bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of resin‐bonded extracoronal attachments with removable partial denture: case report
Authors: Orsi Iara Augusta , Bezzon Osvaldo Luiz , Marchi Simone , Fernandes Flávio Henrique Carriço Nogueira
Published: May 2009

doi:10.1111/j.1741‐2358.2009.00298.x
 
Use of resin‐bonded extracoronal attachments with removable partial denture: case report

Introduction:  Resin‐bonded extracoronal attachments may be indicated for the abutment teeth of removable partial dentures, especially for anterior teeth when a cingulum rest must be provided. This type of treatment has a series of advantages such as minimal tooth reduction, supragingival margins, favourable stress distribution, and improved aesthetic appearance.

Objective:  To report a clinical case of oral rehabilitation using a combination of resin‐bonded extracoronal attachments joined by a Dolder bar with a removable partial denture.

Case report:  A 60‐year‐old male patient with only the canines in the maxillary arch was restored with a combination of resin‐bonded extracoronal attachments joined by a Dolder bar and a removable partial denture.

Conclusion:  Dentures with resin‐bonded extracoronal attachments can have a number of advantages over traditional clasp‐retained removable partial dentures.
The Founding of the Association for Psychological Science: Part 1. Dialectical Tensions Within Organized Psychology
Authors: Cautin Robin L.
Published: May 2009

The founding of the Association for Psychological Science (APS) did not represent the first time a group of psychologists broke away from the American Psychological Association, the parent association of organized psychology in the United States. In fact, the history of organized psychology is replete with examples of splinter groups that sought to better represent the needs and interests of their specific constituencies. All of these breakaway efforts have occurred amid intradisciplinary tensions—the continual push and pull between unity on the one hand and autonomy on the other—that reflect some of the enduring challenges of the field. A historical examination of this dialectic provides a useful framework within which to understand the founding of the APS, its most recent instantiation.
Patterns of Thinking in Militant Extremism
Authors: Saucier Gerard , Akers Laura Geuy , Shen-Miller Seraphine , Kneževié Goran , Stankov Lazar
Published: May 2009

Recurrent features of the thinking pattern (or mind-set) of violent militant extremists are delineated, discussed, and related to previous research and theory. We examined extremist groups from a diverse range of continents, cultures, and political and religious orientations. We compared statements by (and, to some degree, statements about) these groups and formulated 16 themes common to the militant-extremist mind-set. Among these themes are perceptions of a crisis involving violations of posited sacred values, along with justifications for the use of violence to remediate such problems. There are indications that such themes are not infrequent in the general population. For example, research participants failed to strongly disassociate themselves from the sentiments and framings found in the fanatical items, which undercuts the notion that militant-extremist thinking represents bizarre ideation. Militant-extremist thinking appears to represent a major, aggressive form of fanaticism affected by both dispositional and situational factors. Key themes in this thinking pattern might fit together to construct a potentially compelling narrative, which may be a key part of the ideological appeal of salient militant-extremist groups.
Effect of Tobacco Smoke on the Oral Health of US Women of Childbearing Age
Authors: Iida Hiroko , Kumar Jayanth V. , Kopycka‐Kedzierawski Dorota T. , Billings Ronald J.
Published: May 2009

Objectives: To determine the oral health status of US women of childbearing age and to analyze the effect of tobacco smoke on their oral health. Methods: Data from the 1999‐2004 National Health and Nutrition Examination Survey were evaluated for women 15‐44 years of age. The association of exposure to tobacco smoke with untreated caries, mean DMFS, gingivitis, and periodontitis were examined in bivariate and regression analyses controlling for potential confounders. Results: The prevalence of untreated caries was 25%, for gingivitis 49%, and for periodontitis 6%. After adjusting for potential confounders, self‐reported current smoking was a strong independent risk indicator for untreated caries, periodontitis, and to a lesser extent for greater DMFS count. Women with detectable cotinine levels below 15 ng/mL presented with an increased risk for gingivitis. Independent factors associated with increased risk for untreated caries were being Black, having less than a high school education, Medicaid or no health insurance, previous live births, and infrequent and episodic dental visits. Characteristics associated with gingivitis were being Mexican‐American, obese, pregnant, and having infrequent dental visits. Older age, no insurance, and the last dental visit for treatment were independently associated with periodontitis. Conclusions: Dental caries and periodontitis were prevalent among certain subgroups of women of reproductive age. Smoking was found to be a significant risk indicator for various negative oral health outcomes. Barriers to accessing to dental care that were manifested by untreated caries among Black women, mothers, and Medicaid beneficiaries must be better understood.
Dental Providers' Attitudes Regarding the Application of Fluoride Varnish by Pediatric Health Care Providers
Authors: Swigonski Nancy L. , Yoder Karen M. , Maupome Gerardo , Ofner Susan
Published: May 2009

