bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil CO2flux and photoautotrophic community composition in high‐elevation, ‘barren’ soil
Authors: Freeman Kristen R. , Pescador Monte Y. , Reed Sasha C. , Costello Elizabeth K. , Robeson Michael S. , Schmidt Steven K.
Published: February 2009

Soil‐dominated ecosystems, with little or no plant cover (i.e. deserts, polar regions, high‐elevation areas and zones of glacial retreat), are often described as ‘barren’, despite their potential to host photoautotrophic microbial communities. In high‐elevation, subnival zone soil (i.e. elevations higher than the zone of continuous vegetation), the structure and function of these photoautotrophic microbial communities remains essentially unknown. We measured soil CO2flux at three sites (above 3600 m) and used molecular techniques to determine the composition and distribution of soil photoautotrophs in the Colorado Front Range. Soil CO2flux data from 2002 and 2007 indicate that light‐driven CO2uptake occurred on most dates. A diverse community ofCyanobacteria,Chloroflexiand eukaryotic algae was present in the top 2 cm of the soil, whereas these clades were nearly absent in deeper soils (2–4 cm). Cyanobacterial communities were composed of lineages most closely related toMicrocoleus vaginatusandPhormidium murrayi, eukaryotic photoautotrophs were dominated by green algae, and three novel clades ofChloroflexiwere also abundant in the surface soil. During the light hours of the 2007 snow‐free measurement period, CO2uptake was conservatively estimated to be 23.7 g C m−2 season−1. Our study reveals that photoautotrophic microbial communities play an important role in the biogeochemical cycling of subnival zone soil.
Occurrence of phosphate acquisition genes in Prochlorococcus cells from different ocean regions
Authors: Martiny Adam C. , Huang Ying , Li Weizhong
Published: February 2009

The cyanobacterium Prochlorococcus is the numerically dominant phototroph in oligotrophic parts of the oceans. Recently, it was shown that the distribution of phosphate acquisition genes did not match the 16S rRNA phylogeny among isolates from this group but rather appeared related to phosphate availability where the strains had been isolated. To further understand adaptation to phosphate limitation in Prochlorococcus, the distribution of phosphate acquisition genes was investigated in different ocean regions and related to local ortho‐phosphate concentration. In regions characterized by less than 0.1 μM phosphate, most Prochlorococcus cells contain genes involved in phosphate uptake, regulation and utilization of organic phosphates. In contrast, most of these genes are absent in regions with more than 0.1 μM phosphate with the exception of genes involved in transport of phosphate (phoE and pstABCS) and three genes of unknown function. This pattern of phosphate acquisition genes showed no significant correspondence to the distribution of rRNA phylotypes. In addition, it was demonstrated that several genes in a separate genomic island were commonly present in low‐P sites while absent in high‐P sites. Overall, this study further demonstrates a linkage between environmental conditions in the ocean and genome content of Prochlorococcus.
Bladder inhibition or excitation by electrical perianal stimulation in a cat model of chronic spinal cord injury
Authors: Wang Jicheng , Liu Hailong , Shen Bing , Roppolo James R. , De Groat William C. , Tai Changfeng
Published: February 2009

OBJECTIVE

To test the hypothesis that perianal electrical stimulation (PES) in chronic spinal cord‐injured (SCI) cats could induce frequency‐dependent inhibitory or excitatory reflex bladder responses.

MATERIALS AND METHODS

The experiments were conducted ≥4–5 weeks after spinal cord transection at the T9‐T10 level. PES was applied via a pair of hook electrodes to the perianal skin area in three awake female cats with chronic SCI. A double‐lumen balloon catheter was inserted through the urethra into the bladder to monitor bladder pressure and infuse saline (2–4 mL/min).

RESULTS

Under isovolumetric conditions PES at 3–10 Hz significantly inhibited large‐amplitude reflex bladder activity induced by bladder distension above the micturition volume threshold. However, PES at 20–50 Hz induced large‐amplitude bladder contractions when the bladder volume was below the micturition volume threshold. Inhibitory PES (7 Hz) significantly increased the mean (sem) bladder capacity by 40 (10)% when it was applied continuously during cystometrography. The optimum excitatory PES (30 Hz) induced large‐amplitude (>25 cmH2O), long‐duration (>20 s) bladder contractions at a wide range of bladder volumes (10–90% of bladder capacity).

CONCLUSIONS

This study showed that activation of pudendal afferent fibres by PES could induce frequency‐dependent reflex bladder responses in awake cats with chronic SCI, indicating that a possible noninvasive treatment based on PES could be developed to restore both continence and micturition function for patients with SCI.
Association between plasma osteoprotegerin concentrations and urinary albumin excretion in Type 2 diabetes
Authors: Xiang G. D. , Pu J. H. , Zhao L. S. , Sun H. L. , Hou J. , Yue L.
Published: February 2009

Aims  Osteoprotegerin (OPG) is a recently identified inhibitor of bone resorption. Recent studies indicate that OPG is also associated with endothelial dysfunction in Type 2 diabetes. The aim was to investigate the relationship between plasma OPG levels and urinary albumin excretion (UAE) in Type 2 diabetic patients.

Methods  This study included 154 newly diagnosed Type 2 diabetic patients and 46 healthy subjects. Plasma OPG and 24‐h UAE were measured. High‐resolution ultrasound was used to measure flow‐mediated (endothelium‐dependent arterial) dilation (FMD).

