bluuebunny/crossref_metadata_2025 huggingface dataset:
Apigenin, a plant‐derived flavone, activates transient receptor potential vanilloid 4 cation channel
Authors: Ma Xin , He Dongxu , Ru Xiaochen , Chen Yun , Cai Yanfei , Bruce Iain C , Xia Qiang , Yao Xiaoqiang , Jin Jian
Published: November 2011

BACKGROUND AND PURPOSE Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+‐permeable channel with multiple modes of activation. Apigenin is a plant‐derived flavone, which has potential preventive effects on the development of cardiovascular disease. We set out to explore the effects of apigenin on TRPV4 channel activity and its role in vasodilatation.

EXPERIMENTAL APPROACH The effects of apigenin (0.01–30 µM) on TPRV4 channels were investigated in HEK293 cells over‐expressing TRPV4, rat primary cultured mesenteric artery endothelial cells (MAECs) and isolated small mesenteric arterial segments using whole‐cell patch clamp, fluorescent Ca2+ imaging, intracellular recording and pressure myography.

KEY RESULTS Whole‐cell patch clamp and fluorescent Ca2+ imaging in HEK cells over‐expressing TRPV4 showed that apigenin concentration‐dependently stimulated the TRPV4‐mediated cation current and Ca2+ influx. In MAECs, apigenin stimulated Ca2+ influx in a concentration‐dependent manner. These increases in cation current and Ca2+ influx were markedly inhibited by TRPV4‐specific blockers and siRNAs. Furthermore, pressure myography and intracellular recording in small third‐order mesenteric arteries showed that apigenin dose‐dependently evoked smooth muscle cell membrane hyperpolarization and subsequent vascular dilatation, which were significantly inhibited by TRPV4‐specific blockers. TRPV4 blocker or charybdotoxin (200 nM) plus apamin (100 nM) diminished the apigenin‐induced dilatation.

CONCLUSION AND IMPLICATIONS This is the first study to demonstrate the selective stimulation of TRPV4 by apigenin. Apigenin was found to activate TRPV4 channels in a dose‐dependent manner in HEK cells over‐expressing TRPV4 and in native endothelial cells. In rat small mesenteric arteries, apigenin acts on TRPV4 in endothelial cells to induce EDHF‐mediated vascular dilatation.
Anatomic Assessment of Variations in Myocardial Approaches to the Atrioventricular Node
Authors: MATSUYAMA TAKA‐AKI , HO SIEW YEN , MCCARTHY KAREN P. , UEDA AKIKO , MAKIMOTO HISAKI , SATOMI KAZUHIRO , KAMAKURA SHIRO , INOUE SHIN , ISHIBASHI‐UEDA HATSUE
Published: November 2011

Atrial Septum, Coronary Sinus, and Atrioventricular Node.

Introduction:
The tissues in the posteroinferior atrioventricular (AV) junction around the AV node are important in procedures for ablating and manipulation of catheters in and around the coronary sinus (CS). However, information with regard to the histological arrangement of perinodal myocardium relative to the CS is lacking.

Methods and Results:
We examined 21 postmortem human hearts without any abnormalities (9 women; mean age 68.8 ± 14.3 years). After making measurements, the posteroinferior AV junction was removed and processed for histology. Sections were cut parallel to the septum. We assessed the myocardial arrangements from the atrial septum and the CS toward the AV nodal tissue, including the transitional cell zone, and measured the dimensions between the compact AV node and the CS, and the circumference of the CS. We observed 3 patterns of myocardial approaches to the AV node: extension of myocardium from the atrial septum (Group A; n = 6); extension of CS musculature (Group B; n = 6); and both septal and CS musculature (Group C; n = 9). The distance between the AV node and the CS in Group A was significantly longer than in the other groups (mean 11.5 ± 3.1 mm, 1.7 ± 0.6 mm, 3.8 ± 1.5 mm, respectively; P < 0.0001), and the circumference of the CS in Group B was longer than in Group A (mean 31.1 ± 7.9 mm*, 44.4 ± 8.4 mm*, 33.7 ± 6.9 mm, respectively; P < 0.05).

Conclusion:
The myocardial approaches including the transitional cell zone toward the AV node are variable in normal hearts. The location and size of the CS can affect the myocardial arrangements and the area of transitional cells around the AV node.
Risk for Permanent Pacemaker After Transcatheter Aortic Valve Implantation: A Comprehensive Analysis of the Literature
Authors: ERKAPIC DAMIR , DE ROSA SALVATORE , KELAVA AUGUSTIN , LEHMANN RALF , FICHTLSCHERER STEPHAN , HOHNLOSER STEFAN H.
Published: November 2011

Risk for Permanent Pacemaker After Transcatheter Aortic Valve Implantation.

Background: Permanent pacemaker (PM) requirement is a known complication after transcatheter aortic valve implantation (TAVI). There are, however, no systematic data concerning this complication.

Objective: To determine the incidence and potential predictors of permanent PM requirement after TAVI based on published literature.

Methods: We conducted a MEDLINE search to identify potentially relevant literature dealing with PM requirement after TAVI. Data were collected on paper extraction forms by 2 independent investigators.

