bluuebunny/crossref_metadata_2025 huggingface dataset:
A Discussion of Suzanne Mettler’s Degrees of Inequality: How the Politics of Higher Education Sabotaged the American Dream
Authors: McClain Paula D.
Published: June 2016

The discipline of political science in the United States evolved in tandem with the development of democratic education and the modern university system. Since the early years of the twentieth century, political science has been an academic discipline housed in universities and colleges, and most political scientists earn their living as university or college teachers. And yet as individual academics or as a discipline, we rarely stand back from our institutional environment and ask hard questions about what is happening with higher education and what this means for the practice of political science. Suzanne Mettler does precisely this in Degrees of Inequality: How Higher Education Politics Sabotaged the American Dream. And so we have invited a range of political science scholars, many with extensive experience as university leaders, to comment on her book and its implications for the future of political science.
A Discussion of Frank R. Baumgartner and Bryan D. Jones' The Politics of Information: Problem Definition and the Course of Public Policy in America
Authors: Robinson Scott E.
Published: June 2016

In a number of important articles and books—most notably Agendas and Instability in American Politics (1993), The Politics of Attention: How Government Prioritizes Problems (2005)—Frank R. Baumgartner and Bryan D. Jones have pioneered a distinctive approach to the study of agenda setting that has shaped research in both the U.S. politics and comparative politics subfields. The Politics of Information: Problem Definition and the Course of Public Policy in America further expands on the theme of the political determinants, and implications, of “the organization and prioritization of information.” And so we have invited a number of political scientists from a range of subfields to comment on the book and on the research agenda more generally.
Democracy and infant mortality within India: from whether to why
Authors: Bellinger Nisha Mukherjee
Published: June 2016

How does democratic politics affect infant mortality? The bulk of existing research has debated whether democracies have lower levels of infant mortality than non-democracies. Yet, infant mortality varies as much within countries as it does between countries, suggesting that the political processes affecting infant mortality operate at the subnational level. To shed new light on the debate, this paper examines how three core democratic attributes affect infant mortality within a single democracy: India. I argue that higher levels of political representation, citizens’ participation, and electoral competition provide political incentives for elected representatives to reduce infant mortality. The theory is tested on a times-series data set from 15 major Indian states between 1980 and 2011. Overall, the results demonstrate the significance of democratic politics, particularly political representation, in influencing infant mortality.
Behavioral Treatment of Pediatric Sleep Disturbance: Ethical Considerations for Pediatric Psychology Practice
Authors: Byars Kelly C. , Simon Stacey L.
Published: June 2016

Delayed sleep onset and problematic night wakings are common during the infant and toddler years. Such sleep disturbances typically develop as the result of learned associations with specific cues needed for sleep initiation and/or maintenance that are not consistently available at bedtime or immediately available to the child after night wakings (e.g., rocking, feeding, being held). Effective empirically supported behavioral treatments for these common sleep problems exist. Despite the research evidence supporting the effectiveness of these behavioral treatments, widespread dissemination of unsubstantiated concerns about the appropriateness and theorized negative impact of behavioral sleep treatments persists. Some researchers have even raised concerns about the ethics of health providers providing behavioral sleep treatments, particularly extinction-based treatments. As a result, providers of pediatric behavioral sleep services routinely encounter parents who raise concerns about the use of extinction-based behavioral treatments. Unwarranted parental concerns may prevent some families from seeking services that could lead to positive health outcomes. This article discusses important ethical considerations for pediatric psychologists who provide behavioral sleep medicine services. Recommendations for evidence-based clinical practice are made considering American Psychological Association Ethical Principles of Psychologists and Code of Conduct, American Academy of Pediatrics guidelines for safe sleep practices, and current research on behavioral sleep treatment outcomes.
Comparison of biological effects of modulated electro-hyperthermia and conventional heat treatment in human lymphoma U937 cells
Authors: Andocs G , Rehman M U , Zhao Q-L , Tabuchi Y , Kanamori M , Kondo T
Published: June 2016

Loco-regional hyperthermia treatment has long history in oncology. Modulated electro-hyperthermia (mEHT, trade name: oncothermia) is an emerging curative treatment method in this field due to its highly selective actions. The impedance-matched, capacitive-coupled modulated radiofrequency (RF) current is selectively focused in the malignant cell membrane of the cancer cells. Our objective is studying the cell-death process and comparing the cellular effects of conventional water-bath hyperthermia treatment to mEHT. The U937 human histiocytic lymphoma cell line was used for the experiments. In the case of conventional hyperthermia treatment, cells were immersed in a thermoregulated water bath, whereas in the case of mEHT, the cells were treated using a special RF generator (LabEHY, Oncotherm) and an applicator. The heating dynamics, the maximum temperature reached (42 °C) and the treatment duration (30 min) were exactly the same in both cases. Cell samples were analysed using different flow cytometric methods as well as microarray gene expression assay and western blot analysis was also used to reveal the molecular basis of the induced effects. Definite difference was observed in the biological response to different heat treatments. At 42 °C, only mEHT induced significant apoptotic cell death. The GeneChip analysis revealed a whole cluster of genes, which are highly up-regulated in case of only RF heating, but not in conventional heating. The Fas, c-Jun N-terminal kinases (JNK) and ERK signalling pathway was the dominant factor to induce apoptotic cell death in mEHT, whereas the cell-protective mechanisms dominated in case of conventional heating. This study has clearly shown that conventional hyperthermia and RF mEHT can result in different biological responses at the same temperature. The reason for the difference is the distinct, non-homogenous energy distribution on the cell membrane, which activates cell death-related signalling pathways in mEHT treatment but not in conventional heat treatment.
An epithelial marker promoter induction screen identifies histone deacetylase inhibitors to restore epithelial differentiation and abolishes anchorage independence growth in cancers
Authors: Tang H M , Kuay K T , Koh P F , Asad M , Tan T Z , Chung V Y , Lee S C , Thiery J P , Huang RY-J
Published: June 2016

