bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoglin integrates BMP and Wnt signalling to induce haematopoiesis through JDP2
Authors: Baik June , Magli Alessandro , Tahara Naoyuki , Swanson Scott A. , Koyano-Nakagawa Naoko , Borges Luciene , Stewart Ron , Garry Daniel J. , Kawakami Yasuhiko , Thomson James A. , Perlingeiro Rita C. R. 
Published: October 2016

AbstractMechanisms of haematopoietic and cardiac patterning remain poorly understood. Here we show that the BMP and Wnt signalling pathways are integrated in an endoglin (Eng)-dependent manner in cardiac and haematopoietic lineage specification. Eng is expressed in early mesoderm and marks both haematopoietic and cardiac progenitors. In the absence of Eng, yolk sacs inappropriately express the cardiac marker, Nkx2.5. Conversely, high levels of Eng in vitro and in vivo increase haematopoiesis and inhibit cardiogenesis. Levels of Eng determine the activation of both BMP and Wnt pathways, which are integrated downstream of Eng by phosphorylation of Smad1 by Gsk3. By interrogating Eng-dependent Wnt-mediated transcriptional changes, we identify Jdp2 as a key Eng-dependent Wnt target, sufficient to establish haematopoietic fate in early mesoderm when BMP and Wnt crosstalk is disturbed. These studies provide mechanistic insight into the integration of BMP and Wnt signalling in the establishment of haematopoietic and cardiac progenitors during embryogenesis.
Experimental creation of quantum Zeno subspaces by repeated multi-spin projections in diamond
Authors: Kalb N. , Cramer J. , Twitchen D. J. , Markham M. , Hanson R. , Taminiau T. H. 
Published: October 2016

AbstractRepeated observations inhibit the coherent evolution of quantum states through the quantum Zeno effect. In multi-qubit systems this effect provides opportunities to control complex quantum states. Here, we experimentally demonstrate that repeatedly projecting joint observables of multiple spins creates quantum Zeno subspaces and simultaneously suppresses the dephasing caused by a quasi-static environment. We encode up to two logical qubits in these subspaces and show that the enhancement of the dephasing time with increasing number of projections follows a scaling law that is independent of the number of spins involved. These results provide experimental insight into the interplay between frequent multi-spin measurements and slowly varying noise and pave the way for tailoring the dynamics of multi-qubit systems through repeated projections.
Carbon-Coated, Diatomite-Derived Nanosilicon as a High Rate Capable Li-ion Battery Anode
Authors: Campbell Brennan , Ionescu Robert , Tolchin Maxwell , Ahmed Kazi , Favors Zachary , Bozhilov Krassimir N. , Ozkan Cengiz S. , Ozkan Mihrimah 
Published: October 2016

AbstractSilicon is produced in a variety of ways as an ultra-high capacity lithium-ion battery (LIB) anode material. The traditional carbothermic reduction process required is expensive and energy-intensive; in this work, we use an efficient magnesiothermic reduction to convert the silica-based frustules within diatomaceous earth (diatomite, DE) to nanosilicon (nanoSi) for use as LIB anodes. Polyacrylic acid (PAA) was used as a binder for the DE-based nanoSi anodes for the first time, being attributed for the high silicon utilization under high current densities (up to 4C). The resulting nanoSi exhibited a high BET specific surface area of 162.6 cm2 g−1, compared to a value of 7.3 cm2 g−1 for the original DE. DE contains SiO2 architectures that make ideal bio-derived templates for nanoscaled silicon. The DE-based nanoSi anodes exhibit good cyclability, with a specific discharge capacity of 1102.1 mAh g−1 after 50 cycles at a C-rate of C/5 (0.7 A gSi−1) and high areal loading (2 mg cm−2). This work also demonstrates the fist rate capability testing for a DE-based Si anode; C-rates of C/30 - 4C were tested. At 4C (14.3 A gSi−1), the anode maintained a specific capacity of 654.3 mAh g−1 – nearly 2x higher than graphite’s theoretical value (372 mAh g−1).
A study of the temporal robustness of the growing global container-shipping network
Authors: Wang Nuo , Wu Nuan , Dong Ling-ling , Yan Hua-kun , Wu Di 
Published: October 2016