Results: There were 32 relevant published studies comprising data of 5,258 patients without an implanted PM before TAVI. An Edwards‐Sapiens® prosthesis (ESP) was implanted in 2,887 patients, whereas 2,371 patients received a CoreValve® prosthesis (CVP). The crude incidence of PM implantation after TAVI was 15%. Six hundred and fourteen of 2,371 (25.8%) CVP patients and 189 of the 2,887 (6.5%) ESP patients had to receive a permanent PM (odds ratio [OR] 4.91, 95% confidence interval [CI] 4.12–5.86, P < 0.001). Presence of right bundle branch block (RBBB) before TAVI was a significant predictor for development of complete atrioventricular (AV) block and subsequent PM need (OR 1.358, 95% CI 1.001–1.841, P = 0.02). More than 90% of all AV‐block requiring PM implantation occurred immediately or within 7 days after TAVI.

Conclusion: Patients undergoing TAVI with implantation of CVP are at significantly higher risk for development of AV block and subsequent need for permanent PM, particularly if RBBB preexists. Since AV block occurs in >90% within the first week after the procedure, careful monitoring should be performed for at least 7 days after TAVI.
Reflection and Reasoning in Moral Judgment
Authors: Paxton Joseph M. , Ungar Leo , Greene Joshua D.
Published: November 2011

While there is much evidence for the influence of automatic emotional responses on moral judgment, the roles of reflection and reasoning remain uncertain. In Experiment 1, we induced subjects to be more reflective by completing the Cognitive Reflection Test (CRT) prior to responding to moral dilemmas. This manipulation increased utilitarian responding, as individuals who reflected more on the CRT made more utilitarian judgments. A follow‐up study suggested that trait reflectiveness is also associated with increased utilitarian judgment. In Experiment 2, subjects considered a scenario involving incest between consenting adult siblings, a scenario known for eliciting emotionally driven condemnation that resists reasoned persuasion. Here, we manipulated two factors related to moral reasoning: argument strength and deliberation time. These factors interacted in a manner consistent with moral reasoning: A strong argument defending the incestuous behavior was more persuasive than a weak argument, but only when increased deliberation time encouraged subjects to reflect.
Cell‐derived microparticles in atherosclerosis: biomarkers and targets for pharmacological modulation?
Authors: Baron Morgane , Boulanger Chantal M. , Staels Bart , Tailleux Anne
Published: November 2011

Introduction

Microparticle formation, structure and composition

Microparticle isolation, preparation and measurement

Microparticles as markers of cardiovascular diseases

Microparticles as actors in cardiovascular diseases

Pharmacological modulation of plasma MP concentrations

Conclusion

Cardiovascular diseases remain an important cause of morbi‐mortality. Atherosclerosis, which predisposes to cardiovascular disorders such as myocardial infarction and stroke, develops silently over several decades. Identification of circulating biomarkers to evaluate cardiovascular event risk and pathology prognosis is of particular importance. Microparticles (MPs) are small vesicles released from cells upon apoptosis or activation. Microparticles are present in blood of healthy individuals. Studies showing a modification of their concentrations in patients with cardiovascular risk factors and after cardiovascular events identify MPs as potential biomarkers of disease. Moreover, the pathophysiological properties of MPs may contribute to atherosclerosis development. In addition, pharmacological compounds, used in the treatment of cardiovascular disease, can reduce plasma MP concentrations. Nevertheless, numerous issues remain to be solved before MP measurement can be applied as routine biological tests to improve cardiovascular risk prediction. In particular, prospective studies to identify the predictive values of MPs in pathologies such as cardiovascular diseases are needed to demonstrate whether MPs are useful biomarkers for the early detection of the disease and its progression.
Amelanotic melanoma: a detailed morphologic analysis with clinicopathologic correlation of 75 cases
Authors: Cheung Wang L. , Patel Rishi R. , Leonard Aimee , Firoz Bahar , Meehan Shane A.
Published: November 2011

Amelanotic melanoma can have a varied appearance both clinically and microscopically. Here, we present our experiences with 75 cases of amelanotic melanoma defined clinically as a non‐pigmented lesion and histopathologically as a tumor lacking significant melanization. We evaluated microscopic features such as morphology, mitotic count, nuclear atypia and presence of solar elastosis. Our amelanotic melanomas exhibited the following morphology: epitheloid (72%), spindled (18.7%) or desmoplastic (5.3%). In addition, we obtained patient information and clinical presentations on most of the cases (74/75; 98.7%) and follow‐up data on 40% (30/75) of the cases. The majority of amelanotic melanomas in men were found on the trunk (13/45; 29%), head and neck (12/45; 26.7%), and lower limb (13/45; 29%) and in women were found on the lower limb (12/30; 40%), upper limb (10/30; 33.3%) and head and neck (6/30; 20%). In addition, we found that an increase in mitotic index correlated with worse survival (p < 0.026), whereas there were no differences in survival for other pathological features, such as nuclear atypia or solar elastosis. Furthermore, in cases with available tissue, all amelanotic melanoma expressed microphthalmia‐associated transcription factor and tyrosinase, suggesting that the tumor cells retained melanocytic lineage and an enzyme in melanin formation, respectively. As the occurrence of amelanotic melanoma and the expression melanoma markers were similar to pigmented melanoma, we favor that amelanotic melanoma represents a subtype of melanoma rather than poorly differentiated or de‐differentiated melanoma.

