oligopeptide substrates or inhibit FVIIIa inactivation by APC, implying that the FII-mediated protection of FVa from APC proteolysis was due to the ability of FII to inhibit protein-protein interactions between FVa and APC. FII also protected FVa from inactivation by Gla-domainless APC, ruling out a role for the APC Gla domain for these observations. To identify domains of FII responsible for the observed phenomenon, various forms or fragments of FII were employed. Biotin-PheProArg-CMK-inhibited meizothrombin and fII-fragment 12 protected FVa from proteolysis by APC. In contrast, no significant protection of FVa from APC cleavage was observed for Gladomainless-FII, prethrombin-1, prethrombin-2, FII fragment 1 or active site inhibited-thrombin (DEGR-thrombin). Overall, these data demonstrate that the Gla domain of FII linked to kringle 1 and 2 is necessary for the ability of FII to protect FVa from APC cleavage and support the general concept that assembly of the FII activation complex (FXaFVaFIIlipid surface) protects FVa from APC inactivation so that the procoagulant, thrombin generating pathway can act unhindered by APC. Only following FII activation and dissociation of the FII Gla domain fragments from the FII-ase complex, can APC inactivate FVa and down-regulate thrombin generation.
Sex and Age Dimorphism of Myocardial Gene Expression in Nonischemic Human Heart Failure
Authors: Fermin David R. , Barac Ana , Lee Sangjin , Polster Sean P. , Hannenhalli Sridhar , Bergemann Tracy L. , Grindle Suzanne , Dyke David B. , Pagani Francis , Miller Leslie W. , Tan Sarah , dos Remedios Cris , Cappola Thomas P. , Margulies Kenneth B. , Hall Jennifer L.
Published: December 2008

Background—

We report the first comprehensive analysis of gene expression differences by sex and age in left ventricular samples from 102 patients with dilated cardiomyopathy.

Methods and Results—

Gene expression data (HG-U133A gene chip, Affymetrix) were analyzed from 30 females and 72 males from 3 separate centers. More than 1800 genes displayed sexual dimorphism in the heart (adjusted
P
value <0.05). A significant number of these genes were highly represented in gene ontology pathways involved in ion transport and G-protein-coupled receptor signaling. Localization of these genes revealed enrichment on both the sex chromosomes as well as chromosomes 3, 4, and 14. The second goal of this study was to determine the effect of age on gene expression. Within the female cohort, >140 genes were differentially expressed in the <55 years age group compared with the >55 years age group. These genes were highly represented in gene ontology pathways involved in DNA damage. In contrast, zero genes in the male cohort <55 years met statistical significance when compared with the >55 years age group.

Conclusions—

Gene expression in dilated cardiomyopathy displayed evidence of sexual dimorphism similar to other somatic tissues and age dimorphism within the female cohort.
Constructing Tolerance
Authors: Crepaz Markus M. L. , Damron Regan
Published: December 2008

Over the past 30 years, the hitherto rather homogeneous welfare states in Europe have been experiencing a dramatic influx of immigrants, making them much more diverse. The central purpose of the early development of the welfare state was twofold: to bridge class divisions and to mollify ethnic divisions in the vast multiethnic empires of 19th-century Germany and Austria. This research examines the impact of the programmatic and expenditure dimensions of the welfare state on attitudes of natives across modern publics, theorizing that nativist resentment and welfare chauvinism should be reduced in more comprehensive welfare systems. Individual, aggregate, and multilevel analyses reveal that the more comprehensive the welfare state is, the more tolerant natives are of immigrants, indicating that contemporary welfare states have a similar capacity to bridge ethnic divisions as their 19th-century incarnations.
Supporters or Challengers?
Authors: Boulding Carew E. , Gibson Clark C.
Published: December 2008

