bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetics of Cardiovascular Disease: A New ‘Beat' in Coronary Artery Disease
Authors: Turgeon Paul J. , Sukumar Aravin N. , Marsden Philip A.
Published: June 2014

Genome-wide association studies have become a powerful tool in the identification of disease-associated variants. Unfortunately, many of these studies have found that the estimated variability in cardiovascular disease (CVD) risk cannot be fully explained by traditional paradigms of genetic variation in protein-coding genes. Moreover, traditional views do not sufficiently explain the well-known link between CVD and environmental influence. We posit that epigenetics, defined as chromatin-based mechanisms important in the regulation of gene expression that do not involve changes in the DNA sequence per se, represents the missing link. The nuclear-based mechanisms that contribute to epigenetic gene regulation can be broadly separated into three unique but highly interrelated processes, namely DNA methylation and hydroxymethylation, histone density and post-translational modifications, and ribonucleic acid-based mechanisms. Together, they complement the cis/trans perspective on transcriptional control paradigms in blood vessels. Moreover, epigenetics provides a molecular basis for understanding how the environment influences the genome to modify CVD risk over the lifetime of a cell and its offspring. This review is an introduction to epigenetic function and CVD, with a focus on endothelial cell biology. Additionally, we highlight emerging concepts on epigenetic gene regulation that are highly relevant to atherosclerosis and coronary artery disease.
Tone-Deaf Ears in Moths May Limit the Acoustic Detection of Two-Tone Bats
Authors: Mora Emanuel C. , Fernández Yohami , Hechavarría Julio , Pérez Martha
Published: June 2014

Frequency alternation in the echolocation of insectivorous bats has been interpreted in relation to ranging and duty cycle, i.e. advantages for echolocation. The shifts in frequency of the calls of these so-called two-tone bats, however, may also play its role in the success of their hunting behavior for a preferred prey, the tympanate moth. How the auditory receptors (e.g. the A1 and A2 cells) in the moth's ear detect such frequency shifts is currently unknown. Here, we measured the auditory responses of the A1 cell in the noctuid Spodoptera frugiperda to the echolocation hunting sequence of Molossus molossus, a two-tone bat. We also manipulated the bat calls to control for the frequency shifts by lowering the frequency band of the search and approach calls. The firing response of the A1 receptor cell significantly decreases with the shift to higher frequencies during the search and approach phases of the hunting sequence of M. molossus; this could be explained by the receptor's threshold curve. The frequency dependence of the decrease in the receptor's response is supported by the results attained with the manipulated sequence: search and approach calls with the same minimum frequency are detected by the moth at the same threshold intensity. The two-tone bat M. molossus shows a call frequency alternation behavior that may enable it to overcome moth audition even in the mid-frequency range (i.e. 20-50 kHz) where moths hear best.
The Quest for Luschka's Duct: An Eponym Leading a Life of Its Own?
Authors: Boonstra Elizabeth A. , Lorenz Karlotta , Porte Robert J.
Published: June 2014

Background: The German anatomist Hubert von Luschka gave name to several structures in the human body. One of great discussion is the duct of Luschka, part of the biliary system. There are different descriptions of the duct of Luschka. This might lead to confusion in the debate and as to what therapy should best be provided in case of an injured duct of Luschka. Methods: We reviewed the literature on descriptions of Luschka's duct and studied the original German descriptions by Hubert von Luschka. Results: While reading the original work by von Luschka on the hepatobiliary system, we were not able to find a description of either one of the two structures that are nowadays referred to as ‘the duct of Luschka'. Conclusions: von Luschka maybe never described the so-called duct of Luschka. He did, however, describe the peribiliary glands in the intra- and extrahepatic bile ducts and gallbladder wall. These might have been misinterpreted as a duct running along the gallbladder fossa. The lack of a clear definition is the reason for the development of rather confusing and sometimes misleading eponyms as the duct of Luschka. The eponym ‘duct of Luschka' should, therefore, better not be used.
Vascular Access Vulnerability in Intensive Hemodialysis: A Significant Achilles' Heel?
Authors: Cornelis Tom , Usvyat Len A. , Tordoir Jan H. , Wang Yuedong , Wong Michelle , Leunissen Karel M. , van der Sande Frank M. , Kotanko Peter , Kooman Jeroen P.
Published: June 2014

Background: Frequent hemodialysis (HD) may be associated with an increased risk of vascular access complications. Studies addressing vascular access outcomes in frequent HD show conflicting results. Methods: We searched Medline for trials looking at vascular access outcomes in frequent HD. Results: Nineteen studies met the inclusion criteria; only studies with a control group were included for analysis (n = 15). The vascular access event rate was higher in intensive HD as compared to conventional HD (difference of 6.7 events per 100 patient-years, p = 0.009). Overall event rates were not significantly different between conventional and intensive HD when stratified for access type, but were notably higher in the arteriovenous grafts and catheter group as compared to the arteriovenous fistula (AVF) group. Conclusion: Intensive HD is associated with an increased risk of vascular access complications. Overall reported event rates were lower in the AVF group. Further controlled studies should investigate whether a ‘fistula first' strategy may be recommended also for intensive HD.
Magnesium Is Not Consistently Neuroprotective for Perinatal Hypoxia-Ischemia in Term-Equivalent Models in Preclinical Studies: A Systematic Review
Authors: Galinsky Robert , Bennet Laura , Groenendaal Floris , Lear Christopher A. , Tan Sidhartha , van Bel Frank , Juul Sandra E. , Robertson Nicola J. , Mallard Carina , Gunn Alistair J.
Published: June 2014

