bluuebunny/crossref_metadata_2025 huggingface dataset:
The tobacco‐specific nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) induces mitochondrial and nuclear DNA damage in Caenorhabditis elegans
Authors: Bodhicharla Rakesh , Ryde Ian T. , Prasad G.L. , Meyer Joel N.
Published: September 2013

The metabolites of the tobacco‐specific nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) form DNA adducts in animal models. While there are many reports of formation of nuclear DNA adducts, one report also detected NNK‐induced damage to the mitochondrial genome in rats. Using a different DNA damage detection technology, we tested whether this finding could be repeated in the nematode Caenorhabditis elegans. We treated N2 strain (wild‐type) nematodes with NNK in liquid culture, and applied quantitative PCR to analyze NNK‐induced nuclear and mitochondrial DNA (mtDNA) damage. Our results confirm that NNK causes both nuclear and mtDNA damage. However, we did not detect a difference in the level of nuclear versus mtDNA damage in C. elegans. To test whether the mtDNA damage was associated with mitochondrial dysfunction, we used a transgenic nematode strain that permits in vivo measurement of ATP levels and found lower levels of ATP in NNK‐exposed animals when compared with the unexposed controls. To test whether the lower levels of ATP could be attributed to inhibition of respiratory chain components, we investigated oxygen consumption in whole C. elegans and found reduced oxygen consumption in exposed animals when compared with the unexposed controls. Our data suggest a model in which NNK exposure causes damage to both C. elegans nuclear and mitochondrial genomes, and support the hypothesis that the mitochondrial damage is functionally important in this model. These results also represent a first step in developing this genetically tractable organism as a model for assessing NNK toxicity. Environ. Mol. Mutagen. 55:43–50, 2014. © 2013 Wiley Periodicals, Inc.
Sea‐level rise impact on fresh groundwater lenses in two‐layer small islands
Authors: Ketabchi Hamed , Mahmoodzadeh Davood , Ataie‐Ashtiani Behzad , Werner Adrian D. , Simmons Craig T.
Published: September 2013

The fresh groundwater lenses (FGLs) of small islands can be highly vulnerable to climate change impacts, including sea‐level rise (SLR). Many real cases of atoll or sandy islands involve two‐layer hydrogeological conceptualizations. In this paper, the influential factors that affect FGLs in two‐layer small islands subject to SLR are investigated. An analytical solution describing FGLs in circular islands, composed of two geological layers, is developed for the simplified case of steady‐state and sharp‐interface conditions. An application of the developed model is demonstrated to estimate the FGL thickness of some real‐world islands by comparison with existing FGL thickness data. Furthermore, numerical modelling is applied to extend the analysis to consider dispersion effects and to confirm comparable results for both cases. Sensitivity analyses are used to assess the importance of land‐surface inundation caused by SLR, relative to other parameters (i.e. thickness of aquifer layers, hydraulic conductivity, recharge rate and land‐surface slope) that influence the FGL. Dimensionless parameters are used to generalize the findings. The results demonstrate that land‐surface inundation has a considerable impact on a FGL influenced by SLR, as expected, although the FGL volume is more sensitive to recharge, aquifer thickness and hydraulic conductivity than SLR impacts, considering typical parameter ranges. The methodology presented in this study provides water resource managers with a rapid‐assessment tool for evaluating the likely impacts of SLR and accompanying LSI on FGLs.
B7‐H3‐mediated tumor immunology: Friend or foe?
Authors: Wang Ling , Kang Fu‐Biao , Shan Bao‐En
Published: September 2013

B7‐H3 (CD276), a newly identified member of the B7 family of molecules, is often induced in human tumors and its overexpression is closely correlated with survival, prognosis or tumor grade. Although cancer immunotherapy has not been completely translated into clinical successes, interest has been further enhanced by the realization of these costimulatory molecules' potential as targets to modulate clinical immune responses. Despite ample evidence implicating B7‐H3 in tumor immune escape, a steady flow of reports have suggested that it may also have antitumor effects under certain circumstances. The safety and efficacy of targeting B7‐H3 with a monoclonal antibody for the treatment of advanced‐stage central nervous system cancer in children has been proven, making B7‐H3 an attractive therapeutic target for this kind of tumor. In addition, B7‐H3 was shown to promote invasion and accelerate carcinogenesis in tumor progression according to its nonimmunological regulatory roles. In this review, we discuss current understanding of the diverse functions of B7‐H3 in carcinogenesis and cancer progression, and consider future directions for designing cancer immunotherapeutic agents targeting B7‐H3.
Interleukin‐1 receptor antagonist gene polymorphism and hepcidin in rheumatoid arthritis: Correlations with clinical and laboratory indices of disease activity
Authors: Swellam Menha , Gabal Khadiga M. Abu , Youssef Samar Samir
Published: September 2013

