bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractSculpting 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

AbstractAnuran 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

AbstractThe 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

AbstractThe 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

AbstractAdvances 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

AbstractUnrest 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

AbstractElectron 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

AbstractNumerous 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

AbstractThe 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

AbstractGlobally 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

AbstractIntraabdominal 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

AbstractCancer 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

AbstractHigh-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

AbstractDespite 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

AbstractThe 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.