bluuebunny/crossref_metadata_2025 huggingface dataset:
Einstein’s Theory of Gravity and the Problem of Missing Mass
Authors: Ferreira Pedro G. , Starkman Glenn D.
Published: November 2009

Missing Mass Explained?

The motion and distribution of galaxies and clusters of galaxies within the universe suggest that there is far more matter than can be seen directly through telescopes. Alternatively, perhaps our understanding of gravity is flawed, leading to a mismatch between the gravitational field inferred from the observed mass distribution in the universe and the observed gravitational field.
Ferreira and Starkman
(p.
812
) review the viability of modifying theories of gravity to solve the problem of missing mass. It emerges that theories of modified gravity remain viable but have become more complex, involving gravitating invisible elements. However, what you see is still not what you get.
Restoration of Ecosystem Services for Environmental Markets
Authors: Palmer Margaret A. , Filoso Solange
Published: November 2009

Ecological restoration is an activity that ideally results in the return of an ecosystem to an undisturbed state. Ecosystem services are the benefits humans derive from ecosystems. The two have been joined to support growing environmental markets with the goal of creating restoration-based credits that can be bought and sold. However, the allure of these markets may be overshadowing shortcomings in the science and practice of ecological restoration. Before making risky investments, we must understand why and when restoration efforts fall short of recovering the full suite of ecosystem services, what can be done to improve restoration success, and why direct measurement of the biophysical processes that support ecosystem services is the only way to guarantee the future success of these markets. Without new science and an oversight framework to protect the ecosystem service assets which people depend, markets could actually accelerate environmental degradation.
Water and the Oxidation State of Subduction Zone Magmas
Authors: Kelley Katherine A. , Cottrell Elizabeth
Published: November 2009

Tracing Mantle Oxidation

The chemical composition of the Earth's mantle varies with tectonic setting. For example, basaltic melts near subduction zones are more oxidized than magma near divergent plate boundaries.
Kelley and Cottrell
(p.
605
; see the Perspective by

Hirschmann

) examined melts formed in different tectonic environments, using highly sensitive synchrotron-based analytical methods. The oxidation state of Fe increased with water content and mobile trace elements concentrations. Thus, fluids released from wet subducting plates drive mantle oxidation above subduction zones, which may help to explain the spatial differences in oxygen fugacity of the mantle.
A Probable Pollination Mode Before Angiosperms: Eurasian, Long-Proboscid Scorpionflies
Authors: Ren Dong , Labandeira Conrad C. , Santiago-Blay Jorge A. , Rasnitsyn Alexandr , Shih ChungKun , Bashkuev Alexei , Logan M. Amelia V. , Hotton Carol L. , Dilcher David
Published: November 2009

Long-Lost Pollinators

The rise of angiosperms in the Early Cretaceous (∼140 million years ago) was accompanied by coevolution of a variety of insects, including flies, bees, and wasps required for pollination.

Ren
et al.

(p.
840
; see the Perspective by

Ollerton and Coulthard

) show that three families of scorpionflies had already evolved specialized mouth parts for feeding on the nectar of gymnosperms, as early as the Middle Jurassic (∼170 million years ago). The diversity and specialization of these insects and related plant structures suggests that they were also involved in pollination. These families died out later in the Cretaceous as angiosperms began to dominate.
Structure of the LKB1-STRAD-MO25 Complex Reveals an Allosteric Mechanism of Kinase Activation
Authors: Zeqiraj Elton , Filippi Beatrice Maria , Deak Maria , Alessi Dario R. , van Aalten Daan M. F.
Published: November 2009

Solving Pseudokinases

Mutations of the protein kinase LKB1 are associated with cancer in humans. Many kinases are activated by phosphorylation, but LKB1 is activated by STRADα, a pseudokinase that is similar to protein kinases and binds ATP, but does not phosphorylate substrates. By solving the crystal structure of an activating complex containing LKB,

Zeqiraj
et al.

(p.
1707
, published online 5 November) show that STRADα works with another protein, MO25α, to hold LKB1 in an active conformation. The results may help explain the evolutionary origin of pseudokinases, the biological roles of other pseudokinases, and the mechanisms of disease-causing mutations in LKB1.
Dynamical Steering and Electronic Excitation in NO Scattering from a Gold Surface
Authors: Shenvi Neil , Roy Sharani , Tully John C.
Published: November 2009

Simulating Surfaces

Although modern computational chemistry can often match or even exceed experimental accuracy in modeling gas phase reactions, the surface-bound processes involved in most practical catalysis pose a substantially greater challenge to theory (see the Perspective by

Hasselbrink

).

Díaz
et al.

(p.
832
) show that a modification to standard density functional methods can predict reaction barrier heights to within 1 kilocalorie per mole for the widely studied dissociative adsorption of dihydrogen on copper. In a complementary study,

Shenvi
et al.

(p.
829
) apply an efficient algorithmic framework to model transitions among multiple electronic states at a metal surface and successfully account for the complex dependence of nitric oxide scattering on the small molecule's vibrations and rotations.
High Diversity of the Viral Community from an Antarctic Lake
Authors: López-Bueno Alberto , Tamames Javier , Velázquez David , Moya Andrés , Quesada Antonio , Alcamí Antonio
Published: November 2009

Shivering Viromes

Despite its icy reputation, freshwater ponds and lakes do occur in Antarctica, and open freshwater can be found for a few brief weeks during the austral summer. The ecology of these lakes is, as expected, rather specialized to cope with the extreme seasonal conditions. In a metagenomic study,

López-Bueno
et al.