There is an important unmet need to further improve the outcome of neonatal encephalopathy in term infants. Meta-analyses of large controlled trials now suggest that maternal magnesium sulfate (MgSO4) therapy is associated with a reduced risk of cerebral palsy and gross motor dysfunction after premature birth, but that it has no effect on death or disability. Because of this inconsistency, it remains controversial whether MgSO4 is clinically neuroprotective and, thus, it is unclear whether it would be appropriate to test MgSO4 for treatment of encephalopathy in term infants. We therefore systematically reviewed the preclinical evidence for neuroprotection with MgSO4 before or after hypoxic-ischemic encephalopathy (HIE) in term-equivalent perinatal and adult animals. The outcomes were highly inconsistent between studies. Although there were differences in dose and timing of administration, there was evidence that beneficial effects of MgSO4 were associated with confounding mild hypothermia and, strikingly, the studies that included rigorous maintenance of environmental temperature or body temperature consistently suggested a lack of effect. On balance, these preclinical studies suggest that peripherally administered MgSO4 is unlikely to be neuroprotective. Rigorous testing in translational animal models of perinatal HIE is needed before MgSO4 should be considered in clinical trials for encephalopathy in term infants.
SPARKLE (Subtypes of Ischaemic Stroke Classification System), Incorporating Measurement of Carotid Plaque Burden: A New Validated Tool for the Classification of Ischemic Stroke Subtypes
Authors: Bogiatzi Chrysi , Wannarong Thapat , McLeod A. Ian , Heisel Marnin , Hackam Daniel , Spence J. David
Published: June 2014

Background: Previous classification systems of acute ischemic stroke (Causative Classification System, CCS, of acute ischemic stroke, Trial of Org 10172 in Acute Stroke Treatment, TOAST) established the diagnosis of large artery disease (LAD) based on the presence or absence of carotid stenosis. However, carotid plaque burden is a stronger predictor of cardiovascular risk than stenosis. Our objective was to update definitions of ischemic stroke subtypes to improve the detection of LAD and to assess the validity and reliability of a new classification system: SPARKLE (Subtypes of Ischaemic Stroke Classification System). Methods: In a retrospective review of clinical research data, we compared three stroke subtype classifications: CCS, TOAST and SPARKLE. We analyzed a random sample of 275 patients presenting with minor stroke or transient ischemic attack (TIA) in an Urgent TIA Clinic in London, Ont., Canada, between 2002 and 2012. Results: There was substantial overall agreement between SPARKLE and CCS (κ = 0.75), with significant differences in the rate of detection of LAD, cardioembolic and undetermined causes of stroke or TIA. The inter-rater reliability of SPARKLE was substantial (κ = 0.76) and the intra-rater reliability was excellent (κ = 0.91). Conclusion: SPARKLE is a valid and reliable classification system, providing advantages compared to CCS and TOAST. The incorporation of plaque burden into the classification of LAD increases the proportion of cases attributable to LAD and reduces the proportion classified as being of 'undetermined' etiology.
Thromboembolism as a Cause of Renal Artery Occlusion and Acute Kidney Injury: The Recovery of Kidney Function after Two Weeks
Authors: Koivuviita Niina , Tertti Risto , Heiro Maija , Manner Ilkka , Metsärinne Kaj
Published: June 2014

Thromboembolic occlusion is a rare cause of acute kidney injury (AKI). It may lead to permanent loss of renal function. Our patient, who had dilated cardiomyopathy and prosthetic aortic valve, presented with AKI due to thromboembolic arterial occlusion of a solitary functioning kidney. After 2 weeks delay, local intra-arterial thrombolytic treatment with recombinant tissue plasminogen activator was performed without sufficient effect. However, a subsequent percutaneous transluminal angioplasty with stenting was successful. Diuresis began immediately, and renal function was fully recovered after 2 weeks. Although there had been no evident arterial circulation in the kidney, we think that minor flow through subtotal occlusion of the main renal artery made the hibernation of kidney tissue possible and contributed to the recovery. Thus, even after prolonged ischemia, revascularization can be useful.
Monte Carlo Simulation of the Treatment of Eye Tumors with 106Ru Plaques: A Study on Maximum Tumor Height and Eccentric Placement
Authors: Brualla Lorenzo , Zaragoza Francisco J. , Sauerwein Wolfgang
Published: June 2014

Background/Aims: Ruthenium plaques are used for the treatment of ocular tumors. There is, however, a controversy regarding the maximum treatable tumor height. Some advocate eccentric plaque placement, without a posterior safety margin, to avoid collateral damage to the fovea and optic disc, but this has raised concerns about marginal tumor recurrence. There is a need for quantitative information on the spatial absorbed dose distribution in the tumor and adjacent tissues. We have overcome this obstacle using an approach based on Monte Carlo simulation of radiation transport. Methods: CCA and CCB 106Ru plaques were modeled and their geometry embedded in a computerized tomography scan of the eye of a patient. Different tumor sizes and locations were simulated with the general-purpose Monte Carlo code PENELOPE. Results: Cumulative dose-volume histograms were obtained for the tumors and the tissues at risk considered. Plots of isodose lines for both plaques were obtained in a computerized tomography study. Conclusions: Ruthenium eye plaques are an adequate treatment option for tumors up to around 5 mm in height. According to our results, assuming a correct placement of the plaque, a tumor of 6.5 mm apical height is about the maximum size that can be treated safely with the large CCB plaque.
Hereditary Factors in Esophageal Adenocarcinoma
Authors: van Nistelrooij Anna M.J. , Dinjens Winand N.M. , Wagner Anja , Spaander Manon C.W. , van Lanschot J. Jan B. , Wijnhoven Bas P.L.
Published: June 2014