Results  Compared with the normoalbuminuric subgroup, OPG levels in the microalbuminuric subgroup were significantly higher, and OPG levels in macroalbuminuria subgroup were significantly higher than those in the normoalbuminuria and albuminuria subgroups. Multiple regression analysis showed that only FMD (r = −0.26), C‐reactive protein (r = 0.23), fasting blood glucose (r = 0.25), 2‐h blood glucose (r = 0.21), HbA1c (r = 0.28), UAE (r = 0.27) and retinopathy (r = 0.27) were significant factors associated with OPG. Pearson’s correlation analyses showed a positive correlation between OPG and logUAE (r = 0.440) and negative correlations between OPG and FMD (r = −0.284), and between FMD and logUAE (r = −0.602).

Conclusions  Plasma OPG levels are significantly associated with UAE in Type 2 diabetic patients.
Decreasing concentration of interstitial glucose in REM sleep in subjects with normal glucose tolerance
Authors: Bialasiewicz P. , Pawlowski M. , Nowak D. , Loba J. , Czupryniak L.
Published: February 2009

Aims  Sleep is divided into two major stages, non‐rapid eye movement (NREM) and rapid eye movement (REM), which are distinct in various neuroendocrine respects. NREM/REM cycles influence insulin and glucagon secretion; however, glucose concentrations in REM compared with NREM have not been directly explored. The aim was to investigate the differences in glucose concentrations in interstitial fluid (IGC) between NREM/REM cycles using a continuous glucose monitoring system (CGMS).

Methods  Thirteen subjects were eligible for analysis out of the 28 enrolled. All underwent standard polysomnography for the assessment of sleep stages and the exclusion of sleep apnoea syndrome with CGMS and subsequent morning oral glucose tolerance test (exclusion of glucose intolerance or diabetes).

Results  The IGC in REM fell in 12 out of the 13 subjects, whereas the IGC in NREM increased in eight out of the 13 subjects. Therefore, the mean change of IGC differed in direction between sleep stages: −0.028 (−0.045 to −0.011) for REM vs. 0.005 (−0.012 to 0.017) for NREM [median (QR), P = 0.007, n = 13], with the mean difference of 0.038 mmol/l × 5 min−1 (95% confidence interval 0.012, 0.064). The mean glucose concentration in REM sleep was lower than in NREM: 4.29 ± 1.00 vs. 4.53 ± 0.90 mmol/l (mean ± sd, P = 0.003, n = 13).

Conclusions  The decrease in IGC in REM compared with NREM sleep, with lower absolute values, may arise from different physiological events observed in these sleep stages. The REM‐related decline in glucose concentrations may be a risk factor for nighttime hypoglycaemia.
Factors determining normalization of glucose intolerance in middle‐aged Swedish men and women: a 8–10‐year follow‐up
Authors: Alvarsson M. , Hilding A. , Östenson C.‐G.
Published: February 2009

Aims  To examine factors in middle‐aged Swedish men and women predicting the conversion from a state of abnormal glucose regulation to normal glucose tolerance (NGT) after 8–10 years.

Methods  At baseline 3128 men and 4821 women, aged 35–56 years, without previously diagnosed diabetes underwent an oral glucose tolerance test and completed a questionnaire. At follow‐up, 2383 men and 3329 women were re‐examined. The study group consisted of 156 men and 124 women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both at baseline.

Results  The rate of reversal to NGT from IFG or IGT was similar regardless of gender. In participants having IFG or IGT, reversal to NGT was predicted by low fasting and 2‐h insulin, homeostasis model assessment of insulin resistance and of pancreatic β cell function, body mass index and waist circumference without differences between gender and baseline glucose tolerance group. Low 2‐h glucose, however, predicted reversal to NGT in men with IFG at baseline, but not in men with IGT at baseline, or in women with either IFG or IGT at baseline. Men reverting to NGT had higher coffee consumption and women had higher baseline leisure‐time physical activity. In multiple logistic regression, including all participants, low fasting and 2‐h glucose remained independent predictors of reverting to NGT.

Conclusions  Factors predicting reversal to NGT were measures correlated with low insulin resistance, but also lower insulin secretion, perhaps indicating a lower pancreatic β cell workload in those who reverted. In men, but not in women, low 2‐h glucose was of predictive value.
Metabolic syndrome and short‐term heart rate variability in young adults
Authors: Koskinen T. , Kähönen M. , Jula A. , Mattsson N. , Laitinen T. , Keltikangas‐Järvinen L. , Viikari J. , Välimäki I. , Rönnemaa T. , Raitakari O. T.
Published: February 2009

Aims  Heart rate variability (HRV) can be used to estimate autonomic nervous control of the cardiovascular system. In middle‐aged subjects, the metabolic syndrome (MetS) is associated with lower HRV. We hypothesized that alterations in autonomic balance are already present in young adults with the MetS, and analysed the association of short‐term HRV with the MetS (using the National Cholesterol Education Program definition), in 1889 subjects aged 24–39 years.

Methods  Short‐term (3 min) HRV analysis included high‐frequency (HF), low‐frequency (LF) and total (TP) spectral components of HRV and LF/HF ratio.

Results  The presence of the MetS was associated with lower HF, LF and TP in men and women, and with higher LF/HF ratio in women. In men, waist circumference was the strongest individual MetS component that associated with HRV. After adjustments for age and heart rate, MetS was associated with lower HF and higher LF/HF ratio in women, but only with a lower TP in men (all P < 0.05).