(p.
858
) inspected the virus community of Lake Limnopolar on Livingston Island and found an unexpectedly rich genetic diversity. A dominant group of previously unidentified single-stranded DNA viruses was found, and a striking shift after ice-melt in spring from single-stranded to double-stranded DNA viruses was observed, probably as their algal hosts started to bloom with increasing daylight hours. The diverse viruses may donate specialized genes that host organisms can also exploit to aid their survival under winter extremes of heat and light deprivation.
Evolution of Animal Pollination
Authors: Ollerton Jeff , Coulthard Emma
Published: November 2009

Animals pollinated specialized seed plants even before flowering plants evolved.
Capturing the Complexities of Molecule-Surface Interactions
Authors: Hasselbrink Eckart
Published: November 2009

Two large computational studies describe how theory can better account for the way in which molecules scatter from or react with metal surfaces.
Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA Nanoarrays
Authors: Drmanac Radoje , Sparks Andrew B. , Callow Matthew J. , Halpern Aaron L. , Burns Norman L. , Kermani Bahram G. , Carnevali Paolo , Nazarenko Igor , Nilsen Geoffrey B. , Yeung George , Dahl Fredrik , Fernandez Andres , Staker Bryan , Pant Krishna P. , Baccash Jonathan , Borcherding Adam P. , Brownley Anushka , Cedeno Ryan , Chen Linsu , Chernikoff Dan , Cheung Alex , Chirita Razvan , Curson Benjamin , Ebert Jessica C. , Hacker Coleen R. , Hartlage Robert , Hauser Brian , Huang Steve , Jiang Yuan , Karpinchyk Vitali , Koenig Mark , Kong Calvin , Landers Tom , Le Catherine , Liu Jia , McBride Celeste E. , Morenzoni Matt , Morey Robert E. , Mutch Karl , Perazich Helena , Perry Kimberly , Peters Brock A. , Peterson Joe , Pethiyagoda Charit L. , Pothuraju Kaliprasad , Richter Claudia , Rosenbaum Abraham M. , Roy Shaunak , Shafto Jay , Sharanhovich Uladzislau , Shannon Karen W. , Sheppy Conrad G. , Sun Michel , Thakuria Joseph V. , Tran Anne , Vu Dylan , Zaranek Alexander Wait , Wu Xiaodi , Drmanac Snezana , Oliphant Arnold R. , Banyai William C. , Martin Bruce , Ballinger Dennis G. , Church George M. , Reid Clifford A.
Published: November 2009

Toward $1000 Genomes

The ability to generate human genome sequence data that is complete, accurate, and inexpensive is a necessary prerequisite to perform genome-wide disease association studies.

Drmanac
et al.

(p.
78
, published online 5 November) present a technique advancing toward this goal. The method uses Type IIS endonucleases to incorporate short oligonucleotides within a set of randomly sheared circularized DNA. DNA polymerase then generates concatenated copies of the circular oligonucleotides leading to formation of compact but very long oligonucleotides which are then sequenced by ligation. The relatively low cost of this technology, which shows a low error rate, advances sequencing closer to the goal of the $1000 genome.
Epigenetics: The Final Frontier?
Authors: Dove Alan
Published: November 2009

Epigenetics is hot. In recent years, researchers in fields as diverse as cell biology, development, and even microbial pathogenesis have become very interested in heritable traits that don't rely on DNA. The idea itself is not new--cancer biologists have known for decades that mechanisms such as DNA methylation and chromatin modification can transmit changes to subsequent generations of cells without changing DNA sequences--but studying these phenomena has recently been increasing in popularity, aided by new technological innovations.
Peer Review Not Popular at Homeland Security
Authors: Bhattacharjee Yudhijit
Published: November 2009

An analysis of the Department of Homeland Security's $1 billion science and technology directorate has found that very little of its basic science research budget was awarded using peer review.
CIRM Awards Seek to Move Cell Therapies to the Clinic
Authors: Kaiser Jocelyn
Published: November 2009

Five years after it launched, the California Institute for Regenerative Medicine (CIRM) last week awarded its first disease-oriented grants—$230 million to 14 teams—intended to speed stem cell therapies to patients.
Developing Countries to Get Some H1N1 Vaccine—But When?
Authors: Enserink Martin
Published: November 2009

The World Health Organization has promised to supply developing countries with H1N1 vaccine donated by manufacturers and rich countries. But it has secured only about 200 million doses for 95 countries that together are home to a third of the world's population.
When Counting Jobs Isn't Enough
Authors: Mervis Jeffrey
Published: November 2009

A federal pilot project launched this summer aims not just to improve the tracking of jobs created by the $787 billion stimulus package but also to lay the foundation for a system to measure the impact of research on the U.S. economy.
Aufbau Ost: Max Planck's East German Experiment
Authors: Vogel Gretchen
Published: November 2009

The Max Planck Society's expansion into the former East Germany seeded top science into the region, but challenges remain in making sure the successes take root.
No Genome Left Behind
Authors: Pennisi Elizabeth
Published: November 2009

A project to sequence 10,000 vertebrates has just been launched, but sequencing technologies are not yet up to the task.
Seed abortion in the bat pollinated Neotropical tree species,Caryocar brasiliense(Caryocaraceae)
Authors: Collevatti Rosane G. , Estolano Raquel , Garcia Silmara F. , Hay John D.
Published: November 2009

