bluuebunny/crossref_metadata_2025 huggingface dataset:
PENEPMA: A Monte Carlo Program for the Simulation of X-Ray Emission in Electron Probe Microanalysis
Authors: Llovet Xavier , Salvat Francesc
Published: May 2017

The Monte Carlo program PENEPMA performs simulations of X-ray emission from samples bombarded with both electron and photon beams. It is based on the general-purpose Monte Carlo simulation package PENELOPE, an elaborate system for the simulation of coupled electron-photon transport in arbitrary materials, and on the geometry subroutine package PENGEOM, which tracks particles through complex material structures defined by quadric surfaces. After a brief description of the interaction models implemented in the simulation subroutines and of the structure and operation of PENEPMA, we provide an overview of the capabilities of the program along with several examples of its application to the modeling of electron probe microanalysis measurements.
Overcoming essentialisation: a comparative study of ‘living-together’ conceptions
Authors: Patrignani Emma
Published: May 2017

This paper compares two judgments of constitutional courts (French and German) assessing the constitutionality of statutes concerning veil-wearing and focuses on the underlying conceptions of ‘living together’. This means that what is actually compared is the self-understanding of the respective majority in the two societies as stated in the decisions. This is done by disassembling the concept of ‘living together’ into three elements: the notion of the individual, the meaning of belonging to the national community and the space accorded to religion in public. Each section of this paper examines one of these elements as they are entailed in the judgments and positions them critically within the respective legal cultural and historical contexts. The main aim of this paper is methodological in nature and is namely to show how comparative legal cultural studies can avoid essentialisation and rather highlight the complexity of every cultural context.
Constitutional Mobilisation in China
Authors: Son Bui Ngoc
Published: May 2017

This paper examines recent constitutional mobilisation in China, embodied in the weiquan (right defence) movement, Charter 08 and the 2013 constitutionalism debate. It contrasts Chinese and Vietnamese experience of constitutional mobilisation. This paper argues that constitutional mobilisation in China presents both convergence and divergence with those in Vietnam. The convergence stems from domestic dynamics, the impact of globalisation and the shared features of socialist/communist institutional settings. The divergence is due to Chinese constitutional exceptionalism and Vietnam's instrumentalist approach to global constitutionalism. Particularly, without necessary constitutional opportunity created by the constitution-making process, constitutional mobilisation in China has not created a national constitutional dialogue as has happened in Vietnam. This paper draws attention to the new function of socialist constitutions as a frame for social mobilisation and has general implications for the comparative inquiry into the social dynamics of constitutional law.
Effects of combined IUGR and prenatal stress on the development of the hippocampus in a fetal guinea pig model
Authors: Cumberland A. L. , Palliser H. K. , Rani P. , Walker D. W. , Hirst J. J.
Published: May 2017

Intrauterine growth restriction (IUGR) and maternal stress during pregnancy are two compromises that negatively impact neurodevelopment and increase the risk of developing later life neuropsychiatric disorders such as schizophrenia, depression and behavioural disorders. Neurosteroids, particularly allopregnanolone, are important in protecting the developing brain and promoting many essential neurodevelopmental processes. Individually, IUGR and prenatal stress (PS) reduce myelination and neurogenesis within affected fetal brains, however less information is available on the combined effects of these two disorders on the term fetal brain. This study aimed to investigate how IUGR and PS impairs the neurosteroid pathway when combined using a guinea pig model, and how these then disrupt the neurodevelopment of the fetus. Uterine artery blood flow restriction was performed at GA30-35 to induce growth restriction, whilst PS was induced by exposure of the dam to a strobe light during gestation commencing GA40 and repeated every 5 days. Exposure in this model caused reductions in hippocampal CA1 MBP immunostaining of male fetuses in both IUGR alone and IUGR+PS paradigms but only by IUGR in the subcortical white mater, compared with control males. Plasma allopregnanolone was reduced by both stressors irrespective of sex, whereas GFAP or MAP2 expression were not affected by either stressor. Female neurodevelopment, as assessed by these markers, was unimpeded by these compromises. The addition of prenatal stress did not further compound these deficits.
Illicit Ideologies:Moral Economies of Venezuelan Smuggling and Autonomy in the Rebellion of Juan Francisco de León, 1749–1751
Authors: Cromwell Jesse
Published: May 2017

On the afternoon of April 20, 1749, a force of between 400 and 600 armed men amassed on Caracas's central plaza. Entering the city under blue and white flags emblazoned with red crosses, to the sound of beating drums, the deployment comprised a cross section of Venezuela's socio-racial groups, social estates, and occupations. The men followed Juan Francisco de León, a cacao planter and small-town sheriff (teniente), and had shouldered their weapons as a popular protest “in the name of the city [of Caracas], the nobility, and the masses.” Disregarding the potentially ominous specter of so many armed insurgents,Caraqueñosinstead welcomed León's troops with open arms. As one observer remarked, all in the city from shopkeepers “to the nuns give thanks to León, wishing him success and commending him to God.”
Diffusive and martensitic nucleation kinetics in solid-solid transitions of colloidal crystals
Authors: Peng Yi , Li Wei , Wang Feng , Still Tim , Yodh Arjun G. , Han Yilong
Published: May 2017