AbstractWhether they thrive as they grow must be determined for all constantly expanding networks. However, few studies have focused on this important network feature or the development of quantitative analytical methods. Given the formation and growth of the global container-shipping network, we proposed the concept of network temporal robustness and quantitative method. As an example, we collected container liner companies’ data at two time points (2004 and 2014) and built a shipping network with ports as nodes and routes as links. We thus obtained a quantitative value of the temporal robustness. The temporal robustness is a significant network property because, for the first time, we can clearly recognize that the shipping network has become more vulnerable to damage over the last decade: When the node failure scale reached 50% of the entire network, the temporal robustness was approximately −0.51% for random errors and −12.63% for intentional attacks. The proposed concept and analytical method described in this paper are significant for other network studies.
Testing multi-scale processing in the auditory system
Authors: Teng Xiangbin , Tian Xing , Poeppel David 
Published: October 2016

AbstractNatural sounds contain information on multiple timescales, so the auditory system must analyze and integrate acoustic information on those different scales to extract behaviorally relevant information. However, this multi-scale process in the auditory system is not widely investigated in the literature and existing models of temporal integration are mainly built upon detection or recognition tasks on a single timescale. Here we use a paradigm requiring processing on relatively ‘local’ and ‘global’ scales and provide evidence suggesting that the auditory system extracts fine-detail acoustic information using short temporal windows and uses long temporal windows to abstract global acoustic patterns. Behavioral task performance that requires processing fine-detail information does not improve with longer stimulus length, contrary to predictions of previous temporal integration models such as the multiple-looks and the spectro-temporal excitation pattern model. Moreover, the perceptual construction of putatively ‘unitary’ auditory events requires more than hundreds of milliseconds. These findings support the hypothesis of a dual-scale processing likely implemented in the auditory cortex.
Hepatic Deletion of Janus Kinase 2 Counteracts Oxidative Stress in Mice
Authors: Themanns Madeleine , Mueller Kristina M. , Kessler Sonja M. , Golob-Schwarzl Nicole , Mohr Thomas , Kaltenecker Doris , Bourgeais Jerome , Paier-Pourani Jamile , Friedbichler Katrin , Schneller Doris , Schlederer Michaela , Zebedin-Brandl Eva , Terracciano Luigi M. , Han Xiaonan , Kenner Lukas , Wagner Kay-Uwe , Mikulits Wolfgang , Kozlov Andrey V. , Heim Markus H. , Gouilleux Fabrice , Haybaeck Johannes , Moriggl Richard 
Published: October 2016

AbstractGenetic deletion of the tyrosine kinase JAK2 or the downstream transcription factor STAT5 in liver impairs growth hormone (GH) signalling and thereby promotes fatty liver disease. Hepatic STAT5 deficiency accelerates liver tumourigenesis in presence of high GH levels. To determine whether the upstream kinase JAK2 exerts similar functions, we crossed mice harbouring a hepatocyte-specific deletion of JAK2 (JAK2Δhep) to GH transgenic mice (GHtg) and compared them to GHtgSTAT5Δhep mice. Similar to GHtgSTAT5Δhep mice, JAK2 deficiency resulted in severe steatosis in the GHtg background. However, in contrast to STAT5 deficiency, loss of JAK2 significantly delayed liver tumourigenesis. This was attributed to: (i) activation of STAT3 in STAT5-deficient mice, which was prevented by JAK2 deficiency and (ii) increased detoxification capacity of JAK2-deficient livers, which diminished oxidative damage as compared to GHtgSTAT5Δhep mice, despite equally severe steatosis and reactive oxygen species (ROS) production. The reduced oxidative damage in JAK2-deficient livers was linked to increased expression and activity of glutathione S-transferases (GSTs). Consistent with genetic deletion of Jak2, pharmacological inhibition and siRNA-mediated knockdown of Jak2 led to significant upregulation of Gst isoforms and to reduced hepatic oxidative DNA damage. Therefore, blocking JAK2 function increases detoxifying GSTs in hepatocytes and protects against oxidative liver damage.
Glibenclamide impairs responses of neutrophils against Burkholderia pseudomallei by reduction of intracellular glutathione
Authors: Kewcharoenwong Chidchamai , Rinchai Darawan , Nithichanon Arnone , Bancroft Gregory J. , Ato Manabu , Lertmemongkolchai Ganjana 
Published: October 2016