Background: The vast majority of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) cases are sporadic and caused by somatic mutations. However, over the last decades several families have been identified with clustering of EAC. Here, we review data from the published literature in order to address the current knowledge on familial EAC. Summary: Although familial EAC comprises a relatively small group of patients, it is a clinically relevant category due to the poor prognosis of this type of cancer. Efforts should be made to identify specific genetic risk factors for familial EAC to enable identification of relatives at risk, since endoscopic surveillance can diagnose preneoplastic or early neoplastic lesions leading to early treatment, with improved outcome. Key Message: Although familial EAC comprises a relatively small group of patients, this is a clinically relevant category due to the poor prognosis. Efforts should be made to identify specific genetic risk factors for familial EAC in order to facilitate the identification of other family members with a predisposition for this type of cancer. Practical Implications: Approximately 7% of BE and EAC cases are considered familial. Age at diagnosis is generally lower for patients with familial EAC as compared to sporadic cases, while other known risk factors for EAC, such as male gender and Caucasian ethnicity, do not differ between the two groups. In several described families with clustering of EAC the pattern of inheritance seems to be consistent with a rare autosomal dominant genetic trait. However, some association has been found with (attenuated) familial adenomatous polyposis, mismatch repair deficiency and recently with the genes MSR1, ASCC1 and CTHRC1. Nevertheless, no specific genetic predisposition has yet been identified.
Clinical Perspective of Cell-Free DNA Testing for Fetal Aneuploidies
Authors: Gratacós Eduard , Nicolaides Kypros
Published: June 2014

Cell-free DNA testing in maternal blood provides the most effective method of screening for trisomy 21, with a reported detection rate of 99% and a false positive rate of less than 0.1%. After many years of research, this method is now commercially available and is carried out in an increasing number of patients, and there is an expanding number of conditions that can be screened for. However, the application of these methods in clinical practice requires a careful analysis. Current first-trimester screening strategies are based on a complex combination of tests, aiming at detecting fetal defects and predicting the risk of main pregnancy complications. It is therefore necessary to define the optimal way of combining cell-free DNA testing with current first-trimester screening methods. In this concise review we describe the basis of cell-free DNA testing and discuss the potential approaches for its implementation in combination with current tests in the first trimester.
Practical Considerations When Prescribing Icodextrin: A Narrative Review
Authors: Silver Samuel A. , Harel Ziv , Perl Jeffrey
Published: June 2014

Background: Icodextrin is a peritoneal dialysis solution that is commonly used to increase ultrafiltration during the long dwell. The other major clinical benefit of icodextrin is that it is glucose-sparing, which may help preserve peritoneal membrane function. Since it has a different chemical composition than dextrose, and with its increasing use, there are several clinical considerations healthcare providers must familiarize themselves with prior to prescribing icodextrin. Summary: Failure to recognize these special properties of icodextrin can lead to adverse events reaching patients. This narrative review explores the hemodynamic, metabolic, and idiopathic effects of icodextrin to facilitate the safe use of icodextrin in peritoneal dialysis. Key Messages: Hemodynamic effects include hypotension from enhanced ultrafiltration contributing to loss of residual kidney function. Metabolic effects include the chemical structure of icodextrin interfering with biochemical assays, resulting in misleading glucose readings on non-specific glucometers. Idiopathic adverse effects include a diffuse rash and sterile peritonitis. It is also important to remember that not all antibiotic combinations have undergone stability testing in icodextrin. This narrative review will help healthcare providers to confidently prescribe icodextrin to maximize its benefit in peritoneal dialysis patients.
Disfarce e fraude autoral: por uma reconstituição do sujeito empírico na escrita
Authors: Gagliardi Caio
Published: June 2014

Partindo-se de exemplos recentes de fake memoirs, “gênero” que ocupa lugar de destaque na mídia, prateleiras e páginas virtuais das grandes livrarias, este ensaio discute o problema da máscara autoral, considerada em sua dupla implicação, ética e estética, no processo de recepção literária.
O autoarquivamento do autor em seus álbuns – Guimarães Rosa e a Crítica Literária
Authors: Gama Mônica
Published: June 2014

Singular em relação ao nome próprio em geral, o nome de um autor permite que se faça referência ao indivíduo (João Guimarães Rosa, nascido em Cordisburgo, médico, diplomata, pessoa observadora e contínuo anotador, dentre outros), anterior à obra, e ao discurso presente na obra. Na crítica literária acerca da obra de Guimarães Rosa, sobretudo sobre sua obra de estreia, Sagarana, indicam-se as primeiras condutas autorais, assim como as percepções dessas condutas pelos leitores e críticos. Este artigo propõe a observação da autorrepresentação Guimarães Rosa a partir da constituição de seu nome e de sua circulação registradas em textos publicados em periódicos colecionados em álbuns pelo escritor.
Roland Barthes: Da morte do autor ao seu retorno
Authors: Figueiredo Eurídice
Published: June 2014

