bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the differential addiction to anti-apoptotic BCL-2 family for cancer therapy
Authors: Inoue-Yamauchi Akane , Jeng Paul S. , Kim Kwanghee , Chen Hui-Chen , Han Song , Ganesan Yogesh Tengarai , Ishizawa Kota , Jebiwott Sylvia , Dong Yiyu , Pietanza Maria C. , Hellmann Matthew D. , Kris Mark G. , Hsieh James J. , Cheng Emily H. 
Published: July 2017

AbstractBCL-2 family proteins are central regulators of mitochondrial apoptosis and validated anti-cancer targets. Using small cell lung cancer (SCLC) as a model, we demonstrated the presence of differential addiction of cancer cells to anti-apoptotic BCL-2, BCL-XL or MCL-1, which correlated with the respective protein expression ratio. ABT-263 (navitoclax), a BCL-2/BCL-XL inhibitor, prevented BCL-XL from sequestering activator BH3-only molecules (BH3s) and BAX but not BAK. Consequently, ABT-263 failed to kill BCL-XL-addicted cells with low activator BH3s and BCL-XL overabundance conferred resistance to ABT-263. High-throughput screening identified anthracyclines including doxorubicin and CDK9 inhibitors including dinaciclib that synergized with ABT-263 through downregulation of MCL-1. As doxorubicin and dinaciclib also reduced BCL-XL, the combinations of BCL-2 inhibitor ABT-199 (venetoclax) with doxorubicin or dinaciclib provided effective therapeutic strategies for SCLC. Altogether, our study highlights the need for mechanism-guided targeting of anti-apoptotic BCL-2 proteins to effectively activate the mitochondrial cell death programme to kill cancer cells.
In situ stable crack growth at the micron scale
Authors: Sernicola Giorgio , Giovannini Tommaso , Patel Punit , Kermode James R. , Balint Daniel S. , Britton T. Ben , Giuliani Finn 
Published: July 2017

AbstractGrain boundaries typically dominate fracture toughness, strength and slow crack growth in ceramics. To improve these properties through mechanistically informed grain boundary engineering, precise measurement of the mechanical properties of individual boundaries is essential, although it is rarely achieved due to the complexity of the task. Here we present an approach to characterize fracture energy at the lengthscale of individual grain boundaries and demonstrate this capability with measurement of the surface energy of silicon carbide single crystals. We perform experiments using an in situ scanning electron microscopy-based double cantilever beam test, thus enabling viewing and measurement of stable crack growth directly. These experiments correlate well with our density functional theory calculations of the surface energy of the same silicon carbide plane. Subsequently, we measure the fracture energy for a bi-crystal of silicon carbide, diffusion bonded with a thin glassy layer.
Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens
Authors: Tamigney Kenfack Marielle , Mazur Marcelina , Nualnoi Teerapat , Shaffer Teresa L. , Ngassimou Abba , Blériot Yves , Marrot Jérôme , Marchetti Roberta , Sintiprungrat Kitisak , Chantratita Narisara , Silipo Alba , Molinaro Antonio , AuCoin David P. , Burtnick Mary N. , Brett Paul J. , Gauthier Charles 
Published: July 2017

AbstractBurkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the etiologic agents of melioidosis and glanders, respectively, cause severe disease in both humans and animals. Studies have highlighted the importance of Bp and Bm lipopolysaccharides (LPS) as vaccine candidates. Here we describe the synthesis of seven oligosaccharides as the minimal structures featuring all of the reported acetylation/methylation patterns associated with Bp and Bm LPS O-antigens (OAgs). Our approach is based on the conversion of an l-rhamnose into a 6-deoxy-l-talose residue at a late stage of the synthetic sequence. Using biochemical and biophysical methods, we demonstrate the binding of several Bp and Bm LPS-specific monoclonal antibodies with terminal OAg residues. Mice immunized with terminal disaccharide–CRM197 constructs produced high-titer antibody responses that crossreacted with Bm-like OAgs. Collectively, these studies serve as foundation for the development of novel therapeutics, diagnostics, and vaccine candidates to combat diseases caused by Bp and Bm.
AGC family kinase 1 participates in trogocytosis but not in phagocytosis in Entamoeba histolytica
Authors: Somlata  , Nakada-Tsukui Kumiko , Nozaki Tomoyoshi 
Published: July 2017

