bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA Targeting of Neurotropic Flavivirus: Effective Control of Virus Escape and Reversion to Neurovirulent Phenotype
Authors: Heiss Brian L. , Maximova Olga A. , Thach Dzung C. , Speicher James M. , Pletnev Alexander G. 
Published: March 2012

ABSTRACTNeurotropic flaviviruses can efficiently replicate in the developing and mature central nervous systems (CNS) of mice causing lethal encephalitis. Insertion of a single copy of a target for brain-expressed microRNAs (miRNAs) in the 3′ noncoding region (3′NCR) of the flavivirus genome (chimeric tick-borne encephalitis virus/dengue virus) abolished virus neurovirulence in the mature mouse CNS. However, in the developing CNS of highly permissive suckling mice, the miRNA-targeted viruses can revert to a neurovirulent phenotype by accumulating deletions or mutations within the miRNA target sequence. Virus escape from miRNA-mediated suppression in the developing CNS was markedly diminished by increasing the number of miRNA target sites and by extending the distance between these sites in the virus genome. Insertion of multiple miRNA targets into the 3′NCR altered virus neuroinvasiveness, decreased neurovirulence and neuroinflammatory responses, and prevented neurodegeneration without loss of immunogenicity. Although the onset of encephalitis was delayed, a small number of suckling mice still succumbed to lethal intracerebral infection with the miRNA-targeted viruses. Sequence analysis of brain isolates from moribund mice revealed that the viruses escaped from miRNA-mediated suppression exclusively through the deletion of miRNA targets and viral genome sequence located between the two miRNA targets separated by the greatest distance. These findings offer a general strategy to control the reversion of virus to a virulent phenotype: a simultaneous miRNA targeting of the viral genome at many different functionally important regions could prevent virus escape from miRNA-based attenuation, since a deletion of the targeted genomic sequences located between the inserted miRNA binding sites would be lethal for the virus.
Identification of Host-Chromosome Binding Sites and Candidate Gene Targets for Kaposi's Sarcoma-Associated Herpesvirus LANA
Authors: Lu Fang , Tsai Kevin , Chen Horng-Shen , Wikramasinghe Priyankara , Davuluri Ramana V. , Showe Louise , Domsic John , Marmorstein Ronen , Lieberman Paul M. 
Published: March 2012

ABSTRACT

LANA is essential for tethering the Kaposi's sarcoma-associated herpesvirus (KSHV) genome to metaphase chromosomes and for modulating host-cell gene expression, but the binding sites in the host-chromosome remain unknown. Here, we use LANA-specific chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) to identify LANA binding sites in the viral and host-cell genomes of a latently infected pleural effusion lymphoma cell line BCBL1. LANA bound with high occupancy to the KSHV genome terminal repeats (TR) and to a few minor binding sites in the KSHV genome, including the LANA promoter region. We identified 256 putative LANA binding site peaks with
P
< 0.01 and overlap in two independent ChIP-Seq experiments. We validated several of the high-occupancy binding sites by conventional ChIP assays and quantitative PCR. Candidate cellular LANA binding motifs were identified and assayed for binding to purified recombinant LANA protein
in vitro
but bound with low affinity compared to the viral TR binding site. More than half of the LANA binding sites (170/256) could be mapped to within 2.5 kb of a cellular gene transcript. Pathways and Gene Ontogeny (GO) analysis revealed that LANA binds to genes within the p53 and tumor necrosis factor (TNF) regulatory network. Further analysis revealed partial overlap of LANA and STAT1 binding sites in several gamma interferon (IFN-γ)-regulated genes. We show that ectopic expression of LANA can downmodulate IFN-γ-mediated activation of a subset of genes, including the TAP1 peptide transporter and proteasome subunit beta type 9 (PSMB9), both of which are required for class I antigen presentation. Our data provide a potential mechanism through which LANA may regulate several host cell pathways by direct binding to gene regulatory elements.
A prospective Neoproterozoic-Cambrian hydrocarbon/exploration play in the Kirthar Fold Belt, Pakistan
Authors: Siddiqui Nusrat Kamal 
Published: March 2012

