bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic, low-dose TMAO treatment reduces diastolic dysfunction and heart fibrosis in hypertensive rats
Authors: Huc Tomasz , Drapala Adrian , Gawrys Marta , Konop Marek , Bielinska Klaudia , Zaorska Ewelina , Samborowska Emilia , Wyczalkowska-Tomasik Aleksandra , Pączek Leszek , Dadlez Michal , Ufnal Marcin 
Published: September 2018

Several studies have suggested negative effects of trimethylamine oxide (TMAO) on the circulatory system. However, a number of studies have shown protective functions of TMAO, a piezolyte and osmolyte, in animals exposed to high hydrostatic and/or osmotic stress. We evaluated the effects of TMAO treatment on the development of hypertension and its complications in male spontaneously hypertensive rats (SHRs) maintained on water (SHR-Water) and SHRs drinking TMAO water solution from weaning (SHR-TMAO). Wistar-Kyoto (WKY) rats were used as normotensive controls to discriminate between age-dependent and hypertension-dependent changes. Telemetry measurements of blood pressure were performed in rats between the 7th and 16th weeks of life. Anesthetized rats underwent echocardiographic, electrocardiographic, and direct left ventricular end-diastolic pressure (LVEDP) measurements. Hematoxylin and eosin as well as van Gieson staining for histopathological evaluation were performed. Plasma TMAO measured by chromatography coupled with mass spectrometry was significantly higher in the SHR-Water group compared with the WKY group (~20%). TMAO treatment increased plasma TMAO by four- to fivefold and did not affect the development of hypertension in SHRs. Sixteen-week-old rats in the SHR-Water and SHR-TMAO groups (12-wk TMAO treatment) showed similar blood pressures, angiopathy, and cardiac hypertrophy. However, the SHR-TMAO group had lower plasma NH2-terminal pro-B-type natriuretic peptide, LVEDP, and cardiac fibrosis. In contrast to age-matched WKY rats, 60-wk-old SHRs showed hypertensive angiopathy and heart failure with preserved ejection fraction. Compared with the SHR-Water group, the SHR-TMAO group (56-wk TMAO treatment) showed significantly lower plasma NH2-terminal pro-B-type natriuretic peptide and vasopressin, significantly lower LVEDP, and cardiac fibrosis. In conclusion, a four- to fivefold increase in plasma TMAO does not exert negative effects on the circulatory system. In contrast, increased dietary TMAO seems to reduce diastolic dysfunction in pressure-overloaded hearts in rats.NEW & NOTEWORTHY Chronic, low-dose trimethylamine oxide (TMAO) treatment that increases plasma TMAO by four- to fivefold reduces plasma NH2-terminal pro-B-type natriuretic peptide and vasopressin, left ventricular end-diastolic pressure, and cardiac fibrosis in pressure-overloaded hearts in hypertensive rats. Our study provides evidence that a moderate increase in plasma TMAO does not have a negative effect on the circulatory system. In contrast, increased dietary TMAO seems to reduce diastolic dysfunction in the pressure-overloaded heart.
Targeting Lineage-specific MITF Pathway in Human Melanoma Cell Lines by A-485, the Selective Small-molecule Inhibitor of p300/CBP
Authors: Wang Rui , He Yupeng , Robinson Valerie , Yang Ziping , Hessler Paul , Lasko Loren M. , Lu Xin , Bhathena Anahita , Lai Albert , Uziel Tamar , Lam Lloyd T. 
Published: September 2018