In self-compatible plants, the reduction in brood size may be caused either by inbreeding depression, resource limitation, maternal regulation of offspring quality, or by sibling rivalry. We studied seed abortion in Caryocar brasiliense Camb. (Caryocaraceae), a Neotropical tree species, to verify whether seeds sired by self-pollination are aborted. Fruits were sampled from 23 mother trees to estimate seed set and proportion of aborted seeds. Ripened and aborted seeds from 18 mother trees were genotyped using 10 microsatellite loci together with mother trees and all nearby adults (83 adults) to determine the pollen donor by assignment test. From the 541 seeds, 190 were aborted and the mean number of aborted seeds per fruit was 0.627 (SD = 0.807). Proportion of aborted seeds was different among mother trees and among fruits within mother trees. All but three aborted seeds were sired by self-pollination and selfed seeds were aborted in fruits harbouring both selfed and outcrossed seeds. Aborted outcrossed seeds were sired by pollen donors closely related to mother trees. Our results strongly support that seed abortion in C. brasiliense may be the outcome of inbreeding depression and sibling rivalry when selfed and outcross pollinated ovules compete.
Rôles biologiques des antiports vacuolaires NHX : acquis et perspectives d’amélioration génétique des plantes
Authors: Hanana Mohsen , Cagnac Olivier , Zarrouk Mokhtar , Blumwald Eduardo
Published: November 2009

NHX antiporters are membrane proteins that mediate cation and proton exchanges across vacuolar membranes. In particular, they catalyze the Na+–H+exchanges and, consequently, sequester Na+into vacuoles. The latter mechanism protects essential enzymatic reactions in the cytoplasm from toxicity due to excess Na+levels, while adjusting turgor by means of vacuolar Na+as an osmoticum. The function of vacuolar NHX antiporters in plants has been studied primarily in the context of salinity tolerance. The expression of induction of NHX-type genes in response to NaCl treatment was observed for most NHX-type genes characterized, and their overexpression allowed to confer an improved tolerance to salinity, initially in transgenic model plants ( Arabidopsis thaliana (L.) Heynh. and tobacco) and, subsequently, in cultivated plants (tomato, rice, wheat, etc.). As many genes encoding these antiporters have been cloned from both salt-sensitive and salt-tolerant species and because multiple isoforms can be identified in genomes that have been sequenced, it is likely that these antiporters assume functions at various levels beside providing tolerance to salinity. Indeed, in addition to playing a role in other known functions such as pH regulation, ion homeostasis, and osmotic and turgor regulation, they also have an important role in diverse physiological processes, including control of cell growth and proliferation, vesicle biogenesis and trafficking, protein targeting, and more specifically, leaf development, blue-flower coloration, and grape berry maturation. If we take into account the high probability that vacuolar NHX antiporters play a role in multiple physiological processes, it would be possible, by exploiting the available information, to use several molecular methods, such as overexpression or silencing of NHX-type genes, to achieve the selection and improvement of interesting plant characters, including flower coloration, fruit maturation, and tolerance to salinity and drought.
Mounting evidence against the role of ICC in neurotransmission to smooth muscle in the gut
Authors: Goyal Raj K. , Chaudhury Arun
Published: November 2009

How nerves transmit their signals to regulate activity of smooth muscle is of fundamental importance to autonomic and enteric physiology, clinical medicine, and therapeutics. A traditional view of neurotransmission to smooth muscles has been that motor nerve varicosities release neurotransmitters that act on receptors on smooth muscles to cause their contraction or relaxation via electromechanical and pharmacomechanical signaling pathways in the smooth muscle. In recent years, an old hypothesis that certain interstitial cells of Cajal (ICC) may transduce neural signals to smooth muscle cells has been resurrected. This later hypothesis is based on indirect evidence of closer proximity and presence of synapses between the nerve varicosities and ICC, gap junctions between ICC and smooth muscles, and presence of receptors and signaling pathways for the neurotransmitters and ICC. This indirect evidence is at best circumstantial. The direct evidence is based on the reports of loss of neurotransmission in mutant animals lacking ICC due to c-Kit receptor deficiency. However, a critical analysis of the recent data show that animals lacking ICC have normal cholinergic and purinergic neurotransmission and tachykinergic neurotransmission is actually increased. The status of nitrergic neurotransmission in c-Kit deficient animals has been controversial. However, reports suggest that 1) nitrergic neurotransmission in the internal anal sphincter does not require ICC and 2) the in vivo phenotype of ICC deficiency does not resemble nNOS deficiency. 3) The most recent report, in this issue of the Journal, concludes that impaired nitrergic neurotransmission may be due to smooth muscle defects associated with c-Kit receptor deficiency.
Prelesional arterial endothelial phenotypes in hypercholesterolemia: universal ABCA1 upregulation contrasts with region-specific gene expression in vivo
Authors: Civelek Mete , Grant Gregory R. , Irolla Chrysta R. , Shi Congzhu , Riley Rebecca J. , Chiesa Oscar A. , Stoeckert Christian J. , Karanian John W. , Pritchard William F. , Davies Peter F.
Published: November 2009