Cheung WL, Patel RR, Leonard A, Firoz B, Meehan SA. Amelanotic melanoma: a detailed morphologic analysis with clinicopathologic correlation of 75 cases.
Prevalence of temporomandibular disorders in a population of complete denture wearers
Authors: Dallanora Andressa Franceschi , Grasel Cláudia Elisa , Heine Caroline Pereira , Demarco Flávio Fernando , Pereira‐Cenci Tatiana , Presta Andréia Antoniuk , Boscato Noéli
Published: November 2011

doi: 10.1111/j.1741‐2358.2011.00574.x Prevalence of temporomandibular disorders in a population of complete denture wearers

Background: Complete tooth loss among the elderly is still frequent in developing countries and the incidence of temporomandibular disorders (TMD) is a common finding in complete denture wearers.

Objectives: The aim of this study was to evaluate the prevalence of temporomandibular disorders (TMD) in a population of complete denture wearers.

Materials and Methods: The data were collected by four examiners for the diagnosis of use and need for complete dentures followed by the World Health Organization standards and interviews for TMD signs and symptoms evaluation. Exploratory variables included demographic, socio‐economic status and TMD prevalence.

Results: The prevalence of TMD among denture wearers was 55.12%. Chi‐squared test showed no statistical difference between subjects with or without TMD for gender, geographical location and skin colour (p < 0.05). The number of subjects with TMD increased as the period of complete denture wear increased, although no statistical difference between groups were found (p < 0.05).

Conclusions: There is a need of educational programmes aiming at the importance of health care and periodical change of a complete denture, and strategies with a preventive approach to quality general dental care.
Investigation by site‐directed mutagenesis of the role of cytochrome P450 2B4 non‐active‐site residues in protein–ligand interactions based on crystal structures of the ligand‐bound enzyme
Authors: Wilderman P. Ross , Gay Sean C. , Jang Hyun‐Hee , Zhang Qinghai , Stout C. David , Halpert James R.
Published: November 2011

Residues located outside the active site of cytochromes P450 2B have exhibited importance in ligand binding, structural stability and drug metabolism. However, contributions of non‐active‐site residues to the plasticity of these enzymes are not known. Thus, a systematic investigation was undertaken of unique residue–residue interactions found in crystal structures of P450 2B4 in complex with 4‐(4‐chlorophenyl)imidazole (4‐CPI), a closed conformation, or in complex with bifonazole, an expanded conformation. Nineteen mutants distributed over 11 sites were constructed, expressed in Escherichia coli and purified. Most mutants showed significantly decreased expression, especially in the case of interactions found in the 4‐CPI structure. Six mutants (H172A, H172F, H172Q, L437A, E474D and E474Q) were chosen for detailed functional analysis. Among these, the Ks of H172F for bifonazole was ∼ 20 times higher than for wild‐type 2B4, and the Ks of L437A for 4‐CPI was ∼ 50 times higher than for wild‐type, leading to significantly altered inhibitor selectivity. Enzyme function was tested with the substrates 7‐ethoxy‐4‐(trifluoromethyl)coumarin, 7‐methoxy‐4‐(trifluoromethyl)coumarin and 7‐benzyloxyresorufin (7‐BR). H172F was inactive with all three substrates, and L437A did not turn over 7‐BR. Furthermore, H172A, H172Q, E474D and E474Q showed large changes in kcat/KM for each of the three substrates, in some cases up to 50‐fold. Concurrent molecular dynamics simulations yielded distances between some of the residues in these putative interaction pairs that are not consistent with contact. The results indicate that small changes in the protein scaffold lead to large differences in solution behavior and enzyme function.

Database

The atomic coordinates and structure factors have been deposited into the RCSB Protein Data Bank under accession number 3TK3. Rabbit (Oryctolagus cuniculus) cytochrome P450 dependent monooxygenase 2B4, EC 1.14.14.1, UniProt #: P00178
Ideal Timing and Predialysis Nephrology Care Duration for Dialysis Initiation: From Analysis of Japanese Dialysis Initiation Survey
Authors: Yamagata Kunihiro , Nakai Shigeru , Masakane Ikuto , Hanafusa Norio , Iseki Kunitoshi , Tsubakihara Yoshiharu ,   the Committee of Renal Data Registry of the Japanese Society for Dialysis Therapy
Published: November 2011

Previous studies have suggested that early initiation of dialysis therapy was not superior in terms of patient survival. In this study, we analyzed the effects of renal function at the start of renal replacement therapy (RRT), duration of nephrology care, and comorbidity on 12‐month survival of end‐stage renal disease (ESRD) patients. The subjects in this study were 9695 new ESRD patients who started RRT in 2007. The average age of the subjects was 67.5 years, 64.1% of the subjects were male, and 42.9% had diabetes. During the 12‐month period after the start of RRT, 1546 patients died, and 35 patients received renal transplantation. Average estimated glomerular filtration rate (eGFR) at the initiation of dialysis was 6.52 ± 4.20 mL/min/1.73 m2. By unadjusted logistic analysis, one‐year Odds Ratio (OR) of mortality in patients with eGFR more than 4–6 mL/min/1.73 m2 was increased with increased eGFR at dialysis initiation, but the OR was identical among the groups with eGFR less than 4 mL/min/1.73 m2. After adjustment for age, gender, underlying renal diseases, and other clinical characteristics at dialysis initiation, OR was identical among the groups with eGFR less than 8 mL/min/1.73 m2. Furthermore, an OR increment was observed in eGFR less than 4 mL/min/1.73 m2 group. In terms of the duration of nephrology care before dialysis initiation, 6 months or longer of nephrology care significantly decreased the OR of mortality after adjustment of covariance. Not only patients with sufficient residual renal function at the initiation of dialysis, but also patients with very low eGFR at the initiation of dialysis showed poor survival.
Protein Oxidative Stress and Dyslipidemia in Dialysis Patients
Authors: Marques de Mattos Andresa , Marino Larissa Vieira , Ovidio Paula Payão , Jordão Alceu Afonso , Almeida Carla Cristina , Chiarello Paula Garcia
Published: November 2011