Epithelial–mesenchymal transition (EMT), a crucial mechanism in development, mediates aggressiveness during carcinoma progression and therapeutic refractoriness. The reversibility of EMT makes it an attractive strategy in designing novel therapeutic approaches. Therefore, drug discovery pipelines for EMT reversal are in need to discover emerging classes of compounds. Here, we outline a pre-clinical drug screening platform for EMT reversal that consists of three phases of drug discovery and validation. From the Phase 1 epithelial marker promoter induction (EpI) screen on a library consisting of compounds being approved by Food and Drug Administration (FDA), Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is identified to exert EMT reversal effects by restoring the expression of an epithelial marker, E-cadherin. An expanded screen on 41 HDACi further identifies 28 compounds, such as class I-specific HDACi Mocetinosat, Entinostat and CI994, to restore E-cadherin and ErbB3 expressions in ovarian, pancreatic and bladder carcinoma cells. Mocetinostat is the most potent HDACi to restore epithelial differentiation with the lowest concentration required for 50% induction of epithelial promoter activity (EpIC-50).The HDACi exerts paradoxical effects on EMT transcriptional factors such as SNAI and ZEB family and the effects are context-dependent in epithelial- and mesenchymal-like cells. In vitro functional studies further show that HDACi induced significant increase in anoikis and decrease in spheroid formation in ovarian and bladder carcinoma cells with mesenchymal features. This study demonstrates a robust drug screening pipeline for the discovery of compounds capable of restoring epithelial differentiation that lead to significant functional lethality.
A splicing isoform of TEAD4 attenuates the Hippo–YAP signalling to inhibit tumour proliferation
Authors: Qi Yangfan , Yu Jing , Han Wei , Fan Xiaojuan , Qian Haili , Wei Huanhuan , Tsai Yi-hsuan S. , Zhao Jinyao , Zhang Wenjing , Liu Quentin , Meng Songshu , Wang Yang , Wang Zefeng
Published: June 2016

Aberrant splicing is frequently found in cancer, yet the biological consequences of such alterations are mostly undefined. Here we report that the Hippo–YAP signalling, a key pathway that regulates cell proliferation and organ size, is under control of a splicing switch. We show that TEAD4, the transcription factor that mediates Hippo–YAP signalling, undergoes alternative splicing facilitated by the tumour suppressor RBM4, producing a truncated isoform, TEAD4-S, which lacks an N-terminal DNA-binding domain, but maintains YAP interaction domain. TEAD4-S is located in both the nucleus and cytoplasm, acting as a dominant negative isoform to YAP activity. Consistently, TEAD4-S is reduced in cancer cells, and its re-expression suppresses cancer cell proliferation and migration, inhibiting tumour growth in xenograft mouse models. Furthermore, TEAD4-S is reduced in human cancers, and patients with elevated TEAD4-S levels have improved survival. Altogether, these data reveal a splicing switch that serves to fine tune the Hippo–YAP pathway.
Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities
Authors: Bain Calum C. , Hawley Catherine A. , Garner Hannah , Scott Charlotte L. , Schridde Anika , Steers Nicholas J. , Mack Matthias , Joshi Anagha , Guilliams Martin , Mowat Allan Mc I. , Geissmann Frederic , Jenkins Stephen J.
Published: June 2016

Peritoneal macrophages are one of the most studied macrophage populations in the body, yet the composition, developmental origin and mechanisms governing the maintenance of this compartment are controversial. Here we show resident F4/80hiGATA6+ macrophages are long-lived, undergo non-stochastic self-renewal and retain cells of embryonic origin for at least 4 months in mice. However, Ly6C+ monocytes constitutively enter the peritoneal cavity in a CCR2-dependent manner, where they mature into short-lived F4/80loMHCII+ cells that act, in part, as precursors of F4/80hiGATA6+ macrophages. Notably, monocyte-derived F4/80hi macrophages eventually displace the embryonic population with age in a process that is highly gender dependent and not due to proliferative exhaustion of the incumbent embryonic population, despite the greater proliferative activity of newly recruited cells. Furthermore, although monocyte-derived cells acquire key characteristics of the embryonic population, expression of Tim4 was impaired, leading to cumulative changes in the population with age.
Laboratory analogue of a supersonic accretion column in a binary star system
Authors: Cross J. E. , Gregori G. , Foster J. M. , Graham P. , Bonnet-Bidaud J. -M. , Busschaert C. , Charpentier N. , Danson C. N. , Doyle H. W. , Drake R. P. , Fyrth J. , Gumbrell E. T. , Koenig M. , Krauland C. , Kuranz C. C. , Loupias B. , Michaut C. , Mouchet M. , Patankar S. , Skidmore J. , Spindloe C. , Tubman E. R. , Woolsey N. , Yurchak R. , Falize É.
Published: June 2016

