bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid phenotyping for adult‐plant resistance to stripe rust in wheat
Authors: Hickey Lee T. , Wilkinson Peter M. , Knight Cheridan R. , Godwin Ian D. , Kravchuk Olena Y. , Aitken Elizabeth A. B. , Bansal Urmil K. , Bariana Harbans S. , De Lacy Ian H. , Dieters Mark J.
Published: December 2011

With 6 figures and 4 tables

Stripe or yellow rust (YR) is a significant problem in wheat crops worldwide. The deployment of adult‐plant resistance (APR) genes in wheat cultivars is considered a sustainable management strategy, as these genes confer partial resistance that is usually non‐race specific. Screening for APR typically involves assessment of adult plants in the field, where expression may be influenced by environmental factors. We report a high‐throughput screening method for YR APR that can be used to assess fixed lines or segregating populations grown under controlled environmental conditions (CEC). Inoculation of 3‐week‐old wheat plants from lines with known APR responses to YR, when grown under constant light and temperature, provided disease responses typical of adult plants. Two F2 populations (‘H45’ × ‘ST93’ and ‘Wyalkatchem’ × ‘ST93’) segregating for APR were assessed under both CEC and field conditions. These populations showed similar variation in disease response and lines assessed in both environments attained similar rankings. Phenotypic screening using CEC and continuous light provides an opportunity to accelerate the development of new wheat cultivars with durable resistance.
Microarray analysis on archival multiple sclerosis tissue: Pathogenic authenticity outweighs technical obstacles
Authors: Bradl Monika , Lassmann Hans
Published: December 2011

Probably all neuropathologists know this dilemma: on the one hand, they have extremely precious archival material in their possession, which has been collected over many years from many different laboratories. Typically, this material is extremely well characterized, and often, it contains especially significant tissue specimens from unique cases. On the other hand, they face severe scepticism when they plan to use this archival material for large‐scale gene expression studies by microarray analysis, since previous handling in the absence of RNA protection, prolonged storage at room temperature, and fixation with formaldehyde may dramatically reduce the amount of retrievable RNA. Fortunately, this dilemma can be solved. We give here examples from our own, multiple sclerosis‐centered laboratory and explain why archival tissue might be more authentic for the disease process and might yield more information about the molecular and cellular substrates driving CNS inflammation in MS patients than more recently acquired tissues.
Primary pure squamous cell carcinoma of the thyroid: Report and histogenic consideration of a case involving a BRAF mutation
Authors: Ko Young Sin , Hwang Tae Sook , Han Hye Seung , Lim So Duk , Kim Wan Seop , Oh Seo Young
Published: December 2011

Primary squamous cell carcinoma of the thyroid (SCC‐T) is extremely rare. Its clinical presentation is similar to that of anaplastic carcinoma. Metastasis or extension from the head and neck area should be ruled out, as patients with SCC‐T have a poorer prognosis than patients who have a thyroid extension from an adjacent tumor. An 87‐year‐old man presented with a longstanding painless mass in the right thyroid and had experienced 2 months of pain upon swallowing. A right lobectomy was performed with resection of thyroid cartilage, cricoid cartilage, a portion of the first to third tracheal ring and the right neck lymph node. A histological examination revealed pure SCC. The tumor cells showed diffuse immunoreactivity to CK5/6, CK19 and p63. Immunoreactivity to EMA and p53 was focally positive. TTF‐1, galectin 3 and thyroglobulin immunoreactivity was restricted to the non‐neoplastic thyroid tissue. Both tumor cells and non‐neoplastic follicular cells were negative for CD5. The MIB‐1 index was 36%. DNA extracted from the tumor identified a BRAF V600E mutation in exon 15 and a BRAF G468A mutation in exon 11, whereas DNA from non‐tumorous cells did not contain a mutation. These molecular findings may suggest a direct transformation from papillary carcinoma to SCC‐T.
Matrix‐assisted laser desorption/ionization mass spectrometry reveals decreased calcylcin expression in small cell lung cancer
Authors: Lee Hee Seok , Park Jun Won , Chertov Oleg , Colantonio Simona , Simpson John T. , Fivash Matthew J. , Yoo Chong Woo , Lee Geon Kook , Zo Jae Ill , Kim Heung Tae , Kim Hark Kyun
Published: December 2011

To date, most of the proteomic analyses on lung cancer tissue samples have been performed using surgical specimens, which are obtained after a diagnosis is made. To determine if a proteomic signature obtained from bronchoscopic biopsy samples could be found to assist with diagnosis, 50 lung cancer bronchoscopic biopsy samples and 13 adjacent normal lung tissue samples were analyzed using histology‐directed, matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Lung tissue samples were cryosectioned, and sinapinic acid was robotically deposited on areas of each tissue section enriched in epithelial cells, either tumor or normal. Mass spectra were acquired using a MALDI‐time of flight instrument. Small cell lung cancers (SCLCs) demonstrated clearly different protein profiles from normal lung tissue and from non‐small cell lung cancers (NSCLCs). Calcyclin (m/z= 10 094.7) was identified to be underexpressed in small cell lung cancers, as compared with non‐small cell lung cancers and normal lung tissue. An immunohistochemistry study using 152 NSCLCs and 21 SCLCs confirmed significantly reduced calcyclin stain in SCLCs. Thus, protein profiles obtained from bronchoscopic biopsy samples via MALDI MS distinguish cancerous epithelium from normal lung tissue and between NSCLCs and SCLCs.
Review of the past and present distribution of Mediterranean fruit fly (Ceratitis capitata Wiedemann) and Queensland fruit fly (Bactrocera tryoni Froggatt) in Australia
Authors: Dominiak Bernard C , Daniels David
Published: December 2011