Our aim was to investigate and determine the associations between oxidative stress (OS), dyslipidemia and inflammation in patients treated with continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) using observational cross‐sectional study. Twenty patients in CAPD and 48 in HD for at least 8 weeks and aged ≥18 years were included in the study. Individuals with malignant or acute inflammatory disease were excluded. A control group of 17 healthy individuals was also recruited. The biochemical parameter evaluations were analyzed using colorimetric kits for albumin, serum glucose, total cholesterol (TC) and lipid fractions. To determine the inflammatory status, CRP, IL‐6 and TNF‐α were analyzed by automated chemiluminescence kits. Plasma advanced oxidation protein products (AOPP) were determined by spectrophotometry. Mean AOPP levels were significantly higher for the HD group compared to the control, and there was no difference in AOPP concentrations between the control and CAPD groups. Dialysis patients had levels of inflammatory parameters higher than controls, and showed a high prevalence of patients with dyslipidemia, especially in CAPD. In the HD group, AOPP was positively correlated with triglycerides (TG) and inversely associated with HDL. Also the HD group was observed to have negative associations between TNF‐α and HDL, LDL and TC. In the CAPD group, CRP was inversely correlated with HDL. Hemodialysis patients had increased protein OS and associations of inflammation and dyslipidemia were also observed in these dialysis groups. A more detailed characterization of the relations between oxidative stress and other more traditional risk factors has therapeutic importance, since cardiovascular diseases are the leading cause of death among dialysis patients.
Reference intervals forGreyhounds andLurchers using theSysmexXT‐2000iVhematology analyzer
Authors: Campora Carola , Freeman Kathleen P. , Serra Mariana , Sacchini Federico
Published: November 2011

Background

The need for breed‐specific reference intervals (RIs) forGreyhounds has been identified. AsLurchers are a sighthound cross‐breed, specificRIsmay also be needed for these dogs. HematologicRIsforGreyhounds andLurchers using theSysmexXT‐2000iVhematology analyzer have not been established.

Objectives

The aims of this study were to establishRIsforGreyhounds using theSysmexXT‐2000iV, to investigate whetherRIsforGreyhound and nonsighthound dogs could be transferred toLurchers, and to establish newRIsforLurchers if transference was not possible.

Methods

Data were retrieved retrospectively from a database of blood donor dogs.GreyhoundRIswere established using nonparametric methods based on a reference population of 179 dogs. For theRItransference study, 38Lurchers were selected, following guidelines proposed by theClinical andLaboratoryStandardsInstitute. When transference was not appropriate, newRIswere generated using the robust method.

Results

GreyhoundRIsfor theSysmex hematology analyzer reflected known differences in this breed with a tendency toward higherRBCmass and lowerWBCand platelet counts.RIsfor hemoglobin concentration,HCT,MCV,MCH,MCHC, andWBC, neutrophil, lymphocyte, monocyte, and platelet counts forGreyhounds were suitable for transference toLurchers. ForRBCand eosinophil counts, newRIswere established.

Conclusion

Our study suggests thatLurchers share many hematologic characteristics withGreyhounds, but had higher reference limits forRBCand eosinophil counts.
Performance evaluation of the Sysmex pocH‐100iV Diff hematology analyzer for analysis of canine, feline, equine, and bovine blood
Authors: Riond Barbara , Weissenbacher Stefan , Hofmann‐Lehmann Regina , Lutz Hans
Published: November 2011

Background

The Sysmex pocH‐100iV Diff is an impedance hematology analyzer recently introduced for point‐of‐care use in veterinary practices in Europe.

Objective

The purpose of this study was to validate the pocH‐100iV Diff for analysis of blood samples from dogs, cats, horses, and cattle.

Methods

Fresh EDTA‐blood samples from healthy and ill dogs (115), cats (94), horses (91), and cattle (78) were analyzed on the pocH‐100iV Diff and the Cell‐Dyn 3500. Results of the automated WBC differential counts were compared with the manual differential counts for 77 dogs, 65 cats, 40 horses, and 46 cattle. HCT were compared with PCVs obtained by microhematocrit centrifugation. Furthermore, precision, linearity, carry‐over, cell aging, and clinical relevance of the pocH‐100iV Diff results were assessed.

Results

Most of the CBC results obtained by the pocH‐100iV Diff correlated well with those of the Cell‐Dyn 3500. Slightly low correlation was observed for canine MCV and hemoglobin concentration. Lymphocytes correlated well in horses and cattle, but less well in cats and dogs. The mixed cell population termed “OTHRS” (all granulocytes and monocytes for horses and cattle; neutrophils, monocytes, and basophils for cats and dogs) correlated well in all tested species. The instrument overestimated feline and canine eosinophils. In cats, platelet counts showed a strong negative bias.