AbstractThe protozoan parasite Entamoeba histolytica is the aetiologic agent of amoebiasis, an endemic infection in developing countries with considerable morbidity and mortality. Recently, trogocytosis has been recognized as the key step in amoebic cytolysis and invasion, a paradigm shift in understanding pathogenicity of this organism. Here we report that AGC family kinase 1 is specifically involved in trogocytosis of live human cells and does not participate in phagocytosis of dead cells. Live imaging reveals localization of this kinase in the long and thin tunnels formed during trogocytosis but not in the trogosomes (endosomes formed after trogocytosis). Silencing of the specific gene leads to a defect in CHO cell destruction and trogocytosis while other endocytic processes remain unaffected. The results suggest that the trogocytic pathway is likely to be different from phagocytosis though many of the steps and molecules involved may be common.
Norgestimate inhibits staphylococcal biofilm formation and resensitizes methicillin-resistant Staphylococcus aureus to β-lactam antibiotics
Authors: Yoshii Yutaka , Okuda Ken-ichi , Yamada Satomi , Nagakura Mari , Sugimoto Shinya , Nagano Tetsuo , Okabe Takayoshi , Kojima Hirotatsu , Iwamoto Takeo , Kuwano Kazuyoshi , Mizunoe Yoshimitsu 
Published: July 2017

AbstractFormation of bacterial biofilms on medical devices can cause severe or fatal infectious diseases. In particular, biofilm-associated infections caused by methicillin-resistant Staphylococcus aureus are difficult to eradicate because the biofilm is strongly resistant to antibiotics and the host immune response. There is no effective treatment for biofilm-associated infectionss, except for surgical removal of contaminated medical devices followed by antibiotic therapy. Here we show that norgestimate, an acetylated progestin, effectively inhibits biofilm formation by staphylococcal strains, including methicillin-resistant S. aureus, without inhibiting their growth, decreasing the selective pressure for emergence of resistance. 17-Deacetyl norgestimate, a metabolite of norgestimate, shows much weaker inhibitory activity against staphylococcal biofilm formation, indicating that the acetyl group of norgestimate is important for its activity. Norgestimate inhibits staphylococcal biofilm formation by inhibiting production of polysaccharide intercellular adhesin and proteins in the extracellular matrix. Proteome analysis of S. aureus indicated that norgestimate represses the expression of the cell wall-anchored protein SasG, which promotes intercellular adhesion, and of the glycolytic enzyme enolase, which plays a secondary role in biofilm formation. Notably, norgestimate induces remarkable changes in cell wall morphology, characterized by increased thickness and abnormal rippled septa. Furthermore, norgestimate increases the expression level of penicillin binding protein 2 and resensitizes methicillin-resistant S. aureus to β-lactam antibiotics. These results suggest that norgestimate is a promising lead compound for the development of drugs to treat biofilm-associated infections, as well as for its ability to resensitize methicillin-resistant S. aureus to β-lactam antibiotics.
Protecting quantum Fisher information of N-qubit GHZ state by weak measurement with flips against dissipation
Authors: Chen Yu , Zou Jian , Long Zheng-wen , Shao Bin 
Published: July 2017

AbstractIn this paper we propose a scheme by using weak-measurement-based pre- and post-flips (WMPPF) to protect the average quantum Fisher information (QFI) in the independent amplitude-damping channel (ADC) for N-qubit GHZ state and generalized N-qubit GHZ states. We also discuss the weak measurement and quantum measurement reversal (WMQMR) with the same ADC. Based on the analytical and numerical results we obtain the main result: the WMPPF can reduce the effect of dissipation on the average QFI of the phase or the frequency for GHZ state and some generalized GHZ states, and the WMQMR can reduce the effect of dissipation on the average fidelity for GHZ state and generalized GHZ states in ADC. Comparing QFI with fidelity for WMPPF or for WMQMR, a scheme protecting the average fidelity does not necessarily protect the average QFI, even with the same parameters, and vice versa. We also focus on the average QFI versus N in the phase estimation and the frequency estimation of WMPPF, both of which show the advantages over the do-nothing (DN) case. From the investigation of the QFI of weight factor, we find that increasing qubit number can protect it both for WMPPF and for DN.
Decreasing prevalence of dementia in 85-year olds examined 22 years apart: the influence of education and stroke
Authors: Skoog Ingmar , Börjesson-Hanson Anne , Kern Silke , Johansson Lena , Falk Hanna , Sigström Robert , Östling Svante 
Published: July 2017