Atherosclerosis originates as focal arterial lesions having a predictable distribution to regions of bifurcations, branches, and inner curvatures where blood flow characteristics are complex. Distinct endothelial phenotypes correlate with regional hemodynamics. We propose that systemic risk factors modify regional endothelial phenotype to influence focal susceptibility to atherosclerosis. Transcript profiles of freshly isolated endothelial cells from three atherosusceptible and three atheroprotected arterial regions in adult swine were analyzed to determine the initial prelesional effects of hypercholesterolemia on endothelial phenotypes in vivo. Cholesterol efflux transporter ATP-binding cassette transporter A1 (ABCA1) was upregulated at all sites in response to short-term high-fat diet. Proinflammatory and antioxidative endothelial gene expression profiles were induced in atherosusceptible and atheroprotected regions, respectively. However, markers for endoplasmic reticulum stress, a signature of susceptible endothelial phenotype, were not further enhanced by brief hypercholesterolemia. Both region-specific and ubiquitous (ABCA1) phenotype changes were identified as early prelesional responses of the endothelium to hypercholesterolemia.
Multivariate adaptive regression splines models for the prediction of energy expenditure in children and adolescents
Authors: Zakeri Issa F. , Adolph Anne L. , Puyau Maurice R. , Vohra Firoz A. , Butte Nancy F.
Published: November 2009

Advanced mathematical models have the potential to capture the complex metabolic and physiological processes that result in heat production or energy expenditure (EE). Multivariate adaptive regression splines (MARS) is a nonparametric method that estimates complex nonlinear relationships by a series of spline functions of the independent predictors. The specific aim of this study is to construct MARS models based on heart rate (HR) and accelerometer counts (AC) to accurately predict EE, and hence 24-h total EE (TEE), in children and adolescents. Secondarily, MARS models will be developed to predict awake EE, sleep EE, and activity EE also from HR and AC. MARS models were developed in 109 and validated in 61 normal-weight and overweight children (ages 5–18 yr) against the criterion method of 24-h room respiration calorimetry. Actiheart monitor was used to measure HR and AC. MARS models were based on linear combinations of 23–28 basis functions that use subject characteristics (age, sex, weight, height, minimal HR, and sitting HR), HR and AC, 1- and 2-min lag and lead values of HR and AC, and appropriate interaction terms. For the 24-h, awake, sleep, and activity EE models, mean percent errors were −2.5 ± 7.5, −2.6 ± 7.8, −0.3 ± 8.9, and −11.9 ± 17.9%, and root mean square error values were 168, 138, 40, and 122 kcal, respectively, in the validation cohort. Bland-Altman plots indicated that the predicted values were in good agreement with the observed TEE, and that there was no bias with increasing TEE. Prediction errors for 24-h TEE were not statistically associated with age, sex, weight, height, or body mass index. MARS models developed for the prediction of EE from HR monitoring and accelerometry were demonstrated to be valid in an independent cohort of children and adolescents, but require further validation in independent, free-living populations.
Impaired left and right ventricular function following prolonged exercise in young athletes: influence of exercise intensity and responses to dobutamine stress
Authors: Banks Laura , Sasson Zion , Busato Marco , Goodman Jack M.
Published: November 2009

We examined the effect of intensity during prolonged exercise (PE) on left (LV) and right ventricular (RV) function. Subjects included 18 individuals (mean ± SE: age = 28.1 ± 1.1 yr, maximal aerobic power = 55.1 ± 1.6 ml · kg−1· min−1), who performed 150 min of exercise at 60 and 80% maximal aerobic power on two separate occasions. Transthoracic echocardiography assessed systolic and diastolic performance, and blood sampling assessed hydration status and noradrenaline levels before (pre), during (15 and 150 min), and 60 min following (post) PE. β-Adrenergic sensitivity pre- and post-PE was assessed by dobutamine stress. High-intensity PE (15 vs. 150 min) induced reductions in LV ejection fraction (69.3 ± 1.3 vs. 63.5 ± 1.3%, P = 0.000), LV strain (−23.5 ± 0.6 vs. −22.3 ± 0.6%, P = 0.034), and RV strain (−26.3 ± 0.6 vs. −23.0 ± 0.6%, P < 0.01). Both exercise intensities induced diastolic reductions (pre vs. post) in the ratio of septal early wave of annular tissue velocities to late/atrial wave of annular tissue velocities (2.15 ± 0.15 vs. 1.62 ± 0.09; 2.21 ± 0.15 vs. 1.48 ± 0.10), ratio of lateral early wave of annular tissue velocities to late/atrial wave of annular tissue velocities (3.84 ± 0.42 vs. 2.49 ± 0.20; 3.56 ± 0.32 vs. 2.08 ± 0.18), ratio of early to late LV strain rate (2.42, ± 0.16 vs. 1.97 ± 0.13; 2.30 ± 0.15 vs. 1.81 ± 0.11), and ratio of early to late RV strain rate (2.03 ± 0.17 vs. 1.51 ± 0.09; 2.16 ± 0.16 vs. 1.44 ± 0.11) ( P < 0.001). Evidence of β-adrenergic sensitivity was supported by a decreased strain, strain rate, ejection fraction, and systolic pressure-volume ratio response to dobutamine ( P < 0.05) with elevated noradrenaline ( P < 0.01). PE-induced reductions in LV and RV systolic function were related to exercise intensity and β-adrenergic desensitization. The clinical significance of exercise-induced cardiac fatigue warrants further research.
Diagnostic Approach to Small Bowel Involvement in Inflammatory Bowel Disease: View of the Endoscopist
Authors: Papadakis Konstantinos A.
Published: November 2009