Abstract

During the Late Neoproterozoic to Early Mesozoic the Indian Plate was part of Pangaea, the Palaeo supercontinent, with the African Plate to the west, as interpreted by various authors. At the same time, the Indian Plate was juxtaposed with the Central Iranian Plate, which separated it from the Arabian Plate in the vicinity of present-day Oman,
c.
800 Ma ago. Between 612 and 200 Ma (Late Neoproterozoic to the end of the Triassic) these plates remained firmly attached. The changing configuration of the plates from 200 Ma to the present are provided in this paper. The Neoproterozoic–Cambrian rocks are recorded along the eastern border of Pakistan with India, extending into the Indian Territory and comprising part of the Neoproterozoic–Cambrian basin (Lower Indus Basin). The southern part of the Lower Indus Basin, from the Thar Platform in the east, deepens westwards towards Karachi (embayment) and the Kachhi Foredeep, where the Neoproterozoic–Cambrian succession is likely to be deep-seated. However,
c.
5 km uplift of the Kirthar Fold Belt (KFB) across the Western Boundary Thrust (WBT) and the subsequent erosion have exposed the Middle Jurassic Chiltan Limestone, particularly in the central region of the KFB (Landsat images and domal structures with Jurassic outcrops are described in this paper) The limestone rests over older strata, with a possible presence of that of Neoproterozoic–Cambrian age, which is interpreted to be at drillable depth.
Stratigraphy and correlation of the Neoproterozoic deposits of central and western India: an overview
Authors: Kumar S. 
Published: March 2012

Abstract
In the central and western part of India, the Neoproterozoic deposits are identified in the Vindhyan and Marwar Basins. The Vindhyan Basin consists of two sub-basins; one in the eastern part and the other in the western part. The basic problem with the Vindhyan Basin is the correlation of the eastern part with the western part, as the two areas show different stratigraphic successions and the outcrops in the eastern part are not traceable in the western part. In this paper, an attempt is made to suggest intrabasinal correlation within the Vindhyan Basin on the basis of stromatolites, carbon isotope data, microbial mats, fossils and lithology. The Marwar Supergroup is developed in the western Rajasthan and unconformably overlies the Malani Igneous Suite, which has previously been dated as 779–681 Ma. On the basis of the available fossil records, the Jodhpur Group has been assigned an Ediacaran age and the Precambrian–Cambrian boundary is suggested within the Bilara Group. As both the Maihar Sandstone of the eastern part of the Vindhyan Basin and the Jodhpur Sandstone of the Marwar Supergroup have been assigned an Ediacaran age, these have been correlated.
Epidermal Growth Factor Receptor Variant III Contributes to Cancer Stem Cell Phenotypes in Invasive Breast Carcinoma
Authors: Del Vecchio Catherine A. , Jensen Kristin C. , Nitta Ryan T. , Shain A. Hunter , Giacomini Craig P. , Wong Albert J. 
Published: March 2012

Abstract
EGFRvIII is a tumor-specific variant of the epidermal growth factor receptor (EGFR). Although EGFRvIII is most commonly found in glioblastoma, its expression in other tumor types remains controversial. In this study, we investigated EGFRvIII expression and amplification in primary breast carcinoma. Our analyses confirmed the presence of EGFRvIII, but in the absence of amplification or rearrangement of the EGFR locus. Nested reverse transcriptase PCR and flow cytometry were used to detect a higher percentage of positive cases. EGFRvIII-positive cells showed increased expression of genes associated with self-renewal and epithelial–mesenchymal transition along with a higher percentage of stem-like cells. EGFRvIII also increased in vitro sphere formation and in vivo tumor formation. Mechanistically, EGFRvIII mediated its effects through the Wnt/β-catenin pathway, leading to increased β-catenin target gene expression. Inhibition of this pathway reversed the observed effects on cancer stem cell (CSC) phenotypes. Together, our findings show that EGFRvIII is expressed in primary breast tumors and contributes to CSC phenotypes in breast cancer cell lines through the Wnt pathway. These data suggest a novel function for EGFRvIII in breast tumorigenesis. Cancer Res; 72(10); 2657–71. ©2012 AACR.
Endoplasmic Reticulum Stress, the Unfolded Protein Response, Autophagy, and the Integrated Regulation of Breast Cancer Cell Fate
Authors: Clarke Robert , Cook Katherine L. , Hu Rong , Facey Caroline O.B. , Tavassoly Iman , Schwartz Jessica L. , Baumann William T. , Tyson John J. , Xuan Jianhua , Wang Yue , Wärri Anni , Shajahan Ayesha N. 
Published: March 2012