AbstractIndividuals aged 80 years and older constitute the fastest growing segment of the population worldwide, leading to an expected increase in dementia cases. Education level and treatment of vascular risk factors has increased during the last decades. We examined whether this has influenced the prevalence of dementia according to DSM-III-R using population-based samples of 85-year-olds (N = 1065) examined with identical methods 1986–87 and 2008–10. The prevalence of dementia was 29.8% in 1986–87 and 21.7% in 2008–10 (OR 0.66; 95%-CI: 0.50–0.86). The decline was mainly observed for vascular dementia. The proportion with more than basic education (25.2% and 57.7%), and the prevalence of stroke (20% and 30%) increased, but the odds ratio for dementia with stroke decreased from 4.3 to 1.8 (interaction stroke*birth cohort; p = 0.008). In a logistic regression, education (OR 0.70; 95%-CI 0.51–0.96), stroke (OR 3.78; 95%-CI 2.28–6.29), interaction stroke*birth cohort (OR 0.50; 95%-CI 0.26–0.97), but not birth cohort (OR 0.98; 95%-CI 0.68–1.41), were related to prevalence of dementia. Thus, the decline in dementia prevalence was mainly explained by higher education and lower odds for dementia with stroke in later born birth cohorts. The findings may be related to an increased cognitive reserve and better treatment of stroke in later-born cohorts.
Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury
Authors: Lei Jun , Rosenzweig Jason M. , Mishra Manoj K. , Alshehri Wael , Brancusi Flavia , McLane Mike , Almalki Ahmad , Bahabry Rudhab , Arif Hattan , Rozzah Rayyan , Alyousif Ghada , Shabi Yahya , Alhehaily Nader , Zhong Wenyu , Facciabene Andrea , Kannan Sujatha , Kannan Rangaramanujam M. , Burd Irina 
Published: July 2017

AbstractPreterm birth is a major risk factor for adverse neurological outcomes in ex-preterm children, including motor, cognitive, and behavioral disabilities. N-acetyl-L-cysteine therapy has been used in clinical studies; however, it requires doses that cause significant side effects. In this study, we explore the effect of low dose N-acetyl-L-cysteine therapy, delivered using a targeted, systemic, maternal, dendrimer nanoparticle (DNAC), in a mouse model of intrauterine inflammation. Our results demonstrated that intraperitoneal maternal DNAC administration significantly reduced the preterm birth rate and altered placental immune profile with decreased CD8+ T-cell infiltration. Furthermore, we demonstrated that DNAC improved neurobehavioral outcomes and reduced fetal neuroinflammation and long-term microglial activation in offspring. Our study is the first to provide evidence for the role of CD8+ T-cell in the maternal-fetal interface during inflammation and further support the efficacy of DNAC in preventing preterm birth and prematurity-related outcomes.
Influence of C-terminal truncation of murine Serum amyloid A on fibril structure
Authors: Rennegarbe Matthies , Lenter Inga , Schierhorn Angelika , Sawilla Romy , Haupt Christian 
Published: July 2017

AbstractAmyloid A (AA) amyloidosis is a systemic protein misfolding disease affecting humans and other vertebrates. While the protein precursor in humans and mice is the acute-phase reactant serum amyloid A (SAA) 1.1, the deposited fibrils consist mainly of C-terminally truncated SAA fragments, termed AA proteins. For yet unknown reasons, phenotypic variations in the AA amyloid distribution pattern are clearly associated with specific AA proteins. Here we describe a bacterial expression system and chromatographic strategies to obtain significant amounts of C-terminally truncated fragments of murine SAA1.1 that correspond in truncation position to relevant pathological AA proteins found in humans. This enables us to investigate systematically structural features of derived fibrils. All fragments form fibrils under nearly physiological conditions that show similar morphological appearance and amyloid-like properties as evident from amyloid-specific dye binding, transmission electron microscopy and infrared spectroscopy. However, infrared spectroscopy suggests variations in the structural organization of the amyloid fibrils that might be derived from a modulating role of the C-terminus for the fibril structure. These results provide insights, which can help to get a better understanding of the molecular mechanisms underlying the different clinical phenotypes of AA amyloidosis.
BRD3 and BRD4 BET Bromodomain Proteins Differentially Regulate Skeletal Myogenesis
Authors: Roberts Thomas C. , Etxaniz Usue , Dall’Agnese Alessandra , Wu Shwu-Yuan , Chiang Cheng-Ming , Brennan Paul E. , Wood Matthew J. A. , Puri Pier Lorenzo 
Published: July 2017