Recent advances in endoscopic small bowel (SB) techniques have revolutionalized the diagnostic approach of patients with suspected or known inflammatory bowel disease (IBD). Wireless capsule endoscopy (WCE) has become an important diagnostic tool for the evaluation of suspected CD of the SB or in patients with known IBD to rule out SB involvement. The greatest utility of WCE has been observed in cases of suspected CD, where the initial evaluation with traditional radiographic and endoscopic studies has failed to establish the diagnosis. WCE can detect early SB lesions that can be overlooked by traditional radiological studies. The sensitivity of diagnosing SB CD by WCE is superior to other endoscopic or radiological methods such as push enteroscopy, computed tomography or magnetic resonance enteroclysis. The utility of WCE in patients with known CD, IBD unclassified (IBDU) and a select group of patients with ulcerative colitis (UC) can better define the diagnosis and extent of the disease and may lead to reclassification of IBD from UC/IBDU to definitive CD. In addition, previously diagnosed patients with CD may be found to have more significant disease burden in the SB. This information may facilitate more targeted and effective therapies and potentially lead to better patient outcomes. A disadvantage of WCE is its low specificity and the risk of being retained in a strictured area of the SB. Balloon-assisted enteroscopy has essentially replaced push enteroscopy, and has been used to treat CD strictures, obtain biopsies from areas of SB involvement and even retrieving a retained capsule.
Therapy- and Non-Therapy-Dependent Infectious Complications in Inflammatory Bowel Disease
Authors: Epple Hans-Jörg
Published: November 2009

Background: Patients with inflammatory bowel disease (IBD) are susceptible to infections. Results: Independently from immunomodulatory therapy, IBD predisposes to infectious complications. Thus, the incidence of Clostridium difficile infection is increased in IBD patients, and a significant proportion of these patients contracts C. difficile infection outside the hospital and without precedent antibiotic use. Cytomegalovirus infection has been reported in cortico- steroid-naive patients with ulcerative colitis, and infectious gastroenteritis has been linked to initiation and exacerbation of IBD. Finally, in Crohn’s disease there is a substantial risk for abscess formation, and urinary tract infections occur more frequently than in a non-IBD control population. Apart from the disease process itself, factors that predispose to infectious complications in IBD are malnutrition, advanced age, immunosuppressive medications, leukopenia from immunosuppressive medications, and surgery. However, the main risk for infections is clearly related to the use of immunosuppressive agents such as corticosteroids, azathioprine, methotrexate, cyclosporine, and TNF-blocking biologicals. A wide spectrum of infectious complications has been reported in patients treated with these medications, including viral (e.g. CMV, VZV, EBV), bacterial (e.g. Mycobacteria, Listeria, staphylococci), fungal (e.g. Pneumocystis jiroveci, Aspergillus, Candida, Cryptococcus) and protozoal (Toxoplasma) pathogens. The greatest risks obviously relate to the combined use of immunomodulating agents rather than to individual drugs. The risk of infections is also aggravated by an insufficient immunization status as frequently observed in patients with IBD. Conclusion: Physicians treating patients with IBD must be aware of the risk for infectious complications in these patients as well as of strategies to minimize them.
Malignant Transformation in Inflammatory Bowel Disease: Prevention, Surveillance and Treatment – New Techniques in Endoscopy
Authors: Bojarski Christian
Published: November 2009

Patients with a long-standing history of ulcerative colitis (UC) or Crohn’s disease (CD) with a history of inflammation in the colon have a risk for the development of colon cancer. To these patients at least one colonoscopy per year should be offered according to national surveillance guidelines in patients with inflammatory bowel disease (IBD). Following general recommendations, surveillance colonoscopy should be performed without disease activity and four tissue samples each 10 cm should be taken. Beside high-resolution videoendoscopy and magnification endoscopy, the application of dyes applied via a spraying catheter are of additional diagnostic value with a factor 3–4 higher detection rate of intraepithelial neoplasia (IEN). It is under current evaluation if the use of computerized virtual chromoendoscopy techniques (NBI, FICE, High Line/HD+) has the same diagnostic output compared to classical spraying techniques. The detection rate of IEN can be further improved by using newly developed in-vivo histology techniques. A combination of chromoendoscopy with confocal endomicroscopy (CEM) can detect 5-fold higher rates of IEN compared with random biopsy protocols. An alternative technique to CEM is the miniprobe-based CEM. Autofluorescence imaging is an interesting approach for the surveillance of IBD patients with first clinical data published.
Diagnostic Standards in the Pathology of Inflammatory Bowel Disease
Authors: Loddenkemper Christoph
Published: November 2009