Conclusions  MetS is associated with lower HRV in young adults. The individual components of MetS are differentially associated with HRV in men and in women. Our results are consistent with lower vagal activity and a possible increase in sympathetic predominance in women with the MetS. This sex difference in vagal activity and sympathovagal balance may partly explain the greater increase in cardiovascular risk associated with MetS in women than in men.
The prevalence of Type 2 diabetes and its associated health problems in a community‐dwelling elderly population
Authors: Hewitt J. , Smeeth L. , Bulpitt C. J. , Fletcher A. E.
Published: February 2009

Aims  Prevalence estimates of Type 2 diabetes and its associated health problems in elderly populations are rare, especially in the very elderly.

Methods  A sample of 15 095 community‐dwelling older people aged ≥ 75 years were assessed. Type 2 diabetes and associated health problems were identified using self‐reporting, general practitioner records, drug histories, and blood and urine measurements.

Results  There were 1177 people identified as having Type 2 diabetes mellitus, giving an overall prevalence of 7.8% (95% confidence interval 7.1, 8.5), 9.4% (8.4, 10.5) for men and 6.8% (6.1, 7.6) for women. The age, sex and smoking adjusted odds ratios for various health problems, comparing people with and without diabetes were: low vision 1.6 (1.3, 1.9), proteinuria 1.7 (1.4, 2.1), chronic kidney disease stage 4 or 5 1.5 (1.0, 2.1), angina 1.3 (1.1, 1.6), myocardial infarction 1.5 (1.2, 1.8), cerebrovascular event 2.0 (1.8, 2.1) and foot ulceration 1.7 (1.2, 2.4).

Conclusions  The prevalence of Type 2 diabetes is not high in community‐dwelling older people, but diabetes was a contributory factor to a number of health problems.
Predictors of future fasting and 2‐h post‐OGTT plasma glucose levels in middle‐aged men and women—the Inter99 study
Authors: Færch K. , Vaag A. , Witte D. R. , Jørgensen T. , Pedersen O. , Borch‐Johnsen K.
Published: February 2009

Aims  Screening and prevention strategies for Type 2 diabetes require insight into the aetiological and potentially different risk factors leading to early impairments of fasting plasma glucose (FPG) and 2‐h post‐load plasma glucose (2hPG) levels. We studied whether risk factors predicting subtle elevations of FPG levels were different from those predicting elevations of 2hPG levels in men and women.

Methods  We used baseline and 5‐year follow‐up data from middle‐aged men and women with normal glucose tolerance (NGT) at baseline in the Danish population‐based Inter99 study (n = 3164). Anthropometric and non‐anthropometric baseline predictors of the 5‐year FPG and 2hPG levels were estimated in linear regression models stratified by gender.

Results  In men, but not in women, smoking and family history of diabetes predicted increased FPG levels, whereas high physical activity predicted a decline in 2hPG levels. Among the anthropometric variables, large waist circumference was the strongest predictor of increased FPG levels in men, whereas high body mass index (BMI) was the strongest predictor of increased FPG levels in women. In both men and women, BMI and waist circumference were equally strong in predicting 2hPG levels. Furthermore, short height predicted increased 2hPG levels in men, and short height and low hip circumference predicted increased 2hPG levels in women.

Conclusions  Risk factors that predict future FPG levels are different from those predicting future 2hPG levels. Furthermore, different risk factors predict glycaemic levels in men compared with women. These findings indicate that different aetiological pathways may lead to Type 2 diabetes in men and women.
Altered respiratory function is associated with increased metabolic risk, independently of adiposity, fitness and physical activity
Authors: Steele R. M. , Finucane F. M. , Simmons R. K. , Griffin S. J. , Wareham N. J. , Ekelund U. ,   On behalf of the ProActive research team
Published: February 2009

Aims  Reduced lung function is associated with an adverse metabolic risk profile, even after adjusting for body fatness. However, previous observations may have been confounded by aerobic fitness and physical activity. This study aimed to examine the association between lung function and both metabolic risk and insulin resistance in a cohort of White British adults with a family history of Type 2 diabetes, and to explore the extent to which these associations are independent of body fatness, aerobic fitness (VO2max) and objectively measured physical activity.

Methods  Adults (n = 320, mean age 40.4 ± 6.0 years) underwent measurement of physical activity energy expenditure (PAEE), spirometry [forced expiratory volume in 1 s (FEV1)] and forced vital capacity (FVC), aerobic fitness (predicted VO2max), and anthropometric and metabolic status at baseline and again after 1 year (n = 257) in the ProActive trial. Clustered metabolic risk was calculated by summing standardized values for triglycerides, fasting insulin, fasting glucose, blood pressure and the inverse of high‐density lipoprotein‐cholesterol. A cross‐sectional analysis using linear regression with repeated measures was performed.

Results  Both FEV1 and FVC were inversely and statistically significantly associated with metabolic risk and insulin resistance after adjusting for age, sex, smoking status, height, PAEE and fitness. The associations with metabolic risk remained significant after adjusting for measures of body fatness, but those with insulin resistance did not.