O artigo propõe um percurso que passa pela leitura de artigos de Maurice Blanchot e Michel Foucault para chegar à trajetória de Roland Barthes no que concerne ao debate sobre a figura do autor, desde o célebre artigo “A morte do autor” até seu curso A preparação do romance II, ministrado no Collège de France e publicado postumamente. A análise que se faz aqui privilegia o livro Roland Barthes por Roland Barthes que já anunciava a vaga autobiográfica que iria surgir nos anos subsequentes.
O funcionamento da autoria na epístola De Profundis de Oscar Wilde
Authors: Mussalim Fernanda , Rodrigues Kelen Cristina
Published: June 2014

Neste artigo, pretendemos, com base em fundamentos teóricos da Análise do discurso literário proposta por Dominique Maingueneau e, fundamentalmente, com base na concepção de autor formulada por ele em seu livro Discurso literário, verificar os modos pelos quais se dá o imbricamento entre as três instâncias autorais postuladas pelo autor – a saber, a pessoa, o escritor e o inscritor – na consagrada epístola De Profundis do escritor irlandês Oscar Wilde. O intuito é, em última instância, demonstrar que a noção de autor formulada pelo analista do discurso francês permite conferir a certos gêneros de discurso produzidos no campo da literatura, como o relato autobiográfico e as cartas de autores consagrados, um estatuto que está para além de seus valores documental e biográfico.
Narração, realismo e autoria na história e no romance
Authors: Prelorentzou Renato
Published: June 2014

O artigo busca representar um processo de releituras, reescrituras, reaproveitamentos e reflexões acerca de determinados autores contemporâneos do romance e da historiografia. Em comum, esses romancistas e historiadores teriam uma escrita que enfatiza o próprio escrever do texto e, com isto, coloca o narrador em outra posição dentro da estética realista e da retórica historiográfica. Por meio de procedimentos textuais que descrevem e simulam o esboçar, o rasurar, o reescrever, o revisar, o refutar, o recomeçar e o continuar a escrever, os autores analisados entram no texto, questionam e reformulam tanto o realismo dito formal e oitocentista, quanto o método empírico da pesquisa histórica, igualmente associado ao século XIX – ambas as escolas com sobrevivências e desdobramentos ao longo dos últimos cem anos. No movimento de escrita do artigo, a leitura, a análise e a releitura desses autores abrem espaço para alguns imprevistos e reflexões acerca da forma do texto acadêmico.
Conflit entre narration et création dans La maison des temps rompus de Pascale Quiviger
Authors: Ali Suzette
Published: June 2014

Dans notre article, nous étudions les entorses faites à la narration homodiégétique dans le roman La maison des temps rompus de Pascale Quiviger. Ces entorses illustrent les divergences analytiques qui existent dans les observations théoriques du concept de narrateur, et convoquent  le conflit existentiel généré par les romanciers classiques entre la figure du narrateur et la figure de l’écrivain.
What´s in a name? The resurrection of the author in Jamaica Kincaid´s The autobiography of my mother
Authors: Silva Luciano Cabral da
Published: June 2014

Trying to break up the shackles that had held the literary studies still for so many years, Roland Barthes declares that the author is better off dead. Such a surprising statement aimed at wiping away all of the efforts to reach an origin of a literary text, that is to say, a unique answer or a final interpretation. Nevertheless Philippe Lejeune posits that when it comes to autobiographical writings, the presence of the author is to be felt, and even gladly expected. For this reason, hermeneutics is able to interchangeably adopt either Barthes´s perspective or Lejeune´s standpoint. This essay intends to shed some light on Jamaica Kincaid´s The Autobiography of my Mother based on those both perspectives. Xuela, the protagonist, can be taken entirely on her own, that is, strictly textually. In so doing, the author will be dead. On the other hand, she can also be spotted under a different name, that is, Kincaid´s. In so doing, readers are to view the resurrection of an author.
Sobre a autoria na prosa de Samuel Beckett
Authors: André Willian
Published: June 2014

Este estudo tem por objetivo propor uma breve reflexão sobre a noção de autoria na obra de Samuel Beckett, principalmente em sua prosa curta das décadas de 1960 e 1970. Para tanto, apoiados pelas considerações de Maurice Blanchot, S. E. Gontarski, João Adofo Hansen e Hugh Kenner, traçamos um percurso que parte da trilogia romanesca beckettiana do pós-guerra, passando pelas produções subsequentes que culminam na prosa curta ensaiada pelo autor após a publicação de Como é (1961). Conforme nos embrenhamos na trilha percorrida pelo escritor irlandês em sua lida com o fracasso (trilha repleta de lama e oscilações entre claro-cinza-escuro), acomete-nos uma impressão paradoxal: quanto mais severas as investidas de Beckett contra os contornos do eu, atestando a diluição da identidade, mais precisos se tornam os contornos da ideia de “autor” que encima o projeto de toda a sua literatura.
Quando não utilizar dados biográficos na análise literária: Uma discussão baseada na Analítica existencial de Martin Heidegger e no romance O lobo da estepe de Hermann Hesse
Authors: Frankel Roy David
Published: June 2014