Rheumatoid arthritis (RA) is a systemic autoimmune disease, which is manifested as an inflammatory polyarthritis. Authors aimed to analyze the relationship between serum hepcidin, 25 amino acid protein, concentration and the anemia profiles of RA and to estimate whether it could reflect the disease activity of RA. Also, this study was conducted to explore the linkage between interleukin‐1 (IL‐1) receptor antagonist gene (IL‐1RN) polymorphism, proinflammatory cytokine, and RA. One hundred and eighty five RA patients were enrolled in the study. For all, the following criteria were measured: RA disease activities, anemia profiles, serum concentration of hepcidin using enzyme‐linked immunosorbent assay, and DNA samples were used to study genotypes of IL‐1RN gene by polymerase chain reaction. Mean concentration of serum pro‐hepcidin was (93.6 ± 31.5 ng/mL) in 185 RA patients. An increased frequency of the IL‐1RN*1 and IL‐1RN*2 alleles was relative to active RA (DAS28 > 5.1) than those with inactive to moderate RA (DAS28 ≤ 5.1). Both hepcidin and IL‐1RN gene showed significant correlation with each other as well with RA disease activity parameters and anemia profile. IL‐1RN gene was significantly correlated with laboratory anemia profile apart from transferritin. There was a significant difference among pro‐hepcidin concentration and IL‐1RN frequency regarding patients with anemia of chronic disease and those without. In conclusion, both serum concentration of pro‐hepcidin and IL‐1RN genotypes frequency reflect the disease activity, regardless of the anemia states in RA patients, thus they may be another potential markers for disease activity of RA. © 2013 IUBMB Life, 65(10):883‐888, 2013
Advances in pathogenesis and therapy of hemolytic uremic syndrome caused by shiga toxin‐2
Authors: Ibarra Cristina , Amaral María Marta , Palermo Marina S.
Published: September 2013

Shiga toxin (Stx) producing Escherichia coli (STEC) is responsible to bloody diarrhea (hemorrhagic colitis) and the hemolytic uremic syndrome (HUS). STEC strains carry inducible lambda phages integrated into their genomes that encode Stx 1 and/or 2, with several allelic variants each one. O157:H7 is the serotype that was documented in the vast majority of HUS cases although non‐O157 serotypes have been increasingly reported to account for HUS cases. However, the outbreak that occurred in central Europe during late spring of 2011 showed that the pathogen was E. coli O104:H4. More than 4,000 persons were infected mainly in Germany, and it produced more than 900 cases of HUS resulting in 54 deaths. E. coli O104:H4 is a hybrid organism that combines some of the virulence genes of STEC and enteroaggregative E. coli specially production of Stx2 and the adherence mechanisms to intestinal epithelium. The differences in the epidemiology and presentation of E. coli pathogen meant a challenge for public health and scientific research to increase the knowledge of HUS‐pathophysiology and to improve available therapies to treat HUS. © 2013 IUBMB Life, 65(10):827‐835, 2013
Does Bone Resorption Stimulate Periosteal Expansion? A Cross-Sectional Analysis of β-C-telopeptides of Type I Collagen (CTX), Genetic Markers of the RANKL Pathway, and Periosteal Circumference as Measured by pQCT
Authors: Kemp John P , Sayers Adrian , Paternoster Lavinia , Evans David M , Deere Kevin , St Pourcain Beate , Timpson Nicholas J , Ring Susan M , Lorentzon Mattias , Lehtimäki Terho , Eriksson Joel , Kähönen Mika , Raitakari Olli , Laaksonen Marika , Sievänen Harri , Viikari Jorma , Lyytikäinen Leo-Pekka , Smith George Davey , Fraser William D , Vandenput Liesbeth , Ohlsson Claes , Tobias Jon H
Published: September 2013

We hypothesized that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum β-C-telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodeling such as cortical bone mineral density (BMDC). CTX and mid-tibial peripheral quantitative computed tomography (pQCT) scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass, and height. CTX was positively related to PC (β = 0.19 [0.13, 0.24]) (coefficient = SD change per SD increase in CTX, 95% confidence interval)] but inversely associated with BMDC (β = –0.46 [–0.52,–0.40]) and cortical thickness [β = –0.11 (–0.18, –0.03)]. CTX was positively related to bone strength as reflected by the strength-strain index (SSI) (β = 0.09 [0.03, 0.14]). To examine the causal nature of this relationship, we then analyzed whether single-nucleotide polymorphisms (SNPs) within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding receptor activator of NF-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (p < 0.05 cut-off) (n = 2379). Subsequently, we performed a meta-analysis of associations between these SNPs and PC in ALSPAC (n = 3382), Gothenburg Osteoporosis and Obesity Determinants (GOOD) (n = 938), and the Young Finns Study (YFS) (n = 1558). Five of the 15 alleles that were inversely related to BMD were positively related to PC (p < 0.05 cut-off). We conclude that despite having lower BMD, individuals with a genetic predisposition to higher bone resorption have greater bone size, suggesting that higher bone resorption is permissive for greater periosteal expansion. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Energy transfer and flow in the solar wind‐magnetosphere‐ionosphere system: A new coupling function
Authors: Tenfjord P. , Østgaard N.
Published: September 2013