AbstractMyogenic differentiation proceeds through a highly coordinated cascade of gene activation that necessitates epigenomic changes in chromatin structure. Using a screen of small molecule epigenetic probes we identified three compounds which inhibited myogenic differentiation in C2C12 myoblasts; (+)-JQ1, PFI-1, and Bromosporine. These molecules target Bromodomain and Extra Terminal domain (BET) proteins, which are epigenetic readers of acetylated histone lysine tail residues. BETi-mediated anti-myogenic effects were also observed in a model of MYOD1-mediated myogenic conversion of human fibroblasts, and in primary mouse and human myoblasts. All three BET proteins BRD2, BRD3 and BRD4 exhibited distinct and dynamic patterns of protein expression over the course of differentiation without concomitant changes in mRNA levels, suggesting that BET proteins are regulated at the post-transcriptional level. Specific BET protein knockdown by RNA interference revealed that BRD4 was required for myogenic differentiation, whereas BRD3 down-regulation resulted in enhanced myogenic differentiation. ChIP experiments revealed a preferential binding of BRD4 to theMyogpromoter during C2C12 myoblast differentiation, co-incident with increased levels of H3K27 acetylation. These results have identified an essential role for BET proteins in the regulation of skeletal myogenesis, and assign distinct functions to BRD3 and BRD4.
Physiological and transcriptome analysis of He-Ne laser pretreated wheat seedlings in response to drought stress
Authors: Qiu Zongbo , Yuan Mengmeng , He Yanyan , Li Yongfang , Zhang Liang 
Published: July 2017

AbstractDrought stress is a serious problem worldwide that reduces crop productivity. The laser has been shown to play a positive physiological role in enhancing plant seedlings tolerance to various abiotic stresses. However, little information is available about the molecular mechanism of He-Ne laser irradiation induced physiological changes for wheat adapting to drought conditions. Here, we performed a large-scale transcriptome sequencing to determine the molecular roles of He-Ne laser pretreated wheat seedlings under drought stress. There were 98.822 transcripts identified, and, among them, 820 transcripts were found to be differentially expressed in He-Ne laser pretreated wheat seedlings under drought stress compared with drought stress alone. Furthermore, most representative transcripts related to photosynthesis, nutrient uptake and transport, homeostasis control of reactive oxygen species and transcriptional regulation were expressed predominantly in He-Ne laser pretreated wheat seedlings. Thus, the up-regulated physiological processes of photosynthesis, antioxidation and osmotic accumulation because of the modified expressions of the related genes could contribute to the enhanced drought tolerance induced by He-Ne laser pretreatment. These findings will expand our understanding of the complex molecular events associated with drought tolerance conferred by laser irradiation in wheat and provide abundant genetic resources for future studies on plant adaptability to environmental stresses.
Skin renewal activity of non-thermal plasma through the activation of β-catenin in keratinocytes
Authors: Choi J. H. , Song Y. S. , Song K. , Lee H. J. , Hong J. W. , Kim G. C. 
Published: July 2017

AbstractFor recent years, devices that generate non-thermal plasma (NTP) have been introduced into the field of dermatology. Since NTP has demonstrated strong anti-pathogenic activity with safety of use, NTP was first applied to sterilize the skin surface to aid in the healing of various kinds of skin diseases. However, the effect of NTP on skin regeneration has not yet been fully explored. In this study, the effect of NTP on the growth of keratinocytes was tested using the HaCaT human keratinocyte cell line and HRM2 hairless mice. Treatment with NTP allowed confluent keratinocytes to escape from G1 cell cycle arrest and increased the proportion of cells in S and G2 phases. In particular, NTP treatment immediately dispersed E-cadherin-mediated cell-to-cell interactions, resulting in the translocation of β-catenin to the nucleus and leading to the enhanced transcription of target genes including c-MYC and cyclin D1. Moreover, repeated treatment of the mice with NTP also stimulated epidermal expansion by activating β-catenin in the epidermal cells. The symptoms of cellular DNA damage were not detected after NTP treatment. Taken together, these results demonstrate that NTP may be employed as a new type of skin regenerating device.
Language Assessment With Children Who Speak Nonmainstream Dialects: Examining the Effects of Scoring Modifications in Norm-Referenced Assessment
Authors: Hendricks Alison Eisel , Adlof Suzanne M. 
Published: July 2017

Purpose
We compared outcomes from 2 measures of language ability in children who displayed a range of dialect variation: 1 using features that do not contrast between mainstream American English (MAE) and nonmainstream dialects (NMAE), and 1 using contrastive features. We investigated how modified scoring procedures affected the diagnostic accuracy of the measure with contrastive features.