How do nongovernmental organizations (NGOs) affect local politics in developing democracies? Specifically, do NGOs have systematic effects on the fortunes of incumbent political parties in local elections? Existing work predicts starkly contradictory political effects: Some scholars claim that NGOs most likely help incumbents by providing services for which politicians can claim credit, whereas others believe that NGOs most likely hurt incumbents by facilitating political opposition. The authors argue that both of these effects are possible, depending on the size of a jurisdiction's population. In smaller populations, the authors hypothesize that NGOs facilitate collective action and decrease the ability of an incumbent to claim credit for projects; larger jurisdictions water down the effect of NGOs on collective action and permit incumbents' credit claiming. Strong support is found for hypotheses, using electoral, sociodemographic, and NGO data for all of 314 municipalities in Bolivia.
The Cross-National Market in Human Beings
Authors: Pennington Julia R. , Ball A. Dwayne , Hampton Ronald D. , Soulakova Julia N.
Published: December 2008

Human trafficking, as defined here, is moving human beings across borders for the purpose of enslaving them. Human trafficking may be in the sex trade, forced labor or service, extraction of body parts, or other forms of exploited labor or debt bondage. The market is believed to be extensive, with its own distribution channels, pricing systems, and other market functions. The purposes of this article are to present an understanding of cross-border human trafficking as a marketing system, to explicate the societal effects of that system, and to show how the extent of cross-border trafficking may be estimated, using as an example several countries where it is believed to be a substantial problem. Additionally, we seek to show that cross-border human trafficking may be a much more serious problem than what is visible to governments.
Children's Relative Influence in Family Decision Making in Urban China
Authors: Flurry Laura A. , Veeck Ann
Published: December 2008

With its strict population policy and unprecedented economic growth, urban China offers a unique environment in which to examine how radical changes in state policy can affect family consumption behavior. The objectives of this study are to examine children's influence in purchase decision making and to explore factors thought to explain variation observed in children's influence. A survey of 819 urban Chinese families was conducted to directly compare the influence generated among three generations of family members in nuclear and extended family households from both the parents' and the children's perspectives. The analysis found that, while the influence of children varied by product category and by the character of the purchase decision, the children's influence on family decision making was less dominant than would be suggested by the popular image of China's only children.
Symbolic Capital in a Virtual Heterosexual Market
Authors: Herring Susan C. , Zelenkauskaite Asta
Published: December 2008

This study analyzes gender variation in nonstandard typography—specifically, abbreviations and insertions—in mobile phone text messages (SMS) posted to a public Italian interactive television (iTV) program. All broadcast SMS were collected for a period of 2 days from the Web archive for the iTV program, and the frequency and distribution of abbreviations and insertions, as well as overall message lengths, were analyzed according to sender gender. The results reveal that females posted more and longer SMS and followed more, and more varied, nonstandard typographic practices, contrary to previous gender-related findings in the sociolinguistics and computer-mediated communication literatures. A theoretically grounded explanation for these findings is developed in terms of the localized norms of a heterosexual market—and an implicit dating market—in Italian iTV SMS.
A Variant Form of Mucolipidosis IV: Report on 4 Patients From the Indian Subcontinent
Authors: Parayil Sankaran Bindu  , Gayathri Narayanappa , Yasha Thagadur C. , Kovoor Jerry M. E. , Subasree Ramakrishnan , Rao Sudheendra , Panda Samhita , Pramod Kumar Pal
Published: December 2008

The clinical manifestations and histopathologic and neuroimaging findings in 4 Indian patients with a variant form of mucolipidosis IV are described. The presenting symptoms were psychomotor delay, spastic paraplegia, and mild mental retardation. One patient also had visual deterioration due to optic atrophy. None had corneal or retinal abnormalities. Magnetic resonance imaging in 3 patients showed a uniformly thin corpus callosum in all patients and white matter changes in 2 patients. Electron microscopic examination of skin biopsy specimens revealed storage bodies characteristic of mucolipidosis IV. These patients differ from previously described patients with this disorder in the absence of corneal abnormalities and in their presentation with spastic paraplegia during the second decade of life. Correct diagnosis is needed for genetic counseling, prognostication. and reduction of additional familial burden of this rare disease.
Proposal for a Trigonometric Method to Evaluate the Abduction Angle of the Lower Limbs in Neonates
Authors: Lima Thaís , Alves Cyntia , Funayama Carolina A. R.
Published: December 2008