In this paper we describe and quantify the energy transfer, flow, and distribution. Our high‐resolution data set covers 13 years of OMNI, SuperMAG, and Kyoto data. We employ what we consider to be the best estimates for energy sinks and relate these to SuperMAG indices for better coverage and spatial resolution. For the energy input, we have used the method of dimensional analysis that is presented in unit power and makes it appropriate for energy analysis. A cross‐correlation analysis parameterizes the magnetospheric response on the solar wind parameters during a wide range of conditions, ranging from substorms and storms up to a decade. The determined functional form is then evaluated and scaled using superposed epoch analysis of geomagnetic storms, revealing that the effective area of interaction cannot be considered static. Instead, we present a dynamic area which depends to the first order on the cube of the interplanetary magnetic field Bz component. Also, we find that for longer time periods, this area must be increased compared to the area used for geomagnetic storms. We argue that some of the terms in the energy coupling function are contributory to describing magnetosheath conditions and discuss how our coupling function can be related to Maxwell stress components. Also, we quantify the relative importance of the different energy sinks during substorms, geomagnetic storms, and long time series and present the coupling efficiency of the solar wind. Our energy coupling functions are compared with the ε parameter and perform better for almost any event.
Evaluating statistical cloud schemes: What can we gain from ground‐based remote sensing?
Authors: Grützun V. , Quaas J. , Morcrette C. J. , Ament F.
Published: September 2013

Statistical cloud schemes with prognostic probability distribution functions have become more important in atmospheric modeling, especially since they are in principle scale adaptive and capture cloud physics in more detail. While in theory the schemes have a great potential, their accuracy is still questionable. High‐resolution three‐dimensional observational data of water vapor and cloud water, which could be used for testing them, are missing. We explore the potential of ground‐based remote sensing such as lidar, microwave, and radar to evaluate prognostic distribution moments using the “perfect model approach.” This means that we employ a high‐resolution weather model as virtual reality and retrieve full three‐dimensional atmospheric quantities and virtual ground‐based observations. We then use statistics from the virtual observation to validate the modeled 3‐D statistics. Since the data are entirely consistent, any discrepancy occurring is due to the method. Focusing on total water mixing ratio, we find that the mean ratio can be evaluated decently but that it strongly depends on the meteorological conditions as to whether the variance and skewness are reliable. Using some simple schematic description of different synoptic conditions, we show how statistics obtained from point or line measurements can be poor at representing the full three‐dimensional distribution of water in the atmosphere. We argue that a careful analysis of measurement data and detailed knowledge of the meteorological situation is necessary to judge whether we can use the data for an evaluation of higher moments of the humidity distribution used by a statistical cloud scheme.
The Interactive Effects of Self‐Perceptions and Job Requirements on Creative Problem Solving
Authors: Robinson‐Morral Erika J. , Reiter‐Palmon Roni , Kaufman James C.
Published: September 2013

Over the years, researchers have focused on ways to facilitate creativity in the workplace by looking at individual factors and organizational factors that affect employee creativity (Woodman, Sawyer, & Griffin, ). In many cases, the factors that affect creativity are examined independently. In other words, it is uncommon for researchers to look at the interaction among individual and organizational factors. In this study, it is argued that to get a true understanding of how to maximize creativity in the workplace, organizational researchers must look at the interaction between organizational factors and individual factors that affect employee creativity. More specifically, the current study looked at an individual's perceptions about his or her ability to be creative (i.e., individual factor) and perceptions of requirements for creativity in the workplace (i.e., an organizational factor). The results indicated that individuals who have a high belief about their ability to be creative (an individual factor) were most creative when they also perceived requirements for creativity in the workplace (an organizational factor). Furthermore, individuals who had low perceptions of creative ability were still able to perform creatively when they had high perceptions of requirements for creativity. This suggests that, to maximize creativity, organizations should focus on both individual and organizational factors that affect employee creativity.
Experimental evidence that livestock grazing intensity affects cyclic vole population regulation processes
Authors: Villar Nacho , Cornulier Thomas , Evans Darren , Pakeman Robin , Redpath Steve , Lambin Xavier
Published: September 2013

Grazing by domestic ungulates may limit the densities of small herbivorous mammals that act as key prey in ecosystems. Whether this also influences density dependence and the regulation of small herbivore populations, hence their propensity to exhibit multi‐annual population cycles, is unknown. Here, we combine time series analysis with a large‐scale grazing experiment on upland grasslands to examine the effects of livestock grazing intensity on the population dynamics of field voles (Microtus agrestis). Using log‐linear modelling of replicated time series under different grazing treatments, we show that increased sheep densities weaken delayed density dependent regulation of vole population growth, hence reducing the cyclicity in vole population dynamics. While population regulation is commonly attributed to both top‐down and bottom up processes, our results suggest that regulation of cyclic vole populations can be disrupted by the influence of another grazer in the same trophic level. These results support the view that ongoing changes in domestic grazing intensity, by affecting small mammal dynamics, can potentially have cascading impacts on higher trophic levels, and strongly influence the dynamics of upland grassland systems.
Practical Aspects of Recruitment and Retention in Clinical Trials of Rare Genetic Diseases: The Phenylketonuria (PKU) Experience
Authors: DeWard Stephanie J. , Wilson Ashley , Bausell Heather , Volz Ashley S. , Mooney Kimberly
Published: September 2013