Conclusions  Reduced lung function was associated with increased metabolic risk in this cohort of carefully characterized at‐risk individuals. This association was independent of overall and central body fatness, objectively measured physical activity and aerobic fitness.
Looking Again, and Harder, for a Link Between Low Self‐Esteem and Aggression
Authors: Bushman Brad J. , Baumeister Roy F. , Thomaes Sander , Ryu Ehri , Begeer Sander , West Stephen G.
Published: February 2009

ABSTRACT Recent field studies have revived the hypothesis that low self‐esteem causes aggression. Accordingly, we reanalyzed the data from a previous experiment and conducted a new experiment to study direct physical aggression in the form of blasting a fellow participant with aversive noise. We also conducted a field study using a measure of indirect aggression in the form of a consequential negative evaluation. High narcissists were more aggressive than others but only when provoked by insult or humiliation and only toward the source of criticism. The combination of high self‐esteem and high narcissism produced the highest levels of aggression. These results support the view of aggression as stemming from threatened egotism and are inconsistent with the hypothesis that low self‐esteem causes either direct or indirect aggression.
Analysis of cancer data: a data mining approach
Authors: Delen Dursun
Published: February 2009

Abstract: Even though cancer research has traditionally been clinical and biological in nature, in recent years data driven analytic studies have become a common complement. In medical domains where data and analytics driven research is successfully applied, new and novel research directions are identified to further advance the clinical and biological studies. In this research, we used three popular data mining techniques (decision trees, artificial neural networks and support vector machines) along with the most commonly used statistical analysis technique logistic regression to develop prediction models for prostate cancer survivability. The data set contained around 120 000 records and 77 variables. A k‐fold cross‐validation methodology was used in model building, evaluation and comparison. The results showed that support vector machines are the most accurate predictor (with a test set accuracy of 92.85%) for this domain, followed by artificial neural networks and decision trees.
A theoretic framework for intelligent expert systems in medical encounter evaluation
Authors: Melek William W. , Sadeghian Alireza
Published: February 2009

Abstract: This paper describes a novel approach to implementation of a medical diagnosis expert system that can assist physicians with their daily practices. Differential artificial intelligence techniques are incorporated into a multi‐stage expert system to best represent the various phases of the patient diagnosis process. A weighted scoring system is used to represent the subjective analysis stage, while a rule‐based fuzzy expert system is employed to both interpret laboratory tests and imaging findings and suggest the final diagnosis. A model of various patient flow scenarios is presented to demonstrate the functionality of the proposed expert system. An actual example of patient walkthrough is used to demonstrate various computation steps from recording the patient chief complaint to arriving at the final diagnosis. It is shown that the conclusion arrived at by using the proposed system is consistent with a common diagnosis of a third party specialist who is asked to evaluate the performance of the system.
Feasibility of probabilistic neural networks, Kohonen self‐organizing maps and fuzzy clustering for source localization of ventricular focal arrhythmias from intravenous catheter measurements
Authors: Sunay Ahmet Sertaç , Cunedioğlu Uğur , Yιlmaz Bülent
Published: February 2009

Abstract:An important goal of clinical electrophysiological studies is estimation of the source of rhythm disturbances (arrhythmia) in the heart. 15% of ventricular arrhythmias are known to originate from the outer surface of the heart (epicardium). One localization approach targeting the epicardium uses multielectrode catheters placed in the coronary veins. However, epicardial measurement sites from these catheters are limited to locations reached via the coronary veins. This study investigates the feasibility of several pattern classification and neural network approaches for localization of the source of ventricular arrhythmias from sparse measurements acquired from within coronary veins. Specifically, we studied Kohonen self‐organizing maps and fuzzy C‐means clustering methods for the construction of the target vector in neural networks from experimental high‐resolution activation‐time patterns. We also studied two neural network techniques, probabilistic neural networks and backpropagation networks, for the training and test procedures. The results of this study showed that it was possible to localize the arrhythmia source in a relatively small region for approximately 70% of cases. This study, in general, showed that the combination of probabilistic neural networks, Kohonen self‐organizing maps and fuzzy C‐means clustering approaches is feasible in catheter‐based epicardial arrhythmia source localization.
Differentiating types of muscle movements using a wavelet based fuzzy clustering neural network
Authors: Karlιk Bekir , Koçyiğit Yücel , Korürek Mehmet
Published: February 2009

Abstract: The electromyographic signals observed at the surface of the skin are the sum of many small action potentials generated in the muscle fibres. After the signals are processed, they can be used as a control source of multifunction prostheses. The myoelectric signals are represented by wavelet transform model parameters. For this purpose, four different arm movements (elbow extension, elbow flexion, wrist supination and wrist pronation) are considered in studying muscle contraction. Wavelet parameters of myoelectric signals received from the muscles for these different movements were used as features to classify the electromyographic signals in a fuzzy clustering neural network classifier model. After 1000 iterations, the average recognition percentage of the test was found to be 97.67% with clustering into 10 features. The fuzzy clustering neural network programming language was developed using Pascal under Delphi.
Augmentation of a nearest neighbour clustering algorithm with a partial supervision strategy for biomedical data classification
Authors: Salem Sameh A. , Salem Nancy M. , Nandi Asoke K.
Published: February 2009

Abstract: In this paper, a partial supervision strategy for a recently developed clustering algorithm, the nearest neighbour clustering algorithm (NNCA), is proposed. The proposed method (NNCA‐PS) offers classification capability with a smaller amount of a priori knowledge, where a small number of data objects from the entire data set are used as labelled objects to guide the clustering process towards a better search space. Experimental results show that NNCA‐PS gives promising results of 89% sensitivity at 95% specificity when used to segment retinal blood vessels, and a maximum classification accuracy of 99.5% with 97.2% average accuracy when applied to a breast cancer data set. Comparisons with other methods indicate the robustness of the proposed method in classification. Additionally, experiments on parallel environments indicate the suitability and scalability of NNCA‐PS in handling larger data sets.
HOPE, A MODE OF FAITH: AQUINAS, LUTHER AND BENEDICT XVI ON HEBREWS 11:1
Authors: COOPER ADAM G.
Published: February 2009