Solid–solid transitions between crystals follow diffusive nucleation, or various diffusionless transitions, but these kinetics are difficult to predict and observe. Here we observed the rich kinetics of transitions from square lattices to triangular lattices in tunable colloidal thin films with single-particle dynamics by video microscopy. Applying a small pressure gradient in defect-free regions or near dislocations markedly transform the diffusive nucleation with an intermediate-stage liquid into a martensitic generation and oscillation of dislocation pairs followed by a diffusive nucleus growth. This transformation is neither purely diffusive nor purely martensitic as conventionally assumed but a combination thereof, and thus presents new challenges to both theory and the empirical criterion of martensitic transformations. We studied how pressure, density, grain boundary, triple junction and interface coherency affect the nucleus growth, shape and kinetic pathways. These novel microscopic kinetics cast new light on control solid–solid transitions and microstructural evolutions in polycrystals.
Actomyosin meshwork mechanosensing enables tissue shape to orient cell force
Authors: Chanet Soline , Miller Callie J. , Vaishnav Eeshit Dhaval , Ermentrout Bard , Davidson Lance A. , Martin Adam C.
Published: May 2017

Sculpting organism shape requires that cells produce forces with proper directionality. Thus, it is critical to understand how cells orient the cytoskeleton to produce forces that deform tissues. During Drosophila gastrulation, actomyosin contraction in ventral cells generates a long, narrow epithelial furrow, termed the ventral furrow, in which actomyosin fibres and tension are directed along the length of the furrow. Using a combination of genetic and mechanical perturbations that alter tissue shape, we demonstrate that geometrical and mechanical constraints act as cues to orient the cytoskeleton and tension during ventral furrow formation. We developed an in silico model of two-dimensional actomyosin meshwork contraction, demonstrating that actomyosin meshworks exhibit an inherent force orienting mechanism in response to mechanical constraints. Together, our in vivo and in silico data provide a framework for understanding how cells orient force generation, establishing a role for geometrical and mechanical patterning of force production in tissues.
Transcriptomic and macroevolutionary evidence for phenotypic uncoupling between frog life history phases
Authors: Wollenberg Valero Katharina C. , Garcia-Porta Joan , Rodríguez Ariel , Arias Mónica , Shah Abhijeet , Randrianiaina Roger Daniel , Brown Jason L. , Glaw Frank , Amat Felix , Künzel Sven , Metzler Dirk , Isokpehi Raphael D. , Vences Miguel
Published: May 2017

Anuran amphibians undergo major morphological transitions during development, but the contribution of their markedly different life-history phases to macroevolution has rarely been analysed. Here we generate testable predictions for coupling versus uncoupling of phenotypic evolution of tadpole and adult life-history phases, and for the underlying expression of genes related to morphological feature formation. We test these predictions by combining evidence from gene expression in two distantly related frogs,Xenopus laevisandMantidactylus betsileanus, with patterns of morphological evolution in the entire radiation of Madagascan mantellid frogs. Genes linked to morphological structure formation are expressed in a highly phase-specific pattern, suggesting uncoupling of phenotypic evolution across life-history phases. This gene expression pattern agrees with uncoupled rates of trait evolution among life-history phases in the mantellids, which we show to have undergone an adaptive radiation. Our results validate a prevalence of uncoupling in the evolution of tadpole and adult phenotypes of frogs.
Neural circuits for long-term water-reward memory processing in thirsty Drosophila
Authors: Shyu Wei-Huan , Chiu Tai-Hsiang , Chiang Meng-Hsuan , Cheng Yu-Chin , Tsai Ya-Lun , Fu Tsai-Feng , Wu Tony , Wu Chia-Lin
Published: May 2017

The intake of water is important for the survival of all animals and drinking water can be used as a reward in thirsty animals. Here we found that thirsty Drosophila melanogaster can associate drinking water with an odour to form a protein-synthesis-dependent water-reward long-term memory (LTM). Furthermore, we found that the reinforcement of LTM requires water-responsive dopaminergic neurons projecting to the restricted region of mushroom body (MB) β′ lobe, which are different from the neurons required for the reinforcement of learning and short-term memory (STM). Synaptic output from α′β′ neurons is required for consolidation, whereas the output from γ and αβ neurons is required for the retrieval of LTM. Finally, two types of MB efferent neurons retrieve LTM from γ and αβ neurons by releasing glutamate and acetylcholine, respectively. Our results therefore cast light on the cellular and molecular mechanisms responsible for processing water-reward LTM in Drosophila.
Controllable cyanation of carbon-hydrogen bonds by zeolite crystals over manganese oxide catalyst
Authors: Wang Liang , Wang Guoxiong , Zhang Jian , Bian Chaoqun , Meng Xiangju , Xiao Feng-Shou
Published: May 2017

The synthesis of organic nitriles without using toxic cyanides is in great demand but challenging to make. Here we report an environmentally benign and cost-efficient synthesis of nitriles from the direct oxidative cyanation of primary carbon-hydrogen bonds with easily available molecular oxygen and urea. The key to this success is to design and synthesize manganese oxide catalysts fixed inside zeolite crystals, forming a manganese oxide catalyst with zeolite sheath (MnOx@S-1), which exhibits high selectivity for producing nitriles by efficiently facilitating the oxidative cyanation reaction and hindering the side hydration reaction. The work delineates a sustainable strategy for synthesizing nitriles while avoiding conventional toxic cyanide, which might open a new avenue for selective transformation of carbon-hydrogen bonds.
Density structure of Earth’s lowermost mantle from Stoneley mode splitting observations
Authors: Koelemeijer Paula , Deuss Arwen , Ritsema Jeroen
Published: May 2017