It is difficult to precisely measure articular arc movement in newborns using a goniometer. This article proposes an objective method based on trigonometry for the evaluation of lower limb abduction. With the newborn aligned in the dorsal decubitus position, 2 points are marked at the level of the medial malleolus, one on the sagittal line and the other at the end of the abduction. Using the right-sided line between these 2 points and a line from the medial malleolus to the reference point at the anterior superior iliac spine or umbilical scar, an isosceles triangle is drawn, and half of the inferential abduction angle is obtained by calculating the sine. Twenty healthy full-term newborns comprise the study cohort. Intersubject and intrasubject variability among the abduction angle values (mean [SD], 37° [4]°) is low. This method is advantageous because the measurement is precise and because the sine can be used without approximation.
Neurocutaneous Melanosis: Report of Three Cases and Up-to-date Review
Authors: Pavlidou Efterpi , Hagel Christian , Papavasilliou Antigoni , Giouroukos Sotiris , Panteliadis Christos
Published: December 2008

Neurocutaneous melanosis is a rare noninherited embryonic neuroectodermal dysplasia, which is observed sporadically and never affects the entire integument. The hallmark of neurocutaneous melanosis in the neonatal period is the presence of a large bilateral hairy dark nevus with satellite nevi over the trunk and neck. The diagnosis should be considered in neonates with large pigmented nevi and in those with more than 3 hairy dark nevi regardless of their size. Neonates with neurocutaneous melanosis are at risk of developing neurological problems. The most common neurological complications are hydrocephalus, seizures, cranial nerve dysfunction, and signs of spinal cord and root involvement. The authors report 3 cases of histologically confirmed neurocutaneous melanosis and describe the course of neurological symptoms and clinical findings including cognitive tests and neuroimaging. The case reports are complemented by an up-to date review on this clinical entity.
Prevalence of the Fragile X Syndrome Among Estonian Mentally Retarded and the Entire Children's Population
Authors: Puusepp Helen , Kahre Tiina , Sibul Hiljar , Soo Viljo , Lind Ilona , Raukas Elve , Õunap Katrin
Published: December 2008

The aim of this study is to establish the prevalence of fragile X syndrome among Estonian mentally retarded and also among the entire children's population born during the years 1984-2005. The study group consisted of 516 patients (448 boys and 68 girls) who were screened for full mutations in the FMR1 gene during the period 1997-2006. Fourteen boys (2.7%) were found with full mutations of the total mentally retarded individuals tested (3.1% of mentally retarded boys); the full mutation was not detected among girls. The live-birth prevalence of full mutation among boys was 1:13 947. The overall live-birth prevalence of fragile X syndrome was 1:27 115. It was found that the prevalence of fragile X syndrome among mentally retarded individuals in Estonia was the same as in previous studies, but the live-birth prevalence of fragile X syndrome among boys was significantly lower.
Neurologic Sequelae of Neonatal Hypoglycemia in Kayseri, Turkey
Authors: Per Hüseyin , Kumandaş Sefer , Çoskun Abdulhakim , Gümüş Hakan , Öztop Didem
Published: December 2008

Contrary to belief, neonatal hypoglycemia is relatively common and can cause more severe neurological sequelae than is currently believed. Prevention of hypoglycemic brain damage by hindering prolonged and profound neonatal hypoglycemia might contribute to psychomotor development. At Erciyes University, between December 1996 and 2005, of the patients who applied to Paediatric Neurology Department, 60 cases with a history of neonatal hypoglycemia were included in the study. The magnetic resonance imaging (MRI) scans and clinical records of all patients were reviewed retrospectively. It was noted that the sequelae with glucose levels of 0 0 to 40 were more serious and intense. The same results were also observed in cranial MRI evaluation. In conclusion, intractable epilepsy, mental motor retardation, cerebral palsy, and visual disturbance were found to be the most common and severe conditions affecting sufferers of neonatal hypoglycemia. In the first 3 days of life, the close monitoring of patients at risk is critical, and hospitalization of severe cases should be considered.
Pituitary Carcinoma Presenting with Multiple Metastases: Case Report
Authors: Guzel Aslan , Tatli Mehmet , Senturk Senem , Guzel Ebru , Cayli Suleyman Rustu , Sav Aydin
Published: December 2008

