bluuebunny/crossref_metadata_2025 huggingface dataset:
The Grave Defect of Discretion of Judgment Necessary to Establish the Invalidity of Marriage under Canon 1095, 2°
Authors: Reidy Richard F.
Published: June 2014

Canon 1095, 2º provides that “those who suffer from a grave defect of discretion of judgment concerning the essential matrimonial rights and duties mutually to be handed over and accepted” are incapable of marriage because of a lack of capacity to give matrimonial consent. This canon has been frequently relied upon by many tribunals in the adjudication of marriage cases. It has also been the focus of several Papal allocutions to the Roman Rota expressing concern about tribunals granting declarations of nullity “on the pretext of immaturity or psychic weakness.” In 2005, the Instruction Dignitas Connubii amplified the requirements of canon 1095, 2º. This article will seek a proper understanding of a grave defect of discretion of judgment under canon 1095, 2º by first examining how discretion of judgment can be defective and then exploring what constitutes such a defect as grave.
Introduction: Medical Case Histories as Genre: New Approaches
Authors: Class Monika
Published: June 2014

This article outlines a number of new approaches in the history of medicine and medical humanities to the study of medical case histories from a genre-theoretical vantage point. Differentiating between morphological and structuralist concepts of genre, the essay proposes the investigation of similarities and differences among specific series of case histories in order to recover evolving, changing, or decaying patterns and practices in texts and communicative acts about human health during different historical epochs, including antiquity, Renaissance, Enlightenment, Romantic and Victorian age. The article highlights the importance of narrative, and thinking in cases, supports the notion of “epistemic genres” and pays special attention to the distinction between example and exemplar. It discerns three interrelated functions of case histories: propaedeutic, instantiative, and singular. The study of case histories as genre helps to overcome disjunctions in the history of literature and medicine and enhances multidisciplinary research
“If They Smile He Will Flourish”: Mothers, Doctors, and Nineteenth-Century Children’s Literature
Authors: Thompson Catherine L.
Published: June 2014

Within the appropriate boundaries of what constituted middle-class femininity, the concept of republican motherhood allowed middle-class mothers to expand their role in civil society. Domestic literacy and health management emerged as significant ways to contribute to their nation. While mothers read to their children as part of their civic duty, they could peruse their children’s health. Championed as the first-line in the prevention of illness, mothers made important medical choices that helped shaped medical practice during a transitional period in American medicine. Authors recognized the potential to influence mothers’ medical choices through children’s literature, thus children’s stories provide evidence of the importance of mothers as consumers of medical products and services.
Rituals of Performance: Ricardo Darín as Father Julián in Elefante blanco
Authors: Urraca Beatriz
Published: June 2014

El actor argentino Ricardo Darín es indiscutiblemente la cara más conocida del cine de su país. Su personalidad pública es un retrato compuesto por elementos intrafílmicos y extrafílmicos, y se caracteriza principalmente por presentarse como una imagen del argentino medio, del hombre de la calle que opina sobre los problemas sociales de su país, interpelando directamente al poder político desde tribunas mediáticas controvertidas. Este artículo analiza cómo estos factores contribuyen a dar forma al papel del Padre Julián en Elefante blanco (Pablo Trapero, 2012) y cómo, a su vez, la marca de celebridad creada por Darín interactúa con la figura histórica del Padre Carlos Mugica y con el trabajo de los curas villeros en las villas de emergencia que la película describe. Al igual que el sacerdote a quien representa en la película, el actor habita el espacio entre lo ordinario y lo excepcional, entre la vida privada cotidiana y la actuación como figura pública. Dada la casi total ausencia de estudios sobre el estrellato y el trabajo actoral en el cine latinoamericano, este artículo se apoya en textos teóricos referentes a Hollywood, complementándolos con entrevistas con Darín y estudios sociológicos y periodísticos sobre el trabajo de los curas villeros en Argentina.
Lugar común, excepcionalidad y superficie en el cine de Martín Rejtman
Authors: Barros César
Published: June 2014

La cinematografía del director argentino Martín Rejtman es sin duda una de las más influyentes del cine latinoamericano de las últimas dos décadas. Pese al interés que ha suscitado su obra, hay pocos estudios que se concentran exclusivamente en ella, desmarcándola del contexto del llamado Nuevo Cine Argentino. Este artículo tiene el doble objetivo de intentar delinear una estética común a las distintas obras del director argentino y, en el contexto de esta estética, analizar su único documental, Copacabana . El artículo plantea que la estética de Rejtman funciona tensionando nociones como lo común, lo serial, lo nuevo y lo excepcional, a través de un cine que explota el papel de la superficie, formal y temáticamente. Se propone que en Copacabana , documental centrado en la comunidad boliviana del barrio Charrúa de Buenos Aires, hay más continuidades que diferencias en relación con las películas de ficción del director argentino. Copacabana genera un comentario sobre el inmigrante, el otro, y la comunidad nacional, construido a partir de estrategias que, como en el resto de la obra de Rejtman, giran en torno a la superficie, el momento inmanente y la dialéctica entre lo común y lo excepcional.
Reflections on Teaching a Course on Jewish Identities
Authors: Sigalow Emily
Published: June 2014

The article discusses a Jewish Studies course taught at Brandeis University—Half-Jews, Bu-Jews, and Queer Jews: Mapping Jewish Identities in America—during the 2104-2015 school year. The course was designed to be intersectional, relational, and in conversation with larger American discourses on religion, gender, race, and ethnicity. As such, it was cross-listed with Sociology, Women’s and Gender Studies, and Sexuality and Queer Studies. Emily Sigalow, a scholar of Near Eastern and Judaic Studies, considers the course’s subject matter, enrollment, learning environment, and impact. A sample syllabus is included.
The Challenge of Interdisciplinarity: A Conversation about Introductory Courses to Jewish Studies
Authors: Lefkovitz Lori , Shneer David , Tenenbaum Shelly
Published: June 2014

