bluuebunny/crossref_metadata_2025_split huggingface dataset:
EpCAM (CD326) is differentially expressed in craniopharyngioma subtypes and Rathke’s cleft cysts
Authors: Thimsen Vivian , Hölsken Annett , Buchfelder Michael , Flitsch Jörg , Fahlbusch Rudolf , Stefanits Harald , Losa Marco , Jones David T. W. , Buslei Rolf 
Published: July 2016

AbstractThe epithelial cell adhesion molecule (EpCAM) is a type I glycoprotein located on the surface of epithelial cells. It is strongly expressed in many neoplasms and already used in the diagnosis and distinction of various tumour subtypes. Comparative studies about EpCAM expression in cystic sellar lesions are lacking. Therefore, we analysed its distribution pattern in adamantinomatous (aCP) and papillary (pCP) craniopharyngiomas (CP) and Rathke’s Cleft Cysts (RCC) using immunohistochemistry and gene expression profiling. Whereas the protein was not detectable in pCP (n = 10), all aCP (n = 64) showed distinct staining patterns. The vast majority of RCC (n = 10) also appeared positive, but these displayed notably lower labeling scores. Additionally, significantly higher mRNA levels were detectable in aCP (n = 19) when compared to pCP (n = 10) (p = 9.985−8). Furthermore, pediatric aCP cases, in general, exhibited stronger EpCAM staining levels compared to adult ones (p = 0.015). However, we were not able to verify this result on mRNA level. In summary, our findings demonstrate that EpCAM can be used as an additional distinction-marker for cystic lesions of the sellar region. Its unknown function in aCP and the presence of an approved monoclonal bispecific trifunctional antibody for cancer therapy are interesting starting points for further studies.
Engineering MoSx/Ti/InP Hybrid Photocathode for Improved Solar Hydrogen Production
Authors: Li Qiang , Zheng Maojun , Zhong Miao , Ma Liguo , Wang Faze , Ma Li , Shen Wenzhong 
Published: July 2016

AbstractDue to its direct band gap of ~1.35 eV, appropriate energy band-edge positions and low surface-recombination velocity, p-type InP has attracted considerable attention as a promising photocathode material for solar hydrogen generation. However, challenges remain with p-type InP for achieving high and stable photoelectrochemical (PEC) performances. Here, we demonstrate that surface modifications of InP photocathodes with Ti thin layers and amorphous MoSx nanoparticles can remarkably improve their PEC performances. A high photocurrent density with an improved PEC onset potential is obtained. Electrochemical impedance analyses reveal that the largely improved PEC performance of MoSx/Ti/InP is attributed to the reduced charge-transfer resistance and the increased band bending at the MoSx/Ti/InP/electrolyte interface. In addition, the MoSx/Ti/InP photocathodes function stably for PEC water reduction under continuous light illumination over 2 h. Our study demonstrates an effective approach to develop high-PEC-performance InP photocathodes towards stable solar hydrogen production.
Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells
Authors: Huang Zebing , Wang Haiyan , Wang Jingke , Zhao Mengqin , Sun Nana , Sun Fangfang , Shen Jianxin , Zhang Haiying , Xia Kunkun , Chen Dejie , Gao Ming , Hammer Ronald P. , Liu Qingrong , Xi Zhengxiong , Fan Xuegong , Wu Jie 
Published: July 2016

AbstractEmerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis.
Highly Multiplexed RNA Aptamer Selection using a Microplate-based Microcolumn Device
Authors: Reinholt Sarah J. , Ozer Abdullah , Lis John T. , Craighead Harold G. 
Published: July 2016