Bringing treatments for rare genetic diseases to patients requires clinical research. Despite increasing activism from patient support and advocacy groups to increase access to clinical research studies, connecting rare disease patients with the clinical research opportunities that may help them has proven challenging. Chief among these challenges are the low incidence of these diseases resulting in a very small pool of known patients with a particular disease, difficulty of diagnosing rare genetic diseases, logistical issues such as long distances to the nearest treatment center, and substantial disease burden leading to loss of independence. Using clinical studies of phenylketonuria as an example, this paper discusses how, based on the authors’ collective experience, partnership among clinicians, patients, study coordinators, genetic counselors, dietitians, industry, patient support groups, and families can help overcome the challenges of recruiting and retaining patients in rare disease clinical trials. We discuss specific methods of collaboration, communication, and education as part of a long‐term effort to build a community committed to advancing the medical care of patients with rare genetic diseases. By talking to patients and families regularly about research initiatives and taking steps to make study participation as easy as possible, rare disease clinic staff can help ensure adequate study enrollment and successful study completion.
Acceptability of Telemedicine and Other Cancer Genetic Counseling Models of Service Delivery in Geographically Remote Settings
Authors: McDonald Eileen , Lamb Amanda , Grillo Barbara , Lucas Lee , Miesfeldt Susan
Published: September 2013

This work examined acceptability of cancer genetic counseling models of service delivery among Maine residents at risk for hereditary cancer susceptibility disorders. Pre‐counseling, participants ranked characteristics reflecting models of care from most to least important including: mode‐of‐communication (in‐person versus telegenetics), provider level of training (genetic specialty versus some training/experience), delivery format (one‐on‐one versus group counseling), and location (local versus tertiary service requiring travel). Associations between models of care characteristic rankings and patient characteristics, including rural residence, perceived cancer risk, and perceived risk for a hereditary cancer risk susceptibility disorder were examined. A total of 149/300 (49.7 % response rate) individuals from 11/16 Maine counties responded; 30.8 % were from rural counties; 92.2 % indicated that an important/the most important model of care characteristic is provider professional qualifications. Among other characteristics, 65.1 % ranked one‐on‐one counseling as important/the most important. In‐person and local counseling were ranked the two least important characteristics (51.8 % and 52.1 % important/the most important, respectively). Responses did not vary by patient characteristics with the exception of greater acceptance of group counseling among those at perceived high personal cancer risk. Cancer telegenetic services hold promise for access to expert providers in a one‐on‐one format for rurally remote clients.
Microalgae classification using semi-supervised and active learning based on Gaussian mixture models
Authors: Drews- Paulo , Colares Rafael G. , Machado Pablo , de Faria Matheus , Detoni Amália , Tavano Virgínia
Published: September 2013

Microalgae are unicellular organisms that have different shapes, sizes and structures. Classifying these microalgae manually can be an expensive task, because thousands of microalgae can be found in even a small sample of water. This paper presents an approach for an automatic/semi-automatic classification of microalgae based on semi-supervised and active learning algorithms, using Gaussian mixture models. The results show that the approach has an excellent cost-benefit relation, classifying more than 90 % of microalgae in a well distributed way, overcoming the supervised algorithm SVM.
Políticas de diversidad y flexibilidad laboral en el marco de la responsabilidad social empresarial. Un análisis desde la perspectiva de género
Authors: Arredondo Trapero Florina Guadalupe , Velázquez Sánchez Luz María , De la Garza García Jorge
Published: September 2013

El objetivo de este artículo es analizar si la mujer directiva tiene mayor disposición que el hombre a apoyarlas políticas de diversidad y flexibilidad laboral. Las variables diversidad y flexibilidad laboral fueronanalizadas en un grupo de 57 directivos de empresas empleando el análisis de varianza. Los hallazgosmuestran que las empresas peque˜nas y medianas de comercio y servicios que son dirigidas por mujerestienden a implementar políticas de diversidad y flexibilidad respecto a la elección de horarios y fórmulasde trabajo flexible como parte de su responsabilidad social, a diferencia de los hombres.
Identification, expression and characterization of rat isoforms of the serum response factor (SRF) coactivator MKL1
Authors: Ishikawa Mitsuru , Shiota Jun , Ishibashi Yuta , Hakamata Tomoyuki , Shoji Shizuku , Fukuchi Mamoru , Tsuda Masaaki , Shirao Tomoaki , Sekino Yuko , Ohtsuka Toshihisa , Baraban Jay M. , Tabuchi Akiko
Published: September 2013

Megakaryoblastic leukemia 1 (MKL1) is a member of the MKL family of serum response factor (SRF) coactivators. Here we have identified three rat MKL1 transcripts: two are homologues of mouse MKL1 transcripts, full‐length MKL1 (FLMKL1) and basic, SAP, and coiled‐coil domains (BSAC), the third is a novel transcript, MKL1‐elongated derivative of yield (MELODY). These rat MKL1 transcripts are differentially expressed in a wide variety of tissues with highest levels in testis and brain. During brain development, these transcripts display differential patterns of expression. The FLMKL1 transcript encodes two isoforms that utilize distinct translation start sites. The longer form possesses three actin‐binding RPXXXEL (RPEL) motifs and the shorter form, MKL1met only has two RPEL motifs. All four rat MKL1 isoforms, FLMKL1, BSAC, MKL1met and MELODY increased SRF‐mediated transcription, but not CREB‐mediated transcription. Accordingly, the differential expression of MKL1 isoforms may help fine‐tune gene expression during brain development.
Die körperdysmorphe Störung
Authors: Buhlmann Ulrike , Martin Alexandra , Tuschen-Caffier Brunna , Heinrichs Nina
Published: September 2013