Abstract
How breast cancer cells respond to the stress of endocrine therapies determines whether they will acquire a resistant phenotype or execute a cell-death pathway. After a survival signal is successfully executed, a cell must decide whether it should replicate. How these cell-fate decisions are regulated is unclear, but evidence suggests that the signals that determine these outcomes are highly integrated. Central to the final cell-fate decision is signaling from the unfolded protein response, which can be activated following the sensing of stress within the endoplasmic reticulum. The duration of the response to stress is partly mediated by the duration of inositol-requiring enzyme-1 activation following its release from heat shock protein A5. The resulting signals appear to use several B-cell lymphoma-2 family members to both suppress apoptosis and activate autophagy. Changes in metabolism induced by cellular stress are key components of this regulatory system, and further adaptation of the metabolome is affected in response to stress. Here we describe the unfolded protein response, autophagy, and apoptosis, and how the regulation of these processes is integrated. Central topologic features of the signaling network that integrate cell-fate regulation and decision execution are discussed. Cancer Res; 72(6); 1321–31. ©2012 AACR.
Molecular Pathways: The Role of Primary Cilia in Cancer Progression and Therapeutics with a Focus on Hedgehog Signaling
Authors: Hassounah Nadia B. , Bunch Thomas A. , McDermott Kimberly M. 
Published: March 2012

Abstract
Abnormal Hedgehog (Hh) pathway activity has been reported in many cancers, including basal cell carcinomas, medulloblastomas, rhabdomyosarcomas, glioblastomas, and breast and prostate cancers. For this reason, the Hh pathway is a flourishing area for development of anticancer drugs such as Hh ligand antagonists (e.g., 5E1 and robotnikinin), Smo inhibitors (e.g., GDC-0449 and IPI-926), and Gli transcriptional activity inhibitors (e.g., GANT58 and GANT61). It is now clear that primary cilia are required for activation of the Hh pathway in normal vertebrate cells. It is in the primary cilium that both positive and negative effectors of the Hh pathway are processed by posttranslational modifications. In many cancers, preliminary results suggest that primary cilia are lost. As drugs that inhibit different steps of the Hh pathway are developed, it will be important to consider how these drugs will function in the context of primary cilia in the tumor environment. Here, we discuss why some of the Hh inhibitors may be ineffective if primary cilia are lost on cancer cells. Understanding the relationships between clinical inhibitors of the Hh pathway and the presence or absence of primary cilia may turn out to be critical for targeting these therapeutics to the correct population of patients and improving their efficacy. Further work is needed in this area to maximize the potential of these exciting therapeutic targets. Clin Cancer Res; 18(9); 2429–35. ©2012 AACR.
PIK3CA/PTEN Mutations and Akt Activation As Markers of Sensitivity to Allosteric mTOR Inhibitors
Authors: Meric-Bernstam Funda , Akcakanat Argun , Chen Huiqin , Do Kim-Anh , Sangai Takafumi , Adkins Farrell , Gonzalez-Angulo Ana Maria , Rashid Asif , Crosby Katherine , Dong Mei , Phan Alexandria T. , Wolff Robert A. , Gupta Sanjay , Mills Gordon B. , Yao James 
Published: March 2012

