bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Unmistakeable Sauerkrauts’: Local Perceptions of Itinerant German Musicians in New Zealand, 1850–1920
Authors: Owens Samantha
Published: February 2017

Although largely forgotten today, bands of German musicians (generally from the Westpfalz region) were regular visitors to New Zealand’s shores from the 1850s up until the outbreak of World War I, making them among the earliest professional European musical ensembles to be heard in the country. Plying their trade on the streets and in other public spaces, German bands were also routinely hired to perform for garden parties, school sports days, dances and boat trips, as well as on countless other occasions. Yet despite their apparent popularity, contemporary comment published in newspapers of the day demonstrates that reactions to their performances were decidedly mixed. While some members of the public clearly enjoyed the contribution German bands made to local musical life, others were less than delighted by their (often noisy) presence. In 1893, for example, one Wellington resident complained that ‘a German Band … may be heard braying at every street corner at all hours of the day and night’, while noting also that ‘It is the genuine article, all the performers being wanderers from the “Vaterland”, unmistakeable “sauerkrauts”’ Within weeks of the outbreak of World War I, ten members of a German band had been arrested in Auckland and taken to Somes Island in Wellington harbour, where they were interned for the duration of the conflict. This article examines the New Zealand public’s changing perceptions of this particular brand of street musician from colonial times until shortly after the end of the First World War.
From Music to Noise: The Decline of Street Music
Authors: Johnson Bruce
Published: February 2017

The history of live street music is the history of an endangered species, either suppressed or trivialized as little more than ‘local colour’. Five hundred years ago the streets of Elizabethan London were rich with the sounds of street vendors, ballad-makers and musicians, and in general the worst that might be said of the music was that the same songs were too often repeated – what we would now call ‘on high rotation’. By the beginning of the nineteenth century, the poet Wordsworth and advocate of the ‘common man’ was describing street music as ‘monstrous’, and throughout that century vigorous measures were being applied to suppress such sounds, which were now categorized as noise. By the twenty-first century, live street music has been virtually silenced but for the occasional licensed busker or sanctioned parade. Paradoxically, this process of decline is intersected by a technologically sustained ‘aural renaissance’ that can be dated from the late nineteenth century. This article explores the reasons for the gradual extinction of live street music and the transformation of the urban soundscape. It argues connections with issues of class, the rise of literacy, the sacralization of private property and the formation of the politics of modernity.
Experiences of Burmese Chin Refugee Women: Trauma and Survival From Pre- to Postflight
Authors: Alexander Achu Johnson , Arnett Jeffrey Jensen , Jena S. P. K.
Published: February 2017

Since 1988, persecuted people primarily from the Chin state in Burma have fled into India due to large-scale human rights violations. A qualitative study was conducted to understand the narratives of 5 Burmese Chin refugee women retrospectively. Using their drawings as a stimulus, an unstructured interview was employed to help participants recall their life trajectories across 4 temporal periods: (a) preflight, (b) experience of traumatic events, (c) experience of flight, and (d) present status. Results highlighted 2 main concepts—systemic gender inequalities and hope. Participants’ gender-specific experiences of inequalities during their trauma in Burma and postdisplacement lives in India were a result of masculinized ideological frameworks of institutions such as the Burmese military and the Indian police. Simultaneously, they described a sense of hope to return to their home country and work toward its development while also desiring a sense of self-sufficiency through the Burmese model of family economy. Additionally, their means of hope was evident in their continued faith in God. Findings merit the attention of UN High Commissioner for Refugees (UNHCR), local nongovernmental organizations, policymakers, and government officials in India for proposing gender-specific policies and suggesting initiatives for psychosocial issues related to women refugees’ employment opportunities, vulnerability to sexual abuse, and local xenophobic sentiments in India.
Bystander effects elicited by single-cell photo-oxidative blue-light stimulation in retinal pigment epithelium cell networks
Authors: Ishii Masaaki , Rohrer Bärbel
Published: February 2017

‘Bystander effect’ refers to the induction of biological effects in cells not directly targeted. The retinal pigment epithelium consists of hexagonal cells, forming a monolayer interconnected by gap junctions (GJs). Oxidative stress initiated in an individual cell by photostimulation (488 nm) triggered changes in reactive oxygen species (ROS), Ca2+ and mitochondrial membrane potential (ψm). The Ca2+ signal was transmitted to neighboring cells slowly and non-uniformly; the ROS signal spread fast and radially. Increased Ca2+ levels were associated with a loss in ψm. GJ blockers prevented the spreading of the Ca2+, but not the ROS-related signal. The GJ-mediated Ca2+ wave was associated with cell death by 24 h, requiring endoplasmic reticulum–mitochondria Ca2+ transfer. Ensuing cell death was correlated with baseline Ca2+ levels, and baseline Ca2+ levels were correlated with pigmentation. Hence, local oxidative stress in a donor cell can trigger changes in certain connected recipient cells, a signal that required GJ communication and an ROS-Ca2+ dual-hit. Finally, damage apparently occurred in susceptible cells, which correlated with baseline Ca2+ levels.
The ancient CYP716 family is a major contributor to the diversification of eudicot triterpenoid biosynthesis
Authors: Miettinen Karel , Pollier Jacob , Buyst Dieter , Arendt Philipp , Csuk René , Sommerwerk Sven , Moses Tessa , Mertens Jan , Sonawane Prashant D , Pauwels Laurens , Aharoni Asaph , Martins José , Nelson David R. , Goossens Alain
Published: February 2017