Astrophysical flows exhibit rich behaviour resulting from the interplay of different forms of energy—gravitational, thermal, magnetic and radiative. For magnetic cataclysmic variable stars, material from a late, main sequence star is pulled onto a highly magnetized (B>10 MG) white dwarf. The magnetic field is sufficiently large to direct the flow as an accretion column onto the poles of the white dwarf, a star subclass known as AM Herculis. A stationary radiative shock is expected to form 100–1,000 km above the surface of the white dwarf, far too small to be resolved with current telescopes. Here we report the results of a laboratory experiment showing the evolution of a reverse shock when both ionization and radiative losses are important. We find that the stand-off position of the shock agrees with radiation hydrodynamic simulations and is consistent, when scaled to AM Herculis star systems, with theoretical predictions.
Improvement of gemcitabine sensitivity of p53-mutated pancreatic cancer MiaPaCa-2 cells by RUNX2 depletion-mediated augmentation of TAp73-dependent cell death
Authors: Nakamura M , Sugimoto H , Ogata T , Hiraoka K , Yoda H , Sang M , Sang M , Zhu Y , Yu M , Shimozato O , Ozaki T
Published: June 2016

Pancreatic cancer exhibits the worst prognostic outcome among human cancers. Recently, we have described that depletion of RUNX2 enhances gemcitabine (GEM) sensitivity of p53-deficient pancreatic cancer AsPC-1 cells through the activation of TAp63-mediated cell death pathway. These findings raised a question whether RUNX2 silencing could also improve GEM efficacy on pancreatic cancer cells bearing p53 mutation. In the present study, we have extended our study to p53-mutated pancreatic cancer MiaPaCa-2 cells. Based on our current results, MiaPaCa-2 cells were much more resistant to GEM as compared with p53-proficient pancreatic cancer SW1990 cells, and there existed a clear inverse relationship between the expression levels of TAp73 and RUNX2 in response to GEM. Forced expression of TAp73α in MiaPaCa-2 cells significantly promoted cell cycle arrest and/or cell death, indicating that a large amount of TAp73 might induce cell death even in the presence of mutant p53. Consistent with this notion, overexpression of TAp73α stimulated luciferase activity driven by p53/TAp73-target gene promoters in MiaPaCa-2 cells. Similar to AsPC-1 cells, small interfering RNA-mediated knockdown of RUNX2 remarkably enhanced GEM sensitivity of MiPaCa-2 cells. Under our experimental conditions, TAp73 further accumulated in RUNX2-depleted MiaPaCa-2 cells exposed to GEM relative to GEM-treated non-silencing control cells. As expected, silencing of p73 reduced GEM sensitivity of MiPaCa-2 cells. Moreover, GEM-mediated Tyr phosphorylation level of TAp73 was much more elevated in RUNX2-depleted MiaPaCa-2 cells. Collectively, our present findings strongly suggest that knockdown of RUNX2 contributes to a prominent enhancement of GEM sensitivity of p53-mutated pancreatic cancer cells through the activation of TAp73-mediated cell death pathway, and also provides a promising strategy for the treatment of patients with pancreatic cancer bearing p53 mutation.
High-Throughput Single-Cell Derived Sphere Formation for Cancer Stem-Like Cell Identification and Analysis
Authors: Chen Yu-Chih , Ingram Patrick N. , Fouladdel Shamileh , McDermott Sean P. , Azizi Ebrahim , Wicha Max S. , Yoon Euisik
Published: June 2016

Considerable evidence suggests that many malignancies are driven by a cellular compartment that displays stem cell properties. Cancer stem-like cells (CSCs) can be identified by expression of cell surface markers or enzymatic activity, but these methods are limited by phenotypic heterogeneity and plasticity of CSCs. An alternative phenotypic methodology based on in-vitro sphere formation has been developed, but it is typically labor-intensive and low-throughput. In this work, we present a 1,024-microchamber microfluidic platform for single-cell derived sphere formation. Utilizing a hydrodynamic capturing scheme, more than 70% of the microchambers capture only one cell, allowing for monitoring of sphere formation from heterogeneous cancer cell populations for identification of CSCs. Single-cell derived spheres can be retrieved and dissociated for single-cell analysis using a custom 96-gene panel to probe heterogeneity within the clonal CSC spheres. This microfluidic platform provides reliable and high-throughput sphere formation for CSC identification and downstream clonal analysis.
Imatinib and Nilotinib increase glioblastoma cell invasion via Abl-independent stimulation of p130Cas and FAK signalling
Authors: Frolov Antonina , Evans Ian M. , Li Ningning , Sidlauskas Kastytis , Paliashvili Ketevan , Lockwood Nicola , Barrett Angela , Brandner Sebastian , Zachary Ian C. , Frankel Paul
Published: June 2016

Imatinib was the first targeted tyrosine kinase inhibitor to be approved for clinical use and remains first-line therapy for Philadelphia chromosome (Ph+)-positive chronic myelogenous leukaemia. We show that treatment of human glioblastoma multiforme (GBM) tumour cells with imatinib and the closely-related drug, nilotinib, strikingly increases tyrosine phosphorylation of p130Cas, focal adhesion kinase (FAK) and the downstream adaptor protein paxillin (PXN), resulting in enhanced cell migration and invasion. Imatinib and nilotinib-induced tyrosine phosphorylation was dependent on expression of p130Cas and FAK activity and was independent of known imatinib targets including Abl, platelet derived growth factor receptor beta (PDGFRβ) and the collagen receptor DDR1. Imatinib and nilotinib treatment increased two dimensional cell migration and three dimensional radial spheroid invasion in collagen. In addition, silencing of p130Cas and inhibition of FAK activity both strongly reduced imatinib and nilotinib stimulated invasion. Importantly, imatinib and nilotinib increased tyrosine phosphorylation of p130Cas, FAK, PXN and radial spheroid invasion in stem cell lines isolated from human glioma biopsies. These findings identify a novel mechanism of action in GBM cells for two well established front line therapies for cancer resulting in enhanced tumour cell motility.
Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa
Authors: Warrilow Andrew G. S. , Price Claire L. , Parker Josie E. , Rolley Nicola J. , Smyrniotis Christopher J. , Hughes David D. , Thoss Vera , Nes W. David , Kelly Diane E. , Holman Theodore R. , Kelly Steven L.
Published: June 2016