In articulating a theological account of Christian hope faithful to its objective character, Pope Benedict XVI summons the authority of Thomas Aquinas, citing his comments on faith and hope as those terms occur in Hebrews 11:1. Benedict sets off Aquinas's understanding of hope‐filled faith's objectivity by placing it in contrast with Luther's apparently more subjective interpretation of faith in Hebrews 11:1 as conviction. Closer analysis of both Aquinas and Luther, however, suggests a greater overlap in their exegetical conclusions, opening the way for a more nuanced appreciation of a virtue whose living possession and exercise, as the rest of Spe Salvi confirms, involves both objective and subjective dimensions
The GRIM2005 Study of Migraine Consultation in France. III: Psychological Features of Subjects With Migraine
Authors: Radat F , Lantéri-Minet M , Nachit-Ouinekh F , Massiou H , Lucas C , Pradalier A , Mercier F , El Hasnaoui A
Published: February 2009

The objective of this analysis was to describe psychological and cognitive variables in subjects with migraine and to identify those associated with chronicity. Data were collected from 10 000 subjects during face-to-face interview. Subjects with episodic migraine ( n = 1127) or chronic daily headache ( n = 407) with migrainous features were identified using an algorithm based on the International Classification of Headache Disorders, 2nd edn classification. Data on headache impact was obtained with the Headache Impact Test-6, on psychological distress with the Hospital Anxiety and Depression Scale, on coping with the Coping Strategy Questionnaire catastrophizing score and the Brief COPE inventory, on illness perception with the Brief Illness Perception Questionnaire and on locus of control. Psychological variables associated with chronicity include perceived headache impact, psychological distress, the use of catastrophizing and avoidance coping strategies and an externalized locus of control. In conclusion, maladaptive coping strategies should be taken into account in the management of patients with migraine. Longitudinal studies will be necessary to address the causality of the relationship observed.
Cerebrospinal Fluid Cytokine Levels in Migraine, Tension-Type Headache and Cervicogenic Headache
Authors: Bø SH , Davidsen EM , Gulbrandsen P , Dietrichs E , Bovim G , Stovner LJ , White LR
Published: February 2009

Cytokines have been measured in cerebrospinal fluid (CSF) from headache patients [infrequent episodic tension-type headache (TTH) and migraine with or without aura, all during attack, and cervicogenic headache] and compared with levels in pain-free individuals. Both proinflammatory [interleukin (IL)-1β, tumour necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1)] and anti-inflammatory cytokines IL-1 receptor antagonist (IL-1ra), IL-4, IL-10 and transforming growth factor-β1 (TGF-β1)] were included. There were significant group differences in IL-1ra, TGF-β1 and MCP-1 in episodic TTH and migraine compared with controls, and a significant difference in MCP-1 between cervicogenic headache and migraine with aura. Intrathecal MCP-1 correlated with IL-1ra, IL-10 and TGF-β1 in episodic TTH, and MCP-1 with IL-10 in migraine with aura. Cytokine increases were modest compared with those often accompanying serious neurological conditions, and may represent a mild response to pain. We believe this to be the first comparative study of CSF cytokine levels in connection with headache.
Prostaglandin E2(PGE2) Induces Headache in Healthy Subjects
Authors: Wienecke T , Olesen J , Oturai PS , Ashina M
Published: February 2009

The role of prostanoids in nociception is well established. The headache-eliciting effects of prostaglandin E2(PGE2) and its possible mechanisms have previously not been systematically studied in man. We hypothesized that infusion of PGE2might induce headache and vasodilation of cranial vessels. PGE2(0.40 μg kg−1min−1) or saline was infused for 25 min into 11 healthy subjects in a cross-over, double-blind study. Headache intensity was scored on a verbal rating scale from 0 to 10. In addition, we recorded mean flow in the middle cerebral artery (VMCA) by transcranial Doppler and diameter of the superficial temporal artery (STA) by high-resolution ultrasonography. All 11 subjects reported headache on the PGE2day and no subjects reported headache on the placebo day ( P = 0.001). During the immediate phase (0–30 min) ( P = 0.005) and the postinfusion phase (30–90 min) ( P = 0.005), the area under the curve for headache score was significantly larger on the PGE2day compared with the placebo day. PGE2caused dilatation of the STA (23.5%; 95% CI 14.0, 37.8) and the MCA (8.3%; 95% CI 4.0, 12.6). We suggest that PGE2induces headache by activation and sensitization of cranial perivascular sensory afferents.
Morning Headache in Sleep Apnoea: Clinical and Polysomnographic Evaluation and Response to Nasal Continuous Positive Airway Pressure
Authors: Goksan B , Gunduz A , Karadeniz D , Ağan K , Tascilar FN , Tan F , Purisa S , Kaynak H
Published: February 2009