Abstract
Metastatic melanoma is responsible for approximately 80% of deaths from skin cancer. Microphthalmia-associated transcription factor (MITF) is a melanocyte-specific transcription factor that plays an important role in the differentiation, proliferation, and survival of melanocytes as well as in melanoma oncogenesis. MITF is amplified in approximately 15% of patients with metastatic melanoma. However, no small-molecule inhibitors of MITF currently exist. MITF was shown to associate with p300/CBP, members of the KAT3 family of histone acetyltransferase. p300 and CREB-binding protein (p300/CBP) regulate a wide range of cellular events such as senescence, apoptosis, cell cycle, DNA damage response, and cellular differentiation. p300/CBP act as transcriptional coactivators for multiple proteins in cancers, including oncogenic transcription factors such as MITF. In this study, we showed that our novel p300/CBP catalytic inhibitor, A-485, induces senescence in multiple melanoma cell lines, similar to silencing expression of EP300 (encodes p300) or MITF. We did not observe apoptosis and increase invasiveness upon A-485 treatment. A-485 regulates the expression of MITF and its downstream signature genes in melanoma cell lines undergoing senescence. In addition, expression and copy number of MITF is significantly higher in melanoma cell lines that undergo A-485–induced senescence than resistant cell lines. Finally, we showed that A-485 inhibits histone-H3 acetylation but did not displace p300 at promoters of MITF and its putative downstream genes. Taken together, we provide evidence that p300/CBP inhibition suppressed the melanoma-driven transcription factor, MITF, and could be further exploited as a potential therapy for treating melanoma.
c-MYC Drives Breast Cancer Metastasis to the Brain, but Promotes Synthetic Lethality with TRAIL
Authors: Lee Ho Yeon , Cha Junghwa , Kim Seon Kyu , Park Jun Hyung , Song Ki Hoon , Kim Pilnam , Kim Mi-Young 
Published: September 2018

Abstract

Brain metastasis in breast cancer is particularly deadly, but effective treatments remain out of reach due to insufficient information about the mechanisms underlying brain metastasis and the potential vulnerabilities of brain-metastatic breast cancer cells. Here, human breast cancer cells and their brain-metastatic derivatives (BrMs) were used to investigate synthetic lethal interactions in BrMs. First, it was demonstrated that c-MYC activity is increased in BrMs and is required for their brain-metastatic ability in a mouse xenograft model. Specifically, c-MYC enhanced brain metastasis by facilitating the following processes within the brain microenvironment: (i) invasive growth of BrMs, (ii) macrophage infiltration, and (iii) GAP junction formation between BrMs and astrocytes by upregulating connexin 43 (GJA1/Cx43). Furthermore, RNA-sequencing (RNA-seq) analysis uncovered a set of c-MYC–regulated genes whose expression is associated with higher risk for brain metastasis in breast cancer patients. Paradoxically, however, increased c-MYC activity in BrMs rendered them more susceptible to TRAIL (TNF-related apoptosis-inducing ligand)–induced apoptosis. In summary, these data not only reveal the brain metastasis-promoting role of c-MYC and a subsequent synthetic lethality with TRAIL, but also delineate the underlying mechanism. This suggests TRAIL-based approaches as potential therapeutic options for brain-metastatic breast cancer.

Implications:
This study discovers a paradoxical role of c-MYC in promoting metastasis to the brain and in rendering brain-metastatic cells more susceptible to TRAIL, which suggests the existence of an Achilles' heel, thus providing a new therapeutic opportunity for breast cancer patients.
Deletion 6q Drives T-cell Leukemia Progression by Ribosome Modulation
Authors: Gachet Stéphanie , El-Chaar Tiama , Avran David , Genesca Eulalia , Catez Frédéric , Quentin Samuel , Delord Marc , Thérizols Gabriel , Briot Delphine , Meunier Godelieve , Hernandez Lucie , Pla Marika , Smits Willem K. , Buijs-Gladdines Jessica G. , Van Loocke Wouter , Menschaert Gerben , André-Schmutz Isabelle , Taghon Tom , Van Vlierberghe Pieter , Meijerink Jules P. , Baruchel André , Dombret Hervé , Clappier Emmanuelle , Diaz Jean-Jacques , Gazin Claude , de Thé Hugues , Sigaux François , Soulier Jean 
Published: September 2018

Abstract

Deletion of chromosome 6q is a well-recognized abnormality found in poor-prognosis T-cell acute lymphoblastic leukemia (T-ALL). Using integrated genomic approaches, we identified two candidate haploinsufficient genes contiguous at 6q14, SYNCRIP (encoding hnRNP-Q) and SNHG5 (that hosts snoRNAs), both involved in regulating RNA maturation and translation. Combined silencing of both genes, but not of either gene alone, accelerated leukemogeneis in a Tal1/Lmo1/Notch1-driven mouse model, demonstrating the tumor-suppressive nature of the two-gene region. Proteomic and translational profiling of cells in which we engineered a short 6q deletion by CRISPR/Cas9 genome editing indicated decreased ribosome and mitochondrial activities, suggesting that the resulting metabolic changes may regulate tumor progression. Indeed, xenograft experiments showed an increased leukemia-initiating cell activity of primary human leukemic cells upon coextinction of SYNCRIP and SNHG5. Our findings not only elucidate the nature of 6q deletion but also highlight the role of ribosomes and mitochondria in T-ALL tumor progression.