Triterpenoids are widespread bioactive plant defence compounds with potential use as pharmaceuticals, pesticides and other high-value products. Enzymes belonging to the cytochrome P450 family have an essential role in creating the immense structural diversity of triterpenoids across the plant kingdom. However, for many triterpenoid oxidation reactions, the corresponding enzyme remains unknown. Here we characterize CYP716 enzymes from different medicinal plant species by heterologous expression in engineered yeasts and report ten hitherto unreported triterpenoid oxidation activities, including a cyclization reaction, leading to a triterpenoid lactone. Kingdom-wide phylogenetic analysis of over 400 CYP716s from over 200 plant species reveals details of their evolution and suggests that in eudicots the CYP716s evolved specifically towards triterpenoid biosynthesis. Our findings underscore the great potential of CYP716s as a source for generating triterpenoid structural diversity and expand the toolbox available for synthetic biology programmes for sustainable production of bioactive plant triterpenoids.
Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
Authors: Law Philip J. , Berndt Sonja I. , Speedy Helen E. , Camp Nicola J. , Sava Georgina P. , Skibola Christine F. , Holroyd Amy , Joseph Vijai , Sunter Nicola J. , Nieters Alexandra , Bea Silvia , Monnereau Alain , Martin-Garcia David , Goldin Lynn R. , Clot Guillem , Teras Lauren R. , Quintela Inés , Birmann Brenda M. , Jayne Sandrine , Cozen Wendy , Majid Aneela , Smedby Karin E. , Lan Qing , Dearden Claire , Brooks-Wilson Angela R. , Hall Andrew G. , Purdue Mark P. , Mainou-Fowler Tryfonia , Vajdic Claire M. , Jackson Graham H. , Cocco Pierluigi , Marr Helen , Zhang Yawei , Zheng Tongzhang , Giles Graham G. , Lawrence Charles , Call Timothy G. , Liebow Mark , Melbye Mads , Glimelius Bengt , Mansouri Larry , Glenn Martha , Curtin Karen , Diver W Ryan , Link Brian K. , Conde Lucia , Bracci Paige M. , Holly Elizabeth A. , Jackson Rebecca D. , Tinker Lesley F. , Benavente Yolanda , Boffetta Paolo , Brennan Paul , Maynadie Marc , McKay James , Albanes Demetrius , Weinstein Stephanie , Wang Zhaoming , Caporaso Neil E. , Morton Lindsay M. , Severson Richard K. , Riboli Elio , Vineis Paolo , Vermeulen Roel C. H. , Southey Melissa C. , Milne Roger L. , Clavel Jacqueline , Topka Sabine , Spinelli John J. , Kraft Peter , Ennas Maria Grazia , Summerfield Geoffrey , Ferri Giovanni M. , Harris Robert J. , Miligi Lucia , Pettitt Andrew R. , North Kari E. , Allsup David J. , Fraumeni Joseph F. , Bailey James R. , Offit Kenneth , Pratt Guy , Hjalgrim Henrik , Pepper Chris , Chanock Stephen J. , Fegan Chris , Rosenquist Richard , de Sanjose Silvia , Carracedo Angel , Dyer Martin J. S. , Catovsky Daniel , Campo Elias , Cerhan James R. , Allan James M. , Rothman Nathanial , Houlston Richard , Slager Susan
Published: February 2017

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223,P=5.04 × 10−13), 1q42.13 (rs41271473,P=1.06 × 10−10), 4q24 (rs71597109,P=1.37 × 10−10), 4q35.1 (rs57214277,P=3.69 × 10−8), 6p21.31 (rs3800461,P=1.97 × 10−8), 11q23.2 (rs61904987,P=2.64 × 10−11), 18q21.1 (rs1036935,P=3.27 × 10−8), 19p13.3 (rs7254272,P=4.67 × 10−8) and 22q13.33 (rs140522,P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis
Authors: Mor-Vaknin Nirit , Saha Anjan , Legendre Maureen , Carmona-Rivera Carmelo , Amin M Asif , Rabquer Bradley J. , Gonzales-Hernandez Marta J. , Jorns Julie , Mohan Smriti , Yalavarthi Srilakshmi , Pai Dave A. , Angevine Kristine , Almburg Shelley J. , Knight Jason S. , Adams Barbara S. , Koch Alisa E. , Fox David A. , Engelke David R. , Kaplan Mariana J. , Markovitz David M.
Published: February 2017

Novel therapeutics are required for improving the management of chronic inflammatory diseases. Aptamers are single-stranded RNA or DNA molecules that have recently shown utility in a clinical setting, as they can specifically neutralize biomedically relevant proteins, particularly cell surface and extracellular proteins. The nuclear chromatin protein DEK is a secreted chemoattractant that is abundant in the synovia of patients with juvenile idiopathic arthritis (JIA). Here, we show that DEK is crucial to the development of arthritis in mouse models, thus making it an appropriate target for aptamer-based therapy. Genetic depletion of DEK or treatment with DEK-targeted aptamers significantly reduces joint inflammation in vivo and greatly impairs the ability of neutrophils to form neutrophil extracellular traps (NETs). DEK is detected in spontaneously forming NETs from JIA patient synovial neutrophils, and DEK-targeted aptamers reduce NET formation. DEK is thus key to joint inflammation, and anti-DEK aptamers hold promise for the treatment of JIA and other types of arthritis.
mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases
Authors: Palmieri Michela , Pal Rituraj , Nelvagal Hemanth R. , Lotfi Parisa , Stinnett Gary R. , Seymour Michelle L. , Chaudhury Arindam , Bajaj Lakshya , Bondar Vitaliy V. , Bremner Laura , Saleem Usama , Tse Dennis Y. , Sanagasetti Deepthi , Wu Samuel M. , Neilson Joel R. , Pereira Fred A. , Pautler Robia G. , Rodney George G. , Cooper Jonathan D. , Sardiello Marco
Published: February 2017