Morning headache is accepted as part of clinical findings of obstructive sleep apnoea syndrome (OSAS). The prevalence of morning headache is at variable levels from 18% to 74% in patients with OSAS. However, there is controversy over the association of morning headache and OSAS. We studied morning headache prevalance and characteristics in 101 controls with apnoea-hypnoea index (AHI) < 5 and 462 OSAS patients with AHI ≥ 5. Morning headache was reported by only nine (8.9%) subjects in a control group compared with 156 (33.6%) of OSAS patients ( P < 0.01). Morning headache prevalance was significantly higher in severe and moderate OSAS groups. AHI was significantly higher in OSAS patients with morning headache compared with patients without morning headaches. Oxygen saturation nadir during rapid eye movement and non-rapid eye movement sleep as well as mean oxygen saturation value during total sleep time were also found to be significantly lower in morning headache group. However, none of the sleep parameters was found to be determinants of morning headache. Morning headache was more frequently reported by patients of female gender and with primary headache history. Morning headache was totally resolved in 90% of patients treated with nasal continuous positive airway pressure. The history of OSAS should be considered in the differential diagnosis of morning headache.
Whites and African-Americans in Headache Specialty Clinics Respond Equally Well to Treatment
Authors: Heckman BD , Holroyd KA , Tietjen G , O'Donnell FJ , Himawan L , Utley C , Watakakosol R , Stillman M
Published: February 2009

This study sought to determine if Whites and African-Americans respond similarly to headache treatment administered in ‘real-world’ headache specialty treatment clinics. Using a naturalistic, longitudinal design, 284 patients receiving treatment for headache disorders completed 30–day daily diaries that assessed headache frequency and severity at pretreatment and 6–month follow-up and also provided data on their headache disability and quality of life at pretreatment and 1–, 2– and 6–month follow-up. Controlling for socioeconomic status and psychiatric comorbidity, hierarchical linear models found that African-Americans and Whites reported significant reductions in headache frequency and disability and improvements in life quality over the 6–month treatment period. African-Americans, unlike Whites, also reported significant decreases in headache severity. Nevertheless, Africans-Americans had significantly more frequent and disabling headaches and lower quality of life after treatment relative to Whites. Although Whites and African Americans responded favourably to headache treatments, more efficacious treatments are needed given the elevated level of headache frequency that remained in both racial groups following treatment.
Respiratory Dysfunction in Chronic Neck Pain Patients. A Pilot Study
Authors: Kapreli E , Vourazanis E , Billis E , Oldham JA , Strimpakos N
Published: February 2009

The aim of this pilot study was to add weight to a hypothesis according to which patients presenting with chronic neck pain could have a predisposition towards respiratory dysfunction. Twelve patients with chronic neck pain and 12 matched controls participated in this study. Spirometric values, maximal static pressures, forward head posture and functional tests were examined in all subjects. According to the results, chronic neck patients presented with a statistically significant decreased maximal voluntary ventilation ( P = 0.042) and respiratory muscle strength (Pimax and Pemax), ( P = 0.001 and P = 0.002, respectively). Furthermore, the current study demonstrated a strong association between an increased forward head posture and decreased respiratory muscle strength in neck pateits. The connection of neck pain and respiratory function could be an important consideration in relation to patient assessment, rehabilitation and consumption of pharmacological agents.
Population genetic structure of rock ptarmigan in the ‘sky islands’ of French Pyrenees: implications for conservation
Authors: Bech N. , Boissier J. , Drovetski S. , Novoa C.
Published: February 2009

Expected consequences of global warming include habitat reduction in many cool climate species. Rock ptarmigan is a Holarctic grouse that inhabits arctic and alpine tundra. In Europe, the Pyrenean ptarmigan inhabits the southern edge of the species' range and since the last glacial maximum its habitat has been severely fragmented and is restricted to high‐alpine zones or ‘sky islands’. A recent study of rock ptarmigan population genetic in Europe found that the Pyrenean ptarmigan had very low genetic diversity compared with that found in the Alps and Scandinavia. Habitat fragmentation and reduced genetic diversity raises concerns about the viability of ptarmigan populations in the Pyrenees. However, information on population structuring and gene flow across the Pyrenees, which is essential for designing a sound management plan, is absent. In this study, we use seven microsatellites and mitochondrial control region sequences to investigate genetic variation and differentiation among five localities across the Pyrenees. Our analyses reveal the presence of genetic differentiation among all five localities and a significant isolation‐by‐distance effect that is likely the result of short dispersal distances and high natal and breeding philopatry of Pyrenean ptarmigan coupled with severe habitat fragmentation. Furthermore, analysis of molecular variance, principal component analysis and Bayesian analysis of genetic structuring identified the greatest amount of differentiation between the eastern and main parts of the Pyrenean chain separated by the Sègre Valley. Our data also show that the Canigou massif may host an isolated population and requires special conservation attention. We propose a management plan which includes the translocation of birds. If a sky island structure affects genetic divergence in rock ptarmigan, it may also affect the genetic structure of other sky island species having low dispersal abilities.
Reduction of protein kinase C ζ inhibits migration and invasion of human glioblastoma cells
Authors: Guo Hua , Gu Feng , Li Wenliang , Zhang Baogang , Niu Ruifang , Fu Li , Zhang Ning , Ma Yongjie
Published: February 2009