Advances in our understanding of Earth’s thermal evolution and the style of mantle convection rely on robust seismological constraints on lateral variations of density. The large-low-shear-wave velocity provinces (LLSVPs) atop the core–mantle boundary beneath Africa and the Pacific are the largest structures in the lower mantle, and hence severely affect the convective flow. Here, we show that anomalous splitting of Stoneley modes, a unique class of free oscillations that are perturbed primarily by velocity and density variations at the core–mantle boundary, is explained best when the overall density of the LLSVPs is lower than the surrounding mantle. The resolved density variations can be explained by the presence of post-perovskite, chemical heterogeneity or a combination of the two. Although we cannot rule out the presence of a ∼100-km-thick denser-than-average basal structure, our results support the hypothesis that LLSVPs signify large-scale mantle upwelling in two antipodal regions of the mantle.
Progressive approach to eruption at Campi Flegrei caldera in southern Italy
Authors: Kilburn Christopher R.J. , De Natale Giuseppe , Carlino Stefano
Published: May 2017

Unrest at large calderas rarely ends in eruption, encouraging vulnerable communities to perceive emergency warnings of volcanic activity as false alarms. A classic example is the Campi Flegrei caldera in southern Italy, where three episodes of major uplift since 1950 have raised its central district by about 3 m without an eruption. Individual episodes have conventionally been treated as independent events, so that only data from an ongoing episode are considered pertinent to evaluating eruptive potential. An implicit assumption is that the crust relaxes accumulated stress after each episode. Here we apply a new model of elastic-brittle failure to test the alternative view that successive episodes promote a long-term accumulation of stress in the crust. The results provide the first quantitative evidence that Campi Flegrei is evolving towards conditions more favourable to eruption and identify field tests for predictions on how the caldera will behave during future unrest.
An in-plane magnetic chiral dichroism approach for measurement of intrinsic magnetic signals using transmitted electrons
Authors: Song Dongsheng , Tavabi Amir H. , Li Zi-An , Kovács András , Rusz Ján , Huang Wenting , Richter Gunther , Dunin-Borkowski Rafal E. , Zhu Jing
Published: May 2017

Electron energy-loss magnetic chiral dichroism is a powerful technique that allows the local magnetic properties of materials to be measured quantitatively with close-to-atomic spatial resolution and element specificity in the transmission electron microscope. Until now, the technique has been restricted to measurements of the magnetic circular dichroism signal in the electron beam direction. However, the intrinsic magnetization directions of thin samples are often oriented in the specimen plane, especially when they are examined in magnetic-field-free conditions in the transmission electron microscope. Here, we introduce an approach that allows in-plane magnetic signals to be measured using electron magnetic chiral dichroism by selecting a specific diffraction geometry. We compare experimental results recorded from a cobalt nanoplate with simulations to demonstrate that an electron magnetic chiral dichroism signal originating from in-plane magnetization can be detected successfully.
Dynamic diversity of synthetic supramolecular polymers in water as revealed by hydrogen/deuterium exchange
Authors: Lou Xianwen , Lafleur René P. M. , Leenders Christianus M. A. , Schoenmakers Sandra M. C. , Matsumoto Nicholas M. , Baker Matthew B. , van Dongen Joost L. J. , Palmans Anja R. A. , Meijer E W
Published: May 2017

Numerous self-assembling molecules have been synthesized aiming at mimicking both the structural and dynamic properties found in living systems. Here we show the application of hydrogen/deuterium exchange (HDX) mass spectrometry (MS) to unravel the nanoscale organization and the structural dynamics of synthetic supramolecular polymers in water. We select benzene-1,3,5-tricarboxamide (BTA) derivatives that self-assemble in H2O to illustrate the strength of this technique for supramolecular polymers. The BTA structure has six exchangeable hydrogen atoms and we follow their exchange as a function of time after diluting the H2O solution with a 100-fold excess of D2O. The kinetic H/D exchange profiles reveal that these supramolecular polymers in water are dynamically diverse; a notion that has previously not been observed using other techniques. In addition, we report that small changes in the molecular structure can be used to control the dynamics of synthetic supramolecular polymers in water.
Link between light-triggered Mg-banding and chamber formation in the planktic foraminifera Neogloboquadrina dutertrei
Authors: Fehrenbacher Jennifer S. , Russell Ann D. , Davis Catherine V. , Gagnon Alexander C. , Spero Howard J. , Cliff John B. , Zhu Zihua , Martin Pamela
Published: May 2017

The relationship between seawater temperature and the average Mg/Ca ratios in planktic foraminifera is well established, providing an essential tool for reconstructing past ocean temperatures. However, many species display alternating high and low Mg-bands within their shell walls that cannot be explained by temperature alone. Recent experiments demonstrate that intrashell Mg variability in Orbulina universa, which forms a spherical terminal shell, is paced by the diurnal light/dark cycle. Whether Mg-heterogeneity is also diurnally paced in species with more complex shell morphologies is unknown. Here we show that high Mg/Ca-calcite forms at night in cultured specimens of the multi-chambered species Neogloboquadrina dutertrei. Our results demonstrate that N. dutertrei adds a significant amount of calcite, and nearly all Mg-bands, after the final chamber forms. These results have implications for interpreting patterns of calcification in N. dutertrei and suggest that diurnal Mg-banding is an intrinsic component of biomineralization in planktic foraminifera.
A1 beta-casein milk protein and other environmental pre-disposing factors for type 1 diabetes
Authors: Chia J S J , McRae J L , Kukuljan S , Woodford K , Elliott R B , Swinburn B , Dwyer K M
Published: May 2017