Neurodegenerative diseases characterized by aberrant accumulation of undigested cellular components represent unmet medical conditions for which the identification of actionable targets is urgently needed. Here we identify a pharmacologically actionable pathway that controls cellular clearance via Akt modulation of transcription factor EB (TFEB), a master regulator of lysosomal pathways. We show that Akt phosphorylates TFEB at Ser467 and represses TFEB nuclear translocation independently of mechanistic target of rapamycin complex 1 (mTORC1), a known TFEB inhibitor. The autophagy enhancer trehalose activates TFEB by diminishing Akt activity. Administration of trehalose to a mouse model of Batten disease, a prototypical neurodegenerative disease presenting with intralysosomal storage, enhances clearance of proteolipid aggregates, reduces neuropathology and prolongs survival of diseased mice. Pharmacological inhibition of Akt promotes cellular clearance in cells from patients with a variety of lysosomal diseases, thus suggesting broad applicability of this approach. These findings open new perspectives for the clinical translation of TFEB-mediated enhancement of cellular clearance in neurodegenerative storage diseases.
Axon degeneration induces glial responses through Draper-TRAF4-JNK signalling
Authors: Lu Tsai-Yi , MacDonald Jennifer M. , Neukomm Lukas J. , Sheehan Amy E. , Bradshaw Rachel , Logan Mary A. , Freeman Marc R.
Published: February 2017

Draper/Ced-1/MEGF-10 is an engulfment receptor that promotes clearance of cellular debris in C. elegans, Drosophila and mammals. Draper signals through an evolutionarily conserved Src family kinase cascade to drive cytoskeletal rearrangements and target engulfment through Rac1. Glia also alter gene expression patterns in response to axonal injury but pathways mediating these responses are poorly defined. We show Draper is cell autonomously required for glial activation of transcriptional reporters after axonal injury. We identify TNF receptor associated factor 4 (TRAF4) as a novel Draper binding partner that is required for reporter activation and phagocytosis of axonal debris. TRAF4 and misshapen (MSN) act downstream of Draper to activate c-Jun N-terminal kinase (JNK) signalling in glia, resulting in changes in transcriptional reporters that are dependent on Drosophila AP-1 (dAP-1) and STAT92E. Our data argue injury signals received by Draper at the membrane are important regulators of downstream transcriptional responses in reactive glia.
Structure of the homodimeric androgen receptor ligand-binding domain
Authors: Nadal Marta , Prekovic Stefan , Gallastegui Nerea , Helsen Christine , Abella Montserrat , Zielinska Karolina , Gay Marina , Vilaseca Marta , Taulès Marta , Houtsmuller Adriaan B. , van Royen Martin E. , Claessens Frank , Fuentes-Prior Pablo , Estébanez-Perpiñá Eva
Published: February 2017

The androgen receptor (AR) plays a crucial role in normal physiology, development and metabolism as well as in the aetiology and treatment of diverse pathologies such as androgen insensitivity syndromes (AIS), male infertility and prostate cancer (PCa). Here we show that dimerization of AR ligand-binding domain (LBD) is induced by receptor agonists but not by antagonists. The 2.15-Å crystal structure of homodimeric, agonist- and coactivator peptide-bound AR-LBD unveils a 1,000-Å2 large dimerization surface, which harbours over 40 previously unexplained AIS- and PCa-associated point mutations. An AIS mutation in the self-association interface (P767A) disrupts dimer formation in vivo, and has a detrimental effect on the transactivating properties of full-length AR, despite retained hormone-binding capacity. The conservation of essential residues suggests that the unveiled dimerization mechanism might be shared by other nuclear receptors. Our work defines AR-LBD homodimerization as an essential step in the proper functioning of this important transcription factor.
Personality and Augmenting/Reducing (A/R) in auditory event-related potentials (ERPs) during emotional visual stimulation
Authors: De Pascalis Vilfredo , Fracasso Francesca , Corr Philip J.
Published: February 2017

An auditory augmenting/reducing ERP paradigm recorded for 5 intensity tones with emotional visual stimulation was used, for the first time, to test predictions derived from the revised Reinforcement Sensitivity Theory (rRST) of personality with respect to two major factors: behavioral inhibition system (BIS), fight/flight/freeze system (FFFS). Higher BIS and FFFS scores were negatively correlated with N1/P2 slopes at central sites (C3, Cz, C4). Conditional process analysis revealed that the BIS was a mediator of the association between the N1/P2 slope and the FFFS scores. An analysis of covariance showed that lower BIS scorers exhibited larger N1/P2 amplitudes across all tone intensities while watching negative, positive and neutral pictures. Additionally, lower FFFS scorers compared to higher FFFS scorers disclosed larger N1/P2 amplitudes to the highest tone intensities and these differences were even more pronounced while watching positive emotional pictures. Findings were explained assuming the operation of two different, but related processes: transmarginal inhibition for the BIS; the attention/emotional gating mechanism regulating cortical sensory input for the FFFS trait. These findings appear consistent with predictions derived from the rRST, which traced fear and anxiety to separate but interacting neurobehavioural systems.
Genome-wide indel/SSR scanning reveals significant loci associated with excellent agronomic traits of a cabbage (Brassica oleracea) elite parental line ‘01–20’
Authors: Lv Honghao , Wang Qingbiao , Han Fengqing , Liu Xing , Fang Zhiyuan , Yang Limei , Zhuang Mu , Liu Yumei , Li Zhansheng , Zhang Yangyong
Published: February 2017