Glioblastomas are the most aggressive forms of primary brain tumors with their tendency to invade surrounding healthy brain tissues, rendering them largely incurable. In this report, we used small‐interference RNA technology to knock down the expression of protein kinase C (PKC) ζ, which resulted in specific and massive impairment of glioblastoma cell migration and invasion. We also explained the fundamental molecular processes of glioblastoma migration and invasion in which PKCζ is a participant. The silence of PKCζ expression likewise impaired the phosphorylation of LIN‐11, Isl1 and MEC‐3 protein domain kinase (LIMK) and cofilin, which is a critical step in cofilin recycling and actin polymerization. Consistent with the defects in cell adhesion, phosphorylation of integrin β1 was also dampened. Therefore, PKCζ regulated both cytoskeleton rearrangement and cell adhesion, which contributed to cell migration. Additionally, there was down‐regulation of matrix metalloprotease‐9 expression in siPKCζ/LN‐229 cells, which coincided with decreased invasion both in vitro and in vivo. These results indicate that PKCζ is involved in the control of glioblastoma cell migration and invasion by regulating the cytoskeleton rearrangement, cell adhesion, and matrix metalloprotease‐9 expression. Collectively, these findings suggest that PKCζ is a potential therapeutic target for glioblastoma infiltration.
Alterations of myelin‐specific proteins and sphingolipids characterize the brains of acid sphingomyelinase‐deficient mice, an animal model of Niemann–Pick disease type A
Authors: Buccinnà Barbara , Piccinini Marco , Prinetti Alessandro , Scandroglio Federica , Prioni Simona , Valsecchi Manuela , Votta Barbara , Grifoni Silvia , Lupino Elisa , Ramondetti Cristina , Schuchman Edward H. , Giordana Maria Teresa , Sonnino Sandro , Rinaudo Maria Teresa
Published: February 2009

Niemann–Pick disease (NPD) type A is a neurodegenerative disorder caused by sphingomyelin (SM) accumulation in lysosomes relying on reduced or absent acid sphingomyelinase (ASM) activity. NPD‐A patients develop progressive neurodegeneration including cerebral and cerebellar atrophy, relevant Purkinje cell and myelin deficiency with death within 3 years. ASM‘knock‐out’ (ASMKO) mice, an animal model of NPD‐A, develop a phenotype largely mimicking that of NPD‐A. The mechanisms underlying myelin formation are poorly documented in ASMKO mice. In this study we determined the content of four myelin‐specific proteins, myelin basic protein (MBP), 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNP), myelin associated glycoprotein (MAG) and proteolipid protein (PLP), and that of myelin‐enriched sphingolipids in the brains of ASMKO and wild‐type mice in early stages of post‐natal (pn) life. Protein and mRNA analysis revealed that in ASMKO mice beginning from 4 post‐natal weeks (wk‐pn), the expression levels of MAG, CNP, and MBP were below those observed in wild‐type mice and the same applied to PLP at 10 wk‐pn. Moreover, at 4 wk‐pn the expression of SOX10, one of the transcription factors involved in oligodendrocyte development and maintenance was lower in ASMKO mice. Lipid analysis showed that SM and the gangliosides GM3 and GM2 accumulated in the brains of ASMKO mice, as opposed to galactocerebroside and galactosulfocerebroside that, in parallel with the mRNAs of UDP‐galactose ceramide galactosyltransferase and galactose‐3‐O‐sulfotransferase 1, the two transferases involved in their synthesis, decreased. Myelin lipid analysis showed a progressive sphingomyelin accumulation in ASMKO mice; noteworthy, of the two sphingomyelin species known to be resolved by TLC, only that with the lower Rf accumulated. The immunohistochemical analysis showed that the reduced expression of myelin specific proteins in ASMKO mice at 10 wk‐pn was not restricted to the Purkinje layer of the cerebellar cortex but involved the cerebral cortex as well. In conclusion, reduced oligodendrocyte metabolic activity is likely to be the chief cause of myelin deficiency in ASMKO mice, thus shedding light on the molecular dysfunctions underlying neurodegeneration in NPD‐A.
Lipid rafts regulate 2‐arachidonoylglycerol metabolism and physiological activity in the striatum
Authors: Maccarrone Mauro , De Chiara Valentina , Gasperi Valeria , Viscomi Maria Teresa , Rossi Silvia , Oddi Sergio , Molinari Marco , Musella Alessandra , Finazzi‐Agrò Alessandro , Centonze Diego
Published: February 2009

Several G protein‐associated receptors and synaptic proteins function within lipid rafts, which are subdomains of the plasma membranes that contain high concentrations of cholesterol. In this study we addressed the possible role of lipid rafts in the control of endocannabinoid system in striatal slices. Disruption of lipid rafts following cholesterol depletion with methyl‐β‐cyclodestrin (MCD) failed to affect synthesis and degradation of anandamide, while it caused a marked increase in the synthesis and concentration of 2‐arachidonoylglycerol (2‐AG), as well as in the binding activity of cannabinoid CB1 receptors. Surprisingly, endogenous 2‐AG‐mediated control of GABA transmission was not potentiated by MCD treatment and, in contrast, neither basal nor 3,5‐Dihydroxyphenylglycine‐stimulated 2‐AG altered GABA synapses in cholesterol‐depleted slices. Synaptic response to the cannabinoid CB1 receptor agonist HU210 was however intact in MCD‐treated slices, indicating that reduced sensitivity of cannabinoid CB1 receptors does not explain why endogenous 2‐AG is ineffective in inhibiting striatal GABA transmission after cholesterol depletion. Confocal microscopy analysis suggested that disruption of raft integrity by MCD might uncouple metabotropic glutamate 5‐CB1 receptor interaction by altering the correct localization of both receptors in striatal neuron elements. In conclusion, our data indicate that disruption of raft integrity causes a complex alteration of the endocannabinoid signalling in the striatum.
Estradiol induces physical association of neuronal nitric oxide synthase with NMDA receptor and promotes nitric oxide formation via estrogen receptor activation in primary neuronal cultures
Authors: D’Anglemont de Tassigny Xavier , Campagne Céline , Steculorum Sophie , Prevot Vincent
Published: February 2009