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). The recognition of typical morphological features usually allows to distinguish CD from UC. Several infectious diseases like tuberculosis as well as other disorders can mimic IBD and need to be excluded before immunosuppressive treatment is started or surgical intervention planned. IBD is associated with an increased risk for the development of colorectal adenocarcinoma. There is a strong relationship between the presence of intraepithelial neoplasia (IEN) in patients with CD or UC and colon cancer. Thus, the differentiation between biopsies with reactive atypia, low-grade IEN and high-grade IEN is of great importance. Furthermore, distinction between dysplasia-associated lesions or masses (DALM) and sporadic adenoma-like masses (ALM) is crucial as prophylactic colectomy is usually recommended for DALM and polypectomy may be sufficient for ALM. Various features like localization of the lesion, architecture, inflammation and immunohistochemical evaluation of additional markers, e.g. p53 and β-catenin, may be helpful in the distinction of DALM versus ALM. Finally, the use of modern immunosuppressive therapies may go along with an increased susceptibility towards infections, e.g. cytomegalovirus colitis or Epstein-Barr virus-induced lymphoproliferative disorders, and a high degree of awareness by clinicians and pathologists is required in order not to miss these life-threatening complications of IBD.
MDMA Self-Administration in Laboratory Animals: A Summary of the Literature and Proposal for Future Research
Authors: Schenk Susan
Published: November 2009

The prevalence of 3,4-methylenedioxymethamphetamine (MDMA) use has increased globally and the pattern of consumption has changed considerably. Previously, a subculture of MDMA users was fairly restricted to the dance club scene. More recently, use has spread outside of this subculture and now many users consume MDMA frequently and in large amounts and some meet criteria for drug abuse and/or dependence. Because of confounds associated with studying drug users and abusers, animal models have been employed to investigate potential consequences of drug-taking. Among these, self-administration by laboratory animals has been shown to have excellent predictive validity. There have, however, been mixed results with respect to the ability of MDMA to support and maintain self-administration by laboratory animals. This paper reviews the literature on MDMA self-administration in laboratory primates and rodents. Most of the studies in laboratory animals suggest that only low levels of MDMA are self-administered on a daily basis but some have indicated high levels of self-administered MDMA in certain subjects. Differences might be dependent upon the number of test sessions, prior training conditions or other paradigmatic variables. In most cases, MDMA was found to be a lower efficacy reinforcer than other drugs of abuse. It is suggested that the MDMA self-administration develops following a decrease in MDMA-produced serotonin release that occurs with repeated exposure over an extended period of testing. It is hypothesized that the deficit in central serotonin increases the relative MDMA-produced dopamine responses and that this increase in the dopamine response underlies the development and maintenance of MDMA self-administration.
Can the Severity of Dependence Scale Be Usefully Applied to ‘Ecstasy’?
Authors: Bruno Raimondo , Matthews Allison J. , Topp Libby , Degenhardt Louisa , Gomez Rapson , Dunn Matthew
Published: November 2009

Background/Aims: Although use of ‘ecstasy’ (drugs sold as containing 3,4-methylenedioxymethamphetamine) is prevalent, it is typically infrequent, and treatment presentations involving ecstasy as a principal problem drug are relatively rare. Human case reports and animal literature suggest dependence potential, although there may be some unique aspects to this syndrome for ecstasy in comparison to other substances. The Severity of Dependence Scale (SDS) was examined to determine whether this could usefully identify ‘dependent’ ecstasy consumers. Methods: We conducted a cross-sectional survey of 1,658 frequent (at least monthly) ecstasy consumers across Australia, assessing drug use, associated harms and risk behaviours. Dependence was evaluated with the SDS, using a cut-off of ≥4 to identify potential ‘dependence’. Results: One fifth of the participants were screened as potentially dependent. These individuals used ecstasy more frequently, in greater amounts, engaged more extensively in risk behaviours and reported greater role interference than other participants. These findings were independent of methamphetamine use or dependence. The underlying structure of the ecstasy SDS was bifactorial. Conclusions: The SDS has demonstrated construct validity as a screening tool to identify ecstasy users at elevated risk of experiencing adverse consequences, including features of dependence. The underlying structure of dependence symptoms differs for ecstasy compared to other drug classes, and some dependent consumers use the drug infrequently. The unique neurotoxic potential and entactogenic effects of ecstasy may require a distinct nosological classification for the experience of dependence associated with the drug.
Executive Working Memory Deficits in Abstinent Ecstasy/MDMA Users: A Critical Review
Authors: Murphy Philip N. , Wareing Michelle , Fisk John E. , Montgomery Catharine
Published: November 2009

Aims: This review examined studies of executive functioning in abstinent ecstasy (3,4-methylenedioxymethamphetamine, MDMA) users on tasks which had been empirically mapped onto updating, shifting, inhibition and accessing long-term memory executive processes. Studies of some aspects of visuospatial memory performance were also included because of the investment of executive resources in such tasks. Methods:Thirty-three studies were identified for the review following searches of the Psychinfo and Medline databases. Inclusion criteria were the reporting of new empirical findings from participants drug free at the time of testing, in peer-reviewed journals in the English language. Results:Evidence for ecstasy-related performance deficits was strongest for the updating of verbal material, and for visuospatial memory tasks requiring additional processing beyond storage and retrieval. Such processing suggested that the overall level of executive demand was an important consideration. Executive shifting showed little evidence of ecstasy-related impairment, whilst examination of inhibition and long-term memory access presented an unclear picture. Conclusions: All but one of the studies had a cross-sectional design. Although this is a potential weakness with regard to confounds, the necessity of such designs was acknowledged. Studies were generally aware of the need to control for potential confounds, especially the effects of other drugs, through a mixture of group designs and statistical techniques. It was recommended that future studies of executive functioning in ecstasy users should detail the relationship of the tasks and dependent variables reported to specific executive processes and consider the level of executive demand imposed by such tasks.
The Epidemiology of Ecstasy Use and Harms in Australia
Authors: Degenhardt Louisa , Roxburgh Amanda , Dunn Matthew , Campbell Gabrielle , Bruno Raimondo , Kinner Stuart A. , George Jessica , Quinn Brendan , White Nancy , Topp Libby
Published: November 2009