AbstractThe major risk factor for melioidosis, an infectious disease caused by B. pseudomallei, is diabetes mellitus. More than half of diabetic melioidosis patients in Thailand were prescribed glibenclamide. Recent evidence demonstrates that glibenclamide reduces pro-inflammatory cytokine production by polymorphonuclear neutrophils (PMNs) of diabetic individuals in response to this bacterial infection. However, the mechanisms by which glibenclamide affects cytokine production are unknown. We found that PMNs from glibenclamide-treated diabetic individuals infected with live B. pseudomallei in vitro showed lower free glutathione (GSH) levels compared with those of healthy individuals. Glibenclamide decreased GSH levels and glutathione peroxidase (GPx) of PMNs after exposed to live B. pseudomallei. Moreover, glibenclamide reduced cytokine production and migration capacity of infected PMNs, whereas GSH could restore these functions. Taken together, our data show a link between the effect of glibenclamide on GSH and PMN functions in response to B. pseudomallei that may contribute to the susceptibility of diabetic individuals to B. pseudomallei infection.
Implementation of Arithmetic and Nonarithmetic Functions on a Label-free and DNA-based Platform
Authors: Wang Kun , He Mengqi , Wang Jin , He Ronghuan , Wang Jianhua 
Published: October 2016

AbstractA series of complex logic gates were constructed based on graphene oxide and DNA-templated silver nanoclusters to perform both arithmetic and nonarithmetic functions. For the purpose of satisfying the requirements of progressive computational complexity and cost-effectiveness, a label-free and universal platform was developed by integration of various functions, including half adder, half subtractor, multiplexer and demultiplexer. The label-free system avoided laborious modification of biomolecules. The designed DNA-based logic gates can be implemented with readout of near-infrared fluorescence, and exhibit great potential applications in the field of bioimaging as well as disease diagnosis.
Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage
Authors: Lei Beilei , James Michael L. , Liu Ji , Zhou Guanen , Venkatraman Talaignair N. , Lascola Christopher D. , Acheson Shawn K. , Dubois Laura G. , Laskowitz Daniel T. , Wang Haichen 
Published: October 2016

AbstractPresently, no pharmacological treatments have been demonstrated to improve long-term functional outcomes following intracerebral hemorrhage (ICH). Clinical evidence associates apolipoprotein E (apoE) genotype with ICH incidence and outcome. While apoE modifies neuroinflammatory responses through its adaptive role in glial downregulation, intact apoE holoprotein is too large to cross the blood-brain barrier (BBB). Therefore, we developed a 5-amino acid peptide – CN-105 – that mimics the polar face of the apoE helical domain involved in receptor interactions. In the current study, we investigated the therapeutic potential of CN-105 in a mouse model of ICH. Three doses of CN-105 (0.05 mg/kg) was administered by tail vein injection within 24 hours after ICH induction. Functional assessment showed durable improvement in vestibulomotor performance after CN-105 treatment, as quantified by increased Rotarod latencies on Days 1–5 post-ICH, and long-term improvement in neurocognitive performance, as quantified by reduced Morris water maze latencies on Days 29–32 post-ICH. Further, brain water content was significantly reduced, neuroinflammation was decreased and hippocampal CA3 neuronal survival was increased, although hemorrhage volume was not affected by CN-105. We concluded, therefore, that pentapeptide CN-105 improved short- and long-term neurobehavioral outcomes in a murine model of ICH, suggesting therapeutic potential for patients with acute ICH.
Metabolomics of aging assessed in individual parasitoid wasps
Authors: Kapranas Apostolos , Snart Charles J. P. , Williams Huw , Hardy Ian C. W. , Barrett David A. 
Published: October 2016

AbstractMetabolomics studies of low-biomass organisms, such as small insects, have previously relied on the pooling of biological samples to overcome detection limits, particularly using NMR. We show that the differentiation of metabolite profiles of individual 1 mg parasitoid wasps of different ages is possible when using a modified sample preparation and a combination of untargeted NMR and LC-MS based metabolomics. Changes were observed between newly emerged and older wasps in glycerolipids, amino acids and circulatory sugars. This advance in chemical profiling has important implications for the study of the behaviour and ecology of parasitoids and many other species of small organisms because predictions and observations are typically made at the level of the individual. Thus, the metabolomic state of low-biomass individuals can now be related to their behaviour and ecological performance. We discuss specifically the utility of age-related metabolomic profiling but our new approach can be applied to a wide range of biological research.
Disruption of ArhGAP15 results in hyperactive Rac1, affects the architecture and function of hippocampal inhibitory neurons and causes cognitive deficits
Authors: Zamboni Valentina , Armentano Maria , Sarò Gabriella , Ciraolo Elisa , Ghigo Alessandra , Germena Giulia , Umbach Alessandro , Valnegri Pamela , Passafaro Maria , Carabelli Valentina , Gavello Daniela , Bianchi Veronica , D’Adamo Patrizia , de Curtis Ivan , El-Assawi Nadia , Mauro Alessandro , Priano Lorenzo , Ferri Nicola , Hirsch Emilio , Merlo Giorgio R. 
Published: October 2016

