bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell surface Glut1 levels distinguish human CD4 and CD8 T lymphocyte subsets with distinct effector functions
Authors: Cretenet Gaspard , Clerc Isabelle , Matias Maria , Loisel Severine , Craveiro Marco , Oburoglu Leal , Kinet Sandrina , Mongellaz Cédric , Dardalhon Valérie , Taylor Naomi 
Published: April 2016

AbstractCD4 and CD8 T lymphocyte activation requires the generation of sufficient energy to support new biosynthetic demands. Following T cell receptor (TCR) engagement, these requirements are met by an increased glycolysis, due, at least in part, to induction of the Glut1 glucose transporter. As Glut1 is upregulated on tumor cells in response to hypoxia, we assessed whether surface Glut1 levels regulate the antigen responsiveness of human T lymphocytes in both hypoxic and atmospheric oxygen conditions. Notably, Glut1 upregulation in response to TCR stimulation was significantly higher in T lymphocytes activated under hypoxic as compared to atmospheric oxygen conditions. Furthermore, TCR-stimulated human T lymphocytes sorted on the basis of Glut1-Lo and Glut1-Hi profiles maintained distinct characteristics, irrespective of the oxygen tension. While T cells activated in hypoxia divided less than those activated in atmospheric oxygen, Glut1-Hi lymphocytes exhibited increased effector phenotype acquisition, augmented proliferation and an inverted CD4/CD8 ratio in both oxygen conditions. Moreover, Glut1-Hi T lymphocytes exhibited a significantly enhanced ability to produce IFN-γ and this secretion potential was completely dependent on continued glycolysis. Thus, Glut1 surface levels identify human T lymphocytes with distinct effector functions in both hypoxic and atmospheric oxygen tensions.
Monocyte-derived macrophages exhibit distinct and more restricted HIV-1 integration site repertoire than CD4+ T cells
Authors: Kok Yik Lim , Vongrad Valentina , Shilaih Mohaned , Di Giallonardo Francesca , Kuster Herbert , Kouyos Roger , Günthard Huldrych F. , Metzner Karin J. 
Published: April 2016

AbstractThe host genetic landscape surrounding integrated HIV-1 has an impact on the fate of the provirus. Studies analysing HIV-1 integration sites in macrophages are scarce. We studied HIV-1 integration site patterns in monocyte-derived macrophages (MDMs) and activated CD4+ T cells derived from seven antiretroviral therapy (ART)-treated HIV-1-infected individuals whose cells were infected ex vivo with autologous HIV-1 isolated during the acute phase of infection. A total of 1,484 unique HIV-1 integration sites were analysed. Their distribution in the human genome and genetic features, and the effects of HIV-1 integrase polymorphisms on the nucleotide selection specificity at these sites were indistinguishable between the two cell types, and among HIV-1 isolates. However, the repertoires of HIV-1-hosting gene clusters overlapped to a higher extent in MDMs than in CD4+ T cells. The frequencies of HIV-1 integration events in genes encoding HIV-1-interacting proteins were also different between the two cell types. Lastly, HIV-1-hosting genes linked to clonal expansion of latently HIV-1-infected CD4+ T cells were over-represented in gene hotspots identified in CD4+ T cells but not in those identified in MDMs. Taken together, the repertoire of genes targeted by HIV-1 in MDMs is distinct from and more restricted than that of CD4+ T cells.
New potential binding determinant for hERG channel inhibitors
Authors: Saxena P. , Zangerl-Plessl E.-M. , Linder T. , Windisch A. , Hohaus A. , Timin E. , Hering S. , Stary-Weinzinger A. 
Published: April 2016

AbstractHuman ether-à-go-go related gene (hERG) 1 channels conduct the rapid delayed rectifier K+ current (IKr) and are essential for the repolarization of the cardiac action potential. hERG1 inhibition by structurally diverse drugs may lead to life threatening arrhythmia. Putative binding determinants of hERG1 channel blockers include T623, S624 and V625 on the pore helix and residues G648, Y652 and F656, located on segment S6. We and others have previously hypothesized that additional binding determinants may be located on helix S5, which is in close contact with the S6 segments. In order to test this hypothesis, we performed a detailed investigation combining ionic current measurements with two-microelectrode voltage clamp and molecular modeling techniques. We identified a novel aromatic high affinity binding determinant for blockers located in helix S5, F557, which is equally potent as Y652. Modeling supports a direct interaction with the outer pore helix.
Colony-Level Differences in the Scaling Rules Governing Wood Ant Compound Eye Structure
Authors: Perl Craig D. , Niven Jeremy E. 
Published: April 2016