Malassezia globosa cytochromes P450 CYP51 and CYP5218 are sterol 14α-demethylase (the target of azole antifungals) and a putative fatty acid metabolism protein (and a potential azole drug target), respectively. Lanosterol, eburicol and obtusifoliol bound to CYP51 with Kd values of 32, 23 and 28 μM, respectively, catalyzing sterol 14α-demethylation with respective turnover numbers of 1.7 min−1, 5.6 min−1 and 3.4 min−1. CYP5218 bound a range of fatty acids with linoleic acid binding strongest (Kd 36 μM), although no metabolism could be detected in reconstitution assays or role in growth on lipids. Clotrimazole, fluconazole, itraconazole, ketoconazole, voriconazole and ketaminazole bound tightly to CYP51 (Kd ≤ 2 to 11 nM). In contrast, fluconazole did not bind to CYP5218, voriconazole and ketaminazole bound weakly (Kd ~107 and ~12 μM), whereas ketoconazole, clotrimazole and itraconazole bound strongest to CYP5218 (Kd ~1.6, 0.5 and 0.4 μM) indicating CYP5218 to be only a secondary target of azole antifungals. IC50 determinations confirmed M. globosa CYP51 was strongly inhibited by azole antifungals (0.15 to 0.35 μM). MIC100 studies showed itraconazole should be considered as an alternative to ketoconazole given the potency and safety profiles and the CYP51 assay system can be used in structure-activity studies in drug development.
A novel way to detect correlations on multi-time scales, with temporal evolution and for multi-variables
Authors: Yuan Naiming , Xoplaki Elena , Zhu Congwen , Luterbacher Juerg
Published: June 2016

In this paper, two new methods, Temporal evolution of Detrended Cross-Correlation Analysis (TDCCA) and Temporal evolution of Detrended Partial-Cross-Correlation Analysis (TDPCCA), are proposed by generalizing DCCA and DPCCA. Applying TDCCA/TDPCCA, it is possible to study correlations on multi-time scales and over different periods. To illustrate their properties, we used two climatological examples: i) Global Sea Level (GSL) versus North Atlantic Oscillation (NAO); and ii) Summer Rainfall over Yangtze River (SRYR) versus previous winter Pacific Decadal Oscillation (PDO). We find significant correlations between GSL and NAO on time scales of 60 to 140 years, but the correlations are non-significant between 1865–1875. As for SRYR and PDO, significant correlations are found on time scales of 30 to 35 years, but the correlations are more pronounced during the recent 30 years. By combining TDCCA/TDPCCA and DCCA/DPCCA, we proposed a new correlation-detection system, which compared to traditional methods, can objectively show how two time series are related (on which time scale, during which time period). These are important not only for diagnosis of complex system, but also for better designs of prediction models. Therefore, the new methods offer new opportunities for applications in natural sciences, such as ecology, economy, sociology and other research fields.
Facile and Scale Up Synthesis of Red Phosphorus-Graphitic Carbon Nitride Heterostructures for Energy and Environment Applications
Authors: Ansari Sajid Ali , Ansari Mohammad Omaish , Cho Moo Hwan
Published: June 2016

The development of heterostructured materials for efficient solar energy conversion and energy storage devices are essential for practical applications. In this study, a simple and relatively inexpensive method was used to improve the visible light-driven photocatalytic activity and electrochemical supercapacitor behavior of the graphitic carbon nitride (g-C3N4) by elemental red phosphorus (RPh). The as-prepared RPh-g-C3N4 was characterized in detail using a range of spectroscopic techniques to understand the structure, morphology, chemical interaction and chemical state of the materials. The visible light-driven photocatalytic activity and supercapacitive electrode performance were assessed by the photodegradation of model colored, non-colored organic pollutants and electrochemical half-cell measurements, respectively. The RPh-g-C3N4 heterostructure with 30 weight percent of RPh exhibited remarkably high photocatalytic activity for the degradation of pollutants compared to the bare constituent materials, which was further confirmed by the photoelectrochemical study under similar visible photoirradiation conditions. The RPh-g-C3N4 heterostructure supercapacitor electrode displayed a high capacitance of 465 F/g and excellent cyclic stability with capacitance retention of 90% after 1000 cycles at a current of 10 A/g. The superior performance was attributed mainly to the narrow band gap, high surface area, capacitive nature of RPh and nitrogen-rich skeleton of g-C3N4.
Phylogenomic analyses of bat subordinal relationships based on transcriptome data
Authors: Lei Ming , Dong Dong
Published: June 2016