Este artigo busca discutir até que ponto a incorporação de dados biográficos pode trazer contribuições à análise literária realizada. Para problematizar essa questão, são apresentadas as diferentes visões autorais no campo da teoria literária até as emergentes escritas de si. Para exemplificar a discussão teórica através da análise de uma obra, são utilizados conceitos da analítica existencial de Heidegger no romance O Lobo da Estepe, de Hermann Hesse.O Lobo da Estepe é um romance que pode ser observado através de diferentes vieses interpretativos. Ao utilizar, entretanto, o viés heideggariano, percebemos que o uso de dados biográficos pode prejudicar a compreensão da obra. Dessa forma, na medida em que vincula o viés interpretativo ao uso desse tipo de dado, o presente estudo permite problematizar a sua incorporação.
Autor e personagem - François Villon e a nova crítica na França
Authors: Costa Daniel Padilha Pacheco da
Published: June 2014

O corpo poético atribuído a François Villon foi composto na segunda metade do séc. XV, por volta do início do reinado de Luís XI. A partir do séc. XIX, os seus editores consideraram essa atribuição tradicional como autoevidente, de acordo com a concepção moderna de autor como criador da obra e garantia da sua autenticidade. No fim dos anos 1960, o debate sobre a morte do autor questionou o método predominante na época de explicação da obra com base na biografia. A escolha de um poeta particularmente estudado pela tradição biográfica visa a destacar alguns efeitos daquele debate sobre a crítica literária. Até então preocupada com o contexto de enunciação, a crítica de Villon se voltou para a análise da construção linguística da sua personagem poética no texto. Mas a nova crítica não prescinde do pressuposto essencial da crítica biográfica, segundo o qual o célebre malfeitor da época François des Loges seria o autor empírico da obra. Assim, a poesia de Villon é considerada como uma autobiografia ficcional daquele indivíduo histórico sobre si mesmo. A nova crítica de Villon é situada aqui não como uma ruptura com a crítica biográfica (como ela se pretende), mas como uma reformulação sobre bases comuns.
Quand l’auteur joue à disparaître: figurations auctoriales et mystifications à l’époque romantique (Les Veillées du Tasse et Les Soirées de Walter Scott à Paris)”
Authors: Feuillebois Victoire
Published: June 2014

L’article se propose d’illustrer un paradigme théorique récent, celui des « figurations auctoriales », qui a contribué à renouveler l’étude de l’auteur et de l’auctorialité dans les études françaises. Ce paradigme permet de revenir sur le discrédit jeté par le structuralisme et la théorie de la déconstruction sur les manifestations de l’auteur dans le texteet les représentations directes de sa voix: il s’agit pour nous de relire cette présence à la lumière de l’histoire culturelle et de montrer que ces figurations auctoriales n’ont vocation ni à représenter fidèlement l’auteur réel, ni à mimer les instances narratives effectives du texte. C’est ce que montre de manière exemplaire la mystification romantique, où l’auteur joue à disparaître derrière une figure trompeuse, pour mieuxaffirmer son pouvoir narratif. Elleconstitue une stratégie hybride: lesécrivains attirent leurs lecteurs parla promesse d’un contact direct avecl’auteur, mais élaborent une mani-pulation narrative qui renvoie le lec-teur au seul texte.
Leukocyte Invasion of the Brain After Experimental Intracerebral Hemorrhage in Mice
Authors: Mracsko Eva , Javidi Ehsan , Na Shin-Young , Kahn Alexandra , Liesz Arthur , Veltkamp Roland
Published: June 2014

Background and Purpose—

Neuroinflammatory processes contribute to secondary neuronal damage after intracerebral hemorrhage. We aimed to characterize the time course of brain immigration of different leukocyte subsets after striatal injection of either autologous blood or collagenase in mice.

Methods—

Intracerebral hemorrhage was induced by injection of either autologous blood (20 μL) or collagenase (0.03 U) in C57Bl/6J mice. Hematoma volumetry was performed on cryosections. Blood volume was measured by hemoglobin spectrophotometry. Leukocytes were isolated from hemorrhagic hemisphere 1, 3, 5, and 14 days after intracerebral hemorrhage, stained for leukocyte markers, and measured by flow cytometry. Heterologous blood injection from CD45.1 mice was used to investigate the origin of brain-invading leukocytes.

Results—

Collagenase injection induced a larger hematoma volume but a similar blood content compared with blood injection. Cerebral leukocyte infiltration in the hemorrhagic hemisphere was similar in both models. The majority of leukocytes isolated from the brain originated from the circulation. CD4
+
T lymphocytes were the predominant brain leukocyte population in both models. However, cerebral granulocyte counts were higher after collagenase compared with blood injection.

Conclusions—

Brain infiltration of systemic immune cells is similar in both murine intracerebral hemorrhage models. The pathophysiological impact of invading leukocytes and, in particular, of T cells requires further investigation.
Joining Pre-existing International Production Networks: Implications for India's Economic Integration with East Asia
Authors: Suh Jeongmeen , Kim Jong Duk
Published: June 2014

This study provides a conceptual framework to explain the difficulties a late-follower country will need to surmount if it seeks to join pre-existing international production networks (IPNs). To address this problem, we consider the cost minimization problem that confronts multinational firms as they choose how to locate fragmented production processes across borders. By clarifying IPN-related costs, we describe the structural disadvantages that confront late-follower countries and provide several policy implications that may help these countries overcome their disadvantages through targeted efforts. We use our framework to guide our examination of economic data, to analyze the hurdles that limit India's participation in the East Asian IPNs.
Epipactis krymmontana (Orchidaceae), a new species endemic to the Crimean Mountains and notes on the related taxa in the Crimea and bordering Russian Caucasus
Authors: Fateryga Alexander V. , Kreutz Karel C.A.J. , Fateryga Valentina V. , Efimov Petr G.
Published: June 2014