Significance:
The oncogenic role of 6q deletion in T-ALL has remained elusive since this chromosomal abnormality was first identified more than 40 years ago. We combined genomic analysis and functional models to show that the codeletion of two contiguous genes at 6q14 enhances malignancy through deregulation of a ribosome–mitochondria axis, suggesting the potential for therapeutic intervention.
This article is highlighted in the In This Issue feature, p. 1494
Immune Cell Gene Signatures for Profiling the Microenvironment of Solid Tumors
Authors: Nirmal Ajit J. , Regan Tim , Shih Barbara B. , Hume David A. , Sims Andrew H. , Freeman Tom C. 
Published: September 2018

Abstract
The immune composition of the tumor microenvironment regulates processes including angiogenesis, metastasis, and the response to drugs or immunotherapy. To facilitate the characterization of the immune component of tumors from transcriptomics data, a number of immune cell transcriptome signatures have been reported that are made up of lists of marker genes indicative of the presence a given immune cell population. The majority of these gene signatures have been defined through analysis of isolated blood cells. However, blood cells do not reflect the differentiation or activation state of similar cells within tissues, including tumors, and consequently markers derived from blood cells do not necessarily transfer well to tissues. To address this issue, we generated a set of immune gene signatures derived directly from tissue transcriptomics data using a network-based deconvolution approach. We define markers for seven immune cell types, collectively named ImSig, and demonstrate how these markers can be used for the quantitative estimation of the immune cell content of tumor and nontumor tissue samples. The utility of ImSig is demonstrated through the stratification of melanoma patients into subgroups of prognostic significance and the identification of immune cells with the use of single-cell RNA-sequencing data derived from tumors. Use of ImSig is facilitated by an R package (imsig). Cancer Immunol Res; 6(11); 1388–400. ©2018 AACR.
Chronographical Analysis: an Essay in Methodology
Authors: Steineck Raji C. 
Published: September 2018

Abstract
In this essay I discuss the various ways time can be inscribed in texts below the level of explicit propositions about time. I argue that a full chronographical analysis needs to account for the dimensions of the theoretical, the practical, and the aesthetic. Taking Kant’s table of categories as a guide to the fundamental functions of chronographic determination, I propose a methodology of analysis that goes beyond the aspect of quantitative measurement, and includes typological, thetic and modal information about time. Numerous examples from various textual domains such as poetry, historiography, science and law illustrate the wide applicability of the proposed analytical categories. The full matrix of dimensions and determinative functions can be used to describe the chronographic signature of a text, which depends as much on its communicative purpose as on the technologies of calculating and describing time available to its authors.
Learning from the South
Authors: Ciocchini Pablo 
Published: September 2018

Abstract
Over the last three decades, governments in Latin America and Southeast Asia have transitioned from authoritarian to democratic regimes. A series of reforms to criminal procedures have been promoted to improve transparency and accountability and reduce the chronic backlog suffered by courts in the region. These reforms are based on the “ideal” model of societies in the Global North. However, due to the socioeconomic conditions and the institutional history of societies in these regions, these reforms have not achieved the proposed goals. Because of these failures, later reforms in Latin America have prioritised managerial concerns. Thus, they have favoured different types of bargained justice and simplified procedures that usher in convictions based mainly on police reports without a proper cross-examination of evidence. This article argues that jurisdictions in both regions could learn a lot from one another regarding avoiding failures and unintended consequences. To achieve this, the article uses a comparative approach and demonstrates the potential of this by comparing four reform strategies carried out in Argentina and the Philippines.
Are wild insectivorous birds attracted to methyl-jasmonate-treated Pyrenean oak trees?
Authors: Saavedra Irene , Amo Luisa 
Published: September 2018