AbstractDifferential organ growth during development is essential for adults to maintain the correct proportions and achieve their characteristic shape. Organs scale with body size, a process known as allometry that has been studied extensively in a range of organisms. Such scaling rules, typically studied from a limited sample, are assumed to apply to all members of a population and/or species. Here we study scaling in the compound eyes of workers of the wood ant,Formica rufa, from different colonies within a single population. Workers’ eye area increased with body size in all the colonies showing a negative allometry. However, both the slope and intercept of some allometric scaling relationships differed significantly among colonies. Moreover, though mean facet diameter and facet number increased with body size, some colonies primarily increased facet number whereas others increased facet diameter, showing that the cellular level processes underlying organ scaling differed among colonies. Thus, the rules that govern scaling at the organ and cellular levels can differ even within a single population.
RUNX2 Mutation Impairs 1α,25-Dihydroxyvitamin D3 mediated Osteoclastogenesis in Dental Follicle Cells
Authors: Wang X. Z. , Sun X. Y. , Zhang C. Y. , Yang X. , Yan W. J. , Ge L. H. , Zheng S. G. 
Published: April 2016

AbstractCleidocranial dysplasia (CCD), a skeletal disorder characterized by delayed permanent tooth eruption and other dental abnormalities, is caused by heterozygousRUNX2mutations. As an osteoblast-specific transcription factor,RUNX2plays a role in bone remodeling, tooth formation and tooth eruption. To investigate the crosstalk betweenRUNX2and 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) in human dental follicle cells (hDFCs) during osteoclast formation, we established a co-culture system of hDFCs from CCD patient and healthy donors with peripheral blood mononuclear cells (PBMCs). Expression of the osteoclast-associated genes and the number of TRAP+cells were reduced in CCD hDFCs, indicating its suppressed osteoclast-inductive ability, which was reflected by the downregulated RANKL/OPG ratio. In addition, 1α,25-(OH)2D3-stimulation elevated the expression of osteoclast-related genes, as well asRANKLmRNA levels and RANKL/OPG ratios in control hDFCs. Conversely,RUNX2mutation abolished this 1α,25-(OH)2D3-inducedRANKLgene activation and osteoclast formation in CCD hDFCs. Therefore,RUNX2haploinsufficiency impairs dental follicle-induced osteoclast formation capacity through RANKL/OPG signaling, which may be partially responsible for delayed permanent tooth eruption in CCD patients. Furthermore, this abnormality was not rescued by 1α,25-(OH)2D3application because 1α,25-(OH)2D3-induced RANKL activation in hDFCs is mediated principally via theRUNX2-dependent pathway.
Transcriptome Variability in Keratocystic Odontogenic Tumor Suggests Distinct Molecular Subtypes
Authors: Hu Shijia , Divaris Kimon , Parker Joel , Padilla Ricardo , Murrah Valerie , Wright John Timothy 
Published: April 2016

AbstractKeratocystic Odontogenic Tumor (KCOT) is a locally aggressive developmental cystic neoplasm thought to arise from the odontogenic epithelium. A high recurrence rate of up to 30% has been found following conservative treatment. Aggressive tumor resection can lead to the need for extensive reconstructive surgery, resulting in significant morbidity and impacting quality of life. Most research has focused on candidate-genes with a handful of studies employing whole transcriptome approaches. There is also the question of which reference tissue is most biologically-relevant. This study characterizes the transcriptome of KCOT using whole genome microarray and compare it with gene expression of different odontogenic tissues (“dentome”). Laser capture microdissection was used to isolate the neoplastic epithelial tissue in 20 cases. KCOT gene expression was compared with the “dentome” and relevant pathways were examined. Cluster analysis revealed 2 distinct molecular subtypes of KCOT. Several inflammatory pathways were activated in both subtypes. The AKT pathway was activated in one subtype while MAP kinase pathway was activated in the other. Additionally, PTCH1 expression was downregulated in both clusters suggesting involvement in KCOT tumorigenesis. In conclusion, this study provides new insights into the transcriptome of KCOT and highlights pathways that could be of diagnostic and prognostic value.
Optimizing Dynamical Network Structure for Pinning Control
Authors: Orouskhani Yasin , Jalili Mahdi , Yu Xinghuo 
Published: April 2016