Objectives: To ascertain what proportion of dental hygienists and dentists in Indiana, United States, support the application of fluoride varnish in medical offices, and to determine if support differed by dental provider characteristics, practice characteristics, a limited assessment of knowledge about fluoride, or use of fluoride. Methods: Practicing dental hygienists and dentists in 2005 were asked to fill out a mail questionnaire. Logistic regression models tested the association of independent variables with support for medical providers applying varnish. Results: Response rates were 36% (dental hygienists) and 37% (dentists); median year of graduation was 1988 and 1981. Sixty‐six percent of respondents were in solo practices, 82% of dentists in general practice, 5% in dental pediatrics, and 13% were other specialists. While 51.2% of dental professionals agreed that medical practices could apply fluoride varnish, 29% responded “none” should be allowed, and 19% were undecided. In the multivariable logistic regression for support of medical practices applying fluoride versus not supporting it, three practice characteristics and two measures of fluoride use were significant. Provider characteristics and a limited assessment about knowledge about fluoride were not significant. Conclusions: Half of dental professionals felt that it was appropriate for medical providers to apply fluoride varnish; pediatric dental professionals were less supportive. A few dental practice characteristics were associated with acceptance of the use of fluoride varnish by medical care providers: targeting messages to dental hygienists and those with practices in mixed rural‐urban areas may be a useful approach to garner greater support for this medical/dental partnership.
Association Between Periodontal Disease and Metabolic Syndrome
Authors: Morita Toyoko , Ogawa Yoko , Takada Koji , Nishinoue Norihide , Sasaki Yoshiyuki , Motohashi Masafumi , Maeno Masao
Published: May 2009

Objectives: Metabolic syndrome is a complex medical disorder characterized by visceral fat‐type obesity involving hypertension, and abnormal glucose and lipid metabolism. The objective of this study was to investigate the relationship between periodontal disease and components of metabolic syndrome (obesity, lipid abnormality, hypertension, and hyperglycemia) in industrial workers of a single company in Tokyo, Japan. Methods: The study subjects consisted of 2,478 adult employees (2,028 men and 450 women; mean age: 43.3 years). The association between the presence of periodontal pockets and components of metabolic syndrome was investigated cross‐sectionally using multiple logistic regression analysis, odds ratios (ORs), and 95 percent confidence intervals (CIs). Results: Body mass index, blood pressure, triglycerides, fasting blood glucose, and hemoglobin A1c (HbA1c) were significantly elevated (P < 0.05) in patients with periodontal pockets of 4 mm or more. We found that the OR of the presence of periodontal pockets adjusted for age, gender, and smoking habit was 1.8 (96 percent CI = 1.4‐2.3) when the subjects with two positive components and without positive component were compared. And it was 2.4 (96 percent CI = 1.7‐2.7) when the subjects with three or four positive components and without positive component were compared. Conclusions: Our findings suggest an association between periodontal disease and metabolic syndrome in Japanese workers between the ages of 20 and 60 years.
Association Between Socioeconomic Factors and Dental Erosion in Brazilian Schoolchildren
Authors: Mangueira Dayane Franco , Sampaio Fábio Correia , Oliveira Andressa Feitosa
Published: May 2009

Objective: The aim of this study was to evaluate if a higher socioeconomic status is a potential risk factor for dental erosion in 6‐ to 12‐year‐old Brazilian schoolchildren. Methods: A sample of 983 children was drawn from 36 schools. A questionnaire was applied to determine socioeconomic background. Clinical exams for dental erosion were carried out by one trained and calibrated examiner considering location, severity, and surface area affected. Chi‐square tests and multivariate analysis were carried out. Results:Dental erosion was detected in 196 children (19.9 percent). From this total, 61.8 percent of the lesions were found in the primary dentition and 38.2 percent in the permanent dentition. The palatal surface was the most affected. Higher prevalence was observed in males (P = 0.005). Dental erosion was more prevalent in private school children than in public school children (P = 0.029). Also, dental erosion was prevalent in children from families with higher income (21.3 percent) than in children from low‐income families (13.5 percent) without significant difference (P > 0.05). A higher prevalence of erosion was observed in those children whose parents had a high education level (22.7 percent, P = 0.05). Conclusions: The data suggest a high prevalence of dental erosion across this age span. Dental erosion seems to occur most often in primary dentition of boys who attended private schools and whose mothers have a high educational status.
Ketoconazole in the treatment of central serous chorioretinopathy: a pilot study
Authors: Golshahi Azadeh , Klingmüller Dietrich , Holz Frank G. , Eter Nicole
Published: May 2009

Purpose:  The aim of this study was to evaluate a possible effect of systemic ketoconazole on visual acuity (VA) and retinal thickness in patients with acute central serous chorioretinopathy (CSCR).

Methods:  Fifteen consecutive patients were treated with ketoconazole 200 mg/day for a period of 4 weeks. Another 15 patients served as a control group. Baseline examination and review after 4 weeks included VA testing and measurement of neuroretinal or pigment epithelial detachment by optical coherence tomography (OCT). Fluorescein angiography was performed to verify the diagnosis.

Results:  At baseline, mean VA in Snellen units was 0.6 ± 0.2 (logMAR 0.2 ± 0.7) in the treatment group and 0.7 ± 0.3 (logMAR 0.2 ± 0.5) in the control group. On OCT, mean neuroretinal or pigment epithelial detachment measured 288 ± 163 μm in the ketoconazole group and 225 ± 51 μm in the control group, respectively. Four weeks later, mean VA improved in both groups. On OCT, neuroretinal or pigment epithelial detachment decreased in both the treatment and control groups. The differences were not statistically significant.

Conclusions:  Although a pharmacological decrease in endogenous cortisol synthesis appears to be a rational approach in the treatment of CSCR, systemic ketoconazole at 200 mg/day was not associated with a significantly better outcome in this preliminary study.
Ocular findings among young men: a 12‐year prevalence study of military service in Poland
Authors: Nowak Michal S. , Jurowski Piotr , Gos Roman , Smigielski Janusz
Published: May 2009

Purpose:  To determine the prevalence of ocular diseases among young men and to assess the main ocular causes reflecting discharge from military service in Poland.

