bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocannabinoids are conserved inhibitors of the Hedgehog pathway
Authors: Khaliullina Helena , Bilgin Mesut , Sampaio Julio L. , Shevchenko Andrej , Eaton Suzanne
Published: March 2015

Significance

Hedgehog proteins regulate development and tissue homeostasis. They signal through activation of the transmembrane protein Smoothened. Smoothened hyperactivation underlies development of many tumors. Smoothened activity can be modulated by several synthetic small molecules, which have shown promise in the clinic. However, occurrence of resistance-inducing mutations limits their effectiveness. Little is known about endogenous small molecules that may inhibit Smoothened in vivo. Previous work suggested that lipids present in lipoproteins are required for Smoothened inhibition in vivo. Here, we use biochemical fractionation and lipidomics to identify these lipids as endocannabinoids and show that their activity as Smoothened inhibitors has been conserved from flies to mammals. Endocannabinoids may provide useful templates for the design of new therapeutic Smoothened antagonists.
Dynamical phase transition in the open Dicke model
Authors: Klinder Jens , Keßler Hans , Wolke Matthias , Mathey Ludwig , Hemmerich Andreas
Published: March 2015

Significance

Nonequilibrium phenomena in quantum many-body systems are not well understood to date. This applies in particular for open systems, coupled to an external bath. We use a Bose–Einstein condensate in a high-finesse optical resonator with ultralow bandwidth to emulate the open Dicke model. In well-controlled sweeps across the Hepp–Lieb–Dicke phase transition, we observe hysteretic dynamics showing power-law scaling with respect to the transition time, which suggests an interpretation in terms of a Kibble–Zurek mechanism. Our observations indicate the possibility of universal behavior in the presence of dissipation.
Evidence for recent, population-specific evolution of the human mutation rate
Authors: Harris Kelley
Published: March 2015

Significance

Most, but not all, human genetic variation is shared between populations, and whole-genome sequencing is now making it possible to catalogue population-private mutations that occur in only one ethnic group and are especially informative about recent human history. By contrasting frequencies of mutations private to Europe, Asia, and Africa, I have revealed a previously undetected difference between Europeans and other ethnic groups: Europeans experience higher rates of a specific mutation type that has known associations with UV light exposure. Although it is not clear whether the excess mutations are harmful or directly related to the UV sensitivity of light skin, this result demonstrates that the human mutation rate has evolved on a much faster timescale than previously believed.
Activation of protein synthesis in mouse uterine epithelial cells by estradiol-17β is mediated by a PKC–ERK1/2–mTOR signaling pathway
Authors: Wang Yuxiang , Zhu Liyin , Kuokkanen Satu , Pollard Jeffrey W.
Published: March 2015

Significance

Estrogen exposure is the major risk factor for diseases of the endometrium such as endometriosis and endometrial cancer. This is thought to be through its constant stimulation of epithelial cell proliferation. Progesterone blocks the estrogen-induced cell proliferation and exposure to it mitigates the risk for these diseases. However endometriotic tissue and cancer become progesterone resistant. Here we identify an estrogen induced pathway in uterine epithelial cells that activates protein synthesis through mechanistic target of rapamycin (mTOR) in a progesterone independent way. This indicates how protein and DNA synthesis regulation can be differentially controlled in vivo as progesterone blocks only the latter response. Inhibition of mTOR by rapamycin blocked E
2
-induced protein and DNA synthesis, suggesting that it might be a therapeutic target for these diseases.
Up-regulation of lysosomal TRPML1 channels is essential for lysosomal adaptation to nutrient starvation
Authors: Wang Wuyang , Gao Qiong , Yang Meimei , Zhang Xiaoli , Yu Lu , Lawas Maria , Li Xinran , Bryant-Genevier Marthe , Southall Noel T. , Marugan Juan , Ferrer Marc , Xu Haoxing
Published: March 2015

Significance

Lysosomes are the cell’s degradation center. To adapt to different environmental conditions, the cell has evolved a set of delicate mechanisms to rapidly change lysosome function, which is referred to as lysosomal adaptation. Notably, lysosomal adaptation is required for cell survival under low nutrient conditions. In this study, we identified TRPML1, a lysosomal Ca
2+
-permeant ion channel, as an essential player required for lysosomal adaptation. The activity of TRPML1 is potently (up to 10-fold) and rapidly increased upon nutrient starvation. Furthermore, pharmacological inhibition or genetic deletion of TRPML1 completely abolished the effects of starvation on boosting the degradation capability of lysosomes.
Lrp4 in osteoblasts suppresses bone formation and promotes osteoclastogenesis and bone resorption
Authors: Xiong Lei , Jung Ji-Ung , Wu Haitao , Xia Wen-Fang , Pan Jin-Xiu , Shen Chengyong , Mei Lin , Xiong Wen-Cheng
Published: March 2015

Significance

This study provides in vivo evidence that Lrp4 loss in osteoblast (OB)-lineage cells results in high–bone-mass deficit. Lrp4 in OB-lineage cells is required to reduce serum levels of sclerostin and to facilitate sclerostin inhibition of OB differentiation and function. These results demonstrate that Lrp4 is a critical player in bone-mass homeostasis and support a model that Lrp4 acts as a sclerostin receptor, inhibiting Wnt/β-catenin signaling and promoting receptor activator of nuclear kappa B ligand (RANKL)-induced osteoclastogenesis. As mutations in the Lrp4 gene have been identified in high–bone-mass patients, this study provides pathophysiological insight into relevant high–bone-mass disorders.
Activation of TRPM3 by a potent synthetic ligand reveals a role in peptide release
Authors: Held Katharina , Kichko Tatjana , De Clercq Katrien , Klaassen Hugo , Van Bree Rieta , Vanherck Jean-Christophe , Marchand Arnaud , Reeh Peter W. , Chaltin Patrick , Voets Thomas , Vriens Joris
Published: March 2015