Globally type 1 diabetes incidence is increasing. It is widely accepted that the pathophysiology of type 1 diabetes is influenced by environmental factors in people with specific human leukocyte antigen haplotypes. We propose that a complex interplay between dietary triggers, permissive gut factors and potentially other influencing factors underpins disease progression. We present evidence that A1 β-casein cows’ milk protein is a primary causal trigger of type 1 diabetes in individuals with genetic risk factors. Permissive gut factors (for example, aberrant mucosal immunity), intervene by impacting the gut’s environment and the mucosal barrier. Various influencing factors (for example, breastfeeding duration, exposure to other dietary triggers and vitamin D) modify the impact of triggers and permissive gut factors on disease. The power of the dominant trigger and permissive gut factors on disease is influenced by timing, magnitude and/or duration of exposure. Within this framework, removal of a dominant dietary trigger may profoundly affect type 1 diabetes incidence. We present epidemiological, animal-based, in vitro and theoretical evidence for A1 β-casein and its β-casomorphin-7 derivative as dominant causal triggers of type 1 diabetes. The effects of ordinary milk containing A1 and A2 β-casein and milk containing only the A2 β-casein warrant comparison in prospective trials.
CXCR3 mediates ascites-directed tumor cell migration and predicts poor outcome in ovarian cancer patients
Authors: Windmüller C , Zech D , Avril S , Boxberg M , Dawidek T , Schmalfeldt B , Schmitt M , Kiechle M , Bronger H
Published: May 2017

Intraabdominal tumor dissemination is a major hallmark of epithelial ovarian cancer (EOC), but the underlying mechanisms have not been fully elucidated. The CXCR3 chemokine receptor supports migration of tumor cells to metastatic sites, but its role in ovarian cancer metastasis is largely unknown. Herein, we first screened two independent cohorts of high-grade serous ovarian cancers (HGSCs, discovery set n=60, validation set n=117) and 102 metastatic lesions for CXCR3 expression. In primary tumors, CXCR3 was particularly overexpressed by tumor cells at the invasive front. In intraabdominal metastases, tumor cells revealed a strong CXCR3 expression regardless of its expression in the corresponding primary tumor, suggesting a selection of CXCR3-overexpressing cancer cells into peritoneal niches. In support of this, CXCR3 mediated the migration of tumor cell lines OVCAR3 and SKOV3 toward malignant ascites, which was inhibited by a monoclonal anti-CXCR3 antibody in vitro. These results were prospectively validated in ascites-derived tumor cells from EOC patients ex vivo (n=9). Moreover, tumor cell-associated overexpression of CXCR3 in advanced ovarian cancer patients was associated with a reduced progression-free survival (PFS) and overall survival (OS), which remained independent of optimal debulking, age, FIGO stage and lymph node involvement (PFS: hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.30–3.45, P=0.003; OS: HR 2.36, 95% CI 1.50–3.71, P<0.001). These results in ovarian cancer patients identify CXCR3 as a potential new target to confine peritoneal spread in ovarian cancer after primary cytoreductive surgery.
Epigenetic pathway inhibitors represent potential drugs for treating pancreatic and bronchial neuroendocrine tumors
Authors: Lines K E , Stevenson M , Filippakopoulos P , Müller S , Lockstone H E , Wright B , Grozinsky-Glasberg S , Grossman A B , Knapp S , Buck D , Bountra C , Thakker R V
Published: May 2017

Cancer is associated with alterations in epigenetic mechanisms such as histone modifications and methylation of DNA, and inhibitors targeting epigenetic mechanisms represent a novel class of anti-cancer drugs. Neuroendocrine tumors (NETs) of the pancreas (PNETs) and bronchus (BNETs), which may have 5-year survivals of <50% and as low as 5%, respectively, represent targets for such drugs, as >40% of PNETs and ~35% of BNETs have mutations of the multiple endocrine neoplasia type 1 (MEN1) gene, which encodes menin that modifies histones by interacting with histone methyltransferases. We assessed 9 inhibitors of epigenetic pathways, for their effects on proliferation, by CellTiter Blue assay, and apoptosis, by CaspaseGlo assay, using 1 PNET and 2 BNET cell lines. Two inhibitors, referred to as (+)-JQ1 (JQ1) and PFI-1, targeting the bromo and extra terminal (BET) protein family which bind acetylated histone residues, were most effective in decreasing proliferation (by 40–85%, P<0.001) and increasing apoptosis (by 2–3.6 fold, P<0.001) in all 3 NET cell lines. The anti-proliferative effects of JQ1 and PFI-1 remained present for at least 48 hours after removal of the compound. JQ1, but not PFI-1, had cell cycle effects, assessed by propidium iodide staining and flow cytometry, resulting in increased and decreased proportions of NET cells in G1, and S and G2 phases, respectively. RNA Sequencing analysis revealed that these JQ1 effects were associated with increased histone 2B expression, and likely mediated through altered activity of bromodomain-containing (Brd) proteins. Assessment of JQ1 in vivo, using a pancreatic beta cell-specific conditional Men1 knockout mouse model that develops PNETs, revealed that JQ1 significantly reduced proliferation (by ~50%, P<0.0005), assessed by bromodeoxyuridine incorporation, and increased apoptosis (by ~3 fold, P<0.0005), assessed by terminal deoxynucleotidyl transferase dUTP nick end labelling, of PNETs. Thus, our studies demonstrate that BET protein inhibitors may provide new treatments for NETs.
Cyclin-dependent kinase 7 is a therapeutic target in high-grade glioma
Authors: Greenall S A , Lim Y C , Mitchell C B , Ensbey K S , Stringer B W , Wilding A L , O'Neill G M , McDonald K L , Gough D J , Day B W , Johns T G
Published: May 2017

