bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection
Authors: Cabral-Piccin M P , Guillermo L V C , Vellozo N S , Filardy A A , Pereira-Marques S T , Rigoni T S , Pereira-Manfro W F , DosReis G A , Lopes M F 
Published: May 2016

AbstractChagas disease is caused by infection with the protozoan Trypanosoma cruzi. CD8 T-lymphocytes help to control infection, but apoptosis of CD8 T cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. Here, we investigate how apoptosis of activated CD8 T cells affects M1 and M2 macrophage phenotypes. First, we found that CD8 T-lymphocytes and inflammatory monocytes/macrophages infiltrate peritoneum during acute T. cruzi infection. We show that treatment with anti-Fas ligand (FasL) prevents lymphocyte apoptosis, upregulates type-1 responses to parasite antigens, and reduces infection in macrophages cocultured with activated CD8 T cells. Anti-FasL skews mixed M1/M2 macrophage profiles into polarized M1 phenotype, both in vitro and following injection in infected mice. Moreover, inhibition of T-cell apoptosis induces a broad reprogramming of cytokine responses and improves macrophage-mediated immunity to T. cruzi. The results indicate that disposal of apoptotic CD8 T cells increases M2-macrophage differentiation and contributes to parasite persistence.
Size quantization of Dirac fermions in graphene constrictions
Authors: Terrés B. , Chizhova L. A. , Libisch F. , Peiro J. , Jörger D. , Engels S. , Girschik A. , Watanabe K. , Taniguchi T. , Rotkin S. V. , Burgdörfer J. , Stampfer C. 
Published: May 2016

AbstractQuantum point contacts are cornerstones of mesoscopic physics and central building blocks for quantum electronics. Although the Fermi wavelength in high-quality bulk graphene can be tuned up to hundreds of nanometres, the observation of quantum confinement of Dirac electrons in nanostructured graphene has proven surprisingly challenging. Here we show ballistic transport and quantized conductance of size-confined Dirac fermions in lithographically defined graphene constrictions. At high carrier densities, the observed conductance agrees excellently with the Landauer theory of ballistic transport without any adjustable parameter. Experimental data and simulations for the evolution of the conductance with magnetic field unambiguously confirm the identification of size quantization in the constriction. Close to the charge neutrality point, bias voltage spectroscopy reveals a renormalized Fermi velocity of ∼1.5 × 106 m s−1 in our constrictions. Moreover, at low carrier density transport measurements allow probing the density of localized states at edges, thus offering a unique handle on edge physics in graphene devices.
Multifunctional hydrogel nano-probes for atomic force microscopy
Authors: Lee Jae Seol , Song Jungki , Kim Seong Oh , Kim Seokbeom , Lee Wooju , Jackman Joshua A. , Kim Dongchoul , Cho Nam-Joon , Lee Jungchul 
Published: May 2016

AbstractSince the invention of the atomic force microscope (AFM) three decades ago, there have been numerous advances in its measurement capabilities. Curiously, throughout these developments, the fundamental nature of the force-sensing probe—the key actuating element—has remained largely unchanged. It is produced by long-established microfabrication etching strategies and typically composed of silicon-based materials. Here, we report a new class of photopolymerizable hydrogel nano-probes that are produced by bottom-up fabrication with compressible replica moulding. The hydrogel probes demonstrate excellent capabilities for AFM imaging and force measurement applications while enabling programmable, multifunctional capabilities based on compositionally adjustable mechanical properties and facile encapsulation of various nanomaterials. Taken together, the simple, fast and affordable manufacturing route and multifunctional capabilities of hydrogel AFM nano-probes highlight the potential of soft matter mechanical transducers in nanotechnology applications. The fabrication scheme can also be readily utilized to prepare hydrogel cantilevers, including in parallel arrays, for nanomechanical sensor devices.
Probing topological protection using a designer surface plasmon structure
Authors: Gao Fei , Gao Zhen , Shi Xihang , Yang Zhaoju , Lin Xiao , Xu Hongyi , Joannopoulos John D. , Soljačić Marin , Chen Hongsheng , Lu Ling , Chong Yidong , Zhang Baile 
Published: May 2016