Estrogens and nitric oxide (NO) exert wide‐ranging effects on brain function. Recent evidence suggested that one important mechanism for the regulation of NO production may reside in the differential coupling of the calcium‐activated neuronal NO synthase (nNOS) to glutamate NMDA receptor channels harboring NR2B subunits by the scaffolding protein post‐synaptic density‐95 (PSD‐95), and that estrogens promote the formation of this ternary complex. Here, we demonstrate that 30‐min estradiol‐treatment triggers the production of NO by physically and functionally coupling NMDA receptors to nNOS in primary neurons of the rat preoptic regionin vitro. The ability of estradiol to activate neuronal NO signaling in preoptic neurons and to promote changes in protein‐protein interactions is blocked by ICI 182,780, an estrogen receptor antagonist. In addition, blockade of NMDA receptor NR2B subunit activity with ifenprodil or disruption of PSD‐95 synthesis in preoptic neurons by treatment with an anti‐sense oligodeoxynucleotide inhibited the estradiol‐promoted stimulation of NO release in cultured preoptic neurons. Thus, estrogen receptor‐mediated stimulation of the nNOS/PSD‐95/NMDA receptor complex assembly is likely to be a critical component of the signaling process by which estradiol facilitates coupling of glutamatergic fluxes for NO production in neurons.
Aminopeptidase A contributes to the N‐terminal truncation of amyloid β‐peptide
Authors: Sevalle Jean , Amoyel Audrey , Robert Philippe , Fournié‐Zaluski Marie‐Claude , Roques Bernard , Checler Frédéric
Published: February 2009

Several lines of data previously indicated that N‐terminally truncated forms of amyloid‐β (Aβ) peptides are likely the earliest and more abundant species immunohistochemically detectable in Alzheimer’s disease‐affected brains. It is noteworthy that the free N‐terminal residue of full‐length Aβ (fl‐Aβ) is an aspartyl residue, suggesting that Aβ could be susceptible to exopeptidasic attack by aminopeptidase A (APA)‐like proteases. In this context, we have examined whether APA could target Aβ peptides in both cell‐free and cellular models. We first show that the general aminopeptidase inhibitor amastatin as well as two distinct aminopeptidase A inhibitors EC33 and pl302 both significantly increase the recovery of genuine fl‐Aβ peptides generated by cells over‐expressing Swedish‐mutated β amyloid precursor protein (APP) while the aminopeptidase N blocker pl250 did not modify fl‐Aβ recovery. In agreement with this observation, we establish that over‐expressed APA drastically reduces, in a calcium dependent manner, fl‐Aβ but not APP IntraCellular Domain in a cell‐free model of Aβ production. In agreement with the above data, we show that recombinant APA degrades fl‐Aβ in a pl302‐sensitive manner. Interestingly, we also show that EC33 and pl302 lower staurosporine‐stimulated activation of caspase‐3 in wild‐type fibroblasts but not in βAPP/β‐amyloid precursor protein‐like protein 2 (APLP2) double knockout fibroblasts, suggesting that protecting endogenous fl‐Aβ physiological production triggers neuroprotective phenotype. By contrast, EC33 does not modify staurosporine‐induced caspase‐3 activation in wild‐type and Swedish‐mutated βAPP‐HEK293 expressing cells that display exacerbated production of Aβ. Overall, our data establish that APA contributes to the N‐terminal truncation of Aβ and suggest that this cleavage is likely abrogating a protective function associated with physiological but not supraphysiological levels of genuine fl‐Aβ peptides.
p53‐Dependent control of cell death by nicastrin: lack of requirement for presenilin‐dependent γ‐secretase complex
Authors: Pardossi‐Piquard Raphaëlle , Dunys Julie , Giaime Emilie , Guillot‐Sestier Marie‐Victoire , St. George‐Hyslop Peter , Checler Frédéric , Alves da Costa Cristine
Published: February 2009

Nicastrin (NCT) is a component of the presenilin (PS)‐dependent γ‐secretase complexes that liberate amyloid β‐peptides from the β‐Amyloid Precursor Protein. Several lines of evidence indicate that the members of these complexes could also contribute to the control of cell death. Here we show that over‐expression of NCT increases the viability of human embryonic kidney (HEK293) cells and decreases staurosporine (STS)‐ and thapsigargin (TPS)‐induced caspase‐3 activation in various cell lines from human and neuronal origins by Akt‐dependent pathway. NCT lowers p53 expression, transcriptional activity and promoter transactivation and reduces p53 phosphorylation. NCT‐associated protection against STS‐stimulated cell death was completely abolished by p53 deficiency. Conversely, the depletion of NCT drastically enhances STS‐induced caspase‐3 activation and p53 pathway and favored p53 nuclear translocation. We examined whether NCT protective function depends on PS‐dependent γ‐secretase activity. First, a 29‐amino acid deletion known to reduce NCT‐dependent amyloid β‐peptide production did not affect NCT‐associated protective phenotype. Second, NCT still reduces STS‐induced caspase‐3 activation in fibroblasts lacking PS1 and PS2. Third, the γ‐secretase inhibitor DFK167 did not affect NCT‐mediated reduction of p53 activity. Altogether, our study indicates that NCT controls cell death via phosphoinositide 3‐kinase/Akt and p53‐dependent pathways and that this function remains independent of the activity and molecular integrity of the γ‐secretase complexes.