This article takes as its starting point the idea that as all disciplinary boundaries are constructs, the Introduction to Jewish Studies course is a useful place to begin thinking about moving beyond a multidisciplinary menu to an interdisciplinary way of thinking. Jewish Studies is a microcosm of the diversity within the humanities and social sciences and of the variety of subjects and approaches that characterize academic inquiry, and provides rich possibilities for cross-cultural and comparative inquiry. For the same reasons, the field of Jewish Studies is not easily delimited for the purposes of an introductory course. The authors examine approaches to teaching the introduction as a genuinely interdisciplinary course that could make Jewish Studies a model of inquiry for other multidisciplinary fields.
Ambivalence and Interdisciplinarity: The Future of Jewish Studies
Authors: Levitt Laura S.
Published: June 2014

Laura Levitt writes a response to the articles in a special issue of Shofar entitled “New Approaches to Teaching Jewish Studies.” She notes that the collection of articles is presented in the spirit of collaboration and better practices. Considering the current situation in Jewish Studies as “the best and worst of times,” Levitt examines the range of new and ever more sophisticated and nuanced studies of Jewish literatures, cultures, histories, ethnographies, languages, music, performance, and ritual practices against the backdrop of the precarious situation for scholars and Jewish Studies at today’s universities. She speculates on how Jewish Studies might fit into a new interdisciplinary environment.
The “J Survey” between History and Religious Studies
Authors: Levenson Alan T.
Published: June 2014

Alan T. Levenson considers the fundamental issue of what one can and cannot achieve in a semester’s introduction to Jews and/or Judaism. He offers a minimalist, pedagogically driven compromise between coverage and concept, that is, a course that provides both historical development and Jewish concepts, practices, and doctrines. He discusses the assigments and organization of his survey course, which is divided into the four basic eras of Jewish history as defined by the first couple of generations of Wissenschaft des Judentums scholars. A syllabus is included.
Lower bounds for the variance of unbiased estimators in generalized beta distribution of the second kind (GB2)
Authors: Nayeban S. , Rezaei Roknabadi A. , Mohtashami Borzadaran G.
Published: June 2014

In order to give an excellent description of income distributions, although a large number of functional forms have been proposed, but the four-parameter generalized beta model of the second kind (GB2), introduced by J. B. McDonald [18], is now widely acknowledged which is including many other models as special or limiting cases.One of the fundamentals of statistical inference is the estimation problem of a function of unknown parameter in a probability distribution and computing the variance of the estimator or approximating it by lower bounds.In this paper, we consider two famous lower bounds for the variance of any unbiased estimator, which are Bhattacharyya and Kshirsagar bounds. We obtain the general forms of the Bhattacharyya and Kshirsagar matrices in the GB2 distribution. In addition, we compare different Bhattacharyya and Kshirsagar bounds for the variance of any unbiased estimator of some parametric functions such as mode, mean, skewness and kurtosis in GB2 distribution and conclude that in each case, which bound is better to use. The results of this paper can be useful for researchers trying to find the accuracy of the estimators.
Etiological Factors of Non Alcohol Non Gallstone Related Acute Pancreatitis: A Cross sectional hospital based study from Medical College and Hospital, Kolkata, West Bengal
Authors: Banerjee Indraneel , Banerjee Indrajit , Das K N , Sathian Brijesh , Pugazhandhi Bakthavatchalam , Roy Bedanta , Banerjee Shantimoy , Khadka Shovit
Published: June 2014

Background  Gall  stone  diseases and  alcohol  are  the  two  most  common causes  of  acute  pancreatitis. The  present  work  was undertaken  to  identify the  various etiological  factors  in  acute  pancreatitis  after  excluding  alcoholism  and  gall  stone  diseases. The etiology of an attack of non alcohol non gall stone acute pancreatitis is highly variable. The main objective was to identify the causing factor, because it can have an effect on the specific treatment of acute pancreatitis. . This is a rare cross- sectional study of its kind which is the first one to be reported from India. Materials and Methods A cross-sectional community based study was designed and conducted in Medical College and Hospital, Kolkata, West Bengal, India from July 2009 to June 2011. Z test and Chi square test were used to observe the variation between different variables and strength of the relationship with logistic regression.  Odd ratios were calculated and their 95% confidence intervals (95% CI). p < 0.05 was considered as statistically significant. Results CMV was the commonest etiology of non alcohol and non gallstone acute pancreatitis 26.7% followed by HEV 6.7% and Pancreas Divisum 6.7%%, SOD 3.3%, EBV 3.3%, Mumps 3.3%, Hepatitis 3.3%, Tumour 3.3%, Choledochal cyst 3.3%,Drugs 3.3% and Gallstone 3.3%. Logistic regression analysis finding indicates that acute pancreatitis was found more prevalent in < 40 yrs [OR 2.076,95%(CI 0.339, 12.716)] and among patients  having monthly income of <5000 rs/month yrs [OR 1.4,95%(CI 0.224, 8.768)] . According to the severity of CT grading, Patients had Grade D severity  [OR 2.667,95%(CI 0.158, 45.141)], Grade C[OR 1.333,95%(CI 0.104, 17.098)] and Grade E [OR 1.333,95%(CI 0.88, 20.108)]as compared to Grade B severity of CT.  Conclusion In the  study  an  etiological  factor  was  evident  among  almost 3/4th   of the patients  of  non-alcoholic  and  non-gallstone  pancreatitis. The most common etiological factors were CMV followed by HEV.  These  results  rather  suggests  that the most diligent  workup  including  a  biliary  microcrystal  analysis,  a  sphincter  of  Oddi  manometry  and  possible  gene  analysis  for  hereditary  disorders  may  further  reduce   the  apparently  idiopathic  group in  the  analysis  of  such  patients. DOI: http://dx.doi.org/10.3126/nje.v4i3.10663 Nepal Journal of Epidemiology 2014; 4(3): 351-62
Fault‐tolerant control of distributed systems by information pattern reconfiguration
Authors: Staroswiecki M. , Amani A. Moradi
Published: June 2014