AbstractTopological photonic states, inspired by robust chiral edge states in topological insulators, have recently been demonstrated in a few photonic systems, including an array of coupled on-chip ring resonators at communication wavelengths. However, the intrinsic difference between electrons and photons determines that the ‘topological protection’ in time-reversal-invariant photonic systems does not share the same robustness as its counterpart in electronic topological insulators. Here in a designer surface plasmon platform consisting of tunable metallic sub-wavelength structures, we construct photonic topological edge states and probe their robustness against a variety of defect classes, including some common time-reversal-invariant photonic defects that can break the topological protection, but do not exist in electronic topological insulators. This is also an experimental realization of anomalous Floquet topological edge states, whose topological phase cannot be predicted by the usual Chern number topological invariants.
Novel positive allosteric modulators of GABAA receptors with anesthetic activity
Authors: Maldifassi Maria C. , Baur Roland , Pierce David , Nourmahnad Anahita , Forman Stuart A. , Sigel Erwin 
Published: May 2016

AbstractGABAA receptors are the main inhibitory neurotransmitter receptors in the brain and are targets for numerous clinically important drugs such as benzodiazepines, anxiolytics and anesthetics. We previously identified novel ligands of the classical benzodiazepine binding pocket in α1β2γ2 GABAA receptors using an experiment-guided virtual screening (EGVS) method. This screen also identified novel ligands for intramembrane low affinity diazepam site(s). In the current study we have further characterized compounds 31 and 132 identified with EGVS as well as 4-O-methylhonokiol. We investigated the site of action of these compounds in α1β2γ2 GABAA receptors expressed in Xenopus laevis oocytes using voltage-clamp electrophysiology combined with a benzodiazepine site antagonist and transmembrane domain mutations. All three compounds act mainly through the two β+/α− subunit transmembrane interfaces of the GABAA receptors. We then used concatenated receptors to dissect the involvement of individual β+/α− interfaces. We further demonstrated that these compounds have anesthetic activity in a small aquatic animal model, Xenopus laevis tadpoles. The newly identified compounds may serve as scaffolds for the development of novel anesthetics.
MicroRNA-30 inhibits neointimal hyperplasia by targeting Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ)
Authors: Liu Yong Feng , Spinelli Amy , Sun Li-Yan , Jiang Miao , Singer Diane V. , Ginnan Roman , Saddouk Fatima Z. , Van Riper Dee , Singer Harold A. 
Published: May 2016

AbstractThe multifunctional Ca2+/calmodulin-dependent protein kinase II δ-isoform (CaMKIIδ) promotes vascular smooth muscle (VSM) proliferation, migration, and injury-induced vascular wall neointima formation. The objective of this study was to test if microRNA-30 (miR-30) family members are endogenous regulators of CaMKIIδ expression following vascular injury and whether ectopic expression of miR-30 can inhibit CaMKIIδ-dependent VSM cell function and neointimal VSM hyperplasia induced by vascular injury. The CaMKIIδ 3′UTR contains a consensus miR-30 binding sequence that is highly conserved across species. A significant decrease in miR-30 family members and increase in CaMKIIδ2 protein expression, with no change in CaMKIIδ mRNA expression, was observed in medial layers of VSM 7 days post-injury. In vitro, overexpression of miR-30c or miR-30e inhibited CaMKIIδ2 protein expression by ~50% in cultured rat aortic VSM cells, and inhibited VSM cell proliferation and migration. In vivo, lenti-viral delivery of miR-30c into injured rat carotid arteries prevented the injury-induced increase in CaMKIIδ2. Furthermore, neointima formation was dramatically inhibited by lenti-viral delivery of miR-30c in the injured medial smooth muscle. These studies define a novel mechanism for regulating CaMKIIδ expression in VSM and provide a new potential therapeutic strategy to reduce progression of vascular proliferative diseases, including atherosclerosis and restenosis.
Mapping the ecological dimensions and potential distributions of endangered relic shrubs in western Ordos biodiversity center
Authors: Zhu Geng-Ping , Li Hui-Qi , Zhao Li , Man Liang , Liu Qiang 
Published: May 2016