A new obligately self-pollinating species, Epipactis krymmontana, is described from the Crimea. The species is closely related to E. condensata from which it differs by its relatively loose and usually much shorter inflorescence, relatively elongate ovaries, much paler epichile with less protruding bosses and absence of a viscidium. It grows in beech forests, often mixed with oak and hornbeam, on calcareous soils. The new species was previously misidentified in the Crimea as E. purpurata or sometimes as E. condensata, the latter growing in hot, sunny places with sparse vegetation. The presence of typical E. condensata in the Crimea is considered doubtful, but it is undoubtedly present in the Russian Caucasus along with E. condensata subsp. kuenkeleana, which is a new combination proposed in place of E. purpurata subsp. kuenkeleana. Epipactis purpurata should be excluded both from the floras of the Crimea and the Russian Caucasus. An updated key to the species of Epipactis sect. Epipactis in the Crimea and Russian Caucasus is provided.
New Crepidium species (Orchidaceae, Malaxidinae) from the Island of Negros, Philippines
Authors: Margonska Hanna B
Published: June 2014

In 2013, when Mr Ravan Schneider with his wife Josephine came back from their photo tour on the Samar Island National Park (Philippines), they made a short stop in the small village of Marabut. At the food kiosk, Schneider came across in the garden next door some terrestrial orchids. Among others, there was a Crepidium plant with conspicuous leaf coloration. One of the plants had a fresh inflorescence, and he asked the owner if he could have this plant. The owner of the plants said that the plants came from about 10 kilometres from Marabut on a logging and mining road. Schneider was given the plant, which was luck because after typhoon Haynan (2013) not much remained of Marabut. In his garden the plants grew well. Upon blooming in November 2013, the plants and flowers were photographed, samples of the plant were dried and some flowers additionally were preserved in Copenhagen mixture for detailed study.
Thismia gigantea, a new combination in Thismia (Thismiaceae)
Authors: Hroneš Michal
Published: June 2014

Thismia Griffith (1844: 221; Thismiaceae J. Agardh, 1858: 99) comprises about 55 species (e.g. Tsukaya & Okada 2012; Dančák et al. 2013; Lưu et al. 2014). The greatest species diversity is situated in southeastern Asia and in the northern parts of South America (Merckx et al. 2013). Both morphological and molecular data suggest that the genus is not monophyletic being represented by at least two evolutionary lineages, the neotropical Thismia subg. Ophiomeris (Miers) Maas & H.Maas (1986: 144) and the rest of the species in a broadly defined subg. Thismia (Merckx et al. 2006; Merckx & Smets 2014).
Nomenclatural notes on the name Asarum longerhizomatosum (Aristolochiaceae)
Authors: Deng Yunfei , Yu Wenbin
Published: June 2014

Asarum longerhizomatosum C.F. Liang & C.S. Yang (Aristolochiaceae) in Liang (1975: 21) was originally described from Guangxi, China. It was widely adopted in Chinese floras (Liang 1991; Cheng & Yang 1988; Yang & Zhou 2000; Huang et al. 2003; Yang & Yang 2006). However, the name was not validly published in 1975 because two gatherings (C.L. Zhang 001 in CMMI and C.L. Zhang 002 in IBK) were designated as types contrary to the requirements of Article 40.1 & 40.2 of International Code of Nomenclature for Algae, Fungi and Plants (McNeil et al. 2012) for the names published on or after 1 January 1958. Huang et al. (2003) presumed the two elements represented duplicates of a single collection and treated the name as validly published. However,searching for type material in herbaria showed that C.L. Zhang 001 and C.L. Zhang 002 were two different gatherings. Three duplicates of C.L. Zhang 002 are found at IBK. Although no duplicate of C.L. Zhang 001 was traced by us, the previous literatures indicated that at least two duplicates exist, one in CMMI (Liang 1975) and another in PTM (Cheng & Yang 1983). It is noted that “PTM” was the acronym of “Beijing Chinese Traditional Medicine College” whose acronym is BCMM now in Index Herbariorum Sinicorum (Fu et al. 1993) and Index Herbariorum (Thiers, [continousely unpdated]).
Four new Paramphimonhystrella species (Nematoda: Xyalidae)
from the continental slope of New Zealand
Authors: LEDUC DANIEL
Published: June 2014