Given a fault‐tolerance strategy and a distributed control system, the set of recoverable faults depends on the information pattern that is implemented. This paper shows that fault‐tolerance can be achieved, when possible, by the reconfiguration of the information pattern. A necessary and sufficient recoverability condition is provided, and sub‐optimal solutions are developed for actuator and sensor faults under system reconfiguration. Copyright © 2014 John Wiley & Sons, Ltd.
Association of microcephalin 1, syntrophin‐beta 1, and other genes with automatic thoughts in the Japanese population
Authors: Ishitobi Yoshinobu , Inoue Ayako , Aizawa Saeko , Masuda Koji , Ando Tomoko , Kawano Aimi , Ikeda Rie , Maruyama Yoshihiro , Kanehisa Masayuki , Ninomiya Taiga , Tanaka Yoshihiro , Tsuru Jusen , Akiyoshi Jotaro
Published: June 2014

Automatic thoughts may be risk factors for depression and anxiety, and should be detected early. However, the genetic basis of automatic thoughts remains unclear. This study aims to investigate the genetic association of automatic thoughts with SNPs (single nucleotide polymorphisms) involved in cognition, neurogenesis, neuronal cell structure, neurotransmitters, hypothalamus–pituitary adrenal axis and psychiatric illness. The study included 610 healthy participants. We used the Depression and Anxiety Cognition Scale (DACS), a Japanese psychological questionnaire, to assess automatic thoughts. Twenty‐five SNPs including COMT, BDNF, FKBP5, SNTB1 (syntrophin‐beta 1, rs4512418), and MCPH1 (microcephalin 1, rs2911968) were selected according to their minor allele frequency. Linear regression models were used to test association of mean DACS scores with each allele (major‐allele homozygote, heterozygote, and minor‐allele homozygote). The significant α‐value was set at α < 0.002. Statistical analysis was conducted using SNPStats. Call rates for all genotypes were >98%. Eighteen SNPs did not deviate from Hardy–Weinberg equilibrium, and 7 were excluded from statistical analysis. Significant associations of SNTB1 with interpersonal threat and MCPH1 with future denial were observed only in females. SNTB1 and MCPH1 are located on chromosome 8, which may be involved in neuroticism, avoidant personality and depression. Our results demonstrated that DACS scores showing significant interaction with the 2 SNPs may be regarded as appropriate traits to detect the diathesis of automatic thoughts. The 2 SNPs may be important loci in research on cognitive vulnerability to depression and anxiety. © 2014 Wiley Periodicals, Inc.
Prognostic significance of the intratumoral heterogeneity of 18F‐FDG uptake in oral cavity cancer
Authors: Kwon Soo Hyun , Yoon Joon‐Kee , An Young‐Sil , Shin Yoo Seob , Kim Chul‐Ho , Lee Dong Hyun , Jo Kyung Sook , Lee Su Jin
Published: June 2014

Backgrounds

We evaluated the prognostic value of the intratumoral heterogeneity of 18F‐FDG uptake in oral cavity cancer.

Materials and Methods

We enrolled 45 patients who underwent pretreatment 18F‐FDG PET/CT. The intratumoral heterogeneity of 18F‐FDG uptake was represented as the heterogeneity factor (HF), defined as the derivative (dV/dT) of a volume‐threshold function for a primary tumor. We measured the maximum standardized uptake value (SUVmax) and volumetric PET parameters. The relationship between HF and clinical parameters, as well as other PET parameters, was evaluated.

Results

The HF was significantly correlated with SUVmax (r = −0.353, P = 0.017), metabolic tumor volume (r = −0.708, P < 0.0001), and total lesion glycolysis (r = −0.709, P < 0.0001). A multivariate analysis revealed not only cervical lymph node metastasis (hazard ratio = 5.983; P = 0.022) but also HF (hazard ratio = 2.49 × 10−4; P = 0.002) to be independent predictors of overall survival. Those patients with HF < −0.13 showed a worse prognosis than those with HF ≥ −0.13 (P = 0.005).

Conclusions

The intratumoral heterogeneity of 18F‐FDG uptake may be a significant prognostic factor for overall survival in addition to cervical lymph node metastasis in oral cavity cancer. J. Surg. Oncol. 2014 110:702–706. © 2014 Wiley Periodicals, Inc.
The influence of elevated levels of C‐reactive protein and hypoalbuminemia on survival in patients with advanced inoperable esophageal cancer undergoing palliative treatment
Authors: Lindenmann Joerg , Fink‐Neuboeck Nicole , Koesslbacher Mario , Pichler Martin , Stojakovic Tatjana , Roller Regina Elisabeth , Maier Alfred , Anegg Udo , Smolle Josef , Smolle‐Juettner Freyja Maria
Published: June 2014

Background and Objectives

Inflammation perpetuates individual tumor progression resulting in decreased survival in cancer patients. The aim of our study was to evaluate the influence of elevated levels of C‐reactive protein (CRP) as well as low levels of albumin on patients with inoperable esophageal carcinoma.