AbstractPlants emit herbivore-induced plant volatiles (HIPVs) when they are attacked by herbivorous arthropods to attract natural enemies of the herbivores. Previous studies have suggested that insectivorous birds can detect the HIPVs for prey location. The production of HIPVs is partly mediated by the jasmonic acid signalling pathway. Methyl jasmonate is one compound involved in the jasmonic acid signalling pathway. Therefore, spraying of methyl jasmonate (MeJa) solution on plants can induce the emission of volatiles similar to the HIPVs induced by herbivory. We performed two field experiments to test whether insectivorous adult birds are attracted to Pyrenean oak trees (Quercus pyrenaica) treated with MeJa solutions. We used artificial larvae to measure bird predation rate. There were no differences in the predation rates of plasticine larvae between control and MeJa treatments, suggesting that insectivorous birds were not attracted to trees treated with MeJa. We also tested whether blue tit nestlings without previous experience in foraging respond to the scent of Pyrenean oak tree leaves treated with MeJa, to test whether the attraction to MeJa-treated trees is innate. A similar number of nestlings performed begging responses when exposed to the scent of leaves of MeJa-treated trees compared to the scent of leaves of control untreated trees. Furthermore, the duration of the first begging was similar in response to the volatiles emitted by MeJa-treated trees and untreated trees. Despite previous evidence suggesting that insectivorous birds are attracted to HIPVs, our results show that neither insectivorous adult birds nor inexperienced nestlings were attracted to trees treated with MeJa. Further studies are needed to disentangle whether the differences in the emission of volatiles between herbivore-infested trees and MeJa-treated trees can explain this lack of attraction to MeJa-treated Pyrenean oak trees.
Lineages of Capital
Authors: Anievas Alexander , Nişancıoğlu Kerem 
Published: September 2018

AbstractOur reply focuses on three key themes raised in the symposium. First, we discuss an enduring issue in Marxist International Relations: ‘the problematic of the international’ and the problems of methodological internalism. We examine how our interlocutors have responded to this problematic and why we consider these responses insufficient. Specifically, we suggest that the source of our disagreement is grounded in two divergent understandings of the problem of internalism itself. We then reassert the value of our chosen response to the problematic – uneven and combined development (UCD). Second, we respond to the criticism that our extension ofUCDas a ‘transmodal’ general abstraction is problematic by further explicating the significance and role of general abstractions in Marxist theory – a point yet addressed by our critics. Finally, we return to the fundamental question at the core of the transition debate: what is capitalism and how do we theorise it?
Scribe and Owner as Artist in a Sixteenth-Century Yiddish Miscellany
Authors: Wolfthal Diane 
Published: September 2018

AbstractA Miscellany of five secular Yiddish chapbooks was created in late sixteenth-century East Swabia. Two of the chapbooks, “Keyser Oktavian” and a collection of “mayses”, were illustrated by their scribe Yitzhak bar Yuda Reutlingen. A Jewish owner also drew on a blank folio. This essay seeks to address two issues. First, although in the past these drawings have often been dismissed as derivative or crude, this article will dispute this assertion. Then this essay will question the ways in which some scholars have masked the manuscript’s Jewish identity, and will explore how the scribe and owner express the distinctly Jewish nature of the Miscellany through their drawings.
The Rules of Prose in Sixteenth-Century China: Tang Shunzhi (1507-1560) as an Anthologist
Authors: Clifford Timothy Robert 
Published: September 2018

AbstractThis paper examines the role of the anthologist in late imperial Chinese print culture. Specifically, it focuses on the sixteenth-century anthologist Tang Shunzhi. Tang’s first place finish in the 1529 metropolitan examinations came at a pivotal moment. As commercial anthology printers responded to an expanding reading public by applying readers’ aids such as punctuation and commentary to increasingly diverse textual corpora, Tang’s distinctive method of annotation was used to ‘reveal’ the rules of Ming examination prose operating universally across a seemingly endless variety of texts. At the same time, Tang’s own belief in universal rules of prose was the product of an educational movement to supplement the narrow and monotonous examination curriculum by providing students with anthologies of ancient literature. These two Tangs—one revealing uniformity within diversity, the other revealing diversity within uniformity—highlight contradictory trends toward both stereotypy and diversification within sixteenth-century print culture more broadly.
Liulichang: the Institution and Practice of the Antique, Art, and Book Market in Late Qing Beijing
Authors: Yin Tongyun 
Published: September 2018