Significance

The cation channel TRPM3 is highly expressed in the sensory system, where it plays a key role in the detection of noxious heat and the development of inflammatory heat hypersensitivity. Our understanding of the physiological role of TRPM3 in the sensory system and other tissues is hampered by the lack of potent pharmacologic tools, however. This study describes CIM0216, a small-molecule TRPM3 agonist. Our results indicate that CIM0216 is much more potent than established TRPM3 agonists, particularly owing to its ability to open two distinct cation-permeable pores in TRPM3. Using CIM0216 as a pharmacologic tool, we reveal that activation of TRPM3 evokes the release of calcitonin gene-related peptide from sensory nerve terminals and of insulin from pancreatic islets.
Boosting CRISPR/Cas9 multiplex editing capability with the endogenous tRNA-processing system
Authors: Xie Kabin , Minkenberg Bastian , Yang Yinong
Published: March 2015

Significance

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9) system has recently emerged as an efficient and versatile tool for genome editing in various organisms. However, its targeting capability and multiplex editing efficiency are often limited by the guide RNA (gRNA)-expressing device. This study demonstrates a general strategy and platform for precise processing and efficient production of numerous gRNAs in vivo from a synthetic polycistronic gene via the endogenous tRNA-processing system. This strategy is shown to significantly increase CRISPR/Cas9 multiplex editing capability and efficiency in plants and is expected to have broad applications for small RNA expression and genome engineering.
PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations
Authors: Zou Helen Y. , Li Qiuhua , Engstrom Lars D. , West Melissa , Appleman Vicky , Wong Katy A. , McTigue Michele , Deng Ya-Li , Liu Wei , Brooun Alexei , Timofeevski Sergei , McDonnell Scott R. P. , Jiang Ping , Falk Matthew D. , Lappin Patrick B. , Affolter Timothy , Nichols Tim , Hu Wenyue , Lam Justine , Johnson Ted W. , Smeal Tod , Charest Al , Fantin Valeria R.
Published: March 2015

Significance

Overcoming resistance to targeted kinase inhibitors is a major clinical challenge in oncology. Development of crizotinib resistance through the emergence of a secondary ROS1 mutation, ROS1
G2032R
, was observed in patients with ROS1 fusion-positive lung cancer. In addition, a novel ROS1 fusion recently has been identified in glioblastoma. A new agent with robust activity against the ROS1
G2032R
mutation and with CNS activity is needed to address these unmet medical needs. Here we report the identification of PF-06463922, a ROS1/anaplastic lymphoma kinase (ALK) inhibitor, with exquisite potency against ROS1 fusion kinases, capable of inhibiting the ROS1
G2032R
mutation and FIG-ROS1–driven glioblastoma tumor growth in preclinical models. PF-06463922 demonstrated excellent therapeutic potential against ROS1 fusion-driven cancers, and it currently is undergoing phase I/II clinical trial investigation.
Endosymbiotic gene transfer from prokaryotic pangenomes: Inherited chimerism in eukaryotes
Authors: Ku Chuan , Nelson-Sathi Shijulal , Roettger Mayo , Garg Sriram , Hazkani-Covo Einat , Martin William F.
Published: March 2015

Endosymbiotic theory in eukaryotic-cell evolution rests upon a foundation of three cornerstone partners—the plastid (a cyanobacterium), the mitochondrion (a proteobacterium), and its host (an archaeon)—and carries a corollary that, over time, the majority of genes once present in the organelle genomes were relinquished to the chromosomes of the host (endosymbiotic gene transfer). However, notwithstanding eukaryote-specific gene inventions, single-gene phylogenies have never traced eukaryotic genes to three single prokaryotic sources, an issue that hinges crucially upon factors influencing phylogenetic inference. In the age of genomes, single-gene trees, once used to test the predictions of endosymbiotic theory, now spawn new theories that stand to eventually replace endosymbiotic theory with descriptive, gene tree-based variants featuring supernumerary symbionts: prokaryotic partners distinct from the cornerstone trio and whose existence is inferred solely from single-gene trees. We reason that the endosymbiotic ancestors of mitochondria and chloroplasts brought into the eukaryotic—and plant and algal—lineage a genome-sized sample of genes from the proteobacterial and cyanobacterial pangenomes of their respective day and that, even if molecular phylogeny were artifact-free, sampling prokaryotic pangenomes through endosymbiotic gene transfer would lead to inherited chimerism. Recombination in prokaryotes (transduction, conjugation, transformation) differs from recombination in eukaryotes (sex). Prokaryotic recombination leads to pangenomes, and eukaryotic recombination leads to vertical inheritance. Viewed from the perspective of endosymbiotic theory, the critical transition at the eukaryote origin that allowed escape from Muller’s ratchet—the origin of eukaryotic recombination, or sex—might have required surprisingly little evolutionary innovation.
Climate change in the Fertile Crescent and implications of the recent Syrian drought
Authors: Kelley Colin P. , Mohtadi Shahrzad , Cane Mark A. , Seager Richard , Kushnir Yochanan
Published: March 2015