Charakteristisch für die körperdysmorphe Störung (KDS) ist eine übermäßige Beschäftigung mit einem wahrgenommenen Makel oder Defekt im körperlichen Aussehen (z. B. Hautunreinheiten, Falten, Asymmetrien im Gesichtsbereich), die mit einer signifikanten Beeinträchtigung im sozialen und/oder beruflichen Leben einhergeht. Menschen, die an einer KDS leiden, zeigen ritualisierte Verhaltensweisen (z. B. überprüfen sie ihr Äußeres immer wieder in Spiegeln) und leiden zudem häufig unter Angst vor negativer Bewertung sowie Vorstellungen, dass andere Personen negativ über ihr Aussehen sprechen. Aktuelle Studien zur Prävalenz der KDS in der Allgemeinbevölkerung weisen auf eine Punkt-Prävalenz von ca. 2 % hin (Geschlechterverhältnis: ca. 60 % Frauen versus 40 % Männer). Bei der psychotherapeutischen Behandlung der KDS haben sich kognitiv-behaviorale Psychotherapieansätze bewährt. Dennoch liegen derzeit zu wenig randomisiert-kontrollierte Psychotherapiestudien vor, um evidenzbasierte Handlungsempfehlungen zur Psychotherapie geben zu können.
Körperbildstörungen bei körperdysmorpher Störung und Essstörungen
Authors: Kollei Ines , Rauh Elisabeth , Zwaan Martina de , Martin Alexandra
Published: September 2013

Hintergrund: Sowohl die körperdysmorphe Störung (KDS) als auch Essstörungen (ESS) sind durch eine Störung des Körperbildes gekennzeichnet, jedoch ist wenig über Gemeinsamkeiten und Unterschiede hinsichtlich spezifischer Körperbildmerkmale bekannt. Fragestellung: Nach der vergleichenden Befunddarstellung zu perzeptiven, kognitiv-affektiven und behavioralen Körperbildmerkmalen hat die Arbeit das Ziel, kognitiv-affektive Körperbildcharakteristika im direkten Vergleich von KDS mit ESS zu untersuchen. Methode: Personen mit einer KDS (n = 31), Anorexia nervosa (n = 32), Bulimia nervosa (n = 34) und eine gesunde (n = 33) Kontrollgruppe wurden untersucht (Fragebögen, Interviews). Ergebnisse: KDS und ESS zeigten starke Körperunzufriedenheit und körper- und gewichtsbezogene Schamgefühle. Nicht nur bei der KDS, sondern auch bei den ESS zeigte sich eine Vielzahl subjektiver Makel im äußeren Erscheinungsbild. Die KDS-Gruppe sorgte sich jedoch seltener als ESS um Körpergewicht, Brust und Gesäß. Die ESS-Gruppen berichteten erwartungsgemäß stärkere Figur-/Gewichtssorgen und körper-/gewichtsbezogene Schuldgefühle. Diskussion: Körperunzufriedenheit charakterisiert sowohl KDS als auch ESS. Von den kognitiv-affektiven Körperbildmerkmalen differenzieren nur die Ausprägung von Figur-/Gewichtssorgen und körper-/gewichtsbezogene Schuldgefühle die beiden Gruppen. Vergleichsstudien zu perzeptiven und behavioralen Körperbildaspekten stehen aus.
Body Dysmorphic Disorder: Neurobiological Features and an Updated Model
Authors: Li Wei , Arienzo Donatello , Feusner Jamie D.
Published: September 2013

Body dysmorphic disorder (BDD) affects approximately 2 % of the population and involves misperceived defects of appearance along with obsessive preoccupation and compulsive behaviors. There is evidence of neurobiological abnormalities associated with symptoms in BDD, although research to date is still limited. This review covers the latest neuropsychological, genetic, neurochemical, psychophysical, and neuroimaging studies, and synthesizes these findings into an updated (yet still preliminary) neurobiological model of the pathophysiology of BDD. We propose a model in which visual perceptual abnormalities, along with frontostriatal and limbic system dysfunction, may combine to contribute to the symptoms of impaired insight, obsessive thoughts, and compulsive behaviors expressed in BDD. Further research is necessary to gain a greater understanding of the etiology of BDD symptoms and their evolution over time.
Noun incorporation in English
Authors: Feist Jim
Published: September 2013

The article discusses noun incorporation in English — that is, expressions which include a noun in the verbal constituent of an utterance, as in It’s time to legacy build contrasted with It’s time to build a legacy. It concludes that noun incorporation is well established in present-day English, that it has many functions, that it is used productively as an alternative to other constructions, and under definable constraints.
Setting the Catherine wheel in motion
Authors: Earls Clive W.
Published: September 2013