AbstractWe describe a multiplexed RNA aptamer selection to 19 different targets simultaneously using a microcolumn-based device, MEDUSA (Microplate-based Enrichment Device Used for the Selection of Aptamers), as well as a modified selection process, that significantly reduce the time and reagents needed for selections. We exploited MEDUSA’s reconfigurable design between parallel and serially-connected microcolumns to enable the use of just 2 aliquots of starting library and its 96-well microplate compatibility to enable the continued use of high-throughput techniques in downstream processes. Our modified selection protocol allowed us to perform the equivalent of a 10-cycle selection in the time it takes for 4 traditional selection cycles. Several aptamers were discovered with nanomolar dissociation constants. Furthermore, aptamers were identified that not only bound with high affinity, but also acted as inhibitors to significantly reduce the activity of their target protein, mouse decapping exoribonuclease (DXO). The aptamers resisted DXO’s exoribonuclease activity and in studies monitoring DXO’s degradation of a 30-nucleotide substrate, less than 1 μM of aptamer demonstrated significant inhibition of DXO activity. This aptamer selection method using MEDUSA helps to overcome some of the major challenges with traditional aptamer selections and provides a platform for high-throughput selections that lends itself to process automation.
Systematic investigation of transcription factors critical in the protection against cerebral ischemia by Danhong injection
Authors: Wei Junying , Zhang Yanqiong , Jia Qiang , Liu Mingwei , Li Defeng , Zhang Yi , Song Lei , Hu Yanzhen , Xian Minghua , Yang Hongjun , Ding Chen , Huang Luqi 
Published: July 2016

AbstractSystematic investigations of complex pathological cascades during ischemic brain injury help to elucidate novel therapeutic targets against cerebral ischemia. Although some transcription factors (TFs) involved in cerebral ischemia, systematic surveys of their changes during ischemic brain injury have not been reported. Moreover, some multi-target agents effectively protected against ischemic stroke, but their mechanisms, especially the targets of TFs, are still unclear. Therefore, a comprehensive approach by integrating network pharmacology strategy and a new concatenated tandem array of consensus transcription factor response elements method to systematically investigate the target TFs critical in the protection against cerebral ischemia by a medication was first reported and then applied to a multi-target drug, Danhong injection (DHI). High-throughput nature and depth of coverage, as well as high quantitative accuracy of the developed approach, make it more suitable for analyzing such multi-target agents. Results indicated that pre-B-cell leukemia transcription factor 1 and cyclic AMP-dependent transcription factor 1, along with six other TFs, are putative target TFs for DHI-mediated protection against cerebral ischemia. This study provides, for the first time, a systematic investigation of the target TFs critical to DHI-mediated protection against cerebral ischemia, as well as reveals more potential therapeutic targets for ischemic stroke.
Designation of highly efficient catalysts for one pot conversion of glycerol to lactic acid
Authors: Tao Meilin , Dan Zhang  , Guan Hongyu , Huang Guohui , Wang Xiaohong 
Published: July 2016

AbstractProduction of lactic acid from glycerol is a cascade catalytic procedure using multifunctional catalysts combined with oxidative and acidic catalytic sites. Therefore, a series of silver-exchanged phosphomolybdic acid catalysts (AgxH3−xPMo12O40, x = 1 ~ 3, abbreviated as AgxPMo) was designed and applied in glycerol oxidation with O2 as an oxidant to produce lactic acid (LA) without adding any base. Among all, total silver exchanged phosphomolybdic acid (Ag3PMo) was found to be the most active one with LA selectivity of 93% at 99% conversion under mild conditions of 5 h at 60 °C. The exceptionally high efficiency was contributed to the generation of strong Lewis acid sites, enhanced redox potentials and water-tolerance. More importantly, Ag3PMo was tolerant in crude glycerol from biodiesel production. And the reaction mechanism was also discussed. Meanwhile, Ag3PMo acted as a heterogeneous catalyst for 12 recycles without loss of activity.
Focal adhesions control cleavage furrow shape and spindle tilt during mitosis
Authors: Taneja Nilay , Fenix Aidan M. , Rathbun Lindsay , Millis Bryan A. , Tyska Matthew J. , Hehnly Heidi , Burnette Dylan T. 
Published: July 2016