Mediterranean fruit fly (Ceratitis capitata Weidemann, ‘Medfly’) is currently distributed only in Western Australia. Although occasional detections occur in South Australia and the Northern Territory, they invoke a comprehensive and rapid response to prevent establishment. Medfly previously occurred on the eastern coast of mainland Australia. However, it is believed to have been displaced by Queensland fruit fly (Bactrocera tryoni Froggatt, ‘Qfly’), with the last recorded finding of Medfly in 1941 for New South Wales and 1953 in Victoria. Tasmania has not documented any incursions of Medfly since 1920 and the Northern Territory eradicated the last incursion in 1994. In contrast, Qfly is regularly found in parts of Queensland, New South Wales, Victoria, and the Northern Territory. A species closely related to Qfly, B. aquilonis (May), is established in the Northern Territory and northern Western Australia. Occasional detections of Qfly in South Australia and southern Western Australia result in immediate regulatory actions and eradication activities to ensure that it does not become established. South Australia, Tasmania and the Fruit Fly Exclusion Zone are free from fruit flies of economic concern. Any detections of pest fruit fly species in these areas are immediately quarantined and eradicated. The distribution of Qfly has remained largely unchanged for the last half‐century, with established populations along the eastern States and the Northern Territory. The Medfly distribution has also remained unchanged for the last half‐century. Qfly and Medfly do not currently co‐exist in Australia. This is likely because of the differences in egg‐laying habits, competition by larvae in fruit and differences in host range. A similar displacement of Ceratitis by Bactrocera has occurred in other parts of the world.
Pediatric cases of Crimean‐Congo hemorrhagic fever in Turkey
Authors: Tuygun Nilden , Tanir Gonul , Caglayik Dilek Yagci , Uyar Yavuz , Korukluoglu Gulay , Cenesiz Funda
Published: December 2011

Background: The aim of the present study was to identify the epidemiological, clinical and laboratory features of Crimean‐Congo hemorrhagic fever (CCHF) virus infection in children.

Methods: Fifty children infected with CCHF virus in 2005–2010, and hospitalized in the Dr Sami Ulus Maternity and Children's Health and Diseases Training and Research Hospital in Ankara, were included. All the patients had positive IgM and/or polymerase chain reaction for CCHF virus.

Results: Of the 50 patients, 19 were female and 31 were male. Patients were between 8 months and 15 years of age. The majority (82%) of patients had a history of tick bite. Fever (100%), hemorrhagic symptoms (76%), nausea–vomiting (60%), tonsillopharyngitis (50%), malaise (50%), myalgia (46%) and maculopapular rash (24%) were the most common presenting clinical features. Mean platelet count on admission was 110 880/mm3, and the lowest was 7000/mm3. The mean of the lowest white blood cell count was 2860/mm3. Other pathological laboratory findings (asparate aminotransferase, alanine aminotransferase, lactate dehydrogenase and creatine kinase) were elevated, and prothrombin time and activated partial thromboplastin time were prolonged. Twenty‐three patients (46%) were given ribavirin. No side‐effect of ribavirin was seen. No patient died because of CCHF disease.

Conclusion: CCHF virus infections are seen mostly in boys and school children and the adolescent age group. Tick bite is the major risk factor. Fever and hemorrhage are the most frequent presenting symptoms. Tonsillopharyngitis and rash on face or body are probably the most remarkable clinical findings in this disease. The CCHF disease course in Turkey may be mild in children.
Comparison of cerebrospinal fluid in newborns and in infants ≤2 months old with or without meningitis
Authors: Tarvij Eslami Saeedeh , Nassirian Hossain , Mojgan Bayat Mokhtary , Bahieh Zarif Zakerian , Elham Hatami , Alimohamad Nassirian , Ehsan Sobhani
Published: December 2011

Background:  The aim of the present study was to evaluate the characteristics and accuracy of cerebrospinal fluid (CSF) parameters for neonatal meningitis, by comparing CSF data in newborns and in infants ≤2 months of age, with or without meningitis.

Methods:  This case–control study was performed on 120 newborns and infants ≤2 months old. 60 patients with meningitis were considered as the case group and 60 ill patients without meningitis were defined as the control group. Each of the two groups was divided into 0–1 months and 1–2 months old. CSF characteristics were compared in newborns in the case and control groups; in infants ≤2 months old in the case and control groups; and in healthy newborns and healthy infants ≤2 months old.

Results:  The mortality rate was 16.7% in the case group. The differences of CSF parameters in the case and control groups were mostly not significant, except for CSF glucose only in term newborns <7 days old (P= 0.04), and white cell count (WBC) only in 0–7‐day‐old term and preterm neonates (P= 0.04 and P= 0.01, respectively). Polymorphonuclear leukocyte (PMNL) level in the case group was significantly higher than in the control group (P= 0.02). CSF characteristics in healthy newborns were nearly the same as in healthy infants ≤2 months old. Prevalence of positive CSF culture was 31.7% in the case group. The most common pathogen was Neisseria meningitidis in the two age groups. The concomitant positive blood culture in the case group was 26.3%.