Elite parental lines are of great significance to crop breeding. To discover unique genomic loci associated with excellent economic traits in the elite cabbage inbred-line ‘01–20’, we performed comparisons of phenotypes as well as whole-genome insertion-deletion/simple sequence repeat loci between ‘01–20’ and each of its five sister lines. ‘01–20’ has a range of excellent agronomic traits, including early-maturing, and improvements in plant type and leaf colour. Eight unique loci were discovered for ‘01–20’ and ‘01-07-258’, another elite line similar to ‘01–20’ at the whole-genome level. In addition, two excellent double-haploid lines derived from a cross of ‘01–20’ also inherited these loci. Based on the quantitative trait locus association results, five of these loci were found to be associated with important agronomic traits, which could explain why the elite parent ‘01–20’ possesses greener outer leaves, a more compact and upright plant-type, rounder head, shorter core length, and better taste. Additionally, some of these loci have clustering effects for quantitative trait loci associated with different traits; therefore, important genes in these regions were analysed. The obtained results should enable marker-assisted multi-trait selection at the whole-genome level in cabbage breeding and provide insights into significant genome loci and their breeding effects.
Generation of PDGFRα+ Cardioblasts from Pluripotent Stem Cells
Authors: Hong Seon Pyo , Song Sukhyun , Cho Sung Woo , Lee Seungjoo , Koh Bong Ihn , Bae Hosung , Kim Kyun Hoo , Park Jin-Sung , Do Hyo-Sang , Im Ilkyun , Heo Hye Jin , Ko Tae Hee , Park Jae-Hyeong , Youm Jae Boum , Kim Seong-Jin , Kim Injune , Han Jin , Han Yong-Mahn , Koh Gou Young
Published: February 2017

Isolating actively proliferating cardioblasts is the first crucial step for cardiac regeneration through cell implantation. However, the origin and identity of putative cardioblasts are still unclear. Here, we uncover a novel class of cardiac lineage cells, PDGFRα+Flk1− cardioblasts (PCBs), from mouse and human pluripotent stem cells induced using CsAYTE, a combination of the small molecules Cyclosporin A, the rho-associated coiled-coil kinase inhibitor Y27632, the antioxidant Trolox, and the ALK5 inhibitor EW7197. This novel population of actively proliferating cells is cardiac lineage–committed but in a morphologically and functionally immature state compared to mature cardiomyocytes. Most important, most of CsAYTE-induced PCBs spontaneously differentiated into functional αMHC+ cardiomyocytes (M+CMs) and could be a potential cellular resource for cardiac regeneration.
Limb proportions show developmental plasticity in response to embryo movement
Authors: Pollard A. S. , Charlton B. G. , Hutchinson J. R. , Gustafsson T. , McGonnell I. M. , Timmons J. A. , Pitsillides A. A.
Published: February 2017

Animals have evolved limb proportions adapted to different environments, but it is not yet clear to what extent these proportions are directly influenced by the environment during prenatal development. The developing skeleton experiences mechanical loading resulting from embryo movement. We tested the hypothesis that environmentally-induced changes in prenatal movement influence embryonic limb growth to alter proportions. We show that incubation temperature influences motility and limb bone growth in West African Dwarf crocodiles, producing altered limb proportions which may, influence post-hatching performance. Pharmacological immobilisation of embryonic chickens revealed that altered motility, independent of temperature, may underpin this growth regulation. Use of the chick also allowed us to merge histological, immunochemical and cell proliferation labelling studies to evaluate changes in growth plate organisation, and unbiased array profiling to identify specific cellular and transcriptional targets of embryo movement. This disclosed that movement alters limb proportions and regulates chondrocyte proliferation in only specific growth plates. This selective targeting is related to intrinsic mTOR (mechanistic target of rapamycin) pathway activity in individual growth plates. Our findings provide new insights into how environmental factors can be integrated to influence cellular activity in growing bones and ultimately gross limb morphology, to generate phenotypic variation during prenatal development.
Novel Treatment of Chronic Graft-Versus-Host Disease in Mice Using the ER Stress Reducer 4-Phenylbutyric Acid
Authors: Mukai Shin , Ogawa Yoko , Urano Fumihiko , Kudo-Saito Chie , Kawakami Yutaka , Tsubota Kazuo
Published: February 2017

Chronic graft-versus-host disease (cGVHD) is a notorious complication of allogeneic hematopoietic stem cell transplantation and causes disabling systemic inflammation and fibrosis. In this novel study, we focused on a relationship between endoplasmic reticulum (ER) stress and cGVHD, and aimed to create effective treatment of cGVHD. A series of experiments were conducted using a mouse model of cGVHD. Our data suggested (1) that ER stress was elevated in organs affected by cGVHD and (2) that 4-phenylbutyric acid (PBA) could reduce cGVHD-induced ER stress and thereby alleviate systemic inflammation and fibrosis. Because fibroblasts are thought to be implicated in cGVHD-elicited fibrosis and because macrophages are reported to play a role in the development of cGVHD, we investigated cGVHD-triggered ER stress in fibroblasts and macrophages. Our investigation demonstrated (1) that indicators for ER stress and activation markers for fibroblasts were elevated in cGVHD-affected lacrimal gland fibroblasts and (2) that they could be reduced by PBA. Our work also indicated that splenic macrophages from PBA-dosed mice exhibited the lower levels of ER stress and M2 macrophage markers than those from cGVHD-affected mice. Collectively, this study suggests that the reduction of ER stress utilizing PBA can be a clinically translatable method to treat systemic cGVHD.
MicroRNA-130b targets PTEN to mediate drug resistance and proliferation of breast cancer cells via the PI3K/Akt signaling pathway
Authors: Miao Yuan , Zheng Wei , Li Nana , Su Zhen , Zhao Lifen , Zhou Huimin , Jia Li
Published: February 2017