Aims:This paper examines the epidemiology of ecstasy use and harm in Australia using multiple data sources. Design: The data included (1) Australian Customs Service 3,4-methylenedioxymethamphetamine (MDMA) detections; (2) the National Drug Strategy Household and Australian Secondary Student Alcohol and Drug Surveys; (3) data from Australia’s ecstasy and Related Drugs Reporting System; (4) the number of recorded police incidents for ecstasy possession and distribution collated by the N.S.W. Bureau of Crime Statistics and Research; (5) the number of calls to the Alcohol and Drug Information Service and Family Drug Support relating to ecstasy; (6) the Alcohol and Other Drug Treatment Services National Minimum Dataset on number of treatment episodes for ecstasy, and (7) N.S.W. Division of Analytical Laboratories toxicology data on number of deaths where MDMA was detected. Findings: Recent ecstasy use among adults in the general population has increased, whereas among secondary students it has remained low and stable. The patterns of ecstasy consumption among regular ecstasy users have changed over time. Polydrug use and use for extended periods of time (>48 h) remain common among this group. Frequent ecstasy use is associated with a range of risk behaviours and other problems, which tend to be attributed to a number of drugs along with ecstasy. Few ecstasy users present for treatment for problems related to their ecstasy consumption. Conclusions: Messages and interventions to reduce the risks associated with polydrug use and patterns of extended periods of use are clearly warranted. These messages should be delivered outside of traditional health care settings, as few of these users are engaged with such services.
Interactions between 3,4-Methylenedioxymethamphetamine and Ethanol in Humans and Rodents
Authors: Mohamed Wael M.Y. , Hamida Sami Ben , Pereira de Vasconcelos Anne , Cassel Jean-Christophe , Jones Byron C.
Published: November 2009

Methylenedioxymethamphetamine (MDMA, ecstasy) is a widely used recreational drug, often associated with dance parties. Users self-report euphoria, a sense of well-being and increased feelings of affiliation. In experimental animals, MDMA produces an acute, rapid release of serotonin and, to a lesser extent, dopamine and norepinephrine in the brain. It can also produce a dose-dependent, life-threatening hyperthermia in rodents, primates and humans. Moreover, there is evidence of long-term neurological and psychological effects in heavy users. In rats, MDMA increases the locomotor activity. When used recreationally, MDMA is often taken with other drugs including amphetamine, cannabis, cocaine or ethanol (EtOH). Epidemiological data suggest that MDMA-EtOH is one of the most common combinations. In rats, EtOH potentiates MDMA-induced hyperactivity but may attenuate its hyperthermic effect, depending on the ambient temperature. The possibility that EtOH may modify the pharmacokinetics and pharmadynamics of MDMA is of concern in terms of liability for misuse abuse. In this short review, we focus on the known interactions between MDMA and EtOH in humans and rodents.
Weekly γ-Hydroxybutyrate Exposure Sensitizes Locomotor Hyperactivity to Low-Dose 3,4-Methylenedioxymethamphetamine in Rats
Authors: van Nieuwenhuijzen P.S. , Li K.M. , Hunt G.E. , McGregor I.S.
Published: November 2009

Users of the popular party drug 3,4-methylenedioxymethamphetamine (MDMA) sometimes report combining MDMA with γ-hydroxybutyrate (GHB) to enhance the pleasurable effects of both drugs. However, very few studies have examined the influences of this drug combination. The present study investigated the development of locomotor sensitization in laboratory rats given 7 once-weekly exposures to either MDMA, GHB or their combination (MDMA/GHB). The drugs were administered at a high ambient temperature (28°C) to mimic nightclub conditions. MDMA (5 mg/kg), given once weekly, produced a progressively greater locomotor and hyperthermic response over time. In contrast, GHB (500 mg/kg) administered weekly produced consistent low levels of locomotor activity and few changes in body temperature. Rats receiving the mixture of MDMA (5 mg/kg) and GHB (500 mg/kg) showed asymptotic levels of sensitized locomotor activity similar to those seen in rats given MDMA alone, but the development of locomotor sensitization was delayed by coadministered GHB. GHB also delayed the development of MDMA-induced hyperthermia. After a washout period of 5 weeks, rats pre-exposed to MDMA, GHB and MDMA/GHB showed no hyperactivity when tested drug-free in the context in which they had previously received drugs, but displayed a sensitized locomotor response to a low challenge dose of MDMA (2.5 mg/kg). The response to a low dose of methamphetamine (0.5 mg/kg) did not differ among groups. Neurochemical analysis using high-performance liquid chromatography revealed few lasting changes in serotonin, dopamine or their metabolites in the striatum or prefrontal cortex of MDMA- or GHB-pre-exposed rats. These results indicate that GHB modulates the locomotor and hyperthermic response to acute MDMA and that pre-exposure to GHB can sensitize the locomotor response to low doses of MDMA.
GJB2 and GJB6 Genes: Molecular Study and Identification of Novel GJB2 Mutations in the Hearing-Impaired Argentinean Population
Authors: Dalamón Viviana , Lotersztein Vanesa , Béhèran Agustina , Lipovsek Marcela , Diamante Fernando , Pallares Norma , Francipane Liliana , Frechtel Gustavo , Paoli Bibiana , Mansilla Enrique , Diamante Vicente , Elgoyhen Ana Belén
Published: November 2009