Methods:  A retrospective review of the medical records of 105 017 men undergoing a preliminary examination for military service during the period 1993–2004. Sample size for the study was calculated with 99% confidence within an error margin of 5%. All of the study participants were White men of European origin, most of whom live or lived in Poland. Data regarding the vision status were assessed in 1938 eyes of 969 participants. Two groups were distinguished based on the age of the participants: group I aged 18–24 years, and group II aged 25–34 years.

Results:  Presented visual impairment [visual acuity (VA) < 20/40)] followed by colour vision defects were the most common ocular disorders, accounting for 13.2%. There were statistically significant differences in uncorrected VA as well as in the rates of particular refractive errors in between the age groups (p < 0.05). The prevalence of glaucoma and ocular hypertension was significantly higher in older participants. Six hundred and sixty‐seven (68.8%) participants examined medically in the study period were accepted for military service. However, 302 (31.2%) failed their examination and were temporarily or permanently discharged from duty. Fifty‐two of them (17.2%) were discharged because of various ocular disorders. The most common causes were high refractive errors, which accounted for 38.5% of all the ocular discharges, followed by chronic and recurrent diseases of the posterior segment of the eye, which accounted for 19.2%.

Conclusion:  The prevalence of ocular disorders among young men in an unselected military population was closer to the results obtained in other population‐based studies comprising both men and women in the same age group. High refractive errors followed by chronic and recurrent diseases of the posterior segment of the eye are important causes of medical discharges from military service in Poland.
Urban Governance for Adaptation: Assessing Climate Change Resilience in Ten Asian Cities
Authors: Tanner Thomas , Mitchell Tom , Polack Emily , Guenther Bruce
Published: May 2009

Rapidly expanding urban settlements in the developing world face severe climatic risks in light of climate change. Urban populations will increasingly be forced to cope with increased incidents of flooding, air and water pollution, heat stress and vector‐borne diseases. This research, undertaken with a set of partner research institutes, examines how to manage climate‐related impacts in an urban context by promoting planned and autonomous adaptation in order to by improve resilience in a changing climate. It investigates the linkages between the characteristics of pro‐poor good urban governance, climate adaptation and resilience, and poverty and sustainable development concerns. The paper develops an analytical framework by combining governance literature with rapid climate resilience assessments conducted in ten Asian cities. Based on this empirical data, we argue that a number of key characteristics can be identified to assess and build urban resilience to climate change in a way that reduces the vulnerability of the citizens most at risk from climate shocks and stresses. These characteristics form the basis of a climate resilient urban governance assessment framework, and include (1) decentralisation and autonomy, (2) accountability and transparency, (3) responsiveness and flexibility, (4) participation and inclusion and (5) experience and support. This framework can help to assist in the planning, design and implementation of urban climate change resilience‐building programmes in the future.
The category of toric stacks
Authors: Iwanari Isamu
Published: May 2009

In this paper, we show that there is an equivalence between the 2-category of smooth Deligne–Mumford stacks with torus embeddings and actions and the 1-category of stacky fans. To this end, we prove two main results. The first is related to a combinatorial aspect of the 2-category of toric algebraic stacks defined by I. Iwanari [Logarithmic geometry, minimal free resolutions and toric algebraic stacks, Preprint (2007)]; we establish an equivalence between the 2-category of toric algebraic stacks and the 1-category of stacky fans. The second result provides a geometric characterization of toric algebraic stacks. Logarithmic geometry in the sense of Fontaine–Illusie plays a central role in obtaining our results.
Cluster structures for 2-Calabi–Yau categories and unipotent groups
Authors: Buan A. B. , Iyama O. , Reiten I. , Scott J.
Published: May 2009

We investigate cluster-tilting objects (and subcategories) in triangulated 2-Calabi–Yau and related categories. In particular, we construct a new class of such categories related to preprojective algebras of non-Dynkin quivers associated with elements in the Coxeter group. This class of 2-Calabi–Yau categories contains, as special cases, the cluster categories and the stable categories of preprojective algebras of Dynkin graphs. For these 2-Calabi–Yau categories, we construct cluster-tilting objects associated with each reduced expression. The associated quiver is described in terms of the reduced expression. Motivated by the theory of cluster algebras, we formulate the notions of (weak) cluster structure and substructure, and give several illustrations of these concepts. We discuss connections with cluster algebras and subcluster algebras related to unipotent groups, in both the Dynkin and non-Dynkin cases.
Rigid subsets of symplectic manifolds
Authors: Entov Michael , Polterovich Leonid
Published: May 2009

We show that there is an hierarchy of intersection rigidity properties of sets in a closed symplectic manifold: some sets cannot be displaced by symplectomorphisms from more sets than the others. We also find new examples of rigidity of intersections involving, in particular, specific fibers of moment maps of Hamiltonian torus actions, monotone Lagrangian submanifolds (following the works of P. Albers and P. Biran-O. Cornea) as well as certain, possibly singular, sets defined in terms of Poisson-commutative subalgebras of smooth functions. In addition, we get some geometric obstructions to semi-simplicity of the quantum homology of symplectic manifolds. The proofs are based on the Floer-theoretical machinery of partial symplectic quasi-states.
q-series and weight 3/2 Maass forms
Authors: Bringmann Kathrin , Folsom Amanda , Ono Ken
Published: May 2009