In today’s world, internationalisation is the key to survival for higher education institutions (HEIs). Many argue that English has become the most used language worldwide, the international language of wider communication in a variety of domains ranging from the professional to everyday life. Consequently, non-English speaking countries have entered into a process of introducing English-medium higher education as a means of overcoming any competitive disadvantage associated with their particular linguistic situation. As a result, an ideology has emerged amongst HEIs in non-English-speaking countries that internationalisation is synonymous with the introduction of English-medium degree programmes. This development has implications for the position of national languages in their higher education systems, and consequently as international languages of communication. It is, therefore, necessary to investigate the extent to which the adoption of such language-in-education reforms may potentially act as an impetus to a wider language shift in the countries comprising Kachru’s “expanding circle.” This paper explores the current process of “Englishization” within the German higher education system. By means of Strubell’s “Catherine Wheel” conceptual model, a potential language shift from German to English is postulated and its ramifications for German’s status and role as an international language are discussed.
targetHub: a programmable interface for miRNA–gene interactions
Authors: Manyam Ganiraju , Ivan Cristina , Calin George A. , Coombes Kevin R.
Published: September 2013

Motivation: With the expansion of high-throughput technologies, understanding different kinds of genome-level data is a common task. MicroRNA (miRNA) is increasingly profiled using high-throughput technologies (microarrays or next-generation sequencing). The downstream analysis of miRNA targets can be difficult. Although there are many databases and algorithms to predict miRNA targets, there are few tools to integrate miRNA–gene interaction data into high-throughput genomic analyses.

Results: We present targetHub, a CouchDB database of miRNA–gene interactions. TargetHub provides a programmer-friendly interface to access miRNA targets. The Web site provides RESTful access to miRNA–gene interactions with an assortment of gene and miRNA identifiers. It can be a useful tool to integrate miRNA target interaction data directly into high-throughput bioinformatics analyses.

Availability: TargetHub is available on the web at http://app1.bioinformatics.mdanderson.org/tarhub/_design/basic/index.html.

Contact:  coombes.3@osu.edu
Multi-profile Bayesian alignment model for LC-MS data analysis with integration of internal standards
Authors: Tsai Tsung-Heng , Tadesse Mahlet G. , Di Poto Cristina , Pannell Lewis K. , Mechref Yehia , Wang Yue , Ressom Habtom W.
Published: September 2013

Motivation: Liquid chromatography-mass spectrometry (LC-MS) has been widely used for profiling expression levels of biomolecules in various ‘-omic’ studies including proteomics, metabolomics and glycomics. Appropriate LC-MS data preprocessing steps are needed to detect true differences between biological groups. Retention time (RT) alignment, which is required to ensure that ion intensity measurements among multiple LC-MS runs are comparable, is one of the most important yet challenging preprocessing steps. Current alignment approaches estimate RT variability using either single chromatograms or detected peaks, but do not simultaneously take into account the complementary information embedded in the entire LC-MS data.

Results: We propose a Bayesian alignment model for LC-MS data analysis. The alignment model provides estimates of the RT variability along with uncertainty measures. The model enables integration of multiple sources of information including internal standards and clustered chromatograms in a mathematically rigorous framework. We apply the model to LC-MS metabolomic, proteomic and glycomic data. The performance of the model is evaluated based on ground-truth data, by measuring correlation of variation, RT difference across runs and peak-matching performance. We demonstrate that Bayesian alignment model improves significantly the RT alignment performance through appropriate integration of relevant information.

Availability and implementation: MATLAB code, raw and preprocessed LC-MS data are available at http://omics.georgetown.edu/alignLCMS.html

Contact: hwr@georgetown.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
The Xeno-glycomics database (XDB): a relational database of qualitative and quantitative pig glycome repertoire
Authors: Park Hae-Min , Park Ju-Hyeong , Kim Yoon-Woo , Kim Kyoung-Jin , Jeong Hee-Jin , Jang Kyoung-Soon , Kim Byung-Gee , Kim Yun-Gon
Published: September 2013

Summary: In recent years, the improvement of mass spectrometry-based glycomics techniques (i.e. highly sensitive, quantitative and high-throughput analytical tools) has enabled us to obtain a large dataset of glycans. Here we present a database named Xeno-glycomics database (XDB) that contains cell- or tissue-specific pig glycomes analyzed with mass spectrometry-based techniques, including a comprehensive pig glycan information on chemical structures, mass values, types and relative quantities. It was designed as a user-friendly web-based interface that allows users to query the database according to pig tissue/cell types or glycan masses. This database will contribute in providing qualitative and quantitative information on glycomes characterized from various pig cells/organs in xenotransplantation and might eventually provide new targets in the α1,3-galactosyltransferase gene-knock out pigs era.

Availability: The database can be accessed on the web at http://bioinformatics.snu.ac.kr/xdb.

Contact:  byungkim@snu.ac.kr or ygkim@ssu.ac.kr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Mechanical properties of DNA-like polymers
Authors: Peters Justin P. , Yelgaonkar Shweta P. , Srivatsan Seergazhi G. , Tor Yitzhak , James Maher L.
Published: September 2013