High-grade glioma (HGG) is an incurable brain cancer. The transcriptomes of cells within HGG tumors are highly heterogeneous. This renders the tumors unresponsive or able to adapt to therapeutics targeted at single pathways, thereby causing treatment failure. To overcome this, we focused on cyclin-dependent kinase 7 (CDK7), a ubiquitously expressed molecule involved in two major drivers of HGG pathogenesis: cell cycle progression and RNA polymerase-II-based transcription. We tested the activity of THZ1, an irreversible CDK7 inhibitor, on patient-derived primary HGG cell lines and ex vivo HGG patient tissue slices, using proliferation assays, microarray analysis, high-resolution respirometry, cell cycle analysis and in vivo tumor orthografts. The cellular processes affected by CDK7 inhibition were analyzed by reverse transcriptase–quantitative PCR, western blot, flow cytometry and immunofluorescence. THZ1 perturbed the transcriptome and disabled CDK activation, leading to cell cycle arrest at G2 and DNA damage. THZ1 halted transcription of the nuclear-encoded mitochondrial ribosomal genes, reducing mitochondrial translation and oxidative respiration. It also inhibited the expression of receptor tyrosine kinases such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor-α (PDGFR-α), reducing signaling flux through the AKT, extracellular-signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3) downstream pathways. Finally, THZ1 disrupted nucleolar, Cajal body and nuclear speckle formation, resulting in reduced cytosolic translation and malfunction of the spliceosome and thus leading to aberrant mRNA processing. These findings indicate that CDK7 is crucial for gliomagenesis, validate CDK7 as a therapeutic target and provide new insight into the cellular processes that are affected by THZ1 and induce antitumor activity.
MicroRNA-645 is an oncogenic regulator in colon cancer
Authors: Guo S T , Guo X Y , Wang J , Wang C Y , Yang R H , Wang F H , Li X Y , Hondermarck H , Thorne R F , Wang Y F , Jin L , Zhang X D , Jiang C C
Published: May 2017

Despite advances in early diagnosis and the development of molecularly targeted therapy, curative treatment of colon cancer once it has metastasized is yet to be accomplished. This is closely associated with deregulated CRC cell proliferation and resistance to apoptosis. Here we reveal that upregulation of microRNA-645 (miR-645) through DNA copy number gain is responsible for enhanced proliferation and resistance to apoptosis in colon cancer. MiR-645 was upregulated in most colon cancer tissues related to adjacent normal mucosa. This appeared to be associated with amplification of a section of chromosome 20q13.13, where miR-645 is located. Inhibition of miR-645 reduced proliferation and enhanced sensitivity to apoptosis triggered by the chemotherapeutic drugs 5-fluorouracil and cisplatin in CRC cells, and retarded colon cancer xenograft growth. Conversely, overexpression of miR-645 in normal colon epithelial cells enhanced proliferation and triggered anchorage-independent cell growth. Although SRY-related HMG-box 30 (SOX30) was identified as a miR-645 target, its expression was only partially affected by miR-645, suggesting that miR-645 is a fine-tuning mechanism of SOX30 expression. Moreover, overexpression of SOX30 only moderately inhibited promotion of CRC cell proliferation by miR-645, indicating that miR-645 may have more targets that contribute to its pro-proliferation effect in colon cancer. Together, this study reveals that miR-645 can regulate oncogenesis in colon cancer with SOX30 being one of its targets.
Orbital reorientation in MnV2O4 observed by V NMR
Authors: Jo Euna , Park Sejun , Lee Jooseop , Lee Soonchil , Shim Jeong Hyun , Suzuki Takehito , Katsufuji Takuro
Published: May 2017

The simultaneous occurrence of the structural and magnetic phase transitions observed in MnV2O4 is one clear example of strong interplay among the spin, orbital and lattice degrees of freedom. The structure of MnV2O4 is switched by the magnetic field and the linear magnetostriction is very high. The orbital order mediates the interaction between the spin and the lattice generating these phenomena. In this work, we present experimental evidence of an orbital order in MnV2O4 and its reorientation under a rotating magnetic field as obtained by nuclear magnetic resonance(NMR). The shift in the resonance frequency of the V NMR spectrum is symmetrical with respect to 45° as an external magnetic field of 7 T rotates from the c-axis to the b-axis, indicating that the initial easy axis flips to the orthogonal direction most parallel to the field direction. The spectrum of V3+ ions splits into four peaks with a maximum shift of 40 MHz. Our analysis revealed that this is the combined effect of the anisotropic hyperfine field due to an ordered orbital and the dipolar hyperfine field. Reorientation of the orbital order in response to an external magnetic field accompanies the macroscopically observed magnetostriction in MnV2O4.
Prognostic relevance of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors
Authors: Song Yu-Li , Yu Run , Qiao Xin-Wei , Bai Chun-Mei , Lu Chong-Mei , Xiao Yu , Zhong Ding-Rong , Chen Jie , Zhao Yu-Pei , Zhang Tai-Ping , Song Tian-Tian , Gao He-Li , Wan Ying-Hua , Shen Lin , Chen Jie , Lv Bin , Hao Jian-Jiang , Zhang Ye , Tang Laura , Chen Yuan-Jia
Published: May 2017