AbstractThe geometry of the cleavage furrow during mitosis is often asymmetric in vivo and plays a critical role in stem cell differentiation and the relative positioning of daughter cells during development. Early observations of adhesive cell lines revealed asymmetry in the shape of the cleavage furrow, where the bottom (i.e., substrate attached side) of the cleavage furrow ingressed less than the top (i.e., unattached side). This data suggested substrate attachment could be regulating furrow ingression. Here we report a population of mitotic focal adhesions (FAs) controls the symmetry of the cleavage furrow. In single HeLa cells, stronger adhesion to the substrate directed less ingression from the bottom of the cell through a pathway including paxillin, focal adhesion kinase (FAK) and vinculin. Cell-cell contacts also direct ingression of the cleavage furrow in coordination with FAs in epithelial cells—MDCK—within monolayers and polarized cysts. In addition, mitotic FAs established 3D orientation of the mitotic spindle and the relative positioning of mother and daughter centrosomes. Therefore, our data reveals mitotic FAs as a key link between mitotic cell shape and spindle orientation and may have important implications in our understanding stem cell homeostasis and tumorigenesis.
Thymocyte development in the absence of matrix metalloproteinase-9/gelatinase B
Authors: Gounko Natalia V. , Martens Erik , Opdenakker Ghislain , Rybakin Vasily 
Published: July 2016

AbstractMatrix metalloproteinases (MMP) play critical roles in a variety of immune reactions by facilitating cell migration, and affect cell communication by processing both cytokines and cell surface receptors. Based on published data indicating that MMP-9 is upregulated upon T cell activation and also in the thymus upon the induction of negative selection, we investigated the contribution of MMP-9 into mouse T cell development and differentiation in the thymus. Our data suggest that MMP-9 deficiency does not result in major abnormalities in the development of any conventionally selected or agonist selected subsets and does not interfere with thymocyte apoptosis and clearance, and that MMP-9 expression is not induced in immature T cells at any stage of their thymic development.
The autism-related gene SNRPN regulates cortical and spine development via controlling nuclear receptor Nr4a1
Authors: Li Huiping , Zhao Pingping , Xu Qiong , Shan Shifang , Hu Chunchun , Qiu Zilong , Xu Xiu 
Published: July 2016

AbstractThe small nuclear ribonucleoprotein polypeptide N (SNRPN) gene, encoding the RNA-associated SmN protein, duplications or deletions of which are strongly associated with neurodevelopmental disabilities. SNRPN-coding protein is highly expressed in the brain. However, the role of SNRPN protein in neural development remains largely unknown. Here we showed that the expression of SNRPN increased markedly during postnatal brain development. Overexpression or knockdown of SNRPN in cortical neurons impaired neurite outgrowth, neuron migration and the distribution of dendritic spines. We found that SNRPN regulated the expression level of Nr4a1, a critical nuclear receptor during neural development, in cultured primary cortical neurons. The abnormal spine development caused by SNRPN overexpression could be fully rescued by Nr4a1 co-expression. Importantly, we found that either knockdown of Nr4a1 or 3, 3′- Diindolylmethane (DIM), an Nr4a1 antagonist, were able to rescue the effects of SNRPN knockdown on neurite outgrowth of embryonic cortical neurons, providing the potential therapeutic methods for SNRPN deletion disorders. We thus concluded that maintaining the proper level of SNRPN is critical in cortical neurodevelopment. Finally, Nr4a1 may serve as a potential drug target for SNRPN-related neurodevelopmental disabilities, including Prader-Willi syndrome (PWS) and autism spectrum disorders (ASDs).
Comparative chemical array screening for p38γ/δ MAPK inhibitors using a single gatekeeper residue difference between p38α/β and p38γ/δ
Authors: Kondoh Yasumitsu , Honda Kaori , Hiranuma Sayoko , Hayashi Teruo , Shimizu Takeshi , Watanabe Nobumoto , Osada Hiroyuki 
Published: July 2016