Conclusions

The overall performance of the pocH‐100iV Diff was excellent with the noted limitations. The automated differential count can be used as screening tool in conjunction with evaluation of a blood smear.
Belief in a Werther Effect: Third‐Person Effects in the Perceptions of Suicide Risk for Others and the Moderating Role of Depression
Authors: Scherr Sebastian , Reinemann Carsten
Published: November 2011

Werther Effect research has almost solely focused on the behavioral level of media effects. Clinically relevant predispositions like depression as well as the moderating role of media effects on a perceptional level have been omitted so far. To bridge this gap, we reanalyzed the data of an experiment conducted by Rustad, Small, Jobes, Safer, and Peterson: volunteer students’ ratings for their self‐risk of depression and suicide as well as their perceptions of others’ suicide risk were investigated. While a Werther Effect could not be observed, there is a general overestimation of media influences on others—presumed Werther Effects—that are moderated by the personal degree of depression.
Evolution MegaLab: a case study in citizen science methods
Authors: Worthington Jenny P. , Silvertown Jonathan , Cook Laurence , Cameron Robert , Dodd Mike , Greenwood Richard M. , McConway Kevin , Skelton Peter
Published: November 2011

1. Volunteers have helped in scientific surveys of birds and other organisms for decades, but more recently, the use of the Internet has enormously widened the opportunity for citizen science and greatly increased its practice. There is now a need to share experience of which methods work and which do not. Here, we describe how we planned and executed the Evolution MegaLab, one of the largest surveys of polymorphism in wild species so far undertaken.

2. The aim of the Evolution MegaLab was to exploit the occasion of Charles Darwin’s double centenary in 2009 to mobilize the widest possible section of the general public in Europe to help survey shell polymorphism in the banded snails Cepaea nemoralis and Cepaea hortensis. These data were then compared with historical records to detect evolutionary change that may have taken place in the decades between samples.

3. Records of polymorphism in over 7000 populations sampled throughout the natural range of the two species were captured from published and unpublished sources and added to an online database. These data could be explored by the general public via a Google Maps interface on the project website (http://evolutionmegalab.org). The website contained a welcome page that explained what evolution is and how recent changes in climate, and the abundance of predatory birds (song thrushes Turdus philomelos) might have caused an evolutionary change in the shell patterns of banded snails.

4. A network of collaborators in 15 European countries was formed, with each country responsible for translating the website and associated materials, recruiting volunteers and raising any funds required locally. A total of 6461 users registered with the site, and 7629 records were submitted. We used an online quiz to train users and to test their ability, to recognize the correct snails and their morphs. Every user received automated, immediate feedback that compared their data with nearby records from the historical database.

5. The critical tasks achieved by the Evolution MegaLab that any citizen science project must tackle are as follows: (i) design of an appropriate project, (ii) recruitment, motivation and training of volunteers, and (iii) ensuring data quality.
Imaging of extreme-ultraviolet mask patterns using coherent extreme-ultraviolet scatterometry microscope based on coherent diffraction imaging
Authors: Harada Tetsuo , Nakasuji Masato , Kimura Teruhiko , Watanabe Takeo , Kinoshita Hiroo , Nagata Yutaka
Published: November 2011

In extreme-ultraviolet (EUV) lithography, defect-free mask production is a critical issue for high-volume manufacturing. For mask inspection and metrology, we have developed a coherent EUV scatterometry microscope (CSM). It is a simple lensless system. An aerial image of the mask pattern is reconstructed with iterative calculation based on coherent diffraction imaging. Periodic patterns, aperiodic patterns, and phase structures were reconstructed well by the CSM. A defect in a line-and-space pattern was detected as a diffraction signal. The aerial image of the defect is also reconstructed. This paper demonstrates the capability of the CSM to observe complex diffraction amplitudes directly from the pattern and the defect.
Drosophila
CENH3 Is Sufficient for Centromere Formation
Authors: Mendiburo María José , Padeken Jan , Fülöp Stefanie , Schepers Aloys , Heun Patrick
Published: November 2011

A specific histone is sufficient for the formation of a functional and heritable centromere in the fruit fly.
A Photothermoelectric Effect in Graphene
Authors: Basko Denis
Published: November 2011

A curious response of graphene to light and heat may be useful for optoelectronic applications.
Synaptic Switch and Social Status
Authors: Maroteaux Matthieu , Mameli Manuel
Published: November 2011

The strength of synaptic connections in the mammalian brain can influence social status.
The Language of Dendrites
Authors: Branco Tiago
Published: November 2011

Dendrites perform spatial and temporal discrimination during input processing.
Antigens of persistentChlamydia pneumoniaewithin coronary atheroma from patients undergoing heart transplantation
Authors: Borel Nicole , Pospischil Andreas , Dowling Robert D , Dumrese Claudia , Gaydos Charlotte A , Bunk Sebastian , Hermann Corinna , Ramirez Julio A , Summersgill James T
Published: November 2011

Aims

In order forChlamydia pneumoniaeto play a causative role in chronic human disease, it would need to persist within infected tissue for extended periods of time. Current theory suggests thatC pneumoniaemay persist at the site of infection via an alternative replicative form, known as an aberrant body.

Methods

A panel ofC pneumoniae-specific antibodies upregulated by the aberrant body was used to probe tissue specimens from the coronary atheroma from 13 explanted hearts to identify patterns of reactivity in these tissues, as well as to determine the presence and prevalence ofC pneumoniaeaberrant bodies.