Method

Second-grade students (
N
= 299; 167 White, 106 African American, 26 other) completed measures of language variation and ability (the Diagnostic Evaluation of Language Variation–Screening Test and the Clinical Evaluation of Language Fundamentals–Fourth Edition [CELF-4]). The CELF-4 was scored with and without the recommended scoring modifications for children who spoke African American English.

Results
Partial correlations controlling for socioeconomic status revealed small to moderate correlations between measures of language ability and the use of NMAE features. Modified scoring yielded higher scores for children who spoke African American English and a reduced association between the use of NMAE features and CELF-4 scores. Modified scoring also affected the diagnostic accuracy of the CELF-4, resulting in a lower positive likelihood ratio and a higher negative likelihood ratio.

Conclusions
The decision to apply scoring modifications affects both the false positive and false negative rates. Implications for language assessment for children who speak NMAE dialects are discussed, including the need for further investigation.
A subtle cartography
Authors: Grafton Janet 
Published: July 2017

Abstract
The shift from rural to urban is mapped out in fiction, providing crucial reference points in environmental and cultural history. The old-fashioned worlds depicted in L.M. Montgomery’s Jane of Lantern Hill and Dorothy Canfield Fisher’s Understood Betsy are mapped not visually but verbally, conveying a strong sense of place that roots the characters with an intrinsic cartography. In this chapter, the author applies ecocriticism to fiction from the past to explore how personal geography and physical geography are entwined and informed by the other. The author analyzes the ways in which substantial and experiential contact with the land helps the protagonists develop their geographic literacy.
Metaphorical maps in picturebooks
Authors: Kümmerling-Meibauer Bettina , Meibauer Jörg 
Published: July 2017

Abstract
This chapter focuses on the cognitive and narrative functions of metaphorical maps in picturebooks. In contrast to maps that present real or fictional city- and landscapes, metaphorical maps are used to visualize abstract concepts. In particular, two types of metaphorical maps in picturebooks are distinguished: maps of (existing) cities and countries that are shaped like animals and humans, and entities such as the heart and the brain that are structured like maps. In order to understand this map category, children have to develop a basic knowledge of the symbols and functions of maps in general, and to learn that metaphorical maps are imaginative guides which symbolize specific patterns of thinking.
Bruno Munari’s visual mapping of the city of Milan
Authors: Campagnaro Marnie 
Published: July 2017

Abstract
Bruno Munari was one of the most pioneering and ingenious thinkers of the twentieth century. Pablo Picasso called him “the new Leonardo” and Pierre Restany “the Leonardo and the Peter Pan of Italian design.” During his long career as an artist and a designer, Bruno Munari achieved a special bond with the infant universe. He explored the area of visual narration in children’s literature with sublime results. Munari’s witty picturebooks pay special attention to young readers’ capacity to organize and orientate their reading experience by means of visible and invisible details. This chapter examines the picturebook Nella nebbia di Milano (The Circus in the Mist, 1968). The aim of the chapter is to provide an overview of Munari’s original approach and of his capacity to visualize and map places in children’s everyday lives.
Mapping Middle Earth
Authors: Sundmark Björn 
Published: July 2017

Abstract
In this chapter, J. R. R. Tolkien’s fantasy maps in The Hobbit (1937) and The Lord of the Rings (1954–55) are assessed and analyzed. The analysis shows that the five maps – two in The Hobbit and three in The Lord of the Rings – are less uniform than one would assume. It is also clear that the maps in The Hobbit represent a more child-oriented aesthetics than in the latter work. A few examples are then given of how Tolkien’s maps have influenced subsequent writers of fantasy. Finally, it is demonstrated how the Tolkienian fantasy map is transformed when it is moved from the printed page to the screen.