bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the molecular pathologies in cloaca malformation: similarities between mouse and human
Authors: Runck Laura A. , Method Anna , Bischoff Andrea , Levitt Marc , Peña Alberto , Collins Margaret H. , Gupta Anita , Shanmukhappa Shiva , Wells James M. , Guasch Géraldine 
Published: February 2014

AbstractAnorectal malformations are congenital anomalies that form a spectrum from the most benign type with excellent functional prognosis, to very complex, such as cloaca in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs early during embryonic development of the organs derived from the cloaca. Due to the inability to directly investigate human cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca may underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective Shh signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of Keratins in the cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild to severe forms of anorectal malformations including cloaca. We found striking parallels with the Shh mouse model including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early cloacal epithelial differentiation defects may be the underlying cause of severe forms of anorectal malformations in humans. Moreover, deranged hedgehog and BMP signaling is correlated with severe anorectal malformations in both mouse and humans.
Adhesive interactions of N-cadherin limit the recruitment of microtubules to cell–cell contacts through organization of actomyosin
Authors: Plestant Charlotte , Strale Pierre-Olivier , Seddiki Rima , Nguyen Emmanuelle , Ladoux Benoit , Mège René-Marc 
Published: February 2014

ABSTRACT
Adhesive interactions of cadherins induce crosstalk between adhesion complexes and the actin cytoskeleton, allowing strengthening of adhesions and cytoskeletal organization. The underlying mechanisms are not completely understood, and microtubules (MTs) might be involved, as for integrin-mediated cell–extracellular-matrix adhesions. Therefore, we investigated the relationship between N-cadherin and MTs by analyzing the influence of N-cadherin engagement on MT distribution and dynamics. MTs progressed less, with a lower elongation rate, towards cadherin adhesions than towards focal adhesions. Increased actin treadmilling and the presence of an actomyosin contractile belt, suggested that actin relays inhibitory signals from cadherin adhesions to MTs. The reduced rate of MT elongation, associated with reduced recruitment of end-binding (EB) proteins to plus ends, was alleviated by expression of truncated N-cadherin, but was only moderately affected when actomyosin was disrupted. By contrast, destabilizing actomyosin fibers allowed MTs to enter the adhesion area, suggesting that tangential actin bundles impede MT growth independently of MT dynamics. Blocking MT penetration into the adhesion area strengthened cadherin adhesions. Taken together, these results establish a crosstalk between N-cadherin, F-actin and MTs. The opposing effects of cadherin and integrin engagement on actin organization and MT distribution might induce bias of the MT network during cell polarization.
Mutations in Cx30 that are linked to skin disease and non-syndromic hearing loss exhibit several distinct cellular pathologies
Authors: Berger Amy C. , Kelly John J. , Lajoie Patrick , Shao Qing , Laird Dale W. 
Published: February 2014

ABSTRACT
Connexin 30 (Cx30), a member of the large gap-junction protein family, plays a role in the homeostasis of the epidermis and inner ear through gap junctional intercellular communication (GJIC). Here, we investigate the underlying mechanisms of four autosomal dominant Cx30 gene mutations that are linked to hearing loss and/or various skin diseases. First, the T5M mutant linked to non-syndromic hearing loss formed functional gap junction channels and hemichannels, similar to wild-type Cx30. The loss-of-function V37E mutant associated with Clouston syndrome or keratitis-ichthyosis-deafness syndrome was retained in the endoplasmic reticulum and significantly induced apoptosis. The G59R mutant linked to the Vohwinkel and Bart-Pumphrey syndromes was retained primarily in the Golgi apparatus and exhibited loss of gap junction channel and hemichannel function but did not cause cell death. Lastly, the A88V mutant, which is linked to the development of Clouston syndrome, also significantly induced apoptosis but through an endoplasmic-reticulum-independent mechanism. Collectively, we discovered that four unique Cx30 mutants might cause disease through different mechanisms that also likely include their selective trans-dominant effects on coexpressed connexins, highlighting the overall complexity of connexin-linked diseases and the importance of GJIC in disease prevention.
A cascade of ER exit site assembly that is regulated by p125A and lipid signals
Authors: Klinkenberg David , Long Kimberly R. , Shome Kuntala , Watkins Simon C. , Aridor Meir 
Published: February 2014