Methods

The data of 218 patients with advanced esophageal cancer, who were treated at a single center within 12 years, were evaluated retrospectively. Patient's age, gender, body weight, dysphagia, plasma levels of CRP and albumin, the Glasgow Prognostic Score (GPS) combining both indicators, and survival were assessed for statistical evaluation.

Results

Thirty‐nine (18.2%) had hypoalbuminemia and 161 (73.9%) had elevated CRP levels. Patients with hypoalbuminemia (P = 0.001) as well as patients with increased CRP levels (P = 0.001) showed a significantly shorter survival. Weight loss was correlated to elevated plasma CRP (P = 0.022), to diarrhea (P = 0.021), and to dysphagia (P = 0.008). Increasing GPS was significantly associated with poor survival (P = 0.001).

Conclusions

Elevated CRP levels and hypoalbuminemia are significantly associated with reduced survival and are considered to be an appropriate predictor for poor outcome in advanced esophageal carcinoma. The GPS provides additional detailed prognostication and should be therefore taken into consideration when the individual palliative strategy has to be scheduled. J. Surg. Oncol. 2014 110:645–650. © 2014 Wiley Periodicals, Inc.
Risk prediction tools in surgical oncology
Authors: Kinnier Christine V. , Asare Elliot A. , Mohanty Sanjay , Paruch Jennifer L. , Rajaram Ravi , Bilimoria Karl Y.
Published: June 2014

Healthcare has increasingly focused on patient engagement and shared decision‐making. Decision aids can promote engagement and shared decision making by providing patients and their providers with care options and outcomes. This article discusses decision aids for surgical oncology patients. Topics include: short‐term risk prediction following surgery, long‐term risk prediction of survival and recurrence, the combination of short‐ and long‐term risk prediction to help guide treatment choice, and decision aid usability, transparency, and accessibility. J. Surg. Oncol. 2014 110:500–508. © 2014 Wiley Periodicals, Inc.
Wogonin suppresses human alveolar adenocarcinoma cell A549 migration in inflammatory microenvironment by modulating the IL‐6/STAT3 signaling pathway
Authors: Zhao Yue , Yao Jing , Wu Xiao‐Ping , Zhao Li , Zhou Yu‐Xin , Zhang Yi , You Qi‐Dong , Guo Qing‐Long , Lu Na
Published: June 2014

Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment facilitates tumor metastasis. Clinically, it will be a promising choice to suppress tumor metastasis by targeting inflammatory microenvironment. Our previous studies have demonstrated that wogonin (a bioflavonoid isolated from the traditional Chinese medicine of Huang‐Qin) possesses the anti‐metastatic and anti‐inflammatory activity, but we have little idea about its efficacy on inflammatory‐induced tumor metastasis and the mechanism underlying it. In this study, we focused on epithelial mesenchymal transition (EMT), the first step of tumor metastasis, to evaluate the effects of wogonin on tumor metastasis in inflammatory microenvironment. We found that wogonin inhibited THP‐1 conditioned‐medium‐ (CM‐) and IL‐6‐induced EMT by inactivating STAT3 signal. And in wogonin‐treated A549 cells which pretreated with THP‐1 CM or IL‐6, the expression level of E‐cadherin, an EMT negative biomarker, increased while that of N‐cadherin, Vimentin, and EMT‐related transcription factors including Snail and Twist decreased. Moreover, wogonin inhibited IL‐6‐induced phosphorylation of STAT3, prevented p‐STAT3 dimer translocation into the nucleus, and suppressed the DNA‐binding activity of p‐STAT3. Interestingly, similar results were obtained in the tumor xenografts mice, including downregulation of p‐STAT3, N‐cadherin, and Vimentin while up‐regulation of E‐cadherin. Wogonin also inhibit the metastasis of A549 cells in vivo. Taken all data together, we concluded that wogonin suppresses tumor cells migration in inflammatory microenvironment by inactivating STAT3 signal. © 2014 Wiley Periodicals, Inc.
Targeting Fyn in Ras‐transformed cells induces F‐actin to promote adherens junction‐mediated cell–cell adhesion
Authors: Fenton Sarah E. , Hutchens Kelli A. , Denning Mitchell F.
Published: June 2014

Fyn, a member of the Src family kinases (SFK), is an oncogene in murine epidermis and is associated with cell–cell adhesion turnover and induction of cell migration. Additionally, Fyn upregulation has been reported in multiple tumor types, including cutaneous squamous cell carcinoma (cSCC). Introduction of active H‐Ras(G12V) into the HaCaT human keratinocyte cell line resulted in upregulation of Fyn mRNA (200‐fold) and protein, while expression of other SFKs remained unaltered. Transduction of active Ras or Fyn was sufficient to induce an epithelial‐to‐mesenchymal transition in HaCaT cells. Inhibition of Fyn activity, using siRNA or the clinical SFK inhibitor Dasatinib, increased cell–cell adhesion and rapidly (5–60 min) increased levels of cortical F‐actin. Fyn inhibition with siRNA or Dasatinib also induced F‐actin in MDA‐MB‐231 breast cancer cells, which have elevated Fyn. F‐actin co‐localized with adherens junction proteins, and Dasatinib‐induced cell–cell adhesion could be blocked by Cytochalasin D, indicating that F‐actin polymerization was a key initiator of cell–cell adhesion through the adherens junction. Conversely, inhibiting cell–cell adhesion with low Ca2+ media did not block Dasatinib‐induced F‐actin polymerization. Inhibition of the Rho effector kinase ROCK blocked Dasatinib‐induced F‐actin and cell–cell adhesion, implicating relief of Rho GTPase inhibition as a mechanism of Dasatinib‐induced cell–cell adhesion. Finally, topical Dasatinib treatment significantly reduced total tumor burden in the SKH1 mouse model of UV‐induced skin carcinogenesis. Together these results identify the promotion of actin‐based cell–cell adhesion as a newly described mechanism of action for Dasatinib and suggest that Fyn inhibition may be an effective therapeutic approach in treating cSCC. © 2014 Wiley Periodicals, Inc.
Misidentification of sex among harvested bobcats
Authors: Hiller Tim L. , Reding Dawn M. , Clark William R. , Green Richard L.
Published: June 2014