The molecular structure of the DNA double helix has been known for 60 years, but we remain surprisingly ignorant of the balance of forces that determine its mechanical properties. The DNA double helix is among the stiffest of all biopolymers, but neither theory nor experiment has provided a coherent understanding of the relative roles of attractive base stacking forces and repulsive electrostatic forces creating this stiffness. To gain insight, we have created a family of double-helical DNA-like polymers where one of the four normal bases is replaced with various cationic, anionic or neutral analogs. We apply DNA ligase-catalyzed cyclization kinetics experiments to measure the bending and twisting flexibilities of these polymers under low salt conditions. Interestingly, we show that these modifications alter DNA bending stiffness by only 20%, but have much stronger (5-fold) effects on twist flexibility. We suggest that rather than modifying DNA stiffness through a mechanism easily interpretable as electrostatic, the more dominant effect of neutral and charged base modifications is their ability to drive transitions to helical conformations different from canonical B-form DNA.
Exome Sequencing Reveals Novel Rare Variants in the Ryanodine Receptor and Calcium Channel Genes in Malignant Hyperthermia Families
Authors: Kim Jerry H. , Jarvik Gail P. , Browning Brian L. , Rajagopalan Ramakrishnan , Gordon Adam S. , Rieder Mark J. , Robertson Peggy D. , Nickerson Deborah A. , Fisher Nickla A. , Hopkins Philip M.
Published: September 2013

Background:

About half of malignant hyperthermia (MH) cases are associated with skeletal muscle ryanodine receptor 1 (RYR1) and calcium channel, voltage-dependent, L type, α1S subunit (CACNA1S) gene mutations, leaving many with an unknown cause. The authors chose to apply a sequencing approach to uncover causal variants in unknown cases. Sequencing the exome, the protein-coding region of the genome, has power at low sample sizes and identified the cause of over a dozen Mendelian disorders.

Methods:

The authors considered four families with multiple MH cases lacking mutations in RYR1 and CACNA1S by Sanger sequencing of complementary DNA. Exome sequencing in two affecteds per family, chosen for maximum genetic distance, were compared. Variants were ranked by allele frequency, protein change, and measures of conservation among mammals to assess likelihood of causation. Finally, putative pathogenic mutations were genotyped in other family members to verify cosegregation with MH.

Results:

Exome sequencing revealed one rare RYR1 nonsynonymous variant in each of three families (Asp1056His, Val2627Met, Val4234Leu), and one CACNA1S variant (Thr1009Lys) in the fourth family. These were not seen in variant databases or in our control population sample of 5,379 exomes. Follow-up sequencing in other family members verified cosegregation of alleles with MH.

Conclusions:

The authors found that using both exome sequencing and allele frequency data from large sequencing efforts may aid genetic diagnosis of MH. In a sample selected by the authors, this technique was more sensitive for variant detection in known genes than Sanger sequencing of complementary DNA, and allows for the possibility of novel gene discovery.
Gemmobacter megaterium sp. nov., isolated from coastal planktonic seaweeds
Authors: Liu Jin-Jin , Zhang Xin-Qi , Chi Fang-Tao , Pan Jie , Sun Cong , Wu Min
Published: September 2013

A Gram-stain-negative, non-motile and aerobic bacterium, designated CF17T, was isolated from coastal planktonic seaweeds, East China Sea. The isolate grew at 18–37 °C (optimum 25–28 °C), pH 6.5–9.0 (optimum 7.0–8.0) and with 0–5 % NaCl (optimum 1–2 %, w/v) and 0.5–10 % sea salts (optimum 2–3 %, w/v). Growth of strain CF17T could be stimulated prominently by supplementing the growth medium with the autoclaved supernatant of a culture of strain CF5, which was isolated from the same sample along with strain CF17T. The cell morphology of strain CF17T was a bean-shaped rod consisting of a swollen end and a long prostheca. The phylogenetic analysis of 16S rRNA gene sequences indicated that strain CF17T clustered with

Gemmobacter nectariphilus

DSM 15620T within the genus

Gemmobacter

. The DNA G+C content of strain CF17T was 61.4 mol%. The respiratory quinone was ubiquinone Q-10. The major fatty acids included C18 : 1ω7c and C18 : 0. The polar lipids of strain CF17T consisted of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, two uncharacterized phospholipids, one uncharacterized aminolipid, three uncharacterized glycolipids and one uncharacterized lipid. On the basis of phenotypic, phylogenetic and chemotaxonomic data, strain CF17T ( = CGMCC 1.11024T = JCM 18498T) is considered to represent a novel species of the genus

Gemmobacter

, for which the name Gemmobacter
megaterium sp. nov. is proposed.
Cloacibacterium haliotis sp. nov., isolated from the gut of an abalone, Haliotis discus hannai
Authors: Hyun Dong-Wook , Shin Na-Ri , Kim Min-Soo , Kim Joon Yong , Kim Pil Soo , Oh Sei Joon , Whon Tae Woong , Bae Jin-Woo
Published: September 2013

A novel Gram-stain-negative, aerobic, non-motile, yellow-pigmented and rod-shaped bacterium, designated strain WB5T, was isolated from the intestinal tract of an abalone, Haliotis discus hannai, collected from the northern coast of Jeju in Korea. The isolate grew optimally at 30 °C, at pH 7 and in the presence of 0.5 % (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain WB5T was clustered in the genus

Cloacibacterium

and shared the highest sequence similarity with

C. normanense

(98.2 % similarity). The predominant fatty acids were iso-C15 : 0 and iso-C17 : 0 3-OH. Menaquinone-6 was the major respiratory quinone. The genomic DNA G+C content was 29.6 mol%. The DNA–DNA hybridization values indicated <22 % genomic relatedness with other members of the genus

Cloacibacterium

. The results of physiological, biochemical, chemotaxonomic and genotypic analyses showed that strain WB5T represents a novel species of the genus