ABSTRACTThe inner and outer layers of COPII mediate cargo sorting and vesicle biogenesis. Sec16A and p125A (officially known as SEC23IP) proteins interact with both layers to control coat activity, yet the steps directing functional assembly at ER exit sites (ERES) remain undefined. By using temperature blocks, we find that Sec16A is spatially segregated from p125A-COPII-coated ERES prior to ER exit at a step that required p125A. p125A used lipid signals to control ERES assembly. Within p125A, we defined a C-terminal DDHD domain found in phospholipases and PI transfer proteins that recognized PA and phosphatidylinositol phosphates in vitro and was targeted to PI4P-rich membranes in cells. A conserved central SAM domain promoted self-assembly and selective lipid recognition by the DDHD domain. A basic cluster and a hydrophobic interface in the DDHD and SAM domains, respectively, were required for p125A-mediated functional ERES assembly. Lipid recognition by the SAM–DDHD module was used to stabilize membrane association and regulate the spatial segregation of COPII from Sec16A, nucleating the coat at ERES for ER exit.
The Hippo-YAP signaling pathway and contact inhibition of growth
Authors: Gumbiner Barry M. , Kim Nam-Gyun 
Published: February 2014

ABSTRACT
The Hippo-YAP pathway mediates the control of cell proliferation by contact inhibition as well as other attributes of the physical state of cells in tissues. Several mechanisms sense the spatial and physical organization of cells, and function through distinct upstream modules to stimulate Hippo-YAP signaling: adherens junction or cadherin–catenin complexes, epithelial polarity and tight junction complexes, the FAT-Dachsous morphogen pathway, as well as cell shape, actomyosin or mechanotransduction. Soluble extracellular factors also regulate Hippo pathway signaling, often inhibiting its activity. Indeed, the Hippo pathway mediates a reciprocal relationship between contact inhibition and mitogenic signaling. As a result, cells at the edges of a colony, a wound in a tissue or a tumor are more sensitive to ambient levels of growth factors and more likely to proliferate, migrate or differentiate through a YAP and/or TAZ-dependent process. Thus, the Hippo-YAP pathway senses and responds to the physical organization of cells in tissues and coordinates these physical cues with classic growth-factor-mediated signaling pathways. This Commentary is focused on the biological significance of Hippo-YAP signaling and how upstream regulatory modules of the pathway interact to produce biological outcomes.
Src kinases and ERK activate distinct responses to Stitcher receptor tyrosine kinase signaling during wound healing in Drosophila
Authors: Tsarouhas Vasilios , Yao Liqun , Samakovlis Christos 
Published: February 2014

ABSTRACT
Metazoans have evolved efficient mechanisms for epidermal repair and survival following injury. Several cellular responses and key signaling molecules that are involved in wound healing have been identified in Drosophila, but the coordination of cytoskeletal rearrangements and the activation of gene expression during barrier repair are poorly understood. The Ret-like receptor tyrosine kinase (RTK) Stitcher (Stit, also known as Cad96Ca) regulates both re-epithelialization and transcriptional activation by Grainy head (Grh) to induce restoration of the extracellular barrier. Here, we describe the immediate downstream effectors of Stit signaling in vivo. Drk (Downstream of receptor kinase) and Src family tyrosine kinases bind to the same docking site in the Stit intracellular domain. Drk is required for the full activation of transcriptional responses but is dispensable for re-epithelialization. By contrast, Src family kinases (SFKs) control both the assembly of a contractile actin ring at the wound periphery and Grh-dependent activation of barrier-repair genes. Our analysis identifies distinct pathways mediating injury responses and reveals an RTK-dependent activation mode for Src kinases and their central functions during epidermal wound healing in vivo.
Claudin-6, -10d, and -10e contribute to seawater acclimation in the euryhaline puffer fishTetraodon nigroviridis
Authors: Bui Phuong , Kelly Scott P. 
Published: February 2014