Bats, order Chiroptera, are one of the largest monophyletic clades in mammals. Based on morphology and behaviour bats were once differentiated into two suborders Megachiroptera and Microchiroptera Recently, researchers proposed alternative views of chiropteran classification (suborders Yinpterochiroptera and Yangochiroptera) based on morphological, molecular and fossil evidence. Since genome-scale data can significantly increase the number of informative characters for analysis, transcriptome RNA-seq data for 12 bat taxa were generated in an attempt to resolve bat subordinal relationships at the genome level. Phylogenetic reconstructions were conducted using up to 1470 orthologous genes and 634,288 aligned sites. We found strong support for the Yinpterochiroptera-Yangochiroptera classification. Next, we built expression distance matrices for each species and reconstructed gene expression trees. The tree is highly consistent with sequence-based phylogeny. We also examined the influence of taxa sampling on the performance of phylogenetic methods, and found that the topology is robust to sampling. Relaxed molecular clock estimates the divergence between Yinpterochiroptera and Yangochiroptera around 63 million years ago. The most recent common ancestor of Yinpterochiroptera, corresponding to the split between Rhinolophoidea and Pteropodidae (Old World Fruit bats), is estimated to have occurred 60 million years ago. Our work provided a valuable resource to further explore the evolutionary relationship within bats.
Bodily ownership modulation in defensive responses: physiological evidence in brain-damaged patients with pathological embodiment of other’s body parts
Authors: Fossataro C. , Gindri P. , Mezzanato T. , Pia L. , Garbarini F.
Published: June 2016

Do conscious beliefs about the body affect defensive mechanisms within the body? To answer this question we took advantage from a monothematic delusion of bodily ownership, in which brain-damaged patients misidentify alien limbs as their own. We investigated whether the delusional belief that an alien hand is their own hand modulates a subcortical defensive response, such as the hand-blink reflex. The blink, dramatically increases when the threated hand is inside the defensive peripersonal-space of the face. In our between-subjects design, including patients and controls, the threat was brought near the face either by the own hand or by another person’s hand. Our results show an ownership-dependent modulation of the defensive response. In controls, as well as in the patients’ intact-side, the response enhancement is significantly greater when the threat was brought near the face by the own than by the alien hand. Crucially, in the patients’ affected-side (where the pathological embodiment occurs), the alien (embodied) hand elicited a response enhancement comparable to that found when the threat is brought near the face by the real hand. These findings suggest the existence of a mutual interaction between our conscious beliefs about the body and the physiological mechanisms within the body.
The LIM domain protein nTRIP6 acts as a co-repressor for the transcription factor MEF2C in myoblasts
Authors: Kemler Denise , Dahley Oliver , Roßwag Sven , Litfin Margarethe , Kassel Olivier
Published: June 2016

The transcription factor Myocyte enhancer factor 2C (MEF2C) plays a key role in the late differentiation of skeletal muscle progenitor cells, the so-called myoblasts. During myoblast differentiation, both MEF2C expression and transcriptional activity are regulated. We have reported that nTRIP6, the nuclear isoform of the focal adhesion LIM domain protein TRIP6, acts as an adaptor transcriptional co-activator for several transcription factors. It interacts with the promoter-bound transcription factors and consequently mediates the recruitment of other co-activators. Based on a described interaction between MEF2C and TRIP6 in a yeast-two-hybrid screen, we hypothesised a co-regulatory function of nTRIP6 for MEF2C. In proliferating myoblasts, nTRIP6 interacted with MEF2C and was recruited together with MEF2C to the MEF2-binding regions of the MEF2C target genes Myom2, Mb, Tnni2 and Des. Silencing nTRIP6 or preventing its interaction with MEF2C increased MEF2C transcriptional activity and increased the expression of these MEF2C target genes. Thus, nTRIP6 acts as a co-repressor for MEF2C. Mechanistically, nTRIP6 mediated the recruitment of the class IIa histone deacetylase HDAC5 to the MEF2C-bound promoters. In conclusion, our results unravel a transcriptional co-repressor function for nTRIP6. This adaptor co-regulator can thus exert either co-activator or co-repressor functions, depending on the transcription factor it interacts with.
Harvest locations of goose barnacles can be successfully discriminated using trace elemental signatures
Authors: Albuquerque Rui , Queiroga Henrique , Swearer Stephen E. , Calado Ricardo , Leandro Sérgio M.
Published: June 2016

European Union regulations state that consumers must be rightfully informed about the provenance of fishery products to prevent fraudulent practices. However, mislabeling of the geographical origin is a common practice. It is therefore paramount to develop forensic methods that allow all players involved in the supply chain to accurately trace the origin of seafood. In this study, trace elemental signatures (TES) of the goose barnacle Pollicipes pollicipes, collected from ten sites along the Portuguese coast, were employed to discriminate individual’s origin. Barium (Ba), boron (B), cadmium (Cd), chromium (Cr), lithium (Li), magnesium (Mg), manganese (Mn), phosphorous (P), lead (Pb), strontium (Sr) and zinc (Zn) - were quantified using Inductively Coupled Plasma−Mass Spectrometry (ICP-MS). Significant differences were recorded among locations for all elements. A regularized discriminant analysis (RDA) revealed that 83% of all individuals were correctly assigned. This study shows TES can be a reliable tool to confirm the geographic origin of goose barnacles at fine spatial resolution. Although additional studies are required to ascertain the reliability of TES on cooked specimens and the temporal stability of the signature, the approach holds great promise for the management of goose barnacles fisheries, enforcement of conservation policies and assurance in accurate labeling.
PiggyBac transposon-based polyadenylation-signal trap for genome-wide mutagenesis in mice
Authors: Li Limei , Liu Peng , Sun Liangliang , Bin Zhou  , Fei Jian
Published: June 2016