AbstractMammalian p38 mitogen activated protein kinases (MAPKs) are responsive to a variety of cellular stresses. The development of specific pyridinyl imidazole inhibitors has permitted the characterization of the p38 MAPK isoform p38α, which is expressed in most cell types, whereas the physiological roles of p38γ and p38δ are poorly understood. In this study, we report an approach for identifying selective inhibitors against p38γ and p38δ by focusing on the difference in gatekeeper residues between p38α/β and p38γ/δ. Using GST-fused p38α wild type and T106M mutant constructs, wherein the p38α gatekeeper residue (Thr-106) was substituted by the p38γ/δ-type (Met), we performed comparative chemical array screening to identify specific binders of the mutant and identified SU-002 bound to p38αT106M specifically. SU-002 was found to inhibit p38αT106M but not p38α kinase activity in in vitro kinase assays. SU-005, the analog of SU-002, had inhibitory effects against the kinase activity of p38γ and p38δ in vitro but not p38α. In addition, SU-005 inhibited both p38γ and p38δ auto-phosphorylation in HeLa and HEK293T cells. These results demonstrate that the comparative chemical array screening approach is a powerful technique to explore specific inhibitors for mutant proteins with even single amino-acid substitutions in a high-throughput manner.
Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting
Authors: Zhu Yuanjun , Li Ruyi , Lin Yuan , Shui Mengyang , Liu Xiaoyan , Chen Huan , Wang Yinye 
Published: July 2016

AbstractTargeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency.
Compact SIW dual‐band bandpass filter using novel dual‐resonance quasi‐SIW‐transmission‐line‐structure resonators
Authors: Wsx Hezheng , Wu Ying 
Published: July 2016

A compact substrate integrated waveguide (SIW) dual‐band bandpass filter (DBSF) using novel quasi‐SIW‐transmission‐line‐structure resonators is proposed in this study. This dual‐resonance SIW resonator which works in TE100 mode and TE201 mode can be evolved from a conventional SIW‐transmission line or a two‐conductor transmission line. Multiple signals transmission paths bring extra transmission zeros (TZs) and improve the selectivity and out‐band rejection of the DBSF. This filter works at 4.75 GHz/4.82 GHz, 5.38 GHz/5.51 GHz with 3 dB fractional bandwidths of 3.8 and 3.9%, respectively, and has six TZs. The measured results agree with the simulation results well.
Protective responses to sublytic complement in the retinal pigment epithelium
Authors: Tan Li Xuan , Toops Kimberly A. , Lakkaraju Aparna 
Published: July 2016

Significance
The complement system regulates immune defense and inflammation. Abnormal complement activation in the retina is associated with blinding macular degenerations, which have limited treatment options. The retinal pigment epithelium (RPE) is an initial site of injury in macular degenerations, but mechanisms that protect the RPE from complement-mediated damage are unclear. Here, we identify two critical responses to complement in the RPE: accelerated recycling of the complement inhibitor CD59 and lysosome-mediated membrane repair. We show that in models of macular degeneration, excess cholesterol impairs both defense mechanisms, resulting in mitochondrial damage. Drugs that decrease RPE cholesterol restore these mechanisms and help the RPE combat complement attack. Our studies identify promising drug targets to preserve RPE health and function in macular degenerations.
Fortnightly modulation of San Andreas tremor and low-frequency earthquakes
Authors: van der Elst Nicholas J. , Delorey Andrew A. , Shelly David R. , Johnson Paul A. 
Published: July 2016