AbstractExpression profiles of claudin-6, -10d, and -10e in the euryhaline teleost fish Tetraodon nigroviridis revealed claudin-6 in brain, eye, gill, and skin tissue, while claudin-10d and -10e were found in brain, gill and skin only. In fishes, the gill and skin are important tissue barriers that interface directly with surrounding water, but these organs generally function differently in osmoregulation. Therefore, roles for gill and skin claudin-6, -10d, and -10e in the osmoregulatory strategies of Tetraodon were investigated. In the gill epithelium claudin-6, -10d, and -10e co-localized with Na+-K+-ATPase immunoreactive (NKA-ir) ionocytes and differences in sub-cellular localization could be observed in hypo- (freshwater, FW) versus hyperosmotic (seawater, SW) environments. Claudin-10d and -10e abundance increased in the gills of fish acclimated to SW versus FW while claudin-6 abundance decreased in SW. Taken together with our knowledge of claudin-6 and -10 function in other vertebrates, data support the idea that in SW-acclimated Tetraodon, these claudins are abundant in gill ionocytes where they contribute to the formation of a Na+ shunt and 'leaky' epithelium, both of which are characteristic of salt secreting SW fish gills. Skin claudin-10d and -10e abundance also increased in fish acclimated to SW versus those in FW, but so did claudin-6. In skin, claudin-6 was found to co-localize with NKA-ir cells, but claudin-10d and -10e did not. This study provides direct evidence that the gill epithelium contains salinity responsive tight junction proteins that are abundant primarily in ionocytes. These same proteins also appear to play a role in the osmoregulatory physiology of the epidermis.
Highly Diastereoselective Synthesis of Chiral Furans with a Quaternary Carbon Substituent at the 2-Position Using 8-Phenylmenthol as the Chiral Auxiliary
Authors: Katori Aki , Sashihara Yoshiaki , Iwamoto Akihisa , Kojima Satoshi , Yamamoto Yohsuke 
Published: February 2014

Abstract
The reaction of cis-4-oxo-2-pentenal and 8-phenylmenthyl 2-oxocyclopentane-1-carboxylate in the presence of a fluorinated cosolvent afforded the corresponding furan product with a high diastereoselectivity of up to 96% de. Other cyclic β-ketoesters reacted in a likewise diastereoselective manner.
1st Mexican Sclerotherapy Consensus
Authors: Ramírez C. , Lemoine C. , Cázares H. , Ramírez A. , Jiménez E. , Rendón F. , Castañeda R. , Arias L. , Vega F. 
Published: February 2014

Zusammenfassung
Hintergrund: Sklerotherapie existiert seit 1516 und ist eine anerkannte Therapie, die weltweit zum Einsatz kommt. Mexikanische Ärzte nahmen an vielen Konsensen teil, um mannigfaltige Absprachen, Referenzen, Methoden und Verfahren zusammenzutragen, die zur Erstel-lung eines solchen Dokuments universelle Akzeptanz finden, u.a. den European Consensus of Sclerotherapy 2003 und dessen letzte Auflage aus dem Jahre 2006, den argentinischen und lateinamerikanischen Konsensus 2012 sowie verschiedene Quellen der Fachliteratur.
Zielsetzung: Unter Berücksichtigung der weltweit anerkannten Fachliteratur und der Erfahrungen von Sklerose-Experten wurde ein Dokument entwickelt, das Konzepte, Prioritäten, Unterschiede und Variationen im Hinblick auf Diagnose, Einsatz, Therapie und andere Themen im Zusammenhang mit Sklerotherapie vereint. Damit soll eine unter akademischen, medizinischen, rechtlichen und praktischen Gesichtspunkten wertvolle Informationsquelle geschaffen werden.
Methode: Folgende Punkte wurden berücksichtigt: Indikationen, Kontraindikationen, Arten von Sklerosierungsmitteln und verwendete Konzentrationen, Lage des Patienten, Verabreichungsweg, Vorbereitung und Konservierung von Sklerosierungsmitteln, erforderliche Instrumente, Injektionsvolumina, Verabreichungsparameter, Kompression und besondere Hinweise.Die vorhandene Literatur wurde konsultiert hinsichtlich der abgehandelten Themen. Es wurde ein Expertengremium zusammengestellt, das eigene Erfahrungsberichte zur Verfügung stellte. Vor diesem Hintergrund wurden Antworten in Form klinischer Richtlinien formuliert oder allgemeine Empfehlungen abgegeben und Betrachtungen zur Variabilität der Konzepte zum Ausdruck gebracht, um konkrete Antworten auf die spezifischen Fragen zu bieten. Außerdem wird ein Abschnitt mit Betrachtungen integriert, in dem mögliche anerkannte Varianten zu jeder einzelnen Fragestellung erklärt werden. Im Haupttext wird der 100%ige Konsens bezüglich einer Thematik dargestellt, während die blauem Balken von Experten vorgeschlagene Varian-ten aufzeigen. Da die aufgeführten Punkte vor dem Hintergrund von in Mexiko verfügbaren Substanzen diskutiert werden, werden nicht alle Sklerosierungsmittel oder Instrumente besprochen.
BioJS InterMine List Analysis: A BioJS component for displaying graphical or statistical analysis of collections of items from InterMine endpoints
Authors: Kalderimis Alexis , Stepan Radek , Sullivan Julie , Lyne Rachel , Lyne Michael , Micklem Gos 
Published: February 2014