AbstractControlling dynamics of a network from any initial state to a final desired state has many applications in different disciplines from engineering to biology and social sciences. In this work, we optimize the network structure for pinning control. The problem is formulated as four optimization tasks: i) optimizing the locations of driver nodes, ii) optimizing the feedback gains, iii) optimizing simultaneously the locations of driver nodes and feedback gains and iv) optimizing the connection weights. A newly developed population-based optimization technique (cat swarm optimization) is used as the optimization method. In order to verify the methods, we use both real-world networks and model scale-free and small-world networks. Extensive simulation results show that the optimal placement of driver nodes significantly outperforms heuristic methods including placing drivers based on various centrality measures (degree, betweenness, closeness and clustering coefficient). The pinning controllability is further improved by optimizing the feedback gains. We also show that one can significantly improve the controllability by optimizing the connection weights.
Cell-permeable p38 MAP kinase promotes migration of adult neural stem/progenitor cells
Authors: Hamanoue Makoto , Morioka Kazuhito , Ohsawa Ikuroh , Ohsawa Keiko , Kobayashi Masaaki , Tsuburaya Kayo , Akasaka Yoshikiyo , Mikami Tetsuo , Ogata Toru , Takamatsu Ken 
Published: April 2016

AbstractEndogenous neural stem/progenitor cells (NPCs) can migrate toward sites of injury, but the migration activity of NPCs is insufficient to regenerate damaged brain tissue. In this study, we showed that p38 MAP kinase (p38) is expressed in doublecortin-positive adult NPCs. Experiments using the p38 inhibitor SB203580 revealed that endogenous p38 participates in NPC migration. To enhance NPC migration, we generated a cell-permeable wild-type p38 protein (PTD-p38WT) in which the HIV protein transduction domain (PTD) was fused to the N-terminus of p38. Treatment with PTD-p38WT significantly promoted the random migration of adult NPCs without affecting cell survival or differentiation; this effect depended on the cell permeability and kinase activity of the fusion protein. These findings indicate that PTD-p38WT is a novel and useful tool for unraveling the roles of p38 and that this protein provides a reasonable approach for regenerating the injured brain by enhancing NPC migration.
Water orientation and hydrogen-bond structure at the fluorite/water interface
Authors: Khatib Rémi , Backus Ellen H. G. , Bonn Mischa , Perez-Haro María-José , Gaigeot Marie-Pierre , Sulpizi Marialore 
Published: April 2016

AbstractWater in contact with mineral interfaces is important for a variety of different processes. Here, we present a combined theoretical/experimental study which provides a quantitative, molecular-level understanding of the ubiquitous and important CaF2/water interface. Our results show that, at low pH, the surface is positively charged, causing a substantial degree of water ordering. The surface charge originates primarily from the dissolution of fluoride ions, rather than from adsorption of protons to the surface. At high pH we observe the presence of Ca-OH species pointing into the water. These OH groups interact remarkably weakly with the surrounding water and are responsible for the “free OH” signature in the VSFG spectrum, which can be explained from local electronic structure effects. The quantification of the surface termination, near-surface ion distribution and water arrangement is enabled by a combination of advanced phase-resolved Vibrational Sum Frequency Generation spectra of CaF2/water interfaces and state-of-the-art ab initio molecular dynamics simulations which include electronic structure effects.
Uncertainty assessment of PM2.5 contamination mapping using spatiotemporal sequential indicator simulations and multi-temporal monitoring data
Authors: Yang Yong , Christakos George , Huang Wei , Lin Chengda , Fu Peihong , Mei Yang 
Published: April 2016