AbstractPotential distributions of endemic relic shrubs in western Ordos were poorly mapped, which hindered our implementation of proper conservation. Here we investigated the applicability of ecological niche modeling for endangered relic shrubs to detect areas of priority for biodiversity conservation and analyze differences in ecological niche spaces used by relic shrubs. We applied ordination and niche modeling techniques to assess main environmental drivers of five endemic relic shrubs in western Ordos, namely,Ammopiptanthus mongolicus, Amygdalus mongolica, Helianthemum songaricum, Potaninia mongolica, andTetraena mongolica. We calculated niche overlap metrics in gridded environmental spaces and compared geographical projections of ecological niches to determine similarities and differences of niches occupied by relic shrubs. All studied taxa presented different responses to environmental factors, which resulted in a unique combination of niche conditions. Precipitation availability and soil quality characteristics play important roles in the distributions of most shrubs. Each relic shrub is constrained by a unique set of environmental conditions, the distribution of one species cannot be implied by the distribution of another, highlighting the inadequacy of one-fits-all type of conservation measure. Our stacked habitat suitability maps revealed regions around Yellow River, which are highly suitable for most species, thereby providing high conservation value.
Expression of an Oncogenic BARD1 Splice Variant Impairs Homologous Recombination and Predicts Response to PARP-1 Inhibitor Therapy in Colon Cancer
Authors: Ozden Ozkan , Bishehsari Faraz , Bauer Jessica , Park Seong-Hoon , Jana Arundhati , Baik Seung Hyun , Sporn Judith C. , Staudacher Jonas J. , Yazici Cemal , Krett Nancy , Jung Barbara 
Published: May 2016

AbstractBRCA1-associated RING domain protein 1 (BARD1) stabilizes BRCA1 protein by forming a heterodimeric RING-RING complex and impacts function of BRCA1, including homologous recombination (HR) repair. Although colon cancer cells usually express wild type BRCA1, presence of an oncogenic BARD1 splice variant (SV) in select cancers may render BRCA1 dysfunctional and allow cells to become sensitive to HR targeting therapies. We previously reported association of loss of full-length (FL) BARD1 with poor prognosis in colon cancer as well as expression of various BARD1 SVs with unknown function. Here we show that loss of BARD1 function through the expression of a BARD1 SV, BARD1β, results in a more malignant phenotype with decreased RAD51 foci formation, reduced BRCA1 E3 ubiquitin ligase activity and decreased nuclear BRCA1 protein localization. BARD1β sensitizes colon cancer cells to poly ADP ribose polymerase 1 (PARP-1) inhibition even in a FL BRCA1 background. These results suggest that expression of BARD1β may serve as a future biomarker to assess suitability of colon cancers for HR targeting with PARP-1 inhibitors in treatment of advanced colon cancer.
Nrf2/Keap1 system regulates vascular smooth muscle cell apoptosis for vascular homeostasis: role in neointimal formation after vascular injury
Authors: Ashino Takashi , Yamamoto Masayuki , Numazawa Satoshi 
Published: May 2016

AbstractAbnormal increases in vascular smooth muscle cells (VSMCs) in the intimal region after a vascular injury is a key event in developing neointimal hyperplasia. To maintain vascular function, proliferation and apoptosis of VSMCs is tightly controlled during vascular remodeling. NF-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) system, a key component of the oxidative stress response that acts in maintaining homeostasis, plays an important role in neointimal hyperplasia after a vascular injury; however, the role of Nrf2/Keap1 in VSMC apoptosis has not been clarified. Here we report that 14 days after arterial injury in mice, TUNEL-positive VSMCs are detected in both the neointimal and medial layers. These layers contain cells expressing high levels of Nrf2 but low Keap1 expression. In VSMCs, Keap1 depletion induces features of apoptosis, such as positive TUNEL staining and annexin V binding. These changes are associated with an increased expression of nuclear Nrf2. Simultaneous Nrf2 depletion inhibits Keap1 depletion-induced apoptosis. At 14 days after the vascular injury, Nrf2-deficient mice demonstrated fewer TUNEL-positive cells and increased neointimal formation in the neointimal and medial areas. The results suggest that the Nrf2/Keap1 system regulates VSMC apoptosis during neointimal formation, thereby inhibiting neointimal hyperplasia after a vascular injury.
Key role of scale morphology in flatfishes (Pleuronectiformes) in the ability to keep sand
Authors: Spinner Marlene , Kortmann Mareike , Traini Camille , Gorb Stanislav N. 
Published: May 2016