We designed a new type of polyadenylation-signal (PAS) trap vector system in living mice, the piggyBac (PB) (PAS-trapping (EGFP)) gene trapping vector, which takes advantage of the efficient transposition ability of PB and efficient gene trap and insertional mutagenesis of PAS-trapping. The reporter gene of PB(PAS-trapping (EGFP)) is an EGFP gene with its own promoter, but lacking a poly(A) signal. Transgenic mouse lines carrying PB(PAS-trapping (EGFP)) and protamine 1 (Prm1) promoter-driven PB transposase transgenes (Prm1-PBase) were generated by microinjection. Male mice doubly positive for PB(PAS-trapping (EGFP)) and Prm1-PBase were crossed with WT females, generating offspring with various insertion mutations. We found that 44.8% (26/58) of pups were transposon-positive progenies. New transposon integrations comprised 26.9% (7/26) of the transposon-positive progenies. We found that 100% (5/5) of the EGFP fluorescence-positive mice had new trap insertions mediated by a PB transposon in transcriptional units. The direction of the EGFP gene in the vector was consistent with the direction of the endogenous gene reading frame. Furthermore, mice that were EGFP-PCR positive, but EGFP fluorescent negative, did not show successful gene trapping. Thus, the novel PB(PAS-trapping (EGFP)) system is an efficient genome-wide gene-trap mutagenesis in mice.
Deciphering the Counterplay of Aspergillus fumigatus Infection and Host Inflammation by Evolutionary Games on Graphs
Authors: Pollmächer Johannes , Timme Sandra , Schuster Stefan , Brakhage Axel A. , Zipfel Peter F. , Figge Marc Thilo
Published: June 2016

Microbial invaders are ubiquitously present and pose the constant risk of infections that are opposed by various defence mechanisms of the human immune system. A tight regulation of the immune response ensures clearance of microbial invaders and concomitantly limits host damage that is crucial for host viability. To investigate the counterplay of infection and inflammation, we simulated the invasion of the human-pathogenic fungus Aspergillus fumigatus in lung alveoli by evolutionary games on graphs. The layered structure of the innate immune system is represented by a sequence of games in the virtual model. We show that the inflammatory cascade of the immune response is essential for microbial clearance and that the inflammation level correlates with the infection-dose. At low infection-doses, corresponding to daily inhalation of conidia, the resident alveolar macrophages may be sufficient to clear infections, however, at higher infection-doses their primary task shifts towards recruitment of neutrophils to infection sites.
Formation of functional CENP-B boxes at diverse locations in repeat units of centromeric DNA in New World monkeys
Authors: Kugou Kazuto , Hirai Hirohisa , Masumoto Hiroshi , Koga Akihiko
Published: June 2016

Centromere protein B, which is involved in centromere formation, binds to centromeric repetitive DNA by recognizing a nucleotide motif called the CENP-B box. Humans have large numbers of CENP-B boxes in the centromeric repetitive DNA of their autosomes and X chromosome. The current understanding is that these CENP-B boxes are located at identical positions in the repeat units of centromeric DNA. Great apes also have CENP-B boxes in locations that are identical to humans. The purpose of the present study was to examine the location of CENP-B box in New World monkeys. We recently identified CENP-B box in one species of New World monkeys (marmosets). In this study, we found functional CENP-B boxes in CENP-A-assembled repeat units of centromeric DNA in 2 additional New World monkeys (squirrel monkeys and tamarins) by immunostaining and ChIP-qPCR analyses. The locations of the 3 CENP-B boxes in the repeat units differed from one another. The repeat unit size of centromeric DNA of New World monkeys (340–350 bp) is approximately twice that of humans and great apes (171 bp). This might be, associated with higher-order repeat structures of centromeric DNA, a factor for the observed variation in the CENP-B box location in New World monkeys.
A potential panel of six-long non-coding RNA signature to improve survival prediction of diffuse large-B-cell lymphoma
Authors: Sun Jie , Cheng Liang , Shi Hongbo , Zhang Zhaoyue , Zhao Hengqiang , Wang Zhenzhen , Zhou Meng
Published: June 2016

Long non-coding RNAs (lncRNAs) represent an emerging layer of cancer biology and have been implicated in the development and progression of cancers. However, the prognostic significance of lncRNAs in diffuse large-B-cell lymphoma (DLBCL) remains unclear and needs to be systematically investigated. In this study, we obtained and analyzed lncRNA expression profiles in three cohorts of 1043 DLBCL patients by repurposing the publicly available microarray datasets from the Gene Expression Omnibus (GEO) database. In the discovery series of 207 patients, we identified a set of six lncRNAs that was significantly associated with patients’ overall survival (OS) using univariate Cox regression analysis. The six prognostic lncRNAs were combined to form an expression-based six-lncRNA signature which classified patients of the discovery series into the high-risk group and low-risk group with significantly different survival outcome (HR = 2.31, 95% CI = 1.8 to 2.965, p < 0.001). The six-lncRNA signature was further confirmed in the internal testing series and two additional independent datasets with different array platform. Moreover, the prognostic value of the six-lncRNA signature is independent of conventional clinical factors. Functional analysis suggested that six-lncRNA signature may be involved with DLBCL through exerting their regulatory roles in known cancer-related pathways, immune system and signaling molecules interaction.
Impact of climate change on larch budmoth cyclic outbreaks
Authors: Iyengar Sudharsana V. , Balakrishnan Janaki , Kurths Jürgen
Published: June 2016

Periodic outbreaks of the larch budmoth Zeiraphera diniana population (and the massive forest defoliation they engender) have been recorded in the Alps over the centuries and are known for their remarkable regularity. But these have been conspicuously absent since 1981. On the other hand, budmoth outbreaks have been historically unknown in the larches of the Carpathian Tatra mountains. To resolve this puzzle, we propose here a model which includes the influence of climate and explains both the 8–9 year periodicity in the budmoth cycle and the variations from this, as well as the absence of cycles. We successfully capture the observed trend of relative frequencies of outbreaks, reproducing the dominant periodicities seen. We contend that the apparent collapse of the cycle in 1981 is due to changing climatic conditions following a tipping point and propose the recurrence of the cycle with a changed periodicity of 40 years – the next outbreak could occur in 2021. Our model also predicts longer cycles.
Adult vultures outperform juveniles in challenging thermal soaring conditions
Authors: Harel Roi , Horvitz Nir , Nathan Ran
Published: June 2016