Cloacibacterium

, for which the name Cloacibacterium haliotis sp. nov. is proposed. The type strain is WB5T ( = KACC 17210T = JCM 18869T).
DNA methylation profiling in human B cells reveals immune regulatory elements and epigenetic plasticity at Alu elements during B-cell activation
Authors: Lai Anne Y. , Mav Deepak , Shah Ruchir , Grimm Sara A. , Phadke Dhiral , Hatzi Katerina , Melnick Ari , Geigerman Cissy , Sobol Steve E. , Jaye David L. , Wade Paul A.
Published: September 2013

Memory is a hallmark of adaptive immunity, wherein lymphocytes mount a superior response to a previously encountered antigen. It has been speculated that epigenetic alterations in memory lymphocytes contribute to their functional distinction from their naive counterparts. However, the nature and extent of epigenetic alterations in memory compartments remain poorly characterized. Here we profile the DNA methylome and the transcriptome of B-lymphocyte subsets representing stages of the humoral immune response before and after antigen exposure in vivo from multiple humans. A significant percentage of activation-induced losses of DNA methylation mapped to transcription factor binding sites. An additional class of demethylated loci mapped to Alu elements across the genome and accompanied repression of DNA methyltransferase 3A. The activation-dependent DNA methylation changes were largely retained in the progeny of activated B cells, generating a similar epigenetic signature in downstream memory B cells and plasma cells with distinct transcriptional programs. These findings provide insights into the methylation dynamics of the genome during cellular differentiation in an immune response.
Calcium-Dependent Protein Kinases: Hubs in Plant Stress Signaling and Development
Authors: Schulz Philipp , Herde Marco , Romeis Tina
Published: September 2013

These kinases are identified as integrators in plant signaling, with distinct as well as shared phosphorylation substrates mediating pathway specificity.
Associations between measures of central adiposity and periodontitis among older adults
Authors: Muñoz‐Torres Francisco J. , Jiménez Monik C. , Rivas‐Tumanyan Sona , Joshipura Kaumudi J.
Published: September 2013

Objective

To evaluate the association between measures of adiposity and periodontitis among older Puerto Rican adults.

Methods

A cross‐sectional study was conducted among 147 representative adults ≥70 years living in the San Juan metropolitan area. Height, weight, waist circumference (WC), and hip circumference were measured by trained personnel. Periodontal probing depth and attachment loss (AL) were measured by calibrated examiners. Periodontitis was classified according to the Center for Disease Control/American Academy of Periodontology (CDC‐AAP) definitions and using tertiles of mean AL and percent of sites with AL ≥3 mm. Multivariable polytomous logistic regression models adjusted for age, gender, smoking, education, diabetes status, physical activity, and total fruit and vegetable intake were used to model associations between WC, waist‐to‐hip ratio (WHR), and periodontitis.

Results

High WC (men: ≥102 cm versus <102 cm, women: ≥88 cm versus <88 cm) compared with normal showed nonsignificant associations with severe (OR = 2.56, 95% CI: 0.76–8.67), moderate periodontitis (OR = 1.53, 95% CI: 0.65–3.60), and upper tertile of mean AL (OR = 2.28, 95% CI: 0.83–6.23). Elevated WHR versus normal (men: ≥0.95 versus <0.95, women: ≥0.88 versus <0.88) was associated with moderate periodontitis (OR = 2.36, 95% CI: 1.01–5.52) and showed a borderline significant association with the upper tertile of mean AL (OR = 2.52, 95% CI: 0.96–6.63, P = 0.06).

Conclusions

Central adiposity was associated with a greater risk of periodontitis in this population of older adults, although analyses were underpowered. These results hold important public health implications given the high prevalence of adiposity and periodontitis among older adults.
Telomere length and Parkinson's disease in men: a nested case−control study
Authors: Schürks M. , Buring J. , Dushkes R. , Gaziano J. M. , Zee R. Y. L. , Kurth T.
Published: September 2013

Background and purpose

Telomere shortening has been implicated in neurodegenerative disorders. However, available data on the association between telomere length and Parkinson's disease (PD) are inconclusive.

Methods

A nested case−control design was used amongst men participating in the prospective Physicians’ Health Study. A large proportion of participants provided blood samples in 1997 and they were followed through 2010. Men with self‐reported PD were age‐matched to controls in a 1:2 ratio. Quantitative PCR was used to determine the telomere repeat copy number to single gene copy number ratio (TSR) in genomic DNA extracted from peripheral blood leukocytes. TSR was used as a measure for relative telomere length (RTL) in our analyses. Conditional logistic regression was used to determine the risk of PD associated with RTL.

Results

Data on RTL were available from 408 cases and 809 controls. Median TSR was shorter in controls than in cases (47.7 vs. 50.2; P = 0.02). The age‐adjusted odds ratio (OR) for PD was 0.66 [95% confidence interval (CI) 0.46–0.95; Ptrend over quartiles 0.02] comparing the lowest to the highest quartile. The pattern of association was unchanged when comparing RTL below versus above the median (age‐adjusted OR 0.75; 95% CI 0.59–0.96). Associations were similar after additional adjustment for many covariates.

Conclusion

Contrary to what was expected, in this large nested case−control study amongst men shorter telomeres were associated with reduced PD risk. Future research on the nature of this counterintuitive association is warranted.