Pituitary carcinoma, an uncommon tumor in adults, generally presents with craniospinal and systemic metastases. We report a case of pituitary carcinoma with multiple craniospinal metastases in a child. A 9-year-old girl, who had had a ventriculoperitoneal shunt operation 3 years ago, presented with complaints of progressive visual disturbance, headache, speech difficulty, and gait disturbance for the past 2 months. Neurological examination revealed papilledema, visual loss, and dysarthria. Cranial magnetic resonance imaging revealed a large contrast-enhanced tumor in the left frontal region together with multiple lesions in the sellar-parasellar region and posterior fossa. Multiple intraspinal contrast-enhanced metastatic lesions were also seen. Histopathological and immunohistochemical examination of the excised left frontal mass revealed pituitary carcinoma. Treatment with cyclic temozolomide was started after the operation, but the patient died after 2 months without response to medical therapy. This is the first pediatric case, to the authors' knowledge, of a pituitary carcinoma with widespread intracranial and intraspinal metastases.
Cortical Dysplasia and Obstetrical Brachial Plexus Palsy
Authors: Alfonso Israel , Alfonso Daniel T. , Price Andrew E. , Grossman John A. I.
Published: December 2008

We report 2 patients with obstetrical brachial plexus palsy, ipsilateral leg weakness, and contralateral motor cortical dysplasia. To our knowledge, this is the first description of such an association. In both cases, the diagnosis of obstetrical brachial plexus palsy was established clinically shortly after birth and later confirmed neurophysiologically. Motor cortex dysplasia was diagnosed by magnetic resonance imaging (MRI). The association of obstetrical brachial plexus palsy and contralateral motor cortex dysplasia, a condition known to produce congenital hemiparesis, raises the possibility that the cortical dysplasia was a predisposing factor for obstetrical brachial plexus palsy in these cases.
Brainstem Ganglioglioma
Authors: Mpairamidis Evriviadis , Alexiou George A. , Stefanaki Kalliopi , Sfakianos George , Prodromou Neofytos
Published: December 2008

Gangliogliomas are usually benign slow-growing neoplasms, seen mainly in the first 3 decades of life and are prevalently located supratentorial, mostly in the temporal and frontal lobe. The authors present a rare case of a brainstem ganglioglioma in an 11-year-old boy who was referred to their hospital complaining of episodes of blurry vision, loss of memory, gait disturbances, and morning headache with vomiting, lasting for over a month. Computed tomography and magnetic resonance imaging scans revealed a mass on the dorsal surface of the brainstem, compressing the brainstem and producing secondary obstructive hydrocephalus. The patient was operated upon, and the histopathology revealed the presence of a ganglioglioma grade II (World Health Organization classification). On follow-up examination after 1 year, a minor gait imbalance was the only finding. A total resection should be always attempted, where possible in brainstem gangliogliomas. Close follow-up is mandatory, and re-resection or radiotherapy should be considered in case of tumor recurrence.
FIRST: A Practical Approach to the Causes and Management of Febrile Seizures
Authors: Mohammad Reza Mohebbi  , Holden Kenton R. , Butler Ian J.
Published: December 2008

During almost 4 decades of clinical practice of pediatrics and pediatric neurology, the senior authors have rarely made a formal presentation on the topic of “febrile seizures.” In any large pediatric teaching hospital, questions regarding the diagnosis and management of febrile seizures are raised by medical students, pediatric residents, and adult and pediatric neurology residents. The acronym FIRST was developed as a teaching tool to present a simple and pragmatic clinical approach to children presenting with a single seizure or cluster of seizures in 1 day associated with a febrile illness before, during, or after the seizure event(s). FIRST refers to Febrile, Illness, Related, Seizure(s) and Template, with the latter representing an outline of the basic cause(s). The authors propose the use of the Table as a tool to help determine the underlying etiology of febrile seizures because this is the major factor affecting the choice of treatment.
Atypical Teratoid/Rhabdoid Tumor of the Spine in a 4-Year-Old Girl
Authors: Tinsa Faten , Jallouli Manel , Douira Wiem , Boubaker Adnene , Kchir Nidhameddine , Ben Hassine Dalel , Boussetta Khadija , Bousnina Souad
Published: December 2008