Prognostic biomarkers for the pancreatic neuroendocrine tumors are needed. Proteomic study on insulinoma has been rarely reported. We identified the differential expression of proteins between insulinoma and their paired tissues by proteomic analysis, and evaluated the prognostic significance of specific proteins in pancreatic neuroendocrine tumors including insulinoma. The differential expression of select proteins was validated in more than 300 tumors using immunohistochemical staining and western blot. Methylation of UCH-L1 promoter in tumors was examined by methylation specific PCR and validated by sequencing. The concurrent expression of UCH-L1 and α-internexin was correlated with the prognosis in 2 independent collectives of patients with tumors. Sixty-two and 219 proteins were significantly down-regulated and up-regulated in insulinomas, respectively. Demethylation of UCH-L1 promoter was associated with UCH-L1 expression in tumors (p = 0.002). The concurrent expression of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors was significantly associated with better overall survival and disease-free survival in the combination of both cohorts (log rank p = 3.90 × 10−4 and p = 3.75 × 10−5, respectively) and in each of cohorts. The prognostic value of both proteins was also validated in patients with stage II and III tumors (p = 0.017 and p = 0.006, respectively). The proteins UCH-L1 and α-internexin could be independent prognostic biomarkers of pancreatic neuroendocrine tumors.
Interleukin 22 attenuated angiotensin II induced acute lung injury through inhibiting the apoptosis of pulmonary microvascular endothelial cells
Authors: Wu Zhiyong , Hu Zhipeng , Cai Xin , Ren Wei , Dai Feifeng , Liu Huagang , Chang Jinxing , Li Bowen
Published: May 2017

Apoptosis of pulmonary microvascular endothelial cells (PMVECs) was considered to be closely related to the pathogenesis of acute lung injury (ALI). We aim to investigate whether IL-22 plays protective roles in lung injury through inhibiting the apoptosis of PMVECs. ALI model was induced through subcutaneous infusion of angiotensin II (Ang II). Lung injury and infiltration of inflammatory cells were evaluated by determining the PaO2/FiO2, calculation of dry to weight ratio in lung, and immunohistochemisty analysis. Apoptosis of PMVECs was determined using TUNEL assay and flow cytometry, respectively. Immunofluorescence and Western blot analysis were used to determine the expression and localization of STAT3, as well as the nucleus transmission of STAT3 from cytoplasm after IL22 treatment. Pathological findings showed ALI was induced 1 week after AngII infusion. IL22 inhibited the AngII-induced ALI, attenuated the edema in lung and the infiltration of inflammatory cells. Also, it contributed to the apoptosis of PMVECs induced by AngII. Meanwhile, significant increase was noticed in the expression of STAT3, phosphorylation of Y705-STAT3, and migration from cytoplasm to the nucleus after IL-22 treatment (P < 0.05). The activation of STAT3 by IL22 showed significant attenuation after AG490 treatment. Our data indicated that IL22 showed protective effects on lung injury through inhibiting the AngII-induced PMVECs apoptosis and PMVEC barrier injury by activating the JAK2/STAT3 signaling pathway.
Myelination of the brain in Major Depressive Disorder: An in vivo quantitative magnetic resonance imaging study
Authors: Sacchet Matthew D. , Gotlib Ian H.
Published: May 2017

Evidence from post-mortem, genetic, neuroimaging, and non-human animal research suggests that Major Depressive Disorder (MDD) is associated with abnormalities in brain myelin content. Brain regions implicated in this research, and in MDD more generally, include the nucleus accumbens (NAcc), lateral prefrontal cortex (LPFC), insula, subgenual anterior cingulate cortex (sgACC), and medial prefrontal cortex (mPFC). We examined whether MDD is characterized by reduced myelin at the whole-brain level and in NAcc, LPFC, insula, sgACC, and mPFC. Quantitative magnetic resonance imaging (qMRI) permits the assessment of myelin content, in vivo, in the human brain through the measure of R1. In this study we used qMRI to measure R1 in 40 MDD and 40 healthy control (CTL) participants. We found that the MDD participants had lower levels of myelin than did the CTL participants at the whole-brain level and in the NAcc, and that myelin in the LPFC was reduced in MDD participants who had experienced a greater number of depressive episodes. Although further research is needed to elucidate the role of myelin in affecting emotional, cognitive, behavioral, and clinical aspects of MDD, the current study provides important new evidence that a fundamental property of brain composition, myelin, is altered in this disorder.
In-situ STEM imaging of growth and phase change of individual CuAlX precipitates in Al alloy
Authors: Liu Chunhui , Malladi Sairam K. , Xu Qiang , Chen Jianghua , Tichelaar Frans D. , Zhuge Xiaodong , Zandbergen Henny W.
Published: May 2017