Summary: The InterMineTable component is a reusable JavaScript component as part of the BioJS project. It enables users to embed powerful table-based query facilities in their websites with access to genomic data-warehouses such as http://www.flymine.org, which allow users to perform flexible queries over a wide range of integrated data types.Availability: http://github.com/alexkalderimis/im-tables-biojs; http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.8301.
HeatMapViewer: interactive display of 2D data in biology
Authors: Yachdav Guy , Hecht Maximilian , Pasmanik-Chor Metsada , Yeheskel Adva , Rost Burkhard 
Published: February 2014

Summary: The HeatMapViewer is a BioJS component that lays-out and renders two-dimensional (2D) plots or heat maps that are ideally suited to visualize matrix formatted data in biology such as for the display of microarray experiments or the outcome of mutational studies and the study of SNP-like sequence variants. It can be easily integrated into documents and provides a powerful, interactive way to visualize heat maps in web applications. The software uses a scalable graphics technology that adapts the visualization component to any required resolution, a useful feature for a presentation with many different data-points. The component can be applied to present various biological data types. Here, we present two such cases – showing gene expression data and visualizing mutability landscape analysis.Availability: https://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.7706.
treeWidget: a BioJS component to visualise phylogenetic trees
Authors: Schreiber Fabian 
Published: February 2014

Summary: Phylogenetic trees are widely used to represent the evolution of gene families. As the history of gene families can be complex (including lots of gene duplications), its visualisation can become a difficult task. A good/accurate visualisation of phylogenetic trees - especially on the web - allows easier understanding and interpretation of trees to help to reveal the mechanisms that shape the evolution of a specific set of gene/species. Here, I present treeWidget, a modular BioJS component to visualise phylogenetic trees on the web. Through its modularity, treeWidget can be easily customized to allow the display of sequence information, e.g. protein domains and alignment conservation patterns.Availability: http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.7707
Gravitational Radiation from Post-Newtonian Sources and Inspiralling Compact Binaries
Authors: Blanchet Luc 
Published: February 2014

AbstractTo be observed and analyzed by the network of gravitational wave detectors on ground (LIGO, VIRGO, etc.) and by the future detectors in space (eLISA, etc.), inspiralling compact binaries — binary star systems composed of neutron stars and/or black holes in their late stage of evolution — require high-accuracy templates predicted by general relativity theory. The gravitational waves emitted by these very relativistic systems can be accurately modelled using a high-order post-Newtonian gravitational wave generation formalism. In this article, we present the current state of the art on post-Newtonian methods as applied to the dynamics and gravitational radiation of general matter sources (including the radiation reaction back onto the source) and inspiralling compact binaries. We describe the post-Newtonian equations of motion of compact binaries and the associated Lagrangian and Hamiltonian formalisms, paying attention to the self-field regularizations at work in the calculations. Several notions of innermost circular orbits are discussed. We estimate the accuracy of the post-Newtonian approximation and make a comparison with numerical computations of the gravitational self-force for compact binaries in the small mass ratio limit. The gravitational waveform and energy flux are obtained to high post-Newtonian order and the binary’s orbital phase evolution is deduced from an energy balance argument. Some landmark results are given in the case of eccentric compact binaries — moving on quasi-elliptical orbits with non-negligible eccentricity. The spins of the two black holes play an important role in the definition of the gravitational wave templates. We investigate their imprint on the equations of motion and gravitational wave phasing up to high post-Newtonian order (restricting to spin-orbit effects which are linear in spins), and analyze the post-Newtonian spin precession equations as well as the induced precession of the orbital plane.
The role of stem cells in osteoarthritis
Authors: Singh A. , Goel S. C. , Gupta K. K. , Kumar M. , Arun G. R. , Patil H. , Kumaraswamy V. , Jha S. 
Published: February 2014