Abstract
Purpose: We sought to determine whether phosphoinositide 3-kinase (PI3K) pathway mutation or activation state and rapamycin-induced feedback loop activation of Akt is associated with rapamycin sensitivity or resistance.
Experimental Design: Cancer cell lines were tested for rapamycin sensitivity, Akt phosphorylation, and mTOR target inhibition. Mice injected with breast or neuroendocrine cancer cells and patients with neuroendocrine tumor (NET) were treated with rapalogs and Akt phosphorylation was assessed.
Results: Thirty-one cell lines were rapamycin sensitive (RS) and 12 were relatively rapamycin resistant (RR; IC50 &gt; 100 nmol/L). Cells with PIK3CA and/or PTEN mutations were more likely to be RS (P = 0.0123). Akt phosphorylation (S473 and T308) was significantly higher in RS cells (P &lt; 0.0001). Rapamycin led to a significantly greater pathway inhibition and greater increase in p-Akt T308 (P &lt; 0.0001) and p-Akt S473 (P = 0.0009) in RS cells. Rapamycin and everolimus significantly increased Akt phosphorylation but inhibited growth in an in vivo NET model (BON). In patients with NETs treated with everolimus and octreotide, progression-free survival correlated with p-Akt T308 in pretreatment (R = 0.4762, P = 0.0533) and on-treatment tumor biopsies (R = 0.6041, P = 0.0102). Patients who had a documented partial response were more likely to have an increase in p-Akt T308 with treatment compared with nonresponders (P = 0.0146).
Conclusion: PIK3CA/PTEN genomic aberrations and high p-Akt levels are associated with rapamycin sensitivity in vitro. Rapamycin-mediated Akt activation is greater in RS cells, with a similar observation in patients with clinical responses on exploratory biomarker analysis; thus feedback loop activation of Akt is not a marker of resistance but rather may function as an indicator of rapamycin activity. Clin Cancer Res; 18(6); 1777–89. ©2012 AACR.
Exercise Response in Hypertrophic Cardiomyopathy
Authors: Soullier Camille , Obert Philippe , Doucende Gregory , Nottin Stéphane , Cade Stéphane , Perez-Martin Antonia , Messner-Pellenc Patrick , Schuster Iris 
Published: March 2012

Background—
Abnormal left ventricular (LV) deformational mechanics have been demonstrated in patients with hypertrophic cardiomyopathy (HCM) at rest, but there is a lack of information on their adaptation to exercise. The aim of this study was to assess the adaptability of LV strains and torsional mechanics during exercise in HCM patients.

Methods and Results—

Twenty nonobstructive HCM patients (age, 48.3±12.3 years; 14 men) and 20 control subjects underwent speckle-tracking echocardiographic measurement of longitudinal, radial, and circumferential strains, systolic twist, and diastolic untwisting rate (UTR) at rest and submaximal exercise. HCM patients showed lower resting longitudinal (−15.7±5.0% versus −19.4±2.6%,
P
<0.001) and radial (38.1±11.3% versus 44.7±14.4%,
P
<0.05) strains but higher circumferential strain (−21.9±4.0% versus −18.8±2.3%,
P
<0.05) and twist (15.7±3.6° versus 9.3±2.6°,
P
<0.0001) than control subjects. Exercise induced an increase in all strains in control subjects but only a moderate increase in longitudinal strain (to −18.4±5.0%), without significant changes in radial and circumferential strains or twist in HCM patients. Exercise peak UTR was lower (−119.0±31.5°/s versus −137.3±41.1°/s) and occurred later (137±18% versus 125±11% systolic time,
P
<0.05) in HCM than in control subjects. A significant relationship between twist and UTR was obtained in control subjects (ß=−0.0807,
P
<0.001) but not in HCM patients (ß=−0.0051,
P
=0.68).

Conclusions—
HCM patients had severely limited strain adaptability and no LV twisting reserve at exercise. They had reduced and delayed UTR with reduced systolic-diastolic coupling efficiency by twist-untwist mechanics.
H. Bechert, Der Buddhismus I. Der indische Buddhismus und seine Verzweigungen von Heinz Bechert, Johannes Bronkhorst, Jacob Ensink, Jens-Uwe Hartmann, Petra Kieffer-Pülz, Hans-Joachim Klimkeit, Siegfried Lienhard, Ian William Mabbett
Authors: v. Hinüber  
Published: March 2012

AbstractNo Abstract
Kant Et Le Mādhyamika a Propos D'un Livre Récent
Authors: May Jacques 
Published: March 2012