Despite the presence of many famous examples, the precise interplay between basic hypergeometric series and modular forms remains a mystery. We consider this problem for canonical spaces of weight 3/2 harmonic Maass forms. Using recent work of Zwegers, we exhibit forms that have the property that their holomorphic parts arise from Lerch-type series, which in turn may be formulated in terms of the Rogers–Fine basic hypergeometric series.
Algebraic and topological aspects of the schematization functor
Authors: Katzarkov L. , Pantev T. , Toën B.
Published: May 2009

We study some basic properties of schematic homotopy types and the schematization functor. We describe two different algebraic models for schematic homotopy types, namely cosimplicial Hopf alegbras and equivariant cosimplicial algebras, and provide explicit constructions of the schematization functor for each of these models. We also investigate some standard properties of the schematization functor that are helpful for describing the schematization of smooth projective complex varieties. In a companion paper, these results are used in the construction of a non-abelian Hodge structure on the schematic homotopy type of a smooth projective variety.
The two-body problem of ultra-cold atoms in a harmonic trap
Authors: Shea Patrick , van Zyl Brandon P. , Bhaduri Rajat K.
Published: May 2009

We consider two bosonic atoms interacting with a short-range potential and trapped in a spherically symmetric harmonic oscillator. The problem is exactly solvable and is relevant for the study of ultra-cold atoms. We show that the energy spectrum is universal, irrespective of the shape of the interaction potential, provided its range is much smaller than the oscillator length.
Gaussian wave packets in phase space: The Fermi gF function
Authors: Benenti Giuliano , Strini Giuliano
Published: May 2009

A pure quantum state can be equivalently represented by means of its wave function ψ(q) or by the Fermi function gF(q,p), with q and p coordinates and conjugate momenta of the system of interest. We show that a Gaussian wave packet can be conveniently visualized in phase space by the curve gF(q,p)=0. The change in time of the gF=0 curve is calculated for a Gaussian packet evolving freely or under a constant or a harmonic force, and the spreading or shrinking of the packet is easily interpreted in phase space. We also discuss a gedanken prism microscope experiment for measuring the position-momentum correlation. This gedanken experiment, together with the well-known Heisenberg microscope and von Neumann velocimeter, is sufficient to fully determine the state of a Gaussian packet.
Rotating structures and Bryan’s effect
Authors: Joubert Stephan V. , Shatalov Michael Y. , Fay Temple H.
Published: May 2009

In 1890 Bryan observed that when a vibrating structure is rotated the vibrating pattern rotates at a rate proportional to the rate of rotation. During investigations of the effect in various solid and fluid-filled objects of various shapes, an interesting commonality was found in connection with the gyroscopic effects of the rotating object. The effect has also been discussed in connection with a rotating fluid-filled wineglass. A linear theory is developed, assuming that the rotation rate is constant and much smaller than the lowest eigenfrequency of the vibrating system. The associated physics and mathematics are easy enough for undergraduate students to understand.
Optics in a field of gravity
Authors: Eriksen E. , Grøn Øyvind G.
Published: May 2009

An observer at rest in a uniformly accelerated reference frame experiences a parallel gravitational field. As a result, rays of light are formed as circular arcs instead of being straight lines. We deduce how a sphere at rest in this frame and a freely falling sphere in this frame appear to an observer at rest.
Eocene age for Ag–Pb–Zn–Au vein and replacement deposits of the Kokanee Range, southeastern British Columbia
Authors: Beaudoin G. , Roddick J. C. , Sangster D. F.
Published: May 2009

The Ag–Pb–Zn–Au vein and replacement deposits of the Kokanee Range, southeastern British Columbia, are hosted by the Middle Jurassic Nelson batholith and surrounding Cambrian to Triassic metasedimentary rocks in the hanging wall of the transcrustal Slocan Lake Fault, Field relations indicate that mineralization is younger than the Nelson batholith and a Middle Jurassic foliation in the Ainsworth area but coeval or older than Eocene unroofing of the Valhalla metamorphic core complex in the footwall of the Slocan Lake Fault. Lamprophyre and gabbro dykes are broadly coeval with mineralization and have biotite and hornblende K–Ar ages defining a short-lived Middle Eocene alkaline magmatic event between 52 and 40 Ma. An older, Early Cretaceous alkaline magmatic event (141 – 129 Ma) is possible but incompletely documented.K–Ar and step-heating 40Ar/39Ar analyses on hydrothermal vein and alteration muscovite indicate that hydrothermal fluids were precipitating vein and replacement deposits 58–59 Ma ago. Crosscutting relationships with lamprophyre dykes indicate the Kokanee Range hydrothermal system lasted for more than 15 Ma. Eocene crustal extension resulted in a high heat flow and structures which were probably responsible for hydrothermal fluid movement and flow paths.A 100 Ma time interval is documented between batholith emplacement and spatially associated mineralization, ruling out any genetic link between the two. Similar large age differences between granite intrusion and peripheral mineralization have recently been documented for two world-sea le Ag–Pb–Zn vein districts, which suggest that spatial association between granite and Ag–Pb–Zn mineralization is not sufficient to infer a genetic link.
Delta slope processes and turbidity currents in prodeltaic submarine channels, Queen Inlet, Glacier Bay, Alaska
Authors: Phillips Andrew C. , Smith Norman D.
Published: May 2009