Multidrug resistance (MDR) correlates with treatment failure and poor prognosis among breast cancer patients. This study was aimed to investigate the possible mechanism by which microRNA-130b-3p (miR-130b) mediates the chemoresistance and proliferation of breast cancer. MiR-130b was found to be up-regulated in tumor tissues versus adjacent tissues of breast cancer, as well as in adriamycin (ADR) resistant breast cancer cell line (MCF-7/ADR) versus its parental line (MCF-7) and the non-malignant breast epithelial cell line (MCF-10A), demonstrating its crucial relevance for breast cancer biology. We identified that PTEN was a direct target of miR-130b and inversely correlated with miR-130b expression in breast cancer. Moreover, over-expression of miR-130b promoted drug resistance, proliferation and decreased apoptosis of MCF-7 cells, while suppression of miR-130b enhanced drug cytotoxicity and apoptosis, as well as reduced proliferation of MCF-7/ADR cells in vitro and in vivo. Particularly, miR-130b mediated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway as well as the chemoresistance and proliferation of breast cancer cell lines, which was partially blocked following knockdown of PTEN. Altogether, miR-130b targets PTEN to induce MDR, proliferation, and apoptosis via PI3K/Akt signaling pathway. This provides a novel promising candidate for breast cancer therapy.
Structural analysis and evolution of specificity of the SUMO UFD E1-E2 interactions
Authors: Liu Bing , Lois L. Maria , Reverter David
Published: February 2017

SUMO belongs to the ubiquitin-like family (UbL) of protein modifiers. SUMO is conserved among eukaryotes and is essential for the regulation of processes such as DNA damage repair, transcription, DNA replication and mitosis. UbL modification of proteins occurs via a specific enzymatic cascade formed by the crosstalk between the E1-activating enzyme, the E2-conjugating enzyme and the E3-ligase. An essential discrimination step in all UbL modifiers corresponds to the interaction between E1 and E2 enzymes, which is mediated by the recruitment of the E2 to the UFD domain (Ubiquitin-Fold Domain) of the E1 enzyme. To gain insights in the properties of this interface, we have compared the structures of the complexes between E1 UFD domain and E2 in human and yeast, revealing two alternative UFD platforms that interact with a conserved E2. Comparative sequence analysis of the E1 UFD domain indicates that the E2 binding region has been conserved across phylogenetic closely related species, in which higher sequence conservation can be found in the E2 binding region than in the entire UFD domain. These distinctive strategies for E1-E2 interactions through the UFD domain might be the consequence of a high selective pressure to ensure specificity of each modifier conjugation system.
A potent synthetic inorganic antibiotic with activity against drug-resistant pathogens
Authors: Hubick Shelby , Jayaraman Arumugam , McKeen Alexander , Reid Shelby , Alcorn Jane , Stavrinides John , Sterenberg Brian T.
Published: February 2017

The acronymously named “ESKAPE” pathogens represent a group of bacteria that continue to pose a serious threat to human health, not only due to their propensity for repeated emergence, but also due to their ability to “eskape” antibiotic treatment1,2. The evolution of multi-drug resistance in these pathogens alone has greatly outpaced the development of new therapeutics, necessitating an alternative strategy for antibiotic development that considers the evolutionary mechanisms driving antibiotic resistance. In this study, we synthesize a novel inorganic antibiotic, phosphopyricin, which has antibiotic activity against the Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). We show that this potent antibiotic is bactericidal, and exhibits low toxicity in an acute dose assay in mice. As a synthetic compound that does not occur naturally, phosphopyricin would be evolutionarily foreign to microbes, thereby slowing the evolution of resistance. In addition, it loses antibiotic activity upon exposure to light, meaning that the active antibiotic will not accumulate in the general environment where strong selective pressures imposed by antibiotic residuals are known to accelerate resistance. Phosphopyricin represents an innovation in antimicrobials, having a synthetic core, and a photosensitive chemical architecture that would reduce accumulation in the environment.
Relevance of mortalin to cancer cell stemness and cancer therapy
Authors: Yun Chae-Ok , Bhargava Priyanshu , Na Youjin , Lee Jung-Sun , Ryu Jihoon , Kaul Sunil C. , Wadhwa Renu
Published: February 2017

Mortalin/mtHsp70 is a member of Hsp70 family of proteins. Enriched in a large variety of cancers, it has been shown to contribute to the process of carcinogenesis by multiple ways including inactivation of tumor suppressor p53 protein, deregulation of apoptosis and activation of EMT signaling. In this study, we report that upregulation of mortalin contributes to cancer cell stemness. Several cancer cell stemness markers, such as ABCG2, OCT-4, CD133, ALDH1, CD9, MRP1 and connexin were upregulated in mortalin-overexpressing cells that showed higher ability to form spheroids. These cells also showed higher migration, and were less responsive to a variety of cancer chemotherapeutic drugs. Of note, knockdown of mortalin by specific shRNA sensitized these cells to all the drugs used in this study. We report that low doses of anti-mortalin molecules, MKT-077 and CAPE, also caused similar sensitization of cancer cells to chemotherapeutic drugs and hence are potential candidates for effective cancer chemotherapy.
Recombinant Phage Elicits Protective Immune Response against Systemic S. globosa Infection in Mouse Model
Authors: Chen Feng , Jiang Rihua , Wang Yicun , Zhu Mingji , Zhang Xu , Dong Shuai , Shi Hongxi , Wang Li
Published: February 2017

Sporothrix globosa is a type of fungus that typically infects immunocompromised patients. Its prevention continues to pose a challenge. A 70-KDa glycoprotein (Gp70) of Sporothrix has been previously reported to protect host against infection from this fungus. Here, we displayed an epitope peptide (kpvqhalltplgldr) of Gp70 on the major coat protein (pIII), and investigated its efficiency as a vaccine for preventing S. globosa infection. The recombinant phage and the heat-killed S. globosa were used to immunize mice separately. In this study, we evaluated the humoral and cellular immune responses in the mice and demonstrated that recombinant phage could induce mice to produce a stronger immune response and generate antibodies to inhibit S. globosa infection. Furthermore, immunization with recombinant phage could increase the survival rate of S. globosa infection in mice. All these results together indicated that recombinant phages displaying kpvqhalltplgldr are a potential vaccine candidate against S. globosa infection.
Sediment biomarker, bacterial community characterization of high arsenic aquifers in Jianghan Plain, China
Authors: Ye Hengpeng , Yang Zeyu , Wu Xiang , Wang Jingwen , Du Dongyun , Cai Jian , Lv Kangle , Chen Huiyun , Mei Jingkun , Chen Mengqi , Du Hong
Published: February 2017