AbstractFlatfishes bury themselves for camouflage and protection. Whereas species-specific preferences for certain sediments were previously shown, the role of scales in interaction with sediment has not been investigated. Here, scale morphology and sediment friction were examined in four European pleuronectiforms:Limanda limanda, Platichthys flesus, Pleuronectes platessaandSolea solea. All species had different scale types ranging from cycloid to ctenoid scales. On the blind side, the number of scales is higher and scales have less ctenial spines than on the eye side. The critical angle of sediment sliding (static friction) significantly depended on the grain size and was considerably higher on the eye side. The effect of mucus was excluded by repeated measurements on resin replicas of the skin. Our results demonstrate the impact of scale morphology on sediment interaction and give an insight about the ability of scales to keep sand. Exposed scales and a higher number of ctenial spines on the eye side lead to an increase of friction forces, especially for sediments with a smaller grain size. Our results suggest that the evolution of scales was at least partly driven by their interactions with sediment which confirms the relevance of sediment for the distribution and radiation of Pleuronectiformes.
The Effects of Tumstatin on Vascularity, Airway Inflammation and Lung Function in an Experimental Sheep Model of Chronic Asthma
Authors: Van der Velden Joanne , Harkness Louise M. , Barker Donna M. , Barcham Garry J. , Ugalde Cathryn L. , Koumoundouros Emmanuel , Bao Heidi , Organ Louise A. , Tokanovic Ana , Burgess Janette K. , Snibson Kenneth J. 
Published: May 2016

AbstractTumstatin, a protein fragment of the alpha-3 chain of Collagen IV, is known to be significantly reduced in the airways of asthmatics. Further, there is evidence that suggests a link between the relatively low level of tumstatin and the induction of angiogenesis and inflammation in allergic airway disease. Here, we show that the intra-segmental administration of tumstatin can impede the development of vascular remodelling and allergic inflammatory responses that are induced in a segmental challenge model of experimental asthma in sheep. In particular, the administration of tumstatin to lung segments chronically exposed to house dust mite (HDM) resulted in a significant reduction of airway small blood vessels in the diameter range 10+–20 μm compared to controls. In tumstatin treated lung segments after HDM challenge, the number of eosinophils was significantly reduced in parenchymal and airway wall tissues, as well as in the bronchoalveolar lavage fluid. The expression of VEGF in airway smooth muscle was also significantly reduced in tumstatin-treated segments compared to control saline-treated segments. Allergic lung function responses were not attenuated by tumstatin administration in this model. The data are consistent with the concept that tumstatin can act to suppress vascular remodelling and inflammation in allergic airway disease.
Inverted Gabor holography principle for tailoring arbitrary shaped three-dimensional beams
Authors: Latychevskaia Tatiana , Fink Hans-Werner 
Published: May 2016

AbstractIt is well known that by modifying the wavefront in a certain manner, the light intensity can be turned into a certain shape. However, all known light modulation techniques allow for limited light modifications only: focusing within a restricted region in space, shaping into a certain class of parametric curves along the optical axis or bending described by a quadratic-dependent deflection as in the case of Airy beams. We show a general case of classical light wavefront shaping that allows for intensity and phase redistribution into an arbitrary profile including pre-determined switching-off of the intensity. To create an arbitrary three-dimensional path of intensity, we represent the path as a sequence of closely packed individual point-like absorbers and simulate the in-line hologram of the created object set; when such a hologram is contrast inverted, thus giving rise to a diffractor, it creates the pre-determined three-dimensional path of intensity behind the diffractor under illumination. The crucial parameter for a smooth optical path is the sampling of the predetermined curves, which is given by the lateral and axial resolution of the optical system. We provide both, simulated and experimental results to demonstrate the power of this novel method.
Piperlongumine inhibits lung tumor growth via inhibition of nuclear factor kappa B signaling pathway
Authors: Zheng Jie , Son Dong Ju , Gu Sun Mi , Woo Ju Rang , Ham Young Wan , Lee Hee Pom , Kim Wun Jae , Jung Jae Kyung , Hong Jin Tae 
Published: May 2016