Large submarine channels lead away from the coarse-grained fjord-head delta in Queen Inlet, Glacier Bay, Alaska. Coarse sediment loads from Carroll Glacier are transported down the delta foreslope and through the submarine channels, and finer material is dispersed throughout the fjord from overflow plumes. Slides and slumps occur intermittently on the delta foreslope. A recording current meter positioned in a submarine channel 1 m above the bottom and 2.7 km seaward from the delta brink indicated during July 1989 predominantly quasi-continuous downfjord currents, although several small surges were also observed. Flows occurred throughout the daily tidal cycle in both neap and spring periods for intervals of up to several hours, often beginning and ending rapidly. Current velocities ranged from 0 to 120 cm∙s−1, averaging 12 cm∙s−1 over one 56 h period, and 16 cm∙s−1 over a 13 h period. Suspended sediment concentrations 1 m above bottom commonly exceeded 2 g∙L−1 and attained 8.2 g∙L−1. The density added to the bottom flow by high turbidity compensated for density lowered by a slight decrease of salinity attained through mixing with fresh meltwater.The contrast between sporadic surges on the delta foreslope and predominantly quasi-continuous turbidity currents downstream in the submarine channels is interpreted as due to attenuation and overlapping of sediment gravity flows of various sizes and velocities originating at the delta front. The relatively low-density, low-velocity, quasi-continuous currents transport large volumes of sediment through the channels, and probably play an important role in maintaining channel form.
Carbonate sedimentation in an extensional tectonic regime: the Lower Devonian Upper Gaspé Limestones, Quebec Appalachians
Authors: Lavoie Denis
Published: May 2009

Carbonate sedimentation occurred over most of eastern Gaspé Peninsula in Early Devonian time. The resulting succession, known as the Upper Gaspé Limestones, is a 500–1800 m thick unit outcropping in the Connecticut Valley – Gaspé Synclinorium. Detailed stratigraphic and sedimentologic work allows recognition of important thickness and lithofacies variations in a north–south-oriented transect in the eastern part of the peninsula. Variations are spatially associated with Acadian (Middle Devonian) dextral strike-slip faults. Three lithotectonic domains are proposed and interpreted; they are, from north to south, (1) a proximal outer shelf, (2) a distal, gently sloping outer shelf, and (3) a slope or slope toe. Field mapping and reinterpretation of seismic profiles from this area have shown that the faults bounding the three domains are reactivated normal listric faults. Early Devonian vertical movement along these faults caused accelerated subsidence of the central and southern segments of the sedimentary basin and is thought to be responsible for the observed Lower Devonian thickness and megafacies variations in eastern Gaspé.
"Kindleia" fragosa Jordan and "Stylomyleodon" lacus Russell: two amiid fishes from the Late Cretaceous and the Paleocene of Alberta, Canada
Authors: Gaudant Jean
Published: May 2009

Detailed study of the type specimens and of new materials collected in the upper Maastrichtian and Paleocene of Alberta, Canada, leads one to propose new diagnoses of "Kindleia" fragosa Jordan and "Stylomyleodon" lacus Russell, which are two different species of amiid fishes bearing styliform teeth on the vomers and coronoids. Comparison with some amiid fishes from the European Cenozoic shows that both species belong to the genus Cyclurus Agassiz, which was widely distributed in Europe from the Paleocene to the Oligocene.
RNAi and Functional Genomics in Plant Parasitic Nematodes
Authors: Rosso M. N. , Jones J. T. , Abad P.
Published: May 2009

Plant nematology is currently undergoing a revolution with the availability of the first genome sequences as well as comprehensive expressed sequence tag (EST) libraries from a range of nematode species. Several strategies are being used to exploit this wealth of information. Comparative genomics is being used to explore the acquisition of novel genes associated with parasitic lifestyles. Functional analyses of nematode genes are moving toward larger scale studies including global transcriptome profiling. RNA interference (RNAi) has been shown to reduce expression of a range of plant parasitic nematode genes and is a powerful tool for functional analysis of nematode genes. RNAi-mediated suppression of genes essential for nematode development, survival, or parasitism is revealing new targets for nematode control. Plant nematology in the genomics era is now facing the challenge to develop RNAi screens adequate for high-throughput functional analyses.
Hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia in sucrose-fed obese rats via two pathways
Authors: Uebanso Takashi , Taketani Yutaka , Fukaya Makiko , Sato Kazusa , Takei Yuichiro , Sato Tadatoshi , Sawada Naoki , Amo Kikuko , Harada Nagakatsu , Arai Hidekazu , Yamamoto Hironori , Takeda Eiji
Published: May 2009

The mechanism by which replacement of some dietary carbohydrates with protein during weight loss favors lipid metabolism remains obscure. In this study, we investigated the effect of an energy-restricted, high-protein/low-carbohydrate diet on lipid metabolism in obese rats. High-sucrose-induced obese rats were assigned randomly to one of two energy-restricted dietary interventions: a carbohydrate-based control diet (CD) or a high-protein diet (HPD). Lean rats of the same age were assigned as normal control. There was significantly greater improvement in fatty liver and hypertriglyceridemia with the HPD diet relative to the CD diet. Expression of genes regulated by fibroblast growth factor-21 (FGF21) and involved in liver lipolysis and lipid utilitization, such as lipase and acyl-CoA oxidase, increased in obese rats fed the HPD. Furthermore, there was an inverse correlation between levels of FGF21 gene expression (regulated by glucagon/insulin balance) and increased triglyceride concentrations in liver from obese rats. Expression of hepatic stearoyl-CoA desaturase-1 (SCD1), regulated primarily by the dietary carbohydrate, was also markedly reduced in the HPD group (similar to plasma triglyceride levels in fasting animals) relative to the CD group. In conclusion, a hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia effectively relative to a carbohydrate diet. The two cellular pathways at work behind these benefits include stimulation of hepatic lipolysis and lipid utilization mediated by FGF21 and reduction of hepatic VLDL-TG production by SCD1 regulation.
Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin
Authors: Gilson Hélène , Schakman Olivier , Kalista Stéphanie , Lause Pascale , Tsuchida Kunihiro , Thissen Jean-Paul
Published: May 2009