Conclusion:  In the case of meningitis with negative CSF culture and Gram stain, diagnosis can be made on CSF parameters, clinical and laboratory findings and suspicion of meningitis. Therefore, a clinical prediction rule to classify risk for bacterial meningitis on evaluation of CSF parameters in any region should be established. More regional trials are needed to enhance the probability of diagnosis according to CSF parameters.
The PvdRT‐OpmQ efflux pump controls the metal selectivity of the iron uptake pathway mediated by the siderophore pyoverdine in Pseudomonas aeruginosa
Authors: Hannauer Mélissa , Braud Armelle , Hoegy Françoise , Ronot Pascale , Boos Anne , Schalk Isabelle J.
Published: December 2011

Pyoverdine (PVD) is the major siderophore produced by Pseudomonas aeruginosa for iron acquisition. PvdRT‐OpmQ is an ATP‐dependent efflux pump involved in the secretion of newly synthesized pyoverdine (PVD) and of PVD that has transported and released its iron into the bacterium from the periplasm into the extracellular medium. This iron uptake pathway also involves an outer membrane transporter, FpvA, for PVD–Fe uptake from the extracellular medium into the periplasm. In binding assays, FpvA bound PVD in complex with many different metals, with affinities from 2.9 nM for PVD–Fe to 13 µM for PVD–Al. Uptake assays with various FpvA and PvdRT‐OpmQ mutants, monitored by inductively coupled plasma‐atomic emission spectrometry (ICP‐AES) for metal detection, and by fluorescence for PVD detection, showed that both metals and PVD accumulated in P. aeruginosa, due to the uptake of these compounds via the FpvA/PVD pathway. Higher levels of accumulation were observed in the absence of PvdRT‐OpmQ expression. Thus, FpvA has a broad metal specificity for both the binding and uptake of PVD–metal complexes, and the PvdRT‐OpmQ efflux pump exports unwanted metals complexed with PVD from the bacterium. This study provides the first evidence of efflux pump involvement in the export of unwanted siderophore–metal complexes and insight into the molecular mechanisms involved controlling the metal selectivity of siderophore‐mediated iron uptake pathways.
Emigration of the plant pathogen Pseudomonas syringae from leaf litter contributes to its population dynamics in alpine snowpack
Authors: Monteil Caroline L. , Guilbaud Caroline , Glaux Catherine , Lafolie François , Soubeyrand Samuel , Morris Cindy E.
Published: December 2011

The recently discovered ubiquity of the plant pathogen Pseudomonas syringae in headwaters and alpine ecosystems worldwide elicits new questions about the ecology of this bacterium and subsequent consequences for disease epidemiology. Because of the major contribution of snow to river run‐off during crop growth, we evaluated the population dynamics of P. syringae in snowpack and the underlying leaf litter during two years in the Southern French Alps. High population densities of P. syringae were found on alpine grasses, and leaf litter was identified as the main source of populations of P. syringae in snowpack, contributing more than the populations arriving with the snowfall. The insulating properties of snow foster survival of P. syringae throughout the winter in the 10 cm layer of snow closest to the soil. Litter and snowpack harboured populations of P. syringae that were very diverse in terms of phenotypes and genotypes. Neither substrate nor sampling site had a marked effect on the structure of P. syringae populations, and snow and litter had genotypes in common with other non‐agricultural habitats and with crops. These results contribute to the mounting evidence that a highly diverse P. syringae metapopulation is disseminated throughout drainage basins between cultivated and non‐cultivated zones.
Single‐stage reconstruction of complex anterior urethral strictures using overlapping dorsal and ventral buccal mucosal grafts
Authors: Hudak Steven J. , Lubahn Jessica D. , Kulkarni Sanjay , Morey Allen F.
Published: December 2011

Study Type – Therapy (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

This technique has been reported to have an excellent success rate in the bulbar urethra, although no data exists for its use in the penile urethra.

This is the first study to report successful use of the technique in the reconstruction of penile urethral strictures.

OBJECTIVE

To review our initial experience with single‐stage overlapping dorsal and ventral buccal mucosa graft (BMG) urethroplasty for the reconstruction of complex anterior urethral strictures.

PATIENTS AND METHODS

Among 696 urethroplasties performed at two tertiary urethroplasty centres from October 2007 to September 2010, single‐stage urethral reconstruction using urethral plate incision and/or excision and overlapping dorsal and ventral BMGs was used in 36 men (5%) with complex urethral strictures (mean length 4.5 cm).

Demographic and perioperative data was tabulated and outcomes were analysed.

RESULTS

Stricture location was bulbar (61%), penile (19%), or both bulbar and penile (20%).

Dorsal grafts, applied only within the most severely strictured segment, measured a mean 42% of the opposing ventral graft length.

At a mean follow‐up of 15.7 months, 32 of the 36 cases were successful (89%).

Repeat urethroplasty was performed in all four recurrences, three of which were successful at a mean follow‐up of 16 months.