AbstractPiperlongumine has anti-cancer activity in numerous cancer cell lines via various signaling pathways. But there has been no study regarding the mechanisms of PL on the lung cancer yet. Thus, we evaluated the anti-cancer effects and possible mechanisms of PL on non-small cell lung cancer (NSCLC) cellsin vivoandin vitro. Our findings showed that PL induced apoptotic cell death and suppressed the DNA binding activity of NF-κB in a concentration dependent manner (0–15 μM) in NSCLC cells. Docking model and pull down assay showed that PL directly binds to the DNA binding site of nuclear factor-κB (NF-κB) p50 subunit, and surface plasmon resonance (SPR) analysis showed that PL binds to p50 concentration-dependently. Moreover, co-treatment of PL with NF-κB inhibitor phenylarsine oxide (0.1 μM) or p50 siRNA (100 nM) augmented PL-induced inhibitory effect on cell growth and activation of Fas and DR4. Notably, co-treatment of PL with p50 mutant plasmid (C62S) partially abolished PL-induced cell growth inhibition and decreased the enhanced expression of Fas and DR4. In xenograft mice model, PL (2.5–5 mg/kg) suppressed tumor growth of NSCLC dose-dependently. Therefore, these results indicated that PL could inhibit lung cancer cell growth via inhibition of NF-κB signaling pathwayin vitroandin vivo.
Knockout of ho-1 protects the striatum from ferrous iron-induced injury in a male-specific manner in mice
Authors: Wang Li-Fang , Yokoyama Kazunari K. , Lin Chih-Lung , Chen Tzu-Yin , Hsiao Hsiu-Wen , Chiang Pei-Chi , Hsu Chin 
Published: May 2016

AbstractMen have worse survival than premenopausal women after intracerebral hemorrhage (ICH). After ICH, overproduction of iron associated with induction of heme oxygenase-1 (HO-1) in brain was observed. Rodent ICH model using ferrous citrate (FC)-infusion into the striatum to simulate iron overload, showed a higher degree of injury severity in males than in females. However, the participation of HO-1 in sex-differences of iron-induced brain injury remains unknown. The present results showed a higher level of HO-1 expression associated with more severe injury in males compared with females after FC-infusion. Estradiol (E2) contributed to lower levels of FC-induced HO-1 expression in females compared with males. Heterozygote ho-1 KO decreased the levels of FC-induced injury severity, histological lesions, behavioral deficits, autophagy and autophagic cell death in the striatum of males but not in females. Moreover, ho-1 deficiency enhanced the neuroprotection by E2 only in males. These results suggested that over induction of HO-1 plays a harmful role in FC-induced brain injury in a male-specific manner. Suppression of HO-1 combined with E2 exhibits a synergistic effect on neuroprotection against FC-induced striatal injury in males. These findings open up the prospect for male-specific neuroprotection targeting HO-1 suppression for patients suffering from striatal iron overload.
Transcriptome shock invokes disruption of parental expression-conserved genes in tetraploid wheat
Authors: Zhang Huakun , Gou Xiaowan , Zhang Ai , Wang Xutong , Zhao Na , Dong Yuzhu , Li Linfeng , Liu Bao 
Published: May 2016

AbstractAllopolyploidy often triggers phenotypic novelty and gene expression remolding in the resulting polyploids. In this study, we employed multiple phenotypic and genetic approaches to investigate the nature and consequences of allotetraploidization between A- and S-subgenome of tetraploid wheat. Results showed that karyotype of the nascent allopolyploid plants (AT2) is stable but they showed clear novelty in multiple morphological traits which might have positively contributed to the initial establishment of the tetraploids. Further microarray-based transcriptome profiling and gene-specific cDNA-pyrosequencing have documented that transcriptome shock was exceptionally strong in AT2, but a substantial proportion of the induced expression changes was rapidly stabilized in early generations. Meanwhile, both additive and nonadditive expression genes showed extensive homeolog expression remodeling and which have led to the subgenome expression dominance in leaf and young inflorescence of AT2. Through comparing the homeolog-expressing patterns between synthetic and natural tetraploid wheats, it appears that the shock-induced expression changes at both the total expression level and subgenome homeolog partitioning are evolutionarily persistent. Together, our study shed new light on how gene expression changes have rapidly occurred at the initial stage following allotetraploidization, as well as their evolutionary relevance, which may have implications for wheat improvements.