Mutations in the GJB2 gene are responsible for more than half of all cases of recessive non-syndromic deafness. This article presents a mutation analysis of the GJB2, GJB6, OTOF and MTRNR1 genes in 252 patients with sensorineural non-syndromic hearing loss. Thirty-one different mutations were identified in GJB2 and GJB6 in 86 of the 252 (34%) patients. We describe for the first time two new mutations in GJB2: the missense mutation c.29 T>C (p.Leu10Pro) in the N terminal domain and c.326 G>T (p.Gly109Val) in the intracytoplasmic domain of connexin 26. This work shows the high prevalence of GJB2 mutations in the Argentinean population, with frequencies that are comparable to those of the Mediterranean area. Most important, it adds two novel GJB2 mutations to be taken into consideration in the genetic diagnosis of non-syndromic sensorineural hearing loss.
Racial Differences in Parkinson’s Disease Medication Use in the Reasons for Geographic and Racial Differences in Stroke Cohort: A Cross-Sectional Study
Authors: Yacoubian Talene A. , Howard George , Kissela Brett , Sands Charles D. , Standaert David G.
Published: November 2009

Background: Previous studies have suggested that African-American populations have a lower prevalence of Parkinson’s disease (PD); however, because African-Americans are underrepresented in many cohorts, this relationship is poorly understood. We evaluated data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to describe potential racial differences in PD prevalence. Methods: We identified subjects using PD medications from the REGARDS study, a national longitudinal cohort study of 30,000 persons over age 45 with approximately equal representation of African-Americans and Whites. Results: The prevalence of PD medication use across the cohort was 0.78% and was less among African-Americans (0.51%) than among Whites (0.97%; OR 1.90; 95% CI 1.31–2.74). There was an association of gender and PD medication use, with a prevalence of 0.61% in females and 0.97% in males (OR 1.57; 95% CI 1.13–2.18). There was no association with income, education level or geographic region of residence. Conclusions: The lower rate of PD medication use among African-Americans supports the suspected lower prevalence of PD among African-Americans suggested by other studies. While racial differences in PD diagnosis and treatment may contribute to the differences we observed, comparable disparities have not been observed in the REGARDS cohort for other diagnoses. Further studies of the REGARDS cohort may lead to important insights into potential biological differences in PD among African-Americans and Whites.
Prevalence of Tuberous Sclerosis Complex in Taiwan: A National Population-Based Study
Authors: Hong Chien-Hui , Darling Thomas N. , Lee Chih-Hung
Published: November 2009

Background/Aims: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 and TSC2 genes. Previous studies have estimated the prevalence of TSC to be 1:8,000 to 1:30,000. The numbers of patients and the populations accessed in these studies are relatively small. The aim of this study is to evaluate the prevalence of TSC in Taiwan with a population of 23 million people. Methods: 95% of Taiwanese are enrolled in a single national health insurance database. This study uses this database to estimate the prevalence of TSC in a large Chinese population. Results: The prevalence of TSC in Taiwan is estimated at 1:95,136. There is no prevalence difference in rural or urban areas. The ages of the patients ranges from 3 months to 75 years, with a mean of 14 ± 11 years. Prevalence by age is 1:14,608, 1:18,851, and 1:24,617 for ages <6, 12, and 18 years, respectively. Only 15% of patients disclose a family history of TSC. The majority of cases (71.2%) are diagnosed in an outpatient visit by a pediatrician. Conclusion: The low prevalence of TSC in Taiwan might result from differences in penetrance, family planning, ethnic groups, and disease-modifying genes.
Different Prevalence Rates of Parkinson’s Disease in Urban and Rural Areas: A Population-Based Study in Taiwan
Authors: Chen Chih Chuan , Chen Ta Fu , Hwang Yuarn Chung , Wen Ying Rong , Chiu Yueh Hsia , Wu Chia Yun , Chen Rong Chi , Tai John Jen , Chen Tony Hsiu Hsi , Liou Horng Huei
Published: November 2009

Background: Rural living has long been debated as a risk factor for idiopathic Parkinson’s disease (IPD). But few community-based studies compared this difference between urban and rural areas. Methods: Population-based surveys by neurologists using a standardized diagnostic protocol were conducted in the urban areas of Keelung City and compared the prevalence rates of IPD with those we had previously determined in the rural area of Ilan County, Taiwan. Subjects were diagnosed with IPD when at least 2 of the 4 cardinal signs of parkinsonism were present and by exclusion of secondary parkinsonism. Gender-specific age-standardized prevalence rates of IPD by using the 1970 and 2000 US censuses were calculated for comparison. Results: The participation rate was 84.9%. The crude prevalence rate of IPD in persons aged 40 years and over was 706 (95% CI: 551–864) per 100,000 population. The age-adjusted prevalence rates by using the 1970 US census were 633 (95% CI: 620–646) for people aged 40 and over and 230 (95% CI: 227–234) for all ages. Our results were similar to those obtained in Sicily, Rotterdam, and 3 communities in China. Moreover, the prevalence rates of IPD in Keelung, the urban area studied, were twice as high as those in Ilan, the rural area studied (p < 0.001). Conclusions: Our results suggest that urban living is more important as a risk factor for IPD development than rural living in Taiwan.