Primary spinal atypical teratoid/rhabdoid tumor is extremely rare. The authors present a case of atypical teratoid/rhabdoid tumor occurring in a 4-year-old girl. Magnetic resonance imaging The authors showed an intramedullary mass extending from the bulbomedullary junction to T1 with leptomeningeal dissemination. The patient died 2 weeks after diagnosis.
Serum Anti-Myelin—Associated Glycoprotein Antibodies in Egyptian Autistic Children
Authors: Gehan Ahmed Mostafa  , Awad El-Sayed Zeinab , Mohamed Abd El-Aziz Manal , Farouk El-Sayed Mohamed
Published: December 2008

Autoimmunity to brain could play an etiopathogenic role in a subgroup of autistic patients. The frequency of serum anti-myelin—associated glycoprotein antibodies, as an index for autoimmunity to brain, and their relation to family history of autoimmunity were investigated in 32 autistic and 32 healthy matched children. Autistic children had significantly higher serum anti-myelin—associated glycoprotein antibodies than healthy children (2100 [1995] and 1138 [87.5] Buhlmann titre unit, P < .001). Anti-myelin—associated glycoprotein positivity was elicited in 62.5% of autistic children. Family history of autoimmunity in autistic children (50%) was significantly higher than controls (9.4%). Anti-myelin—associated glycoprotein serum levels were significantly higher in autistic children with than those without such history ( P < .05). In conclusion, autism could be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further studies are warranted to shed light on the etiopathogenic role of anti-myelin—associated glycoprotein antibodies and the role of immunotherapy in autism.
A Novel GLRA1 Mutation Associated with An Atypical Hyperekplexia Phenotype
Authors: Gregory Mary L. , Guzauskas Greg F. , Edgar Terence S. , Clarkson Kate B. , Srivastava Anand K. , Holden Kenton R.
Published: December 2008

Hyperekplexia (MIM #149400) is a rare neurological disorder characterized by an exaggerated startle response, infantile hypertonia and hyperreflexia without spasticity, a hesitant gait that usually improves by 3 years of age, and nocturnal myoclonus. Familial hyperekplexia is usually autosomal dominant resulting from mutations in the inhibitory glycine receptor subunit alpha 1 ( GLRA1) gene on chromosome 5q. We identified a 3-generation family with progressively severe phenotypes of hyperekplexia. All affected family members were found to be heterozygous for a novel arginine271proline mutation in GLRA1. Long-term follow-up of the affected members of the third generation, now aged 6 and 7 years, reveals enhanced startle responses and persistent hypertonia of the extremities without clonus or a catch, tight heel cords and abnormal toe-walking gait, and plantar flexor reflexes. The 7-year-old child recently reponded well to a benzodiazepine. Future studies are warranted to examine whether this new missense mutation is solely responsible for this atypical phenotype.
Role of Technological Innovations for Competitiveness and Entrepreneurship
Authors: Tirupati Devanath
Published: December 2008

In recent years, technological innovations have emerged as an important source of competitive strength, and firms in many industries have achieved success by competing through innovation. Taking the business perspective of a small enterprise with focused technological capabilities, we examine here the role of innovations for competitiveness. We present a framework that is useful for classifying and characterising different types of technological innovations and describe their impact on firms’ capabilities. The narrow focus of small enterprises enables them to develop into niche players with specialised capabilities; however, it often prevents them from offering complete products or services. In this context, we identify and discuss the needs of such enterprises for survival and growth and describe two alternative models of support to improve the success rate.