Significance

There is evidence that the 2007−2010 drought contributed to the conflict in Syria. It was the worst drought in the instrumental record, causing widespread crop failure and a mass migration of farming families to urban centers. Century-long observed trends in precipitation, temperature, and sea-level pressure, supported by climate model results, strongly suggest that anthropogenic forcing has increased the probability of severe and persistent droughts in this region, and made the occurrence of a 3-year drought as severe as that of 2007−2010 2 to 3 times more likely than by natural variability alone. We conclude that human influences on the climate system are implicated in the current Syrian conflict.
Place field expansion after focal MEC inactivations is consistent with loss of Fourier components and path integrator gain reduction
Authors: Ormond Jake , McNaughton Bruce L.
Published: March 2015

Significance

The discovery of grid cells in the entorhinal cortex quickly led to the hypothesis that grid cell inputs might be responsible for the generation of discrete place fields downstream in the hippocampus. Simulations have shown that if this conjecture is correct, then lesions of dorsal medial entorhinal cortex (MEC), which expresses the most tightly spaced grids, should cause place fields to expand, whereas lesions of ventral MEC, which expresses the most widely spaced grids, should cause fields to contract. Using muscimol to make small inactivations along the dorsoventral axis of the MEC, we tested this hypothesis. Our results deviate from the prediction but most likely result from a combination of the predicted effects and a weakening of the self-motion signal within the MEC.
The RNA binding protein FXR1 is a new driver in the 3q26-29 amplicon and predicts poor prognosis in human cancers
Authors: Qian Jun , Hassanein Mohamed , Hoeksema Megan D. , Harris Bradford K. , Zou Yong , Chen Heidi , Lu Pengcheng , Eisenberg Rosana , Wang Jing , Espinosa Allan , Ji Xiangming , Harris Fredrick T. , Rahman S. M. Jamshedur , Massion Pierre P.
Published: March 2015

Significance

Altered expression of RNA binding proteins might contribute to cancer development. This study reveals the functional implications and clinical relevance of FXR1, an RNA binding protein, in non-small cell lung cancer (NSCLC). Our results demonstrate that FXR1 promotes tumor progression by regulating two other oncogenes within the same chromosome 3q amplicon. To drive tumor progression, FXR1 forms a new complex with protein kinase C, iota, and posttranscriptionally stabilizes the expression of epithelial cell transforming 2. We show that increased FXR1 expression in NSCLC is a candidate biomarker predictive of poor survival and might represent a novel therapeutic target. In addition, FXR1 expression correlates with poor clinical outcome in multiple human cancers, suggesting broader implications of this RNA binding protein in cancer progression.
Macronutrient balance, reproductive function, and lifespan in aging mice
Authors: Solon-Biet Samantha M. , Walters Kirsty A. , Simanainen Ulla K. , McMahon Aisling C. , Ruohonen Kari , Ballard John William O. , Raubenheimer David , Handelsman David J. , Le Couteur David G. , Simpson Stephen J.
Published: March 2015

Significance

A fundamental tenet of life-history theory is that reproduction and longevity trade off against one another. Experiments on invertebrates show that, rather than competing for limiting resources, reproduction and lifespan are optimized on different dietary macronutrient compositions. In mice, studies have yet to establish the relationship between macronutrient balance, reproduction, and lifespan. We evaluated the effects of macronutrients and energy on lifespan and reproductive function. Indicators of reproductive function (uterine mass, ovarian follicle number, testes mass, epididymal sperm counts) were optimized by high protein (P), low carbohydrate (C) diets whereas lifespan was greatest on low P:C diets. Corpora lutea and estrous cycling were higher in females on lower P:C diets. Macronutrient balance has profound and opposing effects on reproduction and longevity.
Anthropogenic warming has increased drought risk in California
Authors: Diffenbaugh Noah S. , Swain Daniel L. , Touma Danielle
Published: March 2015

Significance

California ranks first in the United States in population, economic activity, and agricultural value. The state is currently experiencing a record-setting drought, which has led to acute water shortages, groundwater overdraft, critically low streamflow, and enhanced wildfire risk. Our analyses show that California has historically been more likely to experience drought if precipitation deficits co-occur with warm conditions and that such confluences have increased in recent decades, leading to increases in the fraction of low-precipitation years that yield drought. In addition, we find that human emissions have increased the probability that low-precipitation years are also warm, suggesting that anthropogenic warming is increasing the probability of the co-occurring warm–dry conditions that have created the current California drought.
Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity
Authors: Washburn Nathaniel , Schwab Inessa , Ortiz Daniel , Bhatnagar Naveen , Lansing Jonathan C. , Medeiros Amy , Tyler Steven , Mekala Divya , Cochran Edward , Sarvaiya Hetal , Garofalo Kevin , Meccariello Robin , Meador James W. , Rutitzky Laura , Schultes Birgit C. , Ling Leona , Avery William , Nimmerjahn Falk , Manning Anthony M. , Kaundinya Ganesh V. , Bosques Carlos J.
Published: March 2015