IntroductionOsteoarthritis (OA) is a progressively debilitating disease that affects mostly cartilage, with associated changes in the bone. The increasing incidence of OA and an ageing population, coupled with insufficient therapeutic choices, has led to focus on the potential of stem cells as a novel strategy for cartilage repair.MethodsIn this study, we used scaffold-free mesenchymal stem cells (MSCs) obtained from bone marrow in an experimental animal model of OA by direct intra-articular injection. MSCs were isolated from 2.8 kg white New Zealand rabbits. There were ten in the study group and ten in the control group. OA was induced by unilateral transection of the anterior cruciate ligament of the knee joint. At 12 weeks post-operatively, a single dose of 1 million cells suspended in 1 ml of medium was delivered to the injured knee by direct intra-articular injection. The control group received 1 ml of medium without cells. The knees were examined at 16 and 20 weeks following surgery. Repair was investigated radiologically, grossly and histologically using haematoxylin and eosin, Safranin-O and toluidine blue staining.ResultsRadiological assessment confirmed development of OA changes after 12 weeks. Rabbits receiving MSCs showed a lower degree of cartilage degeneration, osteophyte formation, and subchondral sclerosis than the control group at 20 weeks post-operatively. The quality of cartilage was significantly better in the cell-treated group compared with the control group after 20 weeks.ConclusionsBone marrow-derived MSCs could be promising cell sources for the treatment of OA. Neither stem cell culture nor scaffolds are absolutely necessary for a favourable outcome. Cite this article: Bone Joint Res 2014;3:32–7.
As the crow flies: Conventions and symbolism in Seven Minutes in the Warsaw Ghetto
Authors: Shaw Nathan 
Published: February 2014

Abstract
In feature-length Holocaust cinema, viewers witness two hours of harrowing events, before being pacified with an ending providing some comfort and relief; often undermining what has gone before. However, in short-film Seven Minutes in the Warsaw Ghetto, this structure is reversed, fitting perfectly with the medium to provide a stronger, lasting impact.
Antioxidant Effect on Oxidation Stability of Blend Fish Oil Biodiesel with Vegetable Oil Biodiesel and Petroleum Diesel Fuel
Authors: Hossain M. , Sujan S.M.A , Jamal M.S. 
Published: February 2014

Two different phenolic synthetic antioxidants were used to improve the oxidation stability of fish oil biodiesel blends with vegetable oil biodiesel and petroleum diesel. Butylhydroxytoluene (BHT) most effective for improvement of the oxidation stability of petro diesel, whereas tert butylhydroquinone (TBHQ) showed good performance in fish oil biodiesel. Fish oil/Rapeseed oil biodiesel mixed showed some acceptable results in higher concentration of antioxidants. TBHQ showed better oxidation stability than BHT in B100 composition. In fish oil biodiesel/diesel mixed fuel, BHT was more effective antioxidant than TBHQ to increase oxidation stability because BHT is more soluble than TBHQ. The stability behavior of biodiesel/diesel blends with the employment of the modified Rancimat method (EN 15751). The performance of antioxidants was evaluated for treating fish oil biodiesel/Rapeseed oil biodiesel for B100, and blends with two type diesel fuel (deep sulfurization diesel and automotive ultra-low sulfur or zero sulfur diesels). The examined blends were in proportions of 5, 10, 15, and 20% by volume of fish oil biodiesel.