Sex and age data are fundamental vital statistics used to characterize wildlife populations, often integral to models used to assess population responses to harvest or make other management decisions. Misidentification errors could ultimately result in poor management decisions by misrepresenting harvest or population structure. We compared field examination and genetic identification of sex of bobcats (Lynx rufus; n = 248) collected during the 2009–2010 harvest season in Oregon, USA. Furtaker‐reported sex assignment and genetics analysis mismatched for 51 (20.6%) cases. In 31 (12.5%) cases, bobcats reported as females were classified as males by genetic analysis, and vice versa for the remaining 20 individuals. Quantification of errors in sex assignment allows for acknowledgment of technique and data limitations and may allow for adjustments to be considered during decision‐making processes. State agencies may consider providing formal training in field identification techniques and subsampling harvested bobcats for genetic sex assignment in an effort to more accurately reflect sex ratios in the harvest. © 2014 The Wildlife Society.
The ‘giant phyllosoma’ are larval stages of Parribacus antarcticus (Decapoda : Scyllaridae)
Authors: Palero Ferran , Guerao Guillermo , Hall Michael , Chan Tin Yam , Clark Paul F.
Published: June 2014

Early reports on larval distributions are frustratingly obscure due to ambiguous identification of plankton samples. A particularly striking case is posed by the so-called ‘giant phyllosoma’ which attain 80 mm in total length and are among the largest larvae known in marine invertebrates. Based on the supposition that these giant larvae are produced by local species, Philip Robertson (1968) assigned them to Parribacus. In the present study, 12 phyllosoma larvae collected in the Coral Sea and corresponding to intermediate stages VI to IX are described in detail. The identity of these freshly caught specimens was confirmed as belonging to Parribacus antarcticus (Lund, 1793) by using DNA barcoding methods. This new collection further allowed us to complete the larval series for the genus. The intermediate stage VI, which was missing in previous accounts, is described here for the first time. Besides the Coral Sea larvae, another five phyllosoma specimens previously deposited in UK and German museum collections are also described. Given that no useful DNA could be obtained from the old collection specimens, these larvae were identified as Parribacus sp. based on morphology only. Furthermore, a complete morphometric analysis of Parribacus larvae was undertaken including information from literature dating back to 1830. The first detailed description of all dactyli from a complete phyllosoma of the genus Parribacus is presented, with further comparison with those from other genera of Scyllaridae.
Phylogeny, historical biogeography and divergence time estimates of the genus Colophon Gray (Coleoptera : Lucanidae)
Authors: Switala Angelika K. , Sole Catherine L. , Scholtz Clarke H.
Published: June 2014

The flightless Cape High-mountain stag beetle genus Colophon (Coleoptera: Lucanidae) is studied. All species are endemic to the Cape Floristic Region of the Western Cape, South Africa. The study aimed to determine the specific and phylogenetic status of the described species of Colophon and to determine the main factors driving their evolution by testing the hypothesis of a lowland origin. This was achieved by analysing the mitochondrial COI, 16S rRNA and nuclear CAD genes, using a maximum likelihood and Bayesian approach. Timing of key biogeographical events in the diversification of Colophon was estimated in BEAST. The combined molecular dataset supports the described species. High genetic divergence was found between the described taxa. The mean estimated divergence of the genus was mid-Cretaceous, with a split into two lineages during the early Paleocene to mid Eocene. Species divergence was shown to have occurred during mid to late Miocene. Most species of Colophon showed an allopatric distribution, although contact zones between geographically adjacent species are likely. Climate seems to be the main driving factor behind Colophon evolution and the hypothesis of a lowland origin appears to be supported.
A complete species phylogeny of the marine midge Pontomyia (Diptera:Chironomidae) reveals a cosmopolitan species and a new synonym
Authors: Huang Danwei , Cranston Peter S. , Cheng Lanna
Published: June 2014

Pontomyia (Diptera : Chironomidae) is an exclusively marine and flightless insect genus with four described species from the Indo-Pacific and one undescribed taxon known only by its larvae, pupal skins and females from the western Atlantic. A previous study of relationships among three of the Indo-Pacific species reported each of them to be monophyletic, with high genetic diversity within P. natans Edwards, 1926, the type species, and P. pacifica Tokunaga, 1932. The evolutionary affinities of the Australian endemic P. cottoni Womersley, 1937, which resembles P. natans, as well as the putative Atlantic species are hitherto undetermined. A complete molecular phylogeny of the genus based on two nuclear and two mitochondrial DNA markers indicates that P. cottoni and a Puerto Rican (Atlantic) larval population are nested within the P. natans clade. Furthermore, P. natans and P. cottoni are inseparable in all morphological characters used previously to distinguish them. Therefore, we synonymise P. cottoni with P. natans, syn. nov., whose known range now encompasses all three ocean basins after including the Puerto Rican population. This distribution warrants further investigation into the life history of Pontomyia, a midge with one of the shortest known adult lifespans among insects.
New insights into the phylogeny, systematics and DNA barcoding of Nemertea
Authors: Kvist Sebastian , Laumer Christopher E. , Junoy Juan , Giribet Gonzalo
Published: June 2014