CONCLUSION

Single‐stage reconstruction of focally obliterative long urethral strictures using overlapping dorsal and ventral BMGs is safe and effective.
Characterizing abundance–occupancy relationships: there is no artefact
Authors: Webb Thomas J. , Freckleton Robert P. , Gaston Kevin J.
Published: December 2011

Positive abundance–occupancy relationships (AORs) are among the most general macroecological patterns: locally common species are regionally widespread, locally rare species are regionally restricted. In a recent contribution, Wilson (Global Ecology and Biogeography, 2011,20, 193–202) made three claims: (1) that AORs are critically dependent on the method used to calculate average abundance; (2) averaging abundance over occupied sites tends to lead to a very high incidence of negative relationships; (3) this represents a statistical artefact that should be considered in studies of AORs. Here we show that this outcome arises in Wilson's simulations purely due to an arbitrary choice of occupancy models and parameter ranges. The resulting negative relationships are not statistical artefacts, but are easily interpreted in terms of spatial aggregation in abundant species. The fact that empirical evidence fails to support a high prevalence of negative AORs suggests, however, that such parameter combinations arise only rarely in nature. We conclude that simulations that are based on untested assumptions, and that produce patterns unsupported by empirical evidence, have limited use in characterizing AORs, and add little to understanding of the processes driving important relationships between local population size and regional occupancy.
THE ‘REFERENCE POINT’ APPROACH TO THE THEORY OF THE FIRM: AN INTRODUCTION
Authors: Walker Paul
Published: December 2011

There is a small but growing literature on the ‘reference point’ approach to incomplete contracts as formulated by Hart and Moore. The reference point approach has begun to be applied to the theory of the firm in 3 recent papers. This introduction reviews the main theoretical aspects of each of these papers. It then discusses the relationship between the reference point approach to the firm, the transaction cost approach and the property rights approach. Here it is argued that the reference point approach is a step back towardsex postinefficiencies, away from reliance onex anteinefficiencies.
A Multilayered Jurisdictional Patchwork: Immigration Federalism in the United States
Authors: VARSANYI MONICA W. , LEWIS PAUL G. , PROVINE DORIS MARIE , DECKER SCOTT
Published: December 2011

This article focuses on the immigration‐related demands currently being placed on local police in the United States and the emergence of what we call a “multilayered jurisdictional patchwork” (MJP) of immigration enforcement. We report results from nationwide surveys of city police chiefs and county sheriffs and intensive fieldwork in three jurisdictions. The enforcement landscape we describe is complicated by the varying and overlapping responsibilities of sheriffs and city police, and by the tendency for sheriffs to maintain closer relationships with federal Immigration and Customs Enforcement (ICE) authorities. We conclude by reflecting on the implications of the MJP—for immigrants, for their communities, and for the evolving relationship between levels of government in the federal system.
Beyond Lock‐in versus Evolution, towards Punctuated Co‐evolution: On Ron Martin's ‘Rethinking Regional Path Dependence’
Authors: DRAHOKOUPIL JAN
Published: December 2011

This contribution discusses Ron Martin's Roepke Lecture in Economic Geography, ‘Rethinking Regional Path Dependence: Beyond Lock‐in to Evolution’. The lecture offered original ideas on how to avoid some of the pitfalls associated with path dependence theories and the equilibristic understanding of the temporality of economic change. This contribution addresses the question of co‐evolution of the economic and the political in regional and local industrial evolution. It questions the conception of temporality that seems implicit in the framework. It is suggested that the notion of punctuated co‐evolution may be a way forwards, avoiding some of the difficulties in Martin's model. The contribution concludes by discussing the analytical limits of path dependence models.

Dans sa ‘Roepke Lecture in Economic Geography’, Ron Martin a présenté une nouvelle réflexion sur les sentiers de dépendance régionaux, écartant l’idée de ‘blocage’ pour s’attacher à celle d’une évolution. Les idées originales qui sont avancées permettent d’éviter certains des pièges liés aux théories du sentier de dépendance, ainsi qu’à l’approche équilibriste de la temporalité du changement économique. Tout en s’intéressant à la coévolution de l’économique et du politique dans les transformations industrielles locales et régionales, la présente contribution interroge la conception de la temporalité, apparemment implicite dans le cadre d’analyse. La notion de coévolution ponctuelle est proposée comme piste de progression pour échapper à certaines difficultés relevées dans le modèle de Martin. La conclusion examine les limites analytiques des modèles de dépendance de sentier.
Options for Moving beyond the Canonical Model of Regional Path Dependence
Authors: SIMANDAN DRAGOS
Published: December 2011

Ron Martin's recent critique of the canonical model of regional path dependence constitutes a significant original contribution to evolutionary economic geography, and is likely to open up a whole new range of promising directions of theoretical debate and empirical research. In the first part of my commentary, I highlight and discuss the following two assumptions implicit in his work: (1) broader and less restrictive models are better than narrow and restrictive ones; and (2) economic geographers are better served by a model that emphasizes change than by one that emphasizes continuity. In the second part of my commentary, I suggest that Martin's own alternative model could be further developed by: (1) replacing the binary distinction between ‘path as movement to stable state’ and ‘path as dynamic process’ with a continuum; (2) avoiding, with the help of mereology, the hasty generalization to regional economies of processes of change originally theorized in the context of institutions; and (3) tracing the implications for evolutionary economic geography of the recent analytical work on contingency — a hitherto under‐theorized concept that has been central to evolutionary reasoning in general, and to the problematic of lock‐ins in particular.