Results

Six of 13 patients had an ischaemic cardiomyopathy secondary to coronary atherosclerosis, while another six patients had an idiopathic, dilated cardiomyopathy. One additional patient, a young (24 years) woman with cardiomyopathy, had no history of atherosclerotic disease. Eleven patients were positive by immunohistochemistry with at least one antibody. Coronary arteries of the two other patients were negative by immunohistochemistry with all antibodies. One of these patients was the 24-year-old woman with grade I disease and no risk factors for coronary artery disease.

Conclusions

The protein antigens of persistentC pneumoniaeinfection found in the atheromatous lesions from patients in this study could potentially be used as markers to detect such infections and some may be virulence factors or immunogens specific toC pneumoniae, thus serving as target molecules for diagnostic use or therapeutic intervention.
A review of the clinical presentation, natural history and inheritance of variegate porphyria: its implausibility as the source of the ‘Royal Malady’
Authors: Hift Richard J , Peters Timothy J , Meissner Peter N
Published: November 2011

It has been suggested that King George III of Great Britain suffered from the haem biosynthetic disorder, variegate porphyria. This diagnosis is pervasive throughout the scientific and popular literature, and is often referred to as the ‘Royal Malady.’ The authors believe it inappropriate to view the case for porphyria purely in terms of symptoms, as has generally been the case in his presumptive acute porphyria diagnosis. Accordingly, this review provides a current description of the natural history and clinical presentation of the porphyrias, against which we measure the case for porphyria in George III and his relatives. The authors have critically assessed the prevalence of porphyria in a population, the expected patterns and frequency of inheritance, its penetrance and its expected natural history in affected individuals, and conclude that neither George nor his relatives had porphyria, based on four principal reasons. First, the rarity of the disease mandates a very low prior probability, and therefore implies a vanishingly low positive predictive value for any diagnostic indicator of low specificity, such as a historical reading of the symptoms. Second, penetrance of this autosomal dominant disorder is approximately 40%, and one may expect to have identified characteristic clinical features of porphyria in a large number of descendants without difficulty. Third, the symptoms of both George III and his relatives are highly atypical for porphyria and are more appropriately explained by other much commoner conditions. Finally, the natural history of the illnesses reported in this family is as atypical for variegate porphyria as are their symptoms.
Correlation between expression of cellular retinol-binding protein 1 and its methylation status in larynx cancer
Authors: Peralta Raúl , Valdivia Alejandra , Alvarado-Cabrero Isabel , Gallegos Francisco , Apresa Teresa , Hernández Dulce , Mendoza Mónica , Romero Pablo , Paniagua Lucero , Ibáñez Miguel , Cabrera Lourdes , Salcedo Mauricio
Published: November 2011

Aims

The authors have previously reported that cellular retinol-binding protein 1 (CRBP1) gene gain and its expression correlated significantly with survival in laryngeal carcinoma patients. The authors hypothesised that inactivation of theCRBP1gene through CpG methylation is associated with patient status and gene expression. In this work, the authors determine the expression and methylation status of theCRBP1gene and its correlation with clinical variables of laryngeal carcinoma patients.

Methods

TheCRBP1gene methylation promoter was assessed by methylation specific PCR analysis in tissue samples from larynx cancer specimens and its expression was assessed by immunohistochemistry on paraffin embedded tissue using tissue microarray. The results were then compared with the clinical pathological variables and outcome measures. The study included 46 samples from patients with non-metastatic squamous cell carcinoma of the larynx without any previous oncological treatments.

Results

Lack of CRBP1 expression was seen in 17 of the 46 laryngeal carcinoma samples, while the remaining 29 samples showed increased expression. Significant associations were found between CRBP1 expression and methylation and patient status. There was a tendency for association in all clinical stages of the disease.CRBP1gene expression and its unmethylated promoter correlated significantly with survival (p<0.05).

Conclusions

An early event of larynx cancer could be CRBP1 expression related to unmethylation of the promoter region. These features could also be associated with good response and survival. The authors hypothesised that increased expression and unmethylated promoter of theCRBP1gene could be considered as markers for larynx cancer.
EXPLORING THE LIKELIHOOD OF CP VIOLATION IN NEUTRINO OSCILLATIONS
Authors: AHUJA GULSHEEN
Published: November 2011

In view of the latest T2K and MINOS observations regarding the mixing angle s13, we have explored the possibility of the existence of CP violation in the leptonic sector. Using hints from the construction of the "db" unitarity triangle in the quark sector, we have made an attempt to construct the "ν1⋅ν3" leptonic unitarity triangle, suggesting a good possibility of having nonzero CP violation.
RESTORATION OF PARITY SYMMETRY THROUGH PRESYMMETRY
Authors: MATUTE ERNESTO A.
Published: November 2011

Presymmetry, the hidden symmetry underlying the charge and generational patterns of quarks and leptons, is utilized for repairing the left–right asymmetry of the standard model with Dirac neutrinos. It is shown that the restoration of parity is consequent with an indispensable left–right symmetric residual presymmetry. Thus, presymmetry substantiates left–right symmetry and the experimental search for the latter is the test of the former, with the nature of neutrinos as a crucial feature that can distinguish the left–right symmetry alone and its combination with presymmetry. This phenomenological implication is in accordance with the fact that Majorana neutrinos are usually demanded in the first case, but forbidden in the second.
RELAXING A LARGE COSMOLOGICAL CONSTANT IN THE ASTROPHYSICAL DOMAIN
Authors: BAUER FLORIAN , SOLÀ JOAN , ŠTEFANČIĆ HRVOJE
Published: November 2011