Age-hardening in Al alloys has been used for over a century to improve its mechanical properties. However, the lack of direct observation limits our understanding of the dynamic nature of the evolution of nanoprecipitates during age-hardening. Using in-situ (scanning) transmission electron microscopy (S/TEM) while heating an Al-Cu alloy, we were able to follow the growth of individual nanoprecipitates at atomic scale. The heat treatments carried out at 140, 160, 180 and 200 °C reveal a temperature dependence on the kinetics of precipitation and three kinds of interactions of nano-precipitates. These are precipitate-matrix, precipitate-dislocation, and precipitate-precipitate interactions. The diffusion of Cu and Al during these interactions, results in diffusion-controlled individual precipitate growth, an accelerated growth when interactions with dislocations occur and a size dependent precipitate-precipitate interaction: growth and shrinkage. Precipitates can grow and shrink at opposite ends at the same time resulting in an effective displacement. Furthermore, the evolution of the crystal structure within an individual nanoprecipiate, specifically the mechanism of formation of the strengthening phase, θ′, during heat-treatment is elucidated by following the same precipitate through its intermediate stages for the first time using in-situ S/TEM studies.
Revealing genome-scale transcriptional regulatory landscape of OmpR highlights its expanded regulatory roles under osmotic stress in Escherichia coli K-12 MG1655
Authors: Seo Sang Woo , Gao Ye , Kim Donghyuk , Szubin Richard , Yang Jina , Cho Byung-Kwan , Palsson Bernhard O.
Published: May 2017

A transcription factor (TF), OmpR, plays a critical role in transcriptional regulation of the osmotic stress response in bacteria. Here, we reveal a genome-scale OmpR regulon in Escherichia coli K-12 MG1655. Integrative data analysis reveals that a total of 37 genes in 24 transcription units (TUs) belong to OmpR regulon. Among them, 26 genes show more than two-fold changes in expression level in an OmpR knock-out strain. Specifically, we find that: 1) OmpR regulates mostly membrane-located gene products involved in diverse fundamental biological processes, such as narU (encoding nitrate/nitrite transporter), ompX (encoding outer membrane protein X), and nuoN (encoding NADH:ubiquinone oxidoreductase); 2) by investigating co-regulation of entire sets of genes regulated by other stress-response TFs, stresses are surprisingly independently regulated among each other; and, 3) a detailed investigation of the physiological roles of the newly discovered OmpR regulon genes reveals that activation of narU represents a novel strategy to significantly improve osmotic stress tolerance of E. coli. Thus, the genome-scale approach to elucidating regulons comprehensively identifies regulated genes and leads to fundamental discoveries related to stress responses.
Room-temperature soft mode and ferroelectric like polarization in SrTiO3 ultrathin films: Infrared and ab initio study
Authors: Peng Wei-wei , Tétot Robert , Niu Gang , Amzallag Emilie , Vilquin Bertrand , Brubach Jean-Blaise , Roy Pascale
Published: May 2017

Due to the remarkable possibilities of epitaxially growing strontium titanate (SrTiO3 or STO) on silicon, this oxide is widely used as a buffer layer for integrating other perovskite oxides which allows for the development of various functional electronic devices on silicon. Moreover, STO is known to be an incipient ferroelectric in bulk but may become ferroelectric when in the form of strained ultrathin films. Given the importance of the potential applications for electronics if this property is demonstrated, we performed a spectroscopic study of STO on Si(001) templates coupling experimental and ab initio investigations. We selected six samples of ultrathin films: three strained samples (of thickness 4, 9 and 48 nm) and three relaxed samples (of equivalent thickness). Their infrared spectra show that both the mechanical stress and the thickness play major roles: higher energy modes evolve as soft modes in thinner strained films. In order to support these observations, the dynamical ab initio calculations allowed deriving the conditions for STO films to become ferroelectric at room temperature as shown by the development of a soft mode and the divergence of the in-plane dielectric constant.
A data mining approach using cortical thickness for diagnosis and characterization of essential tremor
Authors: Serrano J. Ignacio , Romero Juan P. , Castillo Ma Dolores del , Rocon Eduardo , Louis Elan D. , Benito-León Julián
Published: May 2017

Essential tremor (ET) is one of the most prevalent movement disorders. Being that it is a common disorder, its diagnosis is considered routine. However, misdiagnoses may occur regularly. Over the past decade, several studies have identified brain morphometric changes in ET, but these changes remain poorly understood. Here, we tested the informativeness of measuring cortical thickness for the purposes of ET diagnosis, applying feature selection and machine learning methods to a study sample of 18 patients with ET and 18 age- and sex-matched healthy control subjects. We found that cortical thickness features alone distinguished the two, ET from controls, with 81% diagnostic accuracy. More specifically, roughness (i.e., the standard deviation of cortical thickness) of the right inferior parietal and right fusiform areas was shown to play a key role in ET characterization. Moreover, these features allowed us to identify subgroups of ET patients as well as healthy subjects at risk for ET. Since treatment of tremors is disease specific, accurate and early diagnosis plays an important role in tremor management. Supporting the clinical diagnosis with novel computer approaches based on the objective evaluation of neuroimage data, like the one presented here, may represent a significant step in this direction.
Chitosan-Dextran sulfate coated doxorubicin loaded PLGA-PVA-nanoparticles caused apoptosis in doxorubicin resistance breast cancer cells through induction of DNA damage
Authors: Siddharth Sumit , Nayak Anmada , Nayak Deepika , Bindhani Birendra Kumar , Kundu Chanakya Nath
Published: May 2017