La récente critique du modèle canonique des sentiers de dépendance régionaux qu’a présentée Ron Martin constitue un apport original important pour la géographie économique évolutionniste, laissant présager de nouvelles orientations prometteuses pour le débat théorique et la recherche empirique. La première partie de ce commentaire souligne et analyse deux hypothèses implicites dans son travail: les modèles généraux et peu contraignants sont meilleurs que les modèles limités et restrictifs; les géographes économiques ont intérêt à utiliser un modèle qui s’attache au changement plutôt qu’à la continuité. Dans la seconde partie, il est suggéré que le modèle de Martin pourrait lui‐même être développé selon trois axes: remplacer par un phénomène continu la perspective binaire du sentier vu soit ‘comme un mouvement vers un état stable’, soit ‘comme un processus dynamique’; en s’appuyant sur la méréologie, éviter de généraliser hâtivement aux économies régionales les processus de changement conçus à l’origine dans le cadre d’institutions; repérer comment la géographie économique évolutionniste peut être affectée par les récents travaux analytiques sur la contingence — notion peu théorisée jusqu’ici, mais centrale pour la logique évolutionniste en général, et la problématique des blocages (lock‐ins) en particulier.
Exposure of foetal neural progenitor cells to IL‐1β impairs their proliferation and alters their differentiation – a role for maternal inflammation?
Authors: Crampton Sean J. , Collins Louise M. , Toulouse Andre , Nolan Yvonne M. , O’Keeffe Gerard W.
Published: December 2011

J. Neurochem. (2012) 120, 964–973.

During pregnancy, activation of the maternal immune system results in inflammation in the foetal nervous system. The causative agents are pro‐inflammatory cytokines like interleukin‐1β (IL‐1β), produced by the foetus. In this study, we examine the effect of IL‐1β on the proliferation and differentiation of neural progenitor cells (NPCs) to better understand its potential effects on the developing brain. We find that the IL‐1β receptor (IL‐1R1) is expressed in the ventral mesencephalon of the developing brain. Furthermore, IL‐1R1 is expressed on Nestin‐positive, Sox‐2‐positive NPCs. IL‐1β treatment reduced the numbers of proliferating NPCs, an effect prevented by the IL‐1R1 receptor antagonist. LDH and MTT assays, and western blot analysis for cleaved caspase 3 and poly(ADP‐ribose) polymerase, confirmed that this was not due to an increase in cell death but rather an induction of differentiation. To further study the effects of IL‐1β on cell fate determination, we differentiated NPCs in the presence and absence of IL‐1β. Il‐1β promoted gliogenesis and inhibited neurogenesis, an effect that required p38‐MAPK kinase signalling. In summary, these data show that exposure of NPCs to IL‐1β affects their development. This necessitates an examination of the consequences that maternal immune system activation during pregnancy has on the cellular architecture of the developing brain.
Tacrine and its analogues impair mitochondrial function and bioenergetics: a lipidomic analysis in rat brain
Authors: Melo Tânia , Videira Romeu A. , André Sónia , Maciel Elisabete , Francisco Carla S. , Oliveira‐Campos Ana M. , Rodrigues Lígia M. , Domingues Maria R.M. , Peixoto Francisco , Manuel Oliveira M.
Published: December 2011

J. Neurochem. (2012) 120, 993–1013.

Tacrine is an acetylcholinesterase (AChE) inhibitor used as a cognitive enhancer in the treatment of Alzheimer’s disease (AD). However, its low therapeutic efficiency and a high incidence of side effects have limited its clinical use. In this study, the molecular mechanisms underlying the impact on brain activity of tacrine and two novel tacrine analogues (T1, T2) were approached by focusing on three aspects: (i) their effects on brain cholinesterase activity; (ii) perturbations on electron transport chain enzymes activities of non‐synaptic brain mitochondria; and (iii) the role of mitochondrial lipidome changes induced by these compounds on mitochondrial bioenergetics. Brain effects were evaluated 18 h after the administration of a single dose (75.6 μmol/kg) of tacrine or tacrine analogues. The three compounds promoted a significant reduction in brain AChE and butyrylcholinesterase (BuChE) activities. Additionally, tacrine was shown to be more efficient in brain AChE inhibition than T2 tacrine analogue and less active than T1 tacrine analogue, whereas BuChE inhibition followed the order: T1 > T2 > tacrine. The studies using non‐synaptic brain mitochondria show that all the compounds studied disturbed brain mitochondrial bioenergetics mainly via the inhibition of complex I activity. Furthermore, the activity of complex IV is also affected by tacrine and T1 treatments while FoF1‐ATPase is only affected by tacrine. Therefore, the compounds’ toxicity as regards brain mitochondria, which follows the order: tacrine >> T1 > T2, does not correlate with their ability to inhibit brain cholinesterase enzymes. Lipidomics approaches show that phosphatidylethanolamine (PE) is the most abundant phospholipids (PL) class in non‐synaptic brain mitochondria and cardiolipin (CL) present the greatest diversity of molecular species. Tacrine induced significant perturbations in the mitochondrial PL profile, which were detected by means of changes in the relative abundance of phosphatidylcholine (PC), PE, phosphatidylinositol (PI) and CL and by the presence of oxidized phosphatidylserines. Additionally, in both the T1 and T2 groups, the lipid content and molecular composition of brain mitochondria PL are perturbed to a lesser extent than in the tacrine group. Abnormalities in CL content and the amount of oxidized phosphatidylserines were associated with significant reductions in mitochondrial enzymes activities, mainly complex I. These results indicate that tacrine and its analogues impair mitochondrial function and bioenergetics, thus compromising the activity of brain cells.
Myosin II activity regulates neurite outgrowth and guidance in response to chondroitin sulfate proteoglycans
Authors: Yu Panpan , Santiago Lizzie Y. , Katagiri Yasuhiro , Geller Herbert M.
Published: December 2011