Significance

IgG fragment crystallizable domain (Fc) sialylation has emerged as an important but controversial concept for regulating anti-inflammatory activity of antibodies. Moreover, translating this concept to potent anti-inflammatory therapeutics has been hampered by the difficulty of generating suitable sialylated products for human use. We describe for the first time, to our knowledge, the development of a robust, scalable process to generate a sialylated intravenous immunoglobulin (IVIg) drug candidate with maximum Fc sialylation devoid of unwanted modifications. By using a wide panel of physicochemical analytics and in vivo models, we have validated the quality and potent anti-inflammatory activity of this clinical candidate. This report not only confirms the controversial anti-inflammatory activity of IgG-Fc sialylation, it also represents the first sialylated IVIg preparation, to our knowledge, with consistent anti-inflammatory potency suitable for clinical development.
Vapor hydrogen and oxygen isotopes reflect water of combustion in the urban atmosphere
Authors: Gorski Galen , Strong Courtenay , Good Stephen P. , Bares Ryan , Ehleringer James R. , Bowen Gabriel J.
Published: March 2015

Significance

Human activities affect the water cycle in many ways, some of which remain difficult to measure. One such process is emission of water vapor through combustion of fossil fuels, which may be a significant part of the atmospheric water budget in urban centers. It has not previously been possible to uniquely identify combustion-derived water vapor with atmospheric measurements. We introduce a method for the measurement of combustion-derived vapor, and show that this source contributes as much as 13% of surface-level vapor in the atmosphere of one city. The new approach may help researchers monitor sources of greenhouse gas emissions from cities and study the impact of water of combustion on urban weather, quality of life, and atmospheric chemistry.
Impacts of biological globalization in the Mediterranean: Unveiling the deep history of human-mediated gamebird dispersal
Authors: Forcina Giovanni , Guerrini Monica , van Grouw Hein , Gupta Brij K. , Panayides Panicos , Hadjigerou Pantelis , Al-Sheikhly Omar F. , Awan Muhammad N. , Khan Aleem A. , Zeder Melinda A. , Barbanera Filippo
Published: March 2015

Significance

Human-mediated species dispersal stretching back at least 10,000 y has left an indelible stamp on present day biodiversity. A major contributing factor to this process was the trade in a wide range of exotic species that was fueled by elite demand. The black francolin—now extinct in the western Mediterranean but once a courtly gamebird prized for its flavor, curative, and aphrodisiac qualities by European aristocracy—was one of these species. Using historical sources and DNA analysis of modern and archival specimens, we show that this bird was not native to the western Mediterranean, and document its introduction to Cyprus and westward through the Mediterranean Basin via several trade routes that reached as far east as South Asia.
Insulin resistance in brain alters dopamine turnover and causes behavioral disorders
Authors: Kleinridders Andre , Cai Weikang , Cappellucci Laura , Ghazarian Armen , Collins William R. , Vienberg Sara G. , Pothos Emmanuel N. , Kahn C. Ronald
Published: March 2015

Significance

Both types 1 and 2 diabetes are associated with increased risks of age-related decay in cognitive function and mood disorders, especially depression. Insulin action has been shown to regulate neuronal signaling and plasticity. Here we investigate whether brain-specific knockout of insulin receptor (NIRKO) in mice causes behavioral changes and how these are mechanistically linked. We find that NIRKO mice exhibit age-related anxiety and depressive-like behavior. This is due to altered mitochondrial function, aberrant monoamine oxidase (MAO) expression, and increased dopamine turnover in the mesolimbic system, and can be reversed by treatment with Mao inhibitors. Thus, brain insulin resistance alters dopamine turnover and induces anxiety and depressive-like behaviors. These findings demonstrate a potential molecular link between central insulin resistance and behavioral disorders.
Functional analysis of (4
S
)-limonene synthase mutants reveals determinants of catalytic outcome in a model monoterpene synthase
Authors: Srividya Narayanan , Davis Edward M. , Croteau Rodney B. , Lange B. Markus
Published: March 2015

Significance

Terpene synthases catalyze complex, chain length-specific, electrophilic cyclization reactions that constitute the first committed step in the biosynthesis of structurally diverse terpenoids. (4
S
)-limonene synthase [(4
S
)-LS] has emerged as a model enzyme for enhancing our comprehension of the reaction cycle of monoterpene (C
10
) synthases. While the stereochemistry of the cyclization of geranyl diphosphate to (−)-(4
S
)-limonene has been the subject of several mechanistic studies, the structural basis for the stabilization of carbocation intermediates and the termination of the reaction sequence have remained enigmatic. We present extensive experimental evidence that the aromatic amino acids W324 and H579 play critical roles in the stabilization of intermediate carbocations. A possible function of these residues as the terminal catalytic base is also discussed.
Recurrent
BCAM-AKT2
fusion gene leads to a constitutively activated AKT2 fusion kinase in high-grade serous ovarian carcinoma
Authors: Kannan Kalpana , Coarfa Cristian , Chao Pei-Wen , Luo Liming , Wang Yan , Brinegar Amy E. , Hawkins Shannon M. , Milosavljevic Aleksandar , Matzuk Martin M. , Yen Laising
Published: March 2015

