bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage-Derived Neuropilin-2 Exhibits Novel Tumor-Promoting Functions
Authors: Roy Sohini , Bag Arup K. , Dutta Samikshan , Polavaram Navatha Shree , Islam Ridwan , Schellenburg Samuel , Banwait Jasjit , Guda Chittibabu , Ran Sophia , Hollingsworth Michael A. , Singh Rakesh K. , Talmadge James E. , Muders Michael H. , Batra Surinder K. , Datta Kaustubh 
Published: August 2018

AbstractTumor-associated macrophages (TAM) are causally associated with tumorigenesis as well as regulation of antitumor immune responses and have emerged as potential immunotherapeutic targets. Recent evidence suggests TAM phagocytose apoptotic tumor cells within the tumor microenvironment through efferocytosis in an immunologically silent manner, thus maintaining an immunosuppressed microenvironment. The signal transduction pathways coupling efferocytosis and immunosuppression are not well known. Neuropilin-2 (NRP2) is a member of the membrane-associated neuropilin family and has been reported in different immune cells but is poorly characterized. In this study, we show that NRP2 is expressed during macrophage differentiation, is induced by tumor cells, and regulates phagocytosis in macrophages. Furthermore, NRP2 in TAM promoted efferocytosis and facilitated tumor growth. Deletion of NRP2 from TAM impaired the clearance of apoptotic tumor cells and increased secondary necrosis within tumors. This resulted in a break in the immune tolerance and reinitiated antitumor immune responses, characterized by robust infiltration of CD8+ T and natural killer cells. This result suggests NRP2 may act as a molecular mediator that connects efferocytosis and immune suppression. Deletion of NRP2 in TAM downregulated several immunosuppressive and tumor-promoting genes and upregulated immunostimulatory genes in the myeloid compartment. Taken together, our study demonstrates that TAM-derived NRP2 plays a crucial role in tumor promotion through efferocytosis, opening the enticing option for the development of effective immunotherapy targeting TAM.Significance: Neuropilin-2 in macrophages promotes tumor growth by regulating efferocytosis of apoptotic tumor cells and orchestrating immune suppression.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/19/5600/F1.large.jpg. Cancer Res; 78(19); 5600–17. ©2018 AACR.
Coupling integrin dynamics to cellular adhesion behaviors
Authors: Galbraith Catherine G. , Davidson Michael W. , Galbraith James A. 
Published: August 2018

ABSTRACT
Visualizing fluorescent proteins is essential for understanding cellular function. While advances in microscopy can now resolve individual molecules, determining whether the labeled molecules report native behaviors and how the measured behaviors can be coupled to cellular outputs remains challenging. Here, we used integrin alpha-beta heterodimers – which connect extracellular matrix (ECM) and the cytoskeleton – to quantify the mobility and conformation of labeled integrins. We found that while unlabeled and labeled integrins all localized to adhesions and support anchorage-dependent cell function, integrin mobility decreased when the beta rather than the alpha subunit was labeled. In contrast to unlabeled and alpha labeled subunits, beta labeled subunits changed cellular behavior; decreasing protrusive activity and increasing adhesion size and the extent of cell spreading. Labeling the beta subunit changed the integrin conformation, extending the molecule and exposing an epitope that is revealed by activation with Mn2+ treatment. Our findings indicate labeling induced changes in dynamic integrin behavior alter molecular conformation as well as cellular adhesion-dependent function to demonstrate a coupling between molecular inputs and distinct cellular outputs.
This article has an associated First Person interview with the first author of the paper.
RARγ is required for mesodermal gene expression prior to gastrulation in Xenopus
Authors: Janesick Amanda , Tang Weiyi , Shioda Toshi , Blumberg Bruce 
Published: August 2018