J. Neurochem. (2012) 120, 1117–1128.

Chondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix in the CNS that inhibit axonal regeneration after CNS injury. Signaling pathways in neurons triggered by CSPGs are still largely unknown. In this study, using well‐characterized in vitro assays for neurite outgrowth and neurite guidance, we demonstrate a major role for myosin II in the response of neurons to CSPGs. We found that the phosphorylation of myosin II regulatory light chains is increased by CSPGs. Specific inhibition of myosin II activity with blebbistatin allows growing neurites to cross onto CSPG‐rich areas and increases the length of neurites of neurons growing on CSPGs. Using specific gene knockdown, we demonstrate selective roles for myosin IIA and IIB in these processes. Time lapse microscopy and immunocytochemistry demonstrated that CSPGs also inhibit cell adhesion and cell spreading. Inhibition of myosin II selectively accelerated neurite initiation without altering cell adhesion and spreading on CSPGs.
Parental monitoring, sensitivity toward parents, and a child's mate preferences
Authors: DUBBS SHELLI L. , BUUNK ABRAHAM P. , LI JESSICA
Published: December 2011

This study investigated gender differences in parental monitoring and sensitivity toward parents and the extent to which these measures can influence children's mate preferences. In 2 samples (the United States and the Netherlands), females reported experiencing higher levels of parental monitoring and being more sensitive toward their parents' feelings regarding mate choice (e.g., being more upset if their parents did not approve of their partner) than males. Individuals displaying higher sensitivity toward parents rated parental investment and cooperation, and to a lesser extent genetic quality, as being more important in a potential mate than individuals lower in sensitivity toward parents. The level of parental monitoring did not significantly predict the importance of parental investment and cooperation or genetic quality in a potential mate.
Making of romantic attachment bonds: Longitudinal trajectories and implications for relationship stability
Authors: FAGUNDES CHRISTOPHER P. , SCHINDLER INES
Published: December 2011

The current study outlined the timing of romantic attachment formation and its implications for relationship stability. People came to prefer their romantic partners for proximity and as a safe haven roughly 4 months after commitment; it took over 2 years to prefer them as their primary secure base. More anxiously attached people preferred their partner for proximity earlier than less anxiously attached people; more avoidantly attached people reported less preference for their romantic partner for all attachment components at the time of initial commitment compared to less avoidantly attached people. Those who more quickly represented their romantic partner as a secure base were less likely to subsequently break up; accordingly, normative attachment development may be prognostic for relationship stability.
Hypnotic Relaxation Vs Amitriptyline for Tension‐Type Headache: Let the Patient Choose
Authors: Ezra Yacov , Gotkine Marc , Goldman Sylvie , Adahan Haim Moshe , Ben‐Hur Tamir
Published: December 2011

(Headache 2012;52:785‐791)

Background.— Although both pharmacological and behavioral interventions may relieve tension‐type headache, data are lacking regarding treatment preference, long‐term patient compliance, and feasibility of behavioral intervention in a standard neurological outpatient clinic setting.

Objective.— To describe patient choice, long‐term compliance, and clinical outcome in a neurological clinic setting where patients are given the choice of the approach they wish to pursue.

Design.— Patients presenting to the headache clinic with a diagnosis of tension‐type headache that justified prophylactic therapy (frequent episodic tension‐type headache or chronic tension‐type headache) were given the choice of amitriptyline (AMT) treatment or hypnotic relaxation (HR), and were treated accordingly. Patients were given the option to cross‐over to the other treatment group at each visit. HR was performed during standard length neurology clinic appointments by a neurologist trained to perform hypnosis (Y.E.). Follow‐up interviews were performed between 6 and 12 months following treatment initiation to evaluate patient compliance, changes in headache frequency or severity, and quality‐of‐life parameters.

Results.— Ninety‐eight patients were enrolled, 92 agreed to receive prophylactic therapy of some kind. Fifty‐three (57.6%) patients chose HR of which 36 (67.9%) actually initiated this treatment, while 39 (42.4%) chose pharmacological therapy with AMT of which 25 (64.1%) patients actually initiated therapy. Patients with greater analgesic use were more likely to opt for AMT (P = .0002). Eleven of the patients initially choosing AMT and 2 of the patients initially choosing HR crossed over to the other group. Seventy‐four percent of the patients in the HR group and 58% of patients in the AMT group had a 50% reduction in the frequency of headaches (P = .16). Long‐term adherence to treatment with HR exceeded that of AMT. At the end of the study period, 26 of 47 patients who tried HR compared with 10 of 27 who tried AMT continued receiving their initial treatment.

Conclusions.— HR treatment was a more popular choice among patients. Patients choosing HR reported greater symptom relief than those choosing AMT and were found to have greater treatment compliance. Patients receiving HR were less likely to change treatments. HR practiced by a neurologist is feasible in a standard neurological outpatient clinic setting; HR training should be considered for neurologists involved in headache treatment.
Iron Deposition in Pain‐Regulatory Nuclei in Episodic Migraine and Chronic Daily Headache by MRI
Authors: Tepper Stewart J. , Lowe Mark J. , Beall Erik , Phillips Micheal D. , Liu Kecheng , Stillman Mark J. , Horvat Mary , Jones Stephen E.
Published: December 2011

Background.— Progression of migraine toward a more disabling chronic form of at least 15 days/month is linked with frequency of attacks. Magnetic resonance imaging (MRI) findings of iron accumulation in the brain, especially in periaqueductal gray and red nucleus, have been correlated with both duration of illness and frequency of attacks.