We study the problem of relaxing a large cosmological constant in the astrophysical domain through a dynamical mechanism based on a modified action of gravity previously considered by us at the cosmological level. We solve the model in the Schwarzschild–de Sitter metric for large and small astrophysical scales, and address its physical interpretation by separately studying the Jordan's frame and Einstein's frame formulations of it. In particular, we determine the extremely weak strength of fifth forces in our model and show that they are virtually unobservable. Finally, we estimate the influence that the relaxation mechanism may have on pulling apart the values of the two gravitational potentials Ψ(r) and Φ(r) of the metric, as this implies a departure of the model from General Relativity and could eventually provide an observational test of the new framework at large astrophysical scales, e.g. through gravitational lensing.
The structure of the Glenelg-Attadale Lewisianoid Inlier and its relationship to the Moine Thrust Zone
Authors: Barber A. J.
Published: November 2011

Synopsis

The Glenelg-Attadale Lewisianoid Inlier lies adjacent to the Moine Thrust Zone. The inlier is surrounded and divided into Eastern and Western units by Moinian metasediments. The Eastern Unit was emplaced against the Western Unit in the Grenvillian Orogeny. Moinian sediments were deposited unconformably on both units in the Neoproterozoic. During the Late Neoproterozoic Knoydartian and Lower Palaeozoic Caledonian orogenies both the inlier and the overlying Moinian rocks were deformed and metamorphosed in the amphibolite facies. Deformation affected particularly the western and eastern margins of the inlier and a strip of infolded Moinian rocks between Eastern and Western units, with the formation of blastomylonites and isoclinal folding (F1). Above a major décollement in the Moine strip and along the western margin of the inlier, the rocks were folded by easterly plunging reclined (F2) folds. This phase of folding affected mainly the Lewisianoid rocks of the Eastern Unit and the adjacent Moine sediments of the Mountain Belt. Deformation was associated with the formation of a large-scale mushroom interference structure and the extrusion of the inlier northwestwards, towards the foreland, marked by a dominant ESE stretching lineation. In Avernish, reclined F2 folds are cut by randomly-oriented hornblende porphyroblasts, which are altered to biotite and smeared out in localized mylonitic shear zones similar to the mylonites in the Moine Thrust Zone. If these mylonitic shear zones were formed contemporaneously with the mylonites in the Thrust Zone, folding and thrusting events superimposed on the mylonites, must have occurred later than events in the Mountain Belt.
Early Carboniferous stratigraphy in the Firth of Clyde area: new information from the Isle of Bute
Authors: Young G. M. , Caldwell W. G. E.
Published: November 2011

Synopsis

On the Isle of Bute, the Carboniferous Period is represented mainly by volcanic rocks of the Clyde Plateau Volcanic Formation (Viséan, mid- to late Holkerian). Although previously considered to lie on rocks of the Upper Old Red Sandstone (Bute Conglomerate, mainly Famennian) or Kinnesswood Formation of the Inverclyde Group (mainly Tournaisian), exposed contacts in south Bute show the volcanic rocks to lie disconformably on the lower part of the Clyde Sandstone Formation (higher in that same group). Detailed mapping and measurement of stratigraphic sections at several locations in south Bute reveals the Courceyan to Chadian (Inverclyde) sedimentary succession to comprise the Kinnesswood, Ballagan, and the lower part of the Clyde Sandstone formations. In the Ascog area in the east-central part of Bute, the Birgidale Formation (Viséan; Holkerian) overlies these formations and is conformably overlain by volcanic rocks of the Clyde Plateau Volcanic Formation. Newly discovered exposures of the Ballagan Formation at Dunagoil Bay on the west side of south Bute extend the known distribution of the formation on the island. The relatively thin development of Inverclyde formations in south Bute probably reflects the palaeogeographical position of the area on the northeastern shoulder of the now-submerged North-East Arran Trough. The Inverclyde Group rocks are mostly of terrestrial origin but the Ballagan Formation denotes a short-lived shallow marine incursion. Overall, these rocks record a transition from semi-arid to humid climatic conditions, consonant with the suggestion, based on palaeomagnetic investigations, that at the time of deposition the area migrated northwards through arid to tropical palaeolatitudes.
The Early Devonian Acanthodian
Euthacanthus gracilis
from the Midland Valley of Scotland
Authors: Newman Michael J. , Davidson Robert G. , Den Blaauwen Jan L. , Burrow Carole J.
Published: November 2011

Synopsis

The first full description of the Lochkovian acanthodian
Euthacanthus gracilis
, presented here, shows that the species shares many characters with the type species
Euthacanthus macnicoli
supporting its retention in this genus.
Euthacanthus elegans
is deemed to be a junior synonym of
E. gracilis
.
E. gracilis
differs from
E. macnicoli
in having large ‘umbellate’ scales edging the main lateral line canal, and small body scales. The crown morphology of the enlarged lateral line scales are similar to isolated ‘umbellate’ scales described world-wide in the Siluro-Devonian. They have the same general morphology as the sensory line scales on some other acanthodians including the sensory line scales on the head of
Ischnacanthus gracilis
and the lateral lines in
Brochoadmones milesi
. Neither of these articulated forms is closely related to
Euthacanthus
. The crown morphology of the normal flank scales is similar to that of the type species, and also the acritolepid acanthodian
Acritolepis urvantsevi
. Acritolepids are ischnacanthiform acanthodians, and are not closely related to
Euthacanthus
. This similarity indicates that scale crown morphology without histology is not always a useful tool in identifying species or genera from isolated remains.
Integrin α6β4 cooperates with LPA signaling to stimulate Rac through AKAP-Lbc-mediated RhoA activation
Authors: O'Connor Kathleen L. , Chen Min , Towers L. Nicole
Published: November 2011