AbstractLe système Mādhyamika n'avait pas fait jusqu'ici l'objet d'un vaste exposé d'ensemble. Les exposés de Stcherbatsky, La Vallée Poussin, Schayer restaient des introductions, quelque évidents que fussent leurs divers mérites: netteté des idées et vigueur polémique, minutie et soud du document, pénétration philosophique. Les Indledende Bemœrkninger de Poul Tuxen sont malheureusement écrites en une langue peu accessible.
Die Burušaski-Lehnwörter in Der Zigeunersprache
Authors: Berger Hermann 
Published: March 2012

AbstractWenn der äußerste Nordwesten Indiens zwar nicht, wie man früher annahm, als die ursprüngliche Heimat der Zigeuner, so doch wenigstens als ihre letzte Station vor dem Verlassen des indo-arischen Sprachbereichs gelten darf, so ist es nicht verwunderlich, wenn wir neben einigen Dardismen im Zig. auch Vokabeln aus dem Wortschatz des den dardischen Sprachen unmittelbar benachbarten Burušaski vorfinden. Die sicheren Beispiele sind zwar noch nicht sehr zahlreich, aber für die Sprachwissenschaft von ungleich größerem Interesse als die vielen Entlehnungen aus anderen nicht-indischen Sprachen (Persisch, Armenisch, Griechisch usw.), denn sie dienen im Gegensatz zu diesen nicht nur zur weiteren Aufhellung der Wanderwege der Zigeuner, sondern können ausnahmsweise auch neues Licht auf die Geschichte der gebenden Sprache werfen. Wenn wir nämlich, vorsichtig geschätzt, den Auszug der Zigeuner aus Nordwestindien in die Mitte des ersten nachchristlichen Jahrtausends verlegen, so können sie uns einen wenn auch nur bescheidenen Begriff von dem lautlichen Zustand des Bur. in einer Zeit geben, aus der sonst jedes Zeugnis fehlt. Die Veränderungen, die die betreffenden Bur.-Wörter durchgemacht haben, sind freilich in der Regel nicht sehr groß, was wiederum für den tröstlich sein wird, der angesichts des rapiden Lautverfalls mancher indogermanischer Sprachen dem von mir an anderer Stelle begonnenen Nachweis einer Verwandtschaft des Bur. mit dem Baskischen noch mit begreiflichem Mißtrauen gegenübersteht; sie müssen aber trotzdem mit Sorgfalt registriert werden, weil sie die mit Hilfe des Bask. gewonnenen Lautgesetze stützen oder die Entwicklung von Wörtern aufhellen, für die im Bask. keine Entsprechung mehr vorhanden ist.
Judeo-Persian Deverbatives in -ŠN and -ŠT*
Authors: Paper Herbert H. 
Published: March 2012

AbstractThe starting point of this presentation of data is the modern Persian deverbative nominal abstract in -éš. These are freely formed in Persian from the present stems of verbs. A trustworthy standard source on the origin of this suffix is P. Horn, “Neupersische Schriftsprache”, Grundriss der Iranischen Philologie, I, 182
On the Meaning of SKR. (Pra)Bhinnāñjana
Authors: Vogel Claus 
Published: March 2012

Abstract1. Among the many stereotyped similes occurring in Sanskrit literature, ornate and otherwise, those formed with (Pra)Bhinnāñjana require some elucidative comment inasmuch as neither the object nor the point of comparison are entirely clear in this case.
Avestisch Hizu.drājah- und Zānu.drājah
Authors: Schmitt Rüdiger 
Published: March 2012