Methods.— This study therefore evaluated iron deposition as measured with MRI in basal ganglia and pain regulatory nuclei in neurologically healthy control volunteers and in patients with various migraine subtypes: episodic migraine (n = 10) with (n = 4) or without aura (n = 6), and chronic daily headache (n = 11), including medication overuse headache (MOH, n = 8), chronic tension‐type headache (n = 1), and primary chronic migraine (n = 2). The goal was to assess differences in iron deposition among migraine subtypes and controls in the hopes of linking the by‐products of frequent attacks or long duration of illness with these changes.

Results.— The study sought to evaluate the tradeoff between sensitivity and specificity in T2 imaging of patients with migraine, and found that only T2 imaging in the globus pallidus was able to distinguish between episodic and chronic migraine, suggesting that this technique may be the most appropriate to assess migraine frequency. Patients with MOH did not demonstrate T2′ shortening.

Conclusions.— Because iron accumulation should cause shortening of both T2 and T2′, although the lack of significance in observed T2′ difference could be due to increased variance in T2′ the measurement, these results suggest that a mechanism other than increased iron deposition may play a role in the genesis or pathophysiology of MOH.
Radiosurgery for epilepsy: Clinical experience and potential antiepileptic mechanisms
Authors: Quigg Mark , Rolston John , Barbaro Nicholas M.
Published: December 2011

Stereotactic radiosurgery, well established in the noninvasive treatment of focal lesions that are otherwise difficult to access through open surgery, is an emerging technology in the treatment of focal epileptic lesions. Recent studies suggest that seizures from hypothalamic hamartomas and mesial temporal lobe epilepsy remit at clinically significant rates with radiosurgery, but large variations among different studies have raised questions about appropriate treatment protocols and mechanisms. Proposed anticonvulsant mechanisms include neuromodulatory effects or ischemic necrosis of epileptic tissue. An ongoing trial that directly compares efficacy, morbidities, and cost of radiosurgery versus open surgery for mesial temporal lobe epilepsy is underway.
Enhanced frontocentral EEG connectivity in photosensitive generalized epilepsies: A partial directed coherence study
Authors: Varotto Giulia , Visani Elisa , Canafoglia Laura , Franceschetti Silvana , Avanzini Giuliano , Panzica Ferruccio
Published: December 2011

Purpose: Photosensitive epilepsy (PSE) is the most common form of reflex epilepsy presenting with electroencephalography (EEG) paroxysms elicited by intermittent photic stimulation (IPS). To investigate whether the neuronal network undergoes dynamic changes before and during the transition to an EEG epileptic discharge, we estimated EEG connectivity patterns in photosensitive (PS) patients with idiopathic generalized epilepsy.

Methods: EEG signals were evaluated under resting conditions and during 14 Hz IPS, a frequency that consistently induces photoparoxysmal responses (PPRs) in PS patients. Partial directed coherence (PDC), a linear measure of effective connectivity based on multivariate autoregressive models, was used in 10 PS patients and 10 controls. Anterior versus posterior (F3, F4, C3, C4, and P3, P4, O1, O2) and interhemispheric connectivity patterns (F4, C4, P4, O2, and F3, C3, P3, O1) were estimated with focus on beta and gamma band activity.

Key Findings: PDC analysis revealed an enhanced connectivity pattern in terms of both the number and strength of outflow connections in the PS patient group. Under resting condition, the greater connectivity in the PS patients occurred in the beta band, whereas it mainly involved the gamma band during IPS (i.e., the frequencies ranging from 40–60 Hz that include the higher harmonics of the stimulus frequency). Both at rest and during IPS, the differences between the PS patients and controls were due primarily to clearly increased connectivity involving the anterior cortical regions.

Significance: Our findings indicate that PS patients are characterised by abnormal EEG hyperconnectivity, primarily involving the anterior cortical regions under resting conditions and during IPS. This suggests that, even if the occipital cortical regions are the recipient zone of the stimulus and probably hyperexcitable, the anterior cortical areas are prominently involved in generating the hypersynchronization underlying the spike‐and wave discharges elicited by IPS.
Sudden unexpected death in epilepsy: People with nocturnal seizures may be at highest risk
Authors: Lamberts Robert J. , Thijs Roland D. , Laffan Aoife , Langan Yvonne , Sander Josemir W.
Published: December 2011

Purpose:  Most people with epilepsy who die suddenly and whose death is attributed to sudden unexpected death in epilepsy (SUDEP) are found in or by the bed for unknown reasons. We assessed whether those with sleep‐related SUDEP were more likely to have nocturnal seizures, and whether seizure patterns (diurnal vs. nocturnal) differed from people dying suddenly and living controls with epilepsy.

Methods:  Seizure patterns in a cohort of 154 people with epilepsy who died suddenly and after autopsy conformed to the definition of SUDEP and 616 controls living with epilepsy were classified as having “exclusively diurnal” or “nocturnal seizures.” Comparisons were made between the groups. SUDEP was classified as sleep‐related or non–sleep‐related based on eyewitness accounts and the circumstances surrounding death.