AbstractDuring brain development, the small GTPases Rac1/Rac3 play key roles in neuronal migration, neuritogenesis, synaptic formation and plasticity, via control of actin cytoskeleton dynamic. Their activity is positively and negatively regulated by GEFs and GAPs molecules, respectively. However their in vivo roles are poorly known. The ArhGAP15 gene, coding for a Rac-specific GAP protein, is expressed in both excitatory and inhibitory neurons of the adult hippocampus, and its loss results in the hyperactivation of Rac1/Rac3. In the CA3 and dentate gyrus (DG) regions of the ArhGAP15 mutant hippocampus the CR+, PV+ and SST+ inhibitory neurons are reduced in number, due to reduced efficiency and directionality of their migration, while pyramidal neurons are unaffected. Loss of ArhGAP15 alters neuritogenesis and the balance between excitatory and inhibitory synapses, with a net functional result consisting in increased spike frequency and bursts, accompanied by poor synchronization. Thus, the loss of ArhGAP15 mainly impacts on interneuron-dependent inhibition. Adult ArhGAP15−/− mice showed defective hippocampus-dependent functions such as working and associative memories. These findings indicate that a normal architecture and function of hippocampal inhibitory neurons is essential for higher hippocampal functions, and is exquisitely sensitive to ArhGAP15-dependent modulation of Rac1/Rac3.
Characterisation of sensitivity and orientation tuning for visually responsive ensembles in the zebrafish tectum
Authors: Thompson A. W. , Scott E. K. 
Published: October 2016

AbstractSensory coding relies on ensembles of co-active neurons, but these ensembles change from trial to trial of the same stimulus. This is due in part to wide variability in the responsiveness of neurons within these ensembles, with some neurons responding regularly to a stimulus while others respond inconsistently. The specific functional properties that cause neurons to respond more or less consistently have not been thoroughly explored. Here, we have examined neuronal ensembles in the zebrafish tectum responsive to repeated presentations of a visual stimulus, and have explored how these populations change when the orientation or brightness of the stimulus is altered. We found a continuum of response probabilities across the neurons in the visual ensembles, with the most responsive neurons focused toward the spatial centre of the ensemble. As the visual stimulus was made dimmer, these neurons remained active, suggesting higher overall responsiveness. However, these cells appeared to represent the most consistent end of a continuum, rather than a functionally distinct “core” of highly responsive neurons. Reliably responsive cells were broadly tuned to a range of stimulus orientations suggesting that, at least for this stimulus property, tight stimulus tuning was not responsible for their consistent responses.
Genome Sequencing of the Pyruvate-producing Strain Candida glabrata CCTCC M202019 and Genomic Comparison with Strain CBS138
Authors: Xu Nan , Ye Chao , Chen Xiulai , Liu Jia , Liu Liming , Chen Jian 
Published: October 2016

AbstractCandida glabrata CCTCC M202019 as an industrial yeast strain that is widely used to produce α-oxocarboxylic acid. Strain M202019 has been proven to have a higher pyruvate-producing capacity than the reference strain CBS138. To characterize the genotype of the M202019 strain, we generated a draft sequence of its genome, which has a size of 12.1 Mbp and a GC content of 38.47%. Evidence accumulated during genome annotation suggests that strain M202019 has strong capacities for glucose transport and pyruvate biosynthesis, defects in pyruvate catabolism, as well as variations in genes involved in nutrient and dicarboxylic acid transport, oxidative phosphorylation, and other relevant aspects of carbon metabolism, which might promote pyruvate accumulation. In addition to differences in its central carbon metabolism, a genomic analysis revealed genetic differences in adhesion metabolism. Forty-nine adhesin-like proteins of strain M202019 were identified classified into seven subfamilies. Decreased amounts of adhesive proteins, and deletions or changes of low-complexity repeats and functional domains might lead to lower adhesion and reduced pathogenicity. Further virulence experiments validated the biological safety of strain M202019. Analysis of the C. glabrata CCTCC M202019 genome sequence provides useful insights into its genetic context, physical characteristics, and potential metabolic capacity.
Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via β-catenin
Authors: Huang Chu-Wei , Chen Yi-Wen , Lin Yi-Rou , Chen Po-Han , Chou Meng-Hsuan , Lee Li-Jen , Wang Pei-Yu , Wu June-Tai , Tsao Yeou-Ping , Chen Show-Li 
Published: October 2016