To overcome the toxicity, pharmacokinetics and drug resistance associated with doxorubicin (DOX), a strategy was developed by encapsulating DOX- loaded-PLGA-PVA- nanoparticles within chitosan-dextran sulfate nanoparticles (CS-DS) [CS-DS-coated-DOX-loaded -PLGA-PVA-NP] and study the sensitivity against DOX- resistance- breast cancer cells (MCF-7-DOX-R). These CS-DS and PLGA-PVA double coated DOX are spherical, stable, polydispersed and have zeta potential +2.89 mV. MCF-7- DOX-R cells were derived by exposing increasing doses of DOX in MCF-7 cells. These cells were resistance to 500 nM of DOX while parental cells were susceptible at 150 nM. The double coated NP caused more cytotoxicity in cancer and MCF-7-DOX-R cells without affecting the normal cells in comparison to DOX-loaded-PLGA-PVA-NP. These NP enhances the uptake of DOX in MCF-7-DOX-R cells and caused apoptosis by increasing apoptotic nuclei, Bax/Bcl-xL ratio, cleaved product PARP-1, tumor suppressor gene p21, p53, topoisomerase inhibition activity, DNA damage and decreasing the migratory potential of cells. An increased S phase arrest was noted in DOX and DOX- loaded- PLGA-PVA-NP treated cells but reduction of S phase and simultaneous increase of Sub-G1 was observed in double coated-NP. Thus, data revealed that CS-DS- DOX- loaded PLGA-PVA- NP caused DOX-resistance cell death by inducing inhibition of topoisomerase activity followed by DNA damage.
Selection of a horizontal reference plane in 3D evaluation: Identifying facial asymmetry and occlusal cant in orthognathic surgery planning
Authors: Lonic Daniel , Sundoro Ali , Lin Hsiu-Hsia , Lin Pei-Ju , Lo Lun-Jou
Published: May 2017

Facial asymmetry and dental occlusal cant have been detected in two-dimensional cephalometry using different horizontal reference lines, but equivalent 3-dimensional (3D) reference planes have not been thoroughly investigated. In this study, 3D cone-beam computed tomography scans of 83 consecutive patients were evaluated using a standardized 3D frame and three horizontal reference planes, Supraorbitale (Sor), Frontozygomatic (Z), and Frankfurt horizontal (FH) for cant detection. Canting was defined as a vertical difference between left and right sides of 2 mm or more, and in at least two investigated planes. Concordance for negative canting was found in 38 patients, and for positive canting in 22 patients. Discordance in cant detection was found in 23 patients (28%). 29 patients were found to have canting in at least 2 planes. The FH plane was discordant to the other two planes in 4 patients, the Sor plane in 7 patients and the Z plane in 12 patients. Youden’s index showed the highest performance for FH (0.878), followed by Sor (0.823) and Z plane (0.762). This study revealed that the FH plane was the best method for cant detection in 3D imaging. The FH plane and Sor plane can be combined if orbital asymmetry is suspected.
Super-Enhancers and Broad H3K4me3 Domains Form Complex Gene Regulatory Circuits Involving Chromatin Interactions
Authors: Cao Fan , Fang Yiwen , Tan Hong Kee , Goh Yufen , Choy Jocelyn Yeen Hui , Koh Bryan Thean Howe , Hao Tan Jiong , Bertin Nicolas , Ramadass Aroul , Hunter Ewan , Green Jayne , Salter Matthew , Akoulitchev Alexandre , Wang Wilson , Chng Wee Joo , Tenen Daniel G. , Fullwood Melissa J.
Published: May 2017

Stretched histone regions, such as super-enhancers and broad H3K4me3 domains, are associated with maintenance of cell identity and cancer. We connected super-enhancers and broad H3K4me3 domains in the K562 chronic myelogenous leukemia cell line as well as the MCF-7 breast cancer cell line with chromatin interactions. Super-enhancers and broad H3K4me3 domains showed higher association with chromatin interactions than their typical counterparts. Interestingly, we identified a subset of super-enhancers that overlap with broad H3K4me3 domains and show high association with cancer-associated genes including tumor suppressor genes. Besides cell lines, we could observe chromatin interactions by a Chromosome Conformation Capture (3C)-based method, in primary human samples. Several chromatin interactions involving super-enhancers and broad H3K4me3 domains are constitutive and can be found in both cancer and normal samples. Taken together, these results reveal a new layer of complexity in gene regulation by super-enhancers and broad H3K4me3 domains.
Drought and child mortality: a meta-analysis of small-scale surveys from Ethiopia
Authors: Delbiso Tefera Darge , Altare Chiara , Rodriguez-Llanes Jose Manuel , Doocy Shannon , Guha-Sapir Debarati
Published: May 2017

Despite the intuitive connection between drought and mortality, we still lack a sound quantitative synthesis of evidence drawn from the available data. In this study, we estimate the pooled under-five death rates (U5DR) and assess the effect of drought on child death in Ethiopia. Small-scale mortality surveys were searched from the Complex Emergency Database and then aggregated spatially and temporally with drought exposure data from the Global Drought Monitor and food insecurity data from the Famine Early Warning Systems Network. A Bayesian Poisson meta-analysis was performed on 88 surveys conducted in Ethiopia between 2009 and 2014, consisting of 55,219 under-five children. The pooled U5DR was estimated at 0.323/10,000/day (95% credible interval, CrI: 0.254–0.397), which is below both the emergency and the baseline death rate thresholds of sub-Saharan Africa. We failed to find a plausible association between drought and U5DR. However, minimal food insecure areas showed elevated U5DR compared to stressed food insecure areas. Furthermore, the U5DR increases as the prevalence of acute malnutrition increases. Targeted interventions to improve the underlying causes of child malnutrition are crucial. Further, revising and updating the existing mortality thresholds, both the baseline and the emergency, is recommended.