Key Findings:  SUDEP was primarily a sleep‐related (58%) and unwitnessed (86%) event. If sleep‐related, SUDEP was more likely to be unwitnessed [odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6–12]. Those with sleep‐related SUDEP were more likely to have a history of nocturnal seizures than those who had non–sleep‐related SUDEP (OR 3.6, 95% CI 1.4–9.4). Those who died were more likely to have a history of nocturnal seizures than living controls (OR 3.9, 95% CI 2.5–6.0). After correction for previously established SUDEP risk factors (Langan et al., 2005), the presence of nocturnal seizures remained significant (OR 2.6, 95% CI 1.3–5.0).

Significance:  Nocturnal seizures seem to be an independent risk factor for SUDEP. These findings underscore the importance of preventive measures, which may include night supervision.
A Statistical Method for Empirical Testing of Competing Theories
Authors: Imai Kosuke , Tingley Dustin
Published: December 2011

Empirical testing of competing theories lies at the heart of social science research. We demonstrate that a well‐known class of statistical models, called finite mixture models, provides an effective way of rival theory testing. In the proposed framework, each observation is assumed to be generated either from a statistical model implied by one of the competing theories or more generally from a weighted combination of multiple statistical models under consideration. Researchers can then estimate the probability that a specific observation is consistent with each rival theory. By modeling this probability with covariates, one can also explore the conditions under which a particular theory applies.We discuss a principled way to identify a list of observations that are statistically significantly consistent with each theory and propose measures of the overall performance of each competing theory. We illustrate the relative advantages of our method over existing methods through empirical and simulation studies.
Optimization of Cardiac Resynchronization Therapy: Importance of Programmed Parameters
Authors: CUOCO FRANK A. , GOLD MICHAEL R.
Published: December 2011

Optimization of Cardiac Resynchronization Therapy. One of the basic tenets of cardiac resynchronization therapy (CRT) is that optimization of programmed parameters is important to maximize the therapeutic response. Both atrioventricular (AV) and interventricular (VV) timing intervals have been suggested as potential methods to improve response rates. A variety of techniques have been described to determine the optimal AV and VV delays. Many of these methods have demonstrated acute hemodynamic benefits; however, multicenter data proving long‐term clinical benefit have been lacking. Echocardiography‐guided methods have been most commonly employed, but no technique has been shown to be superior. In fact, many of these techniques have poor reproducibility and are time‐consuming. Device‐based algorithms allow for a rapid, simplified approach to CRT optimization; however, their clinical value has also been called into question. This review will describe the different techniques for CRT optimization and evaluate their potential value and limitations. (J Cardiovasc Electrophysiol, Vol. 23, pp. 110‐118, January 2012)
Differential Roles of Grb2 and AP‐2 in p38MAPK‐ and EGF‐Induced EGFR Internalization
Authors: Grandal Michael V. , Grøvdal Lene M. , Henriksen Lasse , Andersen Mette H. , Holst Mikkel R. , Madshus Inger H. , van Deurs Bo
Published: December 2011

The epidermal growth factor receptor (EGFR) is an important regulator of normal growth and differentiation, and it is involved in the pathogenesis of many cancers. Endocytic downregulation is central in terminating EGFR signaling after ligand stimulation. It has been shown that p38 MAPK activation also can induce EGFR endocytosis. This endocytosis lacks many of the characteristics of ligand‐induced EGFR endocytosis. We compared the two types of endocytosis with regard to the requirements for proteins in the internalization machinery. Both types of endocytosis require clathrin, but while epidermal growth factor (EGF)‐induced EGFR internalization also required Grb2, p38 MAPK‐induced internalization did not. Interestingly, AP‐2 knock down blocked p38 MAPK‐induced EGFR internalization, but only mildly affected EGF‐induced internalization. In line with this, simultaneously mutating two AP‐2 interaction sites in EGFR affected p38 MAPK‐induced internalization much more than EGF‐induced EGFR internalization. Thus, it seems that EGFR in the two situations uses different sets of internalization mechanisms.
Genome‐wide analysis of oral squamous cell carcinomas revealed over expression of ISG15, Nestin and WNT11
Authors: Vincent‐Chong VK , Ismail SM , Rahman ZAA , Sharifah NA , Anwar A , Pradeep PJ , Ramanathan A , Karen‐Ng LP , Kallarakkal TG , Mustafa WMW , Abraham MT , Tay KK , Zain RB
Published: December 2011

Oral Diseases (2012) 18, 469–476

Background:  Multistep pathways and mechanisms are involved in the development of oral cancer. Chromosomal alterations are one of such key mechanisms implicated oral carcinogenesis. Therefore, this study aims to determine the genomic copy number alterations (CNAs) in oral squamous cell carcinoma (OSCC) using array comparative genomic hybridization (aCGH) and in addition attempt to correlate CNAs with modified gene expression.

Materials and Methods:  Genome‐wide screening was performed on 15 OSCCs using high‐density aCGH. On the basis of pathway analysis, three genes (ISG15, Nestin and WNT11) which mapped to CNA regions were selected for further evaluation of their mRNA expression using quantitative reverse transcriptase PCR (qRT‐PCR).

Results:  Copy number alterations were observed on multiple genomic regions, including amplifications on 1p, 3q, 5p, 6p, 7p, 8q, 9q, 11q, 12q, 16p, 18p and deletions on 3p, 7q, 8p, 11q, 19q and 20q. Among the three selected genes, ISG15 had the highest mRNA expression level with a 22.5‐fold increase, followed by Nestin with a 4.5‐fold increase and WNT11 with a 2.5‐fold increase.

Conclusions:  This study has identified several major CNAs in oral cancer genomes and indicated that this correlates with over expression of the ISG15, WNT11, and Nestin genes.