Representative biomarkers (e.g.,n-alkanes), diversity and microbial community in the aquifers contaminated by high concentration of arsenic (As) in different sediment depth (0–30 m) in Jianghan Plain, Hubei, China, were analyzed to investigate the potential mechanism of As enrichment in groundwater. The concentration of As was abundant in top soil and sand, but not in clay. The analysis of the distribution ofn-alkanes, CPI values, and wax to totaln-alkane ratio (Wax(n)%) indicated that the organic matter (OM) from fresh terrestrial plants were abundant in the shallow sediment. However,n-alkanes have suffered from significant biodegradation from the depth of 16 m to 30 m. The deposition of fresh terrestrial derived organic matters may facilitate the release of As from sediment to groundwater in the sediment of 0–16 m. However, the petroleum derived organic matters may do the favor to the release of As in the deeper section of borehole (16 m to 30 m). The 16S rRNA gene sequences identification indicated thatAcidobacteria, ActinomycetesandHydrogenophagaare abundant in the sediments with high arsenic. Therefore, microbes and organic matters from different sources may play important roles in arsenic mobilization in the aquifers of the study area.
Identification of two novel Rhizoctonia solani-inducible cis-acting elements in the promoter of the maize gene, GRMZM2G315431
Authors: Li Ning , Chen Jing , Yang Fangfang , Wei Shutong , Kong Lingguang , Ding Xinhua , Chu Zhaohui
Published: February 2017

Plants are continuously exposed to myriad pathogen stresses. However, the molecular mechanisms by which these stress signals are perceived and transduced are poorly understood. In this study, the maize gene GRMZM2G315431 was identified to be highly inducible by Rhizoctonia solani infection, suggesting that the promoter of GRMZM2G315431 (pGRMZM2G315431) might contain a specific cis-acting element responsive to R. solani attack. To identify the R. solani-responsive element in pGRMZM2G315431, a series of binary plant transformation vectors were constructed by fusing pGRMZM2G315431 or its deletion-derivatives with the reporter genes. In the transient gene expression system of Nicotiana benthamiana leaves inoculated with R. solani, GUS quantification suggested that the DNA fragment contains the unknown pathogen-inducible cis-elements in the −1323 to −1212 region. Furthermore, detailed quantitative assays showed that two novel cis-elements, GTTGA in the −1243 to −1239 region and TATTT in the −1232 to −1228 region, were responsible for the R. solani-inducible activity. These two cis-elements were also identified to have R. solani-specific-inducible activity in stable transgenic rice plants, suggesting the existence of a novel regulation mechanism involved in the interaction between R. solani and Zea mays.
Agreement of patient-measured intraocular pressure using rebound tonometry with Goldmann applanation tonometry (GAT) in glaucoma patients
Authors: Tan Shaoying , Yu Marco , Baig Nafees , Hansapinyo Linda , Tham Clement C.
Published: February 2017

This study aims to determine the agreement of patient-measured intraocular pressure (IOP) using rebound tonometry with ophthalmologist-measured IOP using Goldmann applanation tonometry (GAT). Fifty-three glaucoma patients used rebound tonometry (Icare ONE, Icare Finland Oy., Finland) to measure their own IOP in ambient environments for 1 week, 5 times per day. Clinic IOP measurements were performed by ophthalmologists using GAT and by patients using rebound tonometry on examination days 1, 4 and 7 of the same week. The agreement between the two tonometries was evaluated by modified Bland-Altman plots and intra-class correlation coefficient (ICC) was determined. Differences in ICCs of them among the three examination days were evaluated by bootstrap resampling analysis. Respective within-measurement ICC of GAT and rebound tonometry were 0.98 and 0.94 on Day 1, 0.98 and 0.93 on Day 4, and 0.96 and 0.92 on Day 7. In a modified Bland-Altman plot, the mean difference ±1 standard deviation (SD) between the two tonometries was 0.15 ± 0.65 mmHg (p = 0.682). Between-measurement ICC were 0.66, 0.76 and 0.73 on the 3 examination days. There was no significant difference among ICCs. In conclusion, patient-measured IOP using rebound tonometry and ophthalmologist-measured IOP using GAT demonstrate good agreement.
Material-assisted metamaterial: a new dimension to create functional metamaterial
Authors: Tsai Wei-Yi , Wang Chih-Ming , Chen Ching-Fu , Wu Pin Chieh , Chen Yi-Hao , Chen Ting-Yu , Wu Pei Ru , Chen Jia-Wern , Tsai Din Ping
Published: February 2017

A high Q-value reflective type metasurface consisting of 1D Au nanorods, a SiO2 spacer and a Au back reflector is demonstrated. It is shown that the sideband of the resonant mode can be suppressed as the resonant wavelength close to the phonon absorption of SiO2. By combining both designed structured resonance and inherent property of the based materials, a low angle-dependent metasurface with a Q-value of 40 has been demonstrated. The proposed structure will be useful for high sensitivity sensing and narrow band thermal emitter.
GPR155 Serves as a Predictive Biomarker for Hematogenous Metastasis in Patients with Gastric Cancer
Authors: Shimizu Dai , Kanda Mitsuro , Tanaka Haruyoshi , Kobayashi Daisuke , Tanaka Chie , Hayashi Masamichi , Iwata Naoki , Niwa Yukiko , Takami Hideki , Yamada Suguru , Fujii Tsutomu , Nakayama Goro , Fujiwara Michitaka , Kodera Yasuhiro
Published: February 2017