ABSTRACT
The developing vertebrate embryo is exquisitely sensitive to retinoic acid (RA) concentration, particularly during anteroposterior patterning. In contrast to Nodal and Wnt signaling, RA was not previously considered to be an instructive signal in mesoderm formation during gastrulation. Here, we show in Xenopus that RARγ is indispensable for the expression of early mesoderm markers and is, therefore, an obligatory factor in mesodermal competence and/or maintenance. We identified several novel targets upregulated by RA receptor signaling in the early gastrula that are expressed in the circumblastoporal ring and linked to mesodermal development. Despite overlapping expression patterns of the genes encoding the RA-synthesizing enzyme Aldh1a2 and the RA-degrading enzyme Cyp26a1, RARγ1 functions as a transcriptional activator in early mesoderm development, suggesting that RA ligand is available to the embryo earlier than previously appreciated. RARγ1 is required for cellular adhesion, as revealed by spontaneous dissociation and depletion of ncam1 mRNA in animal caps harvested from RARγ1 knockdown embryos. RARγ1 knockdown obliterates somite boundaries, and causes loss of Myod protein in the presomitic mesoderm, but ectopic, persistent expression of Myod protein in the trunk. Thus, RARγ1 is required for stabilizing the mesodermal fate, myogenic commitment, somite boundary formation, and terminal skeletal muscle differentiation.
Coupling of apical-basal polarity and planar cell polarity to interpret the Wnt signaling gradient in feather development
Authors: Lin Jianqiong , Yue Zhicao 
Published: August 2018

ABSTRACT
Sensing a global directional cue to orient cell growth is crucial in tissue morphogenesis. An anterior-posterior gradient of Wnt signaling controls the helical growth of feather branches (barbs), and thus the formation of bilateral feathers. However, it remains unclear how the keratinocytes sense this gradient and orient barb growth. Here, we show that in chicken, owing to feather branching, the global Wnt gradient is subdivided into periodic barbs. Within each barb, the anterior barbule plate cells tilt before the posterior cells. The core planar cell polarity gene Prickle1 is involved, as knockdown of its expression resulted in no cell shape change and no barb tilting. Furthermore, perturbation of the Wnt gradient leads to diffusive Prickle1 expression and loss of barb orientation. Finally, the asymmetric distribution of Wnt6/Fzd10 is coordinated by the apical-basal polarity of the barbule plate keratinocytes, which is in turn regulated by the Par3/aPKC machinery. Our data elucidate a new mechanism through which the global Wnt signaling gradient is interpreted locally to construct complex spatial forms.
Human lung development: recent progress and new challenges
Authors: Nikolić Marko Z. , Sun Dawei , Rawlins Emma L. 
Published: August 2018

ABSTRACTRecent studies have revealed biologically significant differences between human and mouse lung development, and have reported new in vitro systems that allow experimental manipulation of human lung models. At the same time, emerging clinical data suggest that the origins of some adult lung diseases are found in embryonic development and childhood. The convergence of these research themes has fuelled a resurgence of interest in human lung developmental biology. In this Review, we discuss our current understanding of human lung development, which has been profoundly influenced by studies in mice and, more recently, by experiments using in vitro human lung developmental models and RNA sequencing of human foetal lung tissue. Together, these approaches are helping to shed light on the mechanisms underlying human lung development and disease, and may help pave the way for new therapies.
Nodal signaling has dual roles in fate specification and directed migration during germ layer segregation in zebrafish
Authors: Liu Zairan , Woo Stephanie , Weiner Orion D. 
Published: August 2018

ABSTRACT
During gastrulation, endodermal cells actively migrate to the interior of the embryo, but the signals that initiate and coordinate this migration are poorly understood. By transplanting ectopically induced endodermal cells far from the normal location of endoderm specification, we identified the inputs that drive internalization without the confounding influences of fate specification and global morphogenic movements. We find that Nodal signaling triggers an autocrine circuit for initiating endodermal internalization. Activation of the Nodal receptor directs endodermal specification through sox32 and also induces expression of more Nodal ligands. These ligands act in an autocrine fashion to initiate endodermal cell sorting. Our work defines an ‘AND’ gate consisting of sox32-dependent endodermal specification and Nodal ligand reception controlling endodermal cell sorting to the inner layer of the embryo at the onset of gastrulation.
Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling
Authors: Jin Yunyun , Cong Qian , Gvozdenovic-Jeremic Jelena , Hu Jiajie , Zhang Yiqun , Terkeltaub Robert , Yang Yingzi 
Published: August 2018