Significance
The sun and moon exert a gravitational tug on Earth that stretches and compresses crustal rocks. This cyclic stressing can promote or inhibit fault slip, particularly at the deep roots of faults. The amplitude of the solid Earth tide varies over a fortnightly (2-wk) cycle, as the sun and moon change their relative positions in the sky. In this study, we show that deep, small earthquakes on the San Andreas Fault are most likely to occur during the waxing fortnightly tide—not when the tidal amplitude is highest, as might be expected, but when the tidal amplitude most exceeds its previous value. The response of faults to the tidal cycle opens a window into the workings of plate tectonics.
Directed evolution of a sphingomyelin flippase reveals mechanism of substrate backbone discrimination by a P4-ATPase
Authors: Roland Bartholomew P. , Graham Todd R. 
Published: July 2016

Significance
The asymmetric organization of cellular membranes is a critical determinant of cell and tissue physiology. Phospholipid flippases are principle regulators of this membrane asymmetry, and understanding their mechanics will be important for determining how deficiencies of these enzymes lead to several different diseases. The current study has identified a key structural mechanism for the exclusion of sphingomyelin as a flippase substrate. Understanding how these unique enzymes recognize and transport substrates can direct pharmacologic and therapeutic strategies for medical applications. Finally, the specificity of this designer enzyme represents a unique opportunity to modulate membrane biology intentionally through directed perturbations in phospholipid asymmetry.
Diversity of immune strategies explained by adaptation to pathogen statistics
Authors: Mayer Andreas , Mora Thierry , Rivoire Olivier , Walczak Aleksandra M. 
Published: July 2016

Significance
Organisms possess many mechanisms for protecting themselves from pathogens. In addition to the well-studied innate and adaptive immune systems of vertebrates, recently discovered mechanisms such as CRISPR immunity in prokaryotes diversify the known modes of information processing used in immune protection. By classifying these different systems in terms of their rules of heritability and response to the environment, we propose a mathematical framework that recapitulates the observed natural diversity of immune systems. We show how the basic modes of immunity emerge as optimal strategies of a population adapting to a changing pathogenic environment. The proposed framework offers a unified view of immunity across species and helps rationalize the diversity of observed mechanisms.
Dynamic neural activity during stress signals resilient coping
Authors: Sinha Rajita , Lacadie Cheryl M. , Constable R. Todd , Seo Dongju 
Published: July 2016

Significance
We live in a time of increasing terror, stress, and trauma, and yet humans show a remarkable ability to cope under high stress states. How the brain supports such active resilient coping is not well-understood. Findings showed high stress levels are accompanied by dynamic brain signals in circuits representing the stress reaction, adaptation, and behavioral control responses. In addition, a ventromedial prefrontal cortical region showed initial decreases in brain activation, but then mobilized with increased activation, and this dynamic change was correlated with active coping. Conversely, individuals who failed to show such “neuroflexibility” in this specific ventromedial prefrontal region reported higher maladaptive coping behaviors. Findings suggest that strategies to promote such neuroflexibility under stress may increase stress resilience in humans.
Root morphology and mycorrhizal symbioses together shape nutrient foraging strategies of temperate trees
Authors: Chen Weile , Koide Roger T. , Adams Thomas S. , DeForest Jared L. , Cheng Lei , Eissenstat David M. 
Published: July 2016

Significance
Plant growth requires acquisition of soil nutrients in a patchy environment. Nutrient patches may be actively foraged by symbioses comprising roots and mycorrhizal fungi. Here, we show that thicker root tree species (e.g., tulip poplar, pine) respond weakly or not at all to nutrient heterogeneity. In contrast, thinner root tree species readily respond by selectively growing roots [arbuscular mycorrhizal trees (e.g., maple)] or mycorrhizal fungal hyphae [ectomycorrhizal trees (e.g., oak)] in nutrient-rich “hotspots.” Our results thus indicate predictable patterns of nutrient foraging among tree species with contrasting mycorrhiza types and root morphologies. These findings can pave the way for a more holistic understanding of root-microbial function, which is critical to plant growth and biogeochemical cycles in forested ecosystems.