AbstractBecause of the rapid economic growth in China, many regions are subjected to severe particulate matter pollution. Thus, improving the methods of determining the spatiotemporal distribution and uncertainty of air pollution can provide considerable benefits when developing risk assessments and environmental policies. The uncertainty assessment methods currently in use include the sequential indicator simulation (SIS) and indicator kriging techniques. However, these methods cannot be employed to assess multi-temporal data. In this work, a spatiotemporal sequential indicator simulation (STSIS) based on a non-separable spatiotemporal semivariogram model was used to assimilate multi-temporal data in the mapping and uncertainty assessment of PM2.5 distributions in a contaminated atmosphere. PM2.5 concentrations recorded throughout 2014 in Shandong Province, China were used as the experimental dataset. Based on the number of STSIS procedures, we assessed various types of mapping uncertainties, including single-location uncertainties over one day and multiple days and multi-location uncertainties over one day and multiple days. A comparison of the STSIS technique with the SIS technique indicate that a better performance was obtained with the STSIS method.
Quantifying the Anthropogenic Footprint in Eastern China
Authors: Meng Chunlei , Dou Youjun 
Published: April 2016

AbstractUrban heat island (UHI) is one of the most focuses in urban climate study. The parameterization of the anthropogenic heat (AH) is crucial important in UHI study, but universal method to parameterize the spatial pattern of the AH is lacking now. This paper uses the NOAA DMSP/OLS nighttime light data to parameterize the spatial pattern of the AH. Two experiments were designed and performed to quantify the influences of the AH to land surface temperature (LST) in eastern China and 24 big cities. The annual mean heating caused by AH is up to 1 K in eastern China. This paper uses the relative LST differences rather than the absolute LST differences between the control run and contrast run of common land model (CoLM) to find the drivers. The heating effect of the anthropogenic footprint has less influence on relatively warm and wet cities.
Rolling-induced Face Centered Cubic Titanium in Hexagonal Close Packed Titanium at Room Temperature
Authors: Wu H. C. , Kumar A. , Wang J. , Bi X. F. , Tomé C. N. , Zhang Z. , Mao S. X. 
Published: April 2016

AbstractCombining transmission electron microscopes and density functional theory calculations, we report the nucleation and growth mechanisms of room temperature rolling induced face-centered cubic titanium (fcc-Ti) in polycrystalline hexagonal close packed titanium (hcp-Ti). Fcc-Ti and hcp-Ti take the orientation relation: 〈0001〉hcp||〈001〉fcc and "Equation missing", different from the conventional one. The nucleation of fcc-Ti is accomplished via pure-shuffle mechanism with a minimum stable thickness of three atomic layers and the growth via shear-shuffle mechanisms through gliding two-layer disconnections or pure-shuffle mechanisms through gliding four-layer disconnections. Such phase transformation offers an additional plastic deformation mode comparable to twinning.
Effects of long-term salicylate administration on synaptic ultrastructure and metabolic activity in the rat CNS
Authors: Yi Bin , Hu Shousen , Zuo Chuantao , Jiao Fangyang , Lv Jingrong , Chen Dongye , Ma Yufei , Chen Jianyong , Mei Ling , Wang Xueling , Huang Zhiwu , Wu Hao 
Published: April 2016

AbstractTinnitus is associated with neural hyperactivity in the central nervous system (CNS). Salicylate is a well-known ototoxic drug, and we induced tinnitus in rats using a model of long-term salicylate administration. The gap pre-pulse inhibition of acoustic startle test was used to infer tinnitus perception, and only rats in the chronic salicylate-treatment (14 days) group showed evidence of experiencing tinnitus. After small animal positron emission tomography scans were performed, we found that the metabolic activity of the inferior colliculus (IC), the auditory cortex (AC), and the hippocampus (HP) were significantly higher in the chronic treatment group compared with saline group (treated for 14 days), which was further supported by ultrastructural changes at the synapses. The alterations all returned to baseline 14 days after the cessation of salicylate-treatment (wash-out group), indicating that these changes were reversible. These findings indicate that long-term salicylate administration induces tinnitus, enhanced neural activity and synaptic ultrastructural changes in the IC, AC, and HP of rats due to neuroplasticity. Thus, an increased metabolic rate and synaptic transmission in specific areas of the CNS may contribute to the development of tinnitus.
In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [11C]DPA-713 PET and analysis of CSF and plasma
Authors: Coughlin J M , Wang Y , Ambinder E B , Ward R E , Minn I , Vranesic M , Kim P K , Ford C N , Higgs C , Hayes L N , Schretlen D J , Dannals R F , Kassiou M , Sawa A , Pomper M G 
Published: April 2016