AbstractBartholomae postuliert für avest. drājah- neben der ganz geläufigen und etymologisch gerechtfertigten Bedeutung “Strecke, Länge”, die als Simplex nur in dem Bereichsakkusativ drājō “an Länge”, ferner in mehr als einem Dutzend Zusammensetzungen vorkommt, einen Bedeutungsansatz “Strecken, Vorstrecken”, der sich nur in Zusammensetzungen nachweisen lasse. Damit können aber folgende adjektivische (Possessiv-) oder substantivische (Determinativ-) Komposita nicht gemeint sein: aēsö.drājah- (Bartholomae, Sp. 35) “ein aēša- lang”; aiiar.drājah- (Bartholomae, Sp. 158) “Dauer eines Tages”; čartu.drājah- (Bartholomae, Sp. 582) “Länge eines čartu-”; dānu.drājah- (Bartholomae, Sp. 734) “so lang wie ein Fluss”; baši.drājah- (Bartholomae, Sp. 952) “ein baši- lang”; biiär.drājah- (Bartholomae, Sp. 971) “Dauer von zwei Jahren”; frabāzu.dräjah- (Bartholomae, Sp. 985) “Länge eines Unterarms”; frabdö.drājah- (Bartholomae, Sp. 986) “Länge eines Vorderfusses”; frārāni.drājah- (Bartholomae, Sp. 1021) “Länge eines Elle”; yār.drājah- (Bartholomae, Sp. 1287) “Dauer eines Jahres”; vitasti.drājah- (Bartholomae, Sp. 1440) “Länge einer Spanne”; vībäbāzu.drājah- (Bartholomae, Sp. 1448) “Länge eines vībāzu-”. Hierzu tritt noch māz.- drājahiia-, ntr. (Bartholomae, Sp. 1170) “Dauer eines Monats”, das adjektivisches *māz.drājah- “einen Monat lang” voraussetzt. In all diesen Wörtern bezeichnet drājah- also zeitliche und räumliche Länge – ebenso übrigens bei der Verwendung des Simplex als accusativus limitationis -, wie das der zugrunde liegenden Wurzel (idg. *dlIgh-) von Hause aus zukam.
Considérations sur une technique du Rasāyana āyurvédique
Authors: Roşu Arion 
Published: March 2012

AbstractRejuvenation techniques, inspired by a common classical tradition, are described in Caraka (Cikitsā I, 1–4) and in Suśruta (Cikitsā XXVII–XXX), followed up by the Nāvanītaka (Bower Ms., sl.188–200) and by the Astāngahrdayasamhitā (Uttara XXXIX). Valuable mediaeval tīkā comment on the details of these techniques and indeed interesting modern examples of a treatment closely following the ancient medical texts are known.[Contrary to the cure taking place ‘in the open air and in the sun’ (vātātapika), the practice of rejuvenation characterized by the ku is applied indoors in premises called kutī or āgāra, built according to definite rules (site, architecture, etc.). The patient enters at a time astrologically auspicious, after performing certain rites and preparing his mind for a treatment which is as perilous as it is laborious.The rites of the operation and the unusual type of abode, difficult to interpret, permit, however, an examination of the textual data in a different light from that of the scholiasts themselves, who remain very guarded, and even obscure, on important points of detail. Here one must presume an initiation ceremony whose method was used for the legendary sages as well as patients of today. The technique which is called ‘retreat in a hut’ implies the idea of regressus ad uterum. Rejuvenation which constitutes, from the biological point of view, a regeneration of the body (kāyakalpa) must be considered on the symbolical plane as a ‘new birth’: the patient is assimilated to the embryo, and to the uterus correspond both the ‘hut’ described in the classical Āyurvedic treatises and the dark enclosed premises recommended by the modern kavirāj.
Indian manuscripts without autograph? A computer analysis
Authors: Callewaert Winand M. 
Published: March 2012

AbstractThe computer count establishes that, in the case of Nāmdev's poems, there is no consistent relation between two manuscripts of the same ‘recension’. We noticed also that, when looking at variants from different angles, no consistent relation even between manuscripts is seen throughout. This suggests a very nebulous interaction between singing traditions and the fact that we should not look for a ‘critical line’ of Nāmdev or try to prepare an edition of the original version of Nāmdev's poetry. This hypothesis is a challenge to existing ‘critical editions’ of Early Hindi Poetry, in which generally the ‘original’ version is reconstructed after constructing a stemma based on (scribal) variants. If there is no stemma and no justified ‘critical’ line, then what do we have? We have the conviction that, possibly for centuries, a Nāmdev enthusiasm was enchanting people in Rajasthan and Punjab (North-West India), linked vaguely to Nāmdev's hymns of the 14th century.