Significance

High-grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer and is typically detected only at advanced stages due to lack of effective early screening tools. Fusion genes are among the most cancer-specific signatures known and, when highly recurrent, they have the potential to serve as screening tools. Here we identified
BCAM-AKT2
as a cancer-specific fusion gene present in 7% of HGSC tumors, a significant frequency in this highly heterogeneous disease. This fusion results in an aberrant kinase whose constant activity contributes to cancer formation. Thus, the
BCAM-AKT2
fusion gene could be important for understanding and identifying clinically relevant subtypes of HGSC, and could be a novel therapeutic target for developing small-molecule drugs.
Origin of the HIV-1 group O epidemic in western lowland gorillas
Authors: D’arc Mirela , Ayouba Ahidjo , Esteban Amandine , Learn Gerald H. , Boué Vanina , Liegeois Florian , Etienne Lucie , Tagg Nikki , Leendertz Fabian H. , Boesch Christophe , Madinda Nadège F. , Robbins Martha M. , Gray Maryke , Cournil Amandine , Ooms Marcel , Letko Michael , Simon Viviana A. , Sharp Paul M. , Hahn Beatrice H. , Delaporte Eric , Mpoudi Ngole Eitel , Peeters Martine
Published: March 2015

Significance

Understanding emerging disease origins is important to gauge future human infection risks. This is particularly true for the various forms of the AIDS virus, HIV-1, which were transmitted to humans on four independent occasions. Previous studies identified chimpanzees in southern Cameroon as the source of the pandemic M group, as well as the geographically more restricted N group. Here, we show that the remaining two groups also emerged in southern Cameroon but had their origins in western lowland gorillas. Although group P has only been detected in two individuals, group O has spread extensively throughout west central Africa. Thus, both chimpanzees and gorillas harbor viruses that are capable of crossing the species barrier to humans and causing major disease outbreaks.
Cleavage of amyloid precursor protein by an archaeal presenilin homologue PSH
Authors: Dang Shangyu , Wu Shenjie , Wang Jiawei , Li Hongbo , Huang Min , He Wei , Li Yue-Ming , Wong Catherine C. L. , Shi Yigong
Published: March 2015

Significance

Amyloid precursor protein (APP) is cleaved by β-secretase to produce APP C99, which undergoes additional, sequential cleavages by γ-secretase to generate amyloid-β peptides including Aβ40 and Aβ42. Increased ratios of Aβ42 over Aβ40 are thought to cause Alzheimer’s disease. Screening of γ-secretase modulators is hindered by the technical challenges in expression and biochemical manipulation of γ-secretase. In this study, we demonstrate that the archaeal intramembrane protease PSH represents an excellent surrogate of γ-secretase in terms of cleavage of APP C99, ratio of Aβ42 over Aβ40, and modulation of cleavage preferences by known modulators of γ-secretase. Our finding may facilitate discovery of γ-secretase inhibitors and modulators.
Overt and non-overt subjects in Persian
Authors: Haeri Niloofar
Published: March 2015

The phenomenon of prodrop has attracted much attention in recent years both in the field of syntactic theory and in pragmatics (Chomsky, 1981, 1982; Rizzi, 1982; Gundel, 1980; Givon, 1976). Persian is among the many languages which exhibit this phenomenon. The central aim of this paper is to discover the pragmatic contraints governing the distribution of overt and non-overt subjects.

Persian is a SOV language. Verbs carry the person and number information in the form of suffixes. These agreement markers are unique for each person. Non-overt (zero) subjects are allowed and occur very frequently in speech. Looking at natural data, we see that overt subjects appear even when their referents are in focus. Finding the contraints governing the distribution of these overt subjects is the primary question addressed in this paper. For the purposes of this study, we are classifying full noun phrases and pronouns together as overt subjects although pronominalization has its own separate pragmatic functions. Here we are focussing on zero subjects and overt subjects. Our data base consists of six children and four adult narratives. The unity of the narrative as a genre with its usual focus on one main actor make it possible to track the same noun phrase throughout the story in a variety of syntactic and pragmatic environments. This makes the narrative genre ideal for contrasting overt and non-overt subjects.
Subjectivity in translation as interlingual re-instantiation
Authors: Yang Zhong
Published: March 2015

Existing theories of translation are mostly product-oriented, the process of translation is under-theorized. The concept of equivalence, as idealized quality of a translated text, is re-examined from the perspective of functional linguistics. It is argued that equivalence should not be merely interpreted as similar perlocutionary effects of the source text and the target text. The translated text should be maximally equivalent to the source text in the interpersonal, ideational and textual meanings. A process model is constructed to reveal the process of translation as interlingual re-instantiation and the sorts and sources of information dealt with by the translator in his/her endeavour to achieve maximal equivalence. The subjectivity of the translator in making inferences and in rhetorical manoeuvring is analysed based on data from two English translations of Lao Zi’s Book of Tao and Teh.
Targeting IL-17B–IL-17RB signaling with an anti–IL-17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines
Authors: Wu Heng-Hsiung , Hwang-Verslues Wendy W. , Lee Wen-Hsin , Huang Chun-Kai , Wei Pei-Chi , Chen Chia-Lin , Shew Jin-Yuh , Lee Eva Y.-H.P. , Jeng Yung-Ming , Tien Yu-Wen , Ma Che , Lee Wen-Hwa
Published: March 2015

Pancreatic cancer has an extremely high mortality rate due to its aggressive metastatic nature. Resolving the underlying mechanisms will be crucial for treatment. Here, we found that overexpression of IL-17B receptor (IL-17RB) strongly correlated with postoperative metastasis and inversely correlated with progression-free survival in pancreatic cancer patients. Consistently, results from ex vivo experiments further validated that IL-17RB and its ligand, IL-17B, plays an essential role in pancreatic cancer metastasis and malignancy. Signals from IL-17B–IL-17RB activated CCL20/CXCL1/IL-8/TFF1 chemokine expressions via the ERK1/2 pathway to promote cancer cell invasion, macrophage and endothelial cell recruitment at primary sites, and cancer cell survival at distant organs. Treatment with a newly derived monoclonal antibody against IL-17RB blocked tumor metastasis and promoted survival in a mouse xenograft model. These findings not only illustrate a key mechanism underlying the highly aggressive characteristics of pancreatic cancer but also provide a practical approach to tackle this disease.
Doing business in the non-ferrous metals industry: how to survive in a mature market in crisis
Authors: Lipsits Igor Vladimirovitch , Vigdorchik Elena Alexandrovna
Published: March 2015

Subject area

Crisis management, Strategic management.