AbstractSeveral lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer [11C]DPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of [11C]DPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease.
Multiple markers of cortical morphology reveal evidence of supragranular thinning in schizophrenia
Authors: Wagstyl K , Ronan L , Whitaker K J , Goodyer I M , Roberts N , Crow T J , Fletcher P C 
Published: April 2016

AbstractIn vivostructural neuroimaging can reliably identify changes to cortical morphology and its regional variation but cannot yet relate these changes to specific cortical layers. We propose, however, that by synthesizing principles of cortical organization, including relative contributions of different layers to sulcal and gyral thickness, regional patterns of variation in thickness of different layers across the cortical sheet and profiles of layer variation across functional hierarchies, it is possible to develop indirect morphological measures as markers of more specific cytoarchitectural changes. We developed four indirect measures sensitive to changes specifically occurring in supragranular cortical layers, and applied these to test the hypothesis that supragranular layers are disproportionately affected in schizophrenia. Our findings from the four different measures converge to indicate a predominance of supragranular thinning in schizophrenia, independent of medication and illness duration. We propose that these indirect measures offer novel ways of identifying layer-specific cortical changes, offering complementaryin vivoobservations to existing post-mortem studies.
Knockout of NMDA-receptors from parvalbumin interneurons sensitizes to schizophrenia-related deficits induced by MK-801
Authors: Bygrave A M , Masiulis S , Nicholson E , Berkemann M , Barkus C , Sprengel R , Harrison P J , Kullmann D M , Bannerman D M , Kätzel D 
Published: April 2016

AbstractIt has been suggested that a functional deficit in NMDA-receptors (NMDARs) on parvalbumin (PV)-positive interneurons (PV-NMDARs) is central to the pathophysiology of schizophrenia. Supportive evidence come from examination of genetically modified mice where the obligatory NMDAR-subunit GluN1 (also known as NR1) has been deleted from PV interneurons by Cre-mediated knockout of the corresponding gene Grin1 (Grin1ΔPV mice). Notably, such PV-specific GluN1 ablation has been reported to blunt the induction of hyperlocomotion (a surrogate for psychosis) by pharmacological NMDAR blockade with the non-competitive antagonist MK-801. This suggests PV-NMDARs as the site of the psychosis-inducing action of MK-801. In contrast to this hypothesis, we show here that Grin1ΔPV mice are not protected against the effects of MK-801, but are in fact sensitized to many of them. Compared with control animals, Grin1ΔPVmice injected with MK-801 show increased stereotypy and pronounced catalepsy, which confound the locomotor readout. Furthermore, in Grin1ΔPVmice, MK-801 induced medial-prefrontal delta (4 Hz) oscillations, and impaired performance on tests of motor coordination, working memory and sucrose preference, even at lower doses than in wild-type controls. We also found that untreated Grin1ΔPVmice are largely normal across a wide range of cognitive functions, including attention, cognitive flexibility and various forms of short-term memory. Taken together these results argue against PV-specific NMDAR hypofunction as a key starting point of schizophrenia pathophysiology, but support a model where NMDAR hypofunction in multiple cell types contribute to the disease.
Short‐wave infrared photodetector with high responsivity and signal‐to‐noise ratio
Authors: Zhang Yue 
Published: April 2016

Short‐wave infrared photodetectors with a p‐charge layer and double barrier structure are designed and fabricated by molecular beam epitaxy. The current intensity is lowered by three orders of magnitude compared with the detector without the p‐charge layer. The tested responsivity of the detector is 485 A/W at 0.31 V, when the power of the incident light is 10 nW. By adding the p‐charge layer, the signal‐to‐noise ratio of the detector is promoted by 30 times, which reaches 1712 at 0.3 V, when the power of the incident light is 1 nW.