Due to the potentially detrimental consequences of low performance in basic functional tasks, individuals are expected to improve performance with age and show the most marked changes during early stages of life. Soaring-gliding birds use rising-air columns (thermals) to reduce energy expenditure allocated to flight. We offer a framework to evaluate thermal soaring performance and use GPS-tracking to study movements of Eurasian griffon vultures (Gyps fulvus). Because the location and intensity of thermals are variable, we hypothesized that soaring performance would improve with experience and predicted that the performance of inexperienced individuals (<2 months) would be inferior to that of experienced ones (>5 years). No differences were found in body characteristics, climb rates under low wind shear and thermal selection, presumably due to vultures’ tendency to forage in mixed-age groups. Adults, however, outperformed juveniles in their ability to adjust fine-scale movements under challenging conditions, as juveniles had lower climb rates under intermediate wind shear, particularly on the lee-side of thermal columns. Juveniles were also less efficient along the route both in terms of time and energy. The consequences of these handicaps are probably exacerbated if juveniles lag behind adults in finding and approaching food.
Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans
Authors: Loiola Rodrigo Azevedo , dos Anjos Fabyana Maria , Shimada Ana Lúcia , Cruz Wesley Soares , Drewes Carine Cristiane , Rodrigues Stephen Fernandes , Cardozo Karina Helena Morais , Carvalho Valdemir Melechco , Pinto Ernani , Farsky Sandra Helena
Published: June 2016

It has been recently proposed that exposure to polychlorinated biphenyls (PCBs) is a risk factor to type 2 diabetes mellitus (DM2). We investigated this hypothesis using long-term in vivo PCB126 exposure to rats addressing metabolic, cellular and proteomic parameters. Male Wistar rats were exposed to PCB126 (0.1, 1 or 10 μg/kg of body weight/day; for 15 days) or vehicle by intranasal instillation. Systemic alterations were quantified by body weight, insulin and glucose tolerance and blood biochemical profile. Pancreatic toxicity was measured by inflammatory parameters, cell viability and cycle, free radical generation and proteomic profile on islets of Langerhans. In vivo PCB126 exposure enhanced the body weight gain, impaired insulin sensitivity, reduced adipose tissue deposit and elevated serum triglycerides, cholesterol and insulin levels. Inflammatory parameters in the pancreas and cell morphology, viability and cycle were not altered in islets of Langerhans. Nevertheless, in vivo PCB126 exposure increased free radical generation and modified the expression of proteins related to oxidative stress on islets of Langerhans, which are indicative of early β-cell failure. Data herein obtained show that long-term in vivo PCB126 exposure through intranasal route induced alterations on islets of Langerhans related to early end points of DM2.
Cardiomyocyte GTP Cyclohydrolase 1 Protects the Heart Against Diabetic Cardiomyopathy
Authors: Wu Hsiang-En , Baumgardt Shelley L. , Fang Juan , Paterson Mark , Liu Yanan , Du Jianhai , Shi Yang , Qiao Shigang , Bosnjak Zeljko J. , Warltier David C. , Kersten Judy R. , Ge Zhi-Dong
Published: June 2016

Diabetic cardiomyopathy increases the risk of heart failure and death. At present, there are no effective approaches to preventing its development in the clinic. Here we report that reduction of cardiac GTP cyclohydrolase 1 (GCH1) degradation by genetic and pharmacological approaches protects the heart against diabetic cardiomyopathy. Diabetic cardiomyopathy was induced in C57BL/6 wild-type mice and transgenic mice with cardiomyocyte-specific overexpression of GCH1 with streptozotocin and control animals were given citrate buffer. We found that diabetes-induced degradation of cardiac GCH1 proteins contributed to adverse cardiac remodeling and dysfunction in C57BL/6 mice, concomitant with decreases in tetrahydrobiopterin, dimeric and phosphorylated neuronal nitric oxide synthase, sarcoplasmic reticulum Ca2+ handling proteins, intracellular [Ca2+]i and sarcoplasmic reticulum Ca2+ content and increases in phosphorylated p-38 mitogen-activated protein kinase and superoxide production. Interestingly, GCH-1 overexpression abrogated these detrimental effects of diabetes. Furthermore, we found that MG 132, an inhibitor for 26S proteasome, preserved cardiac GCH1 proteins and ameliorated cardiac remodeling and dysfunction during diabetes. This study deepens our understanding of impaired cardiac function in diabetes, identifies GCH1 as a modulator of cardiac remodeling and function and reveals a new therapeutic target for diabetic cardiomyopathy.
Ultrafast measurements of optical spectral coherence by single-shot time-stretch interferometry
Authors: Xu Yiqing , Wei Xiaoming , Ren Zhibo , Wong Kenneth K. Y. , Tsia Kevin K.
Published: June 2016