The prognosis of patients with gastric cancer (GC) with hematogenous metastasis is dismal. Identification of biomarkers specific for hematogenous metastasis is required to develop personalized treatments that improve patients’ outcomes. Global expression profiling of GC tissues with synchronous hepatic metastasis without metastasis to the peritoneal cavity or distant lymph nodes was conducted using next-generation sequencing and identified the G protein-coupled receptor 155 (GPR155) as a candidate biomarker. GPR155 transcription was suppressed in GC cell lines compared with a nontumorigenic cell line. DNA methylation of the GPR155 promoter region was not detected, albeit 20% of GC cell lines harbored copy number loss at GPR155 locus. The expression levels of GPR155 mRNA correlated inversely with those of TWIST1 and WNT5B. Inhibition of GPR155 expression increased the levels of p-ERK1/2 and p-STAT1, significantly increased cell proliferation, and increased the invasiveness of a GC cell lines. GPR155 mRNA levels in GC clinical samples correlated with hematogenous metastasis and recurrence. Multivariate analysis revealed that reduced expression of GPR155 mRNA was an independent predictive marker of hematogenous metastasis. GPR155 may represent a biomarker for diagnosing and predicting hematogenous metastasis of GC.
Role of E-type prostaglandin receptor EP3 in the vasoconstrictor activity evoked by prostacyclin in thromboxane-prostanoid receptor deficient mice
Authors: Li Zhenhua , Zhang Yingzhan , Liu Bin , Luo Wenhong , Li Hui , Zhou Yingbi
Published: February 2017

Prostacyclin, also termed as prostaglandin I2 (PGI2), evokes contraction in vessels with limited expression of the prostacyclin receptor. Although the thromboxane-prostanoid receptor (TP) is proposed to mediate such a response of PGI2, other unknown receptor(s) might also be involved. TP knockout (TP−/−) mice were thus designed and used to test the hypothesis. Vessels, which normally show contraction to PGI2, were isolated for functional and biochemical analyses. Here, we showed that the contractile response evoked by PGI2 was indeed only partially abolished in the abdominal aorta of TP−/− mice. Interestingly, further antagonizing the E-type prostaglandin receptor EP3 removed the remaining contractile activity, resulting in relaxation evoked by PGI2 in such vessels of TP−/− mice. These results suggest that EP3 along with TP contributes to vasoconstrictor responses evoked by PGI2, and hence imply a novel mechanism for endothelial cyclooxygenase metabolites (which consist mainly of PGI2) in regulating vascular functions.
Heavy Chain-Hyaluronan/Pentraxin 3 from Amniotic Membrane Suppresses Inflammation and Scarring in Murine Lacrimal Gland and Conjunctiva of Chronic Graft-versus-Host Disease
Authors: Ogawa Yoko , He Hua , Mukai Shin , Imada Toshihiro , Nakamura Shigeru , Su Chen-Wei , Mahabole Megha , Tseng Scheffer C. G. , Tsubota Kazuo
Published: February 2017

Chronic graft-versus-host disease (cGVHD) is a major complication of hematopoietic stem cell transplantation. Dry eye disease is the prominent ocular sequel of cGVHD and is caused by excessive inflammation and fibrosis in the lacrimal glands. Heavy chain-Hyaluronan/Pentraxin 3 (HC-HA/PTX3) is a complex purified from human amniotic membrane (AM) and known to exert anti-inflammatory and anti-scarring actions. In this study, we utilized a mouse model of cGVHD to examine whether HC-HA/PTX3 could attenuate dry eye disease elicited by cGVHD. Our results indicated that subconjunctival and subcutaneous injection of HC-HA/PTX3 preserved tear secretion and conjunctival goblet cell density and mitigated inflammation and scarring of the conjunctiva. Such therapeutic benefits were associated with suppression of scarring and infiltration of inflammatory/immune cells in the lacrimal glands. Furthermore, HC-HA/PTX3 significantly reduced the extent of infiltration of CD45+ CD4+ IL-17+ cells, CD45+ CD34+ collagen I+ CXCR4+ fibrocytes, and HSP47+ activated fibroblasts that were accompanied by upregulation of collagen type Iα1, collagen type IIIα1 and NF-kB in lacrimal glands. Collectively, these pre-clinical data help prove the concept that subcutaneous and subconjunctival injection of HC-HA/PTX3 is a novel approach to prevent dry eye disease caused by cGVHD and allow us to test its safety and efficacy in future human clinical trials.
Enhanced performance of sulfur-infiltrated bimodal mesoporous carbon foam by chemical solution deposition as cathode materials for lithium sulfur batteries
Authors: Jeong Tae-Gyung , Chun Jinyong , Cho Byung-Won , Lee Jinwoo , Kim Yong-Tae
Published: February 2017

The porous carbon matrix is widely recognized to be a promising sulfur reservoir to improve the cycle life by suppressing the polysulfide dissolution in lithium sulfur batteries (LSB). Herein, we synthesized mesocellular carbon foam (MSUF-C) with bimodal mesopore (4 and 30 nm) and large pore volume (1.72 cm2/g) using MSUF silica as a template and employed it as both the sulfur reservoir and the conductive agent in the sulfur cathode. Sulfur was uniformly infiltrated into MSUF-C pores by a chemical solution deposition method (MSUF-C/S CSD) and the amount of sulfur loading was achieved as high as 73% thanks to the large pore volume with the CSD approach. MSUF-C/S CSD showed a high capacity (889 mAh/g after 100 cycles at 0.2 C), an improved rate capability (879 mAh/g at 1C and 420 mAh/g at 2C), and a good capacity retention with a fade rate of 0.16% per cycle over 100 cycles.
High-throughput flowing upstream sperm sorting in a retarding flow field for human semen analysis
Authors: Wu Jen-Kuei , Chen Peng-Chun , Lin Yu-Nan , Wang Chia-Woei , Pan Li-Chern , Tseng Fan-Gang
Published: February 2017