Although some clades of ribbon worms (phylum Nemertea) are consistently recovered with high support in molecular phylogenies, the placement and inter-relationships of some taxa have proven problematic. Herein, we performed molecular phylogenetic analyses aimed at resolving these recalcitrant splits, using six loci (nuclear 18S rRNA, 28S rRNA, histones H3 and H4, and mitochondrial 16S rRNA and COI) for 133 terminals, with particular emphasis on the problematic families Hubrechtidae and Plectonemertidae. Three different datasets were used for phylogenetic analyses and both maximum likelihood and maximum parsimony methodologies were applied. All but one of the resulting tree topologies agree on the paraphyly of the class Palaeonemertea, whereas Heteronemertea, Hoplonemertea, Polystilifera, Monostilifera and Hubrechtidae are always recovered as reciprocally monophyletic. Hubrechtidae is sister group to Heteronemertea (the Pilidiophora hypothesis) only when length variable regions of 18S rRNA and 28S rRNA are excluded. Moreover, the terrestrial and freshwater family Plectonemertidae is recovered with high support and the implications of this finding are further discussed. Finally, we evaluate the utility of DNA barcoding for specimen identification within Nemertea using an extended dataset containing 394 COI sequences. Results suggest that DNA barcoding may work for Nemertea, insofar as a distinct barcoding gap (the gap between the maximum intraspecific variation and the minimum interspecific divergence) may exist, but its recognition is regularly hampered by low accuracy in species level identifications.
A revision of Chara sect. Protochara, comb. et stat. nov. (Characeae: Charophyceae)
Authors: Casanova Michelle T. , Karol Kenneth G.
Published: June 2014

A revision of a group of ecorticate species of Chara is presented, on the basis of fresh, pressed and spirit-preserved material. The following seven species are recognised, characterised by a very simple morphology, with few or inconspicuous accessory cells (cortication, stipulodes, bract cells, bracteoles) and large gametangia: Chara australis R.Br., C. lucida (A.Braun) Casanova & Karol comb et. stat. nov., C. porteri Casanova, sp. nov., C. protocharoides Casanova & Karol, nom. nov. (=Protochara australis Womersley & Ophel) and C. stuartiana (Kütz.) Casanova & Karol comb. et. stat. nov. from Australia, and C. corallina Klein ex Willd. and C. wallichii A.Braun from Asia. A new section, Chara subg. Charopsis sect. Protochara (Womersley & Ophel) Casanova & Karol, comb. et stat. nov., is erected to accommodate these taxa, formerly placed in sect. Charopsis.
Learning protein–DNA interaction landscapes by integrating experimental data through computational models
Authors: Zhong Jianling , Wasson Todd , Hartemink Alexander J.
Published: June 2014

Motivation: Transcriptional regulation is directly enacted by the interactions between DNA and many proteins, including transcription factors (TFs), nucleosomes and polymerases. A critical step in deciphering transcriptional regulation is to infer, and eventually predict, the precise locations of these interactions, along with their strength and frequency. While recent datasets yield great insight into these interactions, individual data sources often provide only partial information regarding one aspect of the complete interaction landscape. For example, chromatin immunoprecipitation (ChIP) reveals the binding positions of a protein, but only for one protein at a time. In contrast, nucleases like MNase and DNase can be used to reveal binding positions for many different proteins at once, but cannot easily determine the identities of those proteins. Currently, few statistical frameworks jointly model these different data sources to reveal an accurate, holistic view of the in vivo protein–DNA interaction landscape.

Results: Here, we develop a novel statistical framework that integrates different sources of experimental information within a thermodynamic model of competitive binding to jointly learn a holistic view of the in vivo protein–DNA interaction landscape. We show that our framework learns an interaction landscape with increased accuracy, explaining multiple sets of data in accordance with thermodynamic principles of competitive DNA binding. The resulting model of genomic occupancy provides a precise mechanistic vantage point from which to explore the role of protein–DNA interactions in transcriptional regulation.

Availability and implementation: The C source code for compete and Python source code for MCMC-based inference are available at http://www.cs.duke.edu/∼amink .

Contact:  amink@cs.duke.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
TPpred2: improving the prediction of mitochondrial targeting peptide cleavage sites by exploiting sequence motifs
Authors: Savojardo Castrense , Martelli Pier Luigi , Fariselli Piero , Casadio Rita
Published: June 2014

Summary: Targeting peptides are N-terminal sorting signals in proteins that promote their translocation to mitochondria through the interaction with different protein machineries. We recently developed TPpred, a machine learning-based method scoring among the best ones available to predict the presence of a targeting peptide into a protein sequence and its cleavage site. Here we introduce TPpred2 that improves TPpred performances in the task of identifying the cleavage site of the targeting peptides. TPpred2 is now available as a web interface and as a stand-alone version for users who can freely download and adopt it for processing large volumes of sequences.

Availability and implementaion : TPpred2 is available both as web server and stand-alone version at http://tppred2.biocomp.unibo.it .