The palette of laser technology has significantly been enriched by the innovations in ultrafast optical pulse generation. Our knowledge of the complex pulse dynamics, which is often highly nonlinear and stochastic in nature, is however limited by the scarcity of technologies that can measure fast variation/fluctuation of the spectral phase (or coherence) and amplitude in real-time, continuously. To achieve this goal, we demonstrate ultrafast interferometry enabled by optical time-stretch for real- time spectral coherence characterization with microsecond-resolution. Accessing the single-shot interferograms continuously, it further reveals the degree of second-order coherence, defined by the cross-spectral density function, at high speed-a capability absent in any existing spectroscopic measurement tools. As the technique can simultaneously measure both the high-speed variations of spectrally resolved coherence and intensity, time-stretch interferometry could create a new arena for ultrafast pulse characterization, especially favorable for probing and understanding the non-repetitive or stochastic dynamics in real-time.
Simultaneous determination of lead and tin at the bismuth film electrode by square wave stripping voltammetry and chemometric methods
Authors: Tang Wenxian , Bin Jun , Fan Wei , Zhang Zhiming , Yun Yonghuan , Liang Yizeng
Published: June 2016

Square wave stripping voltammetry for the simultaneous determination of lead and tin by using radial basis function artificial neural networks was conducted.
Colorimetric sensing of chromium(vi) ions in aqueous solution based on the leaching of protein-stabled gold nanoparticles
Authors: Jian-feng Guo , Chang-jun Hou , Mei Yang , Dan-qun Huo , Jun-jie Li , Huan-bao Fa , Hui-bo Luo , Ping Yang
Published: June 2016

Herein, we developed a simple, sensitive and non-aggregation-based method for the selective colorimetric detection of chromium(vi) ions (Cr(vi)) in an aqueous solution.
Crystal engineering to control the magnetic interaction between weak ferromagnetic single-chain magnets assembled in a 3D framework
Authors: Su Lei , Song Wei-Chao , Zhao Jiong-Peng , Liu Fu-Chen
Published: June 2016

A synthetic strategy of control of the arrangement and the magnetism of the SCMs by assembly of the chains into a high dimensional network was illustrated in a family of a weak antiferromagnetic chain based 3D framework.
Boronic acid as an efficient anchor group for surface modification of solid polyvinyl alcohol
Authors: Nishiyabu Ryuhei , Shimizu Ai
Published: June 2016

The use of boronic acid as an anchor group allowed the direct surface modification of solid polyvinyl alcohol.
Coumarin-decorated Schiff base hydrolysis as an efficient driving force for the fluorescence detection of water in organic solvents
Authors: Kim Won Young , Shi Hu , Jung Hyo Sung , Cho Daeheum , Verwilst Peter , Lee Jin Yong , Kim Jong Seung
Published: June 2016

A Schiff base bearing coumarin is found to be an excellent indicator of trace amounts of moisture in organic solvents.
Hückel–Hubbard–Ohno modeling of π-bonds in ethene and ethyne with application to trans-polyacetylene
Authors: Timár Máté , Barcza Gergely , Gebhard Florian , Veis Libor , Legeza Örs
Published: June 2016

Quantum chemistry calculations provide the potential energy between two carbon atoms in ethane (H3C–CH3), ethene (H2CCH2), and ethyne (HCCH) as a function of the atomic distance.
Regiospecific protonation of organic chromophores
Authors: Tang Tao , Lin Tingting , Wang FuKe , He Chaobin
Published: June 2016

The positions of multi-protonation and achievable charge density are affected by charge repulsion and delocalization associated with the conformation of protonated oligomers.
Organometallic model complexes elucidate the active gallium species in alkane dehydrogenation catalysts based on ligand effects in Ga K-edge XANES
Authors: Getsoian Andrew “Bean” , Das Ujjal , Camacho-Bunquin Jeffrey , Zhang Guanghui , Gallagher James R. , Hu Bo , Cheah Singfoong , Schaidle Joshua A. , Ruddy Daniel A. , Hensley Jesse E. , Krause Theodore R. , Curtiss Larry A. , Miller Jeffrey T. , Hock Adam S.
Published: June 2016

Ga(iii)-alkyl and alkoxide model compounds demonstrate XANES edge energy shifts similar to those in Ga dehydrogenation catalysts without a change in Ga oxidation state.
Supramolecular control of monooxygenase reactivity in a copper(ii) cryptate
Authors: Chaloner L. , Khomutovskaya A. , Thomas F. , Ottenwaelder X.
Published: June 2016

We report on the formation and self-decomposition of Cu(ii)–hydroperoxo intermediates with a cryptand ligand. The second coordination sphere of the cryptand steers the oxidative reactivity of the intermediates towards the formation of an unprecedented N-oxide.
Reactions of metal cluster anions with inorganic and organic molecules in the gas phase
Authors: Zhao Yan-Xia , Liu Qing-Yu , Zhang Mei-Qi , He Sheng-Gui
Published: June 2016

Progress on the activation and transformation of important inorganic and organic molecules by negatively charged bare metal clusters as well as ligated systems with oxygen, carbon, and nitrogen, among others.
Metallo-Wittig chemistry of an alkylidene to form a terminal titanium oxo complex
Authors: Solowey Douglas P. , Kurogi Takashi , Manor Brian C. , Carroll Patrick J. , Mindiola Daniel J.
Published: June 2016

The synthesis and characterization of a terminal titanium oxo complex generated by alkylidene benzophenone cross-metathesis is reported.
Dietary fucoidan modulates the gut microbiota in mice by increasing the abundance ofLactobacillusandRuminococcaceae
Authors: Shang Qingsen , Shan Xindi , Cai Chao , Hao Jiejie , Li Guoyun , Yu Guangli
Published: June 2016

This study provides a new insight into the well-recognized beneficial effects of dietary fucoidan by demonstrating its positive modulations on gut microbiota.