Follistatin (FS) inhibits several members of the TGF-β superfamily, including myostatin (Mstn), a negative regulator of muscle growth. Mstn inhibition by FS represents a potential therapeutic approach of muscle atrophy. The aim of our study was to investigate the mechanisms of the FS-induced muscle hypertrophy. To test the role of satellite cells in the FS effect, we used irradiation to destroy their proliferative capacity. FS overexpression increased the muscle weight by about 37% in control animals, but the increase reached only 20% in irradiated muscle, supporting the role of cell proliferation in the FS-induced hypertrophy. Surprisingly, the muscle hypertrophy caused by FS reached the same magnitude in Mstn-KO as in WT mice, suggesting that Mstn might not be the only ligand of FS involved in the regulation of muscle mass. To assess the role of activin (Act), another FS ligand, in the FS-induced hypertrophy, we electroporated FSI-I, a FS mutant that does not bind Act with high affinity. Whereas FS electroporation increased muscle weight by 32%, the muscle weight gain induced by FSI-I reached only 14%. Furthermore, in Mstn-KO mice, FSI-I overexpression failed to induce hypertrophy, in contrast to FS. Therefore, these results suggest that Act inhibition may contribute to FS-induced hypertrophy. Finally, the role of Act as a regulator of muscle mass was supported by the observation that ActA overexpression induced muscle weight loss (−15%). In conclusion, our results show that satellite cell proliferation and both Mstn and Act inhibition are involved in the FS-induced muscle hypertrophy.
Diabetes increases brain damage caused by severe hypoglycemia
Authors: Bree Adam J. , Puente Erwin C. , Daphna-Iken Dorit , Fisher Simon J.
Published: May 2009

Insulin-induced severe hypoglycemia causes brain damage. The hypothesis to be tested was that diabetes portends to more extensive brain tissue damage following an episode of severe hypoglycemia. Nine-week-old male streptozotocin-diabetic (DIAB; n = 10) or vehicle-injected control (CONT; n = 7) Sprague-Dawley rats were subjected to hyperinsulinemic (0.2 U·kg−1·min−1) severe hypoglycemic (10–15 mg/dl) clamps while awake and unrestrained. Groups were precisely matched for depth and duration (1 h) of severe hypoglycemia (CONT 11 ± 0.5 and DIAB 12 ± 0.2 mg/dl, P = not significant). During severe hypoglycemia, an equal number of episodes of seizure-like activity were noted in both groups. One week later, histological analysis demonstrated extensive neuronal damage in regions of the hippocampus, especially in the dentate gyrus and CA1 regions and less so in the CA3 region ( P < 0.05), although total hippocampal damage was not different between groups. However, in the cortex, DIAB rats had significantly (2.3-fold) more dead neurons than CONT rats ( P < 0.05). There was a strong correlation between neuronal damage and the occurrence of seizure-like activity ( r2 > 0.9). Separate studies conducted in groups of diabetic ( n = 5) and nondiabetic ( n = 5) rats not exposed to severe hypoglycemia showed no brain damage. In summary, under the conditions studied, severe hypoglycemia causes brain damage in the cortex and regions within the hippocampus, and the extent of damage is closely correlated to the presence of seizure-like activity in nonanesthetized rats. It is concluded that, in response to insulin-induced severe hypoglycemia, diabetes uniquely increases the vulnerability of specific brain areas to neuronal damage.
Costimulation as a Platform for the Development of Vaccines: A Peptide-Based Vaccine Containing a Novel Form of 4-1BB Ligand Eradicates Established Tumors
Authors: Sharma Rajesh K. , Elpek Kutlu G. , Yolcu Esma S. , Schabowsky Rich-Henry , Zhao Hong , Bandura-Morgan Laura , Shirwan Haval
Published: May 2009

Vaccines represent an attractive treatment modality for the management of cancer primarily because of their specificity and generation of immunologic memory important for controlling recurrences. However, the efficacy of therapeutic vaccines may require formulations that not only generate effective immune responses but also overcome immune evasion mechanisms employed by progressing tumor. Costimulatory molecules play critical roles in modulating innate, adaptive, and regulatory immunity and have potential to serve as effective immunomodulatory components of therapeutic vaccines. In this study, we tested the function of a novel soluble form of 4-1BB ligand (4-1BBL) costimulatory molecule in modulating innate, adaptive, and regulatory immunity and assessed its therapeutic efficacy in the HPV-16 E7-expressing TC-1 cervical cancer and survivin-expressing 3LL lung carcinoma mouse models. Vaccination with 4-1BBL activated dendritic cells and enhanced antigen uptake, generated CD8+ T-cell effector/memory responses, and endowed T effector cells refractory to suppression by CD4+CD25+FoxP3+ T regulatory cells. Immunization with 4-1BBL in combination with an E7 peptide or survivin protein resulted in eradication of TC-1 and 3LL tumors, respectively. 4-1BBL was more effective than TLR agonists LPS, MPL, and CpG and an agonistic 4-1BB antibody as a component of E7 peptide-based therapeutic vaccine for the generation of immune responses and eradication of TC-1 established tumors in the absence of detectable toxicity. Therapeutic efficacy was associated with reversal of tumor-mediated nonresponsiveness/anergy as well as establishment of long-term CD8+ T-cell memory. Potent pleiotropic immunomodulatory activities combined with lack of toxicity highlight the potential of 4-1BBL molecule as an effective component of therapeutic cancer vaccines. [Cancer Res 2009;69(10):4319–26]
Role of MUTYH and MSH2 in the Control of Oxidative DNA Damage, Genetic Instability, and Tumorigenesis
Authors: Russo Maria Teresa , De Luca Gabriele , Casorelli Ida , Degan Paolo , Molatore Sara , Barone Flavia , Mazzei Filomena , Pannellini Tania , Musiani Piero , Bignami Margherita
Published: May 2009