The α6β4 integrin promotes carcinoma invasion through its ability to promote directed migration and polarization of carcinoma cells. In this study, we explore how the α6β4 integrin cooperates with lysophosphatidic acid (LPA) to activate Rho and Rac small GTPases. Through the use of dominant negative Rho constructs, C3 exotransferase, and Rho kinase inhibitor, we find that Rho is critical for LPA-dependent chemotaxis and lamellae formation. However, utilization of specific Rho isoforms depends on integrin α6β4 expression status. Integrin α6β4-negative MDA-MB-435 cells utilize only RhoC for motility, whereas integrin α6β4-expressing cells utilize RhoC but additionally activate and utilize RhoA for LPA-dependent cell motility and lamellae formation. Notably, the activation of RhoA by cooperative LPA and integrin α6β4 signaling requires the Rho guanine nucleotide exchange factor AKAP-Lbc. We also determine that integrin α6β4 cannot activate Rac1 directly but promotes LPA-mediated Rac1 activation that is dependent on RhoA activity and de novo β1 integrin ligation. Finally, we find that the regulation of Rac1 and RhoA in response to LPA is differentially regulated by phosphodiesterases, PKA, and phosphatidylinositol 3-kinase, thus supporting their spatially distinct compartmentalization. In summary, signaling from integrin α6β4 facilitates LPA-stimulated chemotaxis through preferential activation of RhoA, which, in turn, facilitates activation of Rac1.
Blood pressure regulation in diabetic patients with and without peripheral neuropathy
Authors: Wang Siqi , Randall David C. , Knapp Charles F. , Patwardhan Abhijit R. , Nelson Kevin R. , Karounos Dennis G. , Evans Joyce M.
Published: November 2011

Cardiac and vascular dysfunctions resulting from autonomic neuropathy (AN) are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure (BP) regulation in patients with peripheral neuropathy and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. We continuously measured electrocardiogram, arterial BP, and respiration during supine rest and 70° head-up tilt in 12 able-bodied subjects, 7 diabetics without, 7 diabetics with possible, and 8 diabetics with definite, sensory, and/or motor neuropathy (D2). During the first 3 min of tilt, systolic BP (SBP) of D2 decreased [−10.9 ± 4.5 (SE) mmHg] but increased in able-bodied (+4.8 ± 5.4 mmHg). Compared with able-bodied, D2 had smaller low-frequency (0.04–0.15 Hz) spectral power of diastolic BP, lower baroreflex effectiveness index (BEI), and more SBP ramps. Except for low-frequency power of SBP, D2 had greater SBP and smaller RR interval harmonic and nonharmonic components at rest across the 0.003- to 0.45-Hz region. In addition, our results support previous findings of smaller HF RR interval power, smaller numbers of baroreflex sequences, and lower baroreflex sensitivity in D2. We conclude that diabetic peripheral neuropathy is accompanied by diminished parasympathetic and sympathetic control of heart rate and peripheral vasomotion and diminished baroreflex regulation. A novel finding of this study lies in the sensitivity of BEI to detect AN, presumably because of its combination of parameters that measure reductions in both sympathetic control of vasomotion and parasympathetic control of heart rate.
The p53 inhibitor pifithrin-α can stimulate fibrosis in a rat model of ischemic acute kidney injury
Authors: Dagher Pierre C. , Mai Erik M. , Hato Takashi , Lee So-Young , Anderson Melissa D. , Karozos Stephanie C. , Mang Henry E. , Knipe Nicole L. , Plotkin Zoya , Sutton Timothy A.
Published: November 2011

Inhibition of the tumor suppressor p53 diminishes tubular cell apoptosis and protects renal function in animal models of acute kidney injury (AKI). Therefore, targeting p53 has become an attractive therapeutic strategy in the approach to AKI. Although the acute protective effects of p53 inhibition in AKI have been examined, there is still relatively little known regarding the impact of acute p53 inhibition on the chronic sequelae of AKI. Consequently, we utilized the p53 inhibitor pifithrin-α to examine the long-term effects of p53 inhibition in a rodent model of ischemic AKI. Male Sprague-Dawley rats were subjected to bilateral renal artery clamping for 30 min followed by reperfusion for up to 8 wk. Pifithrin-α or vehicle control was administered at the time of surgery and then daily for 2 days [brief acute administration (BA)] or 7 days [prolonged acute administration (PA)]. Despite the acute protective effect of pifithrin-α in models of ischemic AKI, we found no protection in the microvascular rarefaction at 4 wk or development fibrosis at 8 wk with pifithrin-α administered on the BA schedule compared with vehicle control-treated animals. Furthermore, pifithrin-α administered on a PA schedule actually produced worse fibrosis compared with vehicle control animals after ischemic injury [21%/area (SD4.4) vs.16%/area (SD3.6)] as well as under sham conditions [2.6%/area (SD1.8) vs. 4.7%/area (SD1.3)]. The development of fibrosis with PA administration was independent of microvascular rarefaction. We identified enhanced extracellular matrix production, epithelial-to-mesenchymal transition, and amplified inflammatory responses as potential contributors to the augmented fibrosis observed with PA administration of pifithrin-α.