Study level/applicability

This case study can be used for teaching MBA and pre-experience Masters students as part of a strategic management course.

Case overview

This case study tells the story of Kirov non-ferrous metals processing plant located in Kirov (USSR, presently the Russian Federation). Founded in 1956, this company had long been one of the USSR's leading manufacturers in the industry of non-ferrous metals processing. The situation changed dramatically in the first half of 1990s. During those years, instead of state-planned economy, Russia saw the formation of market economy. It was the first time when the company (as a result of privatization, it became a joint-stock company with a small number of pure portfolio investment owners) was faced with the need to look for marketing outlets for its products on its own. At the same time, after having been privatized, the company could not receive government investments anymore. Due to all these conditions, in 1995, capacity utilization in this company fell to 16 per cent, and it appeared to be on the verge of bankruptcy.

Expected learning outcomes

The main learning objectives of the case study are: to develop students' skills to analyze complex managerial situations; to help students in understanding the logic of company's strategic choice, depending on the stage of the market life cycle (especially, in case of mature markets); and to provide the training for the students' ability to justify management decisions using the example of companies in B2B markets.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.
The XFEM for nonlinear thermal and phase change problems
Authors: Stapór Pawel
Published: March 2015

Purpose

– Of particular interest is the ability of the extended finite element method (XFEM) to capture transient solution and motion of phase boundaries without adaptive remeshing or moving-mesh algorithms for a physically nonlinear phase change problem. The paper aims to discuss this issue.

Design/methodology/approach

– The XFEM is applied to solve nonlinear transient problems with a phase change. Thermal conductivity and volumetric heat capacity are assumed to be dependent on temperature. The nonlinearities in the governing equations make it necessary to employ an effective iterative approach to solve the problem. The Newton-Raphson method is used and the incremental discrete XFEM equations are derived.

Findings

– The robustness and utility of the method are demonstrated on several one-dimensional benchmark problems.

Originality/value

– The novel procedure based on the XFEM is developed to solve physically nonlinear phase change problems.
Bioconvection peristaltic flow in an asymmetric channel filled by nanofluid containing gyrotactic microorganism
Authors: Akbar Noreen Sher
Published: March 2015

Purpose

– The purpose of this paper is to discuss free convection peristaltic flow in an asymmetric channel with nanofluid containing gyrotactic microorganism.

Design/methodology/approach

– The governing equations for proposed model are simplified using “long wavelength and low Reynolds number approximation.” Numerical solutions have been presented for “velocity, pressure gradient, the solid volume fraction nanoparticles, temperature profile and density of motile microorganisms.” The effects of various flow parameters, i.e Hartmann number, the solid volume fraction of the nanoparticles amplitude ratio, Prandtl number, bioconvection Péclet number, bioconvection constant, bioconvection Rayleigh number are presented.

Findings

– The author finds that the pressure rise increases with an increase in Hartmann number, Grashof number bioconvection, Rayleigh number and buoyancy ratio in the peristaltic pumping section.

Originality/value

– The peristaltic flow nanofluid containing gyrotactic microorganism is explored in the literature for the first time.
Deflated preconditioned conjugate gradients applied to a Petrov-Galerkin generalized least squares finite element formulation for incompressible flows with heat transfer
Authors: Kraft Rosilene A. , Coutinho Alvaro L. G. A.
Published: March 2015

Purpose

– The purpose of this paper is to show benefits of deflated preconditioned conjugate gradients (CG) in the solution of transient, incompressible, viscous flows coupled with heat transfer.

Design/methodology/approach

– This paper presents the implementation of deflated preconditioned CG as the iterative driver for the system of linearized equations for viscous, incompressible flows and heat transfer simulations. The De Sampaio-Coutinho particular form of the Petrov-Galerkin Generalized Least Squares finite element formulation is used in the discretization of the governing equations, leading to symmetric positive definite matrices, allowing the use of the CG solver.

Findings

– The use of deflation techniques improves the spectral condition number. The authors show in a number of problems of coupled viscous flow and heat transfer that convergence is achieved with a lower number of iterations and smaller time.

Originality/value

– This work addressed for the first time the use of deflated CG for the solution of transient analysis of free/forced convection in viscous flows coupled with heat transfer.
Reliability evaluation and analysis of CNC cam shaft grinding machine
Authors: Loganathan M.K. , Gandhi O.P.
Published: March 2015

Purpose

– Reliability assessment does require an effective structural modelling approach for systems, in general and manufacturing systems are no exception. This paper aims to develop it for large manufacturing systems using graph models, a systems approach.

Design/methodology/approach

– Structural graph models for reliability at various hierarchical levels are developed by considering a CNC cam shaft grinding machine. The system reliability expression is obtained by converting the reliability graphs into equivalent matrices, which helps to evaluate and analyse system.