Mismatch repair is the major pathway controlling genetic stability by removing mispairs caused by faulty replication and/or mismatches containing oxidized bases. Thus, inactivation of the Msh2 mismatch repair gene is associated with a mutator phenotype and increased cancer susceptibility. The base excision repair gene Mutyh is also involved in the maintenance of genomic integrity by repairing premutagenic lesions induced by oxidative DNA damage. Because evidence in bacteria suggested that Msh2 and Mutyh repair factors might have some overlapping functions, we investigated the biological consequences of their single and double inactivation in vitro and in vivo. Msh2−/− mouse embryo fibroblasts (MEF) showed a strong mutator phenotype at the hprt gene, whereas Mutyh inactivation was associated with a milder phenotype (2.9 × 10−6 and 3.3 × 10−7 mutation/cell/generation, respectively). The value of 2.7 × 10−6 mutation/cell/generation in Msh2−/−Mutyh−/− MEFs did not differ significantly from Msh2−/− cells. When steady-state levels of DNA 8-oxo-7,8-dihydroguanine (8-oxoG) were measured in MEFs of different genotypes, single gene inactivation resulted in increases similar to those observed in doubly defective cells. In contrast, a synergistic accumulation of 8-oxoG was observed in several organs of Msh2−/−Mutyh−/− animals, suggesting that in vivo Msh2 and Mutyh provide separate repair functions and contribute independently to the control of oxidative DNA damage. Finally, a strong delay in lymphomagenesis was observed in Msh2−/−Mutyh−/− when compared with Msh2−/− animals. The immunophenotype of these tumors indicate that both genotypes develop B-cell lymphoblastic lymphomas displaying microsatellite instability. This suggests that a large fraction of the cancer-prone phenotype of Msh2−/− mice depends on Mutyh activity. [Cancer Res 2009;69(10):4372–9]
Proteasome Inhibition Potentiates Antitumor Effects of Photodynamic Therapy in Mice through Induction of Endoplasmic Reticulum Stress and Unfolded Protein Response
Authors: Szokalska Angelika , Makowski Marcin , Nowis Dominika , Wilczyński Grzegorz M. , Kujawa Marek , Wójcik Cezary , Młynarczuk-Biały Izabela , Salwa Pawel , Bil Jacek , Janowska Sylwia , Agostinis Patrizia , Verfaillie Tom , Bugajski Marek , Gietka Jan , Issat Tadeusz , Głodkowska Eliza , Mrówka Piotr , Stoklosa Tomasz , Hamblin Michael R. , Mróz Paweł , Jakóbisiak Marek , Golab Jakub
Published: May 2009

Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity toward tumor cells by inducing production of reactive oxygen species such as singlet oxygen. PDT leads to oxidative damage of cellular macromolecules, including proteins that undergo multiple modifications such as fragmentation, cross-linking, and carbonylation that result in protein unfolding and aggregation. Because the major mechanism for elimination of carbonylated proteins is their degradation by proteasomes, we hypothesized that a combination of PDT with proteasome inhibitors might lead to accumulation of carbonylated proteins in endoplasmic reticulum (ER), aggravated ER stress, and potentiated cytotoxicity toward tumor cells. We observed that Photofrin-mediated PDT leads to robust carbonylation of cellular proteins and induction of unfolded protein response. Pretreatment of tumor cells with three different proteasome inhibitors, including bortezomib, MG132, and PSI, gave increased accumulation of carbonylated and ubiquitinated proteins in PDT-treated cells. Proteasome inhibitors effectively sensitized tumor cells of murine (EMT6 and C-26) as well as human (HeLa) origin to PDT-mediated cytotoxicity. Significant retardation of tumor growth with 60% to 100% complete responses was observed in vivo in two different murine tumor models (EMT6 and C-26) when PDT was combined with either bortezomib or PSI. Altogether, these observations indicate that combination of PDT with proteasome inhibitors leads to potentiated antitumor effects. The results of these studies are of immediate clinical application because bortezomib is a clinically approved drug that undergoes extensive clinical evaluations for the treatment of solid tumors. [Cancer Res 2009;69(10):4235–43]
NORE1A Tumor Suppressor Candidate Modulates p21CIP1 via p53
Authors: Calvisi Diego F. , Donninger Howard , Vos Michele D. , Birrer Michael J. , Gordon Laura , Leaner Virna , Clark Geoffrey J.
Published: May 2009