ABSTRACT
The differentiated phenotype of articular chondrocytes of synovial joints needs to be maintained throughout life. Disruption of the articular cartilage, frequently associated with chondrocyte hypertrophy and calcification, is a central feature in osteoarthritis (OA). However, the molecular mechanisms whereby phenotypes of articular chondrocytes are maintained and pathological calcification is inhibited remain poorly understood. Recently, the ecto-enzyme Enpp1, a suppressor of pathological calcification, was reported to be decreased in joint cartilage with OA in both human and mouse, and Enpp1 deficiency causes joint calcification. Here, we found that hedgehog (Hh) signaling activation contributes to ectopic joint calcification in the Enpp1−/− mice. In the Enpp1−/− joints, Hh signaling was upregulated. Further activation of Hh signaling by removing the patched 1 gene in the Enpp1−/− mice enhanced ectopic joint calcification, whereas removing Gli2 partially rescued the ectopic calcification phenotype. In addition, reduction of Gαs in the Enpp1−/− mice enhanced joint calcification, suggesting that Enpp1 inhibits Hh signaling and chondrocyte hypertrophy by activating Gαs-PKA signaling. Our findings provide new insights into the mechanisms underlying Enpp1 regulation of joint integrity.
Rab6 promotes insulin receptor and cathepsin trafficking to regulate autophagy induction and activity in Drosophila
Authors: Ayala Carlos I. , Kim Jung , Neufeld Thomas P. 
Published: August 2018

ABSTRACT
The self-degradative process of autophagy is important for energy homeostasis and cytoplasmic renewal. This lysosome-mediated pathway is negatively regulated by the target of rapamycin kinase (TOR) under basal conditions, and requires the vesicle trafficking machinery regulated by Rab GTPases. However, the interactions between autophagy, TOR and Rab proteins remain incompletely understood in vivo. Here, we identify Rab6 as a critical regulator of the balance between TOR signaling and autolysosome function. Loss of Rab6 causes an accumulation of enlarged autophagic vesicles resulting in part from a failure to deliver lysosomal hydrolases, rendering autolysosomes with a reduced degradative capacity and impaired turnover. Additionally, Rab6-deficient cells are reduced in size and display defective insulin–TOR signaling as a result of mis-sorting and internalization of the insulin receptor. Our findings suggest that Rab6 acts to maintain the reciprocal regulation between autophagy and TOR activity during distinct nutrient states, thereby balancing autophagosome production and turnover to avoid autophagic stress.
The N-recognin UBR4 of the N-end rule pathway is targeted to and required for the biogenesis of the early endosome
Authors: Kim Sung Tae , Lee Yoon Jee , Tasaki Takafumi , Mun Su Ran , Hwang Joonsung , Kang Min Jueng , Ganipisetti Srinivasrao , Yi Eugene C. , Kim Bo Yeon , Kwon Yong Tae 
Published: August 2018

ABSTRACT
The N-end rule pathway is a proteolytic system in which single N-terminal residues of proteins act as N-degrons. These degrons are recognized by N-recognins, facilitating substrate degradation via the ubiquitin (Ub) proteasome system (UPS) or autophagy. We have previously identified a set of N-recognins [UBR1, UBR2, UBR4 (also known as p600) and UBR5 (also known as EDD)] that bind N-degrons through their UBR boxes to promote proteolysis by the proteasome. Here, we show that the 570 kDa N-recognin UBR4 is associated with maturing endosomes through an interaction with Ca2+-bound calmodulin. The endosomal recruitment of UBR4 is essential for the biogenesis of early endosomes (EEs) and endosome-related processes, such as the trafficking of endocytosed protein cargos and degradation of extracellular cargos by endosomal hydrolases. In mouse embryos, UBR4 marks and plays a role in the endosome-lysosome pathway that mediates the heterophagic proteolysis of endocytosed maternal proteins into amino acids. By screening 9591 drugs through the DrugBank database, we identify picolinic acid as a putative ligand for UBR4 that inhibits the biogenesis of EEs. Our results suggest that UBR4 is an essential modulator in the endosome-lysosome system.
This article has an associated First Person interview with the first author of the paper.
Verwendung von Blockchain und Custom Tokens zur Projektkoordination – Ein Pilotversuch
Authors: Schützeneder Philipp , Lehner Johannes , Sametinger Johannes 
Published: August 2018