Contact:  gigi@biocomp.unibo.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
Atomic resolution structure of a lysine-specific endoproteinase fromLysobacter enzymogenessuggests a hydroxyl group bound to the oxyanion hole
Authors: Asztalos Peter , Müller Astrid , Hölke Werner , Sobek Harald , Rudolph Markus G.
Published: June 2014

Lysobacter enzymogeneslysyl endoproteinase (LysC) is a trypsin-type serine protease with a high pH optimum that hydrolyses all Lys-Xaa peptide bonds. The high specificity of LysC renders it useful for biotechnological purposes. The K30R variant of a related lysyl endoproteinase fromAchromobacter lyticushas favourable enzymatic properties that might be transferrable to LysC. To visualize structural differences in the substrate-binding sites, the crystal structures of wild-type and the K30R variant of LysC were determined. The mutation is located at a distance of 12 Å from the catalytic triad and subtly changes the surface properties of the substrate-binding site. The high pH optimum of LysC can be attributed to electrostatic effects of an aromatic Tyr/His stack on the catalytic aspartate and is a general feature of this enzyme subfamily. LysC crystals in complex with the covalent inhibitorNα-p-tosyl-lysyl chloromethylketone yielded data to 1.1 and 0.9 Å resolution, resulting in unprecedented precision of the active and substrate-binding sites for this enzyme subfamily. Error estimates on bond lengths and difference electron density indicate that instead of the expected oxyanion a hydroxyl group binds to the partially solvent-exposed oxyanion hole. Protonation of the alkoxide catalytic intermediate might be a recurring feature during serine protease catalysis.
The structure of a deoxygenated 400 kDa haemoglobin reveals ternary- and quaternary-structural changes of giant haemoglobins
Authors: Numoto Nobutaka , Nakagawa Taro , Ohara Ryota , Hasegawa Tomoyo , Kita Akiko , Yoshida Takao , Maruyama Tadashi , Imai Kiyohiro , Fukumori Yoshihiro , Miki Kunio
Published: June 2014

The quaternary structures of invertebrate haemoglobins (Hbs) are quite different from those of vertebrate Hbs. The extracellular giant Hbs of molecular masses of about 400 and 3600 kDa are composed of a dome-shaped dodecameric subassembly which consists of four individual globin subunits. Several crystal structures of 400 kDa Hbs from annelids have been reported, including structures in oxygenated and partially unliganded states, but the structure of the fully deoxygenated state has not been reported. In the present study, crystal structures of V2Hb from the tube wormLamellibrachia satsumahave been determined in both the fully oxygenated and deoxygenated states. A glycosylation site and novel metal-binding sites for divalent cations were clearly observed with no intersubunit interactions in V2Hb. A comparison of the oxygenated and the deoxygenated forms of V2Hb reveals that the ternary- and quaternary-structural changes occur in a manner that maintains the molecularD3symmetry. These structures suggest that the mechanisms of quaternary-structural changes between the oxy and deoxy states for the giant Hbs are identical across species.
Na+/K+exchange switches the catalytic apparatus of potassium-dependent plantL-asparaginase
Authors: Bejger Magdalena , Imiolczyk Barbara , Clavel Damien , Gilski Miroslaw , Pajak Agnieszka , Marsolais Frédéric , Jaskolski Mariusz
Published: June 2014

Plant-type L-asparaginases, which are a subclass of the Ntn-hydrolase family, are divided into potassium-dependent and potassium-independent enzymes with different substrate preferences. While the potassium-independent enzymes have already been well characterized, there are no structural data for any of the members of the potassium-dependent group to illuminate the intriguing dependence of their catalytic mechanism on alkali-metal cations. Here, three crystal structures of a potassium-dependent plant-type L-asparaginase fromPhaseolus vulgaris(PvAspG1) differing in the type of associated alkali metal ions (K+, Na+or both) are presented and the structural consequences of the different ions are correlated with the enzyme activity. As in all plant-type L-asparaginases, immature PvAspG1 is a homodimer of two protein chains, which both undergo autocatalytic cleavage to α and β subunits, thus creating the mature heterotetramer or dimer of heterodimers (αβ)2. The αβ subunits of PvAspG1 are folded similarly to the potassium-independent enzymes, with a sandwich of two β-sheets flanked on each side by a layer of helices. In addition to the `sodium loop' (here referred to as the `stabilization loop') known from potassium-independent plant-type asparaginases, the potassium-dependent PvAspG1 enzyme contains another alkali metal-binding loop (the `activation loop') in subunit α (residues Val111–Ser118). The active site of PvAspG1 is located between these two metal-binding loops and in the immediate neighbourhood of three residues, His117, Arg224 and Glu250, acting as a catalytic switch, which is a novel feature that is identified in plant-type L-asparaginases for the first time. A comparison of the three PvAspG1 structures demonstrates how the metal ion bound in the activation loop influences its conformation, setting the catalytic switch to ON (when K+is coordinated) or OFF (when Na+is coordinated) to respectively allow or prevent anchoring of the reaction substrate/product in the active site. Moreover, it is proposed that Ser118, the last residue of the activation loop, is involved in the potassium-dependence mechanism. The PvAspG1 structures are discussed in comparison with those of potassium-independent L-asparaginases (LlA, EcAIII and hASNase3) and those of other Ntn-hydrolases (AGA and Tas1), as well as in the light of noncrystallographic studies.
Structure ofEscherichia coliGrx2 in complex with glutathione: a dual-function hybrid of glutaredoxin and glutathioneS-transferase
Authors: Ye Jun , Nadar S. Venkadesh , Li Jiaojiao , Rosen Barry P.
Published: June 2014