Four new Paramphimonhystrella species are described from the continental slope of New Zealand. P. glossalga n. sp. is characterised by presence of twelve lips, large buccal cavity, males with short, heavily cuticularised spicules joined distally, and females with large postvulvar sac and hammer-shaped cuticularised piece immediately posterior to vagina. P. barbula n. sp. is characterised by narrow buccal cavity, oval-shaped amphids, conico-cylindrical tail with swollen appearance due to conspicuously enlarged caudal gland, and males with long slender spicules and small gubernaculum. P. scutula n. sp. is characterised by a lozenge-shaped buccal cavity, males with scythe-shaped spicules, females with vulva at almost two thirds of body length from anterior, and a hammer-shaped cuticularised piece immediately posterior to vagina. P. echinocauda n. sp. is characterised by buccal cavity with cylindrical anterior portion and funnel-shaped posterior portion, distal tip of slender spicules with three pointed projections, thin gubernaculum, and tail with several long setae in middle portion, two lateral setae near tail tip and one terminal seta. The presence of a hammer-shaped cuticularised piece in two species of the genus is recorded for the first time; the function of this structure is unknown. The genus diagnosis is emended and a key to all known Paramphimonhystrella species (seven in total) is provided. The present study provides the first record of the genus outside the type locality (Yellow Sea) and extends its depth distribution from <150 m to 1350 m.
New species of Sinella and Coecobrya (Collembola: Entomobryidae) from New Caledonia
Authors: ZHANG FENG , BEDOS ANNE , DEHARVENG LOUIS
Published: June 2014

The genera Sinella and Coecobrya are reported from New Caledonia for the first time, with four new species: Sinella quadriseta sp. nov., S. claviseta sp. nov., S. copiosa sp. nov., and Coecobrya neocaledonica sp. nov. Sinella species studied here exhibit several morphological features that are not found in other non-cave species of the genus: paired teeth on inner edge of unguis closer to the base and distal unpaired tooth very tiny or absent, 2 medio-medial and 1 medio-lateral macrochaetae on Th. II, 2+2 lateral macrochaetae on Abd. III, and abundant short S-chaetae on Abd. IV. The four S-chaetae present on Abd. V are also different from the common pattern in Entomobryidae. C. neocaledonica sp. nov. does not exhibit unique features different from Coecobrya species of other areas.
Gross Moist Stability and MJO Simulation Skill in Three Full-Physics GCMs
Authors: Benedict James J. , Maloney Eric D. , Sobel Adam H. , Frierson Dargan M. W.
Published: June 2014

Previous studies have demonstrated a link between gross moist stability (GMS) and intraseasonal variability in theoretical and reduced-complexity models. In such simplified models, MJO-like moisture modes—convectively coupled tropical disturbances akin to the MJO whose formation and dynamics are linked to moisture perturbations—develop only when GMS is either negative or “effectively” negative when considering additional sources of moist entropy. These simplified models typically use a prescribed, time-independent GMS value. Limited work has been done to assess GMS and its connection to intraseasonal variability in full-physics general circulation models (GCMs).

The time-mean and intraseasonal behavior of normalized GMS (NGMS) are examined in three pairs of GCMs to elucidate the possible importance of NGMS for the MJO. In each GCM pair, one member produces weak intraseasonal variability, while the other produces robust MJOs because of a change in the treatment of deep convection. A strong linear correlation between time-mean NGMS and MJO simulation skill is observed, such that GCMs with less positive NGMS produce improved MJO eastward propagation. The reduction in time-mean NGMS is primarily due to a sharp drop to negative values in the NGMS component related to vertical advection, while the horizontal advection component has a less clear relationship with MJO simulations. Intraseasonal fluctuations of anomalous NGMS modulate the magnitude of background NGMS but generally do not change the sign of background NGMS. NGMS declines ahead of peak MJO rainfall and increases during and after heaviest precipitation. Total NGMS fluctuates during MJO passage but remains positive, suggesting that other sources of moist entropy are required to generate an effectively negative NGMS.
Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor
Authors: Wang Xunde , Mendelsohn Laurel , Rogers Heather , Leitman Susan , Raghavachari Nalini , Yang Yanqin , Yau Yu Ying , Tallack Michael , Perkins Andrew , Taylor James G. , Noguchi Constance Tom , Kato Gregory J.
Published: June 2014

Key Points

Heme-bound iron activates placenta growth factor expression in erythroid cells via EKLF, a crucial erythroid-specific transcription factor. Markers of iron burden predict mortality in adults with sickle cell disease.
Construction and evaluation of a novel humanized HER2-specific chimeric receptor
Authors: Sun Meili , Shi Huan , Liu Chuanyong , Liu Jie , Liu Xianqiang , Sun Yuping
Published: June 2014

Introduction

The human epidermal growth factor receptor 2 (HER2) represents one of the most studied tumor-associated antigens (TAAs) for cancer immunotherapy. The monoclonal antibody (mAb) trastuzumab has improved the outcomes of patients with HER2+ breast cancer. However, a large number of HER2+ tumors are not responsive to, or become resistant to, trastuzumab-based therapy, and thus more effective therapies targeting HER2 are needed.

Methods

HER2-specific T cells were generated by the transfer of genes that encode chimeric antigen receptor (CAR). Using a multistep overlap extension PCR method, we constructed a novel, humanized HER2 CAR-containing, chA21 single-chain variable fragment (scFv) region of antigen-specific mAb and T-cell intracellular signaling chains made up of CD28 and CD3ζ. An interferon γ and interleukin 2 enzyme-linked immunosorbent assay and a chromium-51 release assay were used to evaluate the antitumor immune response of CAR T cells in coculture with tumor cells. Furthermore, SKBR3 tumor–bearing nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice were treated with HER2 CAR T cells to evaluate antitumor activity. Human CD3+ T cell accumulation in tumor xenograft was detected by immunohistochemistry.