AbstractBreast carcinoma amplified sequence 2 (BCAS2) is a core component of the hPrP19 complex that controls RNA splicing. Here, we performed an exon array assay and showed that β-catenin is a target of BCAS2 splicing regulation. The regulation of dendrite growth and morphology by β-catenin is well documented. Therefore, we generated conditional knockout (cKO) mice to eliminate the BCAS2 expression in the forebrain to investigate the role of BCAS2 in dendrite growth. BCAS2 cKO mice showed a microcephaly-like phenotype with a reduced volume in the dentate gyrus (DG) and low levels of learning and memory, as evaluated using Morris water maze analysis and passive avoidance, respectively. Golgi staining revealed shorter dendrites, less dendritic complexity and decreased spine density in the DG of BCAS2 cKO mice. Moreover, the cKO mice displayed a short dendrite length in newborn neurons labeled by DCX, a marker of immature neurons, and BrdU incorporation. To further examine the mechanism underlying BCAS2-mediated dendritic malformation, we overexpressed β-catenin in BCAS2-depleted primary neurons and found that the dendritic growth was restored. In summary, BCAS2 is an upstream regulator of β-catenin gene expression and plays a role in dendrite growth at least partly through β-catenin.
PAK1 confers chemoresistance and poor outcome in non-small cell lung cancer via β-catenin-mediated stemness
Authors: Chen Ming-Jenn , Wu De-Wei , Wang Yao-Chen , Chen Chi-Yi , Lee Huei 
Published: October 2016

AbstractPAK1 confers resistance to the estrogen antagonist tamoxifen in breast cancer. However, a role for PAK1 remains to be elucidated for chemoresistance and prognosis in non-small cell lung cancer (NSCLC). We provide evidence that PAK1 confers cisplatin resistance by increasing β-catenin expression through ERK/GSK3β signaling. The increased β-catenin expression promotes sphere cell formation and expression of stemness markers and this β-catenin-induced stemness is responsible for PAK1-mediated cisplatin resistance. We enrolled 87 NSCLC patients who had received cisplatin-based chemotherapy to confirm the association between PAK1 expression and response to chemotherapy and outcomes. PAK1 expression, evaluated by immunohistochemistry, was positively correlated with pERK and β-catenin expression in lung tumors. Patients with high-PAK1, high-pERK, and high-nuclear β-catenin tumors more frequently showed an unfavorable response to cisplatin-based chemotherapy when compared to their counterparts. Kaplan-Meier and Cox regression analysis also indicated a poorer overall survival (OS) and relapse free survival (RFS) in patients with high-PAK1, high-pERK, and high-nuclear β-catenin tumors. In conclusion, PAK1 confers cisplatin resistance in NSCLC via β-catenin-mediated stemness. Therefore, we suggest that clinical use of a combination of the MEK/ERK inhibitor AZD6244 and cisplatin might improve sensitivity to cisplatin-based chemotherapy and outcomes in NSCLC patients who harbor high-PAK1-expressing tumors.
Effects of Melanocortin 3 and 4 Receptor Deficiency on Energy Homeostasis in Rats
Authors: You Panpan , Hu Handan , Chen Yuting , Zhao Yongliang , Yang Yiqing , Wang Tongtong , Xing Roumei , Shao Yanjiao , Zhang Wen , Li Dali , Chen Huaqing , Liu Mingyao 
Published: October 2016

AbstractMelanocortin-3 and 4 receptors (MC3R and MC4R) can regulate energy homeostasis, but their respective roles especially the functions of MC3R need more exploration. Here Mc3r and Mc4r single and double knockout (DKO) rats were generated using CRISPR-Cas9 system. Metabolic phenotypes were examined and data were compared systematically. Mc3r KO rats displayed hypophagia and decreased body weight, while Mc4r KO and DKO exhibited hyperphagia and increased body weight. All three mutants showed increased white adipose tissue mass and adipocyte size. Interestingly, although Mc3r KO did not show a significant elevation in lipids as seen in Mc4r KO, DKO displayed even higher lipid levels than Mc4r KO. DKO also showed more severe glucose intolerance and hyperglycaemia than Mc4r KO. These data demonstrated MC3R deficiency caused a reduction of food intake and body weight, whereas at the same time exhibited additive effects on top of MC4R deficiency on lipid and glucose metabolism. This is the first phenotypic analysis and systematic comparison of Mc3r KO, Mc4r KO and DKO rats on a homogenous genetic background. These mutant rats will be important in defining the complicated signalling pathways of MC3R and MC4R. Both Mc4r KO and DKO are good models for obesity and diabetes research.