Zusammenfassung
Einer der wichtigsten Aspekte der Blockchain-Technologie ist die vertrauenslose Kommunikation der Teilnehmer im Netzwerk. Der Einsatz dieser Eigenschaft für Anwendungsgebiete abseits von Kryptowährungen wird seit der Entwicklung von Smart Contracts und Custom Tokens immer interessanter. Bisher wurden Anwendungsfälle primär für marktbezogene Transaktionen diskutiert. In diesem Beitrag soll dagegen auf organisationsinterne Steuerungsprozesse fokussiert werden, welche mit dieser Technologie neu gestaltet werden können. Beispiele betreffen die Verteilung und Steuerung von Projekttätigkeiten, die Gestaltung interner Anreizsysteme oder auch Formen der Mitarbeiterbeteiligung. Als konkreter Testfall wird die Waves-Blockchain verwendet, welche eine benutzerfreundliche Möglichkeit bietet, eigene Tokens auf Basis einer öffentlichen Blockchain zu erschaffen und zu transferieren. Diese Möglichkeit wurde für einen Anwendungsfall aus der Projektorganisation genutzt. Eine Projektgruppe bestehend aus Studierenden der Johannes Kepler Universität Linz soll sich untereinander und selbstständig organisieren können. Verschiedene Projektaufgaben weisen eine unterschiedliche Wertigkeit auf, welche durch die „Kepler“-Tokens abgebildet werden. Die Wertigkeit wird je nach Modell entweder von der Projektgruppe selbst bestimmt oder durch den Auftraggeber. Auch Hybrid-Varianten sind möglich, wobei z. B. der Auftraggeber je nach Projektfortschritt oder Projektergebnis eine Anzahl an Tokens an das Team sendet, das sich diese untereinander aufteilt. Die Aufteilung passiert durch Transaktionen auf einer öffentlichen Blockchain, somit ist sie transparent, für alle teilnehmenden Parteien sofort einsehbar und nachvollziehbar. Transaktionen können zwar indirekt rückgängig gemacht werden, dies bleibt aber nicht verborgen. Auf größerer Ebene kann sich ein Ökosystem entwickeln, wobei die eingesetzten Tokens einen reellen Wert entwickeln und gegen Währungen getauscht werden können. Wir erarbeiten Kriterien zur Auswahl einer Blockchain zur Schaffung von Tokens bzw. Kryptowährungen für organisationale Anwendungen. Eine dieser Plattformen testen wir konkret an einer organisationalen Anwendung und sammeln dabei erste Erkenntnisse über die Möglichkeit mittels Custom Tokens Projekte zu steuern und opportunistisches Verhalten einzudämmen.
Truncation in message-oriented phonology: a case study using Korean vocative truncation
Authors: Kawahara Shigeto , Lee Seunghun J. 
Published: August 2018

AbstractThis paper analyzes the vocative truncation pattern in Korean from the viewpoint of Message-Oriented Phonology (MOP), which capitalizes on the idea that sound patterns are governed by a principle that makes message transfer effective. In the traditional naming pattern, Korean first names consist of a generation marker and a unique portion, and the order between these two elements alternates between generations. To derive vocative forms, the generation marker is truncated, and the suffixal [(j)a] is attached to the unique portion. We argue that MOP naturally predicts this type of truncation. As the generation marker is shared by all the members of the same generation, the generation marker is highly predictable and hence does not reduce uncertainty about the intended message. To achieve effective communication, predictable portions are deleted. Our analysis implies that MOP is relevant not only to phonetic implementation patterns, but also to morphophonological patterns. It also provides support for MOP based on data from a non-Indo-European language. Finally, we aim to integrate insights of MOP with a more formal proposal like Optimality Theory, by relating the predictability of a contrast to the ranking of the faithfulness constraint that it protects, following the spirit of the P-map hypothesis.
Practice makes perfect: the consequences of lexical proficiency for articulation
Authors: Tomaschek Fabian , Tucker Benjamin V. , Fasiolo Matteo , Baayen R. Harald 
Published: August 2018