NORE1A (RASSF5) is a proapoptotic Ras effector that is frequently inactivated by promoter methylation in human tumors. It is structurally related to the RASSF1A tumor suppressor and is itself implicated as a tumor suppressor. In the presence of activated Ras, NORE1A is a potent inducer of apoptosis. However, when expressed at lower levels in the absence of activated Ras, NORE1A seems to promote cell cycle arrest rather than apoptosis. The mechanisms underlying NORE1A action are poorly understood. We have used microarray analysis of an inducible NORE1A system to screen for physiologic signaling targets of NORE1A action. Using this approach, we have identified several potential signaling pathways modulated by NORE1A. In particular, we identify the cyclin-dependent kinase inhibitor p21CIP1 as a target for NORE1A activation and show that it is a vital component of NORE1A-mediated growth inhibition. In primary human hepatocellular carcinomas (HCC), loss of NORE1A expression is frequent and correlates tightly with loss of p21CIP1 expression. NORE1A down-regulation in HCC also correlates with poor prognosis, enhanced proliferation, survival, and angiogenic tumor characteristics. Experimental inactivation of NORE1A results in the loss of p21CIP1 expression and promotes proliferation. The best characterized activator of p21CIP1 is the p53 master tumor suppressor. Further experiments showed that NORE1A activates p21CIP1 via promoting p53 nuclear localization. Thus, we define the molecular basis of NORE1A-mediated growth inhibition and implicate NORE1A as a potential component of the ill-defined connection between Ras and p53. [Cancer Res 2009;69(11):4629–37]
The CD4+ T-Cell Response of Melanoma Patients to a MAGE-A3 Peptide Vaccine Involves Potential Regulatory T Cells
Authors: François Violaine , Ottaviani Sabrina , Renkvist Nicolina , Stockis Julie , Schuler Gerold , Thielemans Kris , Colau Didier , Marchand Marie , Boon Thierry , Lucas Sophie , van der Bruggen Pierre
Published: May 2009

Melanoma patients were injected with various vaccines containing a MAGE-A3 peptide presented by HLA-DP4. Anti–MAGE-A3.DP4 T cells were not detectable in the blood before vaccination, but their frequencies after vaccination ranged from 2 × 10−6 to 2 × 10−3 among the CD4+ blood T lymphocytes of the patients. The CD4+ blood T lymphocytes that stained ex vivo with HLA-DP4 tetramers folded with the MAGE-A3 peptide were selected by flow cytometry and amplified under clonal conditions. About 5% of the CD4+ T-cell clones that recognized the MAGE-A3.DP4 antigen had a CD25+ phenotype in the resting state. These CD25+ clones had a high capacity to suppress the proliferation of another T-cell clone after peptide stimulation in vitro. Most of them had high FOXP3 expression in the resting state and an unmethylated FOXP3 intron 1. They produced active transforming growth factor-β but none of cytokines IFN-γ, interleukin-2 (IL-2), IL-4, IL-5, and IL-10. About 20% of CD25− clones had a significant but lower suppressive activity. Most of the CD25− clonal populations contained cells that expressed FOXP3 in the resting state, but FOXP3 demethylation was not observed. We conclude that MAGE-A3.DP4 vaccination can produce CD4+ T cells that may exert regulatory T-cell function in vivo. [Cancer Res 2009;69(10):4335–45]
Epigenetic Silencing of the Tumor Suppressor MicroRNAHsa-miR-124aRegulates CDK6 Expression and Confers a Poor Prognosis in Acute Lymphoblastic Leukemia
Authors: Agirre Xabier , Vilas-Zornoza Amaia , Jiménez-Velasco Antonio , Martin-Subero José Ignacio , Cordeu Lucia , Gárate Leire , San José-Eneriz Edurne , Abizanda Gloria , Rodríguez-Otero Paula , Fortes Puri , Rifón José , Bandrés Eva , Calasanz María José , Martín Vanesa , Heiniger Anabel , Torres Antonio , Siebert Reiner , Román-Gomez José , Prósper Felipe
Published: May 2009

Whereas transcriptional silencing of genes due to epigenetic mechanisms is one of the most important alterations in acute lymphoblastic leukemia (ALL), some recent studies indicate that DNA methylation contributes to down-regulation of miRNAs during tumorigenesis. To explore the epigenetic alterations of miRNAs in ALL, we analyzed the methylation and chromatin status of the miR-124a loci in ALL. Expression of miR-124a was down-regulated in ALL by hypermethylation of the promoter and histone modifications including decreased levels of 3mk4H3 and AcH3 and increased levels of 2mK9H3, 3mK9H3, and 3mK27H3. Epigenetic down-regulation of miR-124a induced an up-regulation of its target, CDK6, and phosphorylation of retinoblastoma (Rb) and contributed to the abnormal proliferation of ALL cells both in vitro and in vivo. Cyclin-dependent kinase 6 (CDK6) inhibition by sodium butyrate or PD-0332991 decreased ALL cell growth in vitro, whereas overexpression of pre-miR124a led to decreased tumorigenicity in a xenogeneic in vivo Rag2−/−γc−/− mouse model. The clinical implications of these findings were analyzed in a group of 353 patients diagnosed with ALL. Methylation of hsa-miR-124a was observed in 59% of the patients, which correlated with down-regulation of miR-124a (P < 0.001). Furthermore, hypermethylation of hsa-miR-124a was associated with higher relapse rate (P = 0.001) and mortality rate (P < 0.001), being an independent prognostic factor for disease-free survival (P < 0.001) and overall survival (P = 0.005) in the multivariate analysis. These results provide the grounds for new therapeutic strategies in ALL either targeting the epigenetic regulation of microRNAs and/or directly targeting the CDK6-Rb pathway. [Cancer Res 2009;69(10):4443–53]