In this paper, we propose a microfluidic device capable of generating a retarding flow field for the sorting and separation of human motile sperm in a high-throughput manner.
Hybrid methylammonium lead halide perovskite nanocrystals confined in gyroidal silica templates
Authors: Malgras Victor , Henzie Joel , Takei Toshiaki , Yamauchi Yusuke
Published: February 2017

We synthesized confined hybrid methylammonium lead halide nanocrystals in a gyroidal mesoporous silica template in order to provide high material diffusion and space for solvent escape.
How water mediates the long-range interactions between remote protein molecules
Authors: Kuffel Anna
Published: February 2017

A mechanism of the influence of the presence of one protein molecule on the internal dynamics of another is proposed.
Monodisperse polystyrene foams via polymerization of foamed emulsions: structure and mechanical properties
Authors: Elsing J. , Stefanov T. , Gilchrist M. D. , Stubenrauch C.
Published: February 2017

A study on how to control the pore size of polystyrene foams generated from foamed emulsion templates and their mechanical properties.
Transiently thermoresponsive polymers and their applications in biomedicine
Authors: Vanparijs Nane , Nuhn Lutz , De Geest Bruno G.
Published: February 2017

The focus of this review is on the class of transiently thermoresponsive polymers.
Synergistic effect between Pt0 and Bi2O3−x for efficient room-temperature alcohol oxidation under base-free aqueous conditions
Authors: Liu Juanjuan , Zou Shihui , Wang Hui , Xiao Liping , Zhao Hongting , Fan Jie
Published: February 2017

The synergistic effect between Pt0 and nearby partially reduced Bi2O3−x species was found to be efficient (conversion of 94.1 ± 2.7%, selectivity to aldehyde >99%) for benzyl alcohol oxidation at room temperature (26 °C) under base-free aqueous conditions.
Slow relaxation of the magnetization observed in an antiferromagnetically ordered phase for SCM-based two-dimensional layered compounds
Authors: Kagesawa Koichi , Nishimura Yuki , Yoshida Hiroki , Breedlove Brian K. , Yamashita Masahiro , Miyasaka Hitoshi
Published: February 2017

We showed 2D-layered compounds exhibiting SCM-like behavior in an AF ordered phase. By introducing counteranions with a different size, Néel temperature and spin-flip inversion field could be tuned.
Classification of baseline toxicants for QSAR predictions to replace fish acute toxicity studies
Authors: Nendza Monika , Müller Martin , Wenzel Andrea
Published: February 2017

Classification of baseline and excess toxicants to replace 50% of fish acute toxicity testing with reliable QSAR predictions.
Collagen peptides ameliorate intestinal epithelial barrier dysfunction in immunostimulatory Caco-2 cell monolayers via enhancing tight junctions
Authors: Chen Qianru , Chen Oliver , Martins Isabela M. , Hou Hu , Zhao Xue , Blumberg Jeffrey B. , Li Bafang
Published: February 2017

Alaska pollock skin derived collagen peptides could be considered as dietary supplements for intestinal barrier function promotion and associated diseases.
Accuracy improvement of quantitative LIBS analysis using wavelet threshold de-noising
Authors: Xie Shichen , Xu Tao , Han Xiaodan , Lin Qingyu , Duan Yixiang
Published: February 2017

Laser-induced breakdown spectroscopy (LIBS) is becoming a rapid and easy technique for quantitative elemental analysis.
Highly sensitive airflow sensors with an ultrathin reduced graphene oxide film inspired by gas exfoliation of graphite oxide
Authors: Xu Zeyang , Wu Kunjie , Zhang Suna , Meng Yancheng , Li Hongwei , Li Liqiang
Published: February 2017

A highly-sensitive, novel airflow sensor is demonstrated with an ultrathin reduced graphene oxide film with tunable interlayer gaps.
Extended cavity pyrene-based iptycenes for the turn-off fluorescence detection of RDX and common nitroaromatic explosives
Authors: Khasanov Albert F. , Kopchuk Dmitry S. , Kovalev Igor S. , Taniya Olga S. , Giri Kousik , Slepukhin Pavel A. , Santra Sougata , Rahman Matiur , Majee Adinath , Charushin Valery N. , Chupakhin Oleg N.
Published: February 2017

Extended cavity pyrene-based iptycenes were synthesized for the turn-off fluorescence detection of RDX and common nitro-aromatic explosives.
Factors affecting bottlebrush polymer synthesis by the transfer-to method using reversible addition–fragmentation chain transfer (RAFT) polymerization
Authors: Radzinski Scott C. , Foster Jeffrey C. , Lewis Sally E. , French Eric V. , Matson John B.
Published: February 2017

The transfer-to method is a unique way to prepare bottlebrush polymers by reversible addition–fragmentation chain transfer (RAFT) polymerization.
High-quality organohalide lead perovskite films fabricated by layer-by-layer alternating vacuum deposition for high efficiency photovoltaics
Authors: Tavakoli Mohammad Mahdi , Simchi Abdolreza , Mo Xiaoliang , Fan Zhiyong
Published: February 2017

Fabrication of efficient perovskite solar cells (with a high fill factor) using layer-by-layer alternating (LBLA) vacuum deposition with highly crystalline and uniform perovskite films.
Applicable β-sulfonium carbanions: facile construction of thiophene derivatives
Authors: Chen Dianpeng , Xing Gangdong , Yao Jinzhong , Zhou Hongwei
Published: February 2017

A sequence of Sonogashira coupling, propargyl-allenyl isomerization, intramolecular addition and [3, 3] sigmatropic rearrangement affords thiophene derivatives.
Selective deprotonation of tetra[3,4]thienylene in the presence of n-BuLi
Authors: Li Lu , Li Bingbing , Li Chunli , Ma Zhiying , Xu Li , Wang Hua
Published: February 2017

The sequential lithiation mechanism for the selective deprotonation of tetra[3,4]thienylene (1) to form Li4-1 in the present of n-BuLi in THF is investigated.