The structure of glutaredoxin 2 (Grx2) fromEscherichia colico-crystallized with glutathione (GSH) was solved at 1.60 Å resolution. The structure of a mutant with the active-site residues Cys9 and Cys12 changed to serine crystallized in the absence of glutathione was solved to 2.4 Å resolution. Grx2 has an N-terminal domain characteristic of glutaredoxins, and the overall structure is congruent with the structure of glutathioneS-transferases (GSTs). Purified Grx2 exhibited GST activity. Grx2, which is the physiological electron donor for arsenate reduction byE. coliArsC, was docked with ArsC. The docked structure could be fitted with GSH bridging the active sites of the two proteins. It is proposed that Grx2 is a novel Grx/GST hybrid that functions in two steps of the ArsC catalytic cycle: as a GST it catalyzes glutathionylation of the ArsC–As(V) intermediate and as a glutaredoxin it catalyzes deglutathionylation of the ArsC–As(III)–SG intermediate.
Structural and biochemical analyses of alanine racemase from the multidrug-resistantClostridium difficilestrain 630
Authors: Asojo Oluwatoyin A. , Nelson Sarah K. , Mootien Sara , Lee Yashang , Rezende Wanderson C. , Hyman Daniel A. , Matsumoto Monica M. , Reiling Scott , Kelleher Alan , Ledizet Michel , Koski Raymond A. , Anthony Karen G.
Published: June 2014

Clostridium difficile, a Gram-positive, spore-forming anaerobic bacterium, is the leading cause of infectious diarrhea among hospitalized patients.C. difficileis frequently associated with antibiotic treatment, and causes diseases ranging from antibiotic-associated diarrhea to life-threatening pseudomembranous colitis. The severity ofC. difficileinfections is exacerbated by the emergence of hypervirulent and multidrug-resistant strains, which are difficult to treat and are often associated with increased mortality rates. Alanine racemase (Alr) is a pyridoxal-5′-phosphate (PLP)-dependent enzyme that catalyzes the reversible racemization of L- and D-alanine. Since D-alanine is an essential component of the bacterial cell-wall peptidoglycan, and there are no known Alr homologs in humans, this enzyme is being tested as an antibiotic target. Cycloserine is an antibiotic that inhibits Alr. In this study, the catalytic properties and crystal structures of recombinant Alr from the virulent and multidrug-resistantC. difficilestrain 630 are presented. Three crystal structures ofC. difficileAlr (CdAlr), corresponding to the complex with PLP, the complex with cycloserine and a K271T mutant form of the enzyme with bound PLP, are presented. The structures are prototypical Alr homodimers with two active sites in which the cofactor PLP and cycloserine are localized. Kinetic analyses reveal that the K271T mutant CdAlr has the highest catalytic constants reported to date for any Alr. Additional studies are needed to identify the basis for the high catalytic activity. The structural and activity data presented are first steps towards using CdAlr for the development of structure-based therapeutics forC. difficileinfections.
Structural basis of the heterodimerization of the MST and RASSF SARAH domains in the Hippo signalling pathway
Authors: Hwang Eunha , Cheong Hae-Kap , Mushtaq Ameeq Ul , Kim Hye-Yeon , Yeo Kwon Joo , Kim Eunhee , Lee Woo Cheol , Hwang Kwang Yeon , Cheong Chaejoon , Jeon Young Ho
Published: June 2014

Despite recent progress in research on the Hippo signalling pathway, the structural information available in this area is extremely limited. Intriguingly, the homodimeric and heterodimeric interactions of mammalian sterile 20-like (MST) kinases through the so-called `SARAH' (SAV/RASSF/HPO) domains play a critical role in cellular homeostasis, dictating the fate of the cell regarding cell proliferation or apoptosis. To understand the mechanism of the heterodimerization of SARAH domains, the three-dimensional structures of an MST1–RASSF5 SARAH heterodimer and an MST2 SARAH homodimer were determined by X-ray crystallography and were analysed together with that previously determined for the MST1 SARAH homodimer. While the structure of the MST2 homodimer resembled that of the MST1 homodimer, the MST1–RASSF5 heterodimer showed distinct structural features. Firstly, the six N-terminal residues (Asp432–Lys437), which correspond to the short N-terminal 310-helix h1 kinked from the h2 helix in the MST1 homodimer, were disordered. Furthermore, the MST1 SARAH domain in the MST1–RASSF5 complex showed a longer helical structure (Ser438–Lys480) than that in the MST1 homodimer (Val441–Lys480). Moreover, extensive polar and nonpolar contacts in the MST1–RASSF5 SARAH domain were identified which strengthen the interactions in the heterodimer in comparison to the interactions in the homodimer. Denaturation experiments performed using urea also indicated that the MST–RASSF heterodimers are substantially more stable than the MST homodimers. These findings provide structural insights into the role of the MST1–RASSF5 SARAH domain in apoptosis signalling.
Unprecedented conformational flexibility revealed in the ligand-binding domains of theBovicola ovisecdysone receptor (EcR) and ultraspiracle (USP) subunits
Authors: Ren Bin , Peat Thomas S. , Streltsov Victor A. , Pollard Matthew , Fernley Ross , Grusovin Julian , Seabrook Shane , Pilling Pat , Phan Tram , Lu Louis , Lovrecz George O. , Graham Lloyd D. , Hill Ronald J.
Published: June 2014

The heterodimeric ligand-binding region of theBovicola ovisecdysone receptor has been crystallized either in the presence of an ecdysteroid or a synthetic methylene lactam insecticide. Two X-ray crystallographic structures, determined at 2.7 Å resolution, show that the ligand-binding domains of both subunits of this receptor, like those of other nuclear receptors, can display significant conformational flexibility. Thermal melt experiments show that while ponasterone A stabilizes the higher order structure of the heterodimer in solution, the methylene lactam destabilizes it. The conformations of the EcR and USP subunits observed in the structure crystallized in the presence of the methylene lactam have not been seen previously in any ecdysone receptor structure and represent a new level of conformational flexibility for these important receptors. Interestingly, the new USP conformation presents an open, unoccupied ligand-binding pocket.