Findings

– Using the obtained reliability expressions at various hierarchical levels of the system, it is possible not only to evaluate its reliability from structure point of view but also to identify weak structural elements from reliability point of view.

Research limitations/implications

– The approach can be extended to include the influence of other parameters, such as human, component and environment, etc., on the system reliability.

Practical implications

– The approach helps to design and develop manufacturing systems from reliability consideration by assessing their possible alternatives among these.

Originality/value

– The suggested methodology is useful for reliability evaluation of large and complex manufacturing systems.
EDITOR'S CHOICE: Small‐scale restoration in intensive agricultural landscapes supports more specialized and less mobile pollinator species
Authors: Kremen Claire , M'Gonigle Leithen K.
Published: March 2015

Agriculture now constitutes 40–50% of terrestrial land use globally. By enhancing habitat suitability and connectivity, restoration within agricultural landscapes could have a major influence on biodiversity conservation. However, habitat management within intensive agricultural landscapes may primarily boost abundances of common, highly mobile generalists, rather than vulnerable or endangered species. We studied pollinator community response to small‐scale habitat restoration in the intensively farmed Central Valley of California to determine whether restoration could also promote more specialized, less common and/or less mobile species.

Composition of pollinator communities was assessed in five experimental and 10 control (unrestored) sites before and after restoration of native plant hedgerows over an 8‐year period, using a before‐after control‐impact design.

We characterized bee and fly species based on functional response traits [floral specialization, habitat specialization, abundance, body size and sociality (bees only)] known to influence the response to habitat change.

We modelled how species occurrences changed with habitat restoration over time as modulated by their response traits.

We found that hedgerows not only significantly enhanced occurrences of native bee and syrphid fly species, but that as hedgerows matured, they had a greater positive effect on species that were more specialized in floral and nesting resources and smaller (less mobile).

Synthesis and applications. Unlike previous studies that suggest habitat restoration in agricultural landscapes only benefits mobile, generalist species, our results suggest that small‐scale habitat restoration can promote species whose traits likely render them particularly vulnerable to habitat degradation. Thus, even within highly intensive agricultural landscapes, small‐scale habitat restoration can be a conservation management tool. However, tailoring habitat enhancements to promote certain species or guilds may be critical for their success as a conservation intervention in agricultural landscapes.
Similar sponge‐associated bacteria can be acquired via both vertical and horizontal transmission
Authors: Sipkema Detmer , de Caralt Sònia , Morillo Jose A. , Al‐Soud Waleed Abu , Sørensen Søren J. , Smidt Hauke , Uriz María J.
Published: March 2015

Marine sponges host diverse communities of microorganisms that are often vertically transmitted from mother to oocyte or embryo. Horizontal transmission has often been proposed to co‐occur in marine sponges, but the mechanism is poorly understood. To assess the impact of the mode of transmission on the microbial assemblages of sponges, we analysed the microbiota in sympatric sponges that have previously been reported to acquire bacteria via either vertical (Corticium candelabrum and Crambe crambe) or horizontal transmission (Petrosia ficiformis). The comparative study was performed by polymerase chain reaction‐denaturing gradient gel electrophoresis and pyrosequencing of barcoded PCR‐amplified 16S rRNA gene fragments. We found that P. ficiformis and C. candelabrum each harbour their own species‐specific bacteria, but they are similar to other high‐microbial‐abundance sponges, while the low‐microbial‐abundance sponge C. crambe hosts microbiota of a very different phylogenetic signature. In addition, nearly 50% of the reads obtained from P. ficiformis were most closely related to bacteria that were previously reported to be vertically transmitted in other sponges and comprised vertical–horizontal transmission phylogenetic clusters (VHT clusters). Therefore, our results provide evidence for the hypothesis that similar sponge‐associated bacteria can be acquired via both vertical and horizontal transmission.
Prevention of Enzymatic Browning of Chinese Yam (Dioscorea spp.) Using Electrolyzed Oxidizing Water
Authors: Jia Guo‐Liang , Shi Jing‐Ying , Song Zhan‐Hua , Li Fa‐De
Published: March 2015

In this study, the effects of electrolyzed oxidizing water (EOW) on the prevention of enzymatic browning of fresh‐cut “Jiu Jinhuang” Chinese yam were investigated. The yams were immersed in the inhibitors for 25 min at 20 °C. Compared with the tap water (TW) treatment, the chromatic attributes were significantly different after 72 h of storage (P < 0.05). The activities of polyphenol oxidase (PPO, EC 1.10.3.1), peroxidase (POD, EC 1.11.1.7), and L‐phenylalanine ammonia lyase (PAL, EC 4.3.1.5) were inhibited when measured at 24 h. The contents of phenolic acids, including gallic and chlorogenic acid, in the group treated with the slightly acidic electrolyzed water (SAEW) were higher than those treated with TW and neutral electrolyzed water (NEW). The group treated with NEW had the highest total phenol content (P < 0.05, at 24 h), while the group treated with SAEW had the highest flavonoid content (P < 0.05) during storage. Without being treated with inhibitors, the Km and Vmax values of yam PPO were 0.0044 mol/L and 0.02627 U/min, respectively, and the Ki of samples treated with SAEW and citric acid (CA) were 15.6607 and 2.3969 μmol/L, respectively. These results indicate that EOW is beneficial as a browning inhibitor.
Calcified Biofilms from Cambrian Oolitic Limestones in China
Authors: Wei LIU , Xingliang ZHANG
Published: March 2015