Results

chA21-28z CAR was successfully constructed, and both CD4+ and CD8+ T cells were transduced. The expanded HER2 CAR T cells expressed a central memory phenotype and specifically reacted against HER2+ tumor cell lines. Furthermore, the SKBR3 tumor xenograft model revealed that HER2 CAR T cells significantly inhibited tumor growth in vivo. Immunohistochemical analysis showed robust accumulation of human CD3+ T cells in regressing SKBR3 lesions.

Conclusions

The results of this study show that novel chA21 scFv-based, HER2-specific CAR T cells not only recognized and killed HER2+ breast and ovarian cancer cells ex vivo but also induced regression of experimental breast cancer in vivo. Our data support further exploration of the HER2 CAR T-cell therapy for HER2-expressing cancers.
Nicastrin and Notch4 drive endocrine therapy resistance and epithelial to mesenchymal transition in MCF7 breast cancer cells
Authors: Lombardo Ylenia , Faronato Monica , Filipovic Aleksandra , Vircillo Valentina , Magnani Luca , Coombes R Charles
Published: June 2014

Introduction

Resistance to anti-estrogen therapies is a major cause of disease relapse and mortality in estrogen receptor alpha (ERα)-positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependence of breast cancer cells on Notch signalling. Here, we investigated the contribution of Nicastrin and Notch signalling in endocrine-resistant breast cancer cells.

Methods

We used two models of endocrine therapies resistant (ETR) breast cancer: tamoxifen-resistant (TamR) and long-term estrogen-deprived (LTED) MCF7 cells. We evaluated the migratory and invasive capacity of these cells by Transwell assays. Expression of epithelial to mesenchymal transition (EMT) regulators as well as Notch receptors and targets were evaluated by real-time PCR and western blot analysis. Moreover, we tested in vitro anti-Nicastrin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. Finally, we generated stable Nicastrin overexpessing MCF7 cells and evaluated their EMT features and response to tamoxifen.

Results

We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and displayed increased levels of Nicastrin and Notch targets. Interestingly, we detected higher level of Notch4 but lower levels of Notch1 and Notch2 suggesting a switch to signalling through different Notch receptors after acquisition of resistance. Anti-Nicastrin monoclonal antibodies and the GSI PF03084014 were effective in blocking the Nicastrin/Notch4 axis and partially inhibiting the EMT process. As a result of this, cell migration and invasion were attenuated and the stem cell-like population was significantly reduced. Genetic silencing of Nicastrin and Notch4 led to equivalent effects. Finally, stable overexpression of Nicastrin was sufficient to make MCF7 unresponsive to tamoxifen by Notch4 activation.

Conclusions

ETR cells express high levels of Nicastrin and Notch4, whose activation ultimately drives invasive behaviour. Anti-Nicastrin mAbs and GSI PF03084014 attenuate expression of EMT molecules reducing cellular invasiveness. Nicastrin overexpression per se induces tamoxifen resistance linked to acquisition of EMT phenotype. Our finding suggest that targeting Nicastrin and/or Notch4 warrants further clinical evaluation as valid therapeutic strategies in endocrine-resistant breast cancer.
A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord
Authors: Borromeo Mark D. , Meredith David M. , Castro Diogo S. , Chang Joshua C. , Tung Kuang-Chi , Guillemot Francois , Johnson Jane E.
Published: June 2014

The proper balance of excitatory and inhibitory neurons is crucial for normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors (TFs), Ascl1 and Ptf1a, have contrasting functions in specifying these neurons. To understand how Ascl1 and Ptf1a function in this process, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a directly regulate distinct homeodomain TFs that specify excitatory or inhibitory neuronal fates. In addition, Ascl1 directly regulates genes with roles in several steps of the neurogenic program, including Notch signaling, neuronal differentiation, axon guidance and synapse formation. By contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Ascl1 and Ptf1a bind sequences primarily enriched for a specific E-Box motif (CAGCTG) and for secondary motifs used by Sox, Rfx, Pou and homeodomain factors. Ptf1a also binds sequences uniquely enriched in the CAGATG E-box and in the binding motif for its co-factor Rbpj, providing two factors that influence the specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding of how these DNA-binding proteins function in neuronal development, particularly as key regulators of homeodomain TFs required for neuronal subtype specification.
Paradox of the drinking-straw model of the butterfly proboscis
Authors: Tsai Chen-Chih , Monaenkova Daria , Beard Charles E. , Adler Peter H. , Kornev Konstantin G.
Published: June 2014

Fluid-feeding Lepidoptera use an elongated proboscis, conventionally modeled as a drinking straw, to feed from pools and films of liquid. Using the monarch butterfly, Danaus plexippus (Linnaeus), we show that the inherent structural features of the lepidopteran proboscis contradict the basic assumptions of the drinking-straw model. By experimentally characterizing permeability and flow in the proboscis, we show that tapering of the food canal in the drinking region increases resistance, significantly hindering the flow of fluid. The calculated pressure differential required for a suction pump to support flow along the entire proboscis is greater than 1 atm (~101 kPa) when the butterfly feeds from a pool of liquid. We suggest that behavioral strategies employed by butterflies and moths can resolve this paradoxical pressure anomaly. Butterflies can alter the taper, the interlegular spacing and the terminal opening of the food canal, thereby controlling fluid entry and flow, by splaying the galeal tips apart, sliding the galeae along one another, pulsing hemolymph into each galeal lumen, and pressing the proboscis against a substrate. Thus, although physical construction of the proboscis limits its mechanical capabilities, its functionality can be modified and enhanced by behavioral strategies.