Abstract
Many studies report shorter acoustic durations, more coarticulation and reduced articulatory targets for frequent words. This study investigates a factor ignored in discussions on the relation between frequency and phonetic detail, namely, that motor skills improve with experience. Since frequency is a measure of experience, it follows that frequent words should show increased articulatory proficiency. We used EMA to test this prediction on German inflected verbs with [a] as stem vowels. Modeling median vertical tongue positions with quantile regression, we observed significant modulation by frequency of the U-shaped trajectory characterizing the articulation of the [a:]. These modulations reflect two constraints, one favoring smooth trajectories through anticipatory coarticulation, and one favoring clear articulation by realizing lower minima. The predominant pattern across sensors, exponents, and speech rate suggests that the constraint of clarity dominates for lower-frequency words. For medium-frequency words, the smoothness constraint leads to a raising of the trajectory. For the higher-frequency words, both constraints are met simultaneously, resulting in low minima and stronger coarticulation. These consequences of motor practice for articulation challenge both the common view that a higher-frequency of use comes with more articulatory reduction, and cognitive models of speech production positing that articulation is post-lexical.
Frequency and time fault diagnosis methods of power transformers
Authors: Gutten Miroslav , Korenciak Daniel , Kucera Matej , Janura Richard , Glowacz Adam , Kantoch Eliasz 
Published: August 2018

Abstract
The authors describe experimental and theoretical analyses of faults of power transformer winding. Faults were caused by mechanical effect of short-circuit currents. Measurements of transformer were carried out in high-voltage laboratory. Frequency and time diagnostic methods (method SFRA - Sweep Frequency Response Analysis, impact test) were used for the analyses. Coils of transformer windings were diagnosed by means of the SFRA method and the time impact test. The analyzed methods had a significant sensitivity to a relatively small deformation of coil. In the analysis a new technique for analyzing the effects of short-circuit currents is introduced. This technique is developed for high-voltage transformers (different types of power). The proposed analyses show that it is necessary to analyze the value of short-circuit current. Short-circuit current represents a danger for the operation of the power transformer. The proposed approach can be used for other types of transformers. Moreover, the presented techniques have a potential application for fault diagnosis of electrical equipment such as: transformers and electrical machines.
Origin of the spade-shaped staters of the Púchov Culture and the first contemporary forgery of that type
Authors: Fröhlich Július 
Published: August 2018

Abstract
The spade-shaped staters from the area characterized by the Púchov Culture in Slovakia differ from other Celtic coins by their special spade-shaped form and also by their material. The known types of the spade-shaped staters were made – with some exceptions – of alloy with different portions of gold and silver. The first stater here, because of its weight, characteristic shape and finding place (near Dubnica nad Váhom, Slovakia), could be classified under the type preceding all other types of the spade-shaped staters. The second piece – a part cut from a spade-shaped stater – represents a contemporary forgery of the same type as it is in the case of the previous coin. The core of the forged specimen is made of high-quality silver plated by a thick gold foil. This kind of forgeries is known mainly from the Hellenistic period, these pieces come from the Macedonian-Thracian region, and they appeared in the Celtic milieu starting with the 3rd century BC.
Robotics for soft skills training
Authors: Rubinacci Franco , Ponticorvo Michela , Passariello Rosa , Miglino Orazio 
Published: August 2018

Abstract
Robotics is a powerful tool in education and it has gained a notable impact in the field of teaching computer science, engineering, math, physics and similar. As educational robotics laboratories stimulate many different abilities in students, such as problem solving and group working, it is possible to use robotics to promote soft skills as well.
Soft skills are necessary to complement hard skills to build the 21st century professionalism, so it seems relevant to start promoting these skills as soon as possible. In this paper, we describe a lab for primary and first grade secondary schools in which robotics is employed to train soft skills in an informal context.