Calcified biofilms are preserved as thin micritic coatings in the Cambrian oolitic limestone of two sections in North and South China. Standard petrographic examination revealed that the biofilms were developed during the early diagenetic stage immediately after the freshly deposited ooids, proceeding in the continuous sequence of depositional processes. The biofilm outlines are highly irregular, with steep sides, tower‐like structures and overhanging projections; the internal fabric of the biofilms is composed of roughly laminated micrite aggregates with channel‐like structures. Biofilms exhibit a strong fluorescent reaction. Detailed SEM examination suggests that the biofilms are biotically dominated by cyanobacteria. Our study demonstrates that microbial colonies, such as biofilms, can develop on ooid cortices and influence the formation and microstructures of those ooids.
Optically Stimulated Luminescence (OSL) Chronology of the Dehenglong Landslide from Longyang Gorge to Liujia Gorge along Upper Yellow River, China
Authors: Xiaohua GUO , Zhongping LAI , Yudong LU , Xiaolin LI , Zheng SUN
Published: March 2015

Giant landslides are common along the upper Yellow River from Longyang Gorge to Liujia Gorge, and some of them even blocked and dammed the upper Yellow River. Chronology is inevitable in studying the mechanism of giant landslides. Controversy exists about the chronology of those giant landslides, and some have not yet dated. The Dehenglong landslide is the largest one among them. In this study, OSL samples were collected from lacustrine silty sediments and loess directly overlying the landslide sediments, as well as fault sediments related to the landslide. This landslide yielded an age of 89 ± 8 ka, which is identical with the fault age of 73 ± 5 ka at two sigma errors. The agreement of a topographic analysis and the absolute age of landslides imply that the formation of the Dehenglong landslide is strongly correlated with the tectonic activity.
Effects of propofol or desflurane on post‐operative spirometry in elderly after knee surgery: a double‐blind randomised study
Authors: KIM Y.‐S. , LIM B.‐G. , KIM H. , KONG M.‐H. , LEE I.‐O.
Published: March 2015

Background

Intravenous or volatile agents reduce respiratory function, which can result in respiratory complications in geriatric patients. We hypothesised that there would be no differences in lung function between anaesthesia established using either drug.

Methods

Elderly patients were randomly assigned to receive either propofol with remifentanil (n = 48) or desflurane (DES) with remifentanil (n = 52) for knee surgery. Spirometry tests including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced mid‐expiratory flow (FEF25–75), and FEV1/FVC ratio were performed preoperatively, and 30 min, 60 min, and 24 h after awakening. Emergence time and post‐operative pain scores were also measured.

Results

Time to emergence was significantly longer in the propofol than in the DES group (17.0 vs. 12.5 min, P = 0.04). Post‐operative FEV1 (1.6 or 1.4 l, P = 0.68 between groups) were significantly lower than preoperative values (2.1 or 2.0 l, P = 0.001 vs. post‐operative values, respectively) in both groups. Reduced FEV1 lasted for 24 h after surgery (1.7 or 1.6 l, P = 0.001 vs. preoperative values, respectively). Post‐operative FVC or FEF25–75 were lower than preoperative values. FEV1/FVC ratio did not change during the study period in both groups. There was no difference in FEV1, FVC, FEF25–75, FEV1/FVC, and post‐operative pain between the two anaesthetic techniques.

Conclusions

Although there is a delay in awakening when using propofol, the effects of propofol on post‐operative spirometry parameters are similar to those of DES when anaesthesia duration is approximately 3 h. Decreased respiratory parameters persisted up to 24 h after anaesthesia, irrespective of the choice of anaesthetic.
mGluR5 in the nucleus accumbens shell regulates morphine‐associated contextual memory through reactive oxygen species signaling
Authors: Qi Chong , Wang Xinjuan , Ge Feifei , Li Yijing , Shen Fang , Wang Junkai , Cui Cailian
Published: March 2015

Emerging evidence indicates that metabotropic glutamate receptor 5 (mGluR5) critically modulates drug and drug‐related behaviors. However, the role of mGluR5 in the opiate‐induced contextual memory remains unclear. Here, we found that microinfusion of the mGluR5 antagonist 3‐((2‐Methyl‐1,3‐thiazol‐4‐yl)ethynyl)pyridine (MTEP) into the nucleus accumbens (NAc) shell, but not into the core, significantly attenuated the expression of morphine conditioned place preference (CPP) in rats. Following the expression of morphine CPP, the protein level of membrane mGluR5 was selectively increased in the NAc shell. In primary striatal neurons, we observed that treatment with the mGluR5 agonist CHPG increased the phosphorylation level of extracellular signal‐regulated kinase (ERK), which was dependent on the mGluR5‐inositol‐1,4,5‐trisphosphate‐reactive oxygen species (ROS) pathway. Moreover, the microinjection of the ROS scavenger Tempol into the NAc shell of rats blocked the expression of morphine CPP. Further, the administration of t‐BOOH, a ROS donor, into the NAc shell rescued the retrieval impairment of morphine CPP produced by MTEP. Our previous study demonstrated that the expression of morphine CPP increased the phosphorylation of ERK selectively in the NAc shell. Thus, results of the present study suggest that mGluR5 in the NAc shell, but not in the core, is essential for the retrieval of morphine contextual memory, which is mediated at least in part, through the ROS/ERK signaling pathway. Uncovering the molecular basis of opiate contextual memory will benefit the development of new therapeutic approaches for the treatment of opiate addiction.