AbstractThe unique characteristic of the late Qing Beijing antique and book market lies in the existence of Liulichang market, a geographically and culturally integrated marketplace on a scale that was not found in other parts of contemporaneous China. Starting with examining the changing urban landscape and reconfiguration of Beijing’s social and cultural spaces in the Ming and Qing dynasties, this paper investigates the uniqueness of Liulichang market through the lens of the distinctive architecture, organizations, and practices of its antique and book shops. The dominance of a regional market preference for particular artworks, represented by the canonization of paintings by the early Qing orthodox masters at Liulichang, demonstrates that the market was not only an economic institution, but also an essential public space for formalizing collective judgment, meanings, and relationships driven by the agendas of the bureaucratic elite class in the Qing capital. The emphasis on specific formative and decisive forces in constructing the regional markets and directing art consumption in late Qing China further aims to add different nuances to our understanding of the fluidity and specificity of different urban cultures in the late Qing dynasty.
Challenges in Modeling Turbulent Heat Fluxes to Snowpacks in Forest Clearings
Authors: Conway Jonathan P. , Pomeroy John W. , Helgason Warren D. , Kinar Nicholas J. 
Published: September 2018

Abstract
Forest clearings are common features of evergreen forests and produce snowpack accumulation and melt differing from that in adjacent forests and open terrain. This study has investigated the challenges in specifying the turbulent fluxes of sensible and latent heat to snowpacks in forest clearings. The snowpack in two forest clearings in the Canadian Rockies was simulated using a one-dimensional (1D) snowpack model. A trade-off was found between optimizing against measured snow surface temperature or snowmelt when choosing how to specify the turbulent fluxes. Schemes using the Monin–Obukhov similarity theory tended to produce negatively biased surface temperature, while schemes that enhanced turbulent fluxes, to reduce the surface temperature bias, resulted in too much melt. Uncertainty estimates from Monte Carlo experiments showed that no realistic parameter set could successfully remove biases in both surface temperature and melt. A simple scheme that excludes atmospheric stability correction was required to successfully simulate surface temperature under low wind speed conditions. Nonturbulent advective fluxes and/or nonlocal sources of turbulence are thought to account for the maintenance of heat exchange in low-wind conditions. The simulation of snowmelt was improved by allowing enhanced latent heat fluxes during low-wind conditions. Caution is warranted when snowpack models are optimized on surface temperature, as model tuning may compensate for deficiencies in conceptual and numerical models of radiative, conductive, and turbulent heat exchange at the snow surface and within the snowpack. Such model tuning could have large impacts on the melt rate and timing of the snow-free transition in simulations of forest clearings within hydrological and meteorological models.
Indian Christians and The Making of Composite Culture in South India
Authors: Doss M. Christhu 
Published: September 2018

While North India erupted in rebellion in 1857, South India was experiencing a range of cross-cultural contests between missionary Christianity and local converts, who protested against Indian culture being dismissed as a work of the devil. Converts in the emerging Christian communities, particularly in South India, made efforts to retain their indigenous cultural ethos as part of their lived experience. Early attempts to balance Indian identity with Christian beliefs and practices were later replicated in a second anti-hegemonic movement by claims of Indian Christians for respectful inclusion into the new composite nation of postcolonial India. This article brings out how these two processes of asserting hybridity and equity developed. The initial impact of hegemonising Christianity created a chasm between missionaries and converts, which especially the latter addressed constructively. After 1857, emboldened British hegemonic and missionary activities sparked further divisive identity politics, feeding fresh rebellious ambitions that needed to be pacified to maintain the empire. As more culturally conscious Indian Christians realised that missionary Christianity was antithetical to their lived experiences as part of an emerging Indian nation, they used educational strategies to strengthen the formation of India’s composite culture, so that India’s Christians could now (re)assert their rightful place within the postcolonial nationalist framework, despite contentions from majoritarian forces.
Stagnation and Institutional Structures
Authors: Kotz David M. , Basu Deepankar 
Published: September 2018

The stagnation in the US economy since 2008 has given rise to a mainstream stagnation literature. This paper offers a critique of that literature and proposes an explanation for the current stagnation based on social structure of accumulation (SSA) theory. It presents historical and econometric evidence for an SSA-based explanation of the current stagnation and considers the implications for the likely near-future course of economic policy and